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DOI: 10.5958/j.2319-5886.2.2.

001

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com Volume 2 Issue 2 April - June
Coden: IJMRHS
th
Received: 8 Jan 2013
Revised: 2nd Feb 2013
Research article

Copyright @2013 ISSN: 2319-5886


Accepted: 10th Feb 2013

ASSESSMENT OF PHARMACOLOGY TEACHING - A CRITICAL APPRAISAL BY


MEDICAL SCHOOL LEARNERS
*Parimala K1, Subash KR2, Jagan N1, Vijay Kumar S1, Viswanathan S1, Chandrasekhar M3
1

Department of Pharmacology, 3Medical Education Unit, Meenakshi Medical College and Research
Institute, Enathur, Kanchipuram, Tamil Nadu, India
2
Department of Pharmacology, Sri Padmavathi Medical College, Hospital and Research Centre, Sai ram
Nagar, Tirupati Airport Road, Renigunta, Tirupati-517520, Andhra Pradesh, India
*Corresponding author email:drparimala2004@yahoo.com
ABSTRACT

Background: Students feedback is an indicator of the success of any teaching methodology followed in
a department. Aim: To identify strengths and weaknesses in the current teaching-learning and evaluation
methodology in pharmacology using feedback from second MBBS students in Meenakshi Medical
College and Research Institute. Materials and Methods: Questionnaire was designed and finalised
after a departmental discussion in concurrence with the Medical Education Unit. The study subjects
were 115 (2011batch) second-year medical students. They were requested to fill the questionnaire. A 10item multiple choice questionnaires were used to explore the students opinion on teaching. The
questionnaires were analyzed. Results: 115 II M.B.B.S students participated and descriptive statistics
was used for analysis of data. The analysis revealed 82.82%, 72.17% and 93.64% students interest
towards writing classification of drugs, weekly test and viva-voice respectively. Conclusion: The
present study has helped us to elicit the student preference regarding pharmacology teaching and its
outcome would be helpful in modifying undergraduate pharmacology teaching patterns.
Keywords: Medical education, Pharmacology Assessment, Medical school learners.
INTRODUCTION

The primary aim of teaching pharmacology to


medical students is to train them on rational and
scientific basis of therapeutics. Pharmacology
teaching is facing a major challenge in the
medical science due to constant reformation.
Generally, there is an opinion that teaching
pharmacology in medical schools has failed to
keep in pace with the rapid changes in medical
practice. Attempts have been made all over India

to make the teaching of pharmacology more


interesting and relevant1. To make pharmacology
teaching more innovative and interesting learning
experience, efforts have been made by
formulating new educational strategies to meet
the
educational
objectives.
Educational
objectives can be evaluated by assessment
procedures and timely feedback to achieve the
learning goal.
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In Meenakshi Medical College and Research


Institute, Pharmacology teaching comprises
mostly of a series of didactic lectures using
power point presentations covering general,
systemic
pharmacology
and
practical
pharmacology
which
includes
animal
experiments and clinical pharmacology sessions
spread over the academic year. To evaluate the
students progress we conduct monthly internal
assessment tests consisting of multiple choice
questions, essay questions, short notes and ultra
short notes for 3 hr time duration including
model practical exams conducted twice in a year.
Regular viva voce exams follow the monthly
internal assessment test to develop their
communication and interaction skills.
Apart from this regular schedule of assessment,
we also introduced a method of assignment on
classification of drugs after each system. To
reinforce the learning process, we implemented
weekly test on the first hour of every week based
on the lectures delivered over the previous week.
The test was conducted for one hour which
covered various portions of the chapter in detail
testing the levels of knowledge.
After
completing
the
above
schedule
meticulously, at the end of the year to understand
the beneficiaries opinion we planned to collect
the students feedback. Currently the students
feedback represents the primary means used by
different programs to assess their methodology2.
Feedback helps in correcting mistakes,
reinforcing good performances and incorporating
students view in teaching methodology. It is
accepted that reviewing the teaching and
evaluation methods by feedback from students
and modifying of methodologies accordingly is
very important for the undergraduate medical
teaching3&4. Thus the present study is an effort to
obtain and analyze critical appraisal on,
The student attitude toward teaching and
learning pharmacology in Meenakshi
Medical College and Research Institute,
Enathur, Kanchipuram.

Assessment of pharmacology teaching using


student feedback.
Methods to improve teaching Pharmacology.

MATERIALS AND METHODS

A questionnaire was designed to obtain feedback


and finalized after a departmental discussion
with the concurrence of Medical Education Unit.
The study subjects were 115-second year MBBS
students of 2011 batch studying in the Meenakshi
Medical College and Research Institute, Enathur,
Kanchipuram.
All the students enrolled in the study were
requested to fill up the questionnaire. The study
was conducted at the end of their academic year
in the Department of Pharmacology. A ten-item
multiple choice questionnaires and an open
ended question for suggestion were provided to
explore the students opinion on teaching and
learning methods imparted. The questionnaire
was analyzed by two observers. The
questionnaire was designed in such a way to
assess the knowledge, their attitude and skills
developed during their one and half year course
in pharmacology. Both the theoretical and
practical pharmacology practiced by different
methods during their study period were evaluated
from the feedback form.
Statistics: Descriptive statistics was used for
analysis of data. Frequency was shown as a
percentage.
RESULTS

One hundred and fifteen students of II MBBS


participated and responded in the questionnaire
study. Based on the pattern of studying
pharmacology, 48.69% studied pharmacology
once or twice a week on a regular basis and
34.78% opted studying only for monthly tests
and viva voce exams which reflects on their
regular preparation for monthly internal
assessment test (Fig.-1). 54.75% of students
preferred lecture notes and textbooks as the
source of studying pharmacology.
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Int J Med Res Health Sci. 2013;2(2):124-129

Pharmacology study pattern

Students %

Daily

Weekly

Monthly

University exams only

Studying habits

Fig: 1. Pharmacology Text Reading Habits


The majority (87.82%) of students approved
writing and maintaining classification of drugs.
53.91% have opined that the assignments had
improved in better understanding about the

different classes of drugs.43.47% of them have


reported its usefulness to memorize and
reproduce in the test and also to apply in their
clinical postings(Fig.-2).
2).

Effect of assignment on classification of drugs

S
Students
%

To Memorize
Memorize &
Reprodu ce

To Understand &
DIfferentiate

Clinical
Application &
Integration
ration

Usefulness
Fig: 2. Student Assignments
Among the assessment methods, 54.78% of
students favoured monthly internal assessment
test for their significant improvement in their
academic performance. In the weekly test

conducted, 72.17% of students found weekly


lectures correlating with weekly tests, 51.30% of
students mentioned that the true or false part
par of
the weekly test created interest (Fig.3).

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Int J Med
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2):124-129

Interesting part of weekly test


Short answers

Fill ups
True or flase

Match the following

Students %

Fig: 3. Weekly test instruments


The majority (66.95%) of students preferred
Among the teaching learning methods
regular tests in clinical pharmacology sessions
practiced, 52.17% of students preferred theory
when
compared
to
the
experimental
lectures followed by clinical pharmacology
pharmacology. Most (93.64%) of the students
sessions 46.95% and group discussions 45.21%
have mentioned regular viva-voce
viva voce exams
(Fig.4).
following monthly internal assessment test had
improved their
their communication skills.
Preferred Teaching Learning Method
60
52.17

STUDENTS %

50

46.95

45.12

40
30

26.08
21.73
15.65

20
10

21.73
13.04

8.69

14.78
10.43

YES
5.21

NO

Teaching Learning Method

Fig: 4. Teaching Learning Methods

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2):124-129

DISCUSSION

Feedback is defined as a response within a


system that influences continuous activity or
productivity of that system. In the present study
on educational context, it would mean a response
from the learner about the teaching learning
process. Feedback is essential to find out the
effectiveness of the process, the need to change
it, as well as, to evolve strategy for its
improvement.
From the feedback evaluation obtained, it is
observed that students like to study
pharmacology by regular test / viva and
interactive classes so by these way students
understand the subject properly5. This very much
correlates in the present study feedback results.
It was found that students preferred writing and
maintaining classification of drugs throughout
their academic year, which were corrected
periodically by the faculty, who played the role
of mentor for the given group of students to
cultivate and sustain the habit. Writing
classification of drugs by medical school learners
has helped them to understand the different
classes of drugs and also to systematically
memorize and reproduce in the written test as
well as the knowledge application in clinical
rotations.
Students opined that monthly internal assessment
test was mostly useful than the weekly written
test for their academic performance in theory
exams, the reason for the following may be a
monthly internal assessment pattern is similar to
that of university examination. The weekly
written test has definitely kept the students in
pace with the portions being completed every
week. By answering the weekly test their
preparation, facing and performing a monthly
internal assessment had become extremely
comfortable and confident . The weekly test had
various parts, students considered true or false
part of the weekly test has created interested in
them, the fact to get such a feedback may be the
chances of getting the wrong answer is only
50%. Also they have mentioned that, Match the

following with extended responses have


stimulated their thought process to find the
correct response. The feedback also emphasized
the students interest towards more interactive
sessions on Clinical pharmacology exercises and
felt it should be given regular emphasis than the
animal experiments. According to Gibbs G et al,
19876active review during the lecture, involving
students in structured discussions, using
questionnaires and asking them to summarize are
the three most important things to be followed
and practiced for an effective teaching-learning
process.
To conclude though the teaching learning
method implemented in the present study
required a lot of strenuous hard work from the
faculty
particularly
preparing
questions,
organizing test and more importantly correcting
all the papers in a week period, it has created an
interest in learning pharmacology among
students. The feedback from learners has clearly
exhibited their likeliness for the variety or
different methodological approach instead of
regular didactic lectures offered by the
department of Pharmacology.
ACKNOWLEDGEMENTS

We sincerely thank our II M.B.B.S Students of


Meenakshi Medical College & Research Institute
for the participation.
REFERENCES

1. Gitanjali B and Shashindran CH. Curriculum


on clinical Pharmacology for medical
undergraduates of India. Indian J Pharmacol.
2006;38: 108-14.
2. Richardson BK. Feedback Acad. Emerg
Med. 2004; 11th Edn, 1-5.
3. Ruth N. Communicating student evaluation
of teaching results: rating interpretation
guides (RIGs) Assess Evaluation Higher
Edu. 2000;25:12134.
4. Victoroff
KZ, Hogan S. Students
perceptions of effective learning experiences
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in dental school: A qualitative study using a


critical incident technique.
J. Dental
education.2006; 70: 124-32.
5. Nilesh Chavda, Preethi Yadav, Mayur
Chaudhari, Kantharia ND. Second year
students feedback on teaching methodology
and evaluation methods in Pharmacology.
National Journal of Physiology, Pharmacy
and Pharmacology. 2011;1: 23-31
6. Gibbs G, Habeshaw S & Habeshaw T.
Improving student learning during lectures.
Medical teacher. 1987; 9:11-20.

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DOI: 10.5958/j.2319-5886.2.2.002

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April - June

th

Received: 12 Jan 2013


Research article

Coden: IJMRHS
th

Revised: 15 Feb 2013

Copyright @2013

ISSN: 2319-5886

Accepted: 18th Feb 2013

ACUTE TOXICOLOGICAL EVALUATION OF PET ETHER EXTRACT OF PORTULACA


OLERACEA (LINN.) ON RODENTS.
*Siva Reddy1, Somasundaram G2
1

Department of Forensic medicine, Sri Venkateshwaraa Medical College Hospital & Research Centre,
Ariyur, Pondicherry. India.
2
Department of Pharmacology, MGMCR&I, Pilayarkuppam, Puducherry, India.
*Corresponding author email: padmasivareddy@gmail.com
ABSTRACT

Introduction: Portulaca oleracea is a common plant used in South Indian culinary; recently there is
increase in research publication on various biological activities of the medicinal herb. The safety of the
medicinal herb well accounted by its widespread accepted use of natives yet scientific evaluation on the
safety of the herb is not reported. Aim To scientifically evaluate the toxicity profile of the pet - ether
extract of Portulaca oleracea by standardized methods. Method A 24hour acute toxicity study followed
by 14 day sub-acute toxicity study with serum haematological, biochemical and histopathological
analysiss is evaluated in rodents. Result No observable serious side effects are recorded in acute and
sub acute toxicity study for 0.5gm/kg and 1gm/kg pet-ether extract of Portulaca oleracea. There are
statistically significant rising (p<0.01) in hemoglobin by 13.25%, 15.42% and 15.04% in Portulaca
oleracea 0.5gm, 1gm, and 2gm/kg body weight respectively when compared to control 10.56%.
Portulaca oleracea 2gm/kg dose administration for 14 days has revealed oxalate crystal deposits in the
kidney. Conclusion The pet ether extracts of Portulaca oleracea 0.5gm, 1gm, and 2gm/kg exhibited
zero mortality rates in both acute and sub-acute toxicity studies and found to increase haemoglobin, total
cholesterol levels in serum which can be seriously evaluated for further research.
Keywords: Portulaca oleracea (LINN.), Acute Toxicity, Sub-acute Toxicity, Rodents.
INTRODUCTION

Toxicological research is the primary step in


screening chemicals before pharmacological
screening for their predictive biological activity.
The current research scenario has shown
tremendous bioprospecting of compounds from
natural origin. Many compounds which are
potential drug candidates during preclinical
research tend to be rejected in the later stages of

research due to unwanted side effects which


takes lots of manpower and financial resources,
such errors can be avoided by initial
toxicological and safety analysis before taking
the drug to pharmacological research. Portulaca
oleracea is a herb widely used by south Indian
population for various ailments and the leaves
are widely used in food preperations. This herb
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belongs to family Portulacaceae . The plant is


reported to have protective biological effect
against bacterial and fungal infection1. Towards
treatment of infertility and preclinical scientific
research on various inflammatory conditions2.
Despite the uses traditionally, there is much less
scientific evidence in established literature on the
safety of this plant. Information concerning
toxicity of Portulaca oleracea from traditional
use has also been scarce. The literature search
also revealed no scientific evidence available
regarding safety of this plant. The present study
is an effort to provide preliminary information on
the acute and subacute toxicological profile of
the Pet - Ether extract of Portulaca oleracea in
rodents the reports were supported with
biochemical, isolated organ and histopathological
observations .
MATERIALS AND METHODS

Plant Material: The leaves of Portulaca


oleracea are used in traditional medicine
similarly in the present study the leaves of the
plant is collected from botanical garden during
the month of May 2009; the collected leaves are
authenticated by Department of Botany,
Annamalai University, Chidambaram.
Extract Preparation: The leaves of Portulaca
oleracea were sold dried for seven days and
pulverized one kg of coarse powder was filtered
through a fine mesh and collected powder is
soaked in 4 litres of petroleum-ether for 3 days at
room temperature. The collected extract is
evaporated to dryness using a rotary vacuum
flash evaporator and the yield was stored in
airtight container for further research.
Animals : Sprague-Dawley rats weighing 200250gms were used for toxicity studies. The
animals are kept in standard conditions of a 12
hour day and 12 hour night cycles at 22 C room
temperature, in polypropylene cages. The
animals were fed on standard pellets (Hindustan
Lever Pvt Ltd., Bangalore) and provided tap
water ad libitum. To acclimatize to laboratory
conditions the animals were housed in

polypropylene cages prior to the experiments for


one week. The experiment was conducted in
Rajah Muthiah Medical college, Department of
Forensic medicine and Toxicology and the
protocol was approved by the Institutional
Animal Ethical Committee (IAEC). All
procedures and techniques used in these studies
were in accordance with accepted principles for
laboratory animal use and care of Annamalai
University.
Acute toxicity : Sprague-Dawley rats of either
sex were randomly divided into four groups, six
animals in each group (n=6). The rats were kept
in the experimental environment for an
acclimatization period of 1 week before starting
the experiment. The animals were fasted
overnight with access to water ad libitum. The
study design included three treatment groups and
one control group, the treatment group received
orally pet-ether extract of Portulaca oleracea in
doses of 0.50,1.00, and 2.00 gms/ kg of body
weight. The control group received 10 ml/ kg
p.o. of Normal saline. The rats were observed up
to 24 hours for general changes in behaviour and
physiological function as well as mortality. The
assessment of behaviour and physiological
function was carried out by procedures
originally4 described by Irwin (1968)3.
Sub-acute toxicity : Sprague-Dawley rats, 6 per
group, were treated orally with Portulaca
oleracea daily for 14 consecutive days. The
study design included four groups. Group -1 the
control, received 10 ml kg p.o. of Normal saline
daily. Group 2, 3 and 4 were treated with daily
doses of the extract i.e. 0.5, 1 and 2 gm/ kg
respectively. The extract of three different
concentrations was prepared such that not more
than 2 ml was given orally. The animals were
monitored closely for signs of toxicity.
Appearance, toxicity signs, cage side observation
and behaviour pattern were assessed daily and
any abnormalities in food and water intake were
registered.
Preparation of serum and isolation of organs:
After fourteen days of observation the rats were
sacrificed on the fifteenth day by cervical
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dislocation, the jugular vein was cut and blood


samples were collected for hematological assay
in vacuum tubes containing 2.5 g of ethylene
diamine tetra acetic acid (EDTA). Hematological
parameters including haemoglobin (HGB), red
blood cells (RBC), white blood cells (WBC),
mean corpuscular volume (MCV), mean
corpuscular haemoglobin (MCH), and mean
corpuscular haemoglobin concentration (MCHC)
were determined by an automatic analyzer.
Another sample of blood was collected into tubes
without anticoagulant to obtain serum was
collected and stored at -20C until assayed for
biochemical parameters the next day.
Biochemical analyses were performed on serum
collected for the determination of the following
parameters: fasting blood glucose, aspartate
transaminase (AST), alanine transaminase
(ALT), alkaline phosphatase (ALP), urea, Blood
urea nitrogen (BUN) and Cholesterol. All
analyses were carried out using the Automated
Clinical Chemistry Analyzer. After collecting
blood, the rats were quickly dissected to remove
and isolate the organs which were blotted with
clean tissue paper and then weighed on a
balance.
Effect of extract on body and organ weights in
rats : Body weights of the rats in each group
were recorded on day 1 and 15. The relative
organ weight (ROW) of each organ was
calculated as follows:

ROW = Absolute Organ Weight (g) / Rat body


weight on sacrifice day X 100.
Histopathological
examination
:
Histopathological examinations were carried out
on the tissue obtained from liver, kidney, spleen
and stomach of each group. Tissues were fixed in
10 % neutral buffered formalin (pH 7.2) and
dehydrated through a series of ethanol solutions,
embedded in paraffin and routinely processed for
histological analysis. Sections of 2 m thickness
were cut and stained with haematoxylin Eosin for
examination.
Analysis of data
The recorded data were statistically analyzed for
the presence of significant differences among
means of groups using one-way ANOVA
followed by Newman-Keuls multiple comparison
test.
Data were presented as mean SEM (n=6).
Graph Pad Prism (GraphPad Software, San
Diego, CA, USA) statistical software was used.
RESULTS AND DISCUSSION

Acute toxicity : All animals in each group are


observed continuously for first four hours
followed by 8th hour and 24th hour. In control and
Portulaca oleracea 0.5 gm there were no signs
of toxicity, whereas the Portulaca oleracea 1gm
and 2gm exhibited Asthenia, defecation,
salivation, urination more than that of control
group (Table-1)

Table.1: Acute Toxicity observation of Portulaca oleracea Extract.


S.No Group
Mortality
Toxicity Signs
1
2
3

D/T
Control N.S 10ml/kg
0/6
Portulaca oleracea 0.5gm/kg 0/6
Portulaca oleracea 1gm/kg 0/6

Portulaca oleracea 2gm/kg

0/6

Latency (hrs)
None
None
Asthenia, defecation, salivation,
urination
Asthenia, defecation, salivation,
urination

N.S-Normal Saline, D/T Death/Treatment

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Sub-acute toxicity
Similar observation as seen in acute toxicity
studies was present for initial two days, later
Asthenia, increased defecation, salivation,
urination were not observed. The cage side
observations for 14 days on general behaviour,
respiratory pattern, cardiovascular signs, reflexes
are normal. The Portulaca oleracea 2gm/kg
group exhibited decreased motor activity and
there were no change in skin and fur. All animals
survived for 14 days. The decreased motor

activity is probably due to the extract effect on


skeletal muscle, a similar observation was made
by Parry O et al, and reported to muscle relaxant
activity4. The analysis of hematological
parameter revealed in all treatment groups the
haemoglobin (p<0.001), RBC (p<0.05) counts,
packed cell volume (p<0.01), mean corpuscular
volume (p<0.01) and mean corpuscular
haemoglobin (p<0.01) were significantly
increased when compared to control treated rats
(TABLE-2).

Table. 2: Hematological parameter of Portulaca oleracea Extract after 14 days.


Groups (n=6)

Hb % (gm)

PCV %

MCV(fl)

MCH(pg)

RBC
(milli/cu.mm)

WBC
(milli/cu.mm)

Control N.S
10.56 0.25 38.14 0.56 86.023.45 20.83 2.25
4.65 0.34
6.65 2.25
10ml/kg
6.76 0.25
Portulaca oleracea 13.250.35** 45.240.45* 95.244.53 28.28 0.55** 6.75 1.25*
0.5gm/kg
6.50 1.22
Portulaca oleracea 15.421.24** 44.141.26* 94.123.56 27.24 1.25** 6.60 0.25*
1gm/kg
6.34 2.24
Portulaca oleracea 15.040.65** 45.162.27* 95.622.22 30.65 2.20** 7.25 2.24*
2gm/kg
Values are mean S.E.M. *P<0.05;**P<0.01; Compared to Control (one-way ANOVA followed by

Newman-Keuls test)
The significant increase in hematological
parameter observed with Portulaca oleracea
0.5gm and 1gm is dose dependent, were as
Portulaca oleracea 1gm and 2gm increase in
dose did not have an increased effect on
parameters clearly establishing the ceiling effect.
The leukocyte count was not affected in all three
treated groups compared to that of the control
group. The leaves of the extract from Portulaca
oleracea are rich in micronutrient and
macronutrient constituting an important source of

protein, essential amino acids, mineral elements


including free oxalic acids, alkaloids, omega-3
fatty acids, coumarins, flavonoids, cardiac
glycosides, anthraquinone, and proteins may
have a synergistic effect on the observed rise in
haemoglobin levels5. The biochemical parameter
screening after 14 days did not reveal any
significant changes except total cholesterol level
in all three treated groups with extract of
Portulaca oleracea (Table-3)

Table.3: Biochemical parameter of Portulaca oleracea Extract after 14 days


Groups (n=6)

ALP
AST
ALT
Urea
(mg/dl)
(IU/L)
(IU/L)
(IU/L)
25.230.39 42.291.90 23.382.53 15.20
Control N.S
2.02
10ml/kg
Portulaca oleracea 24.73 0.39 43.892.50 23.452.93 16.38
2.12
0.5gm/kg
Portulaca oleracea 25.350.39 42.552.34 24.501.50 15.45
0.25
1gm/kg
Portulaca oleracea 26.030.25 41.252.50 24.48 1.33 16.20
2.24
2gm/kg

BUN
Glucose
Cholesterol
(mmol/L) mg/dl
mg/dl
7.520.84 83.576.97 54.242.24
7.520.84

83.576.97 66.143.15*

7.520.84

83.576.97 64.200.26*

7.520.84

83.576.97 68.503.12*

Values are mean+ S.E.M. *P<0.05;**P<0.01; Compared to Control (one-way ANOVA followed by
Newman-Keuls test)
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Relative organ weight (%)

Though the all animals in each group were fed


with the common diet pattern there a significant
increase in total cholesterol level, the total
cholesterol level signifies low density
lipoproteins, very low density lipoproteins, high
density lipoproteins and triglycerides. The
probable rise in cholesterol level without a rise
in body weight and fat free food could be due to
omega 3 free fatty acid. Already there are
investigating reports on Portulaca oleracea as a
rich source of omega 3 fatty acids 6. The body
weight was measured on day 7 and day 14 of sub

acute toxicity study did showed increase in body


weight in all groups, but when compared to
control group the treatment group did not have
any statistical difference. The animals in each
group after euthanasia were carefully dissected
and observed for gross macroscopic tissue/organ
pathology. Necropsy observation revealed no
gross anatomical abnormalities in all the groups.
The organs liver, spleen, stomach and kidney are
dissected and checked for relative organ weights
(Fig; 1, 2, 3 & 4)

1.5
1
0.5
0
Control

P.ole 0.5gm/kg

P.ole 2 gm/kg

P.ole 2 gm/kg

Portulaca oleracea Pet-Ether Extract

Relative organ weight


(%)

Fig.1: Relative organ weight-Liver

1.5
1
0.5
0
Control

P.ole 0.5gm/kg

P.ole 2 gm/kg

P.ole 2 gm/kg

Portulaca oleracea Pet-Ether Extract


Fig2: Relative organ weight-Spleen
There was no statistical relative weight difference for spleen, liver and stomach when compared to that
of control (fig; 1, 2 & 3.).
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Relative organ weight (%)

1.5
1
0.5
0
Control

P.ole 0.5gm/kg

P.ole 2 gm/kg

P.ole 2 gm/kg

Portulaca oleracea Pet-Ether Extract


Fig.3: Relative organ weight-Stomach

ROW (%)

1
0.5
0
Control

P.ole 0.5gm/kg

P.ole 2 gm/kg

P.ole 2 gm/kg

Portulaca oleracea Pet-Ether Extract


Fig.4: Relative organ weight-Kidney
The weight of the kidney of Portulaca oleracea 1gm/kg and 2gm/kg treated group had increased relative
weight of organ by 0.2% but not statistically significant (fig 4).

Fig.5. A Control group with arrow indicating normal glomerular structure and Renal tubules,
B P.oleracea 2gm/kg treated group arrow pinpointing oxalate renal stone and tubular dilation.
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Int J Med Res Health Sci. 2013;2(2):130-136

Hence all the dissected organs with particular


interest of isolated kidney from Portulaca
oleracea 1gm/kg and 2gm/kg were taken for
histopathological studies. The histopathological
studies revealed the presence of epithelial
inflammation
and
oxalate
stones
and
hemorrhagic spots (fig; A, B). Earlier studies on
nutrition content of Portulaca oleracea revealed
half a cup of leaves contain 910 mg of oxalate
which explains the increase in relative organ
weight and histopathalogical appearance of
oxalate stones7. The phytochemical screening of
pet-ether extract of Portulaca oleracea can
reveal the major active constituents responsible
for biological activity of the extract8.
CONCLUSION

The pet-ether extract of Portulaca oleracea


0.5gm/kg, 1gm/kg and 2gm/kg evaluated for
acute toxicity and sub-acute toxicity has no
observable side effects, except for the renal
calculi formation at 1gm/kg and 2gm/kg for 14
days. The study has also provided other
important finding such as the ability of the
Portulaca oleracea pet-ether extract in
increasing the hemoglobin and anticipated High
density lipoprotein level. The observed finding
can be extrapolated for further research of potent
hematinic compound.
ACKNOWLEDGEMENTS

The authors are grateful for the technical


assistance offered by the staff Department of
Pharmacology, Botany and Department of
Forensic medicine and toxicology (Rajah
Muthiah
Medical
College)
Annamalai
University.

3.

4.

5.

6.

7.

8.

Evaluation of the anti-nociceptive and antiinflammatory activities of the pet: ether


extract of portulaca oleracea (linn.). Journal
of Clinical and Diagnostic Research;
2012,6:226-230.
Irwin S. Comprehensive observational
assessment: Ia. A systematic, quantitative
procedure for assessing the behavioral and
physiologic state of t h e m o u s e . P s y c
h o p h a r m a c o l o g i a . 1968;13(3) :
222-57
Parry O, Marks JA, Okwuasab FK. The
skeletal muscle relaxant action of Portulaca
oleracea: Role of potassium ions. J.
Ethnopharmacol. 1993;49:187-94.
Ezekwe
MO,
Omara-Alwala
TR,
Membrahtu
T,
(1999).
Nutritive
characterization of the purslane accessions
as was influenced by the planting date. Plant
Foods Hum Nutr; 54:183-91.
Simopoulos AP, Norman HA, Gillaspy JE,
and J. A. Duke. Common purslane: a source
of omega-3 fatty acids and antioxidants.
Journal of the American College of
Nutrition. 1992; 11(4) 374-82.
Moreau A.G, Savage G.P. Oxalate content
of purslane leaves and the effect of
combining them with yoghurt or coconut
products. Journal of Food Composition and
Analysis. 2009;22(4):303-06
Subash KR, Muthulakshmi Bhaarathi G,
Jagan Rao N, Binoy Vargheese Cheriyan.
Phytochemical screening and acute toxicity
study of ethanolic extract of Alpinia galanga
in rodents. 2013;2(1):93-100.

REFERENCES

1. Oh KB, Chang IM, Hwang KI, Mar W.


Detection of anti-fungal activity in Portulaca
oleracea by a single cell bioassay system. J
Phytother Res; 2002, 14:329-32.
2. Jagan Rao N., Jayasr ee T., Mallikarj una
Rao B., Sandeep Kumar K., Vijay Kumar S..
136

Sivareddy et al.,

Int J Med Res Health Sci. 2013;2(2):130-136

DOI: 10.5958/j.2319-5886.2.2.014

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 18 Jan 2013


Research article

Coden: IJMRHS

Copyright @2013

th

Revised: 15 Feb 2013

ISSN: 2319-5886
th

Accepted: 18 Feb 2013

ANTI DIABETIC EFFECT OF MOMORDICA CHARANTIA (BITTER MELONE) ON


ALLOXAN INDUCED DIABETIC RABBITS.
*Yakaiah Vangoori1,Mishra SS2,Ambudas B3, Ramesh P4, Meghavani G4, Deepika K4, Prathibha A4
1

Assistant Professor and 4PG of Pharmacology, Santhiram Medical College, Nandyal, AP, India
2
Professor of Pharmacology, IMS & SUM Hospital, Bhubaneswar, Odisha, India
3
Lecturer in Pharmacology, BLDEUs Sri BM Patil Medical College Hospital & Research Centre,
Bijapur, Karnataka, India
* Corresponding author email: yakaiahpharma143@gmail.com
ABSTRACT

Objective: to investigate the anti diabetic effect of the bitter melon on Alloxan induced diabetes in
experimental animals (rabbits). Materials and Methods: the alcohol extract of whole fruit was tested
for its efficacy in Alloxan (150mg/kg) induced diabetic rabbit. The diabetic rabbits were divided into
5groups. Group I (control) received 2% gumacasia, groupie (positive control) received standard drug
Metformin (62.5mg+2%GA), group III, IV, V (T1 T2 T3) were treated orally with a daily dose of 0.5(gm)
1gm, 1.5gm respectively for 35 days, for all diabetic rabbits after giving TEST,NC,PC preparations, the
blood samples were collected and determined the blood glucose level 0,1,3,24hrs intervals. 0hr reading
is before drug giving and remaining 3 readings after drugs giving. 24th her reading is considered as 0hr
reading for the next day. Results: administration of alcohol of an extract of bitter melon produced a dose
dependent decrease in blood glucose levels in Alloxan induced rabbits. There was a significant fall in
blood sugar level in High dose (1.5GM/kg) in comparison to low dose (0.5gm/kg) and median dose
(1gm/kg) shown by LSD test. This is comparable to the effect of Metformin. Conclusion: the results of
this study show that chronic oral administration of an extract of Momordica charantia fruit at an
appropriate dosage may be good alternative anti diabetic agent.
Keywords : Hyperglycemia, Metformin, Alloxan, Momordica charantia
INTRODUCTION

Diabetes mellitus is the world largest endocrine


disease with deranged carbohydrate, fat and
protein metabolism. The diabetes mellitus is
mainly classified into two major groups, Type-1
(insulin dependent diabetes mellitus), Type-2
(non-insulin dependent diabetes mellitus. As per

WHO report, approximately 150 million people


have Diabetes mellitus worldwide, and this
number may well double by the year 2025.
Statistical projection suggests that the number of
diabetics will rise from 15 million in the year
1995 to 57 million in 2025 in India. This number
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Yakaiah et al.,

Int J Med Res Health Sciences. 2013;2(2):137-142

is making India the country with the highest


number of diabetics in the world.1 Long-term
complications of diabetes are micro vascular
(neuropathy, retinopathy, nephropathy) and
macro vascular (heart complications)2 diseases.
The anti diabetic drugs are mainly used for to
replace the insulin deficiency or to enhance the
action of insulin and/or decrease the insulin
resistance.
Although
many
drugs
and
interventions are available to manage diabetes,
these are expensive for the large diabetic
population of developing countries like India,
apart from their inherent adverse effects.3 So it is
necessary to look for new cheep alternatives to
manage this major health problem. Different
indigenous drugs have been used in this
subcontinent for several centuries for
the
treatment of Diabetes mellitus with conflicting
reports of their efficacy because of lack of
scientific investigation in a laboratory setting.
One such plant, Momordica charantia (Karela)
whose fruit has long been used traditionally in
the treatment of Diabetes mellitus in South Asian
countries and has rich Ayurvedic reference to
select for the study. In this study, the anti
diabetic potential of this unripe fruit extract of
Momordica charantia (Karela) was screened on
laboratory animal model.4,5
MATERIALS AND METHODS

Institutional Animal Ethics Committee (IAEC)


permission was obtained before starting the
study. The study was conducted strictly in
accordance with the protocol.
Plant material: Fresh green fruits of bitter
gourd popularly known as karela was obtained in
sufficient quantity from a local market in
Nandyal, A.P. in November 2012. They were
carefully washed to remove dust particles and
other foreign materials and dried in shaded areas.
The completely dried fruits were powdered with
electric grinder and stored in well closed bottles.
Alcohol extract preparation: The extract is a
concentrated preparation of vegetables or animal
source Extract: The extract is the process or act

of pulling or drawing out the active principle of a


particular material like plants or animal organs.
In the present study the percolation method was
selected to extract the active principle of bitter
gourd plant material.6 Cold percolation
method: This is a traditional method of
extraction used by the herbalists throughout the
world. This is the original extraction method, and
it's continuing to be the backbone of the present
extracting technology. The distillation devices
are modified Soxhlet extractions made by
Eden Labs 7,8 Extraction procedure: The dried
fine powder of the bitter gourd was weighed in
balance 25g and taken into the sac like cloth
material and placed in the Soxhlet basket. 250ml
of ethyl alcohol was taken as solvent into the
Soxhlet flask. The extract laden solvent falling
from the Soxhlet basket is dark in color and it
becomes clearer, that indicates the extraction
process is finished9. At the end of the extraction
process the solvent is then evaporated and the
remaining mass is measured. The percentage
yields are calculated as mg per gm dried powder
in 250ml of alcohol, 25gms powder was
suspended. 5gms (20%) of extract was obtained.
The extract was suspended in 5ml of 2% Gum
acacia and used for the oral administration in
diabetic rabbits.
Animals used: 25 Rabbits of either sex, adult,
healthy albino rabbits of local strain weighing
between 1 to 4 kg were used in this experiment.
All the animals were kept in an air-conditioned
animal house in the Pharmacology Department at
the Santhiram Medical College, Nandyal,
Kurnool Dist. AP. The animals, rabbits were
offered a natural food like grass and leaves and
allowed a tap water to drink.10
Preparation of diabetic rabbits: the 25 rabbits
weighing between 1 to 4 kg were made diabetic
by injecting intravenously 150mg/kg body
weight of Alloxan monohydrate11,12 Before
giving Alloxan, the normal blood glucose levels
of all rabbits were estimated. After 2hours of
Alloxan injection the Dextrose (5gm) mixed with
water fed to the all-diabetic rabbits orally to
prevent a hypoglycemic condition of rabbits with
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Yakaiah et al.,

Int J Med Res Health Sciences. 2013;2(2):137-142

Alloxan.7 After 72hours of Alloxan injection, the


blood glucose levels of all surviving rabbits were
determined by the glucose oxidase method. The

rabbits with blood glucose levels of 220 to


500mg/dl were considered as diabetic and were
13
employed
to
further
study.

Table.1: Grouping of animals


Groups
Animals
Drug
Control
(2% gum acasia) 5ml
I
Positive control
(Metformin 62.5mg+2% ga) 5ml
II
Test (low dose 0.5gm)
Alcohol extract+2%ga 5ml
III
Medium dose (1gm)
Alcohol extract+2%ga 5ml
IV
High dose (1.5gm)
Alcohol extract+2%ga 5ml
V
All Alloxan diabetic rabbits were randomly divided into five groups (n=5).

Remarks
Placebo
Positive
ExL
ExM
ExH

glucose oxidase method is more accurate, rapid


and time saving method. It requires only a small
amount of blood. So this method is popularly
used in India people suffering from diabetes for
self-monitoring of blood glucose levels.14

For all the diabetic rabbits after giving test,


negative
control
and
positive
control
preparations, the blood samples were collected
and determined the blood glucose 0, 1 & 3hrs
intervals. 0 hour reading is before drug
giving.1 & 3 hours reading is after drug giving.
After administration of drugs to the diabetic
rabbits the blood was collected 1,3 and 24-hour
interval daily up to 35 days and blood glucose
level was determined by the glucose oxidase
method by using Glucometer for 15 days and
then weakly for 3 weeks. The

RESULTS

In the present study, alcohol extract of the unripe


fruit of the Momordica charantia (Bitter gourd)
was assessed for its anti diabetic activity in
Alloxan-induced diabetic rabbits. The results
obtained were recorded (Table 2).

Table.2: Average Blood Glucose levels (mg/dl) of groups I to V before and after treatment up to 35th day.

S.No.
Before
Alloxan
After Alloxan
(72 hrs.)

Group I
78.2

Group II
75

Group III
86

Group IV
88

Group - V
89

311

293

310

300

305

After
Treatment

0 Hr

1
Hr

3 Hr

0
Hr

1
Hr

3
Hr

0
Hr

1
Hr

3
Hr

0
Hr

1
Hr

3
Hr

0 Hr

1 Hr

3 Hr

Day 1

311

308

307

293

283

279

301

307

308

300

292

292

314

319

312

1st week

312

287

278

254

238

244

277

274

283

260

275

279

251

244

247

2nd week

307

298

298

184

173

171

228

224

225

198

204

203

145

158

157

3rd Week

289

286

299

158

149

153

227

232

228

169

175

145

147

141

146

4th Week

293

276

295

150

144

153

202

194

191

166

161

165

145

143

148

5th Week

272

278

274

109

112

130

184

194

199

149

151

146

120

127

131

After 35 days of treatment, there is a significant


decrease in blood glucose levels was seen with
the standard drug Metformin and Ethanolic

extract of M-Charantia but there is no significant


reduction in the control group treated with gum
acacia.
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Yakaiah et al.,

Int J Med Res Health Sciences. 2013;2(2):137-142

Table 3: Mean blood sugar level of different groups:

Time

Group I

Group II

Group III

0 Hour

27216.1

109.23.3

18413.3

1st Hour

278.48.3

112.22.6***

19413.4

3rd Hour

274.811

130.216.1

**

***

**
*

199.615

Group IV
**

149.65.7

***

151.814.2

***

1464.6

Group V
***

1207.8

127.65.2***
13110.2***

P<0.05, **P<0.01, ***P<0.001 compared to the control.

Table.4: Mean Blood Glucose levels (MeanSEM) at 35th day.


Animals
R1
R2
R3
R4
R5
Variation

Control
-18.14
-36.81
-14.45
-52.09
7.83
ns

Metformin
-80.67
-77.19
-69.67
-106.60
-50.78
sig

ExL
-55.02
-41.79
-90.66
-4.10
-77.74
sig

ExM
-80.67
-54.24
-67.21
-68.98
-67.98
less sig

ExH
-142.74
-69.29
-94.03
-160.09
-70.59
sig

DISCUSSION

The present study, we have evaluated the alcohol


extract of the unripe fruit of the Momordica
charantia (Bitter gourd) was assessed for its anti
diabetic activity in Alloxan-induced diabetic
rabbits. The results obtained were recorded. A
placebo-controlled
sub-acute
study
was
conducted on 5 groups of 5-diabetic rabbit
models to show the hypoglycemic effect of 3
increasing doses (0.5 gm / kg, 1.0 gm / kg and
1.5 gm / kg body weight) of the alcohol extract
of M. Charantia suspended in gum acacia. The

result was compared with the established antidiabetic drug Metformin in the dose of 150 mg
per Kg body weight. Gum acacia was taken as
the placebo in this study. The blood sugar level
was recorded daily by Glucometer for 15 days
and then once weekly for another 3 weeks but in
the above table only weekly report is given. The
decrease in the blood sugar level was recorded
daily from the initial value and was shown in the
above table.

The blood sugar levels were highly decreased of


a treatment with high dose of extract. The blood
sugar levels are almost comes to the Normal
levels. The high dose effect of the extract is
almost similar to Metformin effect after 35 days
of treatment. There was significant variation in
the decrease of blood sugar among the diabetic
rabbit models in each group except in dose of 1
gm / Kg (ExM) body weight (Table 3).
Overall comparison between different groups
of rabbits
The fall in the blood sugar was compared among
the groups of animals with ANOVA. It was
found that there was significant variation (P <
0.01) among the groups. Multiple comparison

tests were performed to find out the differences


between the groups.
Comparison with Control: The Dunnetts test
was conducted between the control group and the
groups that were given Metformin and the
extracts in 3 increasing doses. As expected the
fall in the blood sugar level was significant (P <
0.05) in the Metformin group. There was no
significant difference in the fall in the blood
sugar levels with ExL, ExM in comparison with
the control but there was significant (P < 0.05)
fall in blood sugar level in ExH group (Table 4).
Comparison with Metformin: The effect of
Extract in all the 3 doses in lowering blood sugar
level showed no statistically significant
140

Yakaiah et al.,

Int J Med Res Health Sciences. 2013;2(2):137-142

difference with that of Metformin in the doses


used in this study. This result was checked by
two post-ANOVA multiple comparison tests like
LSD test of Fisher accommodates a lot of Type I
error) and FSD test of Scheffe (accommodates a
lot of Type II error). Both the tests gave an
identical result. It gave a strong hint that the
Extracts of M. charantia were as efficient as
Metformin in lowering the blood sugar in
diabetic rabbits and that was achieved in a broad
range of doses ranging from 0.5 gm / Kg to 1.5
gm / Kg, so it might be a much safer alternative
to the established drugs.
Comparison between different doses of the
Extract : There was significant fall in blood
sugar level in ExH dose in comparison to ExL
and ExH dose in comparison with ExM as shown
by LSD test. But such difference was not found
in with Scheffes test.
The present study, the hypoglycemic effect of M.
Charantia fruit extract was compared with
metformin. Similar studies by Akhtar MS et al,
in 1981 and Biyani MK et al (2003) the acute
hypoglycemic effect was compared with
sulphonylureas and concluded positive effect.
So the present study showed the hypoglycaemic
effect of the alcoholic extract of the unripe fruit
of M. charantia in the dose ranging from 0.5 gm
/ Kg to 1.5 gm / Kg body weight of diabetic
rabbits given orally. The hypoglycemic effect
was comparable to that of the standard antidiabetic drug Metformin in the dose of 62.5 mg /
Kg body weight of rabbits. The broad dose range
of hypoglycemic effect of M. charantia may be
an interesting finding which may prove it safer in
comparison to the established hypoglycemic
drugs.

study where blood sugar levels were recorded


daily for 5 weeks. The study showed
hypoglycemic effect of the extract in the oral
dose range of 0.5 to 1.5 gm / kg body weight of
rabbits. The hypoglycemic effect was
comparable to that of established anti-diabetic
drug Metformin in the dose of 62.5 mg / Kg. The
broad dose range of the extract producing a
hypoglycaemic effect in diabetic rabbit was an
interesting observation, we believe that extract of
M-Charantia has the potential to be used as an
adjuvant in the treatment of Diabetes but which
requires further study.
ACKNOWLEDGMENTS: we are grateful to
Santhiram Medical College management and
department staff for their cooperation throughout
this study.
REFERENCES
1

CONCLUSION

M. charantia or Karela was taken traditionally


for control of diabetics in India and in other
countries for long time. Three doses of alcoholic
extract of the powder of unripe fruit of M.
charantia were taken to study the hypoglycemic
effect of in 5 groups of alloxan-induced diabetic
in Rabbits. It was a placebo-controlled open

Ying ZD, Xiwen Q, Fengjie C, Qin G,


Xinghua Z, Yun Wang. Effect of Superfine
Grinding on Antidiabetic Activity of Bitter
Melon Powder. Int. J. Mol. Sci. 2012;13,
14203-18
Yi Zhang and Zhiyu Xiong Satosker RS.
Pharmacology & Pharmacotherapeutics. 19th
Edition, 2005, Pub. Popular Prakashan Pg,
886-93
Walters and Deeker,Indian herbal drug
development-problems, prospects. Pharma
times. 1988;34:13-14
Khanna P. Jain SC, Panagariya A and Dixit
VP. Hypoglycemic activity of Polypeptide P
from Plant source. J.Nat. Prod.1981;44(6) :
648-55
Sharma VN. Sogani RK. Some observations
on Hypoglycemic activity of Momordica
charantia. IJMR 48:471-77, 1960.
Lodikar MM and Rajaramarao MR. Note on
Hypoglycemic principle isolated from
Momordica charantia Linn. Indian Journal of
Pharmacology.1966:28(5) : 129-133
Bell BT-experimental production of diabetes
in
animals
with
alloxan.
Diabetes
times.1986;74:11-18
141

Yakaiah et al.,

Int J Med Res Health Sciences. 2013;2(2):137-142

8
9

10

11

12

13

14

Okey and Ojiako. http:www.endenlabs.org/


extraction methods.html.
Aisle Semiz. Various extraction procedures.
African journal of Biotechnology.2007: 6(3).
273-77
Vogal. Drug discovery & Evaluation
Pharmacological Assays. 2nd Edition 2002.
Pub.. Springer. Medical Publishers, Page
948-50.
Akthar AK. Effect of Momordica Charantia
on blood sugar level of Normal and Alloxan
rabbits. Planta Medica. 1981;42;205-212.
Butt TA. The hypoglycemic response to
glucagon in Normal, Alloxan Diabetic
rabbits. University of Karachi, JPPPakistan.1962.15:1-6
Vijaya. Drug Interaction of Naphroxen with
Tolbutamide.
Journal
of
Pharma.sci.
1987;42:51-52
Desai J. Somani R, Jain K. Anti-diabetic
effect of karela in mice. Indian Journal of
Pharmacology. 2006, S66; 44-47.

142
Yakaiah et al.,

Int J Med Res Health Sciences. 2013;2(2):137-142

DOI: 10.5958/j.2319-5886.2.2.016

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 18 Jan 2013


Research article

Coden: IJMRHS
th

Revised: 20 Feb 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 28 Feb 2013

THE EFFECT OF VERAPAMIL AND DILTIAZEM ON CARDIAC STIMULANT EFFECT OF


ADRENALINE AND CALCIUM CHLORIDE ON ISOLATED FROG HEART
Lakhavat Sudhakar1, Naveen Kumar T2, Tadvi NA3, Venkata Rao Y4
1

Non Medical Assistant, Kakatiya Medical College, Warangal, Andhra Pradesh, India
Associate Professor, Department Pharmacology, Apollo Medical College, Hyderabad, A.P, India
3
Associate Professor, 4Professor and Head, Department Pharmacology, Kamineni Institute of Medical
Sciences, Narketpally, Andhra Pradesh, India
2

*Corresponding author email: doctornaveen1@rediffmail.com


ABSTRACT

Background: Calcium channel blockers block voltage dependent L-type of calcium channel and thus
reduce the frequency of opening of these channels in response to depolarization. The result is a marked
decrease in transmembrane calcium current associated with long lasting relaxation of vascular smooth
muscle, reduction in contractility in cardiac muscle, decrease in pacemaker activity in the SA node and
decrease in conduction velocity in the AV node. Among Calcium channel blockers verapamil, is cardio
selective, nifedipine is vascular smooth muscle selective, while diltiazem exhibits intermediate
selectivity. Methods: In the present study, the effect of two Ca++ channel blocker, Verapamil and
Diltiazem were compared on the isolated frog heart by using adrenaline & calcium chloride as standard
on frog heart contractility. Results and conclusion: Adrenaline and calcium chloride increased the
amplitude of contraction
of isolated perfused frog heart. The L- type of Ca2+ channel blockers
verapamil and diltiazem produced dose dependent (2g, 4g, 8g, and 16g) reduction in the amplitude
of contraction produced by calcium chloride in isolated perfused frog heart. There was no statistical
significant difference (p > 0.05) between the inhibitory effect of diltiazem and verapamil on calcium
chloride induced contraction of isolated frog heart.
Keywords : Verapamil , Diltiazem,Cardiac stimulant effect, Adrenaline, Cacl2
INTRODUCTION

The incidence of ischemic heart diseases is high


all over the world especially in urban
population1. Risk factors are age, male sex,
hyperlipidemia, smoking, hypertension, diabetes
and family history2. Calcium channel blockers
are used for treatment of heart diseases which

include angina, hypertension & arrhythmia 3.


Among Calcium channel blockers verapamil, is
cardio selective (HR, contractility,& conduction
velocity), nifedipine is vascular smooth muscle
selective, while diltiazem exhibits intermediate
selectivity.4 so this study was planned to
143

Sudhakar et al.,

Int J Med Res Health Sci. 2013;2(2):143-146

compare the cardiac depressant effect of the two


calcium channel blockers verapmil and
diltiazem.
Aims and Objectives The aim of the present
study was to compare cardiac depressant effects
of two L-type of calcium channel blockers,
verapamil & diltiazem in Calcium chlorideinduced inotropic effect on isolated frog (Rana
tigrina) heart preparation.
MATERIAL AND METHODS

The study was conducted in the Amphibian


Laboratory in the department of Pharmacology,
Kamineni Institute of Medical Sciences,
Narketpally during the period from 13/10/2009
to 12/04/2011.5 Frogs (Rana tigrina) 12 in
numbers, weighing about 150 250g, reared in
the Central animal house of the Kamineni
Institute of Medical Sciences (KIMS) were used.
The present study was approved by Institutional
Animal Ethcs Commeette.
Double pithed frog was fastened over the frog
board and the heart was removed and mounted
using standard procedures described by Ramesh
KV et al5 The Normal contraction of the heart
was recorded for 3 minutes by using frog ringer
solution. Adrenaline 2g was added into the
vertical limb of the Symes cannula and response
was recorded to test the sensitivity of the tissue.
Calcium chloride 2 mg was added to symes
cannula and increase in responses were recorded.
Then 2 g verapamil was added to the Symes

cannula and the contraction of the heart was


recorded and the difference from normal
contraction (inhibition in height of contraction)
was recorded. The procedure was repeated by
adding calcium channel blocker verapamil in the
dose of 4, 8, 12, and 16 g respectively. The
procedure was repeated in six frog hearts. The
above procedure was repeated with diltiazem in
the same dose (2, 4, 8, 12, and 16 g)
respectively.
Calcium chloride solution (standard) 2 mg was
added each time in to ringer solution because
calcium channel blockers verapamil & diltiazem
act on calcium chloride induced heart
contraction.6
Drugs used in the experiment:
a) Diltiazem 5mg/ml vial ( Dilgard cipla)
b) Verapamil 5mg/2ml amp (Samarth life
science pvt. Ltd.)
c) Adrenaline 1mg/ml amp (Neon laboratories
pvt. Ltd.)
d) Calcium chloride (1%) 10mg/ml (Accord
labs)
RESULTS
The effect of diltiazem (2g, 4g, 8g, 16g)
pretreatment on calcium chloride induced
increase in the amplitude of contractions was
also calculated. Diltiazem pretreatment reduced
the CaCl2 produced increase in amplitude of
contraction in dose dependent quantity, i.e 2g,
4g, 8g, 16g.

Fig.1: Inhibitory effect of Diltiazem.

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Sudhakar et al.,

Int J Med Res Health Sci. 2013;2(2):143-146

Adrenaline (2g) was added to the biophase to


conform the normal functioning of heart as
adrenaline is a standard drug which increases the
contraction of heart. Subsequently 2 mg of
calcium chloride was added to the biophase and
the increase in contraction of heart compared to
the normal contraction was recorded.
Verapamil pretreatment reduced the CaCl2
produced an increase in amplitude of contraction
in dose dependent quantity, i.e. 2g, 4g, 8g,
16g.

Pre-treatment with diltiazem and Verapamil in


the above quantities had not modified the
adrenaline induced increase in amplitude of
contractions suggesting more doses of Verapamil
and diltiazem pre-treatment for blocking the
adrenaline response or probably L type of
Calcium channels may not be involved in
adrenaline response in isolated perfused frog
heart.

Fig.2: Inhibitory Effect of Verapamil


Table 1: Comparison of antagonist effect of diltiazem versus verapamil
Sr.No

Dose

Diltiazem Height of Verapamil Height of t value

p value

(g)

contraction (mm)

contraction (mm)

30.832.37

24.002.76

1.87

0.09

29.162.30

23.333.38

1.42

0.18

27.332.40

20.503.17

1.71

0.11

16

23.164.05

20.833.02

0.461

0.65

*Data presented as mean SD


Comparison of antagonism of CaCl2 produced an increase in amplitude of contraction by diltiazem and
Verapamil showed no statistical significance (P>0.05) by applying student unpairedttest
DISCUSSION

Adrenaline
(2g)
and
CaCl2
(2mg)
administration through the Symes cannula in the
biophase produced an increase in amplitude of
contraction of isolated perfused frog heart
preparations. Pre-treatment with the known Ltype Ca++ channel blockers diltiazem and
verapamil reduced the CaCl2 responses in dose

dependent quantity. Both diltiazem and


verapamil in the doses of 16g completely
blocked CaCl2 induced increase in the amplitude
of contractions.
Comparison of antagonism of CaCl2 produced an
increase in amplitude of contraction by Diltiazem
145

Sudhakar et al.,

Int J Med Res Health Sci. 2013;2(2):143-146

and Verapamil showed no statistical significance


(P>0.05) by applying student unpaired t test.
SUMMARY AND CONCLUSION

6. Ghosh MN, Fundamentals of Experimental


Pharmacology, Hilton and Company , 3rd
ed.2009.Pg26

Adrenaline and calcium chloride increased the


amplitude of contraction of isolated perfused
frog heart. The L- type Ca++ channel blockers
verapamil and diltiazem produced dose
dependent (2g, 4g, 8g, and 16g) reduction
in the calcium chloride produced increase in
amplitude of contraction of isolated perfused
frog heart. There was no statistical significant
difference (p > 0.05) between the inhibitory
effect of Diltiazem and Verapamil on CaCl2
induced contraction on isolated frog heart.
Further studies are needed to explore the role of
calcium channels in the adrenaline induced
positive inotropic effect (increase in amplitude of
contraction)
REFERENCES

1. Fuster V, Kelly BB, editors. Promoting


Cardiovascular Health in the Developing
World: A Critical Challenge to Achieve
Global Health. Washington (DC): National
Academies Press (US); 2010;2:
2. Gupta R, Guptha S, Gupta VP, Agrawal A,
Gaur K, Deedwania PC. Twenty-year trends
in cardiovascular risk factors in India and
influence of educational status. Eur J Prev
Cardiol. 2012;19(6):1258-71
3. Sharma HL,KK. Drugs Therapy of
Hypertension, Angina Pectoris, Arrythmias.
In Principles of Pharmacology by 2011, 3rd
Ed; pg:279- 307
4. Sharma HL,KK. Drugs Therapy of Angina
Pectoris . In Principles of Pharmacology by
2011, 3rd Ed; pg:284.
5. Ramesh KV, Ashok S, Mukta NC. Practical
Pharmacology; 1st ed. Himachal Pradesh:
Arya Publishing Company; 2008. Pg 89.

146
Sudhakar et al.,

Int J Med Res Health Sci. 2013;2(2):143-146

DOI: 10.5958/j.2319-5886.2.2.018

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
Volume 2 Issue 2 April - June Coden: IJMRHS Copyright @2013 ISSN: 2319-5886
st
Received: 21 Jan 2013
Revised: 20th Feb 2013
Accepted: 27th Feb 2013
Research article
AN AUDIT OF INDICATIONS AND COMPLICATIONS ASSOCIATED WITH ELECTIVE
HYSTERECTOMY AT SVMCH AND RC, ARIYUR, PONDICHERRY
*Nidhi Bansal1, Hiremath PB2, Meenal C3, Vishnu Prasad4
1

Assistant Professor, 2Associate Professor, 3Professor, 4CRRI, Dept. of OBG SVMCH & RC
Ariyur,India

*Corresponding author email: drnidhibansal@gmail.com


ABSTRACT
Background: Hysterectomy is the most common gynaecological surgery performed worldwide
Menorrhagia secondary to uterine fibroids and abnormal menstrual bleeding are the two most common
indications for hysterectomy. An important factor impacting on the incidence of complications of
hysterectomy, apart from the indication for surgery, is the surgical approach. Majority of the
hysterectomies are performed by the abdominal route. The incidence of LAVH performed for benign
lesions has progressively increased in recent years. Methods : Surgical indications and details,
histological findings, and postoperative course were reviewed and analysed for 340 patients who
underwent hysterectomy in 2011 and 2012.Results : In our study, fibroid uterus (27.9 %) was the
leading indication for performing hysterectomies followed by a Dysfuctional uterine bleeding (DUB)
22.9% and uterovaginal prolapse (UVP) 21.8%. During the study period (2011-2012), most
hysterectomies were performed abdominally (54.4%). Overall post operative complications including
major and minor, are significantly higher in the abdominal surgery group as compared to the vaginal and
laparoscopic group ( p value= 0.001). Conclusion: We need to ensure that trainees acquire competency
in performing hysterectomies vaginally, which is clearly safer than the abdominal approach.
Keywords: Hysterectomy indications, LAVH, TAH, Intraoperative, Postoperative complications
INTRODUCTION

Hysterectomy is the most common gynecological


surgery performed worldwide. After caesarian
delivery, hysterectomy is the major surgical
procedure most frequently performed in women1,
2
. With increasing advancement in technology
and acquisition of better skills and experience the
abdominal route is fast being replaced by vaginal
and laparoscopic for majority of indications as
many of the surgeons now consider that descent

of the cervix and not the uterine size predicts the


success of the vaginal route of hysterectomy.
Over the past 2 years various hysterectomies
were performed in our hospital through different
routes for a variety of indications.
More than half of the hysterectomies are carried
out due to abnormal uterine bleeding, which is
associated with a wide range of diagnoses that
include
uterine
fibroids,
endometriosis,
147

Nidhi Bansal et al.,

Int J Med Res Health Sci.2013;2(2):147-155

adenomyosis and dysfunctional uterine bleeding


(DUB). Menorrhagia secondary to uterine
fibroids and abnormal menstrual bleeding are the
two most common indications for hysterectomy.
An important factor impacting on the incidence
of complications of hysterectomy, apart from the
indication for surgery, is the surgical approach.
The type of hysterectomy depends on the
disorder be treated, the size of the uterus, and the
skills and preference of the surgeon. The
abdominal approach is indicated in most cases of
uterine cancer, in cases of emergency
hysterectomy, and in patients with large fibroids.
Laparoscopic assisted vaginal hysterectomy
(LAVH) and Vaginal hysterectomy (VH) is
clinically and economically comparable with
Total abdominal hysterectomy (TAH), with
patients' benefits of less estimated blood loss,
less analgesia use, less intra- and postoperative
complication rates, less postoperative pain, rapid
patient
recovery
and
shorter
hospital
3
stay .Studies have reported fewer unspecified
infections or febrile episodes in the vaginal group
versus the abdominal group4. The number of
doses of injectable analgesics used per patient
was significantly more in the TAH group in
comparison
to
LAVH
group.
Overall
complication was 14% in LAVH and 10% in
TAH though the differences were not
significant5.
In LAVH, greater total uterine weight and
morcellation are associated with longer operative
times. Blood loss correlates with uterine weight
when vaginal morcellation is also used. An
increase in the operative time and a higher blood
loss can be expected as the uterine weight
increases and can be predicted taking
morcellation methods into account6.
Assessing surgical approaches according to the
type and severity of complications identifies the
risk factors most strongly associated with each
approach. Further, by giving rise to technical
improvement, such assessment will result in safer
patient treatment.

MATERIALS AND METHODS

Surgical indications and details, histological


findings, and postoperative course were reviewed
and analysed for 340 patients who underwent
hysterectomy in 2011 and 2012 at SVMCH &
RC, Ariyur, Pondicherry. Institutional Research,
Science and Ethical committee approval was
obtained and informed consent was taken from
each patient prior to surgery.
The patients are admitted 2-3 days before surgery
and a complete work up of the case is done. Co
morbid medical conditions like diabetes,
hypertension, heart disease, thyroid disease if
any, are looked into and cardiologist or
physicians opinion is sought for the same.
Patients with Hb<10 gm% are transfused with
blood according to their Hb values. Preoperative
fitness for each patient is obtained from the
anaesthetist prior to posting the case. Depending
on the indication and route of surgery being
performed preoperative preparation is done.
Routinely pre op IV antibiotics like cefotaxime
are given to all patients half an hour before the
surgery. 1 unit of blood is reserved for each
patient on the day of surgery.
Foleys catheterization is done for all the patients
undergoing TAH preoperatively and immediately
following surgery in case of LAVH, VH and
NDVH. Vaginal pack (Roller gauze with
betadine) is routinely kept in all cases of
LAVH/VH/NDVH for 24 hrs. Romovac drain is
considered in those patients in whom intra
operative oozing is noticed.
In the postoperative period all patients are kept
for observation and monitoring in the surgical
ICU. Post operative Hb and PCV is routinely
done the following day morning and patients
with Hb<7 and PCV<21 are given a blood
transfusion and routine IV antibiotics
(Cefotaxime and Metronidazole) are continued
for 48 hours followed by oral antibiotics for 5
days. Metronidazole is discontinued for patients
who have nausea & vomiting as side effects of
the drug. Inj.Gentamycin is added in indicated
cases of VH with meshplasty, diabetic patients,
cardiac or infected cases. Foleys catheter is kept
148

Nidhi Bansal et al.,

Int J Med Res Health Sci.2013;2(2):147-155

for 24 hrs routinely for abdominal hysterectomy


and 48hrs for VH/LAVH/NDVH and extended
bladder drainage is considered in patients who
had required difficult bladder dissection during
surgery. Romovac drain is removed when the
drain output is < 25ml.
Patients with abdominal hysterectomy are
discharged on the 7th or 8th day after suture
removal, while NDVH/VH/LAVH patients are
discharged on the 4th postoperative day. All
patients are advised to review after 6 weeks or
earlier in the event of any unforeseen
complications.
Histopathology reports are routinely reviewed at
6 weeks. However, in patients whom malignancy
is suspected the same is reviewed after 2 weeks.
RESULTS

Statistical analysis of the data was done by using


SPSS version 17. Considering the age wise
distribution pattern of patients who underwent
hysterectomy the majority of women were in the
age group of 40 -49 years (193). However, the
second leading age group was that of young
women 30-39 years (68). The younger women
hysterectomised were about 30 years of age, for
varied indications like fibroid uterus or
adenomyosis. The overall mean age was 46.9
years. Considering the varied pre operative
diagnosis for hysterectomy, the highest mean age

was 57.8 years in cases of genital malignancies


followed by 55.7 years in cases of UVP, whereas
the lowest was 40.7 years in cases of pre
malignant conditions and Adenomyosis .
Preoperative diagnosis showed in Table 1. In our
study, fibroid uterus (27.9 %) was the leading
indication for performing hysterectomies
followed by a DUB (22.9%) and uterovaginal
prolapse (UVP-21.8%)
During the study period (2011-2012), most
hysterectomies were performed abdominally
(54.4%), an approach that is associated with
higher incidence of complications. However, in
2012, the percentage of hysterectomies done
abdominally reduced to 26.8 %( 40/149).On the
contrary, 73.2% of hysterectomies were
performed vaginally (LAVH 61/149, NDVH
10/149, VH 38/149) [Table II, Figure I]
On analysis of 185 patients, who underwent
hysterectomy by an abdominal approach over a
period of 2 years, 5 were for malignant( cervical,
endometrial, ovarian), 29 were for suspected
large adnexal masses and 40 for large fibroid
uterus
(uterine size > 20weeks). Remaining
111 abdominal hysterectomies were done for
benign indications like DUB, fibroid uterus or
Adenomyosis, which could have been considered
for LAVH or NDVH. This is explained by lack
of laparoscopy expertise at our centre during the
early part of our study period.

Table. 1: Preoperative diagnosis


S.No
Diagnosis
No of patients
Dysfunctional uterine bleeding
78
1.
Fibroid uterus
95
2.
Adenomyosis
33
3.
Utero vaginal prolapse
74
4.
Adnexal mass
29
5.
Chronic cervicitis
8
6.
Pre malignant conditions
8
7.
Genital malignancy
5
8.
Post menopausal bleeding
10
9.
Total
340
The route of hysterectomies was performed showed in the Table 2.

Percentage (%)
22.9%
27.9%
9.7%
21.8%
8.5%
2.4%
2.4%
1.5%
2.9%
100%

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Int J Med Res Health Sci.2013;2(2):147-155

Table. 2 : Route of surgery


S.No Route
No of patients 2011 (%)

No of patients 2012 (%)

Total (%)

1.
2.
3.
4.
5.
6.
7.

142(74.3%)
38(19.9%)
Nil
8(4.2%)
2(1.0%)
1(0.5%)
Nil

35(23.5%)
38(25.5%)
10(6.7%)
61(40.9%)
2(1.3%)
Nil
3(2.0%)

177(52.1%)
76(22.4%)
10(2.9%)
69(20.3%)
4(1.2%)
1(0.3%)
3(0.9%)

191

149

340

TAH
VH
NDVH
LAVH
Wertheims
Subtotal
Staging
laparotomy

Total

Fig 1 : Trend of hysterectomies in 2011 & 2012

No pathology

Fibroid

Adenomyosis

Benign
Ovarian
Tumor
Chronic
cervicitis / SIL

EH

Ca Ovary

Ca uterus

Ca cervix

Endometriosis

Total

43.8

40

15

14

78

Fibroid

41.2

75

15

95

Adenomyosis
Prolapse

40.7
55.7

6
70

5
2

22
-

33
74

Adnexal mass

47.7

24

29

Chronic cervicitis
Premalignant
conditions
Genital Malignancy

45.2
40.7

8
1

8
8

57.8

PMB

49.6

10

Total

46.9

125

89

56

25

26

340

Indication

Mean age

Table.3: Correlation of age, Preoperative & Histopathological Diagnosis

DUB

Dysfunctional uterine bleeding, Post menopausal bleeding, Endometrial Hyperplasia

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Int J Med Res Health Sci.2013;2(2):147-155

An analysis of Histopathological reports, 125 out


of 340 women (36.8%), revealed no significant
pathology. Out of these women, a majority of the
70 women (56%) underwent hysterectomy for
UVP, while in 40 women (32%); the indication
for surgery was DUB. In the remaining 15
patients, the indications were fibroid uterus,
Adenomyosis or postmenopausal bleeding
(PMB) [Table 3 ]
Out of 78 women hysterectomised for DUB, a
majority of the 40 women (51.3%) had no
pathology in the uterus, while 15 (19.2%) had
Adenomyosis, 14 had endometrial hyperplasia
(EH-17.9%) and 7 patients (9%) were diagnosed
with fibroid uterus. One patient with a
preoperative diagnosis of DUB, aged 52 years
was diagnosed as having endometrial cancer on
HPR (Not diagnosed on Fractional curettage).
One case of DUB surprisingly showed HPR of
Degenerated products of conception.
95 women (27.9%) in our study underwent
hysterectomy for fibroid uterus, out of which a
majority
of
75
women
(79%)
had
histopathologically proven fibroids.
In the remaining 20 patients, 15 had
Adenomyosis, while 5 patients had normal uteri
with no definitive pathology. 14 other patients

with incidental findings of leiomyoma on HPR


were operated for varied indications like DUB,
Adenomyosis or prolapse uterus.
In the 74 women with UVP, who underwent VH,
majority of 70 women had no pathology on HPR.
Operated 33 cases with a preoperative diagnosis
of Adenomyosis of which only 22 had proven
Adenomyosis on HPR. Total number of HPR
showing Adenomyosis was 56 in our study, out
of which, in 34 patients, the preoperative
diagnosis was not Adenomyosis. This indicates
that the true incidence of Adenomyosis is higher
compared to clinical or sonological diagnosis.
We operated 29 cases of adnexal masses, out of
which 24 were benign tumours, while 2 were
malignant.
In our study, 5 bladder injuries (1.4%) were
noted over a period of 2 years, out of which 2
were in TAH (1.1%) & VH (2.6%) each and 1
was seen in LAVH (1.4%). All were identified
on the table and bladder repair was done. In
addition 3 ureteric injuries were noted, all in the
abdominal hysterectomy group for large adnexal
mass, carcinoma cervix and carcinoma ovary
respectively. These injuries were identified post
operatively. The difference was however not
significant statistically ( p value= 0.84) [Table 4]

Table.4: Intraoperative complications


Hysterectomy
TAH/Subtotal
1.
2.
3.
4.
LAVH
1.
2.
VH/NDVH
1.
2.
Wertheims
1.
Staging Lap
1.
2.
Total No. of
complications

Diagnosis

Haemorrhage
with transfusion

Bladder Bowel
Injury
Injury

Ureteric
Injury

Total
4 / 178

DUB
Chr cervicitis
Adenomyosis
Adnexal mass

Yes
-

Yes
Yes
-

Yes
2/69

Adenomyosis
Fibroid uterus

Yes

Yes
-

UVP
UVP

Yes
Yes

Ca Cervix

Yes

Yes

Ca Ovary
Ca Ovary

Yes

2/86

2/3

Nil

Yes
3

11/340
(3.2%)
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Int J Med Res Health Sci.2013;2(2):147-155

patients in the vaginal group (LAVH, NDVH,


and VH) had significant post operative fever
[Table 5].

