Scripta Medica 44 2

44
asopis Drutva doktora medicine Republike Srpske

Journal of the Medical Society of the Republic of Srpska
Godina: 44. Broj 2 oktobar 2013.
asopis Drutva doktora medicine
Republike Srpske
Vol. 44 No. 2 October 2013.
Medical Society of the
Republic of Srpska
EDITORIAL/
Could the Difference Between Normal and Malignant Stem Cells Eradicate Cancer? Z. IVANOVIC
ORIGINAL ARTICLE/
C-Reactive Protein And Fibrinogen In Type 2 Diabetes Mellitus
S. HASI, M. EEVI, D. KADI, D. DAUTBEGOVI-STEVANOVI
ORIGINAL ARTICLE/
Function of -Cells and Insulin Resistance in Long-Standing Type 2 Diabetes Mellitus D. KADI,
D. DAUTBEGOVI-STEVANOVI, S. HASI
ORIGINAL ARTICLE/
Anesthesia Residents Have Limited Knowledge of Biostatistics
G. ALEMZADEH, S. STOISAVLJEVI-ATARA, G. VORONOV, R. IGI
PRELIMINARY REPORT/
Comparison of Conservative Treatments for Children With Idiopathic Scoliosis D. DZAMIC, I.
PETRONIC, D. NIKOLIC, D. CIROVIC, T. KNEZEVIC, R. BRDAR
CASE REPORTS/
Hemophilia AAcquired During Coronary Artery Bypass Grafting
A. AKINTORIN, B. ALEXANDER, A. ABOU LEILA, J. HUMANEZ, J. CPENCOW
Advanced Esophageal Carcinoma Expressing Human Chorionic Gonadotropin (HCG-b)
G. KUTTY, J. E YAP, S. GUPTA, M. SEKOSAN
IMAGES IN CLINICAL MEDICINE/
Carcinosarcoma of the Uterus Metastasizing to the Scalp
R. GIANANI, S. GANDHI, J. BERO
Mitral Valve Prolapse: Novel Assessment With Real-Time 3D Echocardiography
. S. JONJEV, V. TORBICA, J. RAJI
SPECIAL ARTICLE-CLINICAL PRACTICE/ -
Smoking Abstinence in Patients Scheduled for Elective Surgery
N. STOJAKOVI, . S. JONJEV, R. IGI
CONTINUING MEDICAL EDUCATION/
Questions and Answers S. POPOVI-PEJII
Uslovi za ulazak biomedicinskog asopisa u MEDLINE bazu biomedicinskih podataka
www.scriptamedica.com
71
Scripta Medica
Vol. 44 No 2 October 2013. www.scriptamedica.com
UREIVAKI ODBOR/EDITORIAL BOARD
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72
Scripta Medica
Vol. 44 No 2 October 2013. www.scriptamedica.com 72
Sadraj / Contents
74 EDITORIAL
Could the Difference Between Normal and Malignant Stem Cells
Eradicate Cancer? Z. IVANOVIC
75 ORIGINAL ARTICLE
C-Reactive Protein And Fibrinogen In Type 2 Diabetes Mellitus
S. HASI, M. EEVI, D. KADI, D. DAUTBEGOVI-STEVANOVI
C-reaktivni protein i brinogen u tipu 2 diabetes mellitus-a
79 ORIGINAL ARTICLE
Function of -Cells and Insulin Resistance in Long-Standing
Type 2 Diabetes Mellitus D. KADI, D. DAUTBEGOVI-STEVANOVI,
S. HASI
Funkcija -elija i inzulinska rezistencija kod dugotrajnog tip 2
diabetes mellitus-a
83 ORIGINAL ARTICLE
Anesthesia Residents Have Limited Knowledge of Biostatistics
G. ALEMZADEH, S. STOISAVLJEVI-ATARA, G. VORONOV, R. IGI
Specijalizanti iz anesteziologije nedovoljno poznaju statisktiku
86 PRELIMINARY REPORT
Comparison of Conservative Treatments for Children With
Idiopathic Scoliosis D. DZAMIC, I. PETRONIC, D. NIKOLIC, D. CIROVIC,
T. KNEZEVIC, R. BRDAR
Poreenje konzervativnog tretmana kod dece sa idiopatskom
skoliozom
90 CASE REPORT
Hemophilia AAcquired During Coronary Artery Bypass Grafting
A. AKINTORIN, B. ALEXANDER, A. ABOU LEILA, J. HUMANEZ, J. CPENCOW
Hemolija A koja se pojavila u vreme koronarno-arterijskog
premotavanja
92 CASE REPORT
Advanced Esophageal Carcinoma Expressing Human Chorionic
Gonadotropin (HCG-b)
G. KUTTY, J. E YAP, S. GUPTA, M. SEKOSAN
Pojava hemolije A u vreme koronarno-arterijskog premotavanja
95 IMAGES IN CLINICAL MEDICINE
Carcinosarcoma of the Uterus Metastasizing to the Scalp
R. GIANANI, S. GANDHI, J. BERO
Larcinomsarkon uterusa koji je metastazirao u skalp
96 IMAGES IN CLINICAL MEDICINE
Mitral Valve Prolapse: Novel Assessment With Real-Time 3D
Echocardiography
. S. JONJEV, V. TORBICA, J. RAJI
Prolaps mitralnog zalistka: Nova procena pomou Real-Time 3D
elektrokardiograje
97 SPECIAL ARTICLE-CLINICAL PRACTICE
Smoking Abstinence in Patients Scheduled for Elective Surgery
N. STOJAKOVI, . S. JONJEV, R. IGI
Apstinencija od puenja kod pacijenata predvienih za elektivne
hirurke zahvate