Considering the immediate postoperative


complications, pyrexia was noticed in 14.1% of
patients with TAH. On the contrary, 3.2% of
Table 5: Immediate postoperative complications

Approach to hysterectomy

Complication

Pyrexia
Haemorrhage

TAH

LAVH

VH/NDVH

25
3

3
Nil

Wound sepsis
9
Nil
Nil
Pain
12
1
Nil
Urinary complaints
8
Nil
3
Second laparotomy
2
Nil
Nil
Pulmonary
Nil
Nil
Nil
Embolism
Death
Nil
Nil
Nil
Resuturing
5
Nil
Nil
Vault exploration
3
Nil
1
Total no of pts. With 67
4
10
complication
(37.8%) (5.8%) (11.6%)
Immediate postoperative complications like
haemorrhage, wound sepsis, pain, urinary
complaints were noticed in 20.1% of patients
with abdominal surgery as compared to 5.2% of
patients in the laparoscopic and vaginal group.
Relaparotomy was done in 2 cases of abdominal
hysterectomy and 5 cases were taken for wound
resuturing. No such complications were noticed
in the vaginal group.
Vault exploration had to be done for 4 patients
out of which 3 were following abdominal
hysterectomies.

Wertheims Staging
laparotomy
Nil
Nil
Nil
1
1
1
1
Nil
Nil

1
Nil
Nil
Nil
Nil

No
complications
30
8
11
14
12
2
0

Nil
Nil
0
Nil
Nil
5
4
Nil
Nil
3
2
86/340
(75%)
(66.6%)
(25.3%)
An analysis of major complications in
hysterectomised patients from the time of
discharge up to 6 weeks post op, 1 patient with
abdominal surgery had Deep vein thrombosis, 4
patients had vesico vaginal fistula (2%) and 1
patient had uretero vaginal fistula (0.5%). On the
contrary, only 1 patient of vaginal hysterectomy
had a vault granuloma on 6 weeks follow up. No
patients in the LAVH or NDVH group had any
of the above complications on follow up.
However the difference in the rates of fistula
formation in abdominal vs. vaginal route is not
statistically significant (p value =0. 12) [Table 6]
Table.6: Complications from discharge upto 6 weeks post surgery

Complication
Pain
Poor wound healing
Vault prolapse
Deep vein thrombosis
Vesico vaginal fistula
Uretero vaginal fistula
Vault granuloma
Total no of patients

No. of occurrences
15(TAH) + 2(LAVH)
5(TAH)
1(TAH)
1(TAH)
4(TAH)
1(TAH)
1(VH)
30/340 (8.8%)

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Int J Med Res Health Sci.2013;2(2):147-155

Overall post operative complications including


major and minor, are significantly higher in the
abdominal surgery group as compared to the
vaginal and laparoscopic group ( pvalue= 0.001 )
In our series, the incidence of carcinoma ovary
and carcinoma cervix was 1.17% each whereas
carcinoma endometrium and endometriosis were
least i.e. 0.29% each.
In pre malignant conditions, one case was
cervical dysplasia, 26 were endometrial
hyperplasia, out of which two showed
hyperplasia with atypia.
DISCUSSION

Hysterectomy is the major surgical procedure


most frequently performed in women, after
caesarian delivery.1, 2 In our series, 20% of
hysterectomies were done in the age group of 3039 years. An Indian study in 2010 showed that
33% of hysterectomies were performed in
women less than 35 years of age7. These
numbers could have been further reduced by
using alternative therapeutic options like
levonorgestrel-releasing intrauterine system,
endometrial ablation or fibroid embolisation.
Kripalani et al found that Ormeloxifene was an
effective and a safe therapeutic option for the
medical management of menorrhagia8 . This
would further decrease the number of
hysterectomies for DUB. These figures stress
upon the need for encouraging the treatment of
benign conditions conservatively and offering
hysterectomies more often to women with
defined pathologies in the perimenopausal or
menopausal age group.
Fibroid uterus (27.9%) was the most common
indication for hysterectomy, followed by DUB
and UVP. A Nigerian tertiary hospital
retrospective study showed that uterine fibroid
was the leading indication in 38.7% of patients9.
We do not have the data to analyze the
percentage of women with fibroids who were
symptomatic to justify hysterectomy as the only
treatment modality in our study group. Few
hysterectomies were performed for genital
malignancies at our centre over the study period

of two years.This is due to the non availability of


the onco-surgeons. We deny hysterectomy for
chronic cervicitis, hence the incidence is low at
2.4%.
Most surgeons perform up to 80% of procedures
by the abdominal route 10 . The incidence of
LAVH performed for benign lesions has
progressively increased in recent years11. During
our study period, 54.4% of surgeries were
performed abdominally. However, in the later
part of the study, this was reduced to 26.8%, in
favour of 73.2% of hysterectomies that were
performed vaginally. This is explained by lack of
laparoscopy expertise at our centre during the
early part of our study period .This also indicates
a favourable trend towards adopting a vaginal
approach for hysterectomy in contrast to
abdominal approach at our institute.
The high incidence of abdominal hysterectomies
can in part be explained by personal preference,
but is mainly due to lack of training and
experience leading to reluctance to perform VH
in nulliparous women in the presence of uterine
enlargement or in women with previous pelvic
surgery or previous caesarean section. The above
factors
should
not
be
considered
contraindications to VH, and there are
publications that support this view 12, 13. The
rationale for LH is to convert an abdominal
hysterectomy (AH) into a laparoscopic/vaginal
procedure and thereby reduce trauma and
morbidity10.
Urinary tract injuries are reported in
approximately 1 percent of women who undergo
pelvic surgery14 . Studies have reported that the
rate of injuries varies by indication and
procedure, being highest following radical
hysterectomy for cervical cancer (1 in 87; 95%
CI 61-128) and lowest following vaginal
hysterectomy for prolapse (1 in 3861; 95% CI
2550-6161).
After total abdominal hysterectomy, risk was
lower after hysterectomy for benign conditions15.
In our series, 2.4% of women had urinary tract
injuries (5 bladder injuries, 3 ureteric injuries).
On analysis of these, we noted that amongst the
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Int J Med Res Health Sci.2013;2(2):147-155

bladder injuries, 2 were in TAH(1.1%), 2 in


VH(2.6%) and 1 in LAVH(1.4%).In a study by
Babak Vakili et al, there were 8 cases of ureteral
injury (1.7%) and 17cases of bladder injury
(3.6%) There was no dierence in the rate of
bladder injury among TAH, TVH, and LH (2.5%
vs. 6.3% vs. 2.0%, respectively; P = .123),
although there was a trend toward a higher
incidence of bladder injury with vaginal
hysterectomy16.A similar trend was observed in
our study.
Vakili et al have also reported, that abdominal
hysterectomy was associated with a higher
incidence of ureteral injury as compared to VH
or LH (2.2% vs. 1.2% vs. 0%) but this was not
significant.Vakili et al have concluded that
surgery for prolapse or incontinence increases
the risk of urinary tract injuries. Thus routine use
of cystoscopy during hysterectomy should be
considered16.However, this is difficult to accept
in routine gynaecology practice.
On analysis of surgical fistulas, 4 patients had
VVF (2%) and 1 patient had uretero vaginal
fistula (0.5%).All fistulas were noted in
abdominal surgeries and all patients presented
with urinary leak 10-14 days post surgery.
Surprisingly, all of them were seen in surgeries
performed in a particular unit. The contribution
of surgical fistulas to the total fistula prevalence
in developing countries is small, however it is
often supposed that this complication results
from direct injury to the lower urinary tract at the
time of operation but this is certainly not always
the result of careless, hurried, or rough surgical
technique. In a study on Vesico-vaginal fistulas
in developing countries, of the 165 urogenital
fistulas over the last 12 years, 117 were
associated with pelvic surgery, and 91 followed
hysterectomies; of these only 4% presented with
leakage of urine on the first day post operatively.
In the other cases it was presumed that tissue
devascularization during dissection, inadvertent
suture placement, or pelvic hematoma formation
or infection developing postoperatively resulted
in tissue necrosis with leakage usually
developing 514 days later. Over distension of

the bladder postoperatively may be an additional


factor in many of these latter cases .It is likely
that patients with a habit of infrequent voiding,
or those with inefficient detrusor contractility,
may be at increased risk of postoperative urinary
retention; if this is not recognized early and
managed appropriately, the risk of fistula
formation may be increased. The use of
prophylactic catheterization in the first 2448 h
might be expected to reduce the risk of postoperative fistula formation, but this has never
been proven17.
CONCLUSION

Hysterectomy is a major gynecologic operation


and more cases of hysterectomy should be
performed vaginally, considering the numerous
benefits it has over the abdominal route. We need
to ensure that trainees acquire competency in
performing hysterectomies vaginally, which is
clearly safer than the abdominal approach.
The prophylactic use of antibiotics to reduce
infection and fever, the adequacy of analgesic
regimens, and the correct dosage of prophylactic
heparin treatment are some of the other issues
that should be audited to reduce post operative
complications. Ideally, we should be able to
provide more medical options, such as the
levonorgestrel intrauterine system, whenever
appropriate, and to have available the equipment
and collective skill necessary to provide any
patient with the most appropriate surgical
treatment.
Because, few studies have recently been
conducted regarding the indications for and
complications of elective hysterectomies, the
present study may provide a basis for a future
audit of our gynaecological practice and for the
comparison of our practice with others.
ACKNOWLEDGEMENT
We would like to extend our sincere gratitude to all
our patients who were a part of this study.

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Int J Med Res Health Sci.2013;2(2):147-155

REFERENCES

1. Leung PL, Tsang SW, Yeun PM. An audit on


hysterectomy for benign diseases in public
hospitals in Hong Kong. Hong Kong Med J
2007; 13(3):187-93.
2. ChongsomchaiC,Lumbiganon
P,
Think
Hamrop J, Ounchai J,Vudhikamraksa N.
Placebo-controlled, double-blind,randomized
study of prophylactic antibiotics in elective
abdominal hysterectomy. J Hosp Infect
2002;52(4):302-06.
3. Jahan S et al. A comparative study among
laparoscopicallyassisted
vaginal
hysterectomy, vaginal hysterectomy and
abdominal hysterectomy: Experience in a
tertiary care hospital in Bangladesh. Journal
of Obstetrics & Gynaecology. 2011;31(3) :
254-57.
4. Johnson N,Barlow D, Lethaby A, Tavender
E, Curr E, Gary R. Surgical approach to
hysterectomy for benign gynaecological
disease.Cochrane Database Syst Rev.
2006;CD003677
5. Agarwal L, Agarwal K, Agrawal V, Sharma
M. A case control study to compare
laparoscopically
assisted
vaginal
hysterectomy
and
total
abdominal
hysterectomy. Int J Med Sci Public Health.
2012;1(2): 93-96
6. Li-yun chou et al. Operating time and blood
loss during laparoscopic-assisted vaginal
hysterectomy with in situ morcellation. Acta
Obstetricia et Gynecologica Scandinavica.
2011; 90(9) : 98589
7. Desai S, Sinha T, Mahal A. Prevalence of
hysterectomy among rural and urban women
with and without health insurance in Gujarat,
India. Reprod Health Matters. 2011;
19(37):42-51
8. Kriplani A, Kulshrestha V, Agarwal N. The
efficacy and safety of ormeloxifene in the
management of menorrhagia: a pilot study.
J.Obstet. Gynaecol 2009;35 (4): 74652.
9. Onyecherellem Ogelle, Charles Okafor,
Ahizechukwu C. Eke, Nworah Obiechina,

Sunday Mbamara. Journal of Gynecologic


Surgery. 2010, 26(1): 7-13.
10. Andreas Chrysostomou. Implications of
performing laparoscopic assisted vaginal
hysterectomy versus abdominal hysterectomy
on suitable patients in a South African
hospital setting. SAJOG ; Aug 2008;14(2)
:70-74.
11. Zahra Asgar, Foroogh Bahreini, Haydeh
Samiee, Bita Eslami, Afsaneh Tehranian
Somayeh
Sabet.
Comparison
of
laparoscopically
assisted
vaginal
hysterectomy
and
total
abdominal
hysterectomy. Medical Journal of the Islamic
Republic of Iran. May 2008;22(1): 22-28
12. Raymond CD, Howard T, Stephan C.
Challenging generally accepted contra
indications to vaginal hysterectomy. A
technique for vaginal hysterectomy. Am J
Obstet Gynecol. 2001; 184:1386-91.
13. Porges RF. Changing indications for vaginal
hysterectomy. Am J Obstet Gynecol. 1980;
136: 153-58.
14. Gilmour DT, Das S, Flowerdew G. Rates of
urinary tract injury from gynecologic surgery
and the role of intraoperative cystoscopy.
Obstet Gynecol 2006; 107:1366.
15. Hilton P, Cromwell D. The risk of
vesicovaginal and urethrovaginal fistula after
hysterectomy performed in the English
National Health Service-a retrospective
cohort study examining patterns of care
between 2000 and 2008. BJOG. 2012; 119
(12) : 1447-54
16. Babak Vakili et al. The incidence of urinary
tract injury during hysterectomy: A
prospective analysis based on universal
cystoscopy. American Journal of Obstetrics
and Gynecology (2005) 192, 1599604.
17. Hilton P. Vesico-vaginal fistulas in
developing countries. International Journal of
Gynecology and Obstetrics.2003; 82:28595.

155

Nidhi Bansal et al.,

Int J Med Res Health Sci.2013;2(2):147-155

DOI: 10.5958/j.2319-5886.2.2.019

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 25 Jan 2013


Research article

Coden: IJMRHS

Copyright @2013

th

Revised: 24 Feb 2013

ISSN: 2319-5886
th

Accepted:28 Feb 2013

DRUG UTILIZATION STUDY OF GYNECOLOGY OPD: IN A TERTIARY CARE


HOSPITAL.
*Baig MS1, Bagle TR2, Gadappa SN3, Deshpande Sonali4, Doifode SM5
1

Assistant Professor, Department of Pharmacology, 5Professor & Head, Department of Pharmacology,


3,4
Associate Professor, Department of OBGY, Government Medical College, Aurangabad, Maharashtra,
India.
2
Assistant Professor, Department of Pharmacology, Pravara Institute of Medical sciences, Deemed
University , Loni, Maharashtra, India
*Corresponding author email:shirazdoctor@yahoo.com
ABSTRACT

Background: The treatment of diseases by use of essential medicines, prescribed by generic names, has
been emphasized by WHO and National Health Policy of India. Drugs used in gynaecology are one of
the top selling drugs in India; however they are least studied with respect to drug utilization. Thus
present study was undertaken to analyze drug utilization pattern of gynecology OPD in a tertiary care
hospital. Materials and Methods: A retrospective, cross sectional, observational study of prescriptions
in Gynecology OPD. Data was obtained from an electronic medical record database of patients that
attended Gynecology OPD during the study period. Prescription records of patients were screened as per
inclusion and exclusion criteria and 300 prescriptions were randomly selected by Openepi software.
Patient related and drug related information was collected on a customized data collection sheet.
Results: The mean age of patients was 30.19+9.83 years and common age of presentation was >18-30
years. In infective cases, vaginal discharge (10.33%) was common, and in non-infective cases, menstrual
disorders (24%) were common. The average number of drugs per prescription was 3.47+1.53. In drug
category, minerals (30.94%) were most commonly prescribed, followed by antimicrobials (24.98%), and
NSAIDs (13.37%). Polypharmacy was observed in 96.33% of the prescriptions. Conclusion: It is only
by drug utilization studies that burden of diseases and corresponding utilization of drugs in gynecology
can be measured. In our study majority of the drugs prescribed were generic which were from the
essential medical list NLEM and WHO.
Keywords: Drug utilization, Gynecology, Outpatient department.
INTRODUCTION

Maternal health gives importance because life of


not only the mother but the child is also at stake.
There are only a few comprehensive community-

based studies in low income countries that


quantify burden of gynecological disease in order
to influence health policy with respect to
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Int J Med Res Health Sci. 2013;2(2):156-163

gynecology. These studies have shown a high


prevalence of previously unrecognized morbidity
that places a heavy burden on women.1,2
As per data by All India Origin Chemists and
Distributors-Advanced Working, Action &
Correction System (AIOCD-AWACS) market
research firm, gynecology drugs are one of the
strong selling drugs in pharmaceutical market;
they rank as the 8th in all the super groups with
16.4% growth in the month of February 2012.3
However they are the least studied drugs in terms
of drug utilization studies.
The principal aim of drug utilization research is
to facilitate appropriate use of drugs in patient
populations, minimize the adverse event and
drug interactions leading to better patient
outcome.4Considering the flow of the
gynecology patients and scarcity of data with
respect to drug utilization study (DUS) the
present study was planned to examine the
patterns of drug prescription in the gynecology
outpatient department (OPD) of Government
Medical College and Hospital, Aurangabad a
biggest tertiary care hospital covering eight
districts of Marathwada Maharashtra state.
MATERIALS AND METHODS

Study Design : A retrospective, cross sectional,


observational study.
Study Duration: 1 year from 01 Dec 2010 30
Nov 2011
Study Population: The Electronic Medical
Record (EMR) data was obtained; consisting of
prescription records of 7762 patients that
attended the Gynecology OPD at Government
Medical College & Hospital, Aurangabad,
Maharashtra.
Procedure: The study was conducted after
obtaining the permission from the Institutional
Ethics Committee, and from the Local HMIS
(hospital management information system)
project implementation committee of the
institute. All Ethical issues pertaining to the
study was taken into consideration. The 7762
patients data was screened and analyzed as per

the inclusion and exclusion criteria. After


screening data, 300 patients were randomly
selected usingOpenepi software version 2.3.
Patient related information like age, gender,
number of visits, diagnosis, month of
presentation,
urban/rural,
drug related
information like number of drugs prescribed,
drug doses, drug dosage form, route of
administration, fixed dose combinations of drugs,
drugs prescription by generic or brand names
were collected on a customized data collection
sheet.
Inclusion criteria: Data of patients with age >18
years after screening having details of parameters
under study were included.
Exclusion criteria for screening: Data of
Gynecology In-door patients during the study
duration, emergency patients, Incomplete data.
Parameters studied : The World Health
Organization (WHO) indicators that were
selected to analyze the prescription pattern
included.
1. Average number of drugs prescribed per
prescription per encounter
2. Relationship between patient demographics
and prescription pattern
3. Indications for which various drugs were
prescribed
4. Percentage usage of various drugs, various
dosage forms of the drugs
5. Drugs prescribed by generic name and brand
name, drugs prescribed from Indian National List
of Essential Medicine (NLEM) 2011 & WHO list
of essential medicines 2011, fixed drug
combinations and polypharmacy.5,6
RESULTS

Total 300 gynecology prescriptions were


analyzed. The mean age of presentation was
30.19 + 9.83 years ranging from >18 to 72 years
of age. Among all the prescriptions 276 (92%)
were from urban area and 24 (8%) were from
rural area. The average number of visits was
2.22+1.42. The average number of drugs per
prescription was 3.49+1.53.
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Int J Med Res Health Sci. 2013;2(2):156-163

Out of 300 patients, 180 (60%), 105 (35%) and


15 (5%) patients were in the age group >1830,>30-50 and >50 years respectively. 85
(28.33%) were infective cases and 215 (71.67%)
were non-infective cases. In 31 cases of vaginal
discharge 28 were cases of white vaginal
discharge. Distribution of infective diseases is
given in table1.
Among non-infective group, menstrual disorders
were common, in which dysmenorrhea, followed
by Dysfunctional Uterine Bleeding (DUB).
There were 3 patients of Polycystic Ovarian
Disease (PCOD). In pelvic mass ovarian cyst
was common, there were two patients of
Carcinoma (Ca) Cervix and one patient of
carcinoma endometrium. Distribution of noninfective gynaecological diseases are given in
table 2. Among other diseases infertility was
common; there were 13 patients for Copper-T
(Cu-t) insertion, 4 cases of Diabetes Mellitus
(DM) and 3 cases of Hypertension (HTN).
Distribution of other diseases given in table 3.
A total of 1047 drugs was prescribed. Out of
these 649 (61.99%), 354 (33.81%) and 44
(4.20%) were prescribed in >18-30 years, >30-50
years and >50 years of age group respectively.
Among all drugs, minerals 324 (30%) were most
commonly prescribed. In minerals anti-anemic
drugs were commonly prescribed 192 (18.33%)
followed by calcium supplements 132 (12.60%).
The second most commonly prescribed group of

drugs was antimicrobial drugs 260(24.83%), in


which metronidazole 73 (6.97%) was commonly
prescribed followed by ciprofloxacin 65 (6.20%)
and ampicillin 47(4.50%).
The third group of drugs commonly prescribed
was Nonsteroidal Anti-inflammatory Drugs
(NSAIDs) 140 (13.37%), in which ibuprofen 73
(6.7%) was commonly prescribed followed by
paracetamol 37(3.50%) and other NSAIDs
(3.17%).
Others group of drugs like antihistamines 119
(11.37%) in which ranitidine 88 (8.40%) was
commonly prescribed followed by cetirizine 22
(2.10%). In hormonal preparations 40 (3.82%)
Oral Contraceptive Pills (OCP) 13 (1.2%) was
commonly prescribed followed by cyclical
progesterone 6 (0.57%). There were 12 (1.15%)
drugs from Central Nervous System (CNS) class
and 11 from cardiovascular system (CVS) and
DM. Other prescribed drugs classified according
to pharmacological class are given in Fig 1. Out
of 1047 drugs prescribed, 996 (95.13%) were
prescribed by generic name, 51 (4.87%) by brand
name and 437 (41.73%) prescribed were fixed
dose combination. Among the total drugs
prescribed 986 (94.17%) were from NLEM and
880 (84.05%) were prescribed from WHO list.
Polypharmacy (containing >2 drugs per
prescriptions) was observed in 289 (96.33%)
prescriptions. Distribution of drugs according to
various dosage forms is given in table IV.

Table 1: Distribution of infective diseases according to age.


Infective Diseases
Number of patients
Vaginal discharge
PID
UTI
Abscess
Episiotomy wound
Cough fever
Diarrhea
TineaCorporis
Scabies
Tuberculosis
TOTAL

Age>18-30 yrs
15
14
4
5
3
4
2
3
2
1
53

Age >30-50yrs
11
6
6
2
0
0
1
1
0
0
27

Age >50 yrs


5
0
0
0
0
0
0
0
0
0
5

Total
31
20
10
7
3
4
3
4
2
1
85

Percentage*
10.33
6.67
3.33
2.33
1.00
1.33
1.00
1.33
0.67
0.33
28.33
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Baig et al.,

Int J Med Res Health Sci. 2013;2(2):156-163

Table 2: Distribution of non-infective gynaecological diseases according to age.

Non infective Diseases

Menstrual Disorders
Dysmenorrhea
DUB
Menorrhagia
Bleeding per vaginum
PCOD
Irregular menses
Amenorrhea
Pelvic Mass
Ovarian cyst
Fibroid uterus
Prolapse
Adenomyosis
Ca Cervix
Ca Endometrium
Fibroadenosis
Vesicular mole
TOTAL

Age in years (Number of patients)


Age
>18-30 yrs

Age
>30-50 yrs

Age
>50 yrs

Total

Percentage*

19
4
6
2
3
2
1

12
11
6
2
0
0
0

2
1
1
0
0
0
0

33
16
13
4
3
2
1

11.00
4.33
5.33
1.33
1.00
0.67
0.33

5
2
0
0
0
0
1
0
45

9
5
3
2
1
0
0
1
52

0
0
4
0
1
1
0
0
10

14
7
7
2
2
1
1
1
107

4.67
2.33
2.33
0.67
0.67
0.33
0.33
0.33
35.65

Table 3: Distribution of other diseases according to age.

Other Diseases
Age
>18-30 yrs
30
3
11
3
7
1
2
1
0

Age in years (Number of patients)


Age
Age
Total
>30-50 yrs
>50 yrs
4
0
34
0
0
3
2
0
13
0
0
3
2
0
9
3
0
4
0
0
2
1
0
2
2
2
4

Post Natal Cases


Postpartum psychosis
Cu-t
Lump in breast
Anemia
Backache
Headache
Hypothyroid
Diabetes mellitus
(DM)
1
2
Hypertension (HTN)
88
18
TOTAL
*Note: In table 1-3, percentages are out of 300.

0
2

3
108

Percentage*
11.33
1.00
4.33
1.00
3.00
1.33
0.67
0.67
1.33
1.00
35.99

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Baig et al.,

Int J Med Res Health Sci. 2013;2(2):156-163

Table 4: Distribution of drugs according to various dosage forms.

Sr.No

Dosage forms

Percentage (%)

Tablet

854

81.57

Capsule

135

12.90

Pessary

27

2.58

Topical

15

1.43

Injection

0.86

Syrup

0.67

1047

100

TOTAL

Total (Drugs)

Percentage calculated out of 1047

Fig. 1: Distribution of drugs according to pharmacological class.


DISCUSSION

The data in our study were accessed by EMR


managed by the Hospital Management
information system. It has several advantages
like data safety, reduced prescription errors and
easy retrieval at one-click for records analysis. 7
In our study mean age of presentation was
30.19+9.83 years and the most common age
group was >18-30 years. In studies carried out by
Kaur et al mean age of women attending
Gynecology OPD was 29.80 6.293
years.8Similarly, Shalini et al reported 70%

patients were between 20-29 years.9 In our study


92% patients were from urban areas and 8%
were from rural area. This indicates that majority
of the rural patients depend on the peripheral
health services for gynecologicaldiseases.
Reproductive/Sexual tract infections (RTI/STI)
are major cause of gynecological morbidity all
over the world.9NFHS3, estimates that 11.1% of
women were reported to have STI in India.
10
Thapa et al reported that commonest age group
of STI is 20-29 years and the most common
symptoms are vaginal discharge. 11 According to
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Int J Med Res Health Sci. 2013;2(2):156-163

Patel et al, Pelvic Inflammatory Disease (PID) is


one of the most serious infections and is a
common problem encountered in gynecological
clinics in India and abroad. 12 In our study
urinary tract infection (UTI) was seen in >30-50
years of age group. As per Gupta et al, more than
half of the females with lower urinary tract
symptoms were middle aged between 31-55years
of age.13
Among menstrual disorders in our study in>1830 years of age group dysmenorrhea was
common. As per Harlow et al menstrual
disturbances are between first and fourth most
common reported gynecological complaints in
India.14
According to Adamson et al infertility varies
across regions of the world and is estimated to
affect 8 to 12 per cent of couples worldwide. 15
There were 10.33% cases of infertility, 4 patients
of ovarian cyst, 7 fibroid uterus and 7 of prolapse
in our study. The results of our study are
consistent with Walraven et al, 1Shalini et al, 9
and Bhatia et al16with regards to distribution of
gynecological diseases. The distribution of
gynecological diseases in our study correlates
with the distribution in other studies. This study
has shown the distribution of the majority of
gynaecological diseases across various age
groups which very few studies have reported.
Among all the drugs, 30% prescribed were
minerals in which anti-anemic drugs were
commonly prescribed. In India 55% of the
females have anemia and is more widespread
among both women and children and it has risen
almost 5% points than NFHS-2.17 As per Bhatia
et al approximately one-third of all women in
OPD reported symptoms of anemia.18 In our
study diagnosed cases of anemia was less
compared to anti-anemic drugs prescribed as
majority of anti-anemic drugs prescribed were
based on symptoms of anemia.
The second commonly prescribed group in our
study was antimicrobial drugs, in which
metronidazole was common followed by
ciprofloxacin and ampicillin. In a study by Shah
et al in indoor patients ciprofloxacin (60.90%)

was commonly used followed by ampicillin


(54.54%) and metronidazole (39.69%).
A
number of Indian studies have recorded a high
level of use of ampicillin, metronidazole,
ciprofloxacin,
gentamicin,
cefazolin
in
19
gynecological department. As per Sihavong et
al, recommended drugs for the treatment of
vaginal discharge and lower abdominal pain
syndromes include metronidazole orally or
vaginal suppository.20,21 Metronidazole is
effective for the management of anaerobic
infections, such as intra-abdominal infections,
gynecologic infections and for mixed, aerobic
and anaerobic infection.22 As metronidazole was
commonly prescribed for anaerobic infections
ingynecological diseases along with combination
with other antimicrobial agents, metronidazole
topped list of antimicrobial drugs in our study.
The third commonly prescribed drugs in our
study was NSAIDs. As per Dhaubhadel et al pain
is the most distressing experience of human
beings and pelvic pain is one of the most
common reasons for gynecology consultation. 23
The average number of drugs per prescription in
our study was 3.49+1.53. It is recommended to
limit the number of drugs prescribed per
prescription should be 2, because of increased
risk of drug interactions.24 Around 40% of the
women have STI at a given point in time and
only 1% completes full treatment of both the
partners.20 Due to unawareness of the
gynecological diseases there is less follow-up
which is a contributing factor for the increase in
drugs per prescription.
The drugs utilized in our study correlates with
the pattern of various gynecological diseases
observed in our study, however there were no
DUS that shows the utilization of minerals,
hormones, NSAIDs and antihistamines which
were the other commonly used drugs in our
study.In our study majority of the drugs
prescribed were generic which were from the
essential medical list NLEM and WHO.

161
Baig et al.,

Int J Med Res Health Sci. 2013;2(2):156-163

CONCLUSION

Our study focused on understanding drug


prescription and prescription trends with respect
to Gynecology OPD. It is only by drug utilization
studies that burden of diseases and corresponding
utilization of drugs in gynecology can be
measured.
REFERENCES

1. Walraven G, Zuberi N, Temmerman M. The


Silent Burden of Gynecological disease in
low income countries. BJOG: International
Journal of Obstetrics and Gynaecology.
2005;112:1177-79
2. International Institute for population Sciences
(IIPS) and Macro International 2007.
National Family Health Survey (NFHS-3),
2005-06: Mumbai India: (I): IIPS.
3. Mukherjee R. Antidiabetic drugs post highest
growth in Feb. Times of India. Mumbai
edition. 5th April 2012: 36.
4. World Health Organization.Introduction to
Drug Utilization Research.[Homepage on the
Internet]. 2003. cited 2011 Nov 14
http://www.whocc.no/filearchive/publication
s/drug_utilization_research.pdf
5 National List of Essential Medicines. 2011.
Cited 2011 Nov 10 http://www.aiims.edu/
aiims/departments/pharmacology/National
%20List%20of%20Essential%20Medicines%2
0India%202011.pdf
6. WHO List of Essential Medicines. 2011.
Cited
2011
Nov
10.
http://whqlibdoc.who.Int
/hq/2011/a95053_eng.pdf
7. Kaliyadan F, Venkitakrishnan S, Jayashree
M, Dharmaratnam AD. Electronic medical
records
in
dermatology
practical
implications.
Indian
J
DermatolVenerolleprol. 2009; 75(2): 157161
8. Kaur S, Talwar R, Sabharwal D, Raut DK.
Knowledge about transmission dynamics of

Sexually transmitted infections. Indian


medical Gazette. 2011: 470-75
9. Shalini S, Murthy NS, Shalini CN, Rajanna
MS, Geethamani V. Study of Reproductive
tract infections among women attending
Urban Health Centres in Banglore City.
Indian J Prev.Soc. Med. 2011;42(3):267-72
10. Ravi R, Nair SB. Correlates of Sexually
Transmitted Infections Among Women in
Southern India. The Journal of Family
Welfare. 2011;57(1): 45-54.
11. Thappa DM, Kaimal S. Sexually Transmitted
Infections in India: Current Status (Except
human Immunodeficiency Virus/Aquired
Immunodeficiency Syndrome). Indian J
Dermatol. 2007;52(2):78-82
12. Patel SV, Baxi RK, Kotecha PV. A case
control study of pelvic inflammatory disease
(PID) and its association with IUD
(Intrauterine device). J ObstetGynecol India.
2008; 58(4): 333-37
13. Gupta S, Singh O, Shukla S, Mathur RK.
Epidemiology, perception and treatment of
females presenting with lower urinary tract
symptoms at a government hospital in central
India. The Internet Journal of Surgery.
2009;21(1).
14. Harlow DS, Campbell OR. Epidemiology of
menstrual disorders in developing countries:
a systematic review. Br J ObstetGynaecol.
2004;111:616
15. Adamson PC, Krupp K, Freeman AH,
Klausner JD, Reingold AL, Madhivanan P.
Prevalence and correlates of Primary
Infertility among young Women in Mysore,
India. Indian J Med Res. 2011:134:440-446
16. Bhatia JC, Cleland J, Bhagavan L, Rao NS.
Levels and determinants of gynecological
morbidity in a district in south India. Stud
FamPlann 1997;28:95 103
17. NFHS key findings 2005-06. Cited 2012 Nov
01http://www.measuredhs.com/pubs/pdf/SR1
28/SR128.pdf
18. Bhatia JC, Cleland J. Reported symptoms of
gynecological morbidity and their treatment
162

Baig et al.,

Int J Med Res Health Sci. 2013;2(2):156-163

in south India. Stud FamPlann 1995;26:203


216.
19. Shah BK, Shah VN. Antimicrobial Use by
Department of Obstetrics and Gynecology of
a tertiary care hospital: Analysis for
rationality
and
other
aspects.
J
ObstetGynecol Ind. 2004:54(4); 387-392.
20. Shivong A, Phouthavane T, Lundborg CS,
Sayabounthavong K, Syhakhang, Wahlstrom
R. Reproductive tract infections among
women attending a Gynecology outpatient
department in Vientiane, Lao PDR. Sexually
Transmitted Diseases. 2007;34(10):791-795
21. Ministry of Health and Family Welfare
Government of India. National Guidelines on
Prevention, Management and control of
Reproductive tract infections including
Sexually Transmitted infections. cited 2012
Nov 15
22. Lofmark S, Edlund C, Nord CE.
Metronidazole is still the drug of choice for
treatment of anaerobic infections. Clinical
Infectious Diseases. 2010;50:16-23
23. Dhaubhadel P, Vaidya A, Chaudhary P. Early
detection of precursors of cervical cancer
with cervical cytology and visual inspection
of cervix with acetic acid. J Nepal Med
Assoc. 2008;47(170):71-76
24. Narwane SP, Patel TC, Shetty YC,
Chikhalkar SB. Drug Utilization and Cost
Analysis for Common Skin Diseases in
Dermatology OPD of an Indian Tertiary
Care Hospital-A Prescription Survey. British
Journal of Pharmaceutical Research. 2011;
1(1): 9-18.

163
Baig et al.,

Int J Med Res Health Sci. 2013;2(2):156-163

DOI: 10.5958/j.2319-5886.2.2.022

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 28 Jan 2013


Research article

Coden: IJMRHS
th

Revised: 25 Feb 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 28 Feb 2013

TETANUS IMMUNIZATION: PERCEPTION OF RESIDENTS IN A TERTIARY CARE


TEACHING HOSPITAL IN WESTERN INDIA
*Dhande Priti P, Beri Shirish G, Patel Hardik R
Department of Pharmacology, Bharati Vidyapeeth Deemed University Medical College, Pune,
Maharashtra , India.
*Corresponding author email: ppdhande@yahoo.com
ABSTRACT
Background: Prevention of tetanus is far easier than its treatment where mortality is very high. Most
cases of tetanus occur due to lack of proper vaccination against the disease and incomplete
immunization on exposure. Residents in a tertiary care teaching hospital constitute the first contact
physicians for patients. Aim: To assess the perception about Tetanus immunization among residents in a
tertiary care teaching hospital of Pune city. Methodology: A pre tested questionnaire was used to assess
the knowledge & recommendations about tetanus immunization among randomly selected 157 residents.
Results: 73.25% residents were not aware of the number of doses of tetanus vaccine recommended for
children under the age of 16 years. Around 50% residents were not aware of the recommended number
of doses of tetanus vaccine for adults over the age of 16 years and during pregnancy. Nearly 60% of the
residents considered the wound after every injury to be tetanus prone. 75.8% of residents thought burn
injuries to be prone to the development of tetanus while 13.4% and 36.9% of the residents did not
consider animal bite and human bite to be tetanus prone respectively. 99.4% residents considered tetanus
toxoid administration in wound with rusted iron. The knowledge regarding tetanus immunization in
relation to the wound categories depending on the immunization status of the patients was very poor
amongst the residents. Conclusion: Better awareness and adherence of tetanus prophylaxis
recommendations is needed in residents who are the first tier of health care providers in teaching
hospitals.
Keywords: Tetanus, immunization, awareness
INTRODUCTION

Tetanus is an acute, often fatal, disease caused by


an exotoxin and highly potent neurotoxin,
tetanospasmin, which is produced during the
growth of the anaerobic bacterium Clostridium
tetani. Spores of the bacteria C. Tetani lives in
the soil and are found around the world. In the

spore form, C. Tetani may remain inactive in the


soil, but it can remain infectious for more than 40
years.1 Infection begins when the spores enter the
body through an injury or wound.2 The spores
release bacteria that spread and make a poison
called tetanospasmin. This poison blocks nerve
164

Dhande PP et al.,

Int J Med Res Health sci. 2013;2(2):164-171

signals from the spinal cord to the muscles,


causing severe muscle spasms.3 The time
between infection and the first sign of symptoms
is typically 7 to 21 days.4 Most cases of tetanus
occur in those who have not been properly
vaccinated against the disease and do not receive
the correct treatment on exposure.
Unlike many infectious diseases, recovery from
naturally acquired tetanus does not usually result
in immunity to tetanus. This is due to the
extreme potency of the tetanospasmin toxin;
even a lethal dose of tetanospasmin is
insufficient to provoke an immune response.
Tetanus can be prevented by vaccination with
tetanus toxoid (TT).5 The CDC recommends that
adults receive a booster vaccine every ten years6,
and standard care practice in many places is to
give the booster to any patient with a puncture
wound who is uncertain of when he or she was
last vaccinated, or if he or she has had fewer than
three lifetime doses of the vaccine. The booster
may not prevent a potentially fatal case of
tetanus from the current wound. In children
under the age of seven, the tetanus vaccine is
often administered as a combined vaccine, DPT
vaccine, which also includes vaccines against
diphtheria and pertussis. For adults and children
over seven, the DT vaccine (tetanus and
diphtheria) is commonly used.7
Prevention of wound related tetanus is primarily
through the administration of the toxoid along
with the use of Human Tetanus Immunoglobulin
(HTIG) depending on the risk of the wound to
develop tetanus. Tetanus immunoglobulin is
necessary for immediate protection to tide over
the period that the toxoid needs to achieve levels
of protective immunity.8
Wounds can be divided into categories A and B
based on the type and duration of wounds.
Category A wounds are defined as wounds that
were less than 6 hours old, clear, non-penetrating
and with negligible tissue damage & category B
included all other types of wounds.9 The
schedule recommends the use of TT for Category
A wounds and TT and HTIG for Category B
wounds. The schedule also considers the

immunization status of the patient while planning


tetanus prophylaxis.10
It was observed that any patient with injury was
given tetanus toxoid without elucidating previous
history of vaccination. Neither patient was
followed up to ensure the completeness of
primary immunization. It was also observed that
patients
requiring
anti-human
tetanus
immuneglobulins were treated with only tetanus
toxoid. Repeated administration of tetanus toxoid
can cause over the immunization leading to
hypersensitivity
reactions
even
up
to
11
anaphylactic reactions.
In a study of doctors in Delhi, the authors found
low knowledge levels regarding tetanus
immunization in the study participants.12 Studies
conducted at 5 university-affiliated emergency
departments (ED) in the United States found
substantial under immunization in the ED
particularly with regard to use of tetanus
immunoglobulin), leaving many patients,
especially those from high-risk groups,
unprotected.13
Residents in our setup of a tertiary care hospital
in western India are first contact physicians for
patients. Their knowledge and awareness of
tetanus immunization is essential for prevention
of newer cases of tetanus in future & also
appropriate management of suspected patients
with tetanus. Improper knowledge or attitude of
these residents may put patients at risk of
developing tetanus or on the other end
unnecessary
adverse
effects
of
hyper
immunization. The present study was therefore
planned to assess the awareness and importance
of tetanus immunization among residents of a
tertiary care hospital in Pune city, India.
MATERIALS AND METHODS

This was an observational, cross-sectional study


conducted among residents of Bharati Hospital, a
tertiary care teaching hospital in Pune, during
September-October 2012. An extensive search of
literature available failed to reveal any
information regarding the prevalence of
knowledge regarding tetanus immunization
165

Dhande PP et al.,

Int J Med Res Health sci. 2013;2(2):164-171

among residents in a medical college. The


sample size calculations were thus based on the
assumption that 50% of the residents had the
correct knowledge regarding the immunization
guidelines with a 95% confidence limit and10%
allowable error and applying the formula14 [z2
p(1-p)/d2] the sample size(n) was calculated to be
400. However since the study population (N) was
257, the revised sample size calculation with
finite population correction given by the
formula7 Nz2p(1-p)/[d2(N-1)+z2p(1-p)] [Where
N=study population, z=1.96 for 95% confidence,
p=estimated proportion in study population,
d=acceptable margin of error] gave the corrected
sample size of 157. These 157 residents to be
interviewed were selected by random sampling
from a total of 257 residents after complete
enrolment. 33 residents were from the pre & para
clinical departments, 53 from medical branches
& 71 from surgical branches.
The study was approved by the Institutional
Ethics Committee of the Bharati Vidyapeeth
Medical College, Pune BVDUMC/6 dated
27/02/2012.
Before
commencement
of
interviews, the objectives of the study and the
contents of the questionnaire were explained to
each of the subjects. Information sheet was given
and written consent for participation obtained.
Participants were assured that the data which was
collected would be used only for research

purposes and findings will not be revealed by


name to anybody.
A pre-tested, pre-designed questionnaire was
adapted. Before adaptation of the questionnaire a
thorough peer review and discussions were
undertaken. The questionnaire consisted of five
parts: the residents profile, evaluation of the
residents knowledge on the number of doses of
tetanus vaccine in children, adult and pregnant
women as per the National Immunization
Schedule followed in India, the types of injury
that are tetanus prone, factors to be considered
while giving TT immunization and lastly TT &
HTIG administration in relation to various types
of wounds according to the immunization status
of the patient.
Statistical analysis
The collected data were entered in Microsoft
excel and analysed using the features of excel to
get the results in percentages.
RESULTS

All the 157 residents participated in the study.


Out of these, 33 were from the pre & para
clinical departments, 53 from medical branches
& 71 from surgical branches.
To evaluate the responses given by the study
participants, guidelines cited by Smith JWG et al
in his article on recommendations for prevention
of tetanus in the wounded have been used.15

Table 1: Knowledge of correct doses of Tetanus toxoid as per National Immunization Schedule

Children < 16 Yrs

Correct
Answer
18.47%

Pregnant Women With No Previous 65.61%


H/O Immunization
Pregnancy (Within 3 Years) With 2 56.69%
Doses of T.T In Last Pregnancy
Adult > 16 Yrs
24.84%

Incorrect
Answer
73.25%

Dont Know

Guidelines 15

8.28%

6 Doses

32.48%

1.98%

2 Doses

31.82%

11.46%

1 Dose

50.95%

24.2%

1 Dose

166
Dhande PP et al.,

Int J Med Res Health sci. 2013;2(2):164-171

Table 2: Number of residents who considered a particular wound to be tetanus prone

YES

NO

Dont Know

Guidelines 15,18

After Every Injury:

59.87 %

40.13 %

0%

NO

After Burn:

75.80 %

16.56 %

7.64 %

YES

After Animal Bite:

75.16 %

13.38 %

11.46 %

YES

After Human Bite:

47.13 %

36.94 %

15.93 %

YES

Table 3: Important considerations for tetanus immunization

YES

NO

Dont Know

Guidelines 15

Age Of Wound

70.70 %

25.48 %

3.82 %

YES

Type Of Wound

79.62 %

14.65 %

5.73 %

YES

Previous Immunization Status

89.80 %

8.28 %

1.91 %

YES

Wound With Rusted Iron:

99.36 %

0%

0.64 %

NO

Table 4: Knowledge of residents about tetanus immunization in Cat-A wound according to immunization
status of the patients

Complete Course Nothing T.T


T.T
/Booster Require 1 Dose
Taken
d

T.T
1 Dose
+ HTIG

T.T
Complete
Course

T.T
Guidelines 15
Complete
Course +
HTIG

Within Last 5
Years
5-10 Years Before

68.79%

31.21%

0%

0%

0%

12.10%

65.60%

8.92%

13.38%

0%

Nothing
Required
TT 1 Dose

10 Years Before

0%

43.31%

28.66%

19.75%

8.28%

TT 1 Dose

No Past
Immunization

0%

13.38%

5.09%

29.49%

42.04%

TT Complete
Course

Table 5: Knowledge of residents about tetanus immunization in Cat-B wound according to immunization
status of the patients

Complete
Course Nothing
T.T /Booster Taken Required

T.T
1 Dose

T.T
T.T
1 Dose Compl
+ HTIG ete
Course

T.T
Complete
Course
+ HTIG

Guidelines 15

Within Last 5 Years

14.01%

63.06

18.47

4.46

0%

Nothing Required

5-10 Years Before

0%

31.85

47.13

17.83

3.18

TT 1 Dose

10 Years Before

0%

11.46

27.39

29.94

31.21

6.37

5.09

10.19

78.34

TT 1 Dose +
HTIG
TT Complete +
HTIG

NoPast Immunization 0%

167
Dhande PP et al.,

Int J Med Res Health sci. 2013;2(2):164-171

Table 1 shows the summary of the participants


knowledge about tetanus immunization in
different target groups: 81.53% residents were
not aware of the number of doses of tetanus
vaccine recommended for children under the age
of 16 years and 75.15% residents were not aware
of the number of doses of tetanus vaccine
recommended for adults over the age of 16 years.
Surprisingly only 65.6% residents who
participated in the study knew the correct
schedule of tetanus immunization for pregnant
women with no history of previous immunization
immunization
while 33.8% of them had inadequate knowledge
about the correct number of doses to be
administered to pregnant mothers who had their
last childbirth within 3 years.
As seen in table 2, more than half of the study
population (59.87%) considered every
every cut injury
to be tetanus prone. The majority of the residents
(>75%) considered burn injury and animal bite
wounds to be tetanus prone while most of them
(52.87%) were unaware of the risk with human
bite.
More than 70% of residents were aware that age
of the wound, type of wound and previous

67

immunization status of patients as important


considerations before immunizing a patient
against tetanus. (Table 3) Almost every resident
considered that wound with rusted iron requires
tetanus immunization without considering
considering the
age and type of wound or previous immunization
status.
When respondents were questioned about
recommendation for tetanus immunization in
category A wounds, their knowledge was good
(>65%) for patients who were immunized within
last 5 yrs or 5-10
5 10 yrs before. (Table 4) The
correct response for tetanus immunization in
patients immunized 10 yrs before was only
43.31% while that for an unimmunized person
was very poor (<30%).
(<30%).
Table 5 shows that the knowledge of the study
participants was very poor for tetanus
immunization in category B wounds, for patients
who were immunized within last 5 yrs, 5-10
5 10 yrs
or 10 yrs before. Surprisingly majority of them
recommended correct schedule for patients with
no history of previous immunization with such
wounds.

66

% of Correct Answer

70
60

43

50

32

40
30

27

14

20

Cat - A Wound
Cat - B Wound

10
0
within last 5 years

5--10
10 years before

10 years before

Immunization Status of Patient (Complete Course of TT/Booster)

Fig.1: Comparison of correct responses about tetanus immunization in Cat


Cat-A
A and Cat-B
Cat B wounds
It is clearly evident from the figure-1
figure 1 that the
respondents had correct knowledge about

immunization for category A wounds better than


that for category B wounds.

168
Dhande PP et al.,

Int J Med
ed Res Health
lth sci. 2013;2(2
;2(2):164-171

DISCUSSION

One of the objectives of the study was to


evaluate the knowledge of Tetanus Immunization
in resident doctors who are the first contact
physicians in tertiary care teaching hospitals.
Based on the recommendations of the WHO the
National Immunization Schedule of India has
proposed 3 doses of DPT in the first year of life
as primary immunization and then one booster of
DPT at 16-24 months and then at 5-6 years one
dose of DT and at 10 years and 16 years one dose
of TT respectively.16 The results reveal that
around 3/4th of the student residents lacked the
adequate knowledge of the vaccine schedule in
children below 16 years. Majority of the
residents were not aware of the booster dose of
tetanus toxoid recommended at 16 years of age
one.
Mortality from neonatal tetanus still remains an
important but preventable, cause of neonatal
mortality in India. The Government of India had
set the goal of neonatal tetanus elimination by
the year 2005 through the coverage of all
pregnant women with 2 doses of tetanus toxoid.
It is indeed surprising that even then the goals of
elimination of neonatal tetanus in India are yet to
be achieved as in the year of 2011 total number
of cases of neonatal tetanus reported were 734
and out of them 14 deaths were reported.17 Thus
the knowledge of TT immunization in pregnant
women is essential among all levels of health
care workers including residents to prevent
neonatal tetanus. Vaccination with two doses of
TT immunization given at least 4 weeks is the
chief priority in preventing neonatal tetanus. A
single booster dose of the toxoid is recommended
for repeat pregnancies within a period of 3 years
since the last pregnancy.18 The vaccine is cheap
and available at the government sub-centres for
free. In the present study, around 30-40%
residents lacked the required knowledge of TT
immunization in pregnant women which was
really surprising. This knowledge is essential not
only for residents of obstetrics and gynaecology

department but for all, as these doctors link the


chain of health care professionals.
Almost 60% residents were seen overcautious as
they considered every injury to be tetanus prone.
Similar result was found in a study in UK among
various staff members in the accident and
emergency (A&E) departments, where 22.1% of
respondents considered any cut injury to be
tetanus prone.2 Burn wounds are prone to tetanus
and all patients with 2nd and 3rddegree burns also
need to have up-to-date tetanus shots if
individual has not been immunized within the
last 5 years. In the present study, most of the
residents were aware about the risk of tetanus
following burns and had recommended tetanus
immunization. Even after animal and human bite
injury there is a possibility of contracting
tetanus.19 The bite itself does not cause tetanus
but it allows a break into the skin that can
provide the tetanus bacteria with a way to enter
the body. In any dog bite, the focus is on rabies
prevention, which is well founded. But the
possibility of tetanus should also be kept in mind.
More than 75% residents in the study
recommended tetanus immunization after animal
bite but many of them lacked the knowledge
about the same after human bite. A single case of
human bite leading to tetanus has been
reported.20 Proper guidance about such rare but
possible cases is recommended in residents to
control the incidence of tetanus in India.
Antibiotic prophylaxis against tetanus is neither
practical nor useful in managing wounds thus
proper immunization plays an important role in
prevention of tetanus. The need for active
immunization, with or without passive
immunization, depends on the condition of the
wound and the patients immunization history. In
the present study residents were asked about
important considerations before immunizing a
person for tetanus. 70-80% residents considered
age and type of wound as important factors for
decision on immunization against tetanus. 10%
residents did not consider previous immunization
169

Dhande PP et al.,

Int J Med Res Health sci. 2013;2(2):164-171

status of an individual important for deciding on


tetanus immunization in any situation.
A common association which many people have
on their minds is the rusty nails and Tetanus.
But this concept is somewhat misleading. Rust
itself does not cause tetanus nor does it contain
more C. tetani bacteria. The rough surface of
rusty metal merely provides a prime habitat for a
C. tetani endospore to reside, and the nail affords
a means to puncture skin and deliver endospore
into the wound. Because C. tetani is an anaerobic
bacterium, it and its endospores survive well in
an environment that lacks oxygen. Hence
stepping on a nail, whether it is rusty or not, may
result in a tetanus infection. The major
considerations which most of us forget to
correlate with such cases are condition of the
wound and previous immunization status of the
person. Tetanus immunization should be
recommended only after considering these facts.
Nearly all the residents in the study had this myth
of rust on their mind.
It has been observed that the use of HTIG as
passive immunization against tetanus is very
meagre even after category B wounds are
reported in casualties or any surgical
departments. Though respondents in this study
recommend the use of HTIG in unimmunized
person with category B wounds but this does not
reflect in actual practice. The reason behind this
may be the high cost & unavailability of HTIG
readily in such setups.
CONCLUSION

Better awareness and adherence of tetanus


prophylaxis recommendations is needed in
residents who are the first tier of health care
providers in teaching hospitals.
REFERENCES

1. Lockjaw. Tetanus. A.D.A.M. Medical


Encyclopedia. 2011. 41
2. Savage EJ, Nash S, McGuiness A, Crowcroft
NS. Audit of tetanus prevention knowledge
and practices in accident emergency

departments in England. Emerg Med J 2007;


24 (6): 417-421
3. Borrow R, Balmer P, Roper HM. Tetanus
Update. The immunological basis for
immunization series Module 3: Tetanus
update 2006.WHO; 2006.
4. Centers for Disease Control and Prevention.
Recommended adult immunization schedule-United
States,
2011.
MMWR.
2011;60(4).244
5. Hopkins, A.; Lahiri, T.; Salerno, R.; Heath,
B. (1991). "Diphtheria, tetanus, and pertussis:
recommendation for vaccine use and other
preventive measures. Recommendations of
the Immunization Practices Advisory
committee (ACIP)". MMWR Recomm Rep
40 (RR10): 128
6. CDC. Epidemiology and prevention of
vaccine-preventable diseases. Atkinson W,
Wolfe S, Hamborsky J, eds. 12th ed.
Washington DC: Public Health Foundation;
2011.
7. Porter JD, Perkin MA, Corbel MJ, Farrington
CP, Watkins JT, Begg NT. "Lack of early
antitoxin response to tetanus booster".
Vaccine 1992;10 (5): 3346.
8. Available
from:
http://www.cdc.gov/vaccines/vacgen/immunity-types.htm
9. Ranadip Chowdhury, Abhijit Mukherjee,
Saibendu Kr Lahiri. A study on the
knowledge of tetanus immunization among
internees in a Government Medical College
of Kolkata. National Journal of Community
Medicine 2011; 2 (3): 432-39
10. Park K. Parks Textbook of Preventive &
Social Medicine 20th Edition Banarsidas
Bhanot Publishers 2009:272
11. Preventing Tetanus, Diphtheria, and Pertussis
Among Adolescents: Use of Tetanus Toxoid,
Reduced Diphtheria Toxoid and Acellular
Pertussis Vaccines, K. R. Broder et al.,
MMWR Recommendations and Reports,
March 24, 2006 / 55(RR03), 134, page 18.
12. Dabas P, Agarwal CM, Kumar R, Taneja
DK, Ingle GK, Saha R. Knowledge of
170

Dhande PP et al.,

Int J Med Res Health sci. 2013;2(2):164-171

general public and health professionals about


tetanus immunization. Indian J Paediatr
2005;72 (12): 1035-1037
13. Talan DA, Abrahamian FM, Moran GJ,
Mower WR, Alagappan K, Tiffany BR,
Pollack CV, Steele MT, Dunbar LM, Bajani
MD, Weyant RS, Ostroff SM. Tetanus
immunity and physician compliance with
tetanus
prophylaxis
practices
among
emergency department patients presenting
with wounds. Annals of Emergency
Medicine 2004: 43(3):305-14
14. Abramson JH, Abramson ZH. Survey
Methods in Community Medicine 5th edition
Churchill Livingstone1999:102
15. Smith J W G, Laurence DR, Evans DG.
Prevention of tetanus in the wounded. Brit.
Med.J 1975; 3:453-55
16. Govt. of India Health information of India
2005, Ministry of Health & Family Welfare,
New Delhi.2006
17. Health
Status
Indicators

2011
http://cbhidghs.nic.in/index2.asp?slid=1208
& sublinkid=944
18. Kishore J. National Health Programmes of
India 9th Edition. Century Publications
2011:158
19. Eilbert WP. Dog, Cat and human bites:
Providing safe and cost effective Treatment
in the ED. Emergency Medicine Practice
2003; 5 (8): 1-20
20. Agrawal K, Ramachandrudu T, Hamide A,
Dutta TK. Tetanus caused by human bite of
the finger. Ann Plast Surg. 1995; 34: 20102

171
Dhande PP et al.,

Int J Med Res Health sci. 2013;2(2):164-171

DOI: 10.5958/j.2319-5886.2.2.024

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Received: 30

Volume 2 Issue 2 April - June

Jan 2013

Coden: IJMRHS
th

Revised: 28 Feb 2013

Copyright @2013

ISSN: 2319-5886
nd

Accepted: 2 Mar 2013

Research article
EFFECT OF SUPPLEMENTATION OF TENDER COCONUT WATER ON BLOOD
PRESSURE OF PRIMARY HYPERTENSIVE SUBJECTS
* Gullapalli HS1, Avinash P Tekade 2, Namrata H Gullapalli3
1

Associate Professor, Department of Physiology, Vinayaka Missions Medical college and Hospital,
Karaikal, Puducherry, India
2
Associate Professor, Department of Physiology, Katuri Medical College and Hospital,
Guntur,AP,India
3
Dietitian and nutritionist Vinayaka Missions Medical college and Hospital, Karaikal, Puducherry,India
*Corresponding author email: hgullapalli2000@gmail.com
ABSTRACT

Background: Hypertension is a major health problem worldwide. Increased vascular resistance, sodium
retention & sympathetic over activity contributes to the blood pressure elevation. Plant foods may be
beneficial in decreasing blood pressure (BP). Recently much attention has been focused on plant foods
that may be beneficial in preventing Hypertension, metabolic syndrome and possibly reduce the risk of
various diseases. This clinical study was conducted to test the effectiveness of a structured
intervention on BP of primary hypertensive subjects. Aim: To study the effect of Tender Coconut
Water (TCW) on BP of Primary hypertensive subjects. Methods and Material: 70 subjects were
selected randomly sample for 6 weeks of the intervention program. Among them 40 subjects were
selected as the experimental group and 30 300ml/day for 6 weeks whereas the control group was
instructed to follow the same routine without modifications. One initial, two mid intervention (after
every 15 days) and one final (post intervention) BP recorded for both the groups. The obtained data was
statistically analyzed. Results: The mean systolic BP of experimental group and control group were
decreased from 145.8 mm Hg and 141mm of Hg to 135.3 mm of Hg and 140 mm of Hg respectively.
The mean diastolic BP of experimental group and control group were decreased from 93.7 mm H g and
90.9 mmHg to 86.9 mm of Hg and 89.7 mm of Hg respectively. Conclusion: Irrespective of cause of
hypertension TCW has beneficial effect on BP. TCW contains high amount of potassium which causes
vasodilatation and also improve the endothelial function.
Keywords: Hypertension, Systolic, diastolic blood pressure, Potassium, Tender Coconut water
INTRODUCTION

In India subsequent studies showed a steadily


increasing trend in hypertension prevalence and
it is emerging as the biggest public health
problem today1. They are the principle cause of

death in all developed countries accounting for


50 percent of all deaths and are also emerging as
a prominent public health problem in developing
countries, ranking third with nearly 16 percent of
172

Gullapalli HS et al.,

Int J Med Res Health Sci.2013;2(2):172-176

all deaths. Many developing countries are now in


a phase of epidemiological transition and face the
double burden of communicable and noncommunicable diseases, with the severe
repercussions this has on their very weak
economies2. Both systolic and diastolic BP has a
continuous, graded, strong, independent and an
etiologically significant relationship to the
outcome variables such as cardiovascular
mortality and all-cause mortality2, 3. The DASH
(Dietary Approach to Stop Hypertension) diet
advocates increased usage of fruits, vegetables
and low-fat dairy products and includes whole
grains, nuts, poultry and fish. It has low
quantities of fats, red meat, sweets and sugarcontaining beverages. It is thus rich in potassium,
magnesium, calcium and fiber and has low
amounts of total fat, saturated fat and cholesterol
4, 5 6
.
As the dietary management of hypertension can
prevent cardiovascular, renal and many other
diseases this study was conducted to observe the
effect of TCW in the management of
hypertension.
MATERIALS AND METHODS

This study was performed in the Department of


Physiology of KIMS, after receiving necessary
approval from the Institutional Committee for
Ethics. For the purpose of the study 70 subjects
were selected as first stage random sample using
following inclusion and exclusion criteria. The
subject should be of 30 to 50 years age group and
should not have any other disease than
Hypertension. Subjects below 30 years and
above 50 years and subjects who are having any
other diseases like diabetes, cardiovascular
disease except hypertension are excluded.
Based on inclusion and exclusion criterion, 70
subjects were selected randomly as a sample for
45 days of the intervention program out of which
50 subjects continued till the end of the research
study. Among them 30 subjects were grouped as
the experimental group and remaining 20
subjects were grouped as a control. The general
information like name, age, gender, education,

habits etc.; Anthropometric measurements like


Height, weight, body mass index, dietary
information were collected from all subjects. The
experimental group was educated about
consumption of 300ml/day fresh TCW. Control
group was without any supplementation.
The supplementation was done for 45 days.
Initial or pre intervention estimation of
BP
recording was done in all subjects. Three
readings of BP were taken for more accuracy. BP
measurement was done once in every 15 days of
all subjects. After 45 days of supplementation,
the effects of TCW on BP of primary
hypertensive subjects were recorded. The results
of pre and post intervention were statistically
analyzed. The statistical techniques used are
mean, standard deviation, standard error of mean
and t-test ANOVA value.
RESULTS AND DISCUSSION

Cardiovascular diseases caused 2.3 million


deaths in India in the year 1990; this is projected
to double by the year 2020. Hypertension is
directly responsible for 57 percent of all stroke
deaths and 24 percent of all coronary heart
disease deaths in India 13, 14, 15. Potassium is the
most important ion in the living cell, affecting
almost every cellular function. Potassium is a
fundamental factor in BP regulation 11.
Increasing potassium intake has beneficial effects
on human health. A high-potassium diet lowers
BP in individuals with both raised BP and
average population BP. Increasing potassium
intake reduces cardiovascular disease mortality.
This is mainly attributable to the BP-lowering
effect and may also be partially because of the
direct effects of potassium on the cardiovascular
system. A high-potassium diet may also prevent
or at least slow the progression of renal disease.
An increased potassium intake lowers urinary
calcium excretion and plays an important role in
the management of hypercalciuria and kidney
stones and is likely to decrease the risk of
osteoporosis. Low serum potassium is strongly
related to glucose intolerance, and increasing
potassium intake may prevent the development
173

Gullapalli HS et al.,

Int J Med Res Health Sci.2013;2(2):172-176

of diabetes that occurs with prolonged treatment


with thiazide diuretics. Reduced serum
potassium increases the risk of lethal ventricular
arrhythmias in patients with ischemic heart
disease, heart failure and left ventricular
hypertrophy, and increasing potassium intake
may prevent this. The best way to increase
potassium intake is to increase the consumption
of fruits and vegetables8.The main objective of
the present study is to observe the effect of
supplementation of TCW on blood pressure of
primary hypertensive subjects.

Table 1, shows the mean and SD of systolic and


diastolic BP of control group (n=20) at initial,
midterm and final period of study. The final
systolic BP of control group was not decreased
significantly (p=0.736) at 5% level. The final
diastolic BP of control group was not decreased
significantly (p=0.409) at 5% level. Control
group was without any intervention and asked to
follow the same routine as before the study
period. This may be the reason for only a very
slight decrease in BP.

Table1: Comparison of Blood Pressure of control group


Blood Pressure

Time Point

Mean S.D.

Systolic
Blood
Pressure

Initial
Midterm
Final
Initial
Midterm
Final

141.2 8.03
139.3 7.49
140.0 7.02
90.9 3.46
89.4 4.31
89.7 3.33

Diastolic
Blood
Pressure

F value
0.308 NS
P= 0.736
0.908 NS
P= 0.409

(NS = Not Significant)


Table 2 shows the mean and SD of systolic and
diastolic BP of experimental group (n=30) at
initial, midterm and final period of the study. The
final (post intervention) systolic BP of
experimental group was decreased significantly
than control group (p=0.002) at 5% level. The
final (post intervention) diastolic BP of
experimental group was decreased significantly
than control group (p<0.00001) at 5% level .The
systolic and diastolic BP of experimental group

was decreased by 10.5 mm Hg and 6.8 mm Hg


respectively. The reduction in BP in the
experimental group was highly significant than
the control group. This significant decrease in
blood pressure might be due to the
supplementation of TCW. As TCW is rich in
potassium (290 mg %), calcium (44 mg %),
magnesium (10 mg %) and Vitamin C (2.4 mg
%) has a beneficial effect on blood pressure of
hypertensive subjects 10, 11.

Table 2: Comparison of Blood Pressure of Experimental group


Blood Pressure

Time Point

Mean S.D.

Systolic
Blood
Pressure

Initial
Midterm

145.8 9.46

Diastolic
Blood
Pressure

Initial

Final
Midterm
Final

139.4 9.57
135.3 8.76
93.7 4.03
89.8 4.31
86.9 3.66

F value
9.72 *
P= 0.0002

22.2 *
P < 0.00001

(* = Significant at 5% level of significance)

174

Gullapalli HS et al.,

Int J Med Res Health Sci.2013;2(2):172-176

180
160
140
120
100

Initial systolic

80

Final systolic

60
40
20
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

Fig:1. Comparison of systolic Blood pressure of Experimental group.


120
100
80
Initial Diastolic
60

Final Diastolic

40
20
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

Fig.2: Comparison of diastolic blood pressure of experimental group


The potassium causes vasodilatation and also
improves the endothelial function. The
magnesium has vasodilator property and also
inhibits both the production of nitric oxide and
contraction of vascular smooth muscle walls of
arteries. Calcium and Vitamin C are also
hypotensive. L-Arginine, a physiological
substrate for the production of endothelium
derived relaxing factor, nitric oxide (NO), which
plays an important role in the regulation of
vascular tone and homeostasis which is impaired
in hypertension 7.

CONCLUSION
In the control group there was a very slight
decrease in systolic and diastolic BP which was
statistically not significant. In the experimental
group systolic and diastolic BP was decreased by
10.5 mm Hg and 6.8 mm Hg respectively. The
reduction in BP in the experimental group was
statistically significant at the 5% level of
significance. It indicates the consumption of the
coconut water significantly decreases the blood
pressure in primary hypertensive patients.

175

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Int J Med Res Health Sci.2013;2(2):172-176

ACKNOWLEDGEMENT
We acknowledge our patients who participated in
the study.
REFERENCES

1. WHO Expert Committee. Hypertension


control. WHO Technical Report Series,
1996;862, 2-10
2. Fernando S. Antezana, Epidemiologic
aspects of hypertension in the world. One
medicine, Two Cultures; Hypertension,
1996.10-15
3. Stamler J, Stamler R, Neaton JD. Blood
pressure, systolic and diastolic, and
cardiovascular risks. US population data.
Arch Intern Med 1993;153: 598-615
4. Your guide to Lowering your blood pressure
with DASH. DASH eating plans, 2011;5:1926
5. Sacks FM, Svetkey LP, Vollmer WM, Appel
LJ, Bray GA, Harrsha D, Obarzanek E,
Conlin PR, Miller ER et al. Sodium
collaborative Research Group. Effects on
blood pressure of reduced dietary sodium and
the Dietary Approaches to Stop Hypertension
(DASH) diet. DASH-Sodium Collaborative
Research Group. N. England Journal of
Medicine Jan 2001;344(1):3-10
6. Moore TJ, Svetkey Laura, Apple, Lawrence;
Bray, George & Vollmer, William. The
DASH Diet for Hypertension. NY, New
York: Simon & Schuster. DASH diet 2001.
7. Alleyne T, Roach S, Thomas C, Shirley A.
The control of hypertension by use of
coconut water and mauby: two tropical food
drinks. West Indian Med J. 2005;54(1):3-8.
8. He FJ, MacGregore GA. Beneficial effects of
potassium on human health. Physiological
plant. 2008.133(4):725-35
9. Bhagya D, Lalitha Prema, Thankappan
Rajamohan. Tender coconut water maintains
the level of electrolytes and renin in fructosefed hypertensive rats. Int J Bio/Med Res.
2010;1(3):44-48

10. Styavathi Krishnakutty. Codex alimentarius


commission Joint FAO/WHO food standards
21st session of Codex Committee on
Processed fruits & vegetables at Texas,
U.S.A. from Government of India. Sep 2002.
23-27
11. Marina Carolina Delgado, MD. Potassium in
Hypertension. Current Hypertension Reports
2004; 6:31-35
12. Bhagya DP, Rajamohan T. Beneficial effects
of Tender Coconut Water on Blood Pressure
and
Lipid
levels
in
experimental
hypertension. 25 Feb 2010.
13. Gupta
R.
Trends
in
hypertension
epidemiology in India. Journal of Hum
Hypertension 2004; 18:73-8
14. Murray CJL, Lopez AD. Mortality by cause
for eight regions of the world: Global Burden
of Disease Study. Lancet 1997;349:12691276
15. Rodgers A, Lawes C, MacMahon S.
Reducing the global burden of blood pressure
related cardiovascular disease; Journal of
Human Hypertension.2000;18(1):19-26

176

Gullapalli HS et al.,

Int J Med Res Health Sci.2013;2(2):172-176

DOI: 10.5958/j.2319-5886.2.2.025

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
nd

Volume 2 Issue 2 April - June

Received: 2 Feb 2013

Coden: IJMRHS
nd

Revised: 2 Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 8 Mar 2013

Research article

EFFECT OF ANTIOXIDANTS IN PRE ECLAMPSIA WOMEN AT INCREASED RISK.


*Vijayalakshmi B, Kondam Ambareesha, Kayalvizhi E, Qairunnisa S, Revathi M, Chandrasekhar M
Department of Physiology, Meenakshi Medical College, Kanchipuram, Tamilnadu, India
*Corresponding author email: vijayalakshmib2@gmail.com.
ABSTRACT

Preeclampsia is a leading cause of maternal and neonatal mortality and morbidity. It is a complex
syndrome of undetermined etiologic origin, usually diagnosed during second half of pregnancy.
Elevated levels of oxidative lipid derivatives and reduced antioxidants in the circulation of
preeclamptics may contribute to endothelial damage. There is good evidence for a significant increase in
the levels of malondialdehyde in plasma and erythrocytes. Group I: Normotensive nonpregnant women
(control), Group II: Pregnant women with normal blood pressure, Group III: Preeclamptic
(pretreatment), women Preeclamptic women were subdivided into Group IIIA: Pre eclamptic women
supplemented with Vitamin E (n=20), Group IIIB: Preeclamptic women supplemented with Omega 3
Fatty Acid, Group IIIC: Preeclamptic women supplemented with Vitamin E 400mg + Omega 3 Fatty
Acid. Serum SOD, MDA, GPx, GSH levels were measured in all groups and compared with pre
treatment and post treatments results by using the one way ANOVA followed by the Tukey HSD
procedure. Our results showed that supplementation of Vitamin E, Omega 3 fatty acid alone and in
combination has significantly increased antioxidant enzyme status and significantly decreased oxidative
stress when compared to unsupplemented patients(P< 0.001).
Keywords: Preeclampsia, Vitamin E, Omega 3 fatty acids, SOD, MDA, GPx, GSH
INTRODUCTION

Pre-eclampsia is a leading cause of maternal and


neonatal mortality and morbidity. It is a complex
syndrome of undetermined etiologic origin,
usually diagnosed during second half of
pregnancy. The hypertensive disorders in
pregnancy are common complications of
gestation and form one of the great triad of
complications that continued to be responsible
for the majority of maternal deaths. How
pregnancy per se incites or aggravates
hypertensive vascular disease remain unsolved

despite decades of intensive research. Diffuse


vascular endothelial disruption is believed to
play a major role in the pathophysiologic
mechanisms of pre eclampsia. Thus, spiral
arteries display an abnormally high vascular
resistance with reduced uteroplacental perfusion
as confirmed by Doppler flow velocimetry
studies1.
Pre-eclampsia is a multi organ system disorder
that occurs after the 20th week of gestation and is
characterized by: 1. Hypertension i.e. Blood
177

Vijayalakshmi et al.,

Int J Med ResHealth Sci. 2013;2(2):177-181

pressure > 140/90 mm/Hg2. Proteinuria (urine


protein > 0.3 g/24 hours) with or without
3.Abnormal oedema (Beaulieu MD, 1994)When
the diastolic blood pressure becomes above 110
mm Hg and protein above 3 mg per day the
condition is called severe pre-eclampsia2 and if
the occurrences of seizures are superimposed on
pre-eclampsia the condition is referred to as
eclampsia3
Elevated levels of oxidative lipid derivatives and
reduced antioxidants in the circulation of
preeclamptics may contribute to endothelial
damage. There is good evidence for a significant
increase in the levels of malondialdehyde (MDA)
in plasma and erythrocytes, a marker of lipid
peroxidation in normotensive pregnant women,
which were further increased in women with
pregnancy-induced hypertension4. Evidence of
increased oxidative lipid derivatives in the
decidual placental tissues was observed in
women with established preelampsia5. Elevated
levels of oxidative lipid derivatives, conjugated
dienes and reduced antioxidant capacity in the
maternal circulation have also been reported6.
The free radical scavenging mechanisms include
enzymatic
antioxidants
like
Superoxide
dismutase (SOD), Glutathione peroxidase (GPx),
Glutathione reductase (GSH) and Catalase,
which limit the cellular concentration of free
radicals and prevent excessive oxidative damage.
Until recently, the data supporting the efficacy of
supplementation with vitamin C and vitamin E
for the prevention of preeclampsia have been
limited. 7 Vitamin E, a potent lipid soluble
antioxidant is considered as the most reactive
antioxidant8. The most important function of
vitamin E in the body is to protect the
polyunsaturated fatty acid from oxidation 9
Although omega-3 fatty acids have been known
as essential to normal growth and health since
the 1930s, awareness of their health benefits has
dramatically increased in the past few years.
New versions of ethyl esterized omega-3 fatty
acids, such as E-EPA and combinations of EEPA and E-DHA, have drawn attention as a
highly purified and more effective product than

the traditional ones. Furthermore, n -3 LCPUFA


have a wide range of biological effects, including
beneficial effects on lipoprotein metabolism,
platelet function, endothelial function, vascular
reactivity, cytokine production and coagulation10
Supplementation with Omega 3 Fatty Acid
during pregnancy lowers the risk of premature
birth and can increase the length of pregnancy
and birth weight by altering the balance of
eicosanoids involved in labour and promote fetal
growth by improving placental blood flow.
Intake of Omega 3 Fatty Acid during pregnancy
and breastfeeding may facilitate the child's brain
development. There is also some evidence that
supplementation with Omega 3 Fatty Acid might
help to prevent preeclampsia, postpartum
depression,
menopausal
problems,
postmenopausal osteoporosis, and breast cancer.
Habitual consumption of modest amounts of fish
and other seafood has been associated with a
reduction in the risk of heart disease11
MATERIALS AND METHODS

The subjects for this study were from the


Obstetrics and Gynaecology Department of
Meenakshi Medical College Hospital and
Research Institute, Kancheepuram, Tamil Nadu,
India. After enrolling in the study, a detailed
obstetric history and the informed consent were
obtained. A thorough explanation of the
procedure of this long term study was explained
in detail and blood samples were obtained
basally. The study protocol was approved by an
Institutional Human Ethical Committee of
Meenakshi University
Grouping: The patients were divided into three
groups:
Group I: Normotensive nonpregnant women
control (n = 42), Group II: Pregnant women
with normal blood pressure (n = 50), Group III:
Pre eclamptic women (n = 60)
Preeclamptic women were subdivided into
Group
IIIA:
Pre
eclamptic
women
supplemented with Vitamin E (n=20), Group
IIIB: Pre eclamptic women supplemented with
Omega 3 Fatty Acid (n=20), Group IIIC: Pre
178

Vijayalakshmi et al.,

Int J Med ResHealth Sci. 2013;2(2):177-181

eclamptic women supplemented with Vitamin E


400mg + Omega 3 Fatty Acid (n=20)
The supplements were Vitamin E 400mg, Omega
3 Fatty Acid (DHA 120mg and EPA 180 mg),
Vitamin E 400mg + Omega 3 Fatty Acid once
daily from 22 - 24 weeks for eight weeks. The
three above mentioned drugs were obtained from
Merck Pharmaceutical India after getting official
permission to be used on human subjects and
after complete standardisation. The study groups
were asked to consume their normal habitual
diet, but they were asked to follow the
recommendations for pregnant women.
Blood sample collection was done between 2224 weeks of gestation and after 8 weeks of
supplementation of antioxidants along with the
regular antihypertensive agents. The patients
were requested to be on overnight fasting. Blood
samples were collected between 8.00 AM and
10.00 AM. In each case, 10 ml fasting venous
blood were drawn into a sodium heparin
vacutainer tube for separating plasma and stored
at 4C, until processed. All samples were
processed within 20 hours of sampling. All the
pregnant women were encouraged to book and to
attend regular antenatal checkups.
The blood samples were centrifuged at 1000g for
15 min at 4C; the isolated red cells were washed
4 - 5 times with 0.154 M NaCl to remove plasma
and buffy coat. After the final wash, required
packed red cells were lysed by hypotonic stock
solution and different dilutions were used as
Hemolysates.
Parameters:
Malondialdehyde (MDA) 12: The assay was
estimated according to the method of Nadiger et
al (1986). On the reaction of malondialdehyde
(MDA) with thiobarbituric acid (TBA); forming
a MDA-TBA2 adduct that absorbs strongly at
532 nm. The MDA content in plasma was
expressed as nmol / ml.
Superoxide dismutase (SOD)13:Superoxide
dismutase activity was estimated according to the
method of Hartz et al 1983. The assay procedure

is based on the autoxidation of SOD reagent to


an adrenochrome at alkaline pH by measurement
of changes in the absorption at a wavelength of
480 nm. Superoxide dismutase activity is
evaluated and expressed as IU/gHb
Glutathione peroxidase (GPx)14: Glutathione
peroxidase activity was determined by the
nonenzymatic method by Paglia and Valentine
(1967). Glutathione peroxidase enzymes,
catalyses the reduction of H2O2 and organic
peroxides to water and the corresponding stable
alcohol thus inhibiting the formation of free
radicals. Enzyme activity can be decreased by
negative feedback from excess substrate or from
damage by oxidative modification.
Glutathione reductase (GSH) 15 : Glutathione
Reductase activity was measured according to
the method of Goldberg et al 1983. Glutathione
Reductase catalyses the reduction of glutathione
in the presence of NADPH, which is oxidised to
NADP+. The decrease in absorbance at 340nm is
measured.
Statistics: The data was analayzed by one way
ANOVA (Analysis of variance) followed by the
Tukey HSD procedure. The SPSS software
package version 17 was used to test the
significance of the experiment performed. In
the present study Group II was compared with
Group I (i.e., compared pregnant women with
normal women). Group III compared with Group
II to find out the effect of the preeclampsia effect
on antioxidant status. Group IIIA, Group IIIB,
Group IIIC was compared with Group III (i.e.,
comparison between pre and post treatment).
RESULTS

The results were shown in Figures 1 and 2. In


comparison among the three groups, the mean
values
of
lipid
peroxidation
product
malondialdehyde and the enzymatic antioxidants
superoxide dismutase, glutathione peroxidase
and glutathione reductase are among the three
groups were significant. In addition, the mean
value of pregnancy induced hypertension (Group
III) was statistically more significant (P< 0.001).
179

Vijayalakshmi et al.,

Int J Med ResHealth Sci. 2013;2(2):177-181

Table.1: Comparison of Lipid Peroxidation Product and Antioxidant Enzymes in Group I, Group
II & Group III.
Parameters

Group I
[n=42]

Group II
[n=50]

Group III
[n=60] Pretreatment

MDA (nmol/L)

1.75 0.41

2.760.4

3.740.4

SOD (IU/gmHb)

683.7658.2

597.2161.3

466.8537.5

GPx (IU/gmHb)

30.35 2.2

25.991.5

19.741.2

GSH (IU/gmHb)

12.55 1.9

9.070.8

5.810.7

Table.2: Comparisons of Lipid Peroxidation Product and Antioxidant Enzymes among Subgroups
Group III A, Group III B, Group III C with Group III (Pretreatment)
Parameters

Group III
[n=60]
Pretreatment

Group III A
Vit.E

Post treatment (N=20 in each group)


Group III B
Group III C
Omega 3 Fatty acids Omega 3 Fatty
acids+Vit E

MDA (nmol/L)

3.740.4

3.20 0.2

3.27 0.4

3.296 0.4

SOD (IU/gmHb)

466.8537.5

511.3627.0

512.7950.6

520.5331.27

GPx (IU/gmHb)

19.741.2

23.68 0.9

22.00 1.4

24.8 0.93

GSH (IU/gmHb)

5.810.7

7.86 0.6

6.59 0.88

8.87 0.53

Our results showed that supplementation of


Vitamin E, Omega 3 fatty acid alone and in
combination
has
significantly
increased
antioxidant enzyme status and significantly
decreased oxidative stress when compared to
unsupplemented patients (P< 0.001).
DISCUSSION

In preeclampsia the oxidant/antioxidant balance


is tipped in favour of oxidants at the expense of
antioxidants, because in plasma, elevated levels
of maternal lipid peroxides were measured.16
Antioxidant
enzymes
like
Superoxide
Dismutase, Glutathione Peroxidase, and
Glutathione Reductase form the first line of
defense against ROS and the decrease in their
activities contributes to the oxidant assault on
the cells. Dismutase converts superoxide oxygen
into Hydrogen Peroxide and in preeclamptic
oxidative stress conditions oxidative balance
system is disturbed. During normal pregnancy
there is an increase in oxidative stress and

therefore a parallel increase in antioxidant


activity is seen. The findings implicate oxidative
stress in the disease and cite the biochemical
rationale for clinical trials of antioxidants to
prevent
and
treat
pregnancy
induced
hypertension. Supplementation of antioxidants
along with polyunsaturated fatty acids,
particularly omega-3 fatty acids, may be useful
in the management of preeclampsia.
CONCULSION

Based on the results of the present study, it is


clear that in PIH there is an altered oxidant
status and decreased antioxidant enzyme status
suggesting that there is an indirect evidence for
the presence of oxidative stress in pre eclampsia.
In conclusion Vitamin E and Omega 3 Fatty
acid, alone or its combination protects the
human placenta against the deleterious effects of
reactive oxygen species. Our data support this
hypothesis that, over generation of free radicals
at the initial stage is promptly scavenged by
supplementation with vitamin E and Omega 3
180

Vijayalakshmi et al.,

Int J Med ResHealth Sci. 2013;2(2):177-181

fatty acids thereby reinforcing placental


resistance to oxidative injury. The role of
antioxidants in the prevention of preeclampsia is
controversial. From our study it was found that,
supplementing women with antioxidants,
combination of Vitamin E with Omega 3 fatty
acids (eicosapentanoic acid and docosohexanoic
acid) during preeclampsia may help to
counteract oxidative stress and thereby prevent
or delay the onset of preeclampsia and therefore,
improve the health of the mother and baby.
REFERENCES

1. Aquilina J, Harrington K. Pregnancy


hypertension and uterine artery Doppler
ultrasound. CurrOpinObstet Gynecol. 1996;
8: 435-40.
2. Helewa ME, Burrows RF, Smith J, Williams,
Brain P, Rabkin SW. Definitions, evaluation
and classification of hypertensive disorders
in pregnancy: Report of the Canadian
Hypertension
Society
Consensus
Conference: Can Med Assoc. J. 1997; 157
(6): 715-25
3. Chapell LC, Seed PT, Briley AL, Kelly FJ,
Lee R, Hunt BJ et al. Effect of antioxidants
on the occurrence of pre-eclampsia in
women at increased risk: A randomised trial.
Lancet 1999; 354: 810-16
4. Kabi BC, Goel N, Rao YN, Tripathy R,
Tempe A, Thakur AS. Levels of erythrocytic
malondialdehyde, vitamin E, reduced
glutathione, and G6PD activity and plasma
urate in patient of pregnancy induced
hypertension.
Indian
J
Med
Res
1994;100:23-25.
5. Henriksen T. The role of lipid oxidation and
oxidative
lipid
derivatives
in
the
development of precelampsia.
Semin
Perinatol 2000; 24:2932.
6. Uotila J, Tuimala R, Aarnio t, Pyykko K,
Ahotupa M. Lipid peroxidaiton products,
selenium dependent glutathione peroxidase
and vitamin e in normal pregnancy. Eur J
ObstetgynecolReprodBiol 1991; 42; 95-100.
7. Jeyabalan A, Caritis SN. Antioxidants and
Vijayalakshmi et al.,

the prevention of preeclampsia unresolved


issues. N Engl J Med 2006; 354: 18413.
8. Sandhya P, Thomas GA, Donald DH
Vitamin E supplementation in the prevention
of coronary heart disease. Mayo.Clin .Proc.
2001;76:1-7.
9. Kleijnen J, Knipschild P, RietgT. Vitamin E
and Cardiovascular disease. Eur.J.Clin.
Pharmacol.1989;37:541-44.
10. Connor SL, Connor WE. Are fish oils
beneficial in the prevention and treatment ofcoronary artery disease? Am J ClinNutr
1997; 66:1020- 31.
11. Harris WS: Extending cardiovascular
benefits
of
omega-3
fatty
acids.
CurrAtherosclerosis Rep, 2005; 57: 375-80.
12. Nadiger M.A., Chandrakala M.V. et al
Malondialdehyde level in different organs of
rats subjected to acute alcohol toxicity.
Indian J.Clin.Biochem.1986; 1; 133.
13. Hartz, J.W., Funakoshi, S., and Deutsch,
H.F., The levels of superoxide dismutase and
catalase in human tissues determined
immunochemically. Clin. chimActa. 1973;
46; 125-32
14. Paglia, D.E and Valentine, W.N. Studies on
the
quantitative
and
qualitative
characterization of erythrocyte glutathione
peroxidase J. Lab.Clin.Med., 1967; 70: 15869.
15. Goldberg D.M and Spooner RJ. Glutathione
reductase. In Bergmeyer HU ed. Methods
Enzymol Basel VerlagChemie In methods of
Enzymatic analysis (Bergmeyen, H.V.Ed)
3rdedn. 1983;3: 258-26

181
Int J Med ResHealth Sci. 2013;2(2):177-181

DOI: 10.5958/j.2319-5886.2.2.026

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 4 Feb 2013

Coden: IJMRHS
nd

Revised: 2 Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 7 Mar 2013

Research article

DETECTION OF INDUCIBLE CLINDAMYCIN RESISTANCE AMONG CLINICAL


ISOLATES OF STAPHYLOCOCCI FROM A RURAL TERTIARY CARE HOSPITAL
Makam Sri Rangakumar Manjunath1, Vijaya Rayapu2, *Dhandapany Senthil Pragash2, Ivvala Anand
Shaker3, Sandeep Kasukurthy4
1

Technician C National Institute of Virology, Bangalore, India


Department of Microbiology, 3Department of Biochemistry, Melmaruvathur Adhiparasakthi Institute of
Medical Sciences, Melmaruvathur, 603319, India.
4
Research Assistant, RMRC (ICMR), Port Blair, Andaman & Nicobar Island, India.
2

*Corresponding author email: drsenthiledu@gmail.com


ABSTRACT

Clindamycin has been used successfully to treat pneumonia and soft tissue infections caused by
methicillin-resistant Staphylococcus aureus. However, Clinical failure of clindamycin therapy has been
reported due to multiple mechanisms that confer resistance to Macrolide, Lincosamine and
Streptogramin antibiotics. Methods: A total of 96 staphylococcal isolates from different clinical
specimens were tested for inducible clindamycin resistance by the disk-diffusion induction test using
erythromycin (15g) disk and clindamycin (2g) disc placed 15mm (edge to edge). Results: Inducible
clindamycin resistance was detected in 47.22% of methicillin-resistant Staphylococcus aureus isolates
and in 21.67% of methicillin-sensitive Staphylococcus aureus isolates. In our setting, clindamycin is
safe and effective agent to treat both systemic sand localized Staphylococcal infections, but we
recommend that staphylococci isolates, particularly methicillin-resistant Staphylococcus aureus, are
tested by the D-test routinely to avoid treatment failure.
Keywords: Inducible clindamycin resistance, Methicillin resistant Staphylococcus aureus, D test.
INTRODUCTION
Staphylococcus aureus are recognized to be
caused nosocomial & community acquired
infections in every region of world.1 Skin & Soft
infections are common manifestation of
Staphylococcus diseases in many community
outbreaks.2
Antibiotic
resistance
in
Staphylococcus aureus has become an ever
increasing problem. Large outbreaks of infection
by Methicillin Resistant Staphylococcus aureus

(MRSA) were recorded in many hospitals in


Australia, USA, Britain and Ireland. Many of
these outbreaks appear to have been caused by a
single epidemic strain that was transferred
between hospitals by the movement of patients.3
Clindamycin is a frequent choice for treating
both MRSA & MSSA infections particularly for
skin & soft tissue infections and as an alternative
in the penicillin allergic patients.4
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The Macrolide Lincosamine Streptogramin-B


(MLSB) family of antibiotics is commonly used
in the treatment of Staphylococcus infections. 1
Erythromycin & Clindamycin are separate
antimicrobial agents their mechanisms of action
(inhibition of protein synthesis) and mechanism
of resistance are similar. 5 However, one
important issue in clindamycin treatment is the
risk of clinical failure during therapy.
Therapeutic failures caused by MLSB inducible
resistance are being more commonly reported.1
MLSB resistance can be detected by a simple test
known as disk approximation test or D-test.4,6
Erythromycin are the most effective inducer of
inducible MLSB resistance, Antimicrobial
susceptibility data are important for the
management of infections but false susceptibility
result may be obtained if isolates are not tested
for inducible clindamycin resistance (iMLSB).7
Hence this study was conducted to know the
occurrence of inducible clindamycin resistance
(iMLSB) among MRSA and MSSA in this
region.
MATERIALS AND METHOD

The present study was carried out in the


department of Microbiology, P.E.S. Institute of
Medical Sciences & Research, Kuppam.
Institutional Ethical Committee clearance was
obtained for the study. A total of 96 consecutive,
non-repetitive isolates of Staphylococcus aureus
from various clinical samples such as urine, pus,
sputum, suction tips, stool, blood, body fluids,
vaginal swabs etc., were collected for the study
over a period of 6 months (January 2009 to June
2009) from hospitalized patients. The study
protocol was explained and informed consent
was obtained from the particpants of the study.
The isolates were first identified as
Staphylococcus aureus by standard biochemical
techniques8 and methicillin resistance was tested
by Kirby Bauer disk diffusion method using
Oxacillin disc (1g) obtained from Hi-media
laboratories, on Muller Hinton agar plates
containing 4% Sodium chloride. The plates were

incubated and isolates were considered


methicillin resistant if the zone of inhibition was
10mm or less. After making a lawn culture of the
isolated Staphylococcus, erythromycin (15g)
disk was placed 15mm (edge to edge) from a
clindamycin (2g) disc.1 The plates were
incubated at 37oC and the results read.
Interpretation of the test was done as stated
below:
I. MS phenotype - Staphylococcal isolate
exhibited resistance to erythromycin (zone
size 13 mm) while sensitive to
clindamycin (zone size 21 mm) and
giving circular zone of inhibition around
clindamycin was labelled as having this
phenotype.
II. Inducible MLSB (iMLSB) phenotype Staphylococcal isolate showed resistance
to erythromycin (zone size 13 mm) while
being sensitive to clindamycin (zone size
21 mm) and giving D -shaped zone of
inhibition around clindamycin with
flattening towards erythromycin disc was
labelled as having this phenotype.
III. Constitutive MLSB phenotype - this
phenotype
was
labeled
for
those Staphylococcal isolates,
which
showed resistance to both erythromycin
(zone size 13 mm) and clindamycin
(zone size 14 mm) with circular shape of
the zone of inhibition if any around
clindamycin.
Quality control strains:
Control strains used for disk diffusion test were:
1. Staphylococcus aureus ATCC 25923 (used for
routine quality control).9, 10
2. In house strains of Staphylococcus aureus
showing D-test positive repeatedly was used
as positive control for inducible Clindamycin
resistance.
RESULTS

Out of 96 Staphylococcus aureus, 37.5% were


MRSA & 62.5% were MSSA. Inducible
Clindamycin resistance among Staphylococcus
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aureus was 31.25%. Among MRSA, 47.22%


were D-test positive and 27.78% were D-test
negative. In MSSA 21.67% were D-test positive
and 40% were D-test negative (TABLE: 1).
8(22.22%) isolates in MRSA & 23(38.33%)
isolates in MSSA were sensitive to both
Erythromycin & Clindamycin (TABLE: 1).
The distribution of D-test positive MRSA and
MSSA among various clinical samples is shown
in Table: 2.

Highest number 44(45.83%) of Staphylococcus


isolates was from pus sample, showing inducible
resistance of 16.67% in MRSA & 8.33% in
MSSA (TABLE: 2).Highest number 40(41.66%)
of Staphylococcus isolates were from department
of surgery, 33.33% of MRSA & 46.66% of
MSSA (TABLE: 3).

Table.1: Distribution of inducible Clindamycin Resistance in Staphylococcus aureus*


Staphylococcus
aureus

No of
Isolates

D-Test positive
(E-R;Cd-S)
with D-shape

D-test negative
(E-R; Cd-S)

Sensitive to
(E-S; Cd-S)

Resistant to
(E-R; Cd-R)

MRSA

36 (37.5%)

17 (47.22%)

10 (27.78%)

8 (22.22%)

1 (2.78%)

MSSA

60 (62.5%)

13 (21.67%)

24 (40%)

23 (38.33%)

Total

96(100%)

30(31.25%)

34(35.41%)

31(32.30%)

1(10.41%)

4(11.1%)

6(16.6%) 1(2.7%)

5 (8.3%)

10(16.6%) 12(20%)

Urine

25(26.0%) 4(11.1%)

2 (5.5%)

1 (2.7%) _

3(5%)

7(11.6%)

8(13.3%)

Sputum

11(11.4%) 2(5.5%)

1 (2.7%)

1 (2.7%) _

2(3.33%)

3(5%)

2(3.3%)

Throat
swab

6(6.25%)

2(5.5%)

1 (2.7%)

1(1.67%)

2(3.3%)

Suction
tip

6(6.2%)

2 (5.5%)

1(2.7%)

1(1.67%)

1(1.6%)

1(1.67%)

Plural
fluid

4(4.1%)

1(2.7%)

1(2.78%)

1(1.67%)

1(1.6%)

Total

90(100%) 17(47.2%)

10(27.7%)

8(22.2%) 1(2.7%)

23(38.3%)

13(21.6%) 24(40%)

Resistant to
(E-R; Cd-R)

44(45.8%) 6(16.6%)

Sensitive to
(E-S; Cd-S)

D-test negative
(E-R; Cd-S)

D-Test positive
(E-R;Cd-S)
with D-shape

Sensitive to
(E-S; Cd-S)

Pus

Resistant to
(E-R; Cd-R)

D-test negative
(E-R; Cd-S)

D-Test positive
(E-R; Cd-S) with
D-shape

Table.2:Specimen wise distribution of inducible Clindamycin resistance in Staphylococcus aureus*


Sample No
of
MRSA
MSSA
Isolates

*E-Erythromycin, Cd-Clindamycin, R-Resistant, S-Sensitive, MRSA-Methicillin


Staphylococcus aureus, MSSA Methicillin resistant Staphylococcus aureus

resistant

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Table.3:Department wise distribution of inducible Clindamycin resistance in Staphylococcus


aureus

1(2.78%) 1(2.78%)

3 (5%)

Medicine

22(22.91%) 4(11.11%) 2 (5.55%)

3 (8.33%) _

2(3.33%) 6 (10%)

5 (8.33%)

Ortho

11(11.45%) 2 (5.55%) 2 (5.55%)

2(3.33%) 3 (5%)

2 (3.33%)

OBGY

12(12.5%)

2 (5.55%) 1 (2.78%)

3 (8.33%) -

3 (5%)

2 (3.33%)

1 (1.67%)

Paed

5(5.20%)

1 (2.78%) _

1 (2.78%) _

1(1.67%) 1 (1.67%)

1 (1.67%)

ENT

6(6.25%)

2 (5.55%) 1 (2.78%)

2(3.33%) 1 (1.67%)

Total

96(100%)

17(47.2%) 10(27.8%) 8(22.22%) 1(2.78%) 13(21.6%) 24 (40%)

23(38.3%)

Sensitive to
(E-S; Cd-S)

Sensitive to
(E-S; Cd-S)
_

11(18.33%) 14(23.3%)

E-Erythromycin, Cd-Clindamycin, R-Resistant, S-Sensitive, MRSA-Methicillin


Staphylococcus aureus, MSSA Methicillin resistant Staphylococcus aureus

Resistant to
(E-R; Cd-R)

40(41.66%) 6(16.67%) 4(11.11%)

D-test negative
(E-R; Cd-S)

Surgery

D-Test positive
(E-R; Cd-S) with
D-shape

MSSA

Resistant to
(E-R; Cd-R)

MRSA
D-test negative
(E-R; Cd-S)

No
of
Isolates
D-Test positive
(E-R; Cd-S) with
D-shape

Sample

resistant

Fig 1: Staphylococcal isolate showing resistance to erythromycin disc while being sensitive to
clindamycin disc and giving D-shaped zone of inhibition around clindamycin with flattening towards
erythromycin disc.

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DISCUSSION

Staphylococcus aureus infections are an


important cause of morbidity in hospitals and the
community. The spectrum of diseases produced
by this organism varies from toxin mediated
phenomenon to pyogenic infection either primary
or post operative both in the community as well
as in hospitals. Staphylococcus aureus has been
known to acquire resistance to most antibiotic
including the penicillinase resistant ones like
methicillin.
Drug selection is important in the treatment of
MRSA infections. Inducible clindamycin occurs
in the presence of strong methylase inducers like
Macrolide antibiotics such as Erythromycin or
Azithromycin. MLSB resistant strains are seen
sensitive falsely in the presence of a weak
inducer like clindamycin and Quinupristin.4, 11 A
major concern with regard to use of clindamycin
for staphylococcal infections is the possible
presence of inducible resistance to clindamycin.
Also the incidence of clindamycin resistance
varies by geographical area and therefore local
statistics are crucial to guide empiric therapy.12
The occurrence rate of inducible Clindamycin
resistance in the present study is 47.2% in MRSA
& 21.67% in MSSA. Earlier study in the same
hospital during 2004 revealed 19% Inducible
Clindamycin resistance in MRSA & 19.2% in
MSSA respectively.13 In 2008, Ajantha GS et al 9
observed D-test positives in 74% of MRSA &
45% of MSSA isolates. In 2003, Delialioglu N et
al 14 from turkey reported that 5.4% D-test
positive in MRSA & 10.7% D-test positive in
MSSA. In 2004, it has been reported that 12.31%
in MRSA & 68% in MSSA isolates by Levin TP
et al.15 Similarly in the study conducted by
Matthew V.N.OSulivan et al 200516 reported
27.12% in MRSA & 9.5% in MSSA isolates.
It was also observed that percentages of
inducible resistance and constitutive clindamycin
resistance were higher amongst MRSA as
compared to MSSA. This was in concordance
with few of the studies reported before.1 Some
studies have shown a very high frequency of
inducible resistance MRSA.9 On the contrary,

Schreckenberger et al and Levin TP et al have


shown a higher percentage of inducible
resistance in MSSA as compared to MRSA.12,15
Clindamycin, is a semi synthetic derivative of
Lincosamine, has excellent tissue penetration
like lung, pleural fluid & bile but it is poorly
penetrated in CSF & meningitis and crosses the
placenta & enters fetal tissue. Clindamycin
distributes well into bones & it is an effective
antibiotic in treating Osteomyelitis. It is a rapid
oral absorption, no requirement of dosage
adjustment in the presence of renal disease.17
Staphylococcus showing resistance to Macrolide,
Lincosamine,
Streptogramin-B
(MLSB)
antibiotics generally involved drug inactivation,
target site modification, impermeability (or)
efflux mechanism. 18
Clindamycin resistance can develop in
staphylococcal isolates with inducible phenotype,
and from such isolates, spontaneous constitutive
resistance mutants have arisen both in vitro and
in vivo during clindamycin therapy.1 Reporting
Staphylococcus aureus as susceptible to
clindamycin without checking for inducible
resistance may result in institution of
inappropriate clindamycin therapy.19
Because of the emergence of resistance to
multiple antibiotics among staphylococci the
therapeutic options available for clinicians are
limited. A therapeutic decision is not possible
with-out the relevant clinical and microbiological
data. The increasing frequency of MRSA with in
vitro inducible clindamycin resistance raises a
concern of clindamycin treatment failures.20
Therefore, using in vitro erythromycin resistance
as a surrogate marker for all MLS antibiotics,
and thereby avoiding them as a treatment option,
would be inappropriate. A therapeutic decision is
not possible without the relevant antibiotic
susceptibility data. This is where the D test
becomes significant.21

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CONCLUSION

Due to the emergence of resistance to


antimicrobial agents, the accurate drug
susceptibility data of the infecting microbe are
essential for deciding the therapeutic option. The
Erythromycin-Clindamycin disc approximation
test or the D test is a simple, reliable method to
detect Clindamycin resistance in erythromycin
resistant isolates. The D test is an easy to
perform test which can enable us in guiding the
clinicians regarding the judicious use of
clindamycin in skin and soft tissue infections. 186
ACKNOWLEDGEMENT

The author Makam Sri Rangakumar Manjunath


is very thankful to the Principal and to the
Management of P.E.S. Institute of Medical
Sciences & Research, Kuppam for their generous
support and encouragement during the period of
study.
REFERENCES
1. Gurdal Yilmaz, Kemalettin Aydin, Serap
Iskender, Rahmet Caylan and Ifthar Koksal.
Detection Of Inducible Clindamycin
Resistance Among Staphylococci. J Med
Microbiol. 2007;56:342-45.
2. Fokas S, Tsironi M, Kalkani M, and
Dionysopouloy M. Prevalence of Inducible
Clindamycin Resistance in MacrolideResistant
Staphylococcus
Spp.
Clin
Microbiol Infect. 2005;11:337-40.
3. Gearald L.Mendell, John E. Bennett and
Raphael Dolin, editors. Principles and
practice of infectious diseases. 6th edition:
Churchill Livingstone Inc; 2005;1:396-11.
4. Fiebelkorn KR, Crawford SA, Mc Elmeel
ML and Jorgensen JH. Practical Disk
Diffusion Method for Detection of Inducible
Clindamycin Resistance in Staphylococcus
Aureus & Coagulase negative Staphylococci.
J Clin Microbiol. 2003; 41(10):4740-44.
5. Mallick SK, Basaks, Bose S Inducible
clindamycin resistance in Staphylococcus
Aureus-A Therapeutic Challenge. Journal of

Clinical
and
Diagnostic
Research.
2009;3:1513-18.
6. Clinical and laboratory standards institute.
Performance standards for antimicrobial
susceptibility
testing;
seventeenth
informational
supplement. Clinical
Laboratory
Standards
Institute. 2007;27(1):44-51.
7. Gerard Lina, Alain Quaglia, Marie-Elisadeth
Reverdy,
Roland
Leclercq,
Francois
Vandenesch,
and
Jerome
Etienne.
Distribution of genes encoding resistance to
Macrolides,
Lincosamides,
and
Streptogramins
among
Staphylococci.
Antimicrobial agents & chemotherapy.
1999;43:1062-66.
8. Kloos WE, Banerman TL. Staphylococcus
and Micrococcus. In: Murray PR, Baron EJ,
Pfaller MA, Tenover FC, Yolken RH,
editors. Chapter 22. Manual of Clinical
Microbiology. Washington DC: ASM Press;
1999. pp. 264-82.
9. Ajantha GS, Kulkarni RD, Shetty J,
Shubhada C, Jain P. Phenotypic detection of
Inducible Clindamycin Resistance among
Staphylococcus aureus isolates by using the
lower limit of Recommended inter- disk
distance. IJPM 2008;51:376-78.
10. Angel MR, Balaji V, Prakash J,
Bramahadhatan
KN,
Mathews
MS.
Prevalence of Inducible Clindamycin
Resistance in Gram positive organisms in a
Tertiary care center. IJMM 2008;26:262-64.
11. Christine D. Steward, Patti M. Raney,
Allison K. Morrell, Portia P. Williams, Linda
K. McDougal, Laura Jevitt, John E.
McGowan Jr. and Fred C. Testing for
Induction of Clindamycin Resistance in
Erythromycin-Resistant
Isolates
of
Staphylococcus aureus. Tenover. J. Clin.
Microbiol. 2005, 43(4):1716-21.
12. Schreckenberger PC, Ilendo E, Ristow KL.
Incidence of constitutive and inducible
clindamycin resistance in Staphylococcus
aureus and coagulase negative staphylococci
187

Manjunath etal.,

Int J Med Res Health Sci. 2013;2(2):182-188

in a community and a tertiary care hospital. J


Clin Microbiol. 2004;42(6):2777-79.
13. Navaneeth BV. A preliminary in Vitro Study
on Inducible & Constitutive Clindamycin
Resistance in Staphylococcus aureus from a
South Indian Tertiary Care Hospital. Int J
Infect dis. 2006;10:184-85.
14. Delialioglu N, Aslan G, Ozturk C, Baki V,
Sen S, Emekdas G. Inducible clindamycin
resistance in Staphylococci isolated from
clinical
samples. Jpn
J
Infect
Dis.2005;58:104-6.
15. Levin TP, Suh B, Axelrod P, Truant AL,
Fekete T. Potential Clindamycin resistance in
Clindamycin-susceptible,
Erythromycinresistant Staphylococcus aureus: Report of a
clinical
failure. Antimicrob
Agents
Chemother. 2005;49(3):1222-24.
16. Matthew V. N. O'Sullivan, Yongwei Cai,
Fanrong Kong, Xianyu Zeng and Gwendolyn
L. Gilbert. Influence of disk separation
distance on accuracy of the disk
approximation atest for detection of Inducible
Clindamycin resistance in Staphylococcus
spp. Journal of Clinical Microbiology 2006;
44(11): 4072-76.
17. Martinez Aguilar G, Hammerman WA,
Manson EO, Kaplan SL. Clindamycin
treatment of invasive infections caused by
community acquired Methicillin resistant and
Methicillin
susceptible
Staphylococcus
aureus in children. Pediatr Infect Dis J. 2003;
22:593-98.
18. Madhumati Kamat, M. A. Vagarali, S.G.
Karadasai Inducible clindamycin resistance
in Staphylococci: should clinicians and
microbiologists be concerned? Journal of the
scientific society, 2012;39(1):7-9.
19. Rodrigues Perez LR, Caierao J, Souza
Antunes AL, Alves dAzevedo P. Use of D
test method to detect inducible Clindamycin
resistance
in
Coagulase
Negative
Staphylococci (CoNS). Braz J Ifect Dis
2007;11(2):186-88.
20. Rao GG. Should Clindamycin be used in
treatment of patients with infections caused

by Erythromycin resistance Staphylococci?.


J. Antimicrob.chemother. 2000;45:715-16.
21. Ciraj M, Vinod P, Sreejith G, Rajani K.
Inducible Clindamycin resistance among
clinical isolates of Staphylococci. IJPM
2008; 52(1): 49-51.

188

Manjunath etal.,

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DOI: 10.5958/j.2319-5886.2.2.027

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 8 Feb 2013


Research article

Coden: IJMRHS
th

Revised: 4 Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted:8

Mar 2013

A STUDY ON HEALTH HAZARDS IN DRY CHILI MARKET WORKERS IN THE AGE


GROUP OF 16 TO 55 YEARS OLD
Avinash P Tekade1, Gullapalli HS 2, *Namrata H Gullapalli3
1

Associate Professor, Department of Physiology, Katuri Medical College and Hospital, Guntur, Andhra
Pradesh.
2
Associate Professor, Department of Physiology, Vinayaka Missions Medical College and Hospital,
Karaikal, Puducherry.
3
Dietitian and nutritionist, Vinayaka Missions Medical College and Hospital, Karaikal, Puducherry.
*Corresponding author email: hgullapalli2000@gmail.com
ABSTRACT

Background: The workers who are involved in the handling dry chili face some occupational hazards.
In this industry there is always danger of polluting the environment with very small irritating particle.
Inhalation of this fine particulate matter is responsible for the various respiratory symptoms which
include chronic obstructive disease (COPD) and allergic rhinitis and associated ocular symptoms like
itchy eye, red eye and conjunctivitis. Exposure of this fine chili particle is associated with the skin
problems like burning sensation, irritation and dermatitis. Methods and material: This is the casecontrol observation study in which 378 male workers who are involved in handling the chili powder
were selected after they meet the inclusion and exclusion criteria. 203 control subjects are selected who
are not associated with the chili market at all. Detail history taking and physical examination done all
study and control subjects to see for the respiratory, eye and skin problem. The symptoms are compared
between the study and control subjects. Results: The incidence of the respiratory, eye and skin related
problems are significantly at a higher level than the control subjects. Conclusion: The worker in the dry
chili market significantly facing the health hazards due to the exposure of the finest chili powder which
can be prevented with the some measures such as using face masks, socks and cotton shirts and pants
which will prevent the contact of the body with the fine irritating particles.
Keywords: Chili powder, COPD, Dermatitis, Itchy eye
INTRODUCTION

Guntur the biggest chili market in Asia, India is


one of the leading producers of fresh and dry
chili along with China it is accounting for around
50% of the world total production of chili
market. These chilies producing giants are also

the biggest consumers of fresh chilies, and


consume over 90% of their own production4.
Chili crop has the potential to create more jobs
than rotational crops (such as paddy rice) and

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Int J Med Res Health Sci. 2013;2(2):189-193

alternative crops (such as cucumber, watermelon


etc.) owing to a higher requirement for intensive
care throughout the crop life mainly due to
chilis higher vulnerability to diseases. The
worrying matter for the dry chili market workers
is that they are continuously exposed to irritating
fine particles (e.g. smokers, industrial workers
concerned with fine particles, chili workers).
They show the symptoms of cough,
expectoration, sore throat, etc. In the chili market
the workers who are exposed continuously to the
irritating chili particles and they usually show the
classical symptoms of COPD as cough, sputum
expectoration, exertional dyspnea (increased
efforts to breathing, Heaviness, air hunger, or
gasping)1.
Various documented studies indicate the chronic
inhalation of the fine particle matter will increase
the incidence of the COPD or exacerbate the
symptoms of existing COPD5, 6. In chili markets
workers due to the irritating chili products
particles the problem of allergic rhinitis is more
common, which is characterized by sneezing,
rhinorrhea, obstruction of nasal passages;
conjunctival, nasal, and pharyngeal itching and
lacrimation. 40% of rhinitis patient manifest with
asthma. Rhinitis patient nasal mucosa is pale and
boggy. The conjunctival congestion and
edematous swelling of the turbinates and mucous
membrane with obstruction of the sinus ostia and
eustachian tubes precipitates secondary infection
of the sinuses and middle ear respectively.2
Nasal polyps representing mucosal protrusions
containing edema fluid with variable numbers of
eosinophils can increase obstructive symptoms
and can concurrently arise within the
nasopharynx or sinuses2.
METHODS AND MATERIALS

This study is performed in the Department of


Physiology, Katuri Medical College and Hospital
after getting the clearance certificate for the
study from the Institutional Ethical Committee.
The subjects are selected from the Guntur Chili
Yard which is the biggest in Asia. The selected

study subjects should have been facing the dry


chili exposure at least since last 7 years
continuously. The methods adopted for the
present study are consent taking, history taking,
general & systemic examination. Then the
complete history is obtained regarding their work
and physical examination is carried out. For the
study subjects exclusion criteria and inclusion
criteria applied. The subjects who met the
inclusion and exclusion criteria given below,
such 378 male workers selected were included in
this study.
Inclusion criteria: In the Age group of 16- 55
year
Exclusion criteria: 1. Below 16 years and
above 55 years 2. Congenital abnormality 3. Any
chronic illness
To find the risk at which the study subjects are
exposed compared to non exposed subjects, we
have taken the control group (n = 203) which is
not related to chili market works anyway. All the
participants were informed about the purpose of
studying nature, and informed consent has been
obtained.
Observation: The workers in the dry chili
markets are mostly males. In the process of this
study we found that there are certain conditions
which are more prevalent in the workers of the
dry chili market are following:Respiratory problems: 1. Dry Cough with
wheeze or without wheeze 2. Cough with
expectoration 3. Exertional dyspnea 4. Sore
throats 5. Nasal irritation 6. Nasal polyp
Eye problems: 1. Burning sensation in the eyes
2. Increased tear flow 3. Conjunctivitis
Skin Problems: 1. Burning sensation 2.
Irritation 3. Dermatitis
These problems are significantly higher in the
dry chili market workers than control groups;
obviously the reason is continuous exposure to
the dry chili and its products.

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RESULTS AND DISCUSSION

Table 1: Concise table showing Prevalence of Respiratory, Eye and Skin Problem among workers
Age in years

Respiratory
problems

Group

Eye
problems

Skin
problems

Worker group (N=378)

119(31.48%)

91 (24.07%)

64 (16.93%)

Control group (N=203)

18 (8.86%)

11 (5.41%)

6 (2.95%)

16-55

The Respiratory problem in the control group it


is 8.86%, in chili market workers is 31.48%
which is significantly higher. (Chi sq = 37.46,
df= 1, p < 0.001).
The Eye problem in the control group is 5.41%
and in chili market workers is 24.07% which is
significantly higher. (Chi sq = 56.13, df= 1, p <
0.001)
The Skin problem in the control group it is
2.95%, in chili market workers is 16.93% which
is significantly higher. (Chi sq = 24.32, df= 1, p
< 0.001
It shows the there is a significant increase in the
respiratory, skin and eye related problems.
There is an increase in the respiratory problems
such as cough arising due to the handling of the
chili powder is also supported by some other
studies18. The origin of any respiratory problem
can be traced to the effect of the fine particulate
matter in the development of the COPD. An
important defense mechanism against inhaled
particles in the airways is the mucociliary
escalator. Mucus has a major role in protecting
the airways, particularly as it is a rich source of
antioxidants7. In the large proximal airways,
goblet cells secrete mucus, which traps deposited
particles and is then propelled upwards by
ciliated cells to be either expectorated or
swallowed. Although mucus may in some
circumstances have a protective role, induction
of increased mucus secretion by irritating particle
or the particulate matter8 may contribute to the
development of exacerbations of COPD, by
increasing airway resistance and by the
development of mucus plugging in the smaller

peripheral airways9. Macrophages present in the


airway walls and on the surfaces of the airways
can phagocytose particles, but may, as a result,
release inflammatory mediators such as IL-8 and
tumor necrosis factor (TNF). In COPD, numbers
of macrophages are increased9; consequently, the
levels of inflammatory mediators are elevated in
sputum10. The additional insult of an inhaled
irritant particle could clearly aggravate the
background inflammation in COPD leading to
exacerbations. These mechanisms due to the
inhalation of the fine particulate matter arising
due to the chili handling are involved in the
aggravating the respiratory disease symptoms
mainly COPD. The incidence upper respiratory
tract disease such as allergic rhinitis also
increases. The exposure of fine chili particles
causes the production of the immunoglobulin
(Ig) -E is the proximate cause of perennial
allergic rhinitis. Circulating IgE antibodies bind
to the high affinity IgE receptor on mast cells and
basophils. IgE antibodies, bound to the receptors
cross linked by an allergen, initiate the secretion
of inflammatory mediators including histamine,
leukotrienes, and cytokines. These mediators can
induce both acute and chronic changes that result
in symptoms of allergy sneezing, rhinorrhea,
obstruction of nasal passages; conjunctival,
nasal, and pharyngeal itching and lacrimation11.
The allergic rhinitis is the cause of troublesome
ocular symptoms like itching eyes, watery eyes,
red eyes and swollen eyelids12. Apart from these
problems there is increased incidence of the skin
related problem like the irritant contact
dermatitis can be attributed to the presence of the
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capsaicin in the chili. Capsaicin, the active


principle of hot peppers of the genus Capsicum,
exhibits broad bioactivity. It targets neuronal
structures which contain substance P, clinically
seen as gastrointestinal and dermatologic
irritation, bronchospasm and fibrinolysis13. When
the sensitive skin comes repeatedly in contact
with the chili powder, capsaicin depolarizes
nerves leading to vasodilatation, smooth muscle
stimulation, glandular secretions, and sensory
nerve activation. Because the nerves, and not the
skin itself, are affected, dose-related cutaneous
burning pain, irritation, and erythema, but not
blistering ensue14. The pain has been described
as a dull ache, like sunburn, or like an intense,
radiating heat, throbbing and prickling. These
symptoms are often delayed and may last hours
to days15. This problem, known as Hunan Hand
Syndrome16,17. Hunan hand syndrome, managed
successfully by using a multimodal approach
comprised of a continuous stellate ganglion
block, gabapentin, local ice water, and
fluocinonide application19. The problems arising
due to the handling of chili powder can be
prevented by following ways.
Simple preventive technique can alleviate these
health hazards to the workers.
1.To prevent the respiratory system related
problems the use of a face mask which will
cover the mouth and nose completely and
effectively so that the entry of the fine
particulate matter in the respiratory tract can
be prevented. In effect this will prevent the
problems arising due to the inhalation of the
fine particles on the respiratory tract.
2. Prevention of the Eye related problems use of
the goggles which will cover the eyes
completely and effectively should be
promoted. This will prevent entry of the fine
particulate matter in the eye which can
effectively prevent the eye related problems
arising due to the handling of chili in the
market.
3. For the prevention of the skin related
problems we have to take into account the

atmospheric condition of the Andhra Pradesh


which quite on the hot side, so these workers
should use the thick cotton shirts, pants,
socks and shoes which will cover the body
completely and effectively. Aim behind using
such clothing is to prevent the contact of the
fine particulate matter in the chili market
with the skin so that eventually it will prevent
the skin related problems.
4. Personal cleanliness While using the face
mask, goggles, thick cotton shirts, pants,
socks and shoes precaution should be taken
that these should not be shared among the
workers, which might lead to the spread of
communicable diseases.
CONCLUSION

Chili market workers are suffering from the


health hazards like respiratory, eye and skin
related problems which can be prevented by the
use of some simple preventive techniques.
REFERENCES

1. Principals of internal Medicine. Vol. II, 17th


Edition Harrisons. Allergic Rhinitis page
number 1596 to 1606, 1635 to 1643, 2068 to
2070
2. Prasit K, Nopporn H, Dusit S, Sukhontha S,
nawarat S. Serum cholinesterase levels in
Thai chilli farm workers exposed to chemical
pesticides.J Occup Health.2010;52:89-98
3. Aus AID. Small scale Review of Chili,
Agricultural
Policy
with
Prosperity
Initiative.2009.14-88
4. Gong H, Linn WS, Terrell SL, Anderson KR,
Clark KW, et al. Exposures of elderly
volunteers with and without chronic
obstructive pulmonary disease (COPD) to
concentrated ambient fine particulate
pollution. Inhal Toxicol. 2004;16(11):731-44.
5. Gong H Jr, Linn WS, Clark KW, Anderson
KR, Geller MD, Sioutas C. Respiratory
responses to exposures with fine particulates
and nitrogen dioxide in the elderly with and
192

Avinash et al.,

Int J Med Res Health Sci. 2013;2(2):189-193

without COPD. Inhal Toxicol. 2005


;17(3):123-32.
6. Cross, CE, van der Vliet, A, ONeill, CA, et
al. Oxidants, antioxidants and respiratory
tract lining fluids. Environ Health Perspect
1994; 102(10), 185-191
7. Jany, B, Gallup, M, Tsuda, T, et al. Mucin
gene expression in rat airways following
infection and irritation. Biochem Biophys
Res Commun 1991; 181, 1-8
8. Jeffery, PK Structural and inflammatory
changes in COPD: a comparison with
asthma. Thorax 1998; 53, 129-136.
9. Keatings, VM, Collins, PD, Scott, DM, et al.
Differences in interleukin-8 and tumornecrosis-factor-alpha in induced sputum from
patients with chronic obstructive pulmonary
disease or asthma. Am J Respir Crit Care
Med 1996; 153, 530-534.
10. Bush RK. Etiopathogenesis and management
of perennial allergic rhinitis: a state-of-the-art
review. Treat Respir Med. 2004;3(1):45-57.
11. Klossek JM, Annesi-Maesano I, Pribil C,
Didier A. The burden associated with ocular
symptoms in allergic rhinitis.Int Arch
Allergy Immunol. 2012;158(4):411-17.
12. Tominack RL, Spyker DA. Capsicum and
capsaicin-a review: case report of the use of
hot peppers in child abuse. Clin Toxicol
1987; 25(7): 591- 601.
13. Burnett JW. Capsicum pepper dermatitis.
Cutis. 1989 Jun;43(6):534.
14. Jones LA, Tandberg D, Troutman WG.
Household treatment for Chile burns of the
hands. Clin Toxicol 1987; 25: 483- 491.
15. Williams SR, Clark RF, Dunford JV. Contact
dermatitis associated with capsaicin: Hunan
hand syndrome. Ann Emerg Med 1995; 25:
713- 715.
16. Weinberg RB. Hunan hand. N Engl J Med.
1981;30;5:1020.
17. Blanc P, Liu D, Juarez C, Boushey HA.
Cough in hot pepper workers. Chest.
1991;99(1):27-32.
18. Saxena AK, Mandhyan R. Multimodal
Approach for the Management of Hunan

Hand Syndrome: A Case Report. Pain Pract.


2012 Jun 11.

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Int J Med Res Health Sci. 2013;2(2):189-193

DOI: 10.5958/j.2319-5886.2.2.037

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 10 Feb 2013


Research Article

Coden: IJMRHS
th

Revised: 8 Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 10 Mar 2013

A STUDY ON AUTONOMIC EFFICIENCY IN DIABETIC FEMALES OF MORE THAN TEN


YEARS DURATION
*Ekambaram Gnanadesigan1, BC Vastrad1, Nafees1, Anand P2, Gnanagurudasan3, Balumahendran K4
1

Department of Physiology, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh
Division of Physiology, Rajah Muthiah Dental College, Annamalai University, Annamalai Nagar,
Tamilnadu, India
3
Department of Anatomy, Malabar Medical College, Kozhikode, Kerala, India
4
Division of Biochemistry, Rajah Muthiah Medical College, Annamalai University, Annamalai Nagar,
Tamilnadu, India
2

*Corresponding author email:drdesigan82@yahoo.com


ABSTRACT

Background: Diabetes mellitus is a metabolic disorder affecting various organs of the body. In many
patients with diabetes mellitus, diabetes related complications may be present by the time it is clinically
diagnosed. One such diabetic complication which remains subclinical is diabetic autonomic neuropathy.
Aim: The present investigation aims at assessing the autonomic nervous system efficiency in females
with type 2 diabetes mellitus of more than 10 years duration in rural areas of Kuppam, Andhra Pradesh,
India. Methods: Autonomic nervous system efficiency was assessed by using three parasympathetic
functions to test namely heart rate response to deep breathing, standing from a lying position, Valsalva
maneuver. And two sympathetic function test namely blood pressure response to standing from a lying
position, and sustained handgrip. Results: It was observed that there is a statistically significant decrease
in parasympathetic activity and increase in sympathetic activity in type 2 diabetic females.Conclusion:
We found that the females suffering from type 2 diabetes mellitus for more than 10 years duration
exhibit autonomic dysfunctions in Kuppam, Andhra Pradesh, India.
Keywords: Autonomic function test, Autonomic Nervous System, Diabetes mellitus.
INTRODUCTION

Diabetes mellitus (DM) is a pandemic clinical


condition. Estimates indicate that the total
number of people with DM will double from 171
million in 2000 to 366 million in 2030. By 2030,
more than 75% 0f people with DM will live in
developing countries. The greatest relative
increase is expected to occur in countries in the

Middle East, sub-Saharan Africa, and India1. DM


in these countries is associated with higher
mortality rates because of acute and chronic
complications that occur early in the course of
the disease2. DM affects all the body systems
especially the nervous and cardiovascular
system. A well known relation exist between
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Int J Med Res Health Sci.2013;2(2):194-199

autonomous neural system alterations and


cardiovascular mortality3. There is ample clinical
and cross-sectional epidemiological evidence
connecting diabetes to subsequent autonomic
nervous system dysfunction4-6. Peripheral and
autonomic diabetic neuropathy is a common
chronic complication of DM that occurs nearly in
half of diabetic patients7. Diabetic autonomic
neuropathy in patients with diabetes is an
irreversible complication, but early detection is
important, because although the condition cannot
be reversed, intensive diabetes care may delay it
further development8.
There are many studies done on the evaluation of
autonomic nervous system activity in type 2
diabetes mellitus in developed countries. There is
scarcity of comparable study from developing
countries like India and also the scarcity of data
in diabetic females of rural population. Hence
this study is carried out in the Kuppam area of
Chittoor district of Andhra Pradesh, India.
MATERIALS AND METHODS

This study was conducted in the department of


physiology, PES institute of medical sciences
and research, Kuppam, Andhra Pradesh, India.
This study was undertaken after approval by the
institutional ethical committee overseeing human
studies. Experiments were done in accordance
with Helsinki declaration of 1975. Subjects
above 40 years females of age were included.
The study group comprises 30 females with type
2 diabetes mellitus for more than 10 years
duration who visited the diabetic clinic in PES
hospital during the period 2009-2010. The
control group comprises 30 healthy females. All
the subjects in the study and control groups were
subjected to detailed clinical examination and
other relevant investigations as required.
Diabetic patients with systemic diseases and
kidney failure, heart diseases in which regular
sinus rhythm was lost and neuropathy of other
etiology were excluded from the study. The
control group subjects were free from diabetes
mellitus, hypertension, coronary artery disease or

any other illness expected to interfere with


autonomic function. This comprised volunteers
from hospital staff and their relatives. Informed
consent was taken from all the subjects after
explaining the test procedures and the goal of the
study. In addition to routine general examination
the height and the weight of the subjects were
noted. Body mass index was calculated as weight
(kg) /height (m2). Autonomic function tests were
performed with the help of the Biopac student
lab system (Biopac Systems , India MP36R). The
autonomic functions were assessed using five
simple non-invasive cardiovascular reflex tests
proposed by Ewing et al 9. Three tests for
parasympathetic function and two tests for
sympathetic function were used for the study.
Resting heart rate and blood pressure were also
recorded with these main tests. These
measurements and the tests were carried out by
subjects in both physical and emotional rest.
Tests reflecting Parasympathetic function Heart
rate variation during deep breathing: Before
beginning the test, subjects were taught to
breathe six breaths a minute, five seconds for
each inhale and five seconds for each exhalation
in sitting position. An electrocardiogram was
recorded throughout the period of deep
breathing. The onset of inspiration and expiration
was marked. R-R interval was measured during
expiration and inspiration and used to calculate
heart rate per minute. The difference between
maximum and minimum heart rate was
calculated. A difference of 18 beats or more per
minute was taken as normal, less than this was
taken as an abnormal response.
Immediate heart rate response to standings lying
to standing a characteristic immediate rapid
increase in heart rate occurs which is maximal at
about the 15th beat after standing. A relative
bradycardia then occurs, maximal at about the
30th beat10. Diabetics with autonomic neuropathy
show only a gradual or no increase in heart rate
after standing. The test is performed with the
patient lying quietly on a couch while the heart
rate is continuously recorded. The patient is
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Int J Med Res Health Sci.2013;2(2):194-199

asked to stand unaided, and the point at starting


to stand is marked. The shortest R-R interval
around the 15th beat and the longest R-R interval
around the 30th beat after starting to stand are
measured. The characteristic response is
expressed by the 30:15 ratios. In the present
study 1.04 and above was taken as normal. 1.01
to 1.03 was taken as borderline response. Less
than 1.00 was taken as abnormal response.
Heart rate response to Valsalva maneuver:
During the straining period of the Valsalva
maneuver the blood pressure rises, overshooting
its resting value and the heart slows. In patients
with autonomic damage the blood pressure
slowly falls during straining and slowly returns
to normal after release, with no overshoot rise in
blood pressure and no change in heart rate. The
test is performed by the patients blowing into a
mouthpiece connected to a sphygmomanometer
and holding it at a pressure of 40 mm Hg for 15
seconds (in sitting position) while a continuous
electrocardiogram is recorded. The result is
expressed as Valsalva ratio11, which is the
longest R-R interval after the manoeuvre
(reflecting the overshoot of bradycardia
following release), to the shortest R-R interval
during the manoeuvre (reflecting the tachycardia
during straining).
Tests reflecting sympathetic function
Blood pressure response to standing: On
standing pooling of blood in the legs causes a fall
in blood pressure, which is normally rapidly
corrected by peripheral vasoconstriction12. In
patients with autonomic damage the blood
pressure falls on standing and remains lower than
in lying position. The test is performed by
measuring the patients blood pressure with a
sphygmomanometer while he is lying down
quietly and again when he stands up. The
postural fall in blood pressure is taken as the
difference between the systolic blood pressure
during lying and the systolic blood pressure

during standing. In the present study a mean fall


in systolic blood pressure of 30 mm Hg or more
was taken to indicate postural hypotension
(abnormal response). Postural fall of systolic
blood pressure of 10 mm Hg or less was taken as
normal. And the value 11 to 29 mm Hg was
taken as borderline.
Blood pressure response to sustained
handgrip: During sustained handgrip a sharp
rise in blood pressure occurs, due to a heart rate
dependent increase in cardiac output with
unchanged peripheral vascular resistance12.
Should the normal reflex pathways be damaged,
as in diabetics with extensive peripheral
sympathetic abnormalities, the rise in blood
pressure is less. The maximum voluntary
contraction was first determined using a handgrip
dynamometer. The subject was then asked to
maintain the handgrip (isometric contraction) at
30 percent of that maximum up to three minutes
in sitting position. Blood pressure was recorded
at the beginning and at the end of the procedure.
The rise of diastolic blood pressure was
calculated. In the present study a rise of diastolic
blood pressure of 16 mm Hg or more was taken
as normal, 11 to 15 mm Hg was taken as
borderline and 10 mm Hg or less than that was
taken as an abnormal response.
Statistical analysis: The students t test was
used to compare mean values of autonomic
function test parameters between study and
control group. A P value of < 0.05 was taken as
significant. For comparing age proportions Chisquare test was employed.

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RESULTS

Table 1. Effects on parasympathetic functions between control and study groups


Parasympathetic function tests
Control Group
Diabetic Group
Resting H.R
H.R response to deep breathing
H.R response to immediate standing
H.R response to Valsalva manoeuvre
H.R = Heart rate * P < 0.0001; P < 0.01

76.179.21
29.3710.32
1.170.67
1.270.001

80.1013.21
17.038.24*
1.010.69
1.140.23

Table 2. Effects on sympathetic functions between control and study groups


Sympathetic function tests

Control Group (mm Hg)

Resting systolic B.P


Resting diastolic B.P
B. P response to immediate standing
B.P response to sustained handgrip
B.P = Blood Psressure * P < 0.05; P = 0.001
The mean age in control and study group was 57
years. The mean height in control and study
group was 148 and 155.83 cms respectively;
mean weight of control and study group were
60kg and 63.73kg respectively, the BMI in
control and study group were 26.05 and 26.72
respectively. The mean weight of the study group
is higher than the control group. There is no
significant difference with respect to age
between study and control groups. Chi-square
test value is 0.07, p value p=0. 78
Table 1 shows the effects on parasympathetic
function between control and study group. There
is no difference in resting heart rate between
control and diabetic group (P=0. 1794). Heart
rate response to deep breath between control and
diabetic group (P=0. 0001) is significant. Heart
rate response to immediate standing from lying
position between control and diabetic group
(P=0. 0042) is significant. Heart rate response to
Valsalva maneuver between control and diabetic
group (P=0. 0141) is significant. In the present
study, value 1.21 and above was taken as normal,
less than 1.20 indicates an abnormal response in
Valsalva maneuver test.
Table 2 shows the effects on sympathetic
function between control and study group.