100 LETTER TO THE EDITOR
Antimicrobial Consumption
S. IBALI
Potronja antibiotika
101 CONTINUING MEDICAL EDUCATION
Questions and Answers S. POPOVI-PEJII
Pitanja i odgovori
106 PUBLIKACIJE AUTORA IZ REPUBLIKE
SRPSKE U ASOPISIMA UVRTENIM
U MEDLINE
110 SPECIJALAN LANAK
Uslovi za ulazak biomedicinskog asopisa u MEDLINE bazu
biomedicinskih podataka
M. SKROBI, S. TRBOJEVI, R. GAJANIN
112 . :
M. SKROBI
113 PRIKAZ KNJIGE
115 UPUTSTVO AUTORIMA/INSTRUCTIONS
FOR CONTRIBUTORS
Errata: In previous issue (Vol. 44, No. 1, page 4), following words should be eliminated:
.
73
Scripta Medica
/In This Issue
Za ovaj broj asopisa uvodnik je napisao akademik Zoran
Ivanovi (Bordo, Francuska) i posvetio ga kancerskim
matinim elijama (cancer stem cells), aktuelnoj temi iz
onkologije i molekularne biologije. O tim elijama je dat
i kratak opis u lanku Questions and Answers (Pitanja
i odgovori), koji je priredila prof. dr Snjeana Popovi-
Pejii. U ovoj svesci asopisa objavljena su etiri original-
na istraivanja: dva su posveena dijabetesu (Hasi i sar.,
Kadi i sar.), a jedno poznavanju statistike specijalizanata
iz anesteziologije (Golnaz i sar.). Preliminarno saopenje
je posveeno leenju skolioze u deijem uzrastu (Dami
i sar.). lanke o dijabetesu koji su prezentovani na Prvom
kongresu dijabetologa Republike Srpske sa meunarodnim
ueem odabrao je organizator kongresa, a uredio ih je
glavni urednik SM.
Dva prikaza sluaja su iz anesteziologije (Akintorin i sar.) i
patoloke anatomije (Kutty i sar.). Slede dva kratka lanka
u rubrici Images in clinical medicine (Slike iz klinike med-
icine) autori su Jonjev i sar., odnosno Gianini i sar. Pismo
uredniku prof. dr Save ibalia, doajena infektologije iz
Tuzle, objavljujemo u naoj najitanijoj rubrici (Letters to
the Editor, Pisma uredniku). To pismo se odnosi na lanak
o upotrebi antibiotika u vanbolnikoj praksi Republike
Srpske, koji je objavljen u prolom broju (Scripta Medica,
Vol. 44, No. 1, 2013). lanak posveen klinikoj praksi
(Stojakovi i sar.) tretira zapostavljen, a viestruko koristan
pristup prestanku puenja pre elektivnog hirurkog zah-
vata. Taj etvoronedeljni do osmonedeljni prekid puenja
mogao bi pomoi puaima da, uz dodatni napor i pomo
lekara, zauvek ostave tu naviku.
lanci autora iz Republike Srpske, objavljeni u asopisima
koje registruje MEDLINE, dati su u prilogu. Neki od njih
su nam ranije promakli. Zato smo u ovom broju ukljuili
nekoliko starijih, koji su publikovani pre dve godine. Na
srpskom jeziku su objavljena dva lanka. Prvi je prilog
o uslovima za prihvatanje nekog asopisa u MEDLINE,
najveu meunarodnu bazu podataka koja registruje bio-
medicinske lanke. Autori su prof. dr Milan Skrobi, prof.
dr Stevan Trbojevi i prof. dr Radoslav Gajanin. Drugi
lanak je posveen nedavno preminulom prof. dr Bogdanu
igiu, poznatom banjalukom hirurgu, koji je desetak go-
dina bio urednik ovog asopisa. Autor tog lanka je dekan
Medicinskog fakulteta u Banjaluci prof. dr Milan Skrobi.
Medicinski fakultet u Banjaluci je pomogao nansiranje
ovog broja asopisa. Do pre tri godine fakultet je bio je-
dini izdava, a zbog skoro dvogodinjeg zastoja izlaenja
asopisa Drutvo doktora Republike Srpske privremeno
je preuzelo ulogu izdavaa kako bi se zastoj otklonio, a
ureivanje unapredilo.
Scripta Medica
74
Scripta Medica
UDK 6
EDITORIAL
Could the Difference
Between Normal and
Malignant Stem Cells
Eradicate Cancer?
Normal stem cells provide a reserve for the renewal of
tissues. This system, recognized a half of century ago,
explained the hierarchy of descending cell populations
(generation-age hypothesis
1
and initiated a revolution in
biomedical sciences. However, all aspects of stem cell na-
ture are not yet revealed; even the hierarchy concept has
been questioned, and no one has yet adequately dened
this elusive stem cell. One concept (the chiaroscuro
model) supposes that a stem cell is a metastable functional
entity that varies between a committed progenitor and a
stem cell form.
2