125.0712.67
79.075.12
5.073.45
17.834.12

Diabetic Group (mm Hg)


132.4713.01 *
885.01
11.99 .26
20.4357.2

Resting systolic blood pressure between control


and diabetic group (P=0.0205) is significant.
There is no significant difference between
control and diabetic group (P=0.9044) in resting
diastolic blood pressure. There is a significant in
Blood pressure response to immediate standing
between control and diabetic group (P=0.0003).
Blood pressure response to sustained handgrip
between control and diabetic group (P=0.8048) is
not significant.
DISCUSSION

Cardiovascular autonomic neuropathy (CAN), a


serious complication of diabetes10,13,14, is often
overlooked.CAN encompasses damage to the
autonomic nerve fibers that innervate the heart &
blood vessels, which may result in abnormalities
in heart rate control and vascular dynamics15.
Autonomic dysfunction can occur early after
diagnosis or even before diagnosis of diabetes16.
Table 1 shows there was a significant difference
in the baseline systolic blood pressure observed
between control & study groups (p<0.05).
However the difference in baseline diastolic
blood pressure observed between control and
study group was not significant, there is a
significant decrease in the mean blood pressure
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Int J Med Res Health Sci.2013;2(2):194-199

during immediate standing between control and


study group (p<0.01). In study group 10% (3
patients) had this defect and 20 % ( 6 patients)
subjects fall under the borderline category. In
future these borderline patients may have a more
chance to develop orthostatic hypotension. No
borderline and abnormal results were observed in
the control group. The most commonly
recognized autonomic dysfunction in diabetes is
orthostatic hypotension or fainting when standing
up. In the case of diabetic autonomic
dysfunction, it is due to the failure of the heart
and arteries to appropriately adjust heart rate and
vascular tone to keep blood continually and fully
flowing to the brain. In the present study it was
found that 10% people have a systolic fall more
than 30mmhg on standing and that 20% people
have borderline result. There is no significant
difference in the parameter blood pressure
response to sustained handgrip, in control group
2 subjects (6.6%) had borderline results, and no
abnormal results were observed. In this study
66.7% subjects were above 55 years (55-69
years) particularly they were aged people (above
60 years).It may be due to age factor or stress in
these subjects.
Heart rate variability too seems to be an
important predictor of cardiac autonomic
neuropathy, in the present study it was found that
the mean baseline heart rate in the study and
control group was 80.10 and 76.17 respectively.
It was not statistically significant. In the present
study beat to beat variation in heart rate related to
respiration has been assessed. It was highly
significant (p<0.001) than other test parameters
which indicates defects in parasympathetic
activity. Of the 30 cases studied 26.6% (8
subjects) subjects had borderline results and
26.6% had abnormal results, but in control
subjects only one subject had borderline results
but no abnormal results were observed. This
indicates decreased activity of parasympathetic
nervous system. In another parameter 6.6% (2
subject) control subjects fall
under the
borderline category in heart rate response to
immediate standing, in another parameter 3.3%

(1 subject),13.3%(4 subjects) control subjects fall


under the borderline category in heart rate
response to deep breathing and Valslva
manoeuvre respectively. This variation is less
significant than heart rate response to deep
breathing analysis. In sympathetic function tests
6.6% (2 subjects) control subjects had borderline
results in blood pressure response to sustained
hand grip test. It may be due to the physical
status of subjects such as obesity, stress and
ageing. In the present study most common
abnormal result was the deep breathing test. This
test reflects the parasympathetic activity; this is
the most sensitive study than other parameters.
This indicates defect is more in parasympathetic
activity and also suggests during the course of
diabetes parasympathetic dysfunction may
appear earlier than sympathetic damage. 17
CONCLUSION

It was observed that there is statistically


significant decrease in parasympathetic activity
(p<0.05) and increase in sympathetic activity in
type 2 diabetic female patients in rural areas.
Subclinical autonomic nerve damage occurs
more widely in diabetics than was hitherto
suspected and is assuming greater importance
because of the implications for morbidity and
mortality. Symptomatic autonomic neuropathy
carries a worse prognosis than any other
complication of diabetes. The simplest bedside
tests described above can provide an objective
guide to whether or not autonomic damage is
present, and to what degree. We found that the
severity of autonomic neuropathy in type 2
diabetes mellitus depends upon duration of
disease. Early detection of autonomic neuropathy
would suggest the need for an aggressive
approach to the management of type 2 diabetes
mellitus to reduce mortality and morbidity in
these patients.
ACKNOWLEDGEMENTS

I thank Dr.T.Balasubramanian, Professor of


Physiology, Rajah Muthiah Medical College,
Annamalai University for his advice, and help in
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Int J Med Res Health Sci.2013;2(2):194-199

the publication of this study. I also thank Mrs.


Radika Balasubramanian for her help in
statistical analysis.
REFERENCE
1. Wild S, Roglic G,Green A,Sicree R, King H:
Global prevalence of diabetes: estimates for
the year 2000 and projections for 2030.
Diabetes Care 2004, 27:1047-53
2. Sobngwi E,Mauvais-Jarvis F, Vexiau P,
Mbanya JC, Gautier JF: Diabetes in
Africans.Part 1: epidemiology and Clinical
Specifications. Diabetes Metab 2001,27:62834.
3. Task Force of the European Society of
Cardiology the North American Society of
Pacing and Electrophysiology Heart rate
Variability: Standards of measurements,
physiological interpretation and clinical use.
Circulation, 1996;93:1043-65.
4. Carnethon MR, Liao D, Evans GW, et al.
correlates of the shift in heart rate variability
with an active postural change in a healthy
population sample: the Atherosclerosis Risk
in Communities Study. Am Heart
J.2002;143:808-13
5. Liao D, Cai J, Bran cati FL, et al. Association
of Vagal tone with serum insulin, glucose,
and diabetes mellitus: ARIC study. Diabetes
Res Clin Pract. 1995;30:211-21
6. Singh JP, Larson MG, ODonnell CJ.et al.
Association of hyperglycemia with reduced
heart rate variability (The Framingham heart
study). Am J Cardio.2000; 86:309-312
7. Aring AM, Jones DE, Falko JM: Evaluation
and prevention of diabetic neuropathy. Am
Fam Physician. 2005;71:2123-28
8. Vinik AI, Maser RE, Mitchell BD, Freeman
R. Diabetic autonomic neuropathy, Diabetes
care, 2003;26 (5): 1553-79
9. Ewing DJ, Martyn CN, Young RJ. and
Clarke BF. The value of cardiovascular
autonomic function tests: 10 years experience
in diabetes. Diabetes care.1985; 8:491-98

10. Ewing DJ,Campbell IW, Murray A, Neilson


JMM,Clarke BF. Immediate heart rate
response to standing: simple test for
autonomic neuropathy in diabetes. Br Med J
1978; 145-47.
11. Lewin AB.A simple test of Cardiac function
based upon the heart rate changes induced by
the Valsalva maneuver.Am J Cardiol
1966;18:90-99
12. Ewing DJ.Cardiovascular reflexes and
autonomic neuropathy. Clin Sci Mol Med
1978;55:321-7
13. Maser RE, Mitchell BD, Vinik AI, Freeman
R, The association between cardiovascular
autonomic neuropathy and mortality in
individuals with diabetes care,2003;26(6)
1895-901
14. Maser R, Lenhard M, Decherney G,
Cardiovascular autonomic neuropathy: the
clinical significance of its determination,
Endocrinologist. 2000; 10: 2733
15. Schumer MP, Joyner SA, Pfeifer MA,
Cardiovascular autonomic neuropathy testing
in patients with diabetes, Diabetes
Spectr.1998; 11:227-30
16. Carnethon MR, Golden SH, Folsom AR et
al, prospective investigation of autonomic
nervous system function and the development
of type 2 diabetes: The atherosclerosis risk in
communities study, 1987-1998, circulation,
2003;107;2190-95
17. Ewing DJ, Campbell IW, Clarke BF. The
natural history of diabetic autonomic
neuropathy. Q.f Med1980; 49:95-108

199

Desigan et al.,

Int J Med Res Health Sci.2013;2(2):194-199

DOI: 10.5958/j.2319-5886.2.2.036

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 12 Feb 2013


Research article

Coden: IJMRHS
th

Revised: 8 Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 10 Mar 2013

SERUM HOMOCYSTEINE AND LIPID PROFILE LEVELS IN TYPE 2 DIABETES


MELLITUS PATIENTS
*

Balu Mahendran K1, Santha K1, Santhoshkumar N2, GnanaDesigan E3,Mohammad Anwar4

Division of Biochemistry, 3Division of Physiology, Rajah Muthiah Medical College and Hospital,
Annamalai University, Annamalai Nagar,Tamil Nadu,India.
2
Department of Biochemistry, Shridevi Institute of Medical Sciences & Research Hospital,Tumkur,
Karnataka, India
4
Department of Biochemistry, College of Medicine, Prince Salman Bin Abdul Aziz University, AlKharj, KSA.
ABSTRACT

Serum total homocysteine (tHcy) concentration is associated with increased risk factor for coronary
heart diseases (CHD). The relation between type2 diabetes mellitus compared to the non diabetics is not
clear. The current study represents an association between tHcy and cardiovascular disease is stronger in
diabetics than in non-diabetic subjects. Materials & methods: Thirty type2 diabetic patients of both
sexes with age group between 35-50 years selected as a study group. Thirty healthy, ages, both sexes
subjects were selected as controls. Patients on insulin, Smokers, Alcoholics, Tobacco chewers,
Hypertension, and other systemic illness were excluded from this study. Glucose, Lipid profile
parameters analysed by fully automated analyzer. Total homocysteine is analyzed by enzyme
immunoassay method. Results: The mean level of Glucose, serum Cholesterol, Triglycerides, LDL, and
total Hcy levels are increased in type2 diabetic patients compared to the control group. The HDL level is
significantly decreased in type2 diabetic patients compared to control group. Conclusion: The Serum
total Hcy levels are associated with lipid profile in type2 diabetic patients. An elevated level of total Hcy
leads coronary heart diseases.
Keywords: Type2 diabetes mellitus, Homocysteine, Lipid profile, Coronary heart disease.
INTRODUCTION

Intracellular formation, metabolism, and release


of Homocysteine into the extracellular
compartment determine the concentration of
homocysteine in extracellular media (e.g.,
plasma/serum), which in turn is the basis for
measuring plasma/serum homocysteine as an
extracellular marker for human diseases.
Elevated levels of serum homocysteine have

been associated with state of coronary heart


diseases. High levels of homocysteine in the
serum, above15 mol/L, a medical condition
called hyper homocysteinemia. In patients
with type 2 diabetes mellitus, who is
known to have a 2 to 4 fold increased
risk for coronary heart disease (CHD) 1 .
Homocystinuria refers to a group of rare inborn
200

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Int J Med Res Health Sci. 2013;2(2):200-205

errors of metabolism resulting in high levels of


circulating homocysteine
100 mol/L and
2
urinary homocysteine. Several epidemiological
studies have been shown a relation between total
homocysteine levels and coronary heart diseases
3-7
. In previous studies with diabetic patients, the
association
between
elevated
plasma
homocysteine level and CHD events has been
strong in case control and cross sectional studies
8 12
. The significance of hyper homocysteinemia
in type 2 diabetes is further complicated by the
multiple ways of considering impaired renal
function: decreased creatinine clearance,
albuminuria, or both9,13-18. Type 2 diabetes is
definitely
associated
with
premature
19,20
atherosclerosis
. Hyper homocysteinemia
causes endothelial dysfunction by increasing
oxidant stress21,22 and decreases the release of
nitric oxide, impairing vasodilation2325.
Excess of homocysteine stimulates smooth
muscle cell proliferation and collagen synthesis
promoting
intima-media
thickening2629.
Hyperhomocysteinemia is also considered to
have thrombogenic activity by increasing platelet
aggregation and causing abnormalities in the
coagulation
system3033.
High
plasma
homocysteine level is also shown to be
associated with increased lipid peroxidation34. It
is possible that statins have favorable effects on
endothelial function in individuals with hyper
homocysteinemia 35. Homocysteine as a marker
of vitamin deficiency states 36.
MATERIALS AND METHODS

In the present study, type 2 diabetic 30 patients,


age group 35-50years, either sex, suffering less
than 5 years duration of diabetics, who attending
the out-patient department of Shridevi Institute
of Medical Sciences & Research Hospital,
Tumkur, Karnataka, were included after taking
the inform consent from the patients and the
study was approved by the institutional ethical
committee overseeing human studies. Thirty
healthy, age, and sex matched subjects were
selected as controls. Experiments were done in

accordance with the Helsinki Declaration of


1975.
Exclusion criteria Patients on insulin, Smokers,
Alcoholics, Tobacco chewers, Hypertension, and
other systemic illness were excluded from this
study.
Biochemical analysis: Fasting venous blood
was collected in tubes containing EDTA. Blood
samples were centrifuged at 2000g for 10 min.
Samples were analysed for Fasting Blood
Glucose, Lipid Profile (Total Cholesterol, HDL,
LDL, Triglycerides), by using ERBA EM360
Fully automated analyzer .
Measurement of tHcy: Measurement of tHcy in
serum estimated by an enzyme conversion
immunoassay (EIA). This assay is based on
enzymatic conversion of tHcy (after reduction
and release of endogenous homocysteine from
proteins and/or disulfides) to S-adenosyl-L
homocysteine (SAH) by the action of SAH
hydrolase
(EC
3.3.1.1),
followed
by
quantification of SAH in a competitive
immunoassay with the use of a monoclonal
antibody against SAH 37.
Statistical analysis: All results were shown as
meanSD. The results were evaluated using
Students t-test. P-value <0.05 was considered
statistically significant. Statistical analysis was
performed using SPSS software
RESULTS

In normal individuals (control group) glucose


mean level was 96.44 11mg/dl. In Type 2
diabetic patients the glucose was significantly
raised being 244.4 41.08 mg/dl. Serum total
Cholesterol was 175.92 22.84mg /dl. In Type 2
diabetic patients the mean levels of serum total
cholesterol was significantly raised, the value
being 201.2 29.69mg / dl. The Triglycerides in
the control group are 105.2 27.82 mg/dl, while
inType2 diabetic patients the mean triglycerides
levels have significantly raised to 151.32 36.73
mg/dl. The mean HDL-Cholesterol in normal is
41.96 2.58mg/dl, while the mean value of
HDL-Cholesterol in Type 2 diabetic patients is
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Int J Med Res Health Sci. 2013;2(2):200-205

40.083.29mg/dl. HDL Cholesterol slightly


decreased in Type 2 diabetic patients. The LDLCholesterol mean level in normal individuals was
109.16 25.54 mg/dl. In Type 2 diabetic patients
the LDL- Cholesterol was significantly raised
being 128.08 29.09 mg/dl. The homocysteine
in the control group is 8.924 2.96 mol/l, while

in Type 2 diabetic patients the mean


homocysteine levels have significantly raised to
15.064 4.82 mol/l. There is a significant
difference of glucose, Cholesterol, triglycerides,
HDL, LDL, homocysteine in control group &
Type 2 diabetic group.

Table 1: Biochemical Data of control group and study group


Control Group (n=30)
Study Group (n=30)
Parameter
Mean SD
Mean SD
Homocysteine mol/L
8.924 2.96
15.064 4.82
Glucose (mg/dl)
96.44 11
244.4 41.08
Cholesterol (mg/dl)
175.92 22.84
201.2 29.69
Triglycerides (mg/dl)
105.2 27.82
151.32 36.73
Serum HDL (mg/dl)
41.96 2.58
40.08 3.29
Serum LDL (mg/dl)
109.16 25.54
128.08 29.09

P value
<0.001
<0.000
< 0.001
< 0.001
< 0.045
< 0.001

DISCUSSION

We found a strong and independent association


between elevated Serum homocysteine levels in
Type 2 diabetic patients and risk for CHD events
in our prospective study. Elevated levels of
serum Homocysteine is a risk factor for overall
mortality in type 2 diabetic patients. There are
several prospective studies that have investigated
the relation between tHcy and risk of
cardiovascular disease. Many 38 40 but not all
found a positive relation 41, 42. Several studies
have explained the relation between B vitamins
and serum tHcy levels. It has been suggested that
hyperglycemia may cause an increased loss of
water-soluble B vitamins 43. Lowering serum
homocysteine reduces the risk of CHD in
patients with type 2 diabetes mellitus. Patients
with type 2diabetes with proteinuria more
commonly have hyperhomocysteinemia than
control subjects, and plasma tHcy levels in
subjects with renal failure were markedly
increased 44. In non-diabetic subjects, hyper
homocysteinemia is often a feature of end-stage
renal disease 45, 46.

CONCLUSION

In summary, our study shows that serum


homocysteine levels are significantly raised; it is
an independent risk factor for future CHD events
in patients with type 2 diabetes with or without
known CHD.
REFERENCES

1. Hoogeveen EK, Kostense PJ, Beks PJ,


Mackaay AJ, Jakobs C, Bouter LM, et al.
Hyper homocysteinemia is associated with an
increased risk of cardiovascular disease,
especially in non-insulin-dependent diabetes
mellitus:
a
population-based
study.
Arterioscler Thromb Vasc Biol. 1998;18:13338.
2. Gerritsen T, Vaughn JG, Waisman HA. The
identification of homocysteine in the urine.
Biochem Biophys Res Commun 1962;9:49396.
3. Ueland PM, Refsum H, Brattstrm L. Plasma
homocysteine and cardiovascular disease.:
Francis
RB
Jr,
ed
Atherosclerotic
cardiovascular disease, hemostasis, and

202
Balu et al.,

Int J Med Res Health Sci. 2013;2(2):200-205

endothelial function. New York: Marcel


Dekker,1992:8:183-236.
4. Boushey CJ, Beresford SAA, Omenn GS,
Motulsky AG. A quantitative assessment of
plasma homocysteine as a risk factor for
vascular disease: probable benefits of
increasing folic acid intakes. JAMA
1995;274:1049-57.
5. Verhoef P, Stampfer MJ. Prospective studies
of homocysteine and cardiovascular disease.
Nutr Rev 1995;53:283-88.
6. Brattstrm L. Vitamins as homocysteinelowering agents. J Nutr 1996; 126:1276-80.
7. Den Heijer M, Koster T, Blom HJ, et al.
Hyperhomocysteinemia as a risk factor for
deep-vein thrombosis. N Engl J Med
1996;334:759-62.
8. Araki A, Sako Y, Ito H. Plasma
homocysteine concentrations in Japanese
patients with non-insulin-dependent diabetes
mellitus:
effect
of
parenteral
methylcobalamin treatment. Atherosclerosis.
1993;103:149-57.
9. Munshi MN, Stone A, Fink L, Fonseca V.
Hyper homocysteinemia
following a
methionine load in patients with non-insulindependent
diabetes
mellitus
and
macrovascular
disease.
Metabolism.
1996;45:133-35
10. Hoogeveen EK, Kostense PJ, Beks PJ,
Mackaay AJ, Jakobs C, Bouter LM,et al.
Hyperhomocysteinemia is associated with an
increased risk of cardiovascular disease,
especially in non-insulin-dependent diabetes
mellitus:
a
population-based
study.
Arterioscler Thromb Vasc Biol. 1998;18:13338
11. Okada E, Oida K, Tada H, Asazuma K,
Eguchi
K,
Tohda
G,
et
al.
Hyperhomocysteinemia is a risk factor for
coronary arteriosclerosis in Japanese patients
with type 2 diabetes. Diabetes Care.
1999;22:484-90
12. Smulders YM, Rakic M, Slaats EH, Treskes
M, Sijbrands EJ, Odekerken DA, et al.
Fasting and post-methionine homocysteine

levels in NIDDM. Determinants and


correlations with retinopathy, albuminuria,
and cardiovascular disease. Diabetes Care.
1999;22:125-32
13. Agardh CD, Agardh E, Andersson A, Hult
berg B: Lack of association between plasma
homocysteine levels and microangiopathy in
type 1 diabetes mellitus. Scand J Clin Lab
Invest 1994;54:63741.
14. Chico A, Perez A, Cordoba A, Arcelus R,
Carreras G, de Leiva A, Gonzalez-Sastre F,
Blanco-Vaca F: Plasma homocysteine is
related to albumin excretion rate in patients
with diabetes mellitus: a new link between
diabetic nephropathy and cardiovascular
disease? Diabetologia 1998;41:68493.
15. Smulders Y, Rakic M, Slaats E, Treskes M,
Sijbrands E, Odekerken D, Stehouwer C,
Silberbusch J: Fasting and post-methionine
homocysteine
levels
in
NIDDM:
Determinants
and
correlations
with
retinopathy,
albuminuria,
and
cardiovasculardisease. Diabetes Care.1999;
22:12532.
16. Wollesen F, Brattstrom L, Refsum H, Ueland
P, Berglund L, Berne C: Plasma total
homocysteine and cysteine in relation to
glomerular filtration rate in diabetes mellitus.
Kidney Int 1999; 55:102835.
17. Hultberg B, Agardh E, Andersson A,
Brattstrom L, Isaksson A, Israelsson
B,Agardh CD: Increased levels of plasma
homocysteine
are
associated
with
nephropathy, but not severe retinopathy in
type 1 diabetes mellitus. Scand J Clin Lab
Invest1991; 51:27782.
18. Stabler S, Estacio R, Jeffers B, Cohen J,
Allen R, Schrier R: Total homocysteine is
associated with nephropathy in noninsulindependent diabetes mellitus. Metabolism
1999;48:1096101.
19. Lheto S, Rnnemaa T, Pyrl K, Laakso M,
Laakso M: Cardiovascular risk factors
Clustering
with
endogenous
hyperinsulinaemia predict death from
203

Balu et al.,

Int J Med Res Health Sci. 2013;2(2):200-205

coronary heart disease in patients with type 2


diabetes. Diabetologia 2000;43:14855.
20. Haffner SM, Lehto S, Rnnemaa T, Pyrl
K, Laakso M: Mortality from coronary heart
disease in subjects with type 2 diabetes and
in nondiabetic subjects with and without
prior myocardial infarction. N Engl J Med
1998; 339:22934.
21. Starkebaum G, Harlan JM. Endothelial cell
injury due to copper-catalyzed hydrogen
peroxide generation from homocysteine. J
Clin Invest.1986;77:1370-76.
22. Kanani PM, Sinkey CA, Browning RL,
Allaman M, Knapp HR, Haynes WG. Role of
oxidant stress in endothelial dysfunction
produced by experimental hyperhomocyst(e)
intemia in humans. Circulation. 1999;100:
1161-68.
23. Tawakol A, Omland T, Gerhard M, Wu JT,
Creager MA. Hyperhomocyst(e)inemia is
associated with impaired endotheliumdependent
vasodilation
in
humans.
Circulation. 1997;95:1119-21
24. Woo KS, Chook P, Lolin YI, Cheung AS,
Chan
LT,
Sun
YY,
et
al.
Hyperhomocyst(e)inemia is a risk factor for
arterial endothelial dysfunction in humans.
Circulation. 1997;96:2542-24
25. Stuhlinger MC, Tsao PS, Her JH, Kimoto M,
Balint RF, Cooke JP. Homocysteine impairs
the nitric oxide synthase pathway: role of
asymmetric dimethylarginine. Circulation.
2001;104:2569-75
26. Malinow MR, Nieto FJ, Szklo M, Chambless
LE, Bond G. Carotid artery intimal- medial
wall thickening and plasma homocyst(e)ine
in asymptomatic adults. The Atherosclerosis
Risk in Communities Study. Circulation.
1993;87: 1107-13.
27. Tsai JC, Perrella MA, Yoshizumi M, Hsieh
CM, Haber E, Schlegel R, et al. Promotion of
vascular smooth muscle cell growth by
homocysteine: a link to atherosclerosis. Proc
Natl Acad SciUSA.1994;91:6369-73.
28.Majors A, Ehrhart LA, Pezacka EH.
Homocysteine as a risk factor for vascular

disease. Enhanced collagen production and


accumulation by smooth muscle cells.
Arterioscler
Thromb
Vasc
Biol.
1997;17:2074-81.
29.Voutilainen S, Alfthan G, Nyyssonen K,
Salonen R, Salonen JT. Association between
elevated plasma total homocysteine and
increased common carotid artery wall
thickness. Ann Med. 1998;30:300-06.
30. Rodgers GM, Conn MT. Homocysteine, an
atherogenic stimulus, reduces protein C
activation by arterial and venous endothelial
cells. Blood. 1990;75:895-901
31.Lentz SR, Sadler JE. Inhibition of
thrombomodulin surface expression and
protein C activation by the thrombogenic
agent homocysteine. J Clin Invest.
1991;88:1906-14.
32. Khajuria A, Houston DS. Induction of
monocyte tissue factor expression by
homocysteine: a possible mechanism for
thrombosis. Blood. 2000;96:966-72.
33.Al-Obaidi MK, Philippou H, Stubbs PJ,
Adami A, Amersey R, Noble MM, et al.
Relationships between homocysteine, factor
VIIa, and thrombin generation in acute
coronary
syndromes.
Circulation.
2000;101:372-77
34.Voutilainen S, Morrow JD, Roberts LJ 2nd,
Alfthan G, Alho H, Nyyssonen K, et al.
Enhanced in vivo lipid peroxidation at
elevated plasma total homocysteine levels.
Arterioscler
Thromb
Vasc
Biol.
1999;19:1263-66
35. Li H, Lewis A, Brodsky S, Rieger R, Iden C,
Goligorsky MS. Homocysteine induces 3hydroxy-3-methylglutaryl
coenzyme
a
reductase in vascular endothelial cells: a
mechanism
for
development
of
atherosclerosis? Circulation. 2002;105: 103743
36.Allen RH, Stabler SP, Savage DG,
Lindenbaum J. Diagnosis of cobalamin
deficiency.
Usefulness
of
serum
methylmalonic acid and total homocysteine
204

Balu et al.,

Int J Med Res Health Sci. 2013;2(2):200-205

concentrations. Am J Hematol 1990; 34:9098


37. Frantzen F, Faaren AL, Alfheim I, Nordhei
AK. Enzyme conversion immunoassay for
determining total homocysteine in plasma or
serum. Clin Chem 1998;44:311-16.
38. Stehouwer CDA, Gall M-A, Hougaard P,
Jakobs
C,
Parving
H-H.
Plasma
homocysteine
concentration
predicts
mortality in non-insulin-dependent diabetic
patients with and without albuminuria.
Kidney Int1999;55: 30814.
39. Stampfer MJ, Malinow MR, Willett WC,
Newcomer LM, Upson B, Ullmann D,
Tishler PV, Hennekens CH. A prospective
study of plasma homocyst(e)ine and risk of
myocardial infarction in US physicians.
JAMA. 1992;268:877 81
40. Perry IJ, Refsum H, Morris RW, Ebrahim
SB, Ueland PM, Shaper AG. Prospective
study of serum total homocysteine
concentration and risk of stroke in middleaged British men. Lancet. 1995;346:139598
41.Alfthan G, Pekkanen J, Jauhiainen M,
Pitkaniemi J, Karvonen M, Tuomilehto J,
Salonen JT, et al. Relation of serum
homocysteine and lipoprotein concentrations
to atherosclerotic disease in a prospective
Finnish
population
based
study.
Atherosclerosis. 1994; 106:9 19.
42.Chasan-Taber L, Selhub J, Rosenberg IH,
Malinow MR, Terry P, Tishler PV et al. A
prospective study of folate and vitamin B6
and risk of myocardial infarction in US
Physicians. J Am Coll Nutr 1996;15:136
143.
43.Mooradian AD, Failla M, Hoogwerf B,
Maryniuk M, Wylie-Rosett J. Selected
vitamins and minerals in diabetes. Diabetes
Care. 1994;17: 46479.
44.Masanor , Hideki, Hiroyuk, Eiji Ishimura,
Tetsuo Shoji et al, Impact of Insulin
Resistance
and
Nephropathy
on

Homocysteine in Type 2 Diabetes. Diabetes


Care. 2001;24: 533-38
45. Bostom AG, Shemin D, Lapane K, Miller J,
Sutherland P, Nadeau M, et al : Hyper
homocysteinemia and traditional
Cardio
vascular disease risk factors in end stage
renal disease patients on dialysis: a casecontrol study. Atherosclerosis, 1995;114:93
103
46.Chauveau P, Chadefaux B, Coude M, Aupetit
J, Hannedouche T, Kamoun P, Jungers
P:Hyperhomocysteinemia, a risk factor for
atherosclerosis in chronic uremic patients.
Kidney Int 1993;41:7277

205
Balu et al.,

Int J Med Res Health Sci. 2013;2(2):200-205

DOI: 10.5958/j.2319-5886.2.2.035

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 12 Feb 2013


Research article

Coden: IJMRHS

Copyright @2013

th

Revised: 10 Mar 2013

ISSN: 2319-5886
th

Accepted: 13 Mar 2013

ROLE OF -1-ANTITRYPSIN AND OXIDATIVE STRESS IN EMPHYSEMA


*Anita M Raut1, Suryakar AN2, Smita D.Mhaisekar3, Dilip Mhaisekar4
1

Dept of Biochemistry Dr. Vikhe Patil Institute of Medical Sciences, Ahmednagar, Maharashtra.
Prof. & Registrar , MUHS, Nashik. 3Mhaisekar Hospital , Nanded.
4
Prof & Head, Resp. Med. Dr. Shankarrao Chavan Govt. Medical College , Nanded.
2

*Correspondence author e- mail: anitaraut009@gmail.com


ABSTRACT

In the lungs, deficiency of alpha-1antitrypsin can lead to the development of emphysema. Emphysema
involves destruction of the lungs air sacs (alveoli), where oxygen from the air is exchanged for carbon
dioxide in the blood. Alpha 1-antitrypsin is a protein produced by the liver and that circulates in the
blood. Among other functions, the protein protects the lungs so they can function properly. In people
with the disorder, the liver produces too little or no alpha 1 -antitrypsin. Without enough alpha-1
antitrypsin, neutrophil elastase is free to destroy air sac tissue. 60 emphysema patients were included in
the study. 100 healthy non-smokers were served as controls. Their baseline clinical examination, -1antitrypsin (AAT), malondialdehyde (MDA) and vitamin E were measured. The mean levels of - 1
antitrypsin and vitamin E in the patients at baseline were lower (P< 0.001) than the controls. The
malondialdehyde were high (P<0.001) in the emphysema patients compared to controls. We found
decreased levels of 1- antitrypsin and vitamin E and increased levels of malondialdehyde (MDA).
Thus the present study confirmed the existence of oxidative stress and altered levels of alpha 1antitrypsin in emphysema patients.
Keywords: Emphysema, -1-antitrypsin, Vitamin E, Oxidative stress, ROS, Malondialdehyde
INTRODUCTION

In the lungs, alpha-1 antitrypsin deficiency


produces emphysema, a chronic progressive lung
disease. The disease often becomes noticeable
between the ages groups of 30 to 40 years in
smokers and 10 to 15 years later in non-smokers.
Alpha 1-antitrypsin deficiency damages the tiny
air sacs (alveoli) in the lungs. When the alveoli
are damaged, the lungs aren't able to expand and
contract well enough for the person to breathe

normally. Patients may feel short of breath, and


they may cough or wheeze. As the lungs
deteriorate, many patients develop lung diseases,
such as emphysema, or chronic bronchitis. The
severe, early onset of emphysema that occurs in
patients with circulating deficiency of alpha 1antitrypsin. - 1 antitrypsin attests to the
importance of the protease inhibitor in
maintaining lung parenchymal integrity. It has
206

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Int J Med Res Health Sci. 2013;2(2):206-211

led
to
the
powerful
concept
of
protease:antiprotease balance being crucial to
alveolar homeostasis.1
Body tissues and blood normally contain
powerful enzymes known as proteases that
can attack foreign substances within the body,
which may be harmful, such as tobacco smoke.
However, these protease enzymes must be
carefully regulated because they could attack and
damage normal tissues rather than the intended
target resulting in local tissue damage. Blood and
tissues have a protease inhibitor that binds the
enzyme to prevent unrestricted and potentially
harmful protease activity. The commonest
protease inhibitor in the blood is alpha-1
antitrypsin and its role is to protect the tissues
from protease attack. These proteins play an
important role in controlling inflammation,
coagulation and repair mechanisms in the body. 2
Oxidative stress increases oxidant generation,
which cannot be neutralized with antioxidant
defence mechanisms. Lipids, proteins and
deoxyribonucleic acid are components of the cell
that are more sensitive to oxidative damage.
Oxygen radicals can modify amino acid side
chains, form protein aggregates, cleave peptide
bonds, and make proteins more susceptible to
proteolytic degradation. It has been shown that
neutrophils have a principal effect or role in
pulmonary tissue damage. Neutrophil elastase
can damage air spaces by degrading elastin, and
a variety of extracellular membrane proteins,
proteoglycans, and glycoproteins. Neutrophil
elastase can also stimulate inflammation by
increasing interleukin-8 synthesis. Additionally,
neutrophil
elastase can activate or inactivate
inhibitors of neutrophil collagenase, and
secretory leukoprotease proteinase inhibitor.
Apart from neutrophils, oxidative stress causes
activation of other phagocytes and severe
inflammatory response ensues.3
The reactive oxygen species (ROS) are generated
during normal cellular activity and may exist in
excess in some pathophysiological conditions,
such as inflammation or reperfusion injury.
These molecules oxidize a variety of cellular

constituents, but sulfur-containing amino acid


residues are especially susceptible. While
reversible cysteine oxidation and reduction is
part of well-established signalling systems, the
oxidation and the enzymatically catalysed
reduction of methionine is just emerging as a
novel molecular mechanism for cellular
regulation. The oxidation of methionine to
methionine sulfoxide in signalling proteins such
as ion channels affects the function of these
target proteins. Methionine sulfoxide reductase,
which reduces methionine sulfoxide to
methionine in a thioredoxin-dependent manner,
is therefore not only an enzyme important for the
repair of age- or degenerative disease-related
protein modifications. It is also a potential
missing
link
in
the
post-translational
modification cycle involved in the specific
oxidation and reduction of methionine residues
in cell signalling proteins, which may give rise to
activity-dependent plasticity changes in cellular
excitability and causes deficiency of alpha1antitrypsin.4
Study of the role of alpha 1-antitrypsin in
protection against oxidative
stress and
inflammation in the lung cells of emphysema
patients not only limits the damage but also
inhibits inflammatory responses.
Aims & objectives
In view of the above concept the present work
was planned to study alpha 1-antitrysin and non
enzymatic antioxidants as well as oxidative
balance
during inflammation in emphysema
patients.
MATERIALS & METHODS
Study design
In the present study total 160 patients were
included after taking the consent form, between
the age 25-60 years, either sex, who attend the
OPD of Dr. Vikhe Patil Memorial Hospital
during the period from Jan-Dec 2012.
Patient randomly divided into 2 groups. Group 1
Control healthy subjects (N=100), Group 2
emphysema patients (N=60). The control
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Int J Med Res Health Sci. 2013;2(2):206-211

subjects were completely healthy nonsmokers


and showed no abnormality on clinical
examinations and were completely symptom
less. 5ml blood sample was collected from each
patient. Serum was separated from blood by
centrifugation at 3000 RPM for 10 minutes at
room
temperature. All the samples were
analysed on the same day of collection.
The serum analysed for following biochemical
analysis:
1. The level of serum total lipid peroxide in
terms of Malondiadehyde (MDA) was
determined by the Kei Satoh method.5

2. The activity of 1- antitrypsin (-1-AT)


was assayed by immuno diffusion method of
Macini using Kits of Bioscientifica Co.
Argentina.6
3. Serum Vitamin E ( Tocopherol) was
estimated by the method of Baker and
Frank.7
Stastics: The statistical analysis was performed
by using student t test and P values < 0.001 were
interpreted as very statistically significant. The
values were expressed as mean SD.

RESULTS

Table.1: Illustrate the levels of MDA , AAT & Vitamin C in the healthy controls and emphysema
Sr No.
Parameters
Healthy controls n=100
Emphysema patients n=60
1.
Sr.MDA (mol/L)
1.660.28
4.20.57*
2.
-1antitrypsin (mg/dl)
14623.12
37.410.1*
3.
Sr. Vitamin E (mol/L)
1.030.23
0.360.05*
n= number of cases, All values are expressed in mean SD, *Significant
DISCUSSION

Table No. 1 display malondialdehyde (MDA)


levels in healthy controls and emphysema
patient. Oxygen radicals are toxic and are
thought to be involved in the pathogenesis of a
variety of diseases. In recent years, an increasing
amount of research has focused on the proposal
that an oxidant/antioxidant imbalance occurs in
smokers and in patients with lung diseases as
part of the pathogenesis of the condition.
Nonetheless, obtaining definitive proof that
oxidants contribute to lung disease or that
antioxidant therapy is beneficial in lung disease
remains problematic. Unfortunately, because of
the great variability that exists in the individuals
who smoke and difficulties in measuring
oxidative status, many challenges remain, in
understanding, treating and preventing lung
disease.
Reactive oxygen species (ROS), such as the
superoxide anion liberated by phagocytes
recruited to sites of inflammation, are proposed

to be a major cause of the cell and tissue damage,


including apoptosis, associated with many
chronic inflammatory diseases.8,9 Lung cells, in
particular alveolar epithelial type II cells, are
susceptible to the injurious effects of oxidants.
Lungs are continuously exposed to oxidants,
either generated endogenously by metabolic
reactions or exogenously, such as air pollutants
or cigarette smoke Inhaled environmental
oxidants exacerbate the underlying inflammation
in inflammatory lung diseases. Ozone is a potent
oxidant, which causes cellular damage by lipid
peroxidation as well as loss of functional groups
on biomolecules. Inhalation of ozone may lead to
an increase in neutrophil numbers, increased
airway responsiveness and reduced pulmonary
function in normal subjects.10 This has been
linked to neutrophil infiltration into the airway
epithelium.11
Cigarette smoking, another environmental
hazard, also delivers oxidants and free radicals to
208

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Int J Med Res Health Sci. 2013;2(2):206-211

the lungs. Cigarette smoke contains many


oxidants and free radicals, both in the gas and the
tar phase and causes sequestration of neutrophils
into the pulmonary microcirculation and
accumulation of macrophages in respiratory
bronchioles.12 Once recruited, these cells become
activated and generate ROS in response to a
sufficient level of stimulus (threshold

concentration). ROS, which may also be released


by
lung
epithelial
cells.13,14
may
also stimulate inflammatory cells directly,
thereby amplifying lung inflammatory and
oxidant events. The elevated MDA levels
observed in the present study suggest increased
ROS production and thereby lipid peroxidation
in emphysema patients .

Fig.1: Mechanism of Lipid peroxidation in Emphysema


Table No.1 shows the levels of -1 antitrypsin in
healthy controls, and emphysema patients. There
was a significant decrease in -1 antitrypsin
levels of emphysema patients (P<0.001) as
compared to healthy controls. -1 antitrypsin
(AAT) is important protein, involved in the
bodys defense mechanism that protects against
tissue damage from the proteolytic enzymes of
inflammatory cells.
It is well established that a proteinase /
antiproteinase imbalance occurs in the lungs of
emphysema patients as part of the pathogenesis
. The elastase burden may be increased as a
result of increased recruitment of leukocytes to
the lungs, and there may be a functional
deficiency of 1- antitrypsin due to inactivation
in the lungs by oxidation, which is considered to
contribute to the pathogenesis of this condition.
This functional 1- antitrypsin deficiency is
thought to be due to inactivation of the alpha-

Raut A et al.,

1AT by oxidation of the methionine residue at its


active15 site by oxidants and from phygocytes, as
part of the pathogenesis of emphysema. (Fig. 2)
Table No. 1 describe vitamin E in healthy
controls and Emphysema patients. As compared
to healthy controls vitamin E was significantly
decreased (p<0.001). Vitamin E is the most
important lipophilic antioxidant in humans.
In cell membrane and lipoproteins the essential
antioxidant function of vitamin E is to trap
peroxyl radicals and to break the chain reaction
of lipid peroxidation. Vitamin E will not prevent
the initial formation of secondary radicals in a
lipid rich environment, but does minimize the
formation of secondary radicals. Alphatocopherol is the most potent antioxidant of the
tocopherols and is also the most abundant in
humans.
209

Int J Med Res Health Sci. 2013;2(2):206-211

Fig.2: Destruction of alveolar tissue by elastase released from neutrophil


It quickly reacts with the excess charge
associated with the extra electron being dispersed
across the chromnol ring. This resonanceresonance
stabilized radical might subsequently react in one
of several ways.
The reduced vitamin E level in emphysema
patients could be due to partly its over
consumption as an antioxidant subsequent to
increased production of free radicals by cigarette
smoke and inflammatory reaction. Vitamin E
radical formed by free radical attack interact with
vitamin C.16
CONCLUSION

Ongoing inflammation and oxidative stress


results in the deficiency of alpha 1-antitrpsin
antitrpsin and
damage to airspace structure and disturbance of
the normal maintenance of alveolar structure.
This strongly supports a role for protease,
antiprotease imbalance in the development of
emphysema. Furthermore, cigarette smoke
activates airway epithelium to trigger airway
remodeling. Both of these processes result in
airflow obstruction. Macrophages are activated
by cigarette smoke and recruit neutrophils and
CD81 lymphocytes to cause elastolysis and
emphysema.

ACKNOWLEDGEMENT

Authors are also


also grateful to our CEO Dr. Sujay
Vikhe Patil and Deputy Director Dr. Abhijit
Diwate for their support and encouragement for
carrying out this study.
REFERENCES

1. Coxson HO, Chan IH, Mayo JR, Hlynsky J,


Nakano
Y,
Birmingham
CL.Early
emphysema in patients with anorexia
nervosa. Am J Respir Crit Care Med
2004;170:748
2004;170:74852.
2. Tuder RM, McGrath S, Neptune E. The
pathobiological mechanisms of emphysema
models: what do they have in common? Pulm
Pharmacol Ther. 2003;16:67
2003;16:6778
78
3. Shapiro SD. Proteolysis in the lung. Eur
Respir J Suppl. 2003;44:30
2003;44:3032
32
4. Tuder RM, Yoshida T, Arap W, Pasqualini
R, Petrache I. State of the art: cellular and
molecular
mechanisms
of
alveolar
destruction in emphysema: an evolutionary
perspective. Proc Am Thorac Soc
2006;3:503
2006;3:50310.
210

Raut A et al.,

Int J Med
d Res
Re Health Sci. 2013;2(2):2
2):206-211

5. Kei satoh. Estimation of lipid peroxide


(MDA). Clinica Chemica Acta, 1998, 90:3743.
6. Manildi
E
R
.Simlified
rapid
electoimmunodiffusion
technique
for
measuring alpha 1 antitrypsin in serum
clin.chem 1972,18:1019-21.
7. Baker and Frank. The estimation of Serum
vitamin E ( Tocopherol) by method of
Varleys Practical Clinical Biochemistry
Heimann professional Publishing 6th edition
1988: Pg No. 902..
8 Chan YM, Ait KN, White N, Ip MS, Tan
WC.The burden and impact of COPD in Asia
and Africa. Int J Tuberc Lung Dis 2004;8: 214.
9 Rabe KF. Hurd S, Anzuet. A. et al .Global
strategy for the diagnosis, management and
prevention of chronic obstructive pulmonary
disease. GOLD executive summary. Am J.
Respir Crit care Med. 2007: 176:53255.
10 Cross CE., Vander VA, and ONeil C.
Oxidant antioxidants and respiratory tract
lining fluids. Environment Health Perspect.
1994;102:185-91.
11 Boushy HA, Carry DB, Fahy IV.Asthma. In
murry JF, Nadel JA. Textbook of Respiratory
Medicine, 3rd ed. Philadelphia ,WB Saunder:
2000: p.1247.
12 Suinder GL et al. The definition of
emphysema: Report of the National Heart,
Lung and Blood Institute Division of lung
Diseases Workshop Am. Rev. Respir Dis:
1985;132:182.
13 Massara D, Massara G.D .Pulmonary alveoli
the call for oxyg and other regulators. Am.
J.physiol.lung
cell
mol.
Physiol.
2002:282:L348.
14 Sant HG. Widdicombe J. Reflexes from
airway rapidly adapting receptors. Respir.
Physiol 2001;125:33

15 Joes MM and Franciscs SJ. Antioxidant


enzymes and their implications in
pathophysiologic process. Frontiers in
biosciences. 199;4: 339-45
16 Aysen A, Ilknur B, Meltem O,Fusun Y, Dilek
U, Hale M, Hasim B, Ahmet I and Baki
K.The effects of antioxidantason exerciseinduced lipid peroxidation in patients with
COPD: Respirology.2004;9(1):38-42

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Int J Med Res Health Sci. 2013;2(2):206-211

DOI: 10.5958/j.2319-5886.2.2.034

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April - June

th

Received:15 Feb 2013

Coden: IJMRHS
th

Revised: 12

Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 15 Mar 2013

Research article
XANTHOGRANULOMATOUS CHOLECYSTITIS: CHALLENGES IN MANAGEMENT &
FEASIBILITY OF LAPAROSCOPIC SURGERY
*Vikram Singh Chauhan
Asst.Professor, Department of surgery, School of Medical Sciences and Research,Greater Nodia,
UP,India
*Corresponding author's email address:drbikramc@yahoo.co.in
ABSTRACT

Objective: Xanthogranulomatous cholecystitis (XGC) is a rare, unusual and destructive form of chronic
cholecystitis. It is clinically indistinguishable from other forms of cholecystitis and hence difficult to
diagnose. Due to its propensity to form dense adhesions with stuctures surrounding the gall bladder and
mimic malignancy of gall bladder intra-operatively, its difficult to manage. This retrospective study
was conducted with the aim to review the clinico-pathologic presentation of XGC and the possibility of
its laparoscopic management. Patient and methods: All cases of histo-pathologically diagnosed XGC
from January 2008 to December 2012 at Sharda Hospital, School of Medical Sciences & Research,
Greater Noida were analyzed retrospectively. Results: Sixty two cases of biopsy proved XGC were
studied.The mean age at presentation was 56.4 14.3 years (range 30 72 years), with a male: female
ratio of 1.6:1. Gall bladder wall thickening on ultrasonography was seen in 91.9% cases and all (100%)
had cholelithiasis. Laparoscopic cholecystectomy was possible in 18 (29%) cases, with a high
conversion rate of 71% to open surgery. Two cases of carcinoma gall bladder accompanying XGC were
documented. Both the mean operative time and hospital stay for laparoscopic surgery were longer for
cases with XGC (105 minutes & 4.2 days respectively). No mortality occurred during the study period.
Conclusion: XGC is difficult to diagnose preoperatively due to lack of distinguishing clinical features
and imaging study results. Due to dense peri-cholecystic adhesions laparoscopic surgery though feasible
in some cases is difficult to perform with a high conversion rate. Overall morbidity is also increased due
to same reasons.
Keywords: Cholecystitis, Cholecystectomy, Malignancy, Xanthogranulomatous
INTRODUCTION

Xanthogranulomatouscholecystitis(XGC) is a
rare, more severe &destructive form of
cholecystitis1,2. It is characterized by thickening

of the gall bladder (GB) wall, with dense pericholecysticadhesions and fistula formation3. The
pre-operative clinical picture resembles that of
acute or chronic cholecystitis and on imaging
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Int J Med Res Health Sci. 2013;2(2):212-216

studies it may mimic GB cancer4, 5. It has been


associated with increased chances of perioperative complications and a difficult
cholecystectomy6.
This study analyzed the clinical aspects of XGC,
to assess laparoscopic cholecystectomy as a
modality for treatment& identify causes for
difficult cholecystectomy in XGC.
MATERIALS AND METHODS

All cases of histo-pathologically diagnosed XGC


from January 2008 to December 2012 at Sharda
Hospital, School of Medical Sciences &
Research, Greater Noida were included.
Pathological diagnosis of XGC was made by
following criteria: focal or diffuse mural
affection with histiocyte infiltration, presence of
cholesterol deposits, multinucleated foreign body
giant cells, macrophages phagocytizing lipids
and bile pigments to form xanthoma cells, nonspecific acute/chronic inflammatory infiltrate.
Case records were analyzed retrospectively for
clinical characteristics, comorbidities, imaging
study findings, surgical findings, nature and
duration of surgery, need and cause of
conversion, additional procedures done, histopathological characteristics, and postoperative
course & complications.
RESULTS

Of the 2670 patients who underwent


cholecystectomy during the study period, 62 had
pathologically proven XGC (2.32 %). The mean
Table.1:Patient profile
Pt. Characteristic
Male
Females
Clinical Presentation
Right hypochondrium pain
Fever
Nausea & vomiting
Jaundice
+ Murphyss sign
Palpable lump

age at presentation was 56.4 14.3 years (range


30 72 years), with a male: female ratio of 1.6:1
(Table.1). Altered liver enzymes were seen in 28
(45.2%) cases. Associated co-morbidities
included Type-2 diabetes mellitus in 14 (22.6 %),
hypertension in 10 (16.1 %) and ischemic heart
disease in 4 (6.5 %) cases.
Laparoscopic cholecystectomy was performed in
18 (29 %) cases rest 44 (71 %) cases required
open cholecystectomy, 1 (1.6 %) patient had a
cholecysto-colonic fistula that was treated with
primary closure with omental patch, partial
wedge resection of the liver was done in one (1.6
%) case due to doubt of carcinoma.
Of the 44 cases who underwent open
cholecystectomy, fundus-first cholecystectomy
was needed in 36 (81.8 %) cases, 8 (22.2 %)
cases underwent duct-first cholecystectomy. Of
the 36 cases who underwent fundus-first
cholecystectomy, only a partial cholecystectomy
with stump closure was possible in 18 (50 %) of
cases, in 8 (22.2%) cases the posterior GB wall
could not be dissected of the fossa bed and was
left as such. Common bile duct exploration with
T-tube drainage was done in 4 (6.5 %) cases. The
mean operative time for open surgery was 125
102 minutes (range 55-175 minutes) & for
laparoscopic cholecystectomy was 105 60
minutes (range 75-160 minutes).
Mean hospital stay for open surgery was 7.6
5.4 days (range 6 -14 days), and that for
laparoscopic cholecystectomy was 4.2 2.8 days
(range 3 -8 days).

No. of cases (%)


38 (61.3)
24 (38.7)
55 (88.7)
24 (38.7)
20 (32.3)
08 (12.9)
26 (41.9)
05 (08.1)
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Int J Med Res Health Sci. 2013;2(2):212-216

Table 2: Preoperative Ultrasound findings.


USG findings
Distended Gallbladder
Contracted Gallbladder
Gallbladder wall thickening
Gallbladder stones
Common Bile Duct stones
Gall bladder + Common Bile Duct stones
Pyocele
Sub hepatic abscess
Sub phrenic collection
Fatty liver

No of cases (%)
40 (64.5)
22 (35.5)
57 (91.9)
62 (100)
03 (04.8)
03 (04.8)
08 (12.9)
04 (06.5)
02 (03.2)
14 (22.6)

Table 3: Peroperative findings


Per-operative findings
Gall Bladder

No. of patients (%)


Distended
36 (58.1)
Contracted
24 (38.7)
Wall thickening
62 (100)
Wall edema
48 (77.4)
Abscess
04 (06.5)
White fibrosed
32 (51.6)
03 (4.8)
Common Bile Ductdialation
Stones
Gall bladder
62 (100)
Common Bile Duct
04 (06.5)
Gall bladder + Common Bile
04 (06.5)
Duct
Calots triangle
56 (90.3)
Adhesions
Omentum
44 (70.9)
Colon
26 (41.9)
Duodenum
10 (16.1)
Gallbladder fossa
08 (12.9)
Mirizzis syndrome
01 (01.6)
Cholecysto-colic fistula
01 (01.6)
Postoperative wound infection occurred in 9
28 (45.2 %) cases. In 2 (3.2 %) cases XGC was
(14.5 %) cases, wound gaped in 1 (1.6 %) case
co-existent with carcinoma.
that was sutured secondarily, and there was no
DISCUSSION
mortality. Grossly visible yellowish discoloration
Historically XGC, first described by McCoy et al
of the mucosal surface suggestive of
is a rarer form of cholecystitis affecting the older
xanthomatous change was seen in 38 (61.3 %)
population with an incidence varying from 0.7 cases. Microscopically, foam cells, the hall mark
13.2 %7, 8. 9. Similar age distribution & incidence
of xanthomatous change were seen in all 62
of 56.4 14.3 years, 2.32 % respectively was
(100%) cases, foreign body giant cells in 48
found in this study. The relatively low incidence
(77.4 %) cases, trans-mural inflammation and
and no specific pre-operative indicators (Tables 1
fibrosis in 54 (87.1 %) cases, micro-abscesses in
& 2) make it difficult to diagnose until surgery.
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Int J Med Res Health Sci. 2013;2(2):212-216

All cases included in this series were suspected


only during the course of surgery and confirmed
later histo-pathologically. Male: Female ratio of
1.6:1 is opposite to normally greater incidence of
cholecystitis in females and almost an equal
distribution of XGC in both men & women as
reported by others6. A regional or dietary factor
could be the only plausible explanation for this,
as is also proposed by Kansakar PBS et al who
found the incidence of XGC and cholecystitis in
general to be more in north India as compared to
south10. A 100% association of XGC with
cholelithiasis in our study is also in accordance
with results reported by other authors worldwide
11, 12, 13
. A thickened GB on ultrasound seen in
91.9 % was the only pointing indicator
preoperatively for XGC, which was significantly
higher than 57.6%, as reported by others13&14.
This by itself is not specific for XGC and hence
is a cause of misdiagnosis by clinicians.
Two (3.2%) cases had co-existence of
adenocarcinoma GB along with XGC. In one
case malignancy was suspected per-operatively
and
the
patient
underwent
extended
cholecystectomy with wedge resection of liver.
The other patient was found to be having
carcinoma along with XGC on histo-pathology.
This is comparable to data reported by others in
literature11 & 14. Laparoscopic cholecystectomy
was completed in 18(29%) cases, with a
significant seventy one percent of cases requiring
conversion to open cholecystectomy. This
though lower than those reported by other
authors (81.8 % & 80 %, byGilberto GuzmanValdiviaandKansakar
PBS
et
al
and
8, 10
respectively), is still significantly high . The
major reason for conversion was dense adhesions
between the GB and surrounding structures and
those in the Calots triangle which prevented a
safe
completion
of
the
procedure
laparoscopically. This is evident from the fact
that even in those cases who underwent an open
procedure, there was a high number (81.8%) of
fundus first cholecystectomies suggesting the
Calots had dense adhesions that prevented
adequate dissection of cystic duct /artery directly.

In half of these cases only partial removal of the


GB could be achieved.
The above findings have two important
implications. First is that these adhesions make
the procedure, whether open or laparoscopic
more challenging and hazardous with greater
chances of severe peri-operative morbidity
requiring additional and even secondary
procedures. Secondly dense adhesions mimic
malignancy and may lead to more radical
procedures, than are required. Hence when XGC
is encountered and malignancy is suspected, a
frozen section biopsy may go a long way in
deciding the appropriate procedure on a case to
case basis. We did not have this facility, hence
performed an extended cholecystectomy in one
case where cancer was suspected but others have
opined that frozen-sections are essential in
patients, in whom differentiation of XGC from
malignant lesions is difficult intra-operatively8,14.
In our study, the mean duration of operation was
125 minutes for open and 105 minutes for
laparoscopic cholecystectomy, longer than that
for
their
counterparts
for
routine
cholecystectomy, illustrating that XGC creates
difficulty in operation. Mean hospital stay for
both open and laparoscopic surgery was also
longer, 7.6 &4.2 days respectively, as compared
to routine non XGC cases again pointing to the
above stated fact.
We did not encounter any bleeding, bile leaks in
any cases however post-operative wound
infection occurred in 14.5% cases that required
prolonged antibiotic administration.
CONCLUSION

XGC is a benign condition of the gallbladder


with a low mortality rate. Clinically XGC is
indistinguishable from chronic cholecystitis. It
can mimic carcinoma of gall bladder intra
operatively but carcinoma of gall bladder also
appears to be more frequently associated with
XGC. Frozen section is advisable in cases where
malignancy is suspected as cholecystectomy
alone
is
adequate
treatment
for
XGC.Laparoscopic cholecystectomy is feasible
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Int J Med Res Health Sci. 2013;2(2):212-216

but more challenging, hence one should have a


low threshold for conversion to avoid significant
post-operative complications.
ACKNOWLEDGEMENTS

We have not received any


contributions from non-authors.

substantial

Conflict of interest
The authors have none to declare.
REFERENCES

1. Rao RV, Kumar A, Sikora SS, Saxena R,


Kapoor
VK.
Xanthogranulomatous
cholecystitis: differentiation from associated
gall bladder carcinoma. Trop Gastroenterol.
2005;26:31-33.
2. Kwon AH, Matsui Y, Uemura Y. Surgical
procedures and histopathologic findings for
patients
with
xanthogranulomatous
cholecystitis. J Am Coll Surg. 2004;199:20410.
3. Lee KC, Yamazaki O, Horii K, Hamba H,
Higaki I, Hirata S, et al. Mirizzi syndrome
caused by xanthogranulomatouscholecystitis:
report of a case. Surg Today 1997;27:757-61.
4. Yoshida J, Chijiiwa K, Shimura H,
Yamaguchi K, Kinukawa N, Honda H, et al.
Xanthogranulomatous cholecystitis versus
gallbladder cancer: clinical differentiating
factors. Am Surg 1997;63:367-71.
5. Spinelli A, Schumacher G, Pascher A,
Lopez-Hanninen E, Al-Abadi H, Benckert C,
et al. Extended surgical resection for
xanthogranulomatouscholecystitis mimicking
advanced gallbladder carcinoma: A case
report and review of literature. World J
Gastroenterol 2006;12:2293-96.
6. Eriguchi N, Aoyagi S, Tamae T, Kanazawa
N, Nagashima J, Nishimura K, et al.
Xanthogranulomatouscholecystitis.Kurume
Med J 2001;48:219-21.

7. McCoy JJ Jr, Vila R, Petrossian G, McCall


RA, Reddy KS. Xanthogranulomatous
cholecystitis. Report of two cases. J S C Med
Assoc 1976;72:78-79.
8. GuzmanVG.Xanthogranulomatouscholecystit
is in laparoscopic surgery. J GastrointestSurg
2005;9:494-97.
9. Cardenas-Lailson LE, Torres-Gomez B,
Medina-Sanchez S, Mijares GJM, Hernandez
CJ. Epidemiology of xanthogranulomatous
cholecystitis. Cir. 2005; 73:19-23.
10. Xanthogranulomatouscholecystitis:
A
clinicopathological study from a tertiary care
health institution. Kansakar PBS, Rodrigues
G, Khan SA. Kathmandu University Medical
Journal (2008), Vol. 6, No. 4, Issue 24, 47275
11. Gilberto G Valdivia: Xanthogranulomatous
cholecystitis. An experience of 15 years.
World J Surg. 2004;8:254-57.
12. Singh UR, Agarwal S, Misra K.
Histopathological
study
of
xantho
granulomatous cholecystitis. Indian J Med
Res. 1989;90:285-88.
13. Houston JP, Collins MC, Cameron I, Reed
MWR, Parsons MA, Roberts KM.
Xanthogranulomatous cholecystitis. Br J
Surg. 1994;81:1030-32.
14. Pinocy J, Lange A, Konig C, Kaiserling E,
Becker
HD,
KroberSM.
Xanthogranulomatous
cholecystitis
resembling carcinoma with extensive
tumorous infiltration of the liver and colon.
Langenbecks Arch Surg 2003;388: 48-51.

216

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Int J Med Res Health Sci. 2013;2(2):212-216

DOI: 10.5958/j.2319-5886.2.2.033

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 15 Feb 2013


Research Article

Coden: IJMRHS

Copyright @2013

th

Revised: 18 Mar 2013

ISSN: 2319-5886
th

Accepted: 20 Mar 2013

EVALUATION OF HYPOGLYCEMIC EFFECT OF LAGERSTROEMIA SPECIOSA (BANABA)


LEAF EXTRACT IN ALLOXAN INDUCED DIABETIC RABBITS
*Shareef SM1, Sridhar I2, Mishra SS3, Venkata Rao Y4
1

Asst. Professor, 4Professor and HOD, Department of Pharmacology, Kamineni Institute of Medical
Sciences, Narketpally, Nalgonda, Andhra Pradesh.
2
Asst.Professor, Govt. Medical college, Nizamabad
3
Professor, Institute of Medical Sciences and Sum Hospital, Bhubneswar, Orissa.
*Corresponding author email: drsharifshaik@gmail.com
ABSTRACT

Aims and Objectives: Lagerstroemia speciosa (Banaba) whose tea obtained from the leaves has long
been used traditionally in the treatment of Diabetes mellitus in South Asian countries, especially the
Philippines. In this study we investigated the effect of leaf extract of Lagerstroemia speciosa on fasting
blood glucose levels at different doses in Alloxan induced diabetic rabbits. Materials and Methods:
Diabetes mellitus was induced by a single intravenous injection of Alloxan monohydrate at a dose of
150mg/kg in rabbits. Banaba leaf extract was given orally once a day for 10 weeks. In three graded
doses of 100, 400 and 800 mg/kg respectively. The results were compared with standard antidiabetic
drug Metformin (62.5mg/kg orally) Results: The elevated blood glucose levels in diabetic rabbits were
significantly decreased by treatment with Banaba leaf extract at doses of 400 and 800mg/kg. The
hypoglycemic effect of Banaba Leaf Extract at a dose 800mg/kg was comparable to Metformin
(62.5mg/kg). No significant difference between Banaba Leaf Extract 800mg/kg and Metformin was
observed. Conclusion: Based on these results, we suggest that Banaba leaf extract has favourable effects
in protecting the Alloxan induced hyperglycemia.
Keywords: Hyperglycemia, Alloxan monohydrate, Banaba leaf extract
INTRODUCTION

Type 2 diabetes have developed into a worldwide


epidemic.1 Ironically, the dramatic increase in
the prevalence of type 2 diabetes can be
attributed
to
the
rapid
economic
development and correlated to changes in
lifestyle within the last 50 years. Type 2 diabetes
is closely associated with obesity. Up to 90% of
the patients with type 2 diabetes are either

overweight or obese.2 The readily available


high calorie food and a sedentary lifestyle are
major causes for obesity. Obesity contributes to
insulin resistance and type 2 diabetes. Reducing
obesity and stopping weight gain constitutes a
way to slow down the rate of occurrence of type
2 diabetes.
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Int j Med Res Health sci. 2012;2(2):217-222

Most antidiabetic drugs are hypoglycemic or


anti-hyperglycemic (blood
glucose
level
reducing). However, most of these drugs are
weight gain promoting i.e. adipogenic. Thus,
these drugs treat one of the key symptoms of
type 2 diabetes, hyperglycemia, but exacerbate
the condition of being overweight or obese, one
of
the
leading
causes
of
type
2
diabetes. Therefore, while these drugs are
beneficial over the short term, they are not
optimal for long term health of type 2
diabetic patients.
The most desirable situation would be the
development of new types of antidiabetic drugs
that
are
either
hypoglycemic or
antihyperglycemic without the side effect of
promoting weight gain (adiposity). Herbal
medicines
known
to
be
useful
in
diabetes treatment may be able to lead to
compounds with such a combination of ideal
therapeutic
properties.3
One such plant Lagerstroemia speciosa (Banaba)
whose tea obtained from the leaves has long been
used traditionally in the treatment of Diabetes
mellitus in South Asian countries, especially
Philippines were selected for the study. 4
Lagerstroemia speciosa which is commonly
called as Banaba, crape myrtle in Philippines
belongs to the family Lythraecae. In India it
grows widely in Maharashtra and commonly
called as Queens flower and Pride of India.
It is a deciduous tropical flowering tree, 5 to 7 m
high, sometimes growing to a height of 20
meters. Leaves are large, spatulate, 2-4 inches in
width, 5-8 inches in length. It sheds leaves in the
first months of the year. Before shedding, the
leaves are bright orange or red during which time
it is thought to contain higher levels of corosolic
acid, the active principle considered. Flowers are
racemes, pink to lavender, flowering from March
to June. After flowering, the tree bears large
clumps of oval nut like fruits.5, 6
The present study aims to evaluate the anti
diabetic potential of the leaf extract of
Lagerstroemia speciosa (Banaba) on laboratory
animal model rabbit and its potency compared

with a known standard antidiabetic drug


Metformin with 3 different doses of the extract.
MATERIALS AND METHODS

Banaba Leaf Extract (BLE): The leaf extract


of Lagerstroemia speciosa (Banaba) was
obtained from Indfrag Ltd. The extract was
prepared by water extraction method. The extract
was standardized to 1% corosolic acid, the active
principle. The extract was stored in cool and dry
climate. Accurately weighed quantity of Banaba
leaf extracts suspended in distilled water was
administered to rabbits orally using a feeding
tube.
Drugs and Chemicals: Metformin pure powder
(Franco Indian Pharmaceuticals) was used as a
Standard drug. Metformin was suspended in
distilled water and administered to rabbit orally
via oral feeding tube.
Animals: Newzealand white rabbits (2.5- 4kg)
were used for the study. They were housed in an
air-cooled Central animal house. The animals
were acclimatized to laboratory conditions
(12:12h dark/light, 25 2 C) for a period of 7
days. They had free access to food and water ad
libitum. The experimental protocol was approved
by the Institutional Animal Ethics Committee of
Kamineni Institute of Medical Sciences,
Narketpally. All animals were handled according
to CPCSEA guidelines, Govt. of India. All the
experiments were conducted between 0900 h to
1800 h.
Induction of Diabetes mellitus7,8: Diabetes
mellitus was induced in the rabbits with normal
blood glucose levels by a single injection of
Alloxan monohydrate 150mg/kg body weight
I.V. through an ear marginal vein.(5% w/v in
citrate buffer at a pH of 3.5- 4) After 2 hrs of
Alloxan injection, Dextrose 10% was fed to all
rabbits to prevent hypoglycemia. After 72 hrs,
blood glucose of all rabbits was estimated.
Rabbits with fasting blood glucose levels of 220500mg/dl were considered as diabetic and
selected for further study and blood glucose

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levels were estimated daily for 7 days and then


weekly for 10 weeks.

test for post-hoc analysis was used. P values less


than 0.05 was considered statistically significant.

Treatment Schedule
All the rabbits that were successfully induced
were randomly allocated into five groups of 6
animals each and treated once daily for 10 weeks
as follows: Group 1 received vehicle (distilled
water) 2ml.Groups 2, 3, 4, received Banaba leaf
extract. (In the graded doses of 100, 400 and 800
mg/kg). Group 5 received Metformin
(62.5mg/kg, orally) respectively.9
Estimation of Blood Glucose10
The hypoglycemic effect of Banaba leaf extract
was evaluated by estimating blood glucose levels
by pre-standardized Glucometer with reagent
strips by glucose oxidase method. Fasting Blood
Glucose levels were estimated daily in the first
week after induction of diabetes and then once a
week for 10 weeks.
Statistical analysis11
All data analysis was completed using SPSS
software. Data are expressed as mean SEM.
One way analysis of variance (ANOVA)
followed by Least significant difference (LSD)

RESULTS

Changes in blood sugar, Administration of


Alloxan monohydrate (150mg/kg IV) produced
hyperglycemia within 72 hours and it was
maintained up to 10 weeks in placebo group fed
with distilled water. Pre treatment with BLE
reduced the hyperglycemic effect of Alloxan in a
dose dependent manner. BLE at a dose of
100mg/kg did show a significant reduction in
blood glucose levels but only at the end of 8th
week. BLE at a dose of 400mg/kg showed
statistically significant reduction in comparison
to placebo treated group at the end of 6 weeks,
whereas BLE at a dose of 800mg/kg and
Metformin caused significant reduction in blood
glucose levels as early as 2nd week.
The reduction of blood glucose level was evident
from the 2nd week with BLE at a dose of
800mg/kg and the values reached near normal by
8 - 10 weeks. The hypoglycemic effect of BLE
800mg/kg is comparable to Metformin
(62.5mg/kg) as there is no statistical significance
between these groups at any point of time.

Table 1: Mean Fasting blood glucose level in Alloxan induced diabetic rabbits
Group

Day 1

2nd week

Group I

340.627.8

329.027.5

Group II

339.428.8

305.028.34

Group III

335.421.1

295.424.68

Group IV

323.015.1

244.8*26.1

Group V

305.423.7

230.0*15.3

4th week

6th week

8th week

10th week

323.023.4

308.416.6

303.024.8

295.420.3

286.069.0

274.032.0

257.0*28.7

238.2*28.2

253.620.98

195.20*19.2

164.8**14.4

129.2**7.6

186.6*23.1

149.6**12.4

112.0**5.3

98.0**5.4

179.4*7.0

124.0**7.3

111.4**2.5

93.4**3.6

BLE Banaba Leaf Extract, data represented as MeanSEM, *P< 0.05 as compared to placebo,
**P<0.01(Significant), ***P<0.001(Highly significant)

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Int j Med Res Health sci. 2012;2(2):217-222

Fasting Blood glucose Level


(mg / dL)

400
350
300

Control

250

BLE100

200

BLE 400

150

BLE800

100

metformin

50
0
3 4 5 6 7 8 9 10 17 24 31 38 45 52 59 66 73

Days
Fig.1: Comparison of Mean Fasting blood glucose levels in between groups
DISCUSSION

The existing drugs which are used today in the


treatment of Diabetes address one of the key
symptoms of type 2 diabetes, i.e. hyperglycemia
but on the other hand promote weight gain.
Further due to various reported side effects of
currently used anti diabetic drugs, there exists a
need for their substitution with natural products
which have a hypoglycaemic effect and fewer
side effects.
A considerably large number of plants and herbs
are known for their antidiabetic effects through
folklore but their introduction into modern
therapy can only be done after pharmacological
testing by modern methods. Among several
plants, the strongest candidate was Banaba with
Corosolic acid as active ingredient. We therefore
have chosen to study the effect of Banaba Leaf
Extract on blood glucose levels in Alloxan
induced Diabetic rabbits.
Although Lagerstroemia speciosa has been
shown to produce hypoglycemic effects in some
mouse models of diabetes, there are no reports on
the effects of this substance in alloxan-induced
diabetic rabbits. Thus, the present study aimed to
elucidate the hypoglycemic effects of L. speciosa

in Newzealand white rabbits. The antihyperglycemic effect of banaba in genetically


engineered diabetic mouse model was reported
by Kakuda et al.12 and in alloxan induced
diabetic mice model by NC Tanquilut etal.13
Further studies are required in another animal
species to establish the hypoglycemic effect of
Banaba and also as a prerequisite for conducting
clinical studies.
Alloxan induced diabetes mellitus is a well
established model and shares many features with
human Diabetes mellitus. Alloxan as a cytotoxic
agent to the insulin-secreting cells of the
pancreas effectively induces Diabetes mellitus in
a wide variety of animal models. Alloxan is
capable of inducing both Type I and Type II
diabetes with proper dosage selection and makes
easy to put to use the experimental animals
within 3 days after induction of diabetes mellitus
and can be maintained to prevent death
throughout the experimental period. On the other
hand surgical and genetic methods require high
technical skills and may be associated with a
high percentage of animal death and thus rarely
used.7, 8.
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Int j Med Res Health sci. 2012;2(2):217-222

In the present study, hyperglycemia induced by


Alloxan was maintained up to 10 weeks in the
Placebo group. Significant reduction of blood
glucose levels in alloxan-induced diabetic rabbits
treated was observed only at the end of 8 weeks
at a dose of BLE 100 mg/kg. BLE at a dose of
400mg/kg showed statistically significant
reduction in comparison to placebo treated group
at the end of 6 weeks, whereas BLE at a dose of
800mg/kg and Metformin caused significant
reduction in blood glucose levels as early as 2nd
week. Further, blood glucose levels reduced to
near normal levels with BLE 800mg/Kg. The
hypoglycemic effect of BLE 800mg/kg is
comparable to Metformin (62.5mg/kg) as there is
no statistical significance between these groups.
Banaba had been reported to produce the anti
hyperglycaemic
effect
with
multiple
mechanisms. The leaf decoction was used by
native Philippines in the management of
Diabetes mellitus. The first report on the
hypoglycemic activity of Banaba leaf decoction
was given by Garcia F et al. in 19th century
itself14. Guy Klein etal. reported antiobesity and
hyperlipedimic activity with Lagerstroemia
speciosa15. Studies have shown that biologically
active substances obtained from Banaba leaf
include
Corosolic
acid,
Ellagitannins,
Lagerstroemin, Flosin B and Reginin A which
activate glucose uptake when studied in rat
adipose cells, the physiological target cells of
insulin16. The compound widely studied and
accepted as the most potent active principle is
Corosolic acid.
Corosolic acid induces GLUT4 translocation
onto plasma membrane. Binding of insulin to
receptors on muscle cells leads rapidly to fusion
of those vesicles with the plasma membrane and
insertion of the glucose transporters (GLUT4),
thereby giving the cell an ability to efficiently
take up glucose17,18. Similarly, Corosolic acid
makes the induction of GLUT4 translocation and
uptake of glucose into the cells, lowering glucose
levels in the blood. Furthermore Corosolic acid
stimulates glucose uptake via enhancing insulin
receptor phosphorylation. Corosolic acid also

exhibits antioxidant effect19,20 and anti diabetic


activity as like as vitamin E, which can protect
cell membranes from lipid peroxidation by
scavenging free radicals. It also acts as alphaglucosidase inhibitors, slowing down the
absorption of starchy foods from the intestine,
thereby retarding the rise in blood glucose after
meals. Other beneficial effects reported with the
use of Banaba leaf extract includes anti obesity
action and decrease in the levels of
cholesterol.2122
CONCLUSION

Banaba leaf extract is having hypoglycemic


activity and can be effectively used in the
management of diabetes mellitus. With the
functions and mechanisms discussed, Banaba
could be the best natural anti diabetic remedy for
prevention and treatment of Diabetes mellitus as
a natural gift without any other side-effects
shown in current prescribed anti diabetic drugs.
REFERENCES

1. Zimmet P, Alberti KG, Shaw J. Global and


societal implications of the diabetes
epidemic. Nature 2001; 414: 782-87.
2. Huizinga MM, Rothman RL. Addressing the
diabetes pandemic: A comprehensive
approach. Indian J Med Res. 2006; 124 : 48184.
3. Quisumbing, E. Medical Plants of the.
Philippines. Katha Publishing. Quezon City.
Year; 1978; 640-642.
4. Yeh GY, Kaptchuk JJ, Eisenberg DM,
Phillips RS. Systematic review of herbs and
dietary supplements for glycemic control in
diabetes. Diabetes Care 2003; 26:1277-94.
5. Cheolin Park and Jae-Sik Lee.Banaba: The
natural remedy as antidiabetic drug
Biomedical Research 2011; 22 (2): 125-29
6. Ulbricht C, Dam C, Milkin T, Seamon E,
Weissner
W,
Woods
J.
Banaba
(Lagerstroemia speciosa) an evidence-based
systematic review by the natural standard

221
Shareef et al.,

Int j Med Res Health sci. 2012;2(2):217-222

research
collaboration.
J
Herbal
Pharmacother. 2007; 7(1):99-113.
7. Etuk EU. Animal models for studying
diabetes mellitus, Agricultural and biology
.Journal of North America 2010; 1(2): 13034.
8. Gerhard Vogel H. Drug Discovery and
Evaluation:Pharmacological Assays .
Springer-Verlag Berlin Heidelberg : 2002.
2nd ed p 949-50
9. Utkan T,Yildirim MK, Yildirim S and
Sarioglu
Y.
Effects
of
specific
Phosphodiesterase inhibitors on Alloxan
induced diabetic rabbit cavernous tissue
invitro. International Journal of impotence
research. 2001;(13);24 -30.
10. Sacks DB, Bruns DE, Goldstein DE,
Maclaren NK, McDonald JM, Parrott M:
Guidelines and recommendations for
laboratory analysis in the diagnosis and
management of diabetes mellitus. Clin
Chem.2002;48:43672
11. Dixit JV, Principles and Practice of
Biostatistics. Bhanaridas Bhanot publishers,
Jabalpur. 2011, 5th edition, p213-17.
12. Kakuda T, Sakane I, Takihara T, Ozaki Y,
Takeuchi H, Kuroyanagi M. Hypoglycemic
effect of extracts from Lagerstroemia
speciosa L. leaves in genetically diabetic
KK-AY mice. Biosci Biotechnol Biochem .
1996;60:204-08.
13. Tanquilut NC, Tanquilut, MAC. Estacio
MAC, Torres EB, Rosario JC and Reyes
BAS. Hypoglycemic effect of Lagerstroemia
speciosa (L.) Pers. on alloxan-induced
diabetic mice. Journal of Medicinal Plants
Research, December, 2009;3(12), 1066-71.
14. Garcia F. On the hypoglycemic effect of
decoction of Lagerstroemia speciosa leaves
(banaba) administered orally. Journal of
Philippine Medical Assoc. 1940; 20: 395-402
15. Guy Klein1, Jaekyung Kim2, Klaus
Himmeldirk3, Yanyan Cao4,5 and Xiaozhuo

Chen Antidiabetes and Anti-obesity Activity


of Lagerstroemia speciosa.Advance Access
Publication March 2007 ;4(4):401-07.
16. Hayashi T, Maruyama H, Kasai R, Hattori K,
Takasuga S, Hazeki O, Yamasaki K and
Tanaka T. Ellagitannins from Lagerstroemia
speciosa as activators of glucose transport in
fat cells. Planta Medica. 2002; 68: 173-75.
17. Toshihiromiura, Yasushiitoh, Tetsuokaneko,
Naoyaueda, ToraoIshida, Mitsuofukushima
etal. Corosolic acid induces GLUT4
translocation in genetically type 2 diabetic
mice. Biol .Pharm .Bull. 2004; 27(7):110305.
18. Barun KS, Nurul Huda Bhuiyan, Kishor
Mazumder and KM. Formuzul Haque.
Hypoglycemic activity of Lagerstroemia
speciosa L. extract on streptozotocin-induced
diabetic rat: Underlying mechanism of
action. Bangladesh J Pharmacol 2009; 4: 7983.
19. Unno T, Sakane I, Masumizu T, Kohno M,
Kakuda T. Antioxidative activity of water
extracts of Lagerstroemia speciosa leaves .
Biosci Biotechnol Biochem . 1997;61:177217
20. Saumya S M & P Mahaboob Basha
Antioxidant effect of Lagerstroemia speciosa
Pers (Banaba) leaf extract in streptozotocininduced diabetic mice; Indian of Journal
Experimental Biology February 2011;49:
125-31
21. Takagi S, Miura T, Ishihara E, Ishida
T, Chinzei Y.Effect of corosolic acid on
dietary hypercholesterolemia and hepatic
steatosis in KK-Ay diabetic mice. Biomed
res. 2010;31(4):213-18.
22. Suzuki Y, Unno T, Ushitani M, Hayashi K,
Kakuda T. Antiobesity activity of extracts
from Lagerstroemia speciosa L. leaves on
female
KK-Ay
mice. J
Nutr
Sci
Vitaminol Evid Based Complement Alternat
Med. 2007; 4(4): 40107.

222
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DOI: 10.5958/j.2319-5886.2.2.032

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 18 Feb 2013


Research article

Coden: IJMRHS
th

Revised: 20 Mar 2013

STUDY OF SERUM MALONDIALDEHYDE


GLUTATHIONE IN EMPHYSEMA PATIENTS

AND

Copyright @2013

ISSN: 2319-5886
rd

Accepted: 23 Mar 2013

WHOLE

BLOOD

REDUCED

*Nagaraj R.Shetkar1, Anand Pyati1, Rajesh CS2


1

Asst. Professor, Department of Biochemistry, BLDEUs Shri B M Patil Medical College, Bijapur,
Karnataka.
2
Lecturer, Department of Pharmacology, BLDEUs Shri B M Patil Medical College, Bijapur, Karnataka.
*Corresponding author email: nagarajshetkar@gmail.com
ABSTRACT

Background: Emphysema is associated with high incidence of morbidity and mortality. The imbalance
between oxidants and antioxidants is thought to play an important role in the pathogenesis of
Emphysema. Methods: A total number of 80 subjects comprising of 40 healthy controls and 40
Emphysema cases were studied. In all the subjects, serum levels of malondialdehyde (MDA) as a
biomarker of lipid peroxidation and antioxidant whole blood reduced glutathione (GSH) were estimated.
Results: The level of whole blood reduced glutathione was significantly decreased in emphysema
patients when compared to controls. Serum MDA was significantly increased in Emphysema patients
when compared to controls. Conclusion: The presence of increased systemic oxidative stress in
emphysema patients seems to be associated with current active smoking and systemic inflammation. The
decrease in antioxidants levels appears to be mainly a consequence of increased oxidative stress. This
suggests that oxidative stress is likely to be involved in pathogenesis of emphysema.
Keywords: Oxidative stress, Antioxidants, Emphysema, Whole blood reduced glutathione, MDA.
INTRODUCTION

Emphysema is a long term progressive disease of


the lungs that primarily causes shortness of
breath. It is generally considered one of the two
forms of Chronic Obstructive Pulmonary Disease
(COPD) and Emphysema is associated with
cigarette smokeinduced COPD.1
American Thoracic Society defines Chronic
Obstructive Pulmonary Disease as a disease state
characterized by the presence of air flow
obstruction due to chronic bronchitis or
emphysema; the airflow obstruction is generally

progressive, may be accompanied by airway


hyper-reactivity, and may be partially reversible.2
Emphysema is a pathologic diagnosis that
denotes abnormal permanent enlargement of air
spaces distal to the terminal bronchiole, with
destruction of their walls without obvious
fibrosis.2
Two hypothesis accounts for the destruction of
alveolar walls are the protease antiprotease
mechanism and imbalance of oxidants and
antioxidants.3
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Int J Med Res Health Sci.2013;2(2): 223-228

The proteaseantiprotease imbalance hypothesis


is based on genetic deficiency of the
antiprotease, -1 antitrypsin which is a major
inhibitor of protease (particularly elastase)
secreted by neutrophils during inflammation.1antitrypsin deficiency develop symptomatic
panacinar emphysema which occurs at an earlier
age and increases with severity if individual
smokes. About 1% of all patients with
emphysema have this defect.3
Smoking plays an important role in disturbing
the oxidant antioxidant balance which leads to
the pathogenesis of emphysema. Normally, the
lung contains a healthy complement of
antioxidants (superoxide dismutase, glutathione)
that keeps oxidative damage to a minimum.
Tobacco smoke contains abundant reactive
oxygen species (free radicals) and activated
neutrophils released due to smoking also add to
the pool of reactive oxygen species in the alveoli,
which deplete these antioxidant mechanisms,
leading to tissue damage. A secondary
consequence of oxidative injury is inactivation of
native antiproteases, resulting in functional-1
antitrypsin deficiency even in patients without
enzyme deficiency3
The reduced form of Glutathione present in red
blood cells functions as an efficient scavenger of
hydrogen peroxide and plays an important role in
the prevention of peroxidative lung damage.4 The
reduced form of glutathione is an efficient
antioxidant of both intracellular and extracellular
medium. Cells are thought to be protected by
extracellular GSH from oxidants produced and
released by inflammatory cells, and by
intracellular GSH from oxidants produced in
normal biochemical processes and from
xenobiotics.5, 6
Malondialdehyde is the organic compound with
the formula CH2(CHO)2. This reactive species
occurs naturally and is a marker for oxidative
stress. Reactive oxygen species degrade
polyunsaturated
lipids,
forming
Malondialdehyde. This compound is a reactive
aldehyde and is one of the many reactive
electrophilic species that cause toxic stress in

cells and form covalent protein adducts which


are referred to as advanced lipoxidation end
products (ALE). The product of this aldehyde is
used as a biomarker to measure the level of
oxidative stress in an organism.7
Present study is undertaken to evaluate
antioxidant whole blood reduced glutathione and
serum Malondialdehyde as a marker of oxidative
stress in controls and in emphysema patients.
MATERIALS AND METHODS

A cross sectional study of whole blood reduced


glutathione and serum malondialdehyde in
controls and emphysema patients were carried
out from April 2009 to April 2010. Controls and
emphysema cases were selected from Bapuji
Hospital and Chigateri General Hospital,
Davangere. Each gave an informed consent and
this study was approved by the ethical and
research committee of J.J.M Medical College,
Davangere to use human subjects in the research
study. The patients and controls voluntarily
participated in the study.
A total number of 80 subjects were participated
in the study, of which 40 were healthy controls
and 40 were emphysema cases. Among 40
controls, 30 were male and 10 were female and
their mean age was 57.5 7.4 years and among
40 emphysema cases, 32 were male and 8 were
female and their mean age was 60.7 5.8 years.
There were no significant differences in age
among cases and controls.
Inclusion criteria:
i) Cases: 40 clinically and radiologically
diagnosed cases of emphysema were included.
ii) Controls: 40normal healthy individuals
without any history of smoking and chronic lung
disease were included.
Exclusion criteria: Patients with pneumonia,
asthma or other chronic respiratory disease,
history of diabetes mellitus, hepatic disease,
cardiac failure, recent surgical intervention and
renal disease
Collection of blood samples: About 5ml of
blood was collected from large peripheral vein
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Int J Med Res Health Sci.2013;2(2): 223-228

under aseptic precaution after overnight fasting.


Out of which 2ml was taken in an anticoagulant
(EDTA) bulb for estimation of whole blood
reduced glutathione (GSH) and 3ml in a plain
bulb for estimation of serum malondialdehyde
(MDA).
Estimation of Whole Blood Reduced
Glutathione: Whole blood reduced glutathione
was estimated by Ernest Beutler et al., Method. 8
It is based on the principle that all of the nonprotein sulphydryl groups of red blood cells are
in the form of reduced glutathione (GSH). 5,51 dithiobis-2-nitrobenzoic acid (DTNB) is a
disulphide compound, which is readily reduced
by sulphydryl compounds, forming a highly
colored yellow compound. Optical density
measured at 412nm and is directly proportional
to the GSH concentration.

Estimation of Serum Malondialdehyde :


Serum malondialdehyde estimated by Kei Satoh
Method.9 It is based on the principle of autooxidation of unsaturated fatty acids involves the
formation of semistable peroxides, which then
undergo a series of reactions to form
malondialdehyde (MDA). MDA reacts with
thiobarbituric acid (TBA) to form pink colored
chromogen. The resulting chromogen is
extracted with 4.0ml of n-butyl alcohol and the
absorbance of which is measured at 530 nm.
Statistical analysis: Results are expressed as
mean SD and range values. Unpairedt test is
used for comparing different biochemical
parameters between cases and controls. p value
of < 0.05 was considered as statistical
significance.

RESULTS

Table 1: Comparison of Serum MDA and Whole Blood Reduced Glutathione in Controls and
Emphysema cases
Groups

MDA (nmol/ml)

GSH (mg/dl)

Control

2.52 0.42

32.65 2.23

Emphysema

5.79 0.42

25.39 1.70

Mean difference
t*

3.27
28.11

7.26
17.17

< 0.001

< 0.001

* Unpaired t- test
Table 1 shows biochemical characteristics of the
study subjects. Serum mean level of
malondialdehyde a biomarker of lipid
peroxidation was significantly (p< 0.001)
increased in emphysema patients (5.790.42
nmol/ml) when compared to controls (2.52 0.42
nmol/ml) t Mean level of whole blood reduced
glutathione was significantly (p< 0.001)
decreased in emphysema patients (25.39 1.70
mg/dl) than in controls (32.65 2.23 mg/dl).
These results indicate that increase in oxidative
stress and

decrease in antioxidant level in emphysema cases


when compared to controls
DISCUSSION

Oxidative stress plays an important role in the


pathogenesis of emphysema.
Antioxidants
transform free radicals into less reactive species,
thereby limiting their toxic effects. Even when
present at low concentrations compared with
those of an oxidizable substrate, antioxidants
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significantly delay or prevent oxidation of that


substrate.10
These results indicate that there is increase in
oxidative stress and decrease in antioxidant
levels in emphysema patients when compared to
controls.
When compared to controls,
emphysema patients have significantly decreased
(p value < 0.001) level of GSH. This is in
accordance with the study of Madhuri Parija et
al11,Mukadder calikoglu et al 12andMacNee W et
al.13
Glutathione exists in reduced (GSH) and
oxidized (GSSH) states. In the reduced state, the
thiol group of cysteine is able to donate a
+

reducing equivalent (H + e ) to other unstable


molecules, such as reactive oxygen species. In
donating one electron, glutathione itself becomes
reactive, but readily reacts with another reactive
glutathione to form glutathione disulfide
(GSSG). In healthy cells and tissue, more than
90% of the total glutathione pool is in the
reduced form and less than 10% exists in the
disulfide form (GSSG). An increased GSSG to
GSH ratio is considered indicative of oxidative
stress14
The airways of smokers are exposed to highly
reactive components and the lung is always at the
risk of oxidative injury. Most of the intracellular
glutathione is stored in the reduced form (GSH).
During increased oxidative stress, the free
sulfhydryl (- SH) groups become oxidized
resulting in loss of GSH. The gaseous phase of
cigarette smoke may also irreversibly react with
GSH to form GSH derivatives that cannot be
reduced back, thereby depleting the total
available reduced glutathionepool. 15
After
exposure
to
cigarette
smoke
condensate(CSC) The activities of glutathione
synthesis and redox system enzymes such as
glutathione
peroxidase,
gamma-glutamyl
cysteine synthetase and glucose-6-phosphate
dehydrogenase were transiently decreased in
alveolar epithelial cells, possibly as a result of
the action of highly electrophilic free radicals on
the active site of enzymes. Thus there is a time

dependent depletion of intracellular soluble


GSH, concomitant with the formation of GSH
conjugate 16
The enzymatic redox cycle, which is normally
activated after oxidative stress and the formation
of GSSG, could not be activated because of the
depletion of GSH into non reducible glutathione
components, with the loss of the GSH pool. This
exhaustion of the pool of reduced GSH may
induce a chronic lack of antioxidant protection.
Persistent smokers may inhale more reactive
oxygen species than can be scavenged by the
residual antioxidants, resulting in increased
vulnerability to oxidative stress. This makes the
synthesis of GSH essential for cellular survival
and protection of the lung.15
When compared to controls, emphysema patients
have significantly (p value < 0.001) increased
level of MDA. This is in accordance with the
study of M.K. Daga et al 17, and Gamze kirkil et
al18
MDA is a lipid peroxidation product which is
formed during oxidative process of PUFA by
reactive oxygen species. All of the major classes
of biomolecules may be attacked by free radicals
but lipids are the most susceptible. Cell
membranes are rich sources of polyunsaturated
fatty acids which are readily attacked by
oxidizing radicals. The oxidative destruction of
PUFA by deleterious free radical reactions is
known as lipid peroxidation. Lipid peroxidation
has been implicated in a wide range of cell and
tissue damages, diseases, biological variables and
life habits.19
Oxidative stress has been implicated in the
pathogenesis of tobacco smoke induced chronic
obstructive pulmonary disease and Cigarette
smoke exposes the lung to extreme levels of
oxidative stress. Reactive oxygen species present
in the tobacco smoke may cause damage to
human alveolar epithelial cells by lipid
peroxidation of cell membranes. Increased MDA
concentration in patients with emphysema may
be due to increased production of reactive
oxygen species and hence more lipoxidation
products.20
226

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Int J Med Res Health Sci.2013;2(2): 223-228

CONCLUSION

In conclusion there is an oxidant and antioxidant


imbalance in emphysema patients when
compared to healthy controls and this imbalance
play an important role in the pathogenesis of
emphysema. Hence further studies are required
on beneficial effect of consumption of diet rich
in antioxidants and their effect on preventation of
oxidative damage in emphysema.
REFERENCES

1. Urszula Demkow. The oxidative stress in


emphysema and Chronic Obstructive
Pulmonary Disaease .Centr Eur J Immunol
2009; 34 (2): 143-46
2. Mephie SJ, Papadakis MA, Lawrence MT.
th

Current medical diagnosis and treatment. 47


edition, McGraw Hill Medical Publisher,
New Delhi, 2008;216-21.
3. Kumar V, Abbas A, Fausto N, Aster J. The
Lung. In: Robbins and Cotran pathologic
th

4.

5.

6.

7.

basis of disease. 8 edn. Elsevier, New Delhi


2010;.683-92
Rai RR, Phadke MS. Plasma oxidantantioxidant status in different respiratory
disorders. Indian J Clin Biochem 2006;
21(2): 161-64.
Cantin AM, North SL, Hubbard RC. Normal
alveolar epithelial lining fluid contains high
levels of glutathione. J Appl Physiol 1987;
63:152-57
Meister A. On the antioxidant effects of
ascorbic acid and glutathione. Biochem
Pharmacol. 1992; 44:1905-15.
Malondialdehyde from Wikipedia, the free
th

encyclopaedia (serial online) cited 27 Aug.


2010.
available
from
:http.//en.wikipedia.org/wiki/malondialdehyd
e
8. Beutler E, Duron O, Kelly BM. Improved
method for the determination of blood
glutathione. J Lab Clin Med. 1963; 61(5):
882-88.

9. Satoh K. Serum lipid peroxide in


cerebrovascular disorders determined by a
new colorimetric method. Clinica Chimica
Acta.1978; 90:37-43.
10. Roland Ruhl , Andreas Meyer, and Claus
Vogelmeier. Oxidant-Protease Interaction in
the Lung: Prospects for Antioxidant Therapy.
CHEST. 1996; 110:267-72.
11. Parija M, Bobby Z, Kumar VS, Saradha B.
Oxidative stress and protein glycation in
patients with chronic obstructive pulmonary
disease. Indian J Physiol Pharmacol. 2005;
49(1): 95-98.
12. Calikoglu M, Unlu A, Tamer L, Ercan B,
Bugdayci R, Atik U. The levels of serum
vitamin C, Malondialdehyde and erythrocyte
reduced glutathione in chronic obstructive
pulmonary disease and in healthy smokers.
Clin Chem Lab Med. 2002; 40(10):1028-31.
13. MacNee W. Pulmonary and systemic
oxidant/antioxidant imbalance in chronic
obstructive pulmonary disease. Proc Am
Thorac Soc. 2005;2: 5060.
14. Glutathione from Wikipedia, the free
th

encyclopedia (serial online) cited 27 Aug.


2010.
Available
from
:
http.//en.wikipedia.org/wiki/glutathione.
15. Toorn MV, Maria P, Varies S, Slebos D,
Bruin HG, Abello N, et al. Cigarette smoke
irreversibly modifies glutathione in airway
epithelial
cells.
Am
j
Physiol.
2007;293:1156-62.
16. Rahman I, MacNee W. Oxidant/antioxidant
imbalance in smokers and chronic obstructive
pulmonary disease. Thorax.1996;51: 348-50.
17. Daga MK, Chhabra R, Sharma B, Mishra
TK. Effects of exogenous vitamin E
supplementation on the levels of oxidants and
antioxidants
in
chronic
obstructive
pulmonary disease. J Biosci. 2003; 28(1):711.
18. Kirkil G, Muz MH, Seckin D, Sahin K,
Kucuk O. Antioxidant effect of zinc
picolinate in patients with chronic obstructive
227

Nagaraj et al.,

Int J Med Res Health Sci.2013;2(2): 223-228

pulmonary disease. Respir Med. 2008; 102:


840-44.
19. Ozbay B, Dulger H. Lipid peroxidation and
antioxidant enzymes in Turkish population:
Relation to age, gender, exercise, and
smoking. Tohoku J Exp Med. 2002; 197:11924.
20. Pryor WA, Prier DG, Church DF. Electronspin resonance study of mainstream and
sidestream cigarette smoke: nature of the free
radicals in gas-phase smoke and in cigarette
tar. Environ Health Perspect 1983; 47: 34555.

228

Nagaraj et al.,

Int J Med Res Health Sci.2013;2(2): 223-228

DOI: 10.5958/j.2319-5886.2.2.031

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April - June

th

Received: 20 Mar 2013


Research article

Coden: IJMRHS
nd

Revised: 22 Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 26 Mar 2013

A STUDY ON ANTIOXIDANT LEVELS IN NON SMOKE TOBACCO CONSUMING ORAL


SUB MUCOUS FIBROSIS (OSMF)
*Teklal Patel1, Vikram Kulkarni2
1
2

Dept. of ENT, L N Medical College & RC, Bhopal,India


Dept. of ENT, Chirayu Medical College & Hospital-Bhopal, India

*Corresponding author email: drpatelent@yahoo.com


ABSTRACT

Background: Globally Oral Cancer is the sixth most common cause death with India accounts for 86%
of the worlds oral cancer cases. Chronic tobacco quid consumption often results in a progressive
premalignant condition called Oral Sub mucous Fibrosis (OSMF) whose malignant transformation rate
of is around 7.6%. Free radicals released during the metabolism of tobacco and Areca nut my involved
in the initiation and propagation of mucosal fibrosis. Objective: the objective of the present study is to
measure antioxidant enzymes and lipid peroxidation levels in OSMF to assess oxidative stress like
environment in OSMF patients. Materials and methods: for this study we invited 38 newly diagnosed
OSMF patients both male and female consuming tobacco in the form of quid and the same number of
age matched healthy non tobacco consuming were selected as a control group. In both groups plasma
superoxide dismutase, Glutathione peroxidase, catalase levels and lipid peroxidation rate was measured.
Results and conclusion: we observed very low antioxidant enzyme levels in OSMF patients when
compared with healthy controls (P<0.01) and at the same time also observed very high lipid
peroxidation rate in the study population (P<0.01) compare to control group indicating prevalence of
oxidative stress like environment in tobacco consuming population, which might play a vital role in the
initiation and propagation of various precancerous conditions like OSMF.
Keywords: Oral submucous fibrosis; Antioxidant enzymes, non smoking tobacco consumption
INTRODUCTION

Cancer is one of the most common causes of


mortality and morbidity today, with more than 10
million new cases and more than 6 million deaths
each year worldwide. Global Oral Cancer is the
sixth most common cause of cancer related
death1. India accounts for 86% of the worlds
oral cancer cases, says the study conducted by
the National Institute of Public Health in

February 2011. Oral cancer accounts for


approximately 3040% of all cancers in India.
The strong association between oral cancers with
tobacco use is well established. Many
epidemiological studies showed the risk of
developing oral cancer is five to nine times
greater in smokers than nonsmokers. In addition
to smoking tobacco chewing has been associated
229

Teklal et al.,

Int J Med Res Heatlh Sci. 2013;2(2):229-232

with increased risk of oral cancer2. In the Indian


subcontinent the chronic use of betel quid has
been strongly associated with increased risk for
oral cancer3. The quid typically consists of betel
leaf, Areca nut, tobacco pieces, and lime. In
presence of lime, Areca nut releases high
concentration of alkaloids. Chronic tobacco quid
consumption often results in a progressive
premalignant condition called Oral Sub mucous
Fibrosis (OSMF). From the study done by Pillai
P N et al4 observed that the malignant
transformation rate of OSMF is around 7.6%.
The major etiological factor for the development
of OSMF on chronic consumption of Areca quid
may be due high concentration of alkaloid and
the interaction of these alkaloids with free
radicals liberated from tobacco with the oral
mucosa. Thus the aim of this present study is to
estimate plasma antioxidant enzymes like Super
oxide dismutase (SOD), glutathione peroxidase
(GSH-Px), catalase (CAT) and lipid peroxidation
in OSMF patients evaluate oxidative stress levels
in OSMF and its role in initiation and
development of this disease.
METHODS AND MATERIALS

This study was approved by the Institutional


Ethical Committee, and written consent was
taken from every participant. Study group
comprises 38 newly diagnosed both male and
female OSMF patients of age between 25 to 45
years who have not received any previous
treatment or on any antioxidant therapy and were
confirmed after the detailed case history and
histopathological confirmation. For the control
group same number of age and sex matched
healthy individuals who are non tobacco and
areca quid consumers, who were not suffering
from any systemic illness, were selected. From
both control and study group 5 ml venous blood

was taken, transferred to a heparinised test tube


and centrifuged at 4C and the plasma was stored
at 80oC till the biochemical investigations were
done. In both control and OSMF groups we
estimated antioxidant enzymes like SOD5, GSHPx6 and Catalase7 and the lipid peroxidation rate
was determined by estimating Malondialdehyde
which is also called thiobarbituric acid reactive
substances (TBARS)8. SOD was estimated auto
oxidation method by adding 0.5ml of plasma to
1.8mM epinephrine and 0.6mM EDTA and the
increase in absorbance was read at 480nm. GSHPx was measured by DTNB method .03 ml of
hemolysate to .04% DTNB (Dithiobis nitro
benzoic acid) and 1.215mM H2O2 and the change
in abosrbance was taken at 412nm. Plasma
catalase was assessed by Goths methods adding
0.2ml of plasma to 60mmol/l H2O2 and
32.4nmol/L ammonium molybdate and change
in absorbance was measured at 405nm.
Statistical Analysis
A Student t test was applied to assess the
statistical difference of the above said biological
parameters between OSMF patients and control
group. P <0.05 was considered as significant.
Statistical analysis was done by SPSS 18 version.
RESULTS
Enzymatic antioxidant defense status in OSMF
was assessed by measuring plasma Superoxide
Dismutase, Catalase and Glutathione Peroxidase.
One of the prominent adverse effects of free
radicals was estimated by measuring plasma
Malondialdehyde (MDA). The plasma levels of
these antioxidant enzymes and MDA were
compared with control group (Table I). We
observed very low levels of antioxidant enzymes,
and very high MDA in OSMF when compared to
control group (p < 0.01).

230

Teklal et al.,

Int J Med Res Heatlh Sci. 2013;2(2):229-232

Table-1: Antioxidant enzyme and lipid peroxidation levels in control and OSMF patients.
Parameters
Control n=38
OSMF group n=38
Malondialdehyde (MDA) nmol/ml
1.04 0.14
3.1 0.58*
Superoxide dismutase (SOD) U/g Hb
1104 126
527 84*
Glutathione peroxidase (GSH-Px) U/g Hb
91 6.3
48 4.2*
Catalase (CAT) KU/L
24 5.1
14 3.5*
Results were presented as mean + SD. *P <0.01
DISCUSSION

In the present study by assessing the plasma


levels of antioxidant enzymes SOD, CAT, GSHPX levels and MDA we observed the prevalence
of high oxidative stress like environment in
OSMF because of release of high free radicals
and reactive oxygen species from smokeless
tobacco consumption in the form of quid. The tar
phase of tobacco contains several relatively
stable free radicals; of which the principle radical
identified was a quinone/hydroquinone (Q/QH2)
complex held in the tarry matrix9. This Q/QH2
polymer is an active redox system that is capable
of reducing molecular oxygen to produce
superoxide, eventually leading to hydrogen
peroxide and hydroxyl radicals. Along with this
the high copper content of areca a content of quid
also contributes in the generation of free radicals
by Fenton and Haber - Weiss reactions10.
H2O2 + Cu (I)
Cu (II) + OH + OH(I) Fenton Reaction
H2O2 + O2O2 + OH + OH- (II)
Haber-Weiss Reaction
Through
these
mechanisms
excessively
generated free radicals in tobacco quid
consumption were quenched by bodys first line
of antioxidant mechanism that is chain breaking
mechanism through antioxidant enzymes like
SOD, CAT and GSH-Px. This might be the
reason for decreased concentration of these
enzymes which were observed in the study
population. The same decrease in antioxidant
enzymes in tobacco consuming OSMF were
observed by many researchers11, 12. In the present

study we also observed higher levels of MDA in


tobacco consuming OSMF patients. This may be
due to adverse effects of hydroxyl radical OHradical which was produced by the Q/QH2
polymer of tobacco. OH- oxidizes double bonds
of polyunsaturated fatty acids (PUFA) of cell
membrane, thus produces the end product called
Malondialdehyde (MDA). There is substantial
evidence that the OH- radical generated from
copper through the Fenton reaction can destruct
tissue by initiation and propagation of lipid
peroxidation by absorbing hydrogen from PUFA
of cell membrane to produce MDA. Our results
are positively correlated with other researchers
also11, 13. The oxidative stress like environment
which prevails in this group might render as an
individual more susceptible to damage, which
might have led to the development of sub
mucous fibrosis. The decrease in antioxidant
enzymes in this study might be due to
consumption of these enzymes in quenching of
high levels of free radicals which are generated
due tobacco metabolism.
CONCLUSION

From this study it was concluded that in OSMF


patients very low levels of antioxidant enzymes
and higher lipid peroxidation in Areca quid
consuming OSMF patients. Areca and tobacco
metabolism might produce high levels of free
radicals which might play an important role in
the initiation and propagation of fibrosis of the
oral mucosa.

231

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Int J Med Res Heatlh Sci. 2013;2(2):229-232

REFERENCES

1. Ramachandra Reddy GV, Vasudha KC,


Lakshmaiah M, Nirmal Kumar A .
Estimation of serum beta carotene levels in
oral cancer. JIAOMR 2005; 17: 157-160.
2. Subhash Chandra Bose K, Preran VG, Sunil
D and Manika Singh. Quantitative evaluation
and correlation of serum glycoconjugates:
protein bound hexoses, sialic acid and fucose
in leukoplakia, OSMF and oral Cancer. J Nat
Sc Biol Med 2013; 4: 122-25.
3. Ahmad MS, Ali SA, Chaubey KK.
Epidemiological and etiological study of oral
submucous fibrosis among Gutkha chewers
of Patna, Bihar, India. J Indian Soc Pedod
Prev Dent 2006; 2: 84-89
4. Pillai PN, Burde KN. Increased copper level
in oral tissue of patients with submucous
fibrosis and who chew areca nut products.
West Indian Med J 2005; 54: 270-71.
5. McCord J.M and Fridovich I. Super Oxide
dismutase. J Biol Chem 1969; 18: 655-73.
6. Pagila DM and Valentine WN. Studies on the
quantitative
and
characterization
of
erythrocyte Glutathione Peroxidase. J Lab
Clin Med 1986; 20 : 150-68.
7. Sinha KA. Calorimetric assay of catalase.
Ana Biochem. 1972; 47: 389-94.
8. Satoh K. Serum lipid peroxidation in CVD
determined by the new calorimetric method.
CCA 1978; 90: 37-43.
9. Daniel FC and William AP. Free radical
chemistry of cigarette smoke and its
toxicological implications. Environmental
health perspectives 1985; 64: 111-26.
10. Khanna SS, Karjodkar FR. Circulating
immune complexes and trace elements as
markers in oral pre cancer and cancer: A
randomized, controlled clinical trial. Head
Face Med 2006; 2: 1-10.

11. Suryakant MB, Tupkari JV, Barpande SR.


An estimation of serum Malondialdehyde,
superoxide dismutase and vitamin A in
OSMF and its clinicopathological correlation.
JOMFP. 2007; 11: 23-27.
12. Soma Gupta, Reddy MVR. and Harinath BC.
Role of oxidative stress and antioxidants in
aetiopathogenesis and management of
OSMF. Indian J Clin Biochem 2004; 19:
138-41.
13. Khanna R, Thapa PB, Khanna HD, Khanna
S, Khanna AK, Shukla HS. Lipid
peroxidation and antioxidant enzyme status
in oral carcinoma patients. KUMJ 2005; 12:
334-39

232

Teklal et al.,

Int J Med Res Heatlh Sci. 2013;2(2):229-232

DOI: 10.5958/j.2319-5886.2.2.030

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April - June

th

Received: 25 Feb 2013


Research article

Coden: IJMRHS
th

Revised: 24 Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted:29 Mar 2013

THE PREVALENCE AND ANTECEDENTS OF OCCUPATIONAL STRESS AMONG


RADIOGRAPHERS IN ZIMBABWE: INTERPLAY OF ECONOMICS AND CULTURE.
*Chingarande George R, Ndlovu Bekezela
Radiology Department, University of Zimbabwe, Zimbabwe
*Corresponding author email:gchingarande@yahoo.com; grchingarande@medsch.uz.ac.zw
ABSTRACT

The purpose and objectives of this study were to find out the incidence of Occupational Stress amongst
radiographers and also to find out the main stressors that they are exposed to. A cross sectional survey
using both qualitative and quantitative methodologies and a questionnaire as a research tool was
conducted. The questionnaire was given to all radiographers working in the general radiology
department of the six departments/centres that participated in the study. The results revealed that there is
a high incidence of occupational stress among medical radiographers working in general radiology. The
results also showed that the most frequently encountered stressors in the general radiology department
are pressure to complete tasks/overwork, inadequate salaries and inadequate holiday/vacation time.
There were no significant differences in the incidences of occupational stress between male and female
radiographers. However, there were differences in the perceptions of the two genders on the causes of
stress. This was attributed to the cultural gender role expectations.
Keywords : Occupational stress; Radiographers, Gender role, Culture, Stressors
INTRODUCTION

Occupational stress has been linked to a range of


adverse physical and mental effects, including
insomnia, depression, cardiovascular disease and
anxiety1. Stressful working conditions have also
been reported to impact negatively on employee
well-being by directly contributing to negative
health behaviours or by limiting an individuals
ability to make positive changes to lifestyle
behaviors, such as smoking and sedentary
behaviours2. Occupational stress can result from
the job itself (i.e., heavy workload, lack of
control) or the social and organizational contexts
in which the job is done (i.e., poor

communication, interpersonal conflict). Workers


perceive and respond differently to the
environment in which they work.
Health care workers have been reported to be
among the most stressed professionals3. This has
been attributed to the increased risk of infection,
high job demands, compassion fatigue,
understaffing, inadequate resources, a lack of
control and/or participation in planning, and a
lack of work security. Zimbabwes health care
system is characterized by inadequate staffing,
reduced accessibility by the general population,
shortages of essential drugs and medical
233

Chingarande George et al.,

Int J Med Res Health Sci.2013;2(2):233-238

supplies, and outdated and poorly functioning


equipment (USAID, 2009)4. This, coupled with
long working hours, exposure to infectious
diseases and hazardous substances, the threat of
malpractice litigation and constant encounters
with death and dying conspires to expose
radiographers to occupational stress. The
deleterious effects of occupational stress on work
performance have also been reported5.
Extant literature review reveals that the
prevalence of Occupational stress among
radiographers has not been investigated in
Zimbabwe. The current study sought to address
that lacuna by seeking to establish firstly, the
prevalence of occupational stress among
radiographers in Harare and Chitungwiza, and
secondly its antecedent causes. Harare is the
capital city of Zimbabwe whereas Chitungwiza is
a town about thirty kilometers to the south of
Harare, which was originally established as a
dormitory to the capital. The two were selected
because they were deemed convenient and easily
accessible sites to conduct an exploratory study
of this nature.
MATERIALS AND METHODS

After ethical approval was granted by the


University of Zimbabwe College of Health
Sciences Joint Research and Ethics Committee,
38 consenting radiographers employed in the
government hospitals were enrolled into the
study.
A self report questionnaire was employed as the
data collection instrument. The questionnaire
was arranged into three thematic sections. The
first section was designed to elicit information on
demographic data such as age band, gender,
professional experience, marital status and tenure
with the present employer. The second section
was designed to measure the prevalence of
occupational stress and its causes. The third
section was open-ended and requested the
participants to suggest solutions of alleviating
occupational stress. The questionnaires were

hand delivered and then


completion on agreed dates.

collected

after

RESULTS

A total of 41 questionnaires was delivered and 38


usable questionnaires were returned yielding a
93% response rate. 58% of the participants were
female, while 42% were married. There were no
divorcees and widowed. 68% of the participants
were in the age band 21-30; 21% were in the 3039 age-band, 3% were in the 40-49 band and 8%
were above 50 years old. Furthermore 13% of the
participants had less than one year experience,
37% had more than one year but less than two
years experience, 15% had more than two years
but less than five years, 13% had more than five
years but less than 10 years while 21% had more
than 10 years professional experience. The fact
that 50% of the participants had less than two
years experience is a graphic but a grim
illustration of the impact that brain drain has had
on the radiography profession in Zimbabwe.
Analysis of tenure in current workplace revealed
that 63% of the participants have been with the
current employer for less than two years while
8% had been with their current employer for
more than two years but less than five years and
29% had been at their current workplace for
more than 5 years, with 8% reporting that they
had been with the current employer for more
than ten years.
To establish the prevalence of occupational stress
the radiographers were asked to indicate the
extent to which they agreed with six statements.
These are; Work commitments are affecting my
social relationships; I am so busy I find it
increasingly difficult to concentrate on the job at
hand; I am often exhausted in the morning at the
thought of work; I find it difficult to control my
emotions; I feel so tired during the day, when at
work and I feel that my experience stress at
work. These questions were based on factors and
symptoms of stress which are fatigue, dread of
work, lack of emotional control, no time for
social relationships and being overwhelmed by
work. The options available to the respondents
234

Chingarande George et al.,

Int J Med Res Health Sci.2013;2(2):233-238

ranged from strongly agree (indicating the


severity of the stressor) to strongly disagree
(indicating the absence of the stressor).
A scoring system was designed in which,
strongly disagree was given a value of one with
strongly agree given the maximum value of five.
Thus the higher the individual score, the more
severe the exposure to the stressors hence the
more stressed the individual. This means that the
total score for an extremely stressed person

would be thirty (from 5*6=30) and the least


stressed person would score a total of six (from
6*1=6). Under this system, a score of 12 or less
would mean that the person is experiencing
insignificant occupational stress; a total score
between 13 and 18 would indicate moderate
stress and a total score above 18 would mean the
presence of significant occupational stress. Table
1 below presents a summary of the prevalence of
occupational stress.

Table 1:Prevalence of occupational stress among radiographers.


Stress Category
Number of participants
Prevalence
Insignificant
Moderate
Significant
Total

7
12
19
38

18.4%
31.6%
50%
100%

Table 2: Causes of occupational stress.

Main stressors

Number of participants reporting this variable


as a stressor.

Variable
Lack of control
Lack of recognition
Lack of respect from supervisors
Overwork/arc work pace
Inadequate pay
Fear of illness
Exposure to radiation
Forced overtime/long hrs
Too much pressure
Call duty
Harassment
Job insecurity
Sexism
Lack of prospective promotion
Workplace noise
Poor ventilation
Poor lighting
Poor communication
Inadequate holiday/vacation/time off

Total No (%)
15 (39.4)
18 (47.4)
11 (28.9)
29 (76.3)
24 (63.2)
6 (15.8)
10 (26.3)
12 (31.6)
18 (47.4)
14 (36.8)
7 (18.4)
3 (7.8)
4 (10.5)
11 (28.9)
3 (7.8)
12 (31.6)
4 (10.5)
14 (36.8)
23 (60.5)

Women (%)
8 (53.33)
9 (50.0)
4 (36.4)
15 (51.7)
9 (34.6)
2 (33.3)
5 (50.0)
7 (58.3)
11 (61.1)
6 (42.9)
2 (28.6)
0
1 (25)
4 (36.4)
0
4 (33.3)
1 (25)
8 (57.1)
12 (47.8)

Men (%)
7 (46.66)
9 (50.0)
7 (63.6)
14 (48.3)
15 (65.4)
4 (66.7)
5 (50.0)
5 (41.7)
7 (38.9)
8 (57.1)
5 (71.4)
3 (100)
3 (75)
7 (73.6)
3 (100)
8 (66.7)
3 (75)
6 (42.9)
11 (52.2)

235

Chingarande George et al.,

Int J Med Res Health Sci.2013;2(2):233-238

Fifty percent of the radiographers rated their


occupational stress level in the significant region.
Furthermore, the respondents were presented
with a more direct item, I feel my experience
stress at work. prefaced by an instruction to
indicate the extent to which they agreed with the
statement. A total of 71.1% (27) of the sample
perceived that they were experiencing
occupational stress and only 15.8% (6) of the
sample perceived that they did not experience
any occupational stress. The remaining 13.1%
(5) was undecided.
To establish the major causes of occupational
stress the radiographers were presented with a
list of stressors gleaned from the literature and
asked to indicate the stressors that were
applicable to them. They were also asked to
identify what they believed to be the three main
stressors
The most frequently mentioned stressors were
Overwork/accelerated work pace with (76.3%),
Inadequate pay (63.2%) and Inadequate
holidays/vacations/time away from work with
(60.5%). The top three stressors among females
were Overwork, Inadequate holidays and Too
Much pressure. Males reported Inadequate Pay,
Overwork and Inadequate Holidays as the most
common antecedents of stress.
When asked to list the three main stressors
81.6%
of
the
participants
listed
Overwork/accelerated work pace, inadequate pay
and inadequate holidays/ vacation/ time off.
The most frequently suggested solutions to
occupational stress were; Pay increase,
Reduction of working hours, Provision of more
time for vacation and leave, Increasing the staff
complement and Staff development aimed at
improving staff-supervisor relationships.
DISCUSSION

The main thrust of this study was to investigate


the prevalence of occupational stress among
radiographers working in public hospitals in
Harare and Chitungwiza. Hence extrapolation to
cover all radiographers in Zimbabwe should be

done with extreme caution. In this study 50% of


the
radiographers
reported
experiencing
significant occupational stress. Such a high
incidence of stress can therefore lead to a high
incidence of ill health since the link between
occupational stress and an increase in a whole
spectrum of physical illnesses, from the common
cold to cancer, heart disease, diabetes and sudden
death is well established6. In the long run this
will be negatively repercussive on the
productivity of the radiology departments.
The study revealed that the most common
antecedents of occupational stress were
overwork/Accelerated work pace, inadequate
pay, inadequate holiday/vacation/time, too much
pressure and lack of recognition. A further
finding was that male radiographers consider
inadequate pay as a stressor higher than their
female counterparts. The cultural milieu within
which these radiographers work emphasizes the
role of the male as the bread winner and
protector of the family. This assumes more
significance and salience during perilous times
such as the prevailing economic environment.
Failure to discharge this role is viewed as social
deviance and impotence on the part of the male.
Hence the culture is placing an even higher
burden of stress on the male radiographer.
Wilkes et al (1998)7 reported that work
overloads and time constrains were significant
contributors to work stress among nurses. The
results of the current study are in keeping with
that finding although the focus here is on
radiographers.
Untenable workloads are a
constant characteristic of a healthcare workers
job in developing countries. The workload
conundrum among radiographers in Zimbabwe
can be traced to the economic imbroglio that
blighted the country in the last decade. Economic
hardships resulted in less and less people
affording and accessing private health care; and
more and more people patronizing radiography
services in public hospitals. This increased
patronage spawned increased workload on the
radiographers. The economic meltdown also
gave impetus to a brain drain which saw many
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Chingarande George et al.,

Int J Med Res Health Sci.2013;2(2):233-238

experienced radiographers seeking employment


abroad leaving the public radiography
departments inadequately staffed. This problem
was further complicated by the government
decision to impose a moratorium on recruitment
of staff in the civil service which adversely
affected the health sector in general and
radiography in particular.
The second most commonly cited stressor was
inadequate pay. This finding is in concordance
with the findings of Sehlen (2009)8 and Ernst and
colleagues9. The problem is not unique to
Zimbabwe as the National Institute of
Occupational Safety and Health in the United
States10 (2008) also identifies financial and
economic
factors
as
stress.
However,
remuneration for radiographers working in the
public service in Zimbabwe remains untenably
low with junior cadres earning less than US$400
per month in comparison with a poverty datum
line of $600. The unsustainably low
remuneration incentives radiographers to
moonlight in the private radiology centers.
Ironically the already overworked radiographers,
who should be seeking to rest and recuperate,
seek more work in an effort to mitigate their
financial woes and in the process exacerbate burn
out.
The third most commonly cited stressor was
Inadequate holidays, vacations and time away
from work. This stressor is symbiotically linked
to the other two stressors already discussed.
Inadequate staffing levels and work overload
result in more work and longer working hours for
the radiographers. On the other hand the
radiographers opt to work extra hours as a way of
augmenting their low salaries by boosting their
overtime pay. This creates a vicious cycle in that
inadequate time away from work invariably leads
to burn out; burn out leads to reduced
productivity; reduced productivity results in
work backlogs which in turn have a direct impact
on occupational stress. Both male and female
radiographers cited inadequate time away from
work as stressors. However, further probing,

revealed that their reasons for this were different.


The males want more time away from their
regular jobs so that they can engage in other
income generating activities to fend for the
family while their female counterparts expressed
a desire to spend more time with the family. The
culturally prescribed roles (mother role for the
female and bread winner role for the male)
have a huge influence on how the two genders
perceive the antecedents to occupational stress.
CONCLUSION AND RECOMMENDATIONS

Occupational stress among radiographers in


Zimbabwe is linked to the interplay between
economics and culture. Remuneration of
radiographers, and indeed all civil servants,
remains an intractable issue. While the need for
upward revision of the salaries is not disputed,
the government pleads that it does not have the
requisite resources. There is no easy panacea to
the economics dimension of the cryptic puzzle.
Therefore, while the stakeholders are engaged in
discussions over improvement of remuneration,
it is imperative that other initiatives to alleviate
occupational
stress
be
explored
and
implemented. These include unfreezing the
moratorium on recruitment of radiographers;
reduction in working hours and introduction of
flexible working hours to accord the
radiographers adequate time to rest and
recuperate and also fulfill their culturally
prescribed roles; introduction of work stress
intervention programs designed to teach
radiographers about the nature and sources of
stress, the effects of stress on health, and
personal skills to reduce stress; and the
introduction of regular medical checks.
Specialist services should be made freely
available to those radiographers in need of
treatment for occupational stress.
ACKNOWLEDGEMENTS

The study was fully sponsored from the authors


own resources.

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Int J Med Res Health Sci.2013;2(2):233-238

REFERENCES

1. Cooper CL & Marshall J.. Occupational


sources of stress: a review of the literature
relating to coronary heart disease and mental
ill health. Journal of Occupational
Psychology. 1976; 49, 11-28
2. Nakao
M. Work Related Stress and
Psychosomatic medicine, BioPychosocial
Medicine.2010;4:4
3. Thomas LS, Valli A. Levels of occupational
stress in doctors working in a South African
public sector hospital. S Afr Med J. 2006,
96:1162-68
4. USAID (Zimbabwe). Zimbabwe US foreign
assistance performance. Publication FY 2009
(This a document published by the United
States International Development Zimbabwe
office . Hence, author is USAID
ZIMBABWE
5. Cotton P. & Hart PM. Occupational
Wellbeing and Performance: a Review of
Organisational Health Research. Australian
Psychologist. 2003;38 (1): 118-27.
6. Cohen S, Frank E, Doyle WJ, Skoner DP,
Rabin BS, & Gwaultuey JM. Types of
stressors that increase susceptibility to the
common cold in healthy adults. Health
Psychology 1998; 17: 214-23
7. Wilkes L, Beale B, Hall E, Watts B & Denne
C. Community nurses descriptions of stress
when caring in the home. International
Journal of Palliative Nursing, 1998; 4(1): 612
8. Sehlen S., Vordermark, D., Schafer C,
Herschbach P, Pigorsch S, Rittweger J, et al.
(2009). Job stress and job satisfaction of
physicians, radiographers, nurses and
physicists working in radiotherapy: a
multicenter analysis by the DEGRO Quality
of
Life
Work
Group.
Radiology
Onology.2009; 27:11-11
9. Ernst ME, Messmer PR, Franco M and
Gonzalez JL. Nurses job satisfaction, stress,
and recognition in a pediatric setting. Pediatr
Nurs 2004, 30(3):219-27.

10. National Institute for Occupational Safety


and Health (NIOSH.) Exposure to stressOccupational
hazards
in
hospitals.
Publication No 2008-136.

238

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Int J Med Res Health Sci.2013;2(2):233-238

DOI: 10.5958/j.2319-5886.2.2.029

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 28 Feb 2013


Research article

Coden: IJMRHS
th

Revised: 29 Mar 2013

Copyright @2013

ISSN: 2319-5886
st

Accepted: 31 Mar 2013

A CADAVERIC STUDY INVOLVING VARIATIONS IN EXTERNAL MORPHOLOGY OF


GALL BLADDER
*

Anjankar Vaibhav Prakash1, Panshewdikar Pradnyesh N2, Joshi DS2, Anjankar Ashish Prakash3

Department of Anatomy, L.N. Medical College & Research Center, Bhopal, India
Department of Anatomy, Dr. Shankarrao Chavan Govt. Medical College, Nanded, India
3
Department of Biochemistry, Government Medical College, Nagpur, India
2

*Corresponding author e-mail: vaibhav_anjankar@yahoo.co.in


ABSTRACT

Background: Variations in the pattern of the extra hepatic biliary tract are usual and are commonly
encountered during some radiological investigations or in operation theaters. Such Variations of the
morphology of Gall bladder have been well documented in the literature for many years but a detail
morphological study of variations of the gall bladder and its incidence is very rare. In this era of quick
results, increasing use of diagnostic and interventional procedures makes it important to study variations
of gall bladder morphology. Most of the interventional procedures in this modern era are done
laparoscopically and there is tremendous increase in the number of laparoscopic cholecystectomies. So,
sound knowledge of possible variations in morphology of gall bladder is important. Materials and
Methods: This study was undertaken on 90 cadaveric liver and gall bladder specimens in terms of
length, maximum transverse diameter, shape, external variations of gall bladder, Interior and length of
gall bladder below the inferior border of the liver. Results: GB had length ranging between 7 and 10 cm,
transverse diameter between 2 and 5 cm. The commonest shape observed in this study was pear shaped
in 82.22% of cases. The length of gall bladder below the inferior border of liver varied between 0.4 and
2.5 cm. Conclusion: The growing importance of such variations, lie not only from the point of biliary
disease but also with respect to the various invasive techniques in the diagnosis and treatment of gall
bladder and extrahepatic bile duct disease.
Keywords: Cholecystectomies, Laparoscopically, Variations, Interventional, Malformations.
INTRODUCTION

The gallbladder (GB) is a flask-shaped, blindending diverticulum attached to the common bile
duct by the cystic duct. In life, it is gray-blue in
color and usually lies attached to the inferior
surface of the right lobe of the liver by
connective tissue. In the adult the gallbladder is

between 7 and 10 cm long with a capacity of up


to 50 ml. The gallbladder is described as having
a fundus, body and neck1.
Though human beings are thought to be similar
in their general anatomical phenotype, but when
we come to investigate one particular region with
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Anjankar et al.,

Int J Med Res Health Sci. 2013;2(2):239-242

more detail, it is surprising how frequently we


meet one sort or another type of variations1.
Variations in the anatomy of gall bladder, bile
ducts and the arteries that supply them and liver
are surgically important because failure to
recognize them may lead to inadvertent ductal
ligation, biliary leaks and strictures after
laparoscopic
cholecystectomy
and
other
procedures also. Congenital anomalies of extra
hepatic biliary tree have long been recognized
but are rare and may be of clinical importance
because they may provide surgeons with an
unusual
surprise
during
laparoscopic
cholecystectomy. Several less common and more
complicated anatomic variations can also be
found in relation to extrahepatic biliary tract.
The basic knowledge of embryologic
development and normal anatomy of biliary tree
will help in understanding and identifying this
group of anomalies. Understanding of these
variants is important before laparoscopic
procedures, however, preoperative diagnosis by
routine investigations is difficult and is only seen
in very few cases and they often turn out to be
unexpected findings during laparoscopic
surgeries. This study will be of great help to
surgeons to understand possible morphology of
the gall bladder.
MATERIALS AND METHODS

This study was carried on 90 liver and


gallbladder specimens obtained from formalin
fixed cadavers in the Department of Anatomy of
Dr. Shankarrao Chavan Govt. Medical College,
Nanded. Cadavers with obvious abdominal
surgery and crush injury to the abdominal organs
were excluded from the study. The parameters
studied were the maximum length of gall
bladder, maximum transverse diameter, shape,
external variations of gall bladder, Interior, Level
i.e. length of gall bladder below the inferior
border of the liver.
Maximum length and maximum transverse
diameter were measured using metallic
measuring tape gradated in centimeters. The

shape of gall bladder was noted down. Any


variation in external appearance of gall bladder
was also noted. Part of the gall bladder i.e.
fundus that lie below the inferior border of liver
was noted. Interior of gall bladder was also
visualized to see any abnormality by cutting
across its wall with the help of a scalpel blade.
RESULTS

Maximum length of gall bladder: Average


length of gall bladder was found to be 10.2 cm.
The smallest gall bladder was 4.3 cm in length
and the largest had length 12.4cm. 72.22%
(65/90) GB had length ranging between 7 and 10
cm.
Maximum transverse diameter of gall bladder
Mean breadth of gall bladder was 3.89 cm. The
shortest transverse diameter was 2.4 cm and
largest 5.3 cm. 75.56% (68/90) GB had a
maximum transverse diameter between 2 and 5
cm.
Shape of gall bladder:The gall bladders were
classified according to their shapes. Various
shapes observed were pear shaped, cylindrical
shaped, hourglass shaped, retort shaped, flask or
irregular shaped. The commonest shape found
was pear shaped (74/90, 82.22%). Their
incidences are shown in the Table I.
External appearance of gall bladder: Foldings
of neck and fundus (whether anteriorly or
posteriorly) were noted. Folding of neck or
fundus was noted in 9 out of 90 specimens of
GB.
Length of gall bladder below inferior border
of liver: The length of gall bladder below the
inferior border of liver varied between 0.4 and
2.5 cm.
Interior of gall bladder: In most of the gall
bladders, interior was found to be normal with
numerous rugosities of the mucosa. Gall stones
were observed in five specimens either singly or
in multiples. Some of the gall bladders have had
various degrees of mucosal adhesions and septa.

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Int J Med Res Health Sci. 2013;2(2):239-242

Table 1. Showing length and transverse diameters of gall bladder as recorded by other authors
Sr. No.

Authors

Length of gall

Transverse diameter of gall

bladder

bladder

10 cms

3-5 cms

1.

Turner&Fulcher/(2000) 3

2.

Chari &Shah (2008) 5

7-10 cm

2-5 cm

3.

Vakili& Pomfret (2008)

7-10 cm

4 cm

4.

Jaba Rajguru et al2 (2012)

5-12 cm

2.5-5 cm

5.

Present study (2013)

7-10 cm

2-5 cm

DISCUSSION

The gall bladder, liver and the biliary ductal


system develop from the hepatic endodermal
diverticulum of the foregut, at the beginning of
the fourth week of development .This
diverticulum rapidly proliferates into the septum
transversum and divides into two parts - the
cranial part develops the liver and the bile ducts
while the caudal part gives rise to the gall
bladder and the cystic duct. Any arrest or
deviation from the normal embryological
developmental process may result in some sort of
malformation of the gallbladder and of the biliary
system2.
The measurements of length and breadth of gall
bladder were very similar to that found by Shari
RS and Shah SA1 (2008) and Jaba Rajguru et al2
(2012). Comparison of length and breadth with
other workers has shown in table I. Size of gall
bladder varies in different diseased conditions as
well as in some physiological conditions too. It
may be impossible sometimes to distinguish
between various parts described. The size of GB
may increase after vagotomy, diabetes,
pregnancy, sickle cell disease, after cystic duct or
common bile duct obstruction2.
Shapes of GB vary tremendously and various
authors have described various shapes. The
terminologies describing the shape are also very
confusing. We found pear shaped GB as most
common in 64 patients (71.11%). Jaba Rajguru et

al2 noted pear shaped gall bladder in 85%


specimens. Hollinshed3 (1983), Shaher4 (2005),
Moore and Dalley5 (2006), Chari and Shah1
(2008) noted various shapes of GB.
The gall bladder is relatively constant in its
development and the two most significant
variations are the folded fundus and variation at
the neck of the gall bladder3. The folded fundus
of the gall bladder, also called as the Phrygian
cap, was reported in 3-7.5% of GB by
Lichtenstein & Nicosia6 (1955). They proposed
that it could due to a disproportion between the
size of the gall bladder and that of the gallbladder
bed, but without any pathological significance2.
In our study, we found folded fundus in 5 GB
(5.56%) and folded neck in 4 GB (4.44%).
Deutsch7 (1986) and Gore et al8 (2000) recorded
folded fundus in very few percentage of GB2.
The length of Gall bladder below the inferior
border of the liver in our study was found to be
ranging between 0.4 and 2.5 cm. This is the most
susceptible part of GB that can be damaged in
laparoscopic procedures. This was the pilot
parameter of our study. We couldnt find any
literature regarding this parameter.
The interior showed various features like
adhesions, septa, stones etc. Septum was
observed in only 2 GB (2.22%). Csepel et al
(2003), Chalkoo (2009) and Talpur et al (2010)
also observed septum in some gall bladders2. In
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Anjankar et al.,

Int J Med Res Health Sci. 2013;2(2):239-242

our study, five gall bladders (5/90, 5.56%)


showed the presence of stones in its interior.
However congenital anomalies of gallbladder are
rare and can be accompanied with other biliary
and vascular malformations9. Due to these
anatomical variations, complications seen were
bleeding and biliary leaks leading morbidity10.
The main limitation of our study was the small
sample size. The comparative study involving
GB morphometry in cadavers and sonographic/
radiological findings should be undertaken.
CONCLUSION

The occurrence of bizarre forms of congenital


anomalies and anatomical variations of gall
bladder and extra-hepatic biliary tree though are
not common but can be of clinical importance
and surprising to the surgeons if present. But the
literature regarding morphological variations of
the gall bladder and their incidence is scarce.
These variations generally remain symptoms free
but often lead to complications and therefore
must be correlated clinically. Awareness of these
anomalies will decrease morbidity, and reexploration in such patients. Most of the
interventional procedures in this modern era are
done laparoscopically and there is tremendous
increase
in
number
of
laparoscopic
cholecystectomies. So, thorough knowledge of
possible variations in morphology of gall bladder
is important. This article will be of utmost useful
to the surgeons to understand and identify
possible variations of GB morphology.
REFERENCES

1. Chari RS, Shah SA. Biliary system In:


Townsend CM, Beauchamp RD, Evers BM,
Mattox
KL. Sabiston
Textbook
of
th
Surgery. 18
ed; St. Louis, Mo: WB
Saunders; 2007:chap. 54; 1474-14.
2. Jaba Rajguru, Satyam Khare, Shilpi Jain,
Rashmi Ghai, Mukesh Singla, Prabhat Goel.

Variations In The External Morphology Of


Gall Bladder. J. Anat. Soc. India 2012;61(1)
9-12.
3. Hollinshed WH. Anatomy for Surgeons in
the Liver and the Gall bladder, 3rd Ed; Vol. 2;
Harper and Row, Philadelphia, 1983, 334.
4. Shaher Z: Gallbladder Anomalies; Agenesis,
Hourglass, And Liver Tissue Migration: A
Multimedia Article. The Internet Journal of
Surgery. 2005; 6(2): p. 9
5. Moore KL and Dalley AF. Clinically
Oriented Anatomy in Abdomen . 5th edn,
Lippincott Williams & Wilkins, Philadelphia
,2006 ,302.
6. Lischtenstein M, Nicosia AJ The Clinical
Significance of Accessory Hepato-Biliary
Ducts. Annals of Surgery. 1955; 141 (1):120124.
7. Deutsch AA, Englestein D, Cohen M,
Kunichevsky M, Reiss R. Septum of the
gallbladder, clinical implications and
treatment. Postgrad Med J. 1986; 62: 453-56.
8. Gore RM, Fulcher AS, Taylor AJ,
Ghahremani
GG.
Textbook
of
Gastrointestinal Radiology, in Anomalies and
Anatomic Variants Of The Gallbladder And
Biliary Tract. 2nd ed. WB Saunders Co,
Philadelphia, PA;2000;1305-20.
9. Carbajo MA, Martin del Orono JC, Balanco
JI, CuestaC, Martin F, Toledano M, et al.
Congenital malformations of gallbladder and
cystic duct diagnosed by laparoscopy: high
surgical risk. JSLS 1999; 3: 319-21.
10. Khamiso Altaf Hussain Talpur et al.
Anatomical variations and congenital
anomalies of Extra Hepatic Biliary System
encountered
during
Laparoscopic
Cholecystectomy. J Pak Med Assoc; 2010;
60(2): 89-93.

242

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Int J Med Res Health Sci. 2013;2(2):239-242

DOI: 10.5958/j.2319-5886.2.2.028

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 8 Feb 2013


Research article

Coden: IJMRHS
th

Revised: 26 Mar 2013

Copyright @2013

ISSN: 2319-5886
st

Accepted: 31 Mar 2013

IMPACT OF AGEING ON DEPRESSION AND ACTIVITIES OF DAILY LIVINGS IN


NORMAL ELDERLY SUBJECTS LIVING IN OLD AGE HOMES AND COMMUNITIES OF
KANPUR, U.P.
*Vanshika Sethi1, Vijeylaxmi Verma2, Udhbhav Singh2
1

Assistant Professor, 2 BPT students Physiotherapy Department , Saaii College of Medical Science and
Technology, Chaubeypur , Kanpur,U.P., India

*sethivanshika@gmail.com,sethi_vanshika@yahoo.co.in
ABSTRACT

Introduction: Ageing is a progressive, generalized impairment of functions resulting in loss of adaptive


response to stress and increasing the risk of age related disease. Methodology: A sample of 200 elderly
subjects i.e. 100 from the community (group A) and 100 from Old age home (group B) of sixty & above
years of age were taken by the convenience sampling method. The subjects were collected through
various old age homes and community which includes Vaikunth Dham Old Age Home, Ishwar Prem
Ashram, Swaraj Ashram, Ramkrishna Mission old age home and nearby community located in the
Kanpur and Varanasi. The subjects were assigned a number to maintain the confidentiality of the
subjects and then the scales were used to assess the scores i.e., Geriatric Depression Scale (GDS) and
Barthel index of daily livings were used to check the level of depression & ADLs and then the scores
were compared. The results: The mean GDS scores for group A were 11.32 and for group B were 16.42
with a value of -6.981 with a p value of 0.00* and mean ADLs scores on the Barthel index for group A
were16. 54 and 17.98 for group B within value of -2.898 with a p value of 0.004* which shows there is a
significant difference. Conclusion: Elderly subjects living in Old age home are more affected in terms
of depression and ADLs as compared to community dwelling elder subjects as old people living in their
own homes were most able to cope in their homes. They received more support from relatives and
friends than from health and social services
Key words: Elderly, ADLs, Depression, Community, Old age home
INTRODUCTION

Age classification varied between countries and


over time, reflecting in many instances the social
class differences or functional ability related to
the workforce, but more often than not was a
reflection of the current political and economic
situation. Many times the definition is linked to

the retirement age, which in some instances, was


lower for women than men. This transition in
livelihood became the basis for the definition of
old age which occurred between the ages of 45
and 55 years for women and between the ages of
55 and 75 years for men1.
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Int J Med Res Health Sci. 2013;2(2): 243-249

Elderly people are classified into: - 1) 60 yrs to


70yrs- Young old 2) 70 yrs to 80yrs- Middle old
3) 80yrs &above- Old old 2.
The risk factors for reduced physical function in
elderly people, as identified in longitudinal
studies, relate to comorbidities, physical and
psychosocial health, environmental conditions,
social circumstances, nutrition, and lifestyle3
As the western population is increasingly ageing,
problems connected with old age will dominate
healthcare. Depression, one of the most prevalent
psychiatric disorders, is expected to take an even
more prominent position than presently, as the
risk for developing depression increases with old
age. Depressive symptoms are present in almost
one third of the elderly populations and major
depression may be present up to 4%
Furthermore, once present, the prognosis for
elderly with depression is poor4
There have always been elderly people, but what
is new today that they now form the largest
sector of the population in industrialized
societies. However elderly are not preparing
themselves for long life, nor are we receiving any
information about the aging process at home,
school, community in general. Society tends to
exclude the elderly. They are considered
incompetent and are denied any responsibilities.
This is far removed from previous societies in
which, given their experience, the eldest
members enjoyed a much higher status. They
considered wise, the teachers, and traditions. A
great number of people in this sector are slightly
depressed and tend to consider themselves less
productive than they really are5
Between the year 2000 to 2050, the worldwide
proportion of persons over 65 years of age is
expected to more than double, from the current
6.9% to 16.4%. As healthcare facilities improve
in countries, the proportion of the elderly in the
population & the life expectancy after birth
increase accordingly. This is the trend which has
been in both developed & developing countries.
It is commonly believed that the majority of the
elderly population resides in developed
countries. However, this is a myth, as about 60%

of the 580 million older people in the world live


in developing countries, and by 2020, this value
will increase to70% of total older population 6
Depression is common in medically ill elderly
and associated with greater morbidity and
mortality, increased health service use and
medical costs. Studies have shown that
antidepressant and structured psychotherapy,
alone or combined, are effective in reducing
depressive symptoms among older adults7
Depression and anxiety lead to a serious
impairment of daily functioning and quality of
life. Frail elderly, the effects of depression and
anxiety are especially deep encroaching .The
number of elderly is rapidly growing. Almost a
third of elderly subjects in the community with
sub threshold depression or anxiety will develop
a major depressive or anxiety disorder in three
years8
The prevalence of major depressive disorder at
any given time in community samples of adults
aged 65-67 older ranges from 1-5% in larger
scale epidemiological investigations in the
United States and internationally, with the
majority of studies reporting prevalence at the
lower end of the range. Clinically significant
depressive
symptoms
are
present
in
approximately 15% of the community-dwelling
older adults 9
Major depressive disorder is one of the most
common forms of psychopathology, one that will
affect approximately one in six men and one in
four women in their lifetimes. It is also usually
highly recurrent, with at least 50% of those who
recover from a first episode of depression having
one or more additional episodes in their lifetime,
and approximately 80% of those with a history of
two episodes having another recurrence. Once a
first episode has occurred, recurrent episodes will
usually begin within five years of the initial
episode, and, on average, individuals with a
history of depression will have five to nine
separate depressive episodes in their lifetime10
Disability in Activities of Daily Living (ADL) ,
which are the essential activities that a person
needs to perform to be able to live independently
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Int J Med Res Health Sci. 2013;2(2): 243-249

, is an adverse outcome of frailty that places a


high burden on frail individuals, health care
professionals and health care systems . Frail
elderly people have a higher risk of ADL
disability compared to non-frail elderly people11
The model of the International Classification of
Functioning, Disability and Health (ICF) can
describe the consequences of dementia that
eventually lead to deterioration in BADL(Basic
activity of daily living) and loss of autonomy. In
the context of this review, dementia (health
condition) has a negative influence on mobility,
endurance, lower-extremity strength and balance
(body functions and body structures). Those
body functions are important for BADL
functioning (activity). Depending on the quality
of the BADL performance, patients are less or
more
restricted
in
their
participation
(participation). By training physical components
underlying ADL, or by a direct influence of
exercise on ADL, healthy elderly subjects can
stabilize or improve their ADL score12
The mechanisms by which depression has an
effect on physical disability are not completely
understood. Both behavioral (depressed patients
may have poor lifestyle, such as nonadherence to
medication and self-care regiments) and
biological mechanisms (depression may worsen
medical
diseases
through
changes
in
hypothalamic-pituitary-adrenal axis and the
sympathetic nervous and immunological system)
have been proposed. Each could lead to more
disability13
One might expect that elevated body mass index
(throughout life) could also promote impairments
in ADL through other mechanisms that include
associations with diabetes and possibly knee
joint injuries in later life or difficulties in
walking around the house (more common in
Hawaii but unrelated to body mass index in the
current sample). It may be that impairments in
the ADL are more frequent in the presence of
subclinical frailty where weight loss is a
problem. Long-term follow-up of the effects of
body mass in middle adulthood on the risk of

late-life ADL impairment might reveal a clearer


association14
In a study of patients with and without
depression during the immediate period after
stroke but with similar impairments in ADL
scores, we found, 2 years later, that the depressed
patients had significantly less recovery in their
ADL functions than the no depressed patients.
The recovery curves for ADL function were not
significantly different between patients with
major depression versus those with minor
depression, suggesting that both moderate and
severe forms of depression lead to impaired
recovery in ADL functions. Morris et al who
used an abbreviated version of the Barthel index,
also reported that at 15 months after stroke,
patients with major depression and those with
minor depression had a significantly greater
physical disability than no depressed patients15
As in elderly people living in community & old
age home depression and impairment in
performing activities of daily livings are major
problem therefore assessing the prevalence of
depression and impairment in ADLs forms the
basis of the study.
MATERIALS & METHODS
This study is a survey type of research which
intends to find changes in levels of depression
and activities of daily livings scores in elderly
subjects living in the community and in old age
home.
A sample of 200 elderly subjects i.e. 100 from
the community and 100 from Old age home of
sixty & above years of age were taken by the
convenience sampling method.
The subjects were collected through various old
age homes & which includes Vaikunth Dham
Old Age Home, Ishwar Prem Ashram, Swaraj
Ashram, Ramkrishna Mission old age home and
nearby community located in the Kanpur
&Varanasi.
All subjects signed consent forms & were ready
to take part in the study .The subjects were given
the instructions regarding the procedure & the
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Vanshika et al.,

Int J Med Res Health Sci. 2013;2(2): 243-249

subjects who fulfilled the inclusion criteria &


were ready to actively participate, were selected.
Inclusion criteria
1. Normal elderly male & female with age of
60 years.
2. Able to understand verbal instructions &
completed 8-10 years of formal education.
3. Subjects with stable medications
Exclusion criteria
1.Any
neurological
problems
such
as
Parkinsonism, stroke, cerebellar disorders,
balance disorders, myopathy, myelopathy
which can influence the psychological status of
the subjects.
2.Any cardiovascular or orthopedic problems
which affect their day to day routine activity &
further may become the cause of depression.
3. Significant hearing & vision impairment.
4. Uncontrolled hypertension.
5. Any speech deficit interfering the survey.
6. Unstable seizure / disorder affecting the
psychological status of subjects.
7. Smoking or alcohol intake.
Procedure
Subjects were introduced to the study followed
by the signing of consent forms, general
assessment regarding of socio-demographic data
( name, gender, age), education level, past

medical history, personal history, family history


were gathered from the participant assessment
forms. The subjects were collected from
community & various old age homes & were
divided into two groups a (community) and b
(old age home) for comparison. Total 200
numbers of subjects data were collected, 100 for
Group A (community) and group B (old age
home). The subjects were assigned a number to
maintain the confidentiality of the subjects and
then the scale was used to assess the scores i.e.,
Geriatric Depression Scale (GDS)17and Barthel
Index (BI)18was used to check the level of
depression and impairment in ADLs and then
the scores were entered in the data collection
form.
RESULTS

Reading on GDS and BI were taken during first


interview contact with the subject and were
tabulated as data. The mean value of GDS for the
old age home (group B) was 16.42 with standard
deviation 5.90 and mean value for subjects living
in community (group A) was 11.3 with SD 4.29
and p value was 0.000 which shows there is a
significant difference in the score hence level of
depression is more in elderly people living in an
old age home town community.

Table:1. Analysis of GDS scores in group A and group B


GROUP
MEAN
STANDARD
DEVIATION
11.32
4.29
Community (Group A)
Old age home (Group B)

16.42

-6.981

0.000*

5.90

*Significant difference
The mean value of the Barthel index for the old
age home was 16.54 with standard deviation
4.001and mean value for subjects living in the
community was 17.98 with SD 2.947 and p value

was 0.004 which shows there is a significant


difference in the scores hence Activities of daily
livings are more affected in elderly people living
in an old age home town community.

246

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Int J Med Res Health Sci. 2013;2(2): 243-249

Table:2 Analysis of Activity Of Daily Living by Barthel index between group A & group B
GROUP
MEAN
STANDARD
t
P
DEVIATION
Community
Old age home
*statistically significant
DISCUSSION

17.98

2.947

16.54

4.001

As results of the study shows that depression


level is more in elderly living in an old age home
than in community. It is supported by a study
which suggests that urbanization promotes
nucleation of the family system and a decrease in
care and support for the elderly6. Depression and
physical illness often coexist in the elderly as
they both occur commonly in old age. There is a
close relation between depression and physical
illness. Depression may be caused by a specific
physical disorder possibly as a direct
consequence of the cerebral organic effect of
these conditions. Therefore strategies to decrease
depression should be utilized for persons living
in an old age home. The literature shows the
institutionalized participants were more likely to
report depressed mood, crime, wishing to be
dead, future looking bleak and staying away
from others. Therefore the persons living in an
old age home should be encouraged to intact
with the society and family members to cope up
depression.
Literature shows that older people living in their
own homes were most able to cope in their
homes. They received more support from
relatives and friends than from health and social
services3.Result of the present study also shows
that elderly people living in an Old age home
were more affected in terms of ADLs than
elderly people living in the community.
Relevance to clinical practice:
This research study may serve as a basis for
development and implementation of a new
rehabilitation program to cope up depression and
to improve daily living skills for subjects living
in an old age home and in community by which

-2.898

0.004*

further their level of dependency and depression


can be reduced.
Future research:
1. This study is a survey type study in which no
training was given to the improvement of
ADLs and to decrease the depression hence
in a future training program can be
administered and its after effects may be
noted down.
2. As sample size was small hence large sample
size may be taken to generalize the results.
3. Task oriented goals/activities/training/may be
used to improve the efficiency of subjects
living in an old age home and community.
4. Group involvement and interaction with
society may be suggested for subjects living
in an old age home as loneliness may be the
factor affecting ADLs and depression.
CONCLUSION

Functional status, that is an individuals ability to


perform daily tasks routinely, is an integral
component of mental health care. It enters into a
diagnostic decision as axis V of the DSM-IV and
is particularly useful in gauging the severity of
illness, the effectiveness of psychiatric
interventions(pharmacological,
psychotherapeutic, behavioral), and the need for
supporting services (e.g., meals-on-wheels, chore
services). From the perspective of patients, the
ability to carry out daily living activities directly
influences their ability to live independently in
the community and their quality of life. Hence,
the accurate assessment of functional status is of
paramount importance because an overestimation
places patients at risk, while an underestimation

247

Vanshika et al.,

Int J Med Res Health Sci. 2013;2(2): 243-249

increases they depend beyond that warranted by


their functional status16
In summary, the evidence clearly shows that there
are multiple therapeutic alternatives including
somatic and psychotherapeutic approaches each
with efficacy for treating depression in later life.
Because
Depression in later life, even at subsyndromal
levels is associated with increased physical
Impairment, treatment of depression may provide an
opportunity to improve physical function, clinical
trial of depression intervention for older adults have
begun to evaluate functioning as an outcome
measure.
REFERENCES

1. Definition of an older or elderly person .


www.who.int/healthinfo/survey/agingdefinol
der/en/index.html.
2. Mascarenhas Steffi ,Yardi Sujata .
Retrospective study on limitation of activity
of daily living in geriartric women. Indian
Journal Of Physiotherapy And Occupational
Therapy .2012 ; 6(1): 59-65
3. Beswick DA , Rees K , Dieppe P, Ayis
Salma , Hill Gooberman R , Horwood J And
Shah E. Complex study to improve physical
function and maintain independent living in
elderly people : a systemic review and meta
analysis. Lancet.2008; 371(9614): 725-35
4. Most IS Els, Scheltens Philip, Someren Van
JW Eus. Prevention of depression and sleep
disturbances in elderly with memoryproblems by activation of the biological
clock with light- a randomized clinical
trial.Trials. 2010: 11-19
5. Hernandezequena Carmen, Gonzalez Zubiaur
Marta
.Effects
of
Intergenerational
Interaction
on Aging. Educational
Gerontology. 2008;34:292-05
6. Taqui Ather M, Itrat Ahmed, Qidwai Waris,
Zeeshan Qadri. Depression in the elderly:
Does family system play a role? A crosssectional study.BMC Psychiatry.2007;7: 57
7. Ell Kathleen , Unutzer jurgen, Aranda Maria,
Gibbs E.Nancy, Lee Jiuan ,Xie Bin

.Managing Depression in the Home Health


Care: A Randomized Clinical Trial. Home
Health Care servQ.2007;26(3):81-104
8. Veer-Tazelaar, Marwick Harm van, Oppen
Van Patricia, Ninpels Giel etal., Prevention
of anxiety and depression in the age group of
75 years and over: a randomized controlled
trial testing the feasibility and effectiveness
of a generic stepped care programme among
elderly community residents at high risk of
developing anxiety and depression versus
usual care. BMC Public Health .2006; 6:186
9. Fiske Amy, Wetherell Loebach Julie, Gatz
Marget.Depression In Older Adults.Annu
Rev Clin Psycho. 2009;5: 363-89
10. Burcusa
L.
Stephanie,
Locono
G.William.Risk
for
Recurrence
in
Depression. Clin Psychol. 2007 ; 27(8):95985
11. Vermeulen Joan, Neyens Jacques Cl, Rossum
Van Erik, Spreewenberg Mariek D and
Witte. Predicting Adl Disability In
Community Dwelling Elderly People Using
Physical Frailty Indicators : Systemic Review
. Bmc Geriatrics .2011;11:33
12. Canhota Da Nogueira Manuel Carlos.
Depressive disorders in elderly chienese
patients in macau: a comparison of general
practitioners consultations with a depression
screening scale.Australian and New Zealand
Journal of Psychiatry .2001;35:336-44
13. Li W, Lydia, Conwell Yeates. Effects of
changes in depressive symptoms and
cognitive functioning on physical disability
in home care elders. J Geronetol A Boil Sci
Med Sci .2009; 64 (2):230-36
14. Abbott R D. , Kadota A , Miura Katsuyuki ,
Hayakawa Takehito, Kadowaki Takashi etal.,
Impairment in activity of daily living in older
Japanese men in Hawaii and Japan .Journal
Of Aging Research .2011 ;Article Id 324592
15. Chemerinski Eran, Robinson G. Robert,
Kosier T. James. Improved recovery in
activity of daily living associated with
remission of post stroke depression. Journal
248

Vanshika et al.,

Int J Med Res Health Sci. 2013;2(2): 243-249

of the American heart Association Stroke.


2001; 32:113-17.
16. Rogers C. Joan, Holm Margo B., Raina
Ketki D. Disability in late life major
depression : patterns of self-reported task
ability, task habits and task performance .
Psychiatry Res . 2010 ; 178(3): 475-79
17. Erton FS, ertan t, kiziltan g, uygucgil h,
reliability and validity of the geriatric
depression
scale
in
depression
in
parkinsonisms disease, j neural neurosurg
psychiatry2005;76:1445-47.
18.Lowen C. Sandy, anderson A. Brian,
reliability
of
the modified motor
assessment scale and the barthel index,
PHYS THER. 1988;68:1077-81.

249

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Int J Med Res Health Sci. 2013;2(2): 243-249

DOI: 10.5958/j.2319-5886.2.2.023

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 18 Jan 2013


Review article

Coden: IJMRHS
th

Revised: 20 Feb 2013

Copyright @2013

ISSN: 2319-5886
nd

Accepted: 22 Feb 2013

NEW DRUGS IN THE PIPELINE: A REVIEW


Dr Vivek Lal*
Head, Medical Affairs, Gennova Biopharmaceuticals, Mumbai, Maharashtra, India
*Corresponding author email: ltcolvivek@gmail.com
INTRODUCTION

Pharmacology is a rapidly advancing science. The essence of rational pharmacotherapeutics is to


maximize the efficacy of a pharmaceutical interventional product for a specific indication, with a
simultaneous minimization of its adverse effects. With this primary objective in mind, research and
development activities of pharmaceutical companies and other healthcare research organizations focus
on the development and screening of new chemical entities (NCE). Once a definite pharmacological
action of the NCE has been discovered, which is expected to be of satisfactory therapeutic value, the
molecule is taken for a thorough pre-clinical animal testing in order to determine its feasibility for
human clinical trials. Positive outcomes of the animal studies facilitate the submission of an
Investigational New Drug (IND) application with the requisite drug regulatory authority of that
particular country. The molecule then undergoes Phase I-III Clinical Trials before it can get a marketing
approval. Alternatively, an existing molecule can be modified as per the structure activity relationships
to enhance its efficacy or safety. There are numerous examples of structural modifications yielding
much better pharmacokinetic and or pharmacodynamic profiles. Introduction of new and better drugs
ensure a continuous improvement in the management of patients with all types of ailments. A post
marketing surveillance facilitates evidence based medicine, so also in the detection, assessment and
analysis of adverse events which constitutes the discipline of Pharmacovigilance.
Keywords: Abiraterone, Avanafil, Canagliflozin, Daclatasvir, Linaclotide, Pasireotide, Tafluprost
New drugs in the pipeline
A few important drugs which have got US FDA
approval very recently are discussed below :1. Abiraterone1
Abiraterone acetate has been a recently approved
drug for metastatic, castration resistant (hormone
resistant / refractory) prostatic carcinoma. It is
the first oral drug for this indication, given in
combination with Prednisolone, even in those

patients who have received docetaxel previously


and have not responded adequately.
This drug is a 17--hydroxylase / C17, 20 lyase
inhibitor,
thereby
inhibiting
testosterone
production. 17--hydroxylase / C17, 20 lyase is
an enzyme expressed in the testis, adrenal glands
and prostate tumor tissues, responsible for the
eventual production of testosterone in sequential
steps. Reduction in circulating testosterone
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Vivek Lal et al.,

Int J Med Res Health Sci. 2013;2(2):250-253

brings about an inhibition in the further growth


of the prostate cancer.
The recommended dose of abiraterone is 1000
mg per day in combination with 5mg of
Prednisolone bid. Reported adverse effects
include mineralocorticoid related effects (joint
swelling, hypokalemia, fluid retention) and
altered Liver Function Tests.
2. Avanafil
This drug has been a recently approved, fast
acting phosphodiesterase-5 (PDE-5) inhibitor2,
useful in the treatment of erectile dysfunction. It
acts on a specific PDE-5 found mainly in the
corpus cavernosum of the penis, so also in the
retina. PDE-5 is the enzyme responsible for the
degradation of cyclic GMP (cGMP); its
inhibition leads to increased levels of cGMP in
the corpus cavernosum. cGMP (produced via the
action of guanylate cyclase stimulated by nitric
oxide [NO]) mediates smooth muscle relaxation
of the penile blood vessels, which causes
increased blood flow into the corpus cavernosum
and subsequently penile erection. Maintenance
of penile erection requires sustained levels of
cGMP in the corpus, which is lacking in patients
with erectile dysfunction.
The recommended starting dose of avanafil is
100 mg 30 mins prior to sexual activity; can be
increased to a maximum of 200 mg or reduced to
50 mg.
The drug is relatively quite safe but may rarely
cause cardiovascular effects like angina, DVT &
palpitations. Other common side effects are
minor and comparable with the placebo.
3. Canagliflozin
Canagliflozin is a new Sodium-Glucose coTransporter-2 (SGLT-2) blocker, which inhibits
the resorption of glucose from the kidneys,
thereby causing loss of glucose in the urine and
reduction of blood sugar levels and weight loss3.
An additional justification for using this drug is
the belief that the kidney of diabetics reabsorbs
more glucose, as compared to normal
individuals, which contributes to a further rise in

blood sugar levels. Canagliflozin is awaiting


approval as an adjuvant therapy for patients with
Type-2 Diabetes Mellitus (T2DM).
Even
though cardiovascular risk was projected as a
significant safety issue, the drug has been
recommended for approval by the US FDA drug
safety committee.
The previous congener,
Dapagliflozin, did not get FDA approval due to a
concern of causing malignancies.
The suggested dose of canagliflozin is 100-300
mg per day orally.
In addition to the
cardiovascular side effects, it may also lead to
genital mycotic infections and urinary tract
infections.
This drug may be a valuable addition in the
armamentarium of drugs against T2DM,
especially in obese diabetics.
4. Daclatasvir4
The standard regimen for the treatment of
Hepatitis-C Virus (HCV) infection has been a
combination of pegylated interferon and
ribavirin. However, the overall success rates
with this combination have not been very good,
which led to a search for potential new targets to
inhibit viral replication. The DAAs (Directly
acting Antiviral Agents) like telaprevir and
boceprevir were a new addition in the
armamentarium against HCV.
However,
another novel class of DAAs includes the NS5a
replication complex inhibitors like Daclatasvir,
which has recently received US FDA approval
for multi-drug therapy of HCV infection5.
Even though the exact mechanism has not been
outlined, daclatasvir probably inhibits the
production of certain non-structural proteins of
the HCV required for viral replication. Thus, the
inhibition of NS5a replication complex indirectly
inhibits viral replication. For optimal effect,
daclatasvir has to be administered concurrently
with a polymerase inhibitor like Sofosbuvir. As
such, daclatasvir is expected to be a component
of a multi-drug regimen in the treatment of HCV
infection, which would include ribavirin &
interferon.
251

Vivek Lal et al.,

Int J Med Res Health Sci. 2013;2(2):250-253

The suggested optimum dosage of daclatasvir is


60 mg per day, in combination. ADR profile was
found to be comparable with placebo. Long term
safety in patients has to be evaluated.
5. Linaclotide
Linaclotide, a peptide agonist of guanylate
cyclase 2C, was approved by the US FDA in
Aug 2012 for the treatment of chronic idiopathic
constipation (CIC) and irritable bowel syndrome
with constipation (IBS-C). The drug increases
the concentration of cGMP both intracellularly
and extracellularly, which causes increased fluid
secretion in the gut lumen and an increased
motility6. In addition, higher levels of cGMP
reduce the sensitivity of sensory nerves, which in
turn diminishes intestinal pain.
The exact mechanism of action is by an
enhanced pumping of Cl- ions into the gut lumen
by increased cGMP levels. Water follows the
chloride ions by osmotic action, which leads to a
higher water content in the stools.
The recommended doses are 290 g for IBS-C
patients and 145 g for CIC patients.
The expected side effect of linaclotide is
diarrhea. It is not recommended in individuals
<16 yrs of age, and is contraindicated in children
below 6 yrs. Long term toxicity of the drug
needs further evaluation.
6. Lomitapide7
US FDA has very recently approved a new drug Lomitapide - as an adjunctive treatment of
Homozygous Familial Hypercholesterolemia. It
is a Microsomal Triglyceride Transfer Protein-1
(MTP-1) inhibitor, thereby inhibiting the
assembly and secretion of Very Low Density
Lipoproteins (VLDL) in the liver. This in turn
leads to a reduction in the total cholesterol (TC),
Low Density Lipoprotein Cholesterol (LDLC), apolipoprotein-B (Apo-B) and non-High
Density Lipoprotein Cholesterol (non-HDL-C)
levels in the blood, which has a definite
beneficial effect on the serum lipid profile in
patients
with
homozygous
familial
hypercholesterolemia.
This gives additional

benefit to patients who are already on other lipid


lowering agents, including LDL-apheresis, if
required.
Dosage range for lomitapide is 5-60 mg per day
orally. The biggest concern with its use is a risk
of hepatic toxicity. Other ADRs include GIT
side effects including abdominal pain, nausea,
vomiting, diarrhea, bloating and flatulence.
7. Pasireotide
A somatostatin analogue, Pasireotide blocks the
release of Adrenocorticotrophic Hormone
(ACTH) from the Anterior Pituitary gland by
stimulating somatostatin receptors therein8. This
leads to a subsequent reduction in the secretion
of glucocorticocoids & mineralocorticoids from
the adrenal glands.
The drug is indicated for the treatment of
Cushings disease in patients for whom surgery
is either not an option or has been unsuccessful.
The recommended dose is 600g or 900g
subcutaneously twice a day. In addition to the
alleviation of the signs & symptoms of Cushings
disease, the drug is also associated with
improvements in systolic & diastolic blood
pressure, low density lipoprotein (LDL)
cholesterol, weight and overall quality of life.
Hyperglycemia was the commonest adverse
effect.
Other side effects include nausea,
diarrhea, abdominal pain and gallstones.
Currently, the drug has an orphan drug status in
the USA.
8. Tafluprost
Tafluprost is Prostaglandin F2 (PG F2) analog,
approved for the treatment of Chronic Open
angle Glaucoma (Ocular hypertension)9.
It
facilitates the outflow of aqueous humor from the
anterior chamber, thereby reducing the intraocular pressure.
It is available as preservative free eye drops, in a
concentration of 15 mcg per ml, so also as a
single dose formulation containing 0.3 ml per
dose.

252

Vivek Lal et al.,

Int J Med Res Health Sci. 2013;2(2):250-253

9. Teduglutide10
Another orphan drug (USA), Teduglutide is a
Glucagon like Peptide-2 (GLP-2) analog, which
enhances the absorption of nutrients & water in
patients of Short Bowel Syndrome (SBS). This
is an alternative to parenteral nutrition which is
commonly required in patients of SBS.
SBS results from partial or complete surgical
resection of the small intestine (ileum) due to any
indication mandating it.
This leads to poor
absorption of nutrients and water from the ileum,
leading to malnutrition, for which the only
remedy was parenteral nutrition or total
parenteral nutrition (TPN).
Teduglutide is
expected to be a suitable alternative to TPN.
Currently recommended dose of teduglutide is
0.05mg/kg/day subcutaneously.
The major concern with teduglutide is the
possibility of intestinal malignancies &
polyposis, so also intestinal obstruction,
gallbladder disease and biliary tract / pancreatic
disease.
The drug may not get suitable
marketing status till these issues are satisfactorily
resolved.
REFERENCES

5. Bell, Thomas W. Drugs for hepatitis C:


Unlocking a new mechanism of action.
ChemMedChem. 2010.5 (10): 166365
6. Terri MW, David RL. Linaclotide. A Novel
Approach to the Treatment of Irritable Bowel
Syndrome.
Ann
Pharmacother.
2011;45(12):1535-43.
7. Frederick JR. Lomitapide for homozygous
familial hypercholesterolaemia. Lancet. Jan
2013;381(9860):7-8
8. Boscaro M, Ludlam WH, Atkinson B et al.
Treatment of Pituitary-Dependent Cushings
Disease with the Multireceptor Ligand
Somatostatin Analog Pasireotide (SOM230):
A Multicenter, Phase II Trial. J Clin Endocrin
& Metab. Jan 2009;94(1):115-22.
9. Swymer C, Neville MW. Tafluprost. The first
preservative-free prostaglandin to treat openangle glaucoma and ocular hypertension.
Ann Pharmacother. 2012;46(11):1506-10
10. Palle Bekker Jeppesen, Sanguinetti EL,
Buchman A et al. Teduglutide, a novel
glucagon-like peptide 2 analog, in the
treatment of patients with short bowel
syndrome. Therap Adv Gastroenterol. 2012;
5(3): 15971.

1. Ryan CJ, Smith MR, de Bono JS et al.


Abiraterone in Metastatic Prostate Cancer
without Previous Chemotherapy. New Eng J
Med.2013;368(2):138-48.
2. Jun Kotera, Hideki Mochida, Hirotaka Inoue
et al. Avanafil, a Potent and Highly Selective
Phosphodiesterase-5 Inhibitor for Erectile
Dysfunction. J Urology. 2012;188(2):668-74.
3. Sha S, Devineni D, Ghosh A et al.
Canagliflozin, a Sodium Glucose CoTransporter 2 Inhibitor, Improves Glycemia
and is Well Tolerated in Type 2 Diabetes
Mellitus Subjects with Moderate Renal
Impairment. Diabetes, Obesity& Metabolism
2011;13(7):66972.
4. Paul YK, Marco AL. The Next Generation of
DAAs: What's on the Horizon? Medscape
Education Infectious Diseases Mar 2012.
CME Released: 03/28/2012.
253
Vivek Lal et al.,

Int J Med Res Health Sci. 2013;2(2):250-253

DOI: 10.5958/j.2319-5886.2.2.021

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
rd

Received: 23

Volume 2 Issue 2 April - June

Jan 2013

Coden: IJMRHS
nd

Revised: 22

Feb 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted:28 Feb 2013

Review article

STEM CELLS: A NEW PARADIGM IN PERIODONTAL REGENERATION


Ameet Mani1, Subhangi Mani1, Marawar PP2, *Shinde Sagar K3, Patil Ishwardas D1
1

Reader, 2Prof and H.O.D, 3PGStudent, Department of Periodontology and Implantology, Pravara
Institute of Medical Sciences, Rural Dental College, Loni, Maharashtra.

*Corresponding author email:drsagar710@gmail.com


ABSTRACT

Stem cells are a unique type of cell that forms the basis of the development, growth and survival of a
living organism. Though the term is often used to describe controversial embryonic stem cells, there are
many different types of stem cells, classified by their original location and/or method of formation. Stem
cells are undifferentiated cells that go on developing into any of more than 200 type of cells that adult
Human body hold. Now a days stem cells have significant use in regenerative periodontal therapy.
Recently, reports have begun to emerge demonstrating that populations of adult stem cells reside in the
periodontal ligament of humans and other animals. This opens the way for new cell-based therapies for
periodontal regeneration.This review provides an overview of adult human stem cells and their potential
use in periodontal regeneration.
Key words: Adult stem cell, Periodontal ligament stem cells, Periodontal regeneration
INTRODUCTION

The stem cell is the origin of life. As stated first


by the great pathologist Rudolph Virchow, All
cells come from cells. The ultimate stem cell,
the fertilized egg, is formed by fusion of the
haploid progeny of germinal stem cells. The
fertilized egg is totipotent; since it forms all the
tissues of the developing embryo. In the adult,
tissue is renewed by the proliferation of
specialized stem cells, which divide to form one
cell that remains a stem cell and another cell that
begins the process of differentiation to the
specialized function of a mature cell type.1 Stem
cells are defined by their potential to self-renew
and differentiate into more specialized cell types
within a given tissue.

Certain terms need to be known before


understanding stem cells:
I. Progenitor cell: It is an undifferentiated
precursor cell with the capacity to undergo
differentiation into specialized cell types;
unlike putative stem cells, they do not retain
the capacity for self-renewal.
II. Multipotent stem cells: They are cells that
self-renew and differentiate into several
different specialized cell types, often within a
tissue (e.g., hematopoietic stem cells).
III. Pluripotent stem cells: They are cells
capable of self-renewing and differentiating
into any of the three germ layers (endoderm,
ectoderm, and mesoderm).
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IV. Totipotent stem cells: They are cells derived


from the first few divisions of the fertilized
egg which have the potential to give rise to
all the differentiated cells of the fully
developed organism.
A stem cell "self-renews" i.e., when a stem cell is
called into action, it undergoes cell division. One
daughter cell remains a stem cell, while the other
becomes more committed to forming a particular
cell type (a "committed progenitor") by a process
called "asymmetric division". A stem cell forms
multiple cell types (i.e., it is "multipotent").
Single stem cell completely re-forms a particular
tissue when it is transplanted within the body.
The first definitive evidence came with the work
of Till and McCulloch on blood-forming
(hematopoietic) stem cells in the 1960s.
Researchers believe that virtually every tissue in
the body contains some type of stem cell,
conjuring up thoughts of all types of strategies
for tissue repair. Scientists have found ways of
coaxing these stem cells to develop into most
types of human cells including the periodontium.
Classification of Stem Cells
Embryonic stem cells: They are responsible for
the development of an entire organism.
Adult stem cells: They provide a mechanism for
maintenance of tissue homeostasis by replacing
damaged cells throughout the life of the
organism.
An adult stem cell is defined by several
properties, including its ability to self-renew
i.e. forming a particular cell type (a progenitor)
and one daughter cell that remains a stem cell
(asymmetric division). Committed progenitors
are thought to have a limited capacity for
proliferation by symmetric division; their
daughter cells then form differentiated cells
within the tissue.(fig 2)
The human body contains 220 different types of
cells such as blood, brain, heart tissue, nerve
cells, bones, etc. In 1998, researchers at the
University of Wisconsin and the Johns Hopkins
University in Baltimore MD found a way of
harvesting stem cells from embryos and
maintaining their growth in the lab.

Pramod PM et al.,

Origin, Properties And Culture Of Stem Cells


Origin
Embryonic stem cells (ES cells):(fig 3) They are
derived from embryos at a developmental stage
before the time that implantation would normally
occur in the uterus. The first documentation of
the isolation of embryonic stem cells from
human blastocysts was done in 1998 by
Thomson and co-worker. Since then, techniques
for deriving and culturing human ES cells have
been refined. Blastocysts with a large and
distinct inner cell mass tend to yield ES cultures
most efficiently.2
Adult stem cells: No one knows the origin of
adult stem cells in any mature tissue. Some have
proposed that stem cells are somehow set aside
during fetal development and restrained from
differentiating. The list of adult tissues reported
to contain stem cells is growing and includes
bone marrow, peripheral blood, brain, spinal
cord, dental pulp, blood vessels, skeletal muscle,
epithelia of the skin and digestive system,
cornea, retina, liver, and pancreas
Properties of both adult and embryonic stem
cells: (fig 4)
Self-renewal: It is defining property of stem cells
that allows them to undergo repeated mitotic cell
divisions to create at least one daughter cell
equivalent to the mother cell that retains latent
capacity for differentiation.
Clonogenicity: A stem cell is thought to be
"clonogenic," which means that it can proliferate
to form a colony of cells.
Sources Of Dental Stem Cells
The ultimate goal of tooth regeneration is to
replace the lost structure.
Dental stem cells can be obtained from following
tissue 3: 1. Bone marrow stromal cells(BMMSC)
2. Human Pulp Tissue (DPSCs, post-natal dental
pulp stem cells) 3.Exfoliated Deciduous Teeth
(SHED) 4. Periodontal Ligament (PDLSC) 5.
Apical Papilla
(SCAP) 6. Dental Follicle
Precursors (DFPC) 7.Mesenchymal stem cells
from gingival

255

Int J Med Res Health Sci.2012;2(2):254-260

Periodontal Ligament (PDLSC):(fig


(PDLSC):
5)
Recent study has clearly mentioned presence of
periodontal ligament stem cells in perivascular
niches of periodontal ligaments. Periodontal
ligament stem cells represent a unique population
of postnatal stem cells distinct from bone
marrow-derived
derived mesenchymal stem cells. They
have potential to form cementoblasts and
osteoblasts. They form unique cementum PDL

structure.
Mesenchymal Stem Cells From Gingiva
Tomas I. Mitrano et al in 2010 studied if gingival
connective
ective tissue could be a reservoir of MSCs
that could be used in regenerative procedures
based on tissue engineering.4

tissue and obtain their differentiation into


osteoblasts, cartilage and adipose cells in the
same way that has been described regarding
samples obtained from bone marrow.4
Possible applications of stem cells in dentistry.
Now the areas where these stem cells are used in
dentistry are included in the following text:
In Place Of Connective Tissue Graft:(fig
Graft
6)
Michael K. McGuire in 2008 studied to evaluate
the safety and effectiveness of a tissuetissue
engineered skin product composed of viable
neonatal keratinocytes and fibroblasts and
compared it to a free gingival graft (FGG) in a
procedure to enhance keratinized tissue (KT) and
wound healing around teeth that do not require
root coverage.5

The results clearly demonstrate that it is possible


to isolate MSCs from the gingival connective

Fig 1: Embryonic and adult stem

Fig 3: Embryonic stem cells derived

Fig 2: Differentiation of adult stem cells

Fig 4: Plasticity of adult stem cells


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Int J Med R
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ealth Sci.2012;2(
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260

Fig 5: Sources of stem cells

Stem Cells And Periodontal Regeneration


Periodontal regeneration can be defined
defined as the
complete srestoration of the lost tissues to their
original
architecture
and
function
by
recapitulating the crucial wound healing events
associated with their develo pment.
The periodontium is complex tissue
once
damaged, the periodontium has a limited
capacity for regeneration. Resents approaches
have included gene therapy and the local
administration of biocompatible scaffolds with or
without
ithout the presence of selected growth factors.6
The concept that stem cells may reside in the
periodontal tissues was first proposed almost 20
years ago by Melcher, who queried whether the
three cell populations of the periodontium
(cementoblasts, alveolar
alveolar bone cells and
periodontal ligament fibroblasts) were ultimately
derived from a single population of ancestral
cells or stem cells7. The most compelling
evidence that these cells are present within the
periodontal tissues has been provided by the in
vivo and histological studies of McCulloch and
co-workers
workers 8, 9, 10.
Cell kinetic study of mice have indicated that
group of progenitor cells exhibiting some
classical features of stem cells exist in the
periodontal ligament. In the event of injury
injury to the
periodontium these mesenchymal stem cells
could
be
activated
towards
terminal
differentiation and tissue repair or regeneration.

Fig 6: Regenerating Potential of adult stem cells

Using cloning techniques, a large number of cells


of differing phenotype have been isolated from
the periodontal liga
ligament
ment and regenerating
periodontal tissue. Preliminary studies suggested
that some of the clonal cell lines had
characteristics of stem cells, warranting further
investigation into these properties and their
utilization in cell-based
cell based periodontal regenerative
regenerativ
11
therapies .
The identification of putative mesenchymal stem
cell populations within the periodontium has
stimulated interest in the potential use of stem
cell-based
cell based therapies to treat the damaged caused
by trauma or periodontal disease. Bartold et al
discussed the stem cell
cell-like
like properties and
characteristics of stem cells residing within the
periodontal ligament and speculate on their
future clinical utility.
Periodontal Therapies For Periodontal
Regeneration:
Once tissue destruction has occurred, one of the
major goals of periodontal therapy is to
regenerate the affected tissues to their original
architecture and function 12. Many surgical
procedures have been advocated for periodontal
regeneration. More recent
recently,, synthetic barrier
membranes have been used to encourage the
appropriate progenitor cell population of the
wound site. This procedure has demonstrated
potential for regeneration of the root surface
cementum, alveolar bone and periodontal
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260

ligament. Unfortunately, the clinical results using


this method vary greatly and are often
unpredictable 13. With improving understanding
of the molecular processes associated with tissue
repair and regeneration, polypeptide growth
factors applied to root surfaces have been used to
facilitate periodontal regeneration . To date,
these have included epidermal growth factor,
fibroblast growth factor, insulin- like growth
factor, platelet-derived growth factor, tumourderived growth factor and bone morphogenetic
proteins. Combinations of growth factors such as
those present in platelet-rich plasma preparations
may also be useful in promoting periodontal
regeneration 14.
However, the current literature concerning the
clinical outcomes of using such combinations is
still scant. At the same time that polypeptide
growth factors were being considered for
periodontal regeneration, another approach was
being developed based on our understanding of
tooth root formation and, in particular, cementum
formation. While the precise molecular
mechanisms of cementum formation are still
unclear, one theory (yet to be fully accepted)
suggests that a special matrix is deposited on the
newly formed dentin surface that is instrumental
in permitting the attachment and differentiation
of progenitor cells into cementoblasts .Extracts
of this matrix have been applied to root surfaces
at the time of periodontal surgery with the aim of
inducing periodontal regeneration through the
recreation of the molecular events of
cementogenesis. Whether these proteins act as
instructional messengers, similar to growth
factors, for cells to undergo the processes of
regeneration, or merely as a scaffold permitting
regeneration to proceed is unclear. Nonetheless,
clinical results have been encouraging and these
proteins appear capable of promoting
regeneration of periodontal tissues, albeit not in a
completely predictable or consistent manner.
Thus, key factors in attaining successful
periodontal regeneration are the correct
recruitment of cells to the site and the production
of a suitable extracellular matrix consistent with

the periodontal tissues. Since cell seeding to


enhance regeneration of other tissues (skin,
cartilage, bone, cardiovascular components,
pancreas, etc.) has been used success-fully, it is
seems logical that autologous periodontal
ligament stem cells cultured within a suitable
delivery scaffold, in conjunction with the growth
and differentiation factors present in an
autologous blood clot, will lead to new
periodontal tissue attachment via a tissue
engineering approach.
Potential Clinical Applications For Human
Derived Dental Stem Cells:
For some time the use of mobilized peripheral
blood stem cells has been a recognized therapy
for hematopoietic bone marrow reconstitution in
cancer patients undergoing myeloablative
therapy. The successful outcome of this therapy
has led to investigations of other stem cell
populations, such as bone marrow stromal stem
cells, as potential novel cellular-based therapies
for a number of diseases and congenital defects
of neural, bone, cartilage and muscle tissues.
Together, these studies demonstrate the clinical
potential of bone marrow stromal stem cells and
other mesenchymal stem cells for different tissue
engineering strategies for tissue regeneration.
Importantly, the presence of different
mesenchymal stem cells residing in dental or
craniofacial tissues invites further clinical
investigations into regeneration of tissues of the
orofacial region, including the periodontium,
using these cells.
To test whether periodontal ligament stem cells
possess a tissue regenerative capacity similar to
that of bone marrow stromal stem cells,
researchers have initiated a number of studies to
investigate the use of these cells for periodontal
regeneration. To date, cultured human
periodontal ligament stem cells have been
implanted into surgically created periodontal
defects in nude rats 15. The results indicated that
the periodontal ligament stem cells attached to
both the alveolar bone and cementum surfaces
and there was evidence of formation of a
periodontal ligament-like structure.
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Int J Med Res Health Sci.2012;2(2):254-260

Periodontal fibroblasts and pericyte were


postulated to be potential osteoprogenitor cells
by Wendell W. Neeley et al and they studied a
viable co-culture model for the in vitro study of
osteogenesis16.
Human
micro
vascular
endothelial cells (HMVEC) and human
periodontal ligament (HPDL) fibroblasts were
co-cultured in a layered model and monitored for
the development of runt-related transcription
factor 2 (runx2) and desmin expression by realtime polymerase chain reaction. Conditions
shown to be osteogenic (bone morphogenetic
protein [BMP]-2 and enamel matrix derivative
[EMD]) were compared to a control co-culture
that was unstimulated.
The HMVEC migrated into a layer of collagen
containing only HPDL cells as monitored by
fluorescent labelling. Runx2 and desmin
expressions were increased in stimulated cocultures in week 2 compared to controls. At week
3, the unstimulated control co-cultures developed
the expression of runx2 and desmin, and the cocultures that were stimulated with EMD and
BMP-2 achieved significantly higher levels of
these factors than any of the other conditions.
Signs of osteogenesis were present in the cocultures in unstimulated and stimulated
conditions. However, in the stimulated condition,
osteogenic markers were increased at earlier time
points. As such, this model may provide a good
method for the study of specific cellular
processes that may lead to osteogenesis and
eventually for understanding the regeneration of
periodontal bone in vivo. 16
A new approach to anchor teeth back in the jaw
using stem cells has been developed and
successfully tested in the laboratory for the first
time by researchers at the University of Illinois at
Chicago. The new strategy represents a potential
major advance in the battle against gum disease,
a serious infection that eventually leads to
toothloss.17
Researchers Smit Dangaria et al in UIC's Brodie
Laboratory for Craniofacial Genetics in 2010
used stem cells obtained from the periodontal
ligament of molars extracted from mice,

Pramod PM et al.,

expanded them in an incubator, and then seeded


them on barren rat molars. The stem cell-treated
molars were reinserted into the tooth sockets of
rats. After two and four months, the stem cells
aligned and formed new fibrous attachments
between the tooth and bone, firmly attaching the
replanted tooth into the animal's mouth. Tissue
sections showed that the replanted tooth was
surrounded by newly formed, functional
periodontal ligament fibres and new cementum,
the essential ingredient of a healthy tooth
attachment. In contrast, tooth molars that were
replanted without new stem/progenitor cells were
either lost or loosely attached and were
resorbed.18
CONCLUSION

The dawn of this century is brightened by the


growing understanding and experimentation with
stem cells as primary tools in the expanding
regenerative medicine and tissue engineering
revolution. The tradition of using prosthetic
artificial implants to restore lost or damaged
dental tissue will gradually be supplanted by
more natural alternatives, including biological
tooth replacement or induction. The practice of
dentistry is likely to be revolutionized by
biological therapies based on growth and
differentiation factors that accelerate and/or
induce a natural biological regeneration. This
prospect has flourished from the gained
knowledge provided by the molecular biological
characterization of the genetic makeup of human
cells and from a growing understanding of the
effect of environmental factors. Prevention of
dental diseases will also gain new ground as
more insight is gained into the genetic makeup of
microbial pathogens, their interactions with the
host, and the host repair mechanisms.
It is very important to analyze the current
knowledge, barriers, and challenges in the
clinical use of stem cells with an emphasis on
applications in dentistry. Research on stem cells
continues to advance knowledge about how an
organism develops from a single cell and how
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Int J Med Res Health Sci.2012;2(2):254-260

healthy cells replace damaged cells in adult


organisms
Pamela Robey19, says that because no one knows
for certain what the full possibilities are for the
cells isolated from dental pulp, nor can they
accurately predict if or when they will be used in
clinical settings, patients and professionals need
to make informed decisions.
REFERENCES

1. Stewart Sell MD. Stem Cells-A handbook,


Humana Press Inc.Totowa.NJ.1984:1-3
2. Junying Y and James AT. Embryonic stem
cells .Terese Winslow inc. 2006: 1
3. Huang, SG, and S Shi. Mesenchymal Stem
Cells Derived from Dental Tissues vs. Those
from Other Sources: Their Biology and Role
in Regenerative Medicine., J Dent Res.2009;
88 (9): 792-06.
4. Tomas IM, Melisa SG, Flavio C, Estefania
NL, Patricia AL, Francisca SF, Antonio Q,
Alejandra C, and Antonio S. Culture and
Characterization of Mesenchymal Stem Cells
From Human Gingival Tissue. J Periodontol
2010;81:917-25.
5. Michael K, McGuire, Scheyer ET, Martha
EN, and Philip T. Lavin A Pilot Study to
Evaluate a Tissue-Engineered Bilayered Cell
Therapy as an Alternative to Tissue From the
Palate . J Periodontol 2008;79:1847-56.
6. Rutherford RB, Ryan ME, Kennedy JE,
Tucker MM, Charette MF. Platelet-derived
growth factor and dexamethasone combined
with a collagen matrix induce regeneration of
the periodontium in monkeys. J Clin
Periodontol 1993; 20: 53744.
7. Melcher AH. Cells of periodontium: their
role in the healing of wounds. Ann R Coll
Surg Engl 1985; 67: 13031.
8. McCulloch CA, Nemeth E, Lowenberg B,
Melcher AH Paravascular cells in endosteal
spaces of alveolar bone contribute to
periodontal ligament cell populations. Anat
Rec 1987; 219: 23342.

9. McCulloch CA. Progenitor cell populations


in the periodontal ligament of mice. Anat Rec
1985; 211: 25862.
10. McCulloch CA. Origins and functions of
cells essential for periodontal repair: the role
of fibroblasts in tissue homeostasis. Oral Dis
1995; 1: 271278.
11. Ivanovski S, Haase HR, Bartold PM.
Expression of bon matrix protein mRNAs by
primary and cloned cultures of the
regenerative phenotype of human periodontal
fibroblasts. J Dent Res 2001: 80: 166571.
12. Polson AM. Periodontal regeneration.
Chicago: Quintessence Publishing Co.,
1994;8-137.
13. Laurell L, Gottlow J. Guided tissue
regeneration update. Int J Dent 1998: 48:
38698.
14. Carlson NE, Roach RB. Platelet-rich plasma:
clinical applications in dentistry. J Am Dent
Assoc 2002;133: 1383 86.
15. Seo BM, Miura M, Gronthos S, Barthold PM,
Batouli S Brahim J, Young M, Robey PG,
Wang CY, Shi S. Investigation of multipotent
postnatal stem cells from human periodontal
ligament. Lancet 2004: 364: 14955.
16. Wendell W. Neeley II, David L. Carnes, and
David L. Cochran; Osteogenesis in an In
Vitro Coculture of Human Periodontal
Ligament
Fibroblasts
and
Human
Microvascular
Endothelial
Cells.
J
Periodontol 2010; 81: 139-49.
17. Ben C. Dental implants could be grown
inside patients' mouths. International cool
hunting magazine; Future Tech and Medicine
2010;5:16-21
18. Smit Dangaria et al. Technique to Reattach
Teeth Using Stem Cells Developed Source:
University of Illinois at Chicago.The Journal
Tissue Engineering . 2010;29:22 -33.
19. American Medical Association April 20,
2009 Dental stem cell potential explored,
Availsble from: http://www.ada.org/news/
1088.aspx
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DOI: 10.5958/j.2319-5886.2.2.020

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April - June

th

Received: 18 Feb 2013


Review article

Coden: IJMRHS

Copyright @2013

th

Revised: 12 Mar 2013

ISSN: 2319-5886

Accepted: 20th Mar 2013

CAUSES AND CONSEQUENCES OF OBSTETRIC FISTULA IN ETHIOPIA: A LITERATURE


REVIEW

*Daniel Nigusse Tollosa1, Mengistu Asnake Kibret 2


1
2

Mekelle University, CHS, Department of Public Health, Mekelle, Ethiopia


Path finder international, Country representative, Addis Ababa, Ethiopia

* Corresponding author email: danielnigusse@gmail.com


ABSTRACT
Obstetric fistula (OF) is one of the major potential complications of childbirth mostly young women in
developing countries including Ethiopia. Though few scientific studies have been conducted related to
its causes and consequences, it is challenging to find a comprehensive figure about obstetric fistula in
Ethiopia. Therefore, this paper sought that to review the causes and consequences of obstetric fistula in
Ethiopia. A number of relevant obstetrics and gynaecology websites and journals were reviewed.
Google, Pubmed, and Hinari searching engines were used to find out relevant references. Year of
publication, location, language and its type of publication were the inclusion criteria used for reviewing
literatures. It is observed that obstetric fistula has been a major burdened mainly for women in the rural
Ethiopian and its causes and consequences are very deep and diverse. The great majority of obstetric
fistula causes in Ethiopia is due to Obstetric labour. Distance to the health care facility, transportation
access, economic factors (poverty), poor knowledge related to the problem, poor health seeking
behaviour of the affected women and age at first marriage are the other triggering factors. Stigma and
discrimination of obstetric fistula patients by their husbands and families, economic dependency and
psychological disorder are often mentioned as consequences for OF patients in Ethiopia.
Keywords: Obstetric fistula, Ethiopia
INTRODUCTION

Each year pregnancy related complications


claim the lives of over 500,000 women
worldwide with about 99% of these deaths
occurring in developing countries 1. Current
estimates indicate that for each woman who dies
from pregnancy related complications, another

15 to 30 suffer serious morbidities, and all these


are preventable and treatable conditions 2.
With the current maternal mortality ratio of
676/100,000 and annual deaths of 25,000,
Ethiopia is a major contributor to the worldwide
death toll of mothers 3, and it is estimated that
each year more than 500,000 Ethiopian women
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and
girls
develop
disabilities
from
complications during pregnancy and childbirth
4
.
Obstetric fistula (OF) is one of the major
potential complications of childbirth, causing
misery to many, mostly young women in
developing countries. It is an abnormal
connection between the vagina and bladder
(vesico vaginal fistula) and/or the rectum (recto
vaginal fistula), resulting in uncontrollable
leakage of urine and/or stool and often resulting
from prolonged obstructed labour. The constant
pressure of the fetal presenting part against the
soft tissues around the vagina and bladder
and/or rectum causes ischemic necrosis, leaving
a hole behind with leakage occurring after 3-5
days and the extent of injury depends on the
duration of labour 5.
Approximately 2-3.5 million women may be
living with fistula worldwide, with 50,000100,000 new cases occurring annually, most of
which are in the Sub- Saharan Africa and Asia
5,6
. Though, the exact prevalence not well
known in Ethiopia it is believed that between
26,000 and 40,000 of women with OF live in
Ethiopia4. In an unpublished national survey by
the Addis Ababa Hamlin Fistula Hospital
(Prevalence of Obstetric Fistula in Rural
Ethiopia 2005), it is estimated that the incidence
of OF in rural Ethiopia was found to be 2.2 per
1000 women of reproductive age 4 and also
9,000 of new cases occur every year in Ethiopia,
of which only 1,200 are surgically repaired 6, 7.
A woman's obstetric history is the most salient
element in the development of an obstetric
fistula. It is often stated that fistula patients tend
to be young women with small, immature pelvis
(most commonly primiparas), with an
antecedent history of obstructed labour,
prolonged delay in receiving emergency
obstetric care, sometimes having undergone late
caesarean delivery. Age, parity, duration of
labour, the place of delivery, and whether the
delivery was attended by a qualified person

along with the proportion of caesarean sections


are the most important socio-medical factors in
the development of fistulas 3, 6, 8.
Obstructed labour is primarily responsible for
obstetric fistula. It occurs in about 5% of
pregnancies and accounts for 8% of maternal
deaths 9. The vast majority of OF cases live in
resource-poor countries, and almost all of these
injuries could have been avoided if timely and
competent obstetric care was available,
accessible, and affordable 9.
In resource limited settings, the development of
OF generally linked with the three delays in care
seeking, transportation, and in getting the
services at the facility. Avoiding the three stages
of delay can substantially reduce the risks of
prolonged obstructed labour and thus of
obstetric fistula. In Particularly, lack of
knowledge to recognize pregnancy and labour
complications; powerlessness to seek care;
distance from facilities; lack of transport and
poor roads; unavoidable costs of transport and
health services; and low expectations of the care
they deserve, serious shortages of medical
supplies and equipments, theatre space, and
particularly
trained
personnel,
further
undermine the timeliness and quality of the care
they receive. As a result, they often remain
sufferers for years or decades 9, 10.
Fistula can also be of non-obstetric cause:
laceration, rape and other sexual trauma such as
sexual violence. Mostly, poverty lies behind the
occurrence of most fistulas. Early childbearing
increases the risk, too. Because of poverty most
girls are malnourished and stunted since their
childhood. So, they will have underdeveloped
skeleton and pelvis where the labour will be
obstructed during delivery leading to fistula 8, 10,
11
.
The immediate consequences of such damage
are urinary incontinence, fecal incontinence, and
excoriation of the vulva from the constant
leakage of urine and feces. Other problems
include anaemia, foot drop, contractures at the
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knee or hip joints, and depression. The most


common fetal outcome is still birth and rarely
suicidal may be committed due to social
segregation and depression 4.
The bad odour arising from incontinence often
results in negative social consequences,
including divorce and ostracization from
society. The existing data suggest that large
numbers of women with OF become divorced or
separated from their husbands, particularly
when it becomes evident that their condition is
more chronic rather than transient. Successful
repair of the fistula is assumed to lead to a
smooth reintegration when these women return
home; however, they may still face problems
reintegrating into their local communities
though it is not well investigated and
documented so far. Simply repairing the injuries
is not the end of the challenge 4.
Access to primary health care service,
Fertility trends and Sexual activities in
Ethiopia
About 86.7% of the general population in
Ethiopia have access to primary health care
services 12; low access to safe motherhood
service (37%) and obstetric care service also
very low which is 54 out of 100 13.
The legal age of marriage in Ethiopia is 18 years
for both males and females, but it is widely
ignored and it takes place in earlier ages.
According to the Ethiopian demographic health
survey (2011) report the median age at first
marriage among women age 25-49 is 16.5 years.
The proportion of women married by age 15 is 8
% among women currently age 15-19. About
10% of the total fertility rate in Ethiopia derives
from births to women aged between 15 and 19
years 3. The report also indicated that among
women age 25-49, 29 percent first had sexual
intercourse before age 15, 62 percent before age
18. The median age at first sexual intercourse
for women age 25-49 years is 16.6 years, which
is very close to the median age at first marriage
of 16.5 years. This suggests that Ethiopian

women generally begin sexual intercourse at the


time of their first marriage 3.
Despite the relatively better primary health
service coverage available (86.7%), the health
service utilization rate is very low (32%) in
Ethiopia 12. Hence, the country has one of the
lowest antenatal cares (34%), postnatal care
(7%), and institutional delivery care (10%)
though progressively increasing every year 3.
Though limited studies have been conducted so
far in regards the causes and consequences of
Obstetric fistula (OF) in Ethiopia, there are
some papers that try to reveal the tip of iceberg
in related to the problem. Therefore, this paper
sought that to review the causes and
consequences
(social,
economic
and
psychological) of obstetric fistula in Ethiopia.
METHODS
A number of relevant obstetrics and
gynaecology websites and journals were
reviewed. The following searching terms in
different combination were also used: obstetric
fistula,
causes,
social,
economical,
consequences. It was reviewed both qualitative
and quantitative data to gather evidence on
cause and consequence of obstetric fistula from
different articles. Google, Pubmed, and Hinari
searching engines were used to find out relevant
references. FMOH and WHO reports also used
for this particular review.
Year, location, language and its type of
publication were the inclusion criteria used for
reviewing literature. Studies conducted in the
last one decade; since 2000 G.C, only studies
conducted in Ethiopia and published in English
language, and pre-reviewed studies, guidelines
and official documents addressing causes and
consequences of obstetric fistula were
considered in this review. However, studies not
fulfilling these inclusion criterias were
excluded to be reviewed.

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FINDINGS
For a better description, the following two
themes were identified: causes of Obstetric
fistula and Social, economic and psychological
consequence of Obstetric fistula in Ethiopian.
Causes of obstetric fistula in Ethiopia;
Patient characteristics and Access to services
An epidemiological study conducted among
treated cases of OF at Addis Ababa Fistula
Hospital (AAFH) indicates that 97.4% of the
cases were caused by obstructed labour out of
which 63% of them were during their first birth
10
. Biruk et al. also indicates that 95.4% of the
fistulae were caused by childbirth; coitus,
surgery, trauma and others constitute only less
than five percent of the cases 14. Another study
conducted by Mulu M. indicates that the most
important causes for not reaching a health
institute during labour are distance, economical
factors and poor knowledge in 28.2%, 13.6%
and 9.8% of the cases, respectively 15. More
than 99% of patients taking treatment in AAFH
are illiterate 16. Likewise, Kelli J. was conducted
a record review assessment of 309 patients
performed vesicovaginal operations in AAFH
showed that the women were of average age
22.4 years in the range of 9-45 years and 82% of
them travelled at least 700 kilometres for
treatment, walking an average of twelve hours
and spending an average of 34 hours in a bus 17.
Emergency transport access is a serious concern
(due to poverty) in Ethiopia, in a survey of
patients at AAFH found that on average, it takes
women in labour 11 hours to reach a health care
facility capable of addressing their needs.
Women in labour can spend several hours
travelling on a makeshift stretcher over difficult
terrain which can induce other health
complications for the mother. Where access to
roads is available, delays of several days due to
the difficulty in identifying the danger sign are
often encountered as families try to raise the
money necessary to pay for hiring a vehicle to
transport the patient. Emergency transport costs

are an overwhelming financial burden for


families. In more remote areas, emergency
access costs can easily rise to thousands of birr
for transport of a single patient and
accompanying family members. The delays in
access to health services caused by the
difficulties in raising such sums of money are
one of the important contributors to the
occurrence of obstetric fistula in Ethiopia and
subsequently increased vulnerability in the
country 18. In depth epidemiological analysis of
OF from the data gathered for EDHS, 2005 by
Yibeltal T. showed that more than 3.4% of the
respondents were experienced obstetric fistula
and surprisingly 70% of them also not treated
by the time of data collection. The study also
indicated that the development of OF was
different along with their marital status; women
who were widowed or divorced or separated
were the most affected by OF (6.5%) followed
by then currently-married women (4.0%) and
the never-married ones were the least affected
(0.9%). There was also a statistically significant
association between marital status and
experience of obstetric fistula (p-value<0.001).
According to this study, women with total
children ever born of 5 or more (5.8%) are more
affected by OF compared to those with total
children ever born of 1-4 (3.9%) and zero
(0.9%) 9. The other study conducted by Muleta
M. in AAFH indicated that about 94% of fistula
patients were married and 83.6% had been
through with the delivery caused the fistula
before the age of 2019.
In Ethiopia, the prevalence of OF across the
region was different. Yibeltal T. found that the
highest prevalence was recorded in Afar region
where about 6 % of women had experienced OF
followed by Somali region which was 5.7%.
The lowest prevalence of OF was recorded in
Addis Ababa (1.2%). This study also noted that
Orthodox Christians (2.5%) were the least
affected compared to Protestant (4.2%) and
Muslims (5.3%) 9. In Ethiopia, there is also a
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marked difference in the level of prevalence of


obstetric fistula between urban and rural areas
whereby OF is more common in rural areas
(4.5%) than 1.7% of urban areas. In urban areas,
the highest (4.3%) and the lowest (0.4%)
prevalence of OF were recorded for women of
age groups 35-39, and 15-19 and 25-29
respectively. For rural cases, the lowest
prevalence (2.7%) was observed for women of
age groups 30-34. In both the urban and rural
cases, higher OF prevalence, more than 4%
were recorded for the older age groups i.e.,
more than 35 years with the highest record
being for rural women of age group 40-44 years
(8.7%) 9. Obstetric fistula is highly prevalent
among rural women with less than 18 years of
age at first marriage (5.3%) and urban women
with less than 18 years of age at first birth
(5.9%). Unlike the urban places, the prevalence
of obstetric fistula was yet higher among rural
women of 18 years or more of age at first
marriage (4.5%) and age at first birth (5.2%)
respectively. Tebekaw Y indicated that women
who give birth before 18 years of age are more
affected by OF than those who marry at that
same age 9. While most cases stems from
obstetric causes, others result from direct trauma
caused by rape or other sexual abuses. Muleta
M and William G noted that at the Addis Ababa
fistula hospital, 91 of 7,200 cases over a sixyear period, or about 1.2%, were caused by rape
or other sexual abuse 20.
Social, Economic and Psychological
Consequences of Obstetric Fistula in
Ethiopia
Obstetric Fistula (OF) can have terrible social
consequences: The physical consequences of
fistula including the continuous leaking of urine,
faeces, or both and the resulting odour usually
make a normal life difficult. Fistula patients are
often shunned, abandoned, or divorced. More
than 50% of the women were rejected by their
husbands after the fistulae developed, leaving
them without means 19. In AAFH, for example,

53% of the women had been abandoned by their


husband and one out of five of them have to beg
for food to survive 21, 22. An in-depth interview
conducted in rural Ethiopia shows that; one
untreated women with OF said that My
husband hated me and labelled me as dirty, it
has been long time when we slept to gather.
This study also revealed that among 50 obstetric
fistula patients who are continuing to live in the
same house as their families 10 of them were
not allowed to eat with family members together
4
.
Low self-esteem, feelings of rejection,
depression stress, anxiety, loss of libido and loss
of sexual pleasure were commonly reported by
women with fistula. It also appears that the rates
of separation or divorce increases the longer a
woman lives with a fistula particularly if she
remains childless. Not surprisingly, successful
fistula repair reduces the prevalence of these
psychosocial pathologies 8. WHO has estimated
that the rate of social exclusion in Ethiopia is
53% 22. Other articles document the presence of
these social problems in women with fistulas.
Muleta et al reported 69.2% of fistula victims
were divorced, only 19.2% were members of a
local community association, and 44.2% ate
separately from other family members. Fortyeight of 52 women felt listless and 28 had
suicidal thoughts 21.
Goh et al. conducted a prospective observational
study to screen women in Ethiopia with fistulas
for mental health dysfunction, this study showed
that of the 68 women with fistulas screened, 66
were at risk for mental dysfunction as measured
by the General Health Questionnaire compared
with only 9 of 28 controls. In a prospective
interventional study, 51 women with fistulas in
the north of Ethiopia were screened for mental
health issues before and 2 weeks after surgery
23
.
Though OF have deep social and psychological
consequences, it could be avoided if women
could delay childbearing until after adolescence,
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if skilled attendants could monitor all labours


and if women could have timely access to good
emergency obstetric care. Moreover, most
women who develop fistulas could be treated
surgically to have the damage repaired.
Therefore, the government of Ethiopia has been
done different intervention to improve the
situation and to fight against fistula such as
fistula treatment hospitals (AAFH and its
branch hospitals in different regions) has been
increased in number for identification of fistula
cases for treatment and etc, there has been also
improvement in age at marriage in the last
decades, efforts to increase skilled delivery,
road infrastructures and ambulance services at
district level also give emphasis in the health
sector development plan.
CONCLUSIONS
In conclusion, OF have been a major burdened
mainly for women in the rural Ethiopian and its
causes and consequences are very deep and
diverse. The great majority of OF causes in
Ethiopia is due to Obstetric labour. Various
factors are contributing that still the problem is
getting high public health significance: Distance
to the health care facility, transportation access,
economic factors (poverty), poor knowledge
related to the problem (Illiteracy level), poor
health seeking behaviour of the affected women
and age at first marriage are the most important
factors that contributed to the high prevalence of
Obstetric fistula. Other socio demographic
factors also found to be a factor for the
experience of OF such as marital status,
residency area (Urban Vs Rural). The
prevalence of OF also differs across the regions
in the country; the most marginalized regions
such as Afar and Somali are more affected.
Social consequences such as stigma and
discrimination of OF patients by their husbands
and families, economic dependency (begging
for food to survive), and psychological disorder
(mental disfunction and suicidal thoughts) due

to these deep social and economic burden of the


problem are often mentioned consequences for
OF patients in Ethiopia.
ACKNOWLEDGMENTS
We would like to acknowledge Geneva
Foundation for Medical Education and Research
providing us such an important topic for review
and for their support.
REFERENCES
1. WHO. The World Health Report 2005:
Make Every Mother and Child count.
Geneva, Switzerland: WHO; 2005.
2. UNFPA. Campaign to end fistula. 2008
[http://www.endfistula.org], assessed March
2010.
3. Central Statistical Agency [Ethiopia] and
ICF
International.
2012.
Ethiopia
Demographic and Health Survey 2011.
Addis Ababa, Ethiopia and Calverton,
Maryland, USA: Central Statistical Agency
and ICF International.
4. Muleta, M., Hamlin, Catherine; Fantahun,
Mesganaw; Kennedy, Ruth C. and Biruk
Tafesse. Health and Social Problems
Encountered by Treated and Untreated
Obstetric Fistula Patients in Rural Ethiopia.
JANUARY JOGC JANVIER: 2008.
5. Kayondo et. al. Predictors and outcome of
surgical repair of obstetric fistula at a
regional referral hospital, Mbarara, western
Uganda. BMC Urology; 2010; 11(23):
doi:10.1186 /1471-2490-11-23
6. Sunil T. and Sagna M. Analysis of obstetric
fistula in Ethiopia. Journal of family and
reproductive health. 2009:3(4); 109-16
7. Neilsen H et.al. A community- based longterm follow up of women undergoing
obstetric fistula repair in rural Ethiopia.
BJOG 2009; 116: 125864.
8. De Ridder D, Badlani GH, Browning A,
Singh P, Sombie I, Wall LL. Fistula in the
developing
country.
Available
at:
http://www.icsoffice.org
266

Tollosa DN et al

Int J Med Res Health Sci. 2013;2(2):261-267

/Publications/ICI_4/files-book/comite18.pdf. Accessed date - June/2012.


9. Tebekaw Y. Obstructed social services
leading to obstetric fistula in Ethiopia:
Evidence from DHS data. 2006.
10. Kelly J, Kwast BE. Epidemiologic study of
vesicovaginal
fistulas
in
Ethiopia.
International
Urogynecology
Journal.
1993;83(10);4278-81.
11. Hamlin Fistula International. Fast facts and
FAQS about obstetric fistula. Addis Ababa:
Hamlin Fistula Hospital; 2009. Available
from: http://www.hamlinfistula.org/what-isa-fistula/ fast-facts-and-faqs.html. Accessed
date June 2012
12. MOH. Health and Health Related Indicators.
Planning and Programming Department.
Addis Ababa, Ethiopia; 2007.
13. Maternal and Neonatal Program Index effort
(MNPI): A tool for maternal health
advocates.2002.
14. Biruk Tafesse, Mulu Muleta, Ambaye W.
Michael, Hailegiorgis Aytenfesu. Obstetric
fistula and its physical, social and
psychological dimension: The Etiopian
scenario. Acta Urolgica; 2006, 23; 4: 2531.
15. Mulu Muleta. Obstetric Fistula in
Developing Countries: A Review Article. J
Obstet Gynaecol Can 2006; 28(11):96266.
16. Fran S. Back to beautiful: Obstetric fistula
in Ethiopia. Available at: http:www//
futurechoices.net/Shows/back2beautiful.htm
l Accessed date - June/2012
17. Kelly J. An epidemiological study of vesicovaginal
fistula
in
Addis
Ababa.1995;48(1):15-17
18. Catherine Hamlin.
Preventing fistula:
transports role in empowering communities
for health in Ethiopia: Back to office report.
2004; Addis Ababa Fistula Hospital.

19. Muleta M. Socio-demographic profile and


obstetric experience of fistula patients
managed at the Addis Ababa Fistula
Hospital. Ethiop Med J; 42(1):9-16, 2004.
20. Muleta M and Williams G. Postcoital
injuries treated at the Addis Abeba fistula
hospital, 1991-1997. Lancet. Dec. 11. 1999.
21. Muleta M, Fantahun M, Tafesse B, Hamlin
EC, Kennedy RC. Obstetric fistula in rural
Ethiopia. East Afr Med J 2007; 84:525-33
22. World Health Organization. Obstetric
fistula: guiding principles for clinical
management and program development.
Geneva: World Health Organization; 2006.
Available
at:
http://
whqlibdoc.who.int/publications/2006/92415
93679 eng.pdf. Accessed date - June/2012
23. Goh JT, Sloane KM, Krause HG, Browning
A, Akhter S. Mental health screening in
women with genital tract fistulae. Bjog.
2005; 112(9): 1328-30.

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DOI: 10.5958/j.2319-5886.2.2.017

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 26 Feb 2013


Review article

Coden: IJMRHS

Copyright @2013

st

Revised: 21 Mar 2013

ISSN: 2319-5886
th

Accepted: 24 Mar 2013

SMOKING-A TRUE PERIODONTAL HAZARD


Mani Ameet M1, Mani Shubhangi A2, *Tejnani Avneesh H3, Gupta Ankit 4
1

Reader, 3Postgraduate student, Department of Periodontology, Rural Dental College, Pravara Institute
of Medical Sciences, Loni, Maharashtra, India
2
Reader, Department of Orthodontics, Rural Dental College, Pravara Institute of Medical Sciences,
Loni, Maharashtra, India
4
Senior Resident, General Medicine Department, Himalayan Institute of Medical Sciences,
Jollygrant, Dehradun
*Corresponding Author E-mail : avneesh316@yahoo.co.in,
ABSTRACT

It is now well established that tobacco use in general and cigarette smoking in particular, is a major risk
factor in the incidence and severity of several forms of periodontal diseases.A large number of studies
have been published in the dental literature regarding this possible role. Much of the literature has also
indicated that smokers affected with periodontitis respond less favourably to periodontal treatment be it
non-surgical, surgical or regenerative. Numerous studies of the potential mechanisms whereby smoking
tobacco may predispose to periodontal disease have been conducted, and it appears that smoking may
affect the vasculature, the humoral immune system, and the cellular immune and inflammatory systems,
and have effects throughout the cytokine and adhesion molecule network. The aim of this review is to
consider the evidence for the association between smoking and periodontal diseases and to highlight the
biological mechanisms whereby smoking may affect the periodontium.
Keywords: Smoking, adverse effects, Chronic periodontitis, Neutrophils
INTRODUCTION

The role of tobacco and, more specifically,


cigarette smoking as a public health problem has
long been recognized. The magnitude of this
problem was summarized in the 1989 Surgeon
Generals Report, where it is stated that smoking
is responsible for more than one of every six
deaths in the United States. Dentistry has long
been aware of the effects of tobacco on the soft
tissues of oral cavity and the implications of this

in clinical practice. The effects of cigarette


smoking on bone and connective tissues have
been well documented in the medical literature.1
Tobacco smoking, mostly in the form of cigarette
smoking, is recognized as the most important
environmental risk factor in periodontitis, and,
with respect to this, there is large number of
supporting epidemiological studies. It has usually
been necessary to rely on the vast body of
medical literature that describes the noxious
effects of smoking, and to apply this knowledge
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to the pathogenesis of periodontitis. Therefore,


many of these mechanisms may be implied or
speculative. This review will attempt to build on
previous reviews in the periodontal literature and
make attempts to primarily consider evidence
that directly pertains to the periodontal tissues.2
Smoking and oral cleanliness: Sheiham (1971)
evaluated a group of smokers and nonsmokers
and found that the level of periodontal disease
did not differ significantly when controlled for
oral hygiene.3 Preber et al (1980), Feldman et al
(1983) and Ismail and coworkers (1983) likewise
observed smokers to have decreased levels of
oral hygiene when compared to nonsmokers.4, 5, 6
Effect of smoking on plaque development;
Early observational reports that smokers showed
a higher prevalence of dental plaque than nonsmokers suggested that more severe periodontal
disease in smokers might be because of greater
accumulations of plaque.4 Studies in which the
development of plaque and inflammation was
observed in an experimental gingivitis model,
showed that the rate of plaque formation was
similar between smokers and non-smokers.7
Effect of smoking on the oral flora; The
majority of studies have investigated the
difference in the subgingival microflora between
smoking and non-smoking subjects with
periodontal disease. However, a study of the
microbiota of the oral mucous membrane and
saliva failed to establish a statistically significant
trend for smokers to harbour greater proportions
of putative periodontal pathogens.8 Similarly, an
experimental gingivitis study showed no
differences between smokers and non-smokers in
the alterations to supra- and subgingival
microflora.9
Effect of smoking on the subgingival
microflora in periodontitis: A number of
studies have indicated that smoking has little
effect on the subgingival microflora. Preber et al
(1992) compared the samples from smokers and
non-smokers for the presence and proportion of
A.a. comitans, Porphyromonas gingivalis and
Prevotella intermedia and found no significant
differences between the two groups.10 However,

recent studies have shown higher prevalence of


potential periodontal pathogens in smokers than
non-smokers.11,12,13
Effect of smoking on the prevalence and
severity of periodontal disease:An association
between smoking and acute necrotizing
ulcerative gingivitis (ANUG) was demonstrated
as early as 1946. Results from United States
National Health And Nutrition Examination
Survey (NHANES I) demonstrated that although
current smokers had more plaque and periodontal
destruction than former or never smokers, the
association between periodontal disease and
smoking remained, after adjusting for oral
hygiene and other variables.6
Effect of smoking on gingival blood flow:There
is little or no evidence that smoking induces
gingival vasoconstriction. Early studies by
Kardachi and Clarke (1974) hypothesized that
nicotine induced vasoconstriction,14 but Baab
and Oberg (1987) questioned the hypothesis.15
Later studies using Laser Doppler Flow
demonstrated that the light smokers responded
with a significant increase in blood flow, but
heavy smokers showed no response, indicating a
high level of tolerance. A more recent study
showed that the gingival blood flow had
significantly increased at 3 days following
quitting smoking. This study provides important
information on the recovery of healthy gingival
tissue, post-quitting.16
Oxygen tension in the gingival tissues: Oxygen
saturation of haemoglobin is affected and
attempts have been made to measure this in the
gingival tissue of smokers and non-smokers.
Hanioka et al (2000) showed variable results. In
healthy gingiva, smokers did appear to have
lower oxygen saturation, whereas in the presence
of inflammation, the converse was shown.17 The
same group in another study showed that the
pocket oxygen tension was significantly lower in
smokers compared with nonsmokers.18
Gingival inflammation and bleeding: Some
early studies suggested that smokers experienced
less gingival bleeding than non-smokers.19 The
reduced bleeding on probing was further
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demonstrated in a study by Bergstrom and


Bostrom (2001). They were also able to show a
dose-response effect.20 This reduced response in
smokers has also been shown in studies using the
experimental
gingivitis
model.21
The
development of gingival redness and the volume
of gingival crevicular fluid were also lower in
smokers. The effect of smoking on gingival
bleeding has also been studied in subjects who
quit-smoking, where a relatively rapid recovery
of the inflammatory response was seen.22
In a study the effect of cigarette smoking was
evaluated in experimentally inducted gingivitis.
The findings suggested that smokers have a
reduced capacity to maintain an effective defense
reaction to a given plaque challenge.23
The dose-dependent effect of cigarette smoking
upon gingival bleeding on probing was
investigated in a large representative sample of
the US population
(NHANES III). Results demonstrated that
smoking had a strong suppressive effect on
gingival bleeding. They concluded that smoking
exerts a strong, chronic and dose-dependent
suppressive effect on gingival bleeding on
probing.24
Effect on the gingival vasculature:Smoking has
a long-term chronic effect, impairing the
vasculature of the periodontal tissues rather than
a simple vasoconstructive effect following a
smoking episode. The suppressive effect on the
vasculature can be observed through less
gingival redness, lower bleeding on probing and
fewer
vessels
visible
clinically
and
histologically. This may also have relevance to
the healing response with impairment of
revascularization.2 The hypothesis that cigarette
smoking is causing vasoconstriction in the
healthy human gingival was tested using laser
Doppler flowmetry in healthy casual consumers
of tobacco. Results revealed that cigarette
smoking induced a modest hyperemic response
in the gingiva. They concluded that though the
gingival blood flow increased during smoking,
small repeated vasoconstrictive attacks due to

cigarette smoking may in the long run contribute


to gingival vascular dysfunction.25
Smoking and fibroblast function: The effects
of nicotine and some other components of
tobacco smoke have been tested in invitro studies
on gingival and periodontal ligament fibroblasts.
All published studies, with the exception of the
study of Peacock et al. (1993) have demonstrated
detrimental effects, which could have significant
impact in the inflammatory destructive process
and the healing response. However, most of these
studies used concentrations of nicotine and
cotinine that were far higher than those expected
in plasma of smokers.2
Gingival fibroblasts:Peacock et al (1993) were
the only researchers to show a positive effect of
nicotine on the proliferation and attachment of
gingival fibroblasts to plastic. Significant
inhibition of proliferation of gingival fibroblasts
at very high concentrations of nicotine was
demonstrated by Tipton and Dabbous (1995),
who also showed reduction in the production of
type 1 collagen and fibronectine and an increase
in the collagenase activity in culture media.2
Periodontal ligament fibroblasts: PDL
fibroblast growth and attachment to tissue culture
plates was inhibited by nicotine at high
concentrations and no effects were seen at
concentrations comparable with plasma levels in
smokers in a study conducted by James et al
(1999). Nicotine at high concentrations was also
shown to be cytotoxic by Chang et al (2002).
Gamal and Bayomy (2002) examined PDL
fibroblast attachment to root surfaces and found
that cell attachment was significantly less on root
surfaces obtained from heavy smokers compared
with non-smokers and healthy controls.2
Effect of smoking on the response to
periodontal therapy: Smoking has been
identified as one of the major predictive variables
for response to periodontal therapy. In
maintenance patients followed at least for 5
years, patients who smoked were twice as likely
to lose teeth. The majority of studies involving
nonsurgical therapy have shown less probing
depth reduction and less attachment gain in
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smokers as compared to non-smokers. Among


patients who have been surgically treated for
periodontitis and then longitudinally followed,
smokers exhibited less reduction in probing
depths, less gain in clinical attachment levels,
and less gain in bone height than non-smokers.1, 4
Smoking and neutrophil functions: Neutrophils
are the predominant leukocytes in blood. It has
become widely accepted that neutrophils defend
periodontal tissues against infection by
pathogens and subsequent tissue destruction.
Neutrophils within the gingival crevice provide
the first cellular host mechanism to control
periodontal bacteria. On an average one million
neutrophils per minute enter the oral cavity via
the crevicular fluid. These cells protect the
gingiva against microbial invasion by exhibiting
a complex array of responses.1
Tobacco smoke exposure increases the number
of neutrophils found in the systemic circulation
and those exiting the pulmonary micro
vasculature into the lungs. Despite inducing a
significant systemic neutrophilia, tobacco
smoking does not seem to affect the numbers of
neutrophils entering the gingival sulcus and oral
cavity. Indeed, limited evidence suggests that the
number of neutrophils reaching the gingival
sulcus in smokers may even be reduced. These
findings imply that neutrophil transmigration
across the periodontal microvasculature is
impeded in tobacco smokers. Neutrophils are
primary mediators of protection against
periodontal plaque bacteria. However, neutrophil
bactericidal activity involves multiple nonspecific mechanisms, and the inappropriate
and/or continuous activation of periodontal
neutrophils is thought to contribute to the
degradation of gingival tissues and the
progression of inflammatory periodontal disease.
Neutrophils express functional receptor for
several components and metabolites of tobacco
smoke, such as nicotine, cotinine and aryl
hydrocarbons. The numbers of nicotine receptors
expressed by human neutrophils are increased in
smokers and decline on cessation. Neutrophils
also express several receptors for endogenous

factors such as interleukin-8, ICAM-1, TNF-.


Thus, multiple receptor-agonist couples have
been identified, suggesting that tobacco smoke is
capable of affecting neutrophil function both
directly and indirectly.2
CONCLUSION

From this discussion of the effects of tobacco


smoking on the host response in periodontal
diseases and its effect on periodontium, it is
evident that these effects can occur throughout
the periodontal tissues. Increasing evidence
points to smoking as major risk factors for
periodontitis, affecting the prevalence, extent &
severity of disease. Also, one can make the
general observation that the effects of tobacco
smoking tip the balance towards periodontal
destruction
by
stimulating
destructive/
inflammatory
responses
and
impairing
protective/reparative responses. In addition
smoking may influence the clinical outcome of
non surgical & surgical therapy as well as the
long term success of implant placement & it has
become increasingly important to understand its
impact on the initiation, progression &
management of patients who smoke.
REFERENCES

1. Thomson MR, Ganito ML, Brown FH. The


role of smoking in periodontal diseases : A
review of the literature. J West Soc
Periodontol :Periodont Abstr 1993;41:5-9.
2. Palmer RM, Wilson RF, Hasan AS, Scott
DA. Mechanisms of action of environmental
factors tobacco smoking. J Clin Periodontol
2005 ; 32 (6): 180-95.
3. Sheiham A. Periodontal disease and oral
cleanliness in tobacco smokers. J Periodontol
1971 ; 42 : 259-63.
4. Preber H, kant T, Bergstrom J. Cigarette
smoking, oral hygiene and periodontal health
in Swedish army conscripts. J Clin
Periodontol ; 1980; 7:106-13.
5. Feldman RS, Bravacos S, Rose CL.
Association between smoking different
271

Ameet etal.,

Int J Med Res Health Sci. 2013;2(2):268-272

tobacco products and periodontal disease


indexes. J Periodontol 1983 ; 54 : 481-87.
6. Ismail AI, Burt BA, Eklund SA.
Epidemiologic patterns of smoking and
periodontal disease in the United States. J
Am Dent Assoc 1983 ; 106 : 617-21.
7. Bergstrom J, Preber H. The influence of
cigarette smoking on the development of
experimental gingivitis. J Periodont Res 1986
; 21 : 668- 76.
8. Mager DL, Haffajee AD, Socransky SS.
Effects of periodontitis and smoking on the
microbiota of oral mucous membranes and
saliva in systemically healthy subjects. J Clin
Periodontol 20003 ; 30 : 1031-37.
9. Lie MA , Van der Weijden GA,
Timmermann MF, Loos BG, Van
Steenbergen TJ, Van der Velden U. Oral
microbiota in smokers and non-smokers in
natural
and
experimentally
induced
gingivitis. J Clin Periodontol 1998b ; 25 :
677-86.
10. Preber H, Bergstrom J, Linder LE.
Occurrence of periopathogens in smokers and
non-smoker patients. J Clin Periodontol 1992
; 19 : 667-71.
11. Haffajee AD, Socransky SS. Relationship of
cigarette smoking to the subgingival
microflora. J Clin Periodontol 2001 ; 28 :
377-88.
12. Eggert FM, Mcleod H, Flowerdew G. Effects
of smoking and treatment status on
periodontal bacteria. J Periodontol 2001; 72 :
1210-20.
13. Van Winkelhoff A, Bosch-Tijhof C, Winkel
E, Vander Reijden W. Smoking affects the
subgingival microflora in periodontitis. J
Periodontol 2001 ; 72 : 666-71.
14. Kardachi BJR, Clarke NG. Aetiology of
acute necrotizing ulcerative gingivitis : a
hypothetical explanation. J Periodontol 1974
; 45 :830-32
15. Baab DA, Oberg PA. The effect of cigarette
smoking on gingival blood flow in humans. J
Clin Periodontol 1987 ; 14 : 418-24.

16. Morozumi T, Kubota T, Sato T, Okuda K,


Yashie H. Smoking cessation increases
gingival blood flow and gingival crevicular
fluid. J Clin Periodontol 2004;31:267-72.
17. Hanioka T, Tanaka M, Takaya K, Matsumori
Y, Shizukuishi S. Pocket oxygen tension in
smokers and non-smokers with periodontal
disease. J Periodontol 2000; 71 : 550-54.
18. Hanioka T, Tanaka M, Ojima K Takaya K,
Matsumori Y, Shizukuishi S. Oxygen
sufficiency in the gingiva of smokers and
non-smokers with periodontal disease. J
Periodontol 2000a ; 71 : 1846-51.
19. Bergstrom J, Floderus-Myrhed B. Co-twin
study of the relation between smoking and
some periodontal disease factors. Community
Dent Oral Epidemiol 1983;11:113-16.
20. Bergstrom J, Bostrom L. Tobacco smoking
and periodontal hemorrhagic responsiveness.
J Clin Periodontol 2001 ; 28 : 680-85.
21. Preber H, Bergstrom T. cigarette smoking in
patients referred for periodontal treatment. J
Dent Res 1986 ; 94 : 102-8.
22. Nair P, Sutherland G, Palmer R, Wilson R,
Scott D. Gingival bleeding on probing
increases after quitting smoking. J Clin
Periodontol 2003 ;30: 435-37.
23. Danielsen B, Maniji F, Nagelkerke N,
Fejerkov O, Baelum V. Effect of cigarette
smoking on the transition dynamics in
experimental gingivitis. J Clin Periodontol
1990 ; 17 : 159-64.
24. Dietrich T, Bernimoulin J, Glynn RJ. The
effect of cigarette smoking on gingival
bleeding. J Periodontol 2004 ; 75 : 16-22.
25. Mavropoulos A, Aars H, Brodin P.
Hyperaemic response to cigarette smoking in
healthy gingival. J Clin Periodontol 2003 ; 30
: 214-21.

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Int J Med Res Health Sci. 2013;2(2):268-272

DOI: 10.5958/j.2319-5886.2.2.015

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April - June

th

Received: 8 Jan 2013


Case report

Coden: IJMRHS
th

Revised: 30 Jan 2013

Copyright @2013

ISSN: 2319-5886

Accepted: 15th Feb 2013

BILATERAL ELONGATED STYLOID PROCESS: ITS ANATOMICAL EMBRYOLOGICAL


AND CLINICAL IMPLICATIONS.
*Bagoji Ishwar B1, Hadimani Gavishiddappa A1, Patil Balasaheb G2, Bannur Balappa M2, Bharatha
Ambadasu3.
1

Lecturer, 2Professor, Dept. of Anatomy, 3Lecturer, Dept. of Pharmacology, Sri B M Patil Medical
College Hospital & Research Center, BLDE University, Bijapur, Karnataka, India.

*Corresponding author email: ishwarbagoji@gmail.com


ABSTRACT

The styloid process is a slender, elongated, cylindrical bony projection from temporal bone. It normally
varies in length from 2 cm to 3 cm. During a routine demonstration of skull for MBBS students we
found the bilateral elongated styloid process in dry human skull. The length of elongation measured on
the right and left side was 6.0 & 5.9 cms respectively. Such abnormal elongation of the styloid process
may cause compression on a number of vital vessels and nerves related to it, producing inflammatory
changes that include continuous chronic pain in the pharyngeal region. Mechanical stresses stretching
the second brachial arch during fetal development probably induce variable involvement of Reichert's
cartilage in morphogenesis of the styloid process. It is important that clinicians especially dentists and
otolaryngologists are aware of the natural variations of the styloid process and do not consider the
styloid process with a length of 30 mm as an abnormality or as an anomaly.
Keywords: Styloid process, Reicherts cartilage, Eagles syndrome
INTRODUCATION

The styloid process is a thin and sharp bone


structure, protruding downward and forward
from the underside of the temporal bone. It is
situated between the carotid internal and external
arteries, posterior to the pharynx, which cover
stylohyoid, styloglossus and stylopharyngeal
muscles (Gray, 1977). The normal length of
styloid process is 20-25mm, between the apex of
the process and lesser Cornu of hyoid bone there
is attachment called as stylohyoid ligament. The
tip of the process is situated laterally from the
pharyngeal wall and immediately behind the

tonsillar fossa and critically between the internal


and external carotid arteries and has attachment
of three muscles and two ligaments. Rarely
stylohyoid ligament ossifies and increase the
length of the styloid process and called as the
elongated styloid process when it is longer than
30mm (Monsour). The apex of the styloid
process is clinically important, because it is
located between internal and external carotid
arteries. The facial nerve runs anterior and
medial
to
the
styloid
process.
The
glossopharyngeal nerve exists through the
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Int J Med Res Health Sci. 2013;2(2):273-276

jugular foramen and curves, in close proximity


under the styloid process. The accessory and
vagus nerves also run medial to the styloid
process.
The
approximation
of
the
glossopharyngeal nerve with the stylohyoid
ligament is the basis for the glossopharyngeal
neurological symptoms seen in Eagles syndrome
(Eagle WW).
The elongation of styloid process is considered
an anomaly which can be accompanied by
calcification
of
the
stylohyoid
and
stylomandibular ligaments, which can trigger a
series of symptoms such as dysphasia,
odynophagia, facial pain, ear pain, headache,
tinnitus and trismus. This set of symptoms
associated with the elongated styloid process is
called Eagle's syndrome (Lages et al.,2006).
Several other symptoms are attributed to the

Fig:1. Showing right styloid process

syndrome, including: neck pain, foreign body


sensation in the throat, pain on the rotation of the
head, and pain when swallowing (Guimaraes et
al., 2006, Rosa et al., 2008).However none of
these signs and symptoms are pathognomonic for
the Eagle's syndrome (Lages et al.).
CASE REPORT

During the routine osteological study of the skull


the lengths of the styloid process of both sides
were measured in centimetres from the base of
the skull to its tip. The lengths of both right and
left styloid processes were almost the same,
measuring 6.0 cm on the right side and 5.9 cm on
the left side. (Figure 1&2) This length is about
150% longer than the length of a normal-sized
styloid process.

Fig:2. Showing left styloid process

DISCUSSION

Styloid process length ranges from 5 mm to 50


mm (Standring et al).The normal length of the
styloid process ranges from 25 mm to 30 mm
(Eagle WW). Other studies accept that a length
of over 30 mm is considered elongated (Murtagh
R. et al). The elongation of the SP and structural
changes in stylohyoid ligament with its clinical
symptoms and signs were first described by
Eagle. Therefore, it is also called as the Eagles
syndrome (Eagle WW). Eagle described fully
about the elongated styloid process or eagle

syndrome, in his study in ear nose throat patient


and dento maxillofacial cases. Eagle studied that
elongated styloid process term use only when the
length of styloid process more than 30 mm or
when there is stylohyoid ligament ossification. It
has been suspected that an elongated styloid
process could be caused by: congenital
elongation of the styloid process due to the
persistence of the cartilaginous analog of the
Styloid (Murtagh R).

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Fig 3: Occipital view showing of both right & left styloid processes.
Kouladouros et al. (2009) reported that the
etiology can be explained by a genetic alteration
or according to three different theories. The first
theory, the hyperplasic reaction, suggests that the
styloid process had been stimulated by a
pharyngeal trauma leading to the ossification of
the styloid ligament. The second theory,
metaplastic reaction, also includes a traumatic
stimulus
causing
multiples
metaplastic
alterations in the cells of the styloid ligament,
which results in its total or partial ossification.
The third theory, anatomic variation, suggests
that the styloid process and the styloid ligament
are not usually ossified, but rather, an anatomic
variation.
The stylohyoid chain components are derived
embryologically from the first and second
branchial arches in four distinct segments:
tympanohyal, stylohyal, ceratohyal and hypohyal
segments. These segments are derived from
Reicherts cartilages that ossify in two parts. The
styloid process develops from the tympanohyal
and stylohyal segments that usually fuse at
puberty. The lesser horn of the hyoid bone arises
from the hypohyal segment. Connecting these
two structures, the stylohyoid ligament originates
from the ceratohyal segment (Rodriguez et al).

CONCLUSION

The elongated styloid process is a diagnosis that


should be considered in the evaluation of
recurrent neck, throat or facial pain and
dysphasia with or without radiation of pain to the
ipsilateral ear. Eagles syndrome is an
uncommon but important cause of chronic head
and neck pain. The elongated styloid process can
cause craniofacial and cervical pain, difficulties
in swallowing, secondary glossopharyngeal
neuralgia, radiating pain into the orbit and
maxillary region. Abnormal elongation of the
styloid process may cause compression on a
number of vital vessels and nerves related to it,
producing inflammatory changes that include
continuous chronic pain in the pharyngeal region,
radiating otalgia, phantom foreign body
sensation (Globus hystericus), pain in the
pharyngeal region, and dysphasia. Awareness of
the elongated styloid process is immensely
important in the field of Dentistry,
Otolaryngology, surgery & radiology.
ACKNOWLEDGEMENT

We thank Mr. Ekanath P Jadhav, Asst. Hospital


Administrator, Sri BM Patil Medical College
Hospital & Research Center, Bijapur for his
constant guidance.

275
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REFERENCES

1. Gray H. Anatomy descriptive and applied.


London. Longmans, Green and Company,
1977. Pgno;
2. Monsour PA, Young WG. Variability of the
styloid process & stylohyoid ligament in
panoramic radiographs oral surg. Oral
pathol.1986;61: 522-26
3. Eagle WW. The symptoms, diagnosis and
treatment of the elongated styloid process.
Am Surg. 1962;28:1-5
4. Lages LPD, Monte TL, Freitas SAP, Falcao
CAM. Alongamento do processo estiloidee
sindrome
de
Eagle:
consideracoes
anatomicas,
clinicas,
diagnosticoe
prevalencia. Odontologia. Cln Cientf.
2006;5:183-88
5. Guimaraes
SMR,
Carvalho
ACPC,
Guimaraes JP, Gomes MBG, Cardoso
MMM. & Reis HN. Prevalencia de alteracao
morfologica do processoestiloide em
pacientes com desordem temporomandibular.
Radiologia Brasileira. 2006;39:407-11
6. Rosa RR, Kohatsu LI, Moraes LC, Medici
FE, Moraes MEL, Castilho JCM. Sindrome
de Eagle:revisao da literatura sobre
variacoes, diagnostico etratamento. Revista
de Odontologia da Universidade Cidade de
Sao Paulo. 2008; 20:288-94.
7. Standing S. Skull and Mandible. In Gray's
Anatomy. The Anatomical basis of clinical
practice. Elsevier, Edinburg.2005: 39th
edition; 470
8. Murtagh R, Caracciolo J, Fernandez G. CT
Findings associated with Eagle syndrome.
AJNR. 2001, 22:1401-02.
9. Piagkou
M,
Anagnostopoulou
S,
Kouladouros K, Piagkos G. Eagles
syndrome: a review of the literature. Clinical
Anatomy. 2009; 22: 545-58.

10. Rodriguez Vazquez JF, MeridaVelasco JR,


Verdugo LS, Sanchez-Montesinos I, MeridaVelasco JA. Morphogenesis of the second
pharyngeal arch cartilage (Reicherts
cartilage) in human embryos. J Anat. 2006;
208: 17989.

276
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Int J Med Res Health Sci. 2013;2(2):273-276

DOI: 10.5958/j.2319-5886.2.2.013

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April-June

Received: 8 Jan 2013


Case report

Coden: IJMRHS
th

Revised: 28 Jan 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 9 Feb 2013

A RARE CASE OF NEUROLIPOMA


*Bharati P Baviskar1, Suryakant D Dongre2, Vishnu SYadkikar3
1

Associate Professor, 2Professor & Head,Department of Pathology, Pravara Institute of Medical


Sciences, Loni. 3 Professor, Department of Orthopaedics, Pravara Institute of Medical Sciences, Loni.

* Corresponding author email: baviskar.bharati@gmail.com


ABSTRACT
A painful swelling over the left ankle joint was excised. Histopathology revealed it to be a neuroliploma.
This case is reported here for its uncommon site that is involvement peroneal nerve, no association with
skeletal deformity and occurrence in a male patient.
Key Words: Neurolipoma, Neuralfibrolipoma, Lipomatosis of nerve, Fibrolipomatous Hamartoma.
INTRODUCTION
CASE

Neurolipoma usually manifests as a soft,


slowly
growing
mass
consisting
of
proliferating fibrous fatty tissue surrounding
and infiltrating major nerves and
their
branches. Principally it involves volar aspect
of the hands and wrist. Lower extremity
cases are extremely rare. 1 Median nerve is
most commonly involved. The unusual sites
of involvement are radial, peroneal and
cranial nerves. Males are more affected than
females. The lesion is almost seen during
first three decades of life. About one third of
cases are associated with overgrowth of bone
and macrodactyly.
We report here a rare case involving peroneal
nerve
without
any
skeletal
deformity
occurring in a young male patient.

A 15 years male presented with a swelling


over the left ankle. The swelling was 5 x
4cm, soft to firm in consistency, globular in
appearance and painful. It was gradually
increasing in size.
X ray of left ankle joint revealed normal
bones and soft tissue swelling around ankle
joint. No other abnormalities of bone were
found.
Grossly a single yellow white, fibro-fatty mass
of 5 x 4 x 0.4 cm soft to firm in consistency
was
received. Microscopy showed mature
adipose tissue admixed with fibrous tissue
dissecting between and separating individual
nerve bundles. Perineural fibrous tissue was
seen arranged concentrically around the mass.
No evidence of lipoblastic activity or cellular
pleomorphism was seen. The diagnosis was
given as Neurolipoma.
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Etiology: Neurolipoma is also known as


neural
fibrolipoma,
fibrolipomatous
hamartoma, intramural lipoma, lipomatosis of
nerve.2 Etiology is unknown. There may be a

genetic disorder but there is no history of any


hereditary disorder/syndrome . There is a history
of
trauma
in
some
cases.

Fig:1.Tumour showing yellow fatty and shiny white areas.

Fig:3. Proliferating nerve with adipocytes. (100X)

Fig:2. Adipose tissue admixed with fibrous tissue

Fig:4. Adipose tissue, neural tissue and fibroblasts (400X)

DISCUSSION

The median nerve is affected in most


cases.3,4 Rarely lesions are found in other
nerves such as ulnar, radial. Peroneal and
cranial nerves are involved very rarely.5,6
Grossly it appears as a soft, gray yellow,
fusiform,sausage shaped mass that has
diffusely infiltrated and replaced portion of a
large nerve and its branches.Microscopically
neurolipoma shows adipose and fibrous tissue
between and around nerve bundles. The diffuse

infiltrative character of
the lesion is
pathognomic. Fibrofatty tissue may be seen
outside the involved nerve. There is marked
thickening of the perineurium. A rare case
may show foci of metaplastic bone. Though
immunohistochemistry is not essential for
diagnosis; immunohistochemical profile of
neurofibrolipoma was first reported by Akisue
et al in his case report in 2002 showing CD34
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Int J Med Res Health Sci. 2013;2(2):277-280

antigen reactivity on fibrous spindle cells.7 No


ultrastructural finding is conclusive.
Lipoma of peripheral nerves occur with
sufficient frequency to pose problems in
diagnosis.8 In lipoma of a nerve there is fat
around nerve without infiltration within nerve
bundles. A clear distinction from diffuse
lipomatosis with overgrowth of bone is not
always possible histologically, but diffuse
lipomatosis is a primary lesion of the subcutis
and muscle and only secondarily affects nerves.9
Neuroma and neurofibroma can be distinguished
from neurolipoma by nerve element. Neuroma
and neurofibroma shows proliferation of neural
elements while neurolipoma shows atrophy of
nerve bundles.
It is usually seen in the age group of 11-39
years. Females predominate when lipofibroma is
accompanied by macrodactyly, whereas males
are more commonly affected when macrodactyly
is absent. The present case has occurred in 15
year male. There is usually a slow growing mass
present. The patient may show increasing pain,
tenderness, diminished sensation or paraesthesia
associated with gradually increasing mass
causing compression neuropathy.10,11 There may
be loss of muscle strength. MRI scans are
characteristic and pathognomic and it can be
diagnosed preoperatively.12
Carpal tunnel syndrome is a late complication of
some lesions. Pain and sensory loss may be
partially or completely relieved by dividing
the
transverse
carpal
ligament
and
decompressing
the nerve. The tumour was
excised by careful dissection and separating
clearly from the neurovascular bundle followed
by repositioning of tendons. The initial complaint
of pain was relieved and mobility was restored.
ACKNOWLEDGEMENT

We acknowledge the support and academic


guidance of Dr. Baviskar PK, Dr. Baviskar MP,
Dr. Karle RR, Dr. Pandure MM.

REFERENCES

1. Neural fibrolipoma In: Benign Lipomatous


tumors. Enzinger and Weiss Soft tissue
tumors, 4th ed.Philadelphia:2001:617-618.
2. Houpt P, Storm van Leeuven JB, Van Den
Bergen HA, Intraneural lipofibroma of the
median nerve. J Hand Surg (Am). 1989:
14:706
3. Sondergaard
G,
Mikkelsen
S.
Fibrolipomatous hamartoma of the median
nerve. J. Hand Surg. 1987;2:224-26
4. Jacob RA. Buchino J J. Lipofibroma of the
superficial branch of the radial nerve. J.
Hand Surg (Am). 1989;14(4):704-06
5. Bibbo C, Warren AM. Fibrolipomatous
hamartoma of nerve. J Foot Ankle Surg.
1994;33:64 -66
6. Donley BG, Neel M, Mitias HM. Neural
fibrolipoma of the foot: a case report in Foot
Ankle
Int. 1996. Nov, 17(11):7123Surg,33:64.
7. Akiuse T, Matsumoto K, Yamamoto T,
Kizaki T, Fujita I, Yoshiya S, Kurosaka M.
Neural fibrolipoma of the superficial
peroneal nerve in the ankle: a case report
with immunohistochemical analysis
in
Pathol Int. 2002;52(11):730-33.
8. Terzis JK, Daniel RK, Williams HB,
Spencer PS. Benign fatty tumors of the
peripheral
nerves. Ann. Plast
Surg.
1978;1:193-216.
9. Silverman
TA,
Enzinger
FM,
Fibrolipomatous hamartoma of nerve: a
clinicopathologic analysis of 26 cases. Am.
J. Surg. Pathol. 1985;9:7
10. Chatillon CE, Guiot MC, Jacques L.
Lipomatous, vascular, and chondromatous
benign tumors of the peripheral nerves:
Representative cases and review of the
literature. Neurosurg Focus. 2007;22:75-79
11. Murphey
MD, Smith WS, Smith SE,
Kransdorf MJ, Temple HT. From the
archives of the AFIP. Imaging of
musculoskeletal
neurogenic tumors:
radiologic- pathologic
correlation. In
Radiographics. 1999;19(5):1253- 80.
279

Bharati et al.,

Int J Med Res Health Sci. 2013;2(2):277-280

12. De Maeseneer M, Jaovisidha S, Lenchik L,


Witte D et al, Fibrolipomatous hamartoma:
MR imaging findings.Skeletal Radiol
.1997; 26:155-60

280

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DOI: 10.5958/j.2319-5886.2.2.012

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 8 Jan 2013


Case Report

Coden: IJMRHS

Copyright @2013

th

Revised: 9 Feb 2013

ISSN: 2319-5886
th

Accepted:15 Feb 2013

UTERINE DIDELPHYS WITH CERVICAL INCOMPETENCE


*Aher Gautam S1, Gavali Urmila G2, Kulkarni Meghana3
1

Professor, 2Assistant Professor; 3Resident, Dept of OBGY, Padmashree Dr. Vithalrao Vikhe Patil
Medical College & Hospital, Near Govt. Milk Dairy, Vilad Ghat, Ahmednagar, Maharashtra.

*Corresponding author email: drgsaher@gmail.com


ABSTRACT

Uterine didelphys represents a uterine malformation where the uterus is present as a paired organ. There
is presence of double uterine bodies with two separate services, and often a double or septate vagina as
well. We report a case of single pregnancy in the right sided uterine body of a didelphic uterus with
cervical incompetence. Case report: A 24 year G3A 2 with 14 weeks pregnancy came for routine
antenatal check-up. On examination she had uterine didelphys with 2 cervices & complete longitudinal
vaginal septum. Ultrasonography showed didelphys uterus with pregnancy in right hemiuterus and
cervical incompetence. Cervical encirclage was done (Mc donalds). The patient had an uneventful
antenatal period except for a persistent breech presentation. She was taken up for elective LSCS on at 39
weeks. An inverted T incision was given to deliver a 3Kg healthy male baby by breech extraction.
Postoperative period remained an uneventful. Discussion: Mullerian anomaly rate is reported between
0.1-1%in general population with significantly higher rates associated with infertility and reproductive
wastage.
Keywords: Uterine didelphys, Cervical incompetence
INTRODUCTION

A uterus didelphys is a type of Mllerian duct


anomaly (class III) where there is complete
duplication of uterine horns as well
as duplication of the cervix, with no
communication between them. The incidence is
1/3,000 women7. We report a case of single
pregnancy in the right sided uterine body of a
didelphic uterus with cervical incompetence.
CASE REPORT

A 24 year G3A2 with 14 weeks pregnancy came


for routine antenatal check-up. Prior had two
spontaneous mid trimester abortion. P/A

examination revealed enlarged uterus of 14-16


weeks size, which was abnormally elongated,
deviated towards the right. P/S examination
revealed two cervical openings with complete
vaginal septum. P/V examination revealed two
cervices and gravid cervix was with the short
cervical length. There was a left sided mass
attached to the gravid uterus. Ultrasonography
showed Didelphys uterus with pregnancy in right
hemiuterus. Cervical encirclage (Mc Donalds)
was done. The patient had an uneventful
antenatal period except for a persistent breech
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Int J Med Res Health sci. 2013;2(2):281-283

presentation. Patient was admitted to the hospital


at 37th week and was given head low position and
strict bed rest under tocolytic cover. At 39 weeks
she had premature rupture of membranes for

which she was taken up for emergency LSCS.


An inverted T incision was given to deliver a 2.9
Kg healthy female baby by breech extraction.
Postoperative period remained an uneventful.

Fig.1: Visual inspection of external genitalia- unremarkable.

Fig.2: Local examination showing vaginal septum.

Fig.3: P/S showing 2 cervices and vaginal septum.

Fig.4: Intra operative photo showing well developed


left horn of uterus without pregnancy

DISCUSSION

Mullerian anomaly rate is reported between 0.11% in the general population with significantly
higher rates associated with infertility and
reproductive wastage2. It results from the failed
distal fusion that occurs between the 12th and 16th
week of pregnancy and is characterized by two
symmetric, widely divergent uterine horns and
two cervixes3.The processes during which the
lower segments of the paired mllerian ducts
fuse to form the uterus, cervix, and upper vagina
is termed lateral fusion7. Failure of fusion results
in anomalies such as bicornuate or didelphys

uterus. The chance of seeing a pregnancy to term


is significantly reduced, down to only 20%, with
every third pregnancy ending in abortion and
over half of the pregnancy in premature
deliveries. This is seen in our patient who had
previous 2 midtrimester abortions. According to
a study only 40% of pregnancies resulted in
living children 2. The volume of uterus in each
duplicated segment is reduced. American
Fertility Society (AFS) Classification Scheme:
Class III (didelphys uterus) results from the
complete nonfusion of both mullerian ducts. The
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Int J Med Res Health sci. 2013;2(2):281-283

individual horns are fully developed and almost


normal in size. Two cervices are inevitably
present. A longitudinal or transverse vaginal
septum may be noted as well. Since each horn is
almost a fully developed uterus, patients have
been known to carry pregnancies to full term.1
Rock and Adam modified the AFS classification,
he included Class 3 which describes anomalies in
a patent but often duplicated or partially
duplicated reproductive tract and includes
disorders of lateral fusion such as didelphys,
unicornuate, bicornuate, and septate uteri (AFS
classes II, III, IV, and V) 4. It may present with
Infertility &Miscarriage. Breech presentation
was present in 43% and premature delivery are
common in almost (21%)6. Associated unilateral
hematometrocolpos and ipsilateral renal agenesis
and vaginal septum is commonly seen. Multiple
gestations
with
pregnancies
occurring
simultaneously in each uterine body are reported
and a case of triplet pregnancy with twin fetuses
on one side and a single fetus on the other side is
also reported. Cesarean section was performed in
82% of patients reported by Heinonen6. Uterus
didelphys, in certain studies, has also been found
associated with higher rates of infertility,
spontaneous abortion, intrauterine growth
retardation, and postpartum haemorrhage.8 A
specific association of uterus didelphys,
unilateral hematocolpos and ipsilateral renal
agenesis has been described.
CONCLUSION

Didelphic uterus is a very rare anomaly and it


can lead to recurrent pregnancy loss due to
decreased uterine volume and associated cervical
incompetence. Spontaneous abortion rates range
from 32%-52% and premature birth rates from
20%-45%. By adequate bed rest, tocolytics and
cervical encirclage, pregnancy in these patients
can reach term.

REFERENCES

1. Gholoum S, Puligandla PS, Hui T, Su W,


Quiros E, Laberge JM. Management and
outcome of patients with combined vaginal
septum, bifid uterus, and ipsilateral renal
agenesis
(Herlyn-Werner-Wunderlich
syndrome). J Pediatr Surg. 2006;41(5):98792
2. Jindal G, Kachhawa S, Meena GL, Dhakar
GJ. Uterus didelphys with unilateral
obstructed
hemivagina
with
hematometrocolpos and hematosalpinx with
ipsilateral renal agenesis. Hum Reprod Sci.
2009;2(2):87-89
3. Wein Campbell. Surgical Management of
Intersexuality, Cloacal Malformation, and
other Abnormalities of the Genitalia in Girls
Obstructive Genital Anomalies. Walsh
Urology, 9th ed.; Pgno: 155
4. Adam: Grainger & Allison's Diagnostic
Radiology, 5th ed.pg no 2001
5. Moawad NS. Uterus didelphys and
longitudinal vaginal septum coincident with
an obstructive transverse vaginal septum. J
Pediatr Adolesc Gynecol.2009; 22(5): 16365.
6. Heinonen PK. Uterus didelphys: a report of
26 cases. European Journal of Obstetrics
&Gynecology and Reproductive Biology.
1984;17(5):34550.
7. Grimbizis GF, Camus M, Tarlatzis BC,
Bontis JN, Devroey P.Clinical implications
of uterine malformations and hysteroscopic
treatment results. Human Reproduction
Update. 2001;7 (2): 16174.
8. Pui M (2004). Imaging diagnosis of
congenital
uterine
malformation.
Computerized
Medical
Imaging
and
Graphics.2004; 28 (7): 42533.

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DOI: 10.5958/j.2319-5886.2.2.011

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April - June

Received: 8 Jan 2013


Case Report

Coden: IJMRHS
th

Revised: 11 Feb 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted: 18 Feb 2013

RESIDUAL NON-UNION IN A CASE OF TWO AND HALF YEAR OLD CHILD


CONGENITAL PSEUDOARTHROSIS OF IPSILATERAL TIBIA AND FIBULA TREATED
BY INTRAMEDULLARY FIXATION WITH K-WIRE AND ALLOGENIC CANCELLOUS
STRUT GRAFT: A CASE REPORT.
*Siddaram N Patil1, Sankar Rao P2, Ranjith K Yalamanchili3
1

Professor, 2Assistant Professor, 3PGstudent, Dept of Orthopaedics, Mamata Medical College & General
Hospital, Khammam, AP, India.
*Corresponding author email: drsnp_2006@yahoo.co.in
ABSTRACT

The pseudarthrosis usually develops during the first two years of life; however, there are reports of cases
in which fractures developed before birth and reports of late-onset pseudarthrosis. There is a strong
association between Congenital pseudoarthrosis and Type I neurofibromatosis. CPT develops in about
5.7% of patients with NF-I and 40% of patients with pseudoarthrosis were found to have NF-I. Main
pathology is hyperplasia of fibroblasts with the formation of dense fibrous tissue at fracture site causing
osteolysis, and persistence of pseudarthrosis. The difficulty in treating this condition occurs because of
two factors. 1) Biologic: poor healing ability of the dysplastic segment of bone and 2) Mechanical:
technical difficulty to fix small and osteopenic bone fragments in children without damaging the distal
physis. A multitude of treatment protocols focusing on stimulating the healing process by using different
bone grafting techniques were documented6. The graft materials most commonly used included
osteoperiosteal graft, massive only graft, autogenous iliac crest bone graft, and vascularised bone graft.
Keywords: Congenital Pseudarthrosis, Tibia, Fibula, Nonunion bone grafting, Vascularised bone graft
INTRODUCTION

Congenital Pseudarthrosis of the tibia and fibula


is Congenital Pseudarthrosis of the tibia and
fibula is one of the most most perplexing and
challenging problems in paediatric orthopaedics
because of the difficulty in achieving and
maintaining union. It is an uncommon entity with
a reported incidence of 1:140,000 to 1:250,000
neonates1. It refers to nonunion of a fracture that
develops spontaneously or after trivial trauma in
a dysplastic bone segment of the lower third of

tibial and fibular diaphysis. Congenital


pseudarthrosis of the fibula with or without ankle
deformity often precedes or accompanies the
same condition in the ipsilateral tibia2.
Sometimes it even develops between the time of
successful bone grafting of a pseudarthrosis of
the tibia and skeletal maturity2. The
pseudarthrosis usually develops during the first
two years of life; however, there are reports of
cases in which fractures developed before birth
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and reports of late-onset pseudarthrosis3. There is


a strong association between Congenital
pseudoarthrosis and Type I neurofibromatosis4.
CPT develops in about 5.7% of patients with NFI and 40% of patients with pseudoarthrosis were
found to have NF-I4,5. Main pathology is
hyperplasia of fibroblasts with the formation of
dense fibrous tissue at fracture site causing
osteolysis, and persistence of pseudarthrosis5.
The difficulty in treating this condition occurs
because of two factors. 1) Biologic: poor healing
ability of the dysplastic segment of bone and 2)
Mechanical: technical difficulty to fix small and
osteopenic bone fragments in children without
damaging the distal physis. A multitude of
treatment protocols focusing on stimulating the
healing process by using different bone grafting
techniques were documented6. The graft
materials most commonly used included
osteoperiosteal graft, massive onlay graft,
autogenous iliac crest bone graft, and
vascularised bone graft. The fixation methods
also varied widely between cortical fixation
using bone or metal plates, intramedullary rods
of different types, external skeletal fixation, and
lastly combination of external fixation
augmented by intramedullary rods7. Although

Bone morphogenetic proteins have shown


clinical efficacy in the treatment of adult tibial
nonunions and in spinal fusion, its logical
application in cases of pseudoarthrosis along
with corticocancellous allograft has not resulted
in enhanced bone healing8.
CASE REPORT

We report a two and a half year old female child


with history of bowing of right leg since 2
months of age that was gradually increasing and
deformity of the lower third of right leg after
trivial trauma at the age of 20 months. Child,
who used to walk with support from 16 months
of age was unable to stand or walk after trauma.
Father is a known case of neurofibromatosis I
and has multiple neurocutaneous lesions and
caffe au lait spots. Child has multiple Caffe au
lette spots with no neurocutaneous lesions.
Anterior angulation of lower third leg with
shortening of the tibial component by 3cm and
abnormal mobility in both anteroposterior and
mediolateral planes with no stiffness of affected
ankle joint were significant findings. [Fig 1]. X
ray findings : Atrophic fracture ends of lower
third tibia and fibula with obliteration of
medullary canal and anterior angulation.

Fig.1: Clinicla profile of a two and half year old female child with congenital pseudoartbosis tibia and fibula. 1a:
Clinical Photograph of left leg bowing 1b:Pre op X ray Left leg with dysplastic fracture ends and obliterated
medullary canal of tibia fibula 1c: MRI showing dysplastic ends and fibrous tissue at fractured ends with
decreased signal intensity in the medulary canal at the pseudoarthrosis site suggesting obliteration of the
medullary canal 1d & 1e: showing multiple coffee latte spots over the trunk and abdomen.
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Fig.2: Surgical Procedure of resection of pseudoarthrosis and intramedullary fixation with allogenous
cancellous bone graft. 2a. Intraoperative finding of fibrous tissue around dyplastic tibial ends at the site
of pseudoarthrosis of the tibia. 2b. Allogenous cancellous bone graft from childs fathers Iliac crest. 2c.
Retrograde fixation of graft to resected tibia with a k-wire. 2d. Intraoperative picture of allogenous graft
fixation with k wires passed retrogradely. 2e. C-arm picture showing correction of deformity with
fixation of graft insitu. 2f. Postoperative picture showing deformity correction without limb length
discrepancy by ensuing allograft sizing the resected specimen of tibia. 2g. Postoperative splinting in
above knee cast. 2h. Clinical picture of parent with neurocutaneous lesions over the body showing
surgical scar from iliac crest over allograft donation site. 2i. Postpoerative healed surgical scar with k
wires insitu. 2j resected gross specimen of sclerotic and dysplastic tibial ends over pseudoarthrosis site.
2k. Histopathology slide of excised tissue show cellular proliferating fibrous tissue with immature bone
is observed (40X)
The child was initially planned for excision of
fibrosis and dysplastic ends of the tibia and
fixation. The abnormal part of tibia dysplastic
bony fractured ends and fibrous tissue was
resected leaving a gap of 5cm. A thick

allogenous cancellous strut graft from the iliac


crest of the child`s father after due major cross
matching the blood group was taken. The bone
gap was reconstructed by passing a 1.5mm Kwire of 30cm length in a retrograde manner
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under c- arm guidance from distal tibia through


talus, calcaneum to heel. A 1mm k wire is passed
to fix the fibula after resecting the fibrous tissue
and freshening the edges to provide internal
splintage to the leg. The deformity was clinically
corrected and there was no limb length
discrepency without neurovascular compromise.
Post operatively child was immobilised in an
above knee plaster cast. Suture removal was

done after healing of surgical wounds and there


was no signs of infection. [Fig 2] Child was
followed for up to 3 months, with check
radiographs taken every month and there were no
clinical signs of infection on inspection after
removing the cast. At the end of 3 months, there
was no signs of bony union and the allogenous
cancels graft was sclerotic. [Fig 3]

Fig.3: 3months post surgery followup scenario 3a. X-ray showing alignment with k-wires insitu and no signs of
union and sclerosis of allograft 3b. Arrowmarks in the X-ray pointing to sclerosed and atrophied allograft 3c. The
gross specimen of allograft after 3months.
DISCUSSION

The treatment goal for congenital pseudarthrosis


of the tibia is to achieve bony union and avoid
recurrent fracture and limb length discrepancy.
The pathologic process of the disorder is the
growth of abnormal, fibromatosis-like tissue
either within the periosteum (dysplastic type) or
within the endosteal/marrow tissue (cystic type),
or the coexistence of both (mixed type) 9,10.
Complete excision of the abnormal tissue is
necessary to treat the problem, evidenced by
visualising normal bleeding and marrow cavity11.
Resection of the abnormal tissue, followed by
fragment approximation, intramedullary nailing,
and bone grafting, is a relatively easy procedure
and is suggested as an initial treatment for
congenital pseudarthrosis of the tibia12. This

treatment has a union rate of approximately


86%13, 14.
In the present case, after resection of 4cm of
dysplastic bone, reconstruction with allogenous
cancellous graft with intramedullary nail was
technically challenging because of the small
medullary canal of the tibia, which is only
1.5mm diameter at isthmus. In literature,
documented intramedullary fixation was done
with Titanium Elastic nails, Enders Nails7, 15. Use
of external frames such as a Taylor spatial frame,
JESS, Illizarov are reserved usually for older
children. In the present case due to non
availability of TENS and Enders of diameter of
1.5mm, a K-wire is used as an intramedullary
device to provide stability and alignment in this
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child. Excision and grafting with vascular fibular


grafts or cortical fibular strut grafts are
recommended in literature. Vascularised fibular
grafts are technically demanding and autologous
cortical strut grafts in a child less than 3 years is
practically not feasible. Hence, we have tried
allogenous cancellous strut graft from the parent
after ensuing major compatibility as a grafting
choice coupled with intramedullary k-wire
fixation in treating a pseudoarthrosis of the tibia
in a child less than 3 years old. Attention to
internal fixation and fibular continuity are crucial
for maintaining alignment and consequently
union1. Hence, after resection of fibrous tissue
around fibular pseudoarthrosis and the excision
of periosteum, fibula was fixed with 1 mm kwire to act as an internal splint and maintain
fibular continuity. Toward these goals,
immediate contact of bone ends with
compression and ample bone graft and biological
enhancers are likely to achieve union most
frequently. Although similar principles were
followed in this case, it resulted in non union.
CONCLUSION

Pseudoarthrosis is both a biological and


mechanical issue. Mechanically although
stabilised, biological pathology predominated in
this case and resulted in failure. In conclusion,
there was no predictor identified for nonunion in
this study. Hopefully, in the future, combined
surgical and medical treatments that effectively
modulate or block the biochemical pathways
responsible for congenital pseudoarthrosis will
downgrade its recalcitrant status.
REFERENCES

1. Johnston CE, Birch JG. A tale of two tibias: a


review of treatment options for congenital
pseudarthrosis of the tibia. J Child Orthop.
2008;2:133-49.
2. Hsu LCS, O`brein ACMC, J.P and Hodgson;
Valgus deformity of ankle in children with
fibular pseudoarthrosis. JBJS. 1972;54:58594

3. Abumunaser LA, Alsayyad MJ. Congenital


Pseudarthrosis of the Tibia with Complex
Deformity and Multiple Previous Surgeries
Treated by Taylor Spatial Frame at Age of 16
Years; JKAU. Med. Sci., 2010;17(1):67-78
4. Leskel HV, Kuorilehto T, Risteli J,
Koivunen J, Nissinen M, Peltonen S,
Kinnunen P, Messiaen L, Lehenkari P,
Peltonen J. Congenital pseudarthrosis of
neurofibromatosis
type
1:
Impaired
osteoblast differentiation and function and
altered NF1 gene expression. Bone.2009;
44:243250.
5. Lehman WB, Atar D, Feldman DS, Gordon
JC, Grant AD. Congenital pseudoarthrosis of
the tibia. J Pediatr Orthop B. 2000; 9:103-7.
6. Kim HW, Weinstein SL. Intramedullary
fixation and bone grafting for congenital
pseudarthrosis of the tibia. Clin Orthop Relat
Res. 2002;405:250-57.
7. Cui G, Lei W, Li J; Histopathology of
congenital pseudarthrosis of the tibia.
Zhonghua Yi Xue Za Zhi. 82:48791.
8. Wientroub
S,
Grill
F.
Congenital
pseudarthrosis of the tibia: part 1. European
Pediatric Orthopaedic Society multicenter
study of congenital pseudoarthrosis. J Pediatr
Orthop B 2000; 9:12.
9. Baker JK, Cain TE, Tullos HS;
Intramedullary fixation for congenital
pseudoarthrosis tibia; . J Bone Joint Surg
Am. 1992;74-A;2;Feb.
10. Joseph B, Mathew G. Management of
congenital pseudarthrosis of the tibia by
excision of the pseudarthrosis, onlay
grafting,and intramedullary nailing. J Pediatr
Orthop B 2000;9:1623.
11. Joseph B, Somaraju VV, Shetty SK (2003)
Management of congenital pseudarthrosis of
the tibia under age 3 years of age: effect of
early surgery on union of the pseudarthrosis
and growth of the limb. J Pediatr Orthop
23:740746.
12. Plawecki S, Carpentier E, Lascombes P,
Prevot J, Robb JE. Treatment of congenital
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pseudarthrosis of the tibia by the Ilizarov


method. J Pediatr Orthop. 1990;10(6):786-90.
13. Fabry G, Lammens J, Van Melkebeek J,
Stuyck J. Treatment of congenital
pseudarthrosis with the Ilizarov technique. J
Pediatr Orthop. 1988;8(1):67-70.
14. Weiland AJ, Weiss AP, Moore JR, Tolo VT.
Vascularized fibular grafts in the treatment of
congenital pseudarthrosis of the tibia. J Bone
Joint Surg Am. 1990;72(5):654-62.
15. Pho RW, Levack B, Satku K, Patradul A.
Free vascularised fibular graft in the
treatment of congenital pseudarthrosis of the
tibia. J Bone Joint Surg Br. 1985;67(1):6470.

289
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Int J Med Res Health Sci. 2013;2(2):284-289

DOI: 10.5958/j.2319-5886.2.2.010

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April-June

th

Received: 18 Jan 2013


Case Report

Coden: IJMRHS

Copyright @2013

st

Revised: 1 March 2013

ISSN: 2319-5886
th

Accepted: 8 March 2013

COMPLETE DORSAL WALL DEFECT IN A DRY HUMAN SACRUM: A CASE REPORT


*Swathi Poornima C
Assistant Professor, Department of Anatomy, Dr.Pinnamaneni Siddhartha Institute of Medical Sciences
& Research Foundation, Krishna District, Andhra Pradesh, India
* Correspondence author email: swathi79poornima@gmail.com.
ABSTRACT

The human sacrum is a triangular bone formed by the fusion of five separate vertebras along with the
intervertebral discs. Gross morphology of sacrum shows a concave ventral surface, a convex dorsal
surface and a triangular sacral canal. The sacral canal consists of an anterior wall formed by the fusion
of the posterior aspects of sacral vertebral bodies and the dorsal wall is formed by the fused laminae,
spines and ossified ligamentum flava. During the routine course of osteology for undergraduates one of
the sacrum showed complete absence of the dorsal wall of the sacral canal. Anatomical variations
frequently occur around the dorsal wall of the sacral canal especially in relation to sacral hiatus. The
variations may be attributed to the dependency of the sacrum to the load related fusion of the bone
structure. Knowledge of such variations is of profound importance in spinal injuries, neurosurgeries and
caudal epidural anaesthesia.
Keywords: Sacrum, Sacral canal, Agenesis, Caudal epidural anaesthesia
INTRODUCTION

Sacrum is a triangular bone formed by the fusion


of five vertebrae and forms the posteriosuperior
wall of the pelvic cavity. Sacrum articulates with
four bones, the last lumbar vertebra above via a
disc space and facet joint complex, the coccyx
below with a ligamentous attachment and
occasional bone union, and on either side with
ilium forming the sacroiliac joint. Sacral canal is
a triangular canal formed by the sacral vertebral
foramina. Sacral canal is bounded by the ventral
wall which if formed by the fusion of dorsal
aspects of sacral vertebral bodies and a dorsal
wall formed by the fusion of posterior elements

which include the laminae, spines and the


ossified ligamentum flava. The sacral canal
consists of Cauda equina, filum terminale and
spinal meninges. Sacrum resembles its lumbar
counterparts in the ossification of its segments.
Each sacral vertebra has five ossification centers
which include a primary centre, one in each
epiphyseal plate and two for the two vertebral
arches. Understanding of the anatomy and
development aspects of sacral canal and sacral
hiatus plays an important role in surgical
treatments and caudal epidural blocks.

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Case Report
During routine Osteology discussion classes for
undergraduates in the Department of Anatomy at
Dr. PSIMS & RF, it was observed in one of the
dry human sacrum that its dorsal wall of sacral
canal was completely absent (agenesis of dorsal

Fig.1: Dorsal surface of sacrum

wall) Fig 1. Remaining


ing features of the sacrum
were normal with four sacral foramina showing
no features of sacralisation or lumbarisation Fig
1&2.

Fig .2 Ventral surface of the sacrum with four sacral foramina

* Indicating
ndicating complete absence of the dorsal wall of the sacral canal,
canal, SFSF Sacral foramina.
DISCUSSION

Many studies have been conducted on the shapes


of the sacral hiatus and various shapes have been
described
in
literature.
Developmental
malformations occur ranging from variations in
the sacral hiatus to caudal agenesis. Most
commonly observed hiatal shapes include
inverted U, inverted V, whereas irregular,
dumbbell and bifid include variations in the
shape. Rare variations include hiatal agenesis and
complete dorsal wall agenesis. Stanford Helm II
in their study observed 3% hiatal agenesis, while
completely fused walls at apex of sacral hiatus
was observed by Trotter et al in 0.74% sacrum1,2.
Senoglu et al have observed 2.08% of sacra to
have total posterior closure defect3.Patil
Dhananjay et al in their study of dry human sacra
observed 2.91% of sacra with complete absence
of the dorsal wall of sacral canal4.
Trotter et al have
have observed 1.8% and Vinod
Kumar et al have observed 1.49% of sacra with
complete absence of dorsal wall2,5. Nagar SK in

270 dry human sacra has observed 1.5% of them


without the dorsal wall of sacral canal6.
Sound knowledge of position, shape and the
morphology
morphology of sacral canal are important for
caudal epidural anaesthesia. Surgical treatment
of sacral lesions requires understanding of the
underlying anatomy and various morphometric
parameters of the sacrum
sacrum.. Significant leaps have
been made towards the unde
understanding
rstanding of the
sacral region by both anatomists and surgeons,
there is still much to be learned with advances in
surgical methods and instrumentation in the field
of spinal surgery driving a continued need to
better understand the anatomy of the region.
CONCLUSION

To conclude, knowledge of dorsal wall agenesis


of sacral canal is of great value for neurosurgical
and radiological approaches. Studies and case
reports of variations in cadavers and dry human
bones should form basis and guiding tools
tools for
clinical
clinical and surgical procedures in near future.
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Re Health Sci. 2013;2(2):2
2):290-292

REFERENCES

1. Stanford HH, Jeffrey D, Gross and Kenneth


G, Varley. Mini-Surgical Approach for
Spinal endoscopy in the Presence of Stenosis
of the Sacral Hiatus. Pain Physician. 2004;
7:32325
2. Trotter M. Variations of the sacral canal.
Their significance in administration of caudal
analgesia. Anaesthesia and analgesia. 1947;
26(5):192-202.
3. Senoglu N, Senoglu M, Oksuzl Y et al.
Landmarks of the sacral hiatus for caudal
epidural block: an anatomical study. British
Journal of Anaesthesia. September 2005; 1-4.
4. Patil DS, Jadav HR et al. Anatomical Study
of Sacral Hiatus for Caudal Epidural Block.
National Journal of Medical Research. 2012;
2(2):272-75.
5. Vinod Kumar, Pandey SN, Bajpai RN et al.
Morphometrical study of sacral hiatus.
Journal of Anatomical Society of India.1992;
41(1):7-13.
6. Nagar SK. A study of Sacral Hiatus in dry
human sacra. Journal of Anatomical Society
of India.2007; 53(2):18-21.

292

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Int J Med Res Health Sci. 2013;2(2):290-292

DOI: 10.5958/j.2319-5886.2.2.009

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April-June

Received: 20 Jan 2013


Case report

Coden: IJMRHS

Copyright @2013

nd

Revised: 22 Feb 2013

ISSN: 2319-5886
th

Accepted:28 Feb 2013

RADIATION AND CHEMOTHERAPY INDUCED SECONDARY LEUKEMIA IN A CASE


TREATED FOR CARCINOMA CERVIX: A CASE REPORT
*Pandure Mangal M1, Ghosh Deepak K2.
1

Assistant Professor, 2Professor Department of Pathology. Rural Medical College, Pravara Institute of
Medical Sciences, Loni,Maharashtra, India
*Corresponding author email: mangal.garute@yahoo.com
ABSTRACT

Secondary leukemias are usually forms of leukemias which are developed due to therapy administered
for a previous malignancy. Radiotherapy or chemotherapy induced leukemia is a complication which
follows treatment of a different primary malignancy. A case of acute monoblastic leukemia following
treatment of the invasive carcinoma cervix (treated by radiotherapy and chemotherapy) is reported. This
secondary leukemia developed one year after treatment. This case is being presented due to its rarity.
Keywords: Acute monoblastic leukemia, Radiation, Chemotherapy induced leukemia, Carcinoma
cervix, Pelvic radiation
INTRODUCTION

The term secondary leukemia is usually


employed to indicate either leukemia arising
from myelodysplasia or acute leukemia
developing after exposure to environmental or
therapeutic toxins or radiation (therapy related).1
Cervical cancer patients, treated with radiation
therapy have statistically significant risk of
developing acute non lymphoblastic leukemia;
approximately 1-9 years after radiotherapy.2
Secondary acute myeloid leukaemia can occur
following exposure to cytotoxic agent (e.g.
Drugs, radiation and toxic chemicals) or as a
subsequent
event
following
another
hematological disorder, usually myelodysplasia.
The risk of developing a second malignancy is
estimated to range from 8% to 12% in a 20 year
period after diagnosis of the first cancer. 1

CASE REPORT

A 65 years old female presented with a history of


vaginal discharge of two months duration, in Oct
2010. Clinical examination reveals infiltrative
growth involving both lips of the cervix.
Histopathological examination of the cervical
growth showed moderately differentiated
squamous cell carcinoma. Clinical staging of this
carcinoma
cervix
was
IIIB.
Routine
hematological parameters were within normal
limits. Patient received radiation therapy and
chemotherapy for carcinoma cervix for a period
of six weeks. She received external beam
radiation to pelvis 50GY in 28 fractions along
with brachytherapy for 6 weeks. She also
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received chemotherapy, Cisplatin 40mg/m2


weekly for six weeks.
After one year of the above treatment, a patient
again presented with complaints of back pain
radiating to chest and the fatigue of fifteen days
duration in Oct 2011 (Approximately one year
after first diagnosis of cancer cervix). Routine
hematological examination showed Hemoglobin:
9.9gm/dl, total leukocyte count: 27,000/ cumm.
Differential count showed: Monoblast: 80%,

Fig1: Routine Leishmans stain (x 400)

Neutrophil: 10% and lymphocyte: 10%. Platelet


count was 01 lacs/cumm. Peripheral blood smear
showed features of acute monoblastic leukemia
on Leishmans stain (Fig 1), Nonspecific esterase
was
positive
indicating
monoblastic
differentiation (Fig 2). She was diagnosed as a
case of Acute Monoblastic Leukemia (M5a) after
an approximate period of one year following the
start of treatment for carcinoma cervix.

Fig 2: Special stain Nonspecific estarase (x 400)

DISCUSSION

Secondary leukemias usually result from


chemotherapy for a different primary cancer but
it also probably reflects an increased
susceptibility to the cancer.1 Therapy related
acute non lymphoblastic leukemia and
myelodydplasia are now recognized as the two
most serious complications following the use of
cytotoxic drugs. The major use of such drugs is
in the treatment of malignant diseases.
Development of secondary leukemia following
high dose radiotherapy for primary cancer has
been reported even after a period of more than 20
years after treatment.3
Secondary leukemia accounts for 10-30% of all
acute myeloid leukemia (AML).1 The majority of
secondary leukemias result from the use of
cytotoxic drugs bindings to the enzyme DNA
topoisomerase. The risk of transforming acute

myeloid leukaemia in women treated with


alkylating agent is 7% at 10 yrs.1
Our patient developed acute monoblastic
leukemia after completion of one year treatment
for carcinoma cervix.(Combined radiotherapy
and chemotherapy)
Therapy induced second malignant neoplasms
occurs mainly due to the effects of ionizing
radiation or chemotherapy or both. These agents
induce non-lethal DNA damage to the bone
marrow cells which subsequently undergo
malignant transformation resulting in leukemia.
Various chemotherapeutic drugs such as
alkylating agents and platinum compounds are
mutagenic in vitro and in laboratory animals.4
Carcinoma of the uterine cervix is the most
common female genital malignancy in
developing countries.[4] Majority of the patient
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Int J Med Res Health Sci. 2013;2(2):293-296

present with advanced disease. Cisplatin based


concurrent chemo radiation is now the treatment
of choice for this disease. Due to increased
survival rates among such patients, treatment
related second malignancy is also increasingly
being recognized in these cases.4
Margaret A et al., and Chatuvediet. al.,
concluded that patients treated with radiotherapy
for carcinoma cervix are at increased risk of
developing a second cancer like that of the
urinary bladder, ovaries, rectum, colon, female
genital sites other than the cervix, bone and
connective tissue. Following radiation therapy
for both cervical and endometrial cancer, there is
a small increased risk of developing leukemia.[2,5]
Following radiation therapy for cervical cancers
there is a 20% increased risk of cancer
developing close to or at an intermediate site,
which may increase up to 40% if patient are
followed up for a period of 10 years or more.5
There is a 30% increased risk of developing
acute non lymphoblastic leukemia.5
The risk of development of platinum induced
leukemia depends on the cumulative dose of
platinum administered. In multivariate analysis,
the risk of developing acute myeloid leukemia
was higher among patients whose initial
management was with platinum based therapy
than those undergoing radiotherapy alone.[4]
Platinum based chemotherapy of primary ovarian
cancer increases risk of secondary leukemia. In a
large study, 10,000 women with ovarian cancer,
who were treated for six months with cumulative
dose of platinum and followed up for a period of
ten years, 71 cases developed leukemia. The
cumulative dose of platinum was estimated to be
500 to 1000mg over a period of six months.4,6
Lois B et al, performed a study on patient of
ovarian cancer and concluded that the risk of
developing secondary leukemia was significantly
increased after treatment with platinum based
chemotherapy for primary ovarian cancer. They
concluded that the magnitude of the risk was
directly dependent on the cumulative dose of the
drug as also the duration of the treatment. The
risk of developing secondary leukemia was also

significantly higher among the small number of


patients who received both platinum and
radiotherapy for primary carcinoma.6
Our patient received a cumulative dose of 300
mg of platinum together with radiation 50 GY
infractions. Boice J D Jr.et. al., studied the
relationship between dose and response of
radiotherapy in 1, 50,000 women with invasive
carcinoma of the uterine cervix. All of them
received radiotherapy; of these 195 cases
developed leukemia. They concluded that the
risk of development of leukemia increased with
increasing radiation dose to an average dose of
about 400 rad was reached.7
Studies by MJ Ratain,et.al., on 119 patients of
non-small cell carcinoma of the lung treated with
combination chemotherapy cisplatin and other
drugs, showed that four of these patients
developed non lymphoblastic leukemia,1-4 years
after the start of treatment.8
Of the 1, 99,268 patients of invasive tumor of
vulva, cervix, uterus, anus and recto sigmoid
junction who were treated with radiation and non
radiation chemotherapy. Post treatment, risk of
secondary leukemia peaked 5-10 years after
primary treatment and remained elevated even
10-15 years after treatment. The conclusion was
that pelvic radiation was associated with an
increased risk of secondary leukemia.9
A population based cohort study on 18,657
patients with testicular cancer treated with
radiotherapy
without
chemotherapy
was
associated with threefold elevated risk of
leukemia. Radiation dose to active bone marrow
and cumulative dose of cisplatin were both
predictive of excess leukemia risk. The estimated
relative risk of leukemia at cumulative dose of
650 mg cisplatin which is commonly
administered in testicular cancer is higher. Larger
doses of 1000mg are linked with statistically
significant six fold increased risk.10
In one of the studies on 1,572 women treated
with radiotherapy for cervical cancer and ovarian
cancer, five of the patients developed non
lymphocytic leukemia. The author (Marushi I)
concluded that there was a significantly
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increased risk of developing secondary leukemia


in patients treated with large doses of radiation
for other primary malignant neoplasms.11
Patients with secondary leukemias usually have
an initial complete of remission rate over 50% of
chemotherapy, but many of them may show
relapse after varying intervals of time Despite
intensive post-remission therapy only about 10%
may be long-term survivors.12
CONCLUSION

A rare case of secondary leukemia (Acute


Monoblastic leukemia) developing in a patient
with primary squamous cell carcinoma of the
cervix has been presented.
This case report and review of relevant literature
shows that there is a high risk of developing a
second cancer in the patient, treated for primary
malignant neoplasm. This risk is dependent on
the cumulative dose of both radiotherapy and
chemotherapy. There is increased risk of
secondary leukemia developing in patients of
carcinoma of the cervix treated with radiotherapy
and / or chemotherapy and this risk persists for
about twenty years following the therapy. It is
therefore
recommended that patient of
carcinoma cervix should with regular follow up
for a period of least twenty years after
completion of radiotherapy and/or chemotherapy.
REFERENCES

1. Giuseppe
Leone,
Luca
MeleAlssandroPulsoni, Francesco Equitani,
Livio Pagano. Cattedra di Ematologica. The
incidence
of
secondary
leukemia.
Haematologica 1999;84:937-45
2. Anil K Chatuvedi, Eric A Engels, Ethel S.
Glibert, Bingshu E. et al. Second Cancer
Among 104760 Survivors of Cancer;
Evaluation of long term risk. JNCI J Natl
Cancer Inst 2007;99(21):1634-43.
3. J A Whittaker and J A Holmen. Leukemia
and Related Disorder. 3rd E dn; 1998. pp22951.

4. Dipti R Samantha, Suredra N Senapati,


Praveen
K
Sharma,
AsitMohanty,
SangarikaSamantaray. Acute myelogenous
leukemia following treatment of invasive
cervix carcinoma. Journal of Cancer
Research and Therapeutic. 2009;5(4):302-04.
5. Margaret A Tucker, and Joseph FF.
Treatment-Related
Cancer
After
Gynaecologic Malignancy. Cancer 1987; 60:
2117-22. .
6. Lois B. Travis, Eric JH, Kjell B, Charles FL,
BetsyAKoher, Tom W. et. al.
Risk of
leukemia
after
PlatinumBased
chemotherapy for ovarian cancer. The New
England Journal Of Medicine 1999; 340:
351-57.
7. Boice JD Jr, Blettner M, Kleinerman
RA,StvallM, Molony WC,Enghom G, Austin
DE, Cookfair DL, Krementz ET et al.
Radiation dose and leukemia risk in patient
treated for cancer of cervix. J Natl Cancer
Inst 1987; 79(6):1295-311
8. MJ Ratain, LSKaminer, JD Bitran, RA
Larson, MMLe Beau, C Skosey et al.Acute
nonlyphocyticleukaemia
following
ectoposide and cisplatin combination
chemotherapy for advanced non small
carcinoma of the lung. Blood 1987;
70(5);1412-17.
9. Jason DW, Caryn M, St Chair , Israel
Deutsch, Williams M, Burke, Prakash G,
Xuming Sun et al. Pelvic Radiotherapy and
the risk of Secondary leukemia and Multiple
Myeloma. Cancer. 2010; 116: 2486-92.
10. Lois B. Travis, Michael Andersson, Mary
Gospodarowicz, et al. Treatment associated
leukemia following Testicular. Journal of
National Cancer Institute.2000; 92 (14):
1165-71.
11. Murohashi I. Leukemia in patient following
radiotherapy for malignant neoplasm in the
pelvic region. Leukemia Research 1985;
9(9): 1201-08.
12. Rowe JM. Treatment of Secondary leukemia.
Leukemia. April 2002;16(4):748-50
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DOI: 10.5958/j.2319-5886.2.2.008

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April-June

Received: 28 Feb 2013


Case report

Coden: IJMRHS

Copyright @2013

th

Revised: 20 Mar 2013

ISSN: 2319-5886

Accepted: 22nd Mar 2013

DYKE-DEVIDOFF-MASSON SYNDROME: A CASE REPORT


*More Sumeet S1, Jadhavar Avinash L1, Garkal Shailendra M1, Tewari Suresh C2
1

Senior Resident, 2 Professor and HOD, Department of Medicine, Pravara Rural Hospital & Medical
College, Loni, Ahmednagar, Maharashtra, India.
*Corresponding author email: sumeet_more2002@yahoo.com
ABSTRACT

Dyke-Davidoff-Masson syndrome (DDMS) is characterized by seizures, facial asymmetry, contralateral


hemiplegia and mental retardation. The characteristic radiologic features are cerebral hemiatrophy with
homolateral hypertrophy of the skull and sinuses. We report a case of DDMS in an 18 years old girl who
presented with a history of generalized tonic clonic seizures, hemiparesis and hemiatrophy of right
side.
Keywords: Dyke-Davidoff-Masson syndrome, Hemiatrophy, Seizure, Hemiplegia.
INTRODUCTION

Dyke-Davidoff and Masson described the plain


skull radiographical features of Dyke-DavidoffMasson Syndrome (DDMS) in 19331. This was
described in a series of 9 patients with
hemiparesis, seizures, facial asymmetry and
mental retardation. The radiographical features
of the skull were asymmetry, ipsilateral osseous
hypertrophy of the calvarium and hyperpneumatization of the sinuses2.
CASE REPORT

A 18 years old female with a history of epilepsy


from her 2 years of life, presented to us with
increasing frequency of generalized tonic-clonic
seizures of about one to two in a month and not
on any medication. The patient had normal
developmental milestones upto 2 years of age
when she had a seizure, followed by weakness in

right side of body with facial involvement. At


present she had facial asymmetry, right sided
hypertonia, brisk deep tendon reflexes, an
extensor plantar reflex and hemiatrophy on right
side.
Her
routine
haematological
and
biochemical investigations were within normal
limits. MRI of Brain revealed left cerebral
hemiatrophy with areas of gliosis secondary to
old ischemic or traumatic insult in frontotemporo-parieto-occipital region on left side,
thickening of bony calvarium on left hemi
cranium with hyperpneumatised ipsilateral
frontal sinus and mastoid air cells, contralateral
cerebellar atrophy. All these features are
suggestive of DDMS.
When the clinical features of cerebral
hemiatrophy are associated with the radiological
features of cerebral atrophy, osseous hypertrophy
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Int J Med Res Health Sci. 2013;2(2):297-300

of the calvarium and hyper-pneumatisation of the


sinuses dilatation, DDMS has to be considered3,4.
The pathogenesis of DDMS is thought to
originate from a childhood cerebral insult due to
trauma,
inflammation
or
vascular
malformations/occlusions of the middle cerebral
artery4, 5. In this case as described above, patient
had history of a seizure episode at 2 years of age.

Such insult occurring early in life causes


compensatory cranial changes like calvarial
thickening and sinus enlargement due to a
relative vacuum created by the hypoplastic
brain5-9. A possible etiological relation between
cerebral atrophy and seizures has been reported
in two different studies from India 7,8.

Fig 1: Unilateral cerebral atrophy on left side with Fig 2: Ipsilateral osseous hypertrophy of the calvarium
contralateral cerebellar atrophy.
and hyper-pneumatization of the sinuses

Fig 3: Left cerebral hemiatrophy with thickening of bony calvarium on left hemi-caranium
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DISCUSSION

DDMS is a rare condition characterized


clinically by variable degree of facial asymmetry,
seizures, contralateral hemiparesis, mental
retardation and learning disabilities in association
with the classical radiological findings of
asymmetry of cerebral hemispheric growth with
atrophy on one side, ipsilateral osseous
hypertrophy and hyperpneumatization of
sinuses1,10-12. Both sexes and any of the
hemispheres may be affected but male gender
and left hemisphere involvement are more
frequent13. Age of presentation depends on time
of neurologic insult and characteristic changes
may be seen only in adolescence. The clinical
findings may be of variable degree depending on
the extent of the brain injury. Varying degree of

Fig 4: MR Angiography suggestive of paucity of branches


from M2 and M3 segments of Lt. middle cerebral artery.

atrophy of one half of the body, sensory loss,


speech and language disorder, mental retardation
or
learning
disability
and
psychiatric
manifestations like schizophrenia may also be
present. In this case, the left hemisphere is
smaller in size with prominence of sulcal space,
sylvian fissure alongwith resultant mild dilatation
and pulling of ipsilateral ventricle suggestive of
areas of gliosis secondary to old ischemia or
traumatic insult and chronic wallerian
degeneration of axons in left cerebral peduncle.
MR Angiography is suggestive of paucity of
branches from M2 and M3 segments of left
middle cerebral artery. A proper history,
thorough clinical examination and radiologic
findings provide the correct diagnosis.

Fig.5: Chronic wallerian degeneration of axons in


left cerebral peduncle.

CONCLUSION

Although Dyke- Davidoff-Masson syndrome is a


rare condition but other differential diagnosis to
be considered in a patient of cerebral
hemiatrophy is Sturge-Weber Syndrome, some
brain tumors, Silver Syndrome, as well as

Conditions, that are associated with unilateral


magelancephaly as in the linear-nevus syndrome.
A proper history, thorough clinical examination
and its typical radiological findings can derive its
correct diagnosis.
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REFERENCES

1. Dyke CG, Davidoff LM, Masson LB.


Cerebral hemiatrophy with homolateral
hypertrophy of the skull and sinus. Surg
Gynecol Obstet 1933; 57: 588-600.
2. George Peter, Shenoy Basti Ram. DYKEDAVIDOFF-MASSON SYNDROME: AN
UNCOMMON CAUSE OF REFRACTORY
EPILEPSY IDENTIFYIED BY NEUROIMAGING. Journal of Clinical and
Diagnostic Research [serial online] 2011
August [cited: 2013 Mar 11 ]; 5:833-34.
3. Ono K, Komai K, Ikeda T. Dyke-DavidoffMasson syndrome manifested by seizure in
late childhood: a case report. J Clin Neurosci.
2003; 10:367-71.
4. Aguiar PH, Liu CW, Leito H, Issa F, Lepski
G, Figueiredo EG, Gomes- Pinto F, Marino J.
MR and CT imaging in the Dyke-DavidoffMasson syndrome. Report of three cases and
contribution to pathogenesis and differential
diagnosis. Arq Neuropsiquiatr.1998; 56: 80307.
5. Afifi A K, Godersky J C, Menezes A et al.
Cerebral hemiatrophy, hypoplasia of the
internal carotid artery and Intracranial
aneurysm Arch Neurol 1987; 44: 232-35.
6. Parker J C, Gaede J T. Occurrence of
vascular anomalies in unilateral cerebral
hypoplasia cerebral hemiatrophy. Arch
Pathol Lab Med 1970; 90: 265-70.
7. Nair KP, Jayakumar PN, Taly AB,
Arunodaya GR, Swamy HS, Shanmugam V.
CT in simple partial seizures in children: a
clinical and computed tomography study.
Acta Neurol Scand 1997; 95:197-200.
8. Garg RK, Karak B. Cerebral hemiatrophy: a
possible etiological relation with febrile
seizures.Indian Pediatr 1998; 35: 79-81.
9. Sener RN, Jinkins JR. MR of craniocerebral
hemiatrophy. Clin Imaging l992; 16: 93-97.

10. Tasdemir HA, Incesu L, Yazicioglu AK,


Belet U, Gungor L. Dyke Davidoff Masson
syndrome. Clin Imaging 2002; 26: 13-17.
11. Sharma S, Goyal D, Negi A, Sood RG,
Jhobta A, Surya M. Dyke-Davidoff Masson
syndrome. Indian J Radiol Imaging 2006: 16:
165-66.
12. Dix JE, Coil WS. Cerebral hemiatrophy:
Classification on the basis of MR Imaging
findings of mesial temporal sclerosis and
childhood febrile seizures. Radiology 1997;
203: 269-74.
13. Manas R Behera, Sibabrata Patnaik and
Ashwini K Mohanty. Dyke-Devidoff-Masson
Syndrome. J Neurosci Rural Pract. 2012 SepDec; 3(3): 41113.

300

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DOI: 10.5958/j.2319-5886.2.2.007

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April-June

th

Received: 28 Feb 2013


Case report

Coden: IJMRHS
nd

Revised: 22 Mar 2013

Copyright @2013

ISSN: 2319-5886

Accepted: 24th Mar 2013

TUBERCULOUS PAROTID LYMPHADENITIS IN A HIV POSITIVE PATIENT: A CASE


REPORT
* Garkal Shailendra M1, More Sumeet S1, Jadhavar Avinash L1, Tewari Suresh C2
Senior Resident, 2 Professor and HOD, Department of Medicine, Pravara Rural Hospital & Medical
College, Loni, Ahmednagar, Maharashtra, India.
1

*Corresponding author email: drshailendragarkal@gmail.com


ABSTRACT

Tuberculosis is a chronic, granulomatous disease. Primary lesion usually occurs in the lung. Extra
pulmonary infection commonly involves head, neck and the abdomen. In an attempt to highlight an
uncommon presentation, we document a case of extra pulmonary tuberculosis in the parotid gland
(tuberculous parotitis), without evidence of pulmonary tuberculosis. A 15 year old HIV positive female
patient was reported with chief complaint of repeated history of loose stools, vomiting, and swelling in
the left parotid region and difficulty in opening of the mouth. She was diagnosed to be having
tuberculosis of parotid gland after Ultrasonography (USG), fine needle aspiration cytology (FNAC),
histopathological examination and was treated medically.
Keywords: HIV, Tuberculosis, Tuberculous Parotitis.
INTRODUCTION

Tuberculosis is a chronic, granulomatous disease


commonly affecting the lungs. It is one of the
leading infectious diseases in the world. India
accounts for nearly one third of the global burden
of tuberculosis.1 One third of the 42 million
people living with HIV/ AIDS worldwide are coinfected with tuberculosis. Approximately about
two million HIV infected persons living in India
are coinfected with tuberculosis.
Tuberculosis is one of the main causes of death
in HIV positive patients involving multiple
organs, particularly the lungs. Tubercular
involvement of parotid gland is extremely

unusual even in countries with high incidence of


this infection such as India. Less than 200 cases
have been reported since the first description of
this condition by Von Stubenrauch in 1894.2
CASE

A 15 yrs old female, patient reported with the


chief complaint of repeated history of loose
stools and vomiting since 1 month and swelling
in the left parotid region and difficulty in
opening of mouth since 15 days.
Medical history revealed that patient was
diagnosed as HIV positive one year ago and she
was on antiretroviral therapy.
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Int J Med Res Health Sci.2013;2(2):301-304

Physical examination revealed a soft to firm


nonmobile, nontender swelling which was 33
cm in diameter. It was extending from pinna to
the outer canthus of the eye and down upto the
lower border of the mandible. There was no
facial nerve involvement and cervical
lymphadenopathy. Intraoral examination did not
reveal any significant findings.
Her routine haematological and biochemical
investigations showed raised ESR and WBC
count. X-ray chest was normal. USG parotid
revealed multiple heterogeneous moderately
enhancing soft tissue density lesions in
superficial as well as deep lobe of parotid gland
on left side suggestive of intra parotid lymph
nodes.

Fig 1 : Anterior view of patient showing left parotid


enlargement

FNAC of left parotid showed moderately cellular


smears comprised of inflammatory cells mainly
lymphocytes, macrophages and some epitheloid
cells. Background showed hemorrhage and
necrosis.
Suggestive
of
granulomatous
inflammation.
A final diagnosis of tuberculosis of parotid gland
in a HIV positive patient was made. Patient was
referred to DOT centre where she was started on
antitubercular drugs under CAT- I. For the initial
2 months she was put on, Isoniazid, Rifampicine,
Ethambutol and Pyrazinamide on alternate days.
One month after initiation of therapy parotid
swelling was reduced.

Fig 2: Anterior view showing reduced swelling after


antitubercular therapy

Fig 3,4 :Ultrasonography of parotid gland showing multiple intra parenchymal lymph node

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Fig 5: Fine needle aspiration cytology showing Granulomatous lesion with epitheloid cells and lymphocytes.
DISCUSSION

Extrapulmonary forms of tuberculosis account


for approximately 20% of overall active
tuberculosis, but the salivary glands appear to be
rarely affected. This may be due to the inhibitory
effect of saliva on mycobacteria.3 Tuberculosis of
the parotid gland is uncommon and less than 200
cases have been reported since the first
description of this condition by Von Stubenrauch
in 1994. Tuberculous parotitis occurs in 2.5% 10% of parotid gland lesion even in countries
where the disease is endemic such as India.3
Tuberculosis of parotid glands may be clinically
misdiagnosed as parotitis, Warthins tumours,
mixed tumours and sometimes malignant
tumours. Histo-pathologically there are two types
of Granulomatous parotitis: (i) localised disease
with a solid mass corresponding to tuberculosis
in the lymph node of the parotid, (ii) diffuse
disease involving parenchyma with nodules of
irregular size and consistency.3
The pathogenesis of parotid tuberculosis remains
unclear. Involvement of the parotid gland and
lymph nodes may occur in two ways: (i) a focus
of mycobacterial infection in the oral cavity
liberates the mycobacterium which ascends into
the salivary gland via its duct or passes to its
associated lymph nodes via lymphatic vessels.4,5
(ii) second pathway involves hematogenous or

lymphatic spread from a distant primary lung


focus.3,5,6
Tuberculous intraparotid lymphadenopathy has
been described by Ubbi et al among others.7
similar finding was observed in our case. HIV
infection is considered as the most prominent
risk factor in acquiring active tuberculosis and
tuberculosis involving the parotid gland.8
Diagnosis was invariably established on the basis
of histopathological examination. In parotid
lesions FNAC has a sensitivity of 81- 100% and
specificity of 94-100%.
REFERENCES

1. Park K: Tuberculosis: epidemiology of


communicable diseases. In: Parks Text Book
of Preventive and social medicine, 18th Edn.;
Banarsidas Bhahot Publishers Jabalpur,
2005;pp:146 -47.
2. Von Stubenrauch L. Einen Uberfall von
tuberculoser
Parotitis. Arch
Klin
Chir. 1894;47:2632.
3. Birkent H, Karahatay S, Akcam T, Durmaz
A, Ongoru O: Primary parotid Tuberculosis
mimicking parotid Neoplasm: A case report.
Journal of Medical Case Reports, 2008; 2:6263

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4. Frank J. Primary tuberculosis of the parotid


gland. Ann Surg 1902;36:945-50.
5. Lee IK, Liu JW. Tuberculous parotitis: case
report and literature review. Ann Otol Rhinol
Laryngol 2005;114:547-51.
6. Hamdan AL, Hadi U, Shabb N. Tuberculous
Parotitis: a forgotten entity Otolaryngology Head
Neck Surg. 2002; 126:581-82
7. Ubbi SS, Neoptolemos JP, Walkin DFL.
Incidence and diagnosis of parotid gland
Tuberculosis in Asians in Leicester. Br. J.Surg.
1988;75:313.
8. Rinaggio J: Tuberculosis. Dental clinics of North
America, 2003; 47(3):449-65.

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DOI: 10.5958/j.2319-5886.2.2.006

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April-June

th

Received: 5 Mar 2013


Case report

Coden: IJMRHS
th

Revised:24 Mar 2013

Copyright @2013

ISSN: 2319-5886

Accepted: 26th Mar 2013

OSTEOCHONDROMA ON DORSAL SURFACE OF THE SCAPULA IN 11 YEARS OLD


CHILD- A CASE REPORT
Yadkikar SV1, Yadkikar VS 2
1

Assistant Prof, 2Prof. & Unit Head, Department of Orthopaedics, Rural Medical College, Pravara
institute of Medical Science (DU), Loni, Maharashtra, India
ABSTRACT

Osteochondroma is the most common benign neoplasm of skeleton with an incidence of 30-40%
amongst benign bone tumor. Its usually seen in the second decade of life common sites of occurrence
are distal end of femur, proximal tibia but scapula is an unusual sight to occur with an overall incidence
of 3-4 % worldwide. Common presenting complaints are swelling, pain, pseudo winging. Many times it
may be presented as painless lump. As per radiological image there are two types-Sessile and
pedunculated. Plain X-Ray in AP and Lateral View are Diagnostic for this lesion. On X-Ray it appears
to be growth arising from parent bone. Investigation like CT scan is helpful in delineating lesions on
either surface of scapula. Grossly it appears as an irregular grayish white mass with a cartilaginous cap
which is characteristic of the lesion. Complete Excision is the treatment of choice. However recurrence
and malignant transformation are not unknown. Usually following a complete excision there is a full
functional recovery. Uncommon site of occurrence and peculiar symptoms of the patient stimulated us
to write this case report.
Keywords: Osteochondroma of scapula, Benign bone tumour
INTRODUCTION

Osteochondroma is
common benign bone
1-4
tumor , with an overall incidence of about 3040 %4. The cartilage cap covering tumor is
characteristic feature4. It is said that it arises
because of a congenital defect in perichondrium4.
Its frequently seen in the first two decades of
life4. Common sites of occurrence are around the
distal end of femur, proximal tibia, proximal
humerus4, but scapula is an uncommon sight to
occur1, 2,4. Many articles are available stating
presence of osteochondroma on Ventral surface
of scapula associated with pulmonary

complications1. Dorsal surface of scapula is a


rare sight. Many times lesion are asymptomatic
but patient may present with complaints like pain
, pseduowinging4. Pain could be due to irritation
of overlying soft tissues, bursitis of overlying
swelling, fracture through the stalk of lesion,
malignant transformation3, 4. Plane X-ray of chest
in PA & Lateral Scapular view is often
diagnostic2. However, the diagnosis of lesions on
locations like ventral surface of scapula, Ilium,
spine- CT Scan & MRI Scan are helpful for 2,3,4.
Histopathology confirms the diagnosis2,3,4.
Complete excision is treatment of choice1,2,4.
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But recurrence & malignant transformation can


occur4. In this 11 year old female patient unusual
site of occurrence (dorsal surface of scapula) &
peculiar symptoms of inability to sleep only in
supine position stimulated us to write this case
report
Case report
11 years old female child presented with chief
complaints of swelling on the left side of the
upper back and inability to sleep only in supine
position due to pain since 1 year. It was
gradually progressive & was not associated with
any history of trauma, fever, weight loss or
history of similar complaints in the past.
On examination of the left scapular region: It
was single, well defined, Oval swelling on the
dorsal surface of left scapula away from the
midline & away from the lateral border of
scapula, measuring approximately 3cmx 2cm, it
was located near centre of scapular blade,
overlying skin was normal, no dilated veins were
seen on the surface of swelling, there was no
local rise of temperature, it was non tender, firm
to hard in consistency with well defined margins.
It was attached to underlying structures (scapula)
and not to the overlying soft tissues and skin. It
was non mobile, non translucent. It was not
associated with restriction of left shoulder
movements. There was no sensory or motor

deficit in left upper limb. There was no evidence


of any other swelling in the body.
Chest X-Ray in PA and Scapular lateral views
were taken which showed a Well defined
lobulated sessile swelling arising from dorsal
surface of the left scapula. The swelling was very
well visualized on lateral scapular view. Both
corticocancellous portions of swelling were well
blended with the corticocancellous host bone.
There was no evidence of any pathological
fracture. As our patient was very poor
socioeconomic status, therefore CT scan or MRI
of the left scapula could not be done.
Provisional Diagnosis of Exostosis and
osteochondroma was made. After which Patient
was subjected to excisional biopsy under general
anesthesia. The patient was given right lateral
position. Curvilinear incision was given over the
swelling and it was exposed by soft tissue
dissection of overlying muscle and fascia. It was
excised in toto. On Physical examination the
swelling was of grayish white in color, irregular
in shape and firm to hard in consistency. The
dimensions of the swelling were 4x2x1 cm and it
weighed 20 gm. Cut surface was grayish white in
color and it was having a cartilaginous cap.
Histopathology confirmed the diagnosis of
osteochondroma.
Postoperative period was uneventful and was
not associated with restriction of left shoulder
movement. During the follow up of 1 year there
was no evidence of recurrence.

Fig. 1&2 Preoperative clinical pictures


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Fig.3:Intra operative procedures

Fig.5: Histopathology (400 X High power)

Fig.4: Depicting dimensions of the excised mass

Fig.6:Post operative final range of motion left shoulder

DISCUSSION

Osteochondroma is one of the most common


benign bone tumor2-4. It is postulated that it is a
developmental anomaly of bone resulting in
formation of exophytic outgrowth from surface
of bone4. This tumor has a peculiar cartilaginous
cap on its surface4. It has about 30-40%
incidence2,4. It is frequently seen in first &
second decades of life4 with common sites of
occurrence are distal end of femur, proximal
tibia, proximal humerus4. However scapula,
Ilium, ends of the clavicle, carpal &tarsal bones
are rare sites of occurrence4. Frequently
osteochondromas are asymptomatic but patient
may present with cosmetic complaints2,4.
However there maybe complaint of pain due to
mechanical irritation of surrounding muscles &
soft tissues, bursitis around lesion, fracture

through the stalk of lesion or malignant


transformation2-5
Overall incidence of scapular osteochondroma is
around 4% 2-4. Patient usually have cosmetic
complaints but may also complain of pain &
psuedowinging2. Peculiar symptom of pain only
on lying down in the supine position as in this
case might be the presenting complaint. There
are numerous articles about osteochondromas on
ventral surface of scapula associated with
pulmonary
complications3.
However
osteochondromas on dorsal surface doesnt have
any pulmonary complications. They are usually
solitary 4. Standard AP & Lateral scapular views
are the investigations of choice4. On X rays they
present as an irregular mass protruding from the
surface of host bone4. It could be sessile or
pedunculated5. Corticocancellous bone of tumor
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Int J Med Res Health Sci.2013;2(2):305-308

is continuous with corticocancellous bone of


In
locations
like
scapula,
host2,4.
osteochondromas usually arise near the
cartilaginous border of bone4. For lesions of the
spine, ventral surface of scapula CT Scan&MRI
are better investigation modalities1,4. There is a
better evaluation of cartilage cap thickness (2mm
or more) on MRI SCAN4. When thickness of
cartilage cap increases more than 2mm its a
probable indicator of malignant transformation4.
Lesions could be differentially diagnosed as
chondrosarcoma,
myositis
osscificans1,4.
Histopathology confirms the diagnosis, which
shows areas of endochondral ossification on the
basal surface of hyaline cartilage4. Grossly it
presents as an irregular bony mass with grayish
cartilage cap normally measuring 1-3mm in
thickness4
Growth of the tumor halts after the period of
skeletal maturity4, so for asymptomatic lesions,
no treatment is required4. But for symptomatic
lesion complete excision is the treatment of
choice1-4. However recurrence & malignant
transformation of the lesion cannot be overruled4
CONCLUSION

Scapula is one of the rare site of occurrence for


osteochondroma. For complaints of swelling
over the scapula associated with difficulty in
lying down only in supine position ,
osteochondroma can be considered as one of
differential diagnosis.
REFERENCES

1. Frost, Parada, Manoso, Edward A, Paul B.


Scapular Osteochondroma treated with
surgical excision: Orthopaedic surgery
service
Madigan
Army
Medical
centre,Tacoma,Washington US. Pubmed
Orthopaedic 2010;33(11):804
2. Mahajan S, Mahajan N, Paranjit Singh,
Shikari AB.Scapula a rare Localization of
osteochondroma.
Internet
journal
of

orthopaedic Surgery. 2009; 14(1): DOI 10.


5580 /2930
3. Marcia F, Blacksin And Joseph B Neoplasm
Of Scapula. American Journal Of
Roentgenology.2000, 174 (6): 1729-35
4. Current concepts in bone & soft tissue
tumors, Textbook of Orthopaedic Oncology
by Dr Ajay Puri & Agarwal MG. 2nd ed ,
Publisher Paras medical books Pvt.Ltd.
Hyderabad ,Chapter 7. Benign bone Lesion.
Pg no72-77
5. Kyoji O, Kel T, Ryuji S, Naoto H. Large
bursa
formation
associated
with
osteochondroma of scapula: A case report &
review of the literature. Japanese journal of
clinical oncology 1999;29(7); 356-360
6. Pongkripetch M, Sirikilchayanonta V.
Analysis of bone tumours in Ramathibodi
Hospital Thailand during 1977-1986: Study
of 652 cases.J Med Assoc Thai 1989; 72:
621-28.
7. Tomo H, Ito Y, Aono M, Takaoka K.Chest
wall
deformity
associated
with
osteochondroma of the scapula: a Case report
and review of the literature.J Shoulder Elbow
Surg.2005;14(1): 103-106
8. Samilson RL, Morris JM, Thompson RW.
Tumours of scapula.Clin Orthop. 1968;58:
105-15
9. Christmas OD,Goldernberg RR.Untreated
Solitary Osteochondroma.Report of two
cases. J bone Joint Surg Am.1968;50(3): 50812
10. Essadki B, Moujtahid M, Lamine A, Fikry,
Essadki O, Zryouil B. Solitary ost
eochondroma of limbs:Clinical review of 76
cases and pathogenic hypothesis. Acta
Orthop Belg. 2000;66: 146-53.

308

Yadkikar et al.,

Int J Med Res Health Sci.2013;2(2):305-308

DOI: 10.5958/j.2319-5886.2.2.005

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April-June

Received: 20 Feb 2013


Case report

Coden: IJMRHS
nd

Revised: 22 Mar 2013

Copyright @2013

ISSN: 2319-5886
th

Accepted:28 Mar 2013

BILATERAL BREAST INVOLVEMENT IN ACUTE MYELOID LEUKEMIA.


*Hakeem A1, Mandakini BT1, Asif K2, Firdaus2, Shagufta1
Department of Pathology, 2Department of Medicine, Khaja BandanaWaz Institute of Medical Sciences,
Gulbarga, Karnataka, India
1

*Corresponding author email: attar.hakeem@gmail.com


ABSTRACT

Breast involvement by leukemic infiltration is usually bilateral, but may be unilateral. Clinically patients
can present with either single or multiple masses, or with diffuse breast engorgement, with or without
nodularity. The affected patients are predominantly young adults. We present a case of an adolescent
girl with acute myeloid leukemia having bilateral breast infiltration by leukemic cells.
Keywords: Breast, Acute myeloid leukemia, Bilateral
INTRODUCTION

Involvement of breasts with haemato,logic


malignancy is uncommon1,2,3. It is most often
due to lymphoma, less frequently leukemia and
rarely multiple myeloma. Lymphomatous and
leukemic
breast
involvement
constitutes
approximately 0.25% of all breast tumors. All
forms of leukemia have been reported to occur in
breasts3. Breast infiltration by leukemic cells
may occur either on presentation or during
relapse of leukemic disease or may also develop
in women who undergo radiation therapy for
breast carcinoma3. We reported a case of a 13
year old girl, AML M2, with bilateral leukemic
breast infiltration.
CASE

Patient was an adolescent girl, aged 13 years,


who had attained menarche 1 year ago. Her main

complaints were generalized weakness and


bilateral painful breast engorgement of 4 months
duration. She also complained of severe
backache, since 1 year for which she consulted
an orthopaedicean, who referred her to a
physician and routine investigations were carried
out. As the patient was unaffordable she was not
given timely treatment and patient expired within
2 weeks.
Lab Findings: Report findings were Hb-3gm,
Platelets-6000/cumm, Peripheral smear showed
Acute Myeloid Leukemia M2. FNAC of both
breasts were done and the smears revealed
myeloid blasts along with epithelial cells of the
breasts. She was diagnosed as a case of AML
M2 with bilateral leukemic breast infiltration and
was referred to cancer centre

309

Hakeem et al.,

Int J Med Res Health Sci.2013;2(2):309-311

.
Fig.1: Photograph showing bilateral tense breast engorgement

Fig. 2: Blood smear showing myeloid blasts


(FEILDS STAIN,100X)

Fig.3: FNAC smear showing myeloid blasts along


with epithelial cells of breast(MGG,100X)

DISCUSSION
Breast involvement by leukemic infiltration is
usually bilateral, but may be unilateral. Clinically
patients can present with either single or multiple
masses or with diffuse breast engorgement, with
or without nodularity3. Myeloid sarcoma is
described as a tumor mass consistency of
myeloblasts or immature myeloid cells involving
extramedullary tissues. It can be initial
manifestation of myeloproliferative disorders,
MDS, or relapse of previously treated AML6, 8, 9.
Manteleone et al. reported a case of an 11.5 year
old girl, with M1 AML who had isolated
extramedullary relapse developed in both breasts,
12 months after diagnosis and 7 months off
chemotherapy4.
Sato E et al reported a case of CD56 positive

AML M1, with t(16;21) (p11;q22)presenting


an extramedullary tumor in the right breast at
relapse. Because of the high occurrence rate of
relapse, they consider various additional
chromosomal abnormalities of CD56 as
prognostic factors of this condition5. Satomi
Asai, assessed the ultrasonographic appearance
and clinical implication of bilateral breast
involvement in three cases of acute leukemia
L1, L3 & M1 of the FAB subtype. Their studies
suggested bilateral breast involvement occurred
as a part of the diffuse and generalized leukemic
process7.
Granulocytic sarcoma also known as one variant
of myeloid sarcoma in the WHO classification,
in an extramedullary solid tumor comprised of
310

Hakeem et al.,

Int J Med Res Health Sci.2013;2(2):309-311

myeloid precursor cells. The most common form


is granulocytic sarcoma composed mainly of
myeloblastsn
neutrophils
and
myeloid
precursors. The less common form is monoblastc
sarcoma. This tumor occurs commonly in patient
with AML and less common in patients with
MDS or CML. The incidence of granulocytic
sarcoma varies from 3-9% I AML patients and
most frequently occur in AML with maturation
(M2). However other subtypes including FAB,
M4 or M5 or M7 have also been described. The
most common sites of involvement include
bones, soft tissues, lymphnodes and skin.
However breast involvement is rare. It most
often represents relapse, or the initial
presentation of AML; in that case, granulosytic
sarcoma is misdiagnosed most frequently as a
ltymphoma or sarcoma9
CONCLUSION
Breast involvement in acute myeloid leukemia is
rare in young children and adolescent females.
However regular breast examination should be
performed as a part of routine follow up in all
girls with AML. In any patient with a known
malignancy, any enlarging breast mass, even one
with a reassuring benign sonographic
appearance, must be investigated promptly,
initially with FNAC or core-needle biopsy.

2. Orell RS, Sterret FG, Darrel Whitaker.


Manual and Atlas of Fine needle aspiration
cytology. Breast. Churchill Livingstone;
1993.162-65
3. Khoury NJ et al. Letters to editor. Bilateral
Breast involvement in Acute Myeloid
Leukemia. Eur Radiol. 2000;10:1031
4. Manteleone et al. Letters to editor. Bilateral
Breast relapses in Acute Myeloid Leukemia.
J Pediatr Hematol Oncol 2001;23(2) :126-29.
5. Sato et al. CD 56 positive Acute Myeloid
Leukemia presenting an extrtamedullary
tumor in the right breast at relapse.
2002;43(7):560-66.
6. Slavcheva V, Lukanov T, Tzvetkov N. Two
cases of extramedullry myeloid tumor in
patients with continuous remission of Acute
Myeloid Leukemia. 2008; 13(4):589-92
7. Satomi Asai at al. Letters to editor.
Ultrasonographic appearance and clinical
implication of bilateral breast infiltration with
leukemic cells.
8. Jelic puskaric B et al. Myeloid sarcomka
involving the breast. Coll Antropol.2010;
34(2)641-44
9. Ben yousuf Y et al. Acute myeloid leukemia
with synchronous granulocytic sarcoma of
the breast and spine. Clinical and
experimental medical sciences, 2013;1(2):4958.

ACKNOWLEDGEMENT

The work was indeed a mammoth task to


accomplish and would not have been possible
without active co-operation, constant strategic
support and encouragement by our beloved
PRESIDENT- (Khaja Bandanawaz Institute of
Medical Sciences) -DR.SYED SHAH KHUSRO
HUSSAINI.
REFERENCES

1. Wintrobes Clinical Haematology. Unusual


presentation of Acute Leukemias.1998.10th
edn.2272-19
311

Hakeem et al.,

Int J Med Res Health Sci.2013;2(2):309-311

DOI: 10.5958/j.2319-5886.2.2.004

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com
th

Volume 2 Issue 2 April-June

Received: 20 Jan 2013


Case report

Coden: IJMRHS

Copyright @2013

nd

Revised: 22 Feb 2013

ISSN: 2319-5886
th

Accepted:28 Feb 2013

UNILATERAL BIFID URETER AND ITS CLINICAL SIGNIFICANCE - A CASE REPORT


*Ansari Mohammad Mujahid, Joshi DS, Rahman MA.
Department of Anatomy, LSBRKM Government Medical College, Jagdalpur, Dist.Bastar Chhattisgarh,
India.
*Corresponding author e-mail: mohammad_ansari2001@yahoo.com
ABSTRACT

Context: Congenital anomaly is commonly found in the urinary system in which collecting system is
frequently encountered. Among other type bifid ureter is one of the common variations. Objective: To
describe and analyze the clinical and the embryological significance of the unilateral bifid ureter.
Design: The presence of unilateral bifid ureter was seen as an incidental finding during dissection of the
anatomy of an adult male cadaver. The cause of such variation is a fusion of ureteric bud during
intrauterine development. Outcome: The knowledge of such relationship is important for a surgeon
during renal surgeries. This is one of the rare case reported with no other renal and collecting system
congenital anomalies found with left sided bifid ureter. Conclusion: Surgeons and Nephrologists must
keep the unilateral bifid ureter in their mind while making differential diagnosis of ureteric calculus.
Surgery is nearly always required in the bifid ureter to cure the problem when associated with
complication such as reimplantation surgery in vesicoureteric reflux, uretropyelostomy in saddle reflux
bifid ureter. The unilateral bifid ureter may be similar to the collecting system obstruction in the form of
ureteric stone and utmost care should be taken by Surgeons during renal and ureteric calculi surgeries.
Keywords: Isolated bifid ureter, Reimplantation surgery, Congenital anomaly, Uretropyelostomy.
INTRODUCTION

Congenital
anomalies
of
urinary
and
reproductive system are very common and
around 10% of newly born baby are encountered
with such anomalies. Enormous diseases are
found in the urinary system of which 40% are
related to congenital anatomical variation.
Ureteric duplication may be partial or complete.
Complete duplications are less common where
two ureter drain one kidney and have separate
orifices into the urinary bladder known as

duplications of ureter and occurs 1 in 160


individuals1. Incomplete duplication is known as
bifid ureter. Various diseases are found in
relation with bifid ureter congenitally of which
gonadal dysgenesis2 is one in which
differentiation of kidney is abnormal and
associated upper urinary tract anomalies are
found which accounts around 88.8%. Patients
with double ureter may be accompanied by other
ureteral anomalies such as ectopic ureter and

Ansari et al.,

Int J Med Res Health Sci. 2013;2(2): 312-316

312

have an increased risk of developing urinary tract


infection,, pain, hydronephrosis and stone
formation3.. Duplications of the ureter in adults
are often symptomless, but in children the risk of
infection is increased twentyfold4. In the
available literature, most authors have reported
their experiences of single to few cases each. The
finding of double ureters in members of the same
family is a rare occurrence, but after a thorough
investigation and detail studies of families of
children with a duplex urinary tract, it was
suggested that the inheritance of this anomaly
was by an autosomal dominant gene1.
Duplication of pelvicalyceal
pelvicalyceal system is among the
common anomalies of the urinary tract,
tract, majority
is unilateral. Bilateral duplication is less common
than unilateral duplication and similarly lower
urinary tract abnormalities are less common than
upper pelvicalyceal system anomalies which
occurs due to metanephric diverticulum
abnormal development.5

Testicular vessels

CASE REPORT

The present case was found as bifid ureter during


routine dissection on the left side of male
cadaver approximately
approximately 60 years of age.
age. The
upper two separate limbs of bifid ureter were
emerging out from the pelvis (hilus) of kidney as
a separate entity.
entity The bifid ureters were running
lateral to the vasculatures of posterior abdominal
wall (Fig.1).As
(Fig. ).As the two lim
limbs
bs of bifid ureter
descends down in the posterior abdominal wall it
runs parallel to the main vasculature lower
abdomen near pelvic cavity. After entry into the
pelvic cavity near the opening of bifid ureter into
the urinary bldder (2-3cm
3cm near to vesicoureteric
vesicoureteric
junction) both the limbs of bifid ureter fuses and
form a single ureter. No abnormality was seen
near the opening of ureter into urinary bladder
(Fig.2).
(Fig. In the pelvic cavity near the opening of
ureter into the urinary bladder (Fig.3).
(Fig. The ureter
on the right side was found to be normal (Fig.4).
(Fig.

Rt Ureter

Ureter 1

Ureter 2
Fig:1. Bifid Ureter and relation with Abdominal Vasculatures Fig 2. Right Single Ureter and Left Bifid Ureter

Fusion of Ureter 1 & 2

Opening of single ureter into urinary baldder


Fig 3. Fusion of Ureter 1&2 and opening of into Urinary Bladder

Fig.4 Complete View of Right and Left Side Ureters

313

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Int J Med
ed Res Health
lth Sci
Sci. 2013;2(2)
3;2(2): 312-316
316

Examination of other abdominal and pelvic


viscera and other structure revealed no other
morphological abnormality.
DISCUSSION

Complete duplications are less common where


two ureter drain one kidney and have separate
orifices into the urinary bladder known as
duplication of the ureter. Duplication in the
ureter is either complete or incomplete. This
variation having an incidence around 3.0%6. As
far as gender prevalence were compared in
females occurrence was 5 times more common
than in males.7 Incomplete duplication is
commonly known as bifid ureter whose
occurrence three times more common than a little
rare variety of complete duplication8.Right sided
duplication ois more frequent than left sided9.The
incidence of congenital anomalies of urinary
system in newborn babies ranges from 8-10%10
and duplication of the upper urinary tract is one
of the commoner anomalies and occurs in about
1 in 160 individuals11.The reported incidence of
bifid ureter varies widely. It depends whether the
survey based on autopsy or clinical data. Two
large autopsy series have provided data regarding
partial or complete ureteral duplication by Nation
and Campbell, in 16,000 autopsies identified 230
cases. The reported incidence in general is 1 in
147 or 0.68%11. Campbell in his personal series
of 51,880 autopsies 342 cases was identified. The
reported incidence in general is 1 in 152 or
0.66%11.Combining Nations and Campbell
autopsy series the projected incidence of
duplication is 1 in 125 or 0.8 %11. It has been
suggested by many researchers that bifid ureter is
associated with genetic mutation of PAX2 gene
which is responsible for development of kidney
and ureter12. According to studies of Russell13 et
al described the incidence of ureteral duplication
3% on routine urography. Angulo14 et al., stated
the association of bifid ureter with one serious
congenital
abnormality
i.e.
congenital
15
hydronephrosis. Bhandarker et al., contra lateral
orthotopic quadrafid ureter, and noted they gave

the close association of the bifiid ureter with


contra -lateral orthotopic quadrafid ureter.
Goltzs16 syndrome high cephalic kidney and
duplication of the pelvis, unilateral pulmonary
hypoplasia 17,18 had been stated by many research
workers that above mentioned diseases and
syndromes had a strong link with bifid ureter.
In the present case report of unilateral bifid
ureter we found on the right side without any
gross and congenital abnormalities. Buslingers
M19 have reported the bifid ureter with
complication such as frequent urinary tract
infection, calculi, uretero ureteric reflux, ureteric
stenosis ,urinary lithiasis, pyelonephritis, nonfunctioning of kidney units but in our case no
gross surgical abnormality observed. Rege20 et
al., have reported the incidence of bifid ureter
more common in Females but in my case report
the cadaver is a male human being.
Developmental basis: The occurrence of bifid
ureter has a very strong link with the defective
intrauterine
development.
The
basic
developmental error is division of ureteric bud at
penetration into the metanephric tissue which
give rise to the formation of either duplication of
ureter or bifid ureter. Bifid ureter is a
symptomatic condition and usually observed
during renal surgeries, autopsy or anatomical
dissection. It may be diagnosed when there are
reflux symptoms irritates the patient and then
undergoes
for
thorough
urinary
tract
investigation
for,
urinary
calculi
21
et al., pyelonephritis and
Giannokopoulos
uretero- hydronephrosis Chalouhy 22 et al.,
present case the individual had lived through 50
to 60 years of life without a surgical intervention
related to complication of bifid ureter.
CONCLUSION
Usually the cases of bifid ureter may be detected
during a routine investigation or an incidental
finding at autopsy and the majority of the cases
remain asymptomatic and if a complication
occurs
surgical
intervention
becomes
necessary.In the present case the individual is
314

Ansari et al.,

Int J Med Res Health Sci. 2013;2(2): 312-316

male with left sided bifid ureter (bifid ureter


more common in females and occurrence more
on the right side) around 60 years of age found
without surgical intervention related to the
complication of bifid ureter is rare variety of
unilateral bifid ureter.
ACKNOWLEDGEMENT

I am thankful to Dr. Saleem Basha Tamboli


(Associate Professor and Head of Department of
Pharmacology, Dr. Shankarrao Chavan Govt.
Medical College Nanded) for critical evaluation
and proof reading of the manuscript.
REFERENCES
1. Atwell JD, Cook PL, Howell CJ. Familial
incidence of bifid and double
ureter.
Archives of Disease in Childhood. 1974; 49:
390-393.
2. Haider M Al Attia ; Cephalad Renal Ectopia,
Duplication of Pelvicalyceal System and
Patent Ductus Arteriosus in an Adult Female
. Scand J Urol Nephrol. 1999; 33: 257259
3. Yamamoto K. Duplication of the renal pelvis
and ureter: associated anomalies and
pathological conditions. Radiat Med 1983;
1:55-64.
4. Das's, Dhar P, Mehra RD, Unilateral Isolated
bifid ureter J Anat Soc India.2001;50(1)
43-44
5. Kulkarni V, Ramesh BR, Prakash BS.
Bilateral bifid ureter with accessory renal
artery. Indian Journal of basic Medical
Sciences.2002;3(3):72-74
6. Setsuko Tohno, Cho Azuma, Yoshiyki
Tohno. A case of double renal pelvis and
ureters associated with double Superior
venacavae. J Nara Med Assoc. 2008;59(5):
183-87.
7. George S Bisset III, Janet LS. The Duplex
collecting system in girls with urinary tract
infection ; Prevalence and Significance. AJR.
March 1987; 148: 497-500
8. Ray Dyer, Stephen Miller, Bonnie L
Anderson, James E Drake, John SS. The
Ansari et al.,

Segmental Nephrogram. AJR. August 1985;


145: 321- 22.
9. Khin PP, Srigit Das , Israa MS, Azian Latiff,
Norzana Ghafar, Farihah Haji Suhaimi.
Accessory renal vessels at the upper and
lower pole of the kidney: A cadaveric study
with clinical implications. Morphological
study. Bratisl lek listy. 2010; 111(5): 308-10.
10. Burkland CE. The significance of genetic and
environmental factors in urogenital disease.
Journal of Urology.1958;79:532.
11. Campbells Urology. Volume 3, 8th edition :
2040-54.
12. Choi KL, McNoe LA, French MC. Absence
of PAX2 gene mutations in patients with
primary familial vesicoureteric reflux. J Med
Genet. 1998; 35: 338-39
13. Russell RCG, Williams NS. Bulstrode, CJK,
Bailey and Loves Short practice of Surgery.
Arnold Publishers, New York. 2000, 24th
Edition :1308- 1309
14. Angulo CJ, Unda Urzaiz M, Florescorral N.
Blind ending bifid ureter associated with
adult
congenital. Archives Esp Urology.
1991;44: 869-71.
15. Bhandarkar AD, Rahu AM, Rao MS.Single
Unilateral ectopic bifid ureter with
contralateral orthotopic quadrafid ureter A
rare combination. Journal of Postgraduate
medicine.1997; 43:104-05
16. Gunduz K, Gunalp, Erden. Bifid ureter in
Goltzs
syndrome.OphthGenetics.1997;18:143-9.
17. Al Attia HM. Cephalad Renal Ectopia
duplication of pelvi-calyceal system and
patent ductus arteriosus in an adult female.
Scandevenian Journal of Urology &
nephrology. 1990; 33;257-9.
18. Prasad R, Mukerji PK, Kant S, Singh AK,
and NarianVS. Indian Journal of Chest
Diseases & allied sciences 1996;38: 205-09.
19. Busslinger
M,
Kaiser
G.
Surgical
significance of duplex kidney with bifid
ureter. European journal of
Paediatric
Surgery.1992;2: 150-51.
315

Int J Med Res Health Sci. 2013;2(2): 312-316

20. Rege VM, Deshmukh SS, Borwankar SS,


Gandhi RK. Blind Ending Bifid Ureter.
Journal of Postgraduate Medicine.1986; 32 :
233-35
21. Giannokopoulos X, Chambilomatis P,
Thirothoulakis M, Seferiadis G. The blind
ending bifid uretr. Urology & Nephrology.
1994; 26 : 161-65.
22. Chalouhy E, Harram R, Ezzo G. Various
aspects of Uretero-Ureteral reflux in
incomplete ureteral duplication. Journal of
Medicine Libnan,1992; 40 : 16-21.

316

Ansari et al.,

Int J Med Res Health Sci. 2013;2(2): 312-316

DOI: 10.5958/j.2319-5886.2.2.003

International Journal of Medical Research


&
Health Sciences
www.ijmrhs.com

Volume 2 Issue 2 April-June

th

Received: 7 Mar 2013

Coden: IJMRHS
th

Revised: 28 Mar 2013

Copyright @2013

ISSN: 2319-5886

Accepted: 31st Mar 2013

Case Report
A RARE CASE OF GIST PRESENTED AS LEIOMYOMA
*Hiremath PB1, Nidhi Bansal2 , Meenal C3 , Thulasiraman VN 4, Arun Kumar SP5, Reshma Hiremath6
1

Associate Professor, 2 Assistant Professor, 3 Professor & Head, Dept. of Obstetrics & Gynaecology,
SVMCH & RC, Ariyur, Puducherry
4
Professor, Dept. of General Surgery, SVMCH & RC, Ariyur, Puducherry
5
Professor & Head , Dept. of Pathology, SVMCH & RC, Ariyur, Puducherry
6
IMO Mapusa, Goa.
*Corresponding author email: hiremath0312@gmail.com
ABSTRACT

Gastrointestinal stromal tumour (GIST) is the most commonly identified mesenchymal tumour of the
gastrointestinal tract. There is a great deal of dilemma in diagnosing GIST . Confirmation is possible
only by histopathological examination and by immunohistochemistry. Complete surgical removal
followed by long term postoperative chemotherapy is essential for the optimal cure.

Keywords: GIST, Ileum, cellular leiomyoma, Imatinib


INTRODUCTION

Gastrointestinal stromal tumor (GIST) is a most


common mesenchymal tumor of gastrointestinal
tract (G.I)tract (80%)1. The incidence of GIST is
1020 million people per year with a malignant
potential of 20-30%1,2. Presentations include
abdominal mass (5-50%), obstruction (5%),
haemorrhage and rarely perforation (0.8%)4,5.
CASE REPORT

A 50year old, post menopausal, an asymptomatic


woman came with an ultrasound report showing
uterus
measuring
9x4.6x4.9cm
with
heterogenous echotexture, evidence of 6x4.2cm
isoechoeic lesion seen antero-superior to uterus
with internal vascularity and attached to the

uterus. Both ovaries not clearly seen. Impression


Pedunculated fibroid
Right ovarian mass
Endometriotic deposit. P4L4A2. All FTND and a
known case of hypertension on regular treatment.
On examination general condition was fair, pulse
rate of 82/min, BP of 130/90mmHg. Abdominal
examination was normal, no mass palpable. On
bimanual examination, uterus was irregularly
enlarged to 14-16 weeks size, both the fornices
free, no mass palpable. Investigations: Hb11gms%, Blood group O+ve, RBS-142mgs%,
Blood urea - 28mg%, Serum Creatinine0.8mg%, HIV- negative, HbsAg- negative , chest
x ray - normal, ECG- normal. USG as mentioned
above.
Patient
was
taken
for
Laparoscopy.
Intraoperative findings uterus not visualized,
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omentum completely adherent and covering the


uterus and pulling the bladder up. Bladder
separated from the anterior
anterior abdominal wall. The
decision to convert laparoscopy to laparotomy
was taken.
At laparotomy, 8 x 8 cm omental mass
completely adherent to the small intestine
intestine and the
uterus was visualized.
visualized. Omental adhesions freed
from the uterus. Uterus showed multiple
multiple small
fibroids, Right side ovary was normal, left ovary
was cystic. Total abdominal hysterectomy with
left salphingo-ovariotomy
salphingo ovariotomy (TAH, LSO) was
done. Right ovary could not be removed due to
the adhesions. The mass was infiltrating the
small intestine (ileum)
(ileum) covered by omentum,
ileal lumen was intact and was difficult to
enucleate. Hence the decision to do partial
resection and end to end anastomosis was taken,

haemostasis achieved, saline irrigation done.


Romovac drain was inserted and the abdomen
closed in layers. Post operatively patient
recovered well, discharged on 10th post-operative
operative
day.
Histopathology report revealed Gastrointestinal
stromal tumor (GIST) with 33-4
4 mitotic figures
/10 HPF . No evidence
evidence of necrosis. Impression
GIST / Cellular leiomyoma. Pathologists advised
CD117 to confirm the diagnosis. On
Immunohistochemistry, the tumor was found to
be positive for CD117, CD34, negative for SMA.
Thus a final diagnosis of gastrointestinal stromal
tumor was established on histopathology
histopathology and
immunohistochemistry. Subsequently, the patient
was referred to the on
oncologist
cologist for further
management and was started on Imatinib therapy
for three years.

Fig .1 : USG showing abdomino pelvic mass

Fig.2 : Intraoperative finding of ileal mass

Fig.3: Gross specimen of uterus showing


Multiple fibroids

Fig.4: Histopathology (40X)


(
) showing tumor with Giant
cells suggesting acute inflammatory cellular infiltration

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ath PB et al.,

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ed Re
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lth Sc
Sci.2013;2(2)
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DISCUSSION
Gastrointestinal stromal tumour (GIST) is most
common mesenchymal tumour of gastrointestinal
tract (GI)tract (80%)1. The incidence of GIST is
1020 million people per year with a malignant
potential of 20-30%.Presentations include
abdominal mass (5-50%), obstruction (5%),
haemorrhage and rarely perforation (0.8%)1,2.
GIST tumors arise either from stem cells that
differentiate towards Interstitial Cells of Cajal or
directly from Interstitial Cells of Cajal
(ICCs)..GIST are most often characterized by
strong immunoreactivity to the KIT protein, the
CD117 antigen3. On the other hand, leiomyoma,
leiomyosarcoma , schwannoma , lipoma, ,
hemangioma, are negative for CD1174.
Risk criteria were first published in 2001 and
were amended as more was learned about the
importance of mitotic rate, anatomic primary
site, and size, in large part due to large case
series developed by Miettinen, Lasota and
colleagues5,6.
GISTs are chemotherapy and radiotherapy
resistant and there remains high
risk of
7-10
recurrence after tumor resection
. All GISTs
have a potential for malignancy and the
standard therapy is complete surgical removal
with negative tumor margins 11 . 50% of patients
with GIST will have a relapse after surgery,
necessitating
the
need
for
adjuvant
9
chemotherapy .
The culprit for the pathogenesis of this tumour is
the mutations of the KIT proto-oncogene and the
tumors show a immunoreactivity to the KIT
protein, the CD117 antigen 12,13. KIT tyrosine
kinase inhibitor has showed a hope of improved
outcome in advanced GIST. Imatinib mesylate is
one such tyrosine kinase blocker being
considered as the drug of choice for advanced
tumour14-16. Imatinib is also being used for
palliative therapy or in patients with recurrent
disease.
CONSENT

Consent for publication of this case report was


taken from the patient, copy of which is available
with the corresponding author.
ACKNOWLEDGEMENT

We would like to extend our heartfelt gratitude to


the head of dept, Obstetrics & Gynecology and
Professor, Dept of General surgery and Dept of
Pathology.
REFERENCES

1. Efremidou
EI,
Liratzopoulos
N,
Papageorgiou MS, Romanidis K. Perforated
GIST of the small intestine as a rare cause of
acute abdomen: surgical treatment and
adjuvant
therapy.
Case
report.
J
Gastrointestin Liver Dis 2006, 15:297-99.
2. Oida Y, Motojuku M, Morikawa G, Mukai
M, Shimizu K, Imaizumi T, Makuuchi H:
Laparoscopic-assisted
resection
of
gastrointestinal stromal tumor in small
intestine. Hepatogastroenterology 2008,
55:14649.
3. Hirota S, Isozaki K, Moriyama Y, Hashimoto
K, Nishida T, Ishiguro S, et al.: Gain-offunction mutations of c-kit in human
gastrointestinal stromal tumors. Science 1998;
279(5350.):577-80.
4. Rubin BP, Fletcher JA, Fletcher CD:
Molecular Insights into the Histogenesis and
Pathogenesis of Gastrointestinal Stromal
Tumors. Int J Surg Pathol 2000,8(1):510
5. Miettinen M, Makhlouf H, Sobin LH, Lasota
J: Gastrointestinal stromal tumors of the
jejunum and ileum: a clinicopathologic,
immunohistochemical, and molecular genetic
study of 906 cases before imatinib with longterm follow-up. Am J Surg Pathol 2006,
30:47789.
6. Miettinen M, Sobin LH, Lasota J:
Gastrointestinal stromal tumors of the
stomach: a clinicopathologic, immunehisto
chemical, and molecular genetic study of
1765 cases with long-term follow-up. Am J
Surg Pathol 2005,29:5268.
319

Hiremath PB et al.,

Int J Med Res Health Sci.2013;2(2):317-320

7. Pierie JP, Choudry U, Muzikansky A, Yeap


BY, Souba WW, Ott MJ. The effect of
surgery and grade on outcome of
gastrointestinal
stromal
tumors. Arch
Surg 2001; 136(4):383-89.
8. Edmonson JH, Marks RS, Buckner JC,
Mahoney MR. Contrast of response to
dacarbazine, mitomycin, doxorubicin, and
cisplatin (DMAP) plus GM-CSF between
patients
with
advanced
malignant
gastrointestinal stromal tumors and patients
withother advanced leiomyosarcomas. Cancer
Invest 2002; 20(5):605-12.
9. DeMatteo RP, Lewis JJ, Leung D, Mudan SS,
Woodruff JM, Brennan MF: Two hundred
gastrointestinal stromal tumors: recurrence
patterns and prognostic factors for
survival. Ann Surg 2000; 231(1)51-58.
10. Miettinen M, Makhlouf H, Sobin LH, Lasota
J: Gastrointestinal stromal tumors of the
jejunum and ileum: a clinicopathologic,
immunohistochemical, and molecular genetic
study of 906 cases before imatinib with longterm
followup. AmJSurg
Pathol. 2006;
30(4):477-89.
11. Casali PG, Jost L, Reichardt P, Schlemmer M,
Blay JY: Gastrointestinal stromal tumors:
ESMO
clinical
recommendations
for
diagnosis, treatment and follow-up. Ann
Oncol 2008; 19(2); 35-38
12. Fletcher CD, Berman JJ, Corless C, Gorstein
F, Lasota J, Longley BJ, et al.: Diagnosis of
gastrointestinal stromal tumors: a consensus
approach. Int J Surg Pathol 2002; 10(2):8189.
13. Miettinen M, Lasota J: Gastrointestinal
stromal
tumors--definition,
clinical,
histological,
immunohistochemical,
and
molecular genetic features and differential
diagnosis. Virchows Arch 2001; 438(1):1-12.
14. Joensuu H, Roberts PJ, Sarlomo-Rikala M,
Andersson LC, Tervahartiala P, Tuveson D, et
al.: Effect of the tyrosine kinase inhibitor
STI571 in a patient with a metastatic

gastrointestinal stromal tumor. N Engl J


Med 2001; 344(14.);1052-6.
15. Demetri GD, von Mehren M, Blanke CD, Van
den Abbeele AD, Eisenberg B, Roberts PJ, et
al.: Efficacy and safety of imatinib mesylate
in
advanced
gastrointestinal
stromal
tumors. N Engl J Med 2002; 347(7):472-80.
16. Dematteo RP, Ballman KV, Antonescu CR,
Maki RG, Pisters PW, Demetri GD, et
al.:Adjuvant imatinib mesylate after resection
of localised, primary gastrointestinal stromal
tumour: a randomised, double-blind, placebocontrolled
trial. Lancet 2009;373;(9669):
1097-104.

320

Hiremath PB et al.,

Int J Med Res Health Sci.2013;2(2):317-320