Regardless of how we dene these fundamental phenom-
ena, stem cell research has prompted, in the second decade
of 21
st
century, a real medical revolution: cellular therapy.
Five decades after the paradigm of hematopoietic stem
cells was established, the stem cell concept emerged in
oncology, where the observed primitive cells were called
cancer initiating cells or cancer stem cells. Although
the stem cell concept identies these cancer-initiating
cells as the main target of anti-cancer therapies, there is
still debate about the process.
3

At the same time, stem cell research indicates that both
normal and cancer stem cells have much in common. Both
have the anaerobic metabolism of a primitive cell phe-
notype
4
that was, so far, typically associated with cancer
cells. In addition, normal and cancer stem cells exhibit
many common features related to this primitive cell phe-
notype, including membrane antigens or markers, expres-
sion of transcription factors and activation of signals for
cell quiescence/self-renewal.
The main challenge now is to identify differences between
normal and cancer cells that will allow selective eradica-
tion of cancer stem cells without compromising normal tis-
sue stem cell potential.
5
Some recent studies point to dis-
similarities that could be of capital importance, such as a
difference in the PI-3 kinase pathway.
6

In line with the practice of following particular hot topics,
this issue of Scripta Medica contains a short segment in
the Questions & Answers.
7
From a review paper entitled
Complexity of cancer stem cells, the characterization of
cancer stem cells is presented.
8
References
1. Rosendaal M, Hodgson GS, Bradley TR. Organization of haemo-
poietic stem cells: The generation-age hypothesis. Cell Tissue
Kinet 1979;12.1:17.
2. Quesenberry PJ, Colvin GA, Lambert JF. The chiaroscuro stem
cell: a unied stem cell theory. Blood 2002; 100.13: 4266.
3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next gen-
eration. Cell 2011; 144.5: 646.
4. Ivanovic Z. Respect anaerobic nature of stem cells to exploit
their potential in regenerative medicine; Regen Med 8(6)
DOI:10.2217/RME.13.65 (2013).
5. Karsten U, Goletz S. What makes cancer stem cell markers dif-
ferent? SpringerPlus 2013; 2.1:301.
6. Yilmaz OH, Morrison SJ. The PI-3kinase pathway in hemato-
poietic stem cells and leukemia-initiating cells: a mechanistic
difference between normal and cancer stem cells. Blood Cells
Mol Dis. 2008; 41.1:73.
7. Popovo-Pejii S. Questions and Answers. Scr Med
2013;44:101-4.
8. Sugihara E, Saya H. Complexity of cancer stem cells. Int J Can-
cer 2013;132:1249-59.
Zoran Ivanovic
Aquitaine-Limousin Branch of French Blood Institute & UMR5164
CNRS/Segalen University, Bordeaux, France
Correspondence
Zoran Ivanovic MD, PhD, HDR
Etablissement Franois du Sang Aquitaine Limousin,
Place Amlie Raba Lon CS 21010
33075 Bordeaux, France
75
Scripta Medica
UDK 616.379-008.64-085
Sabaheta Hasi
1
,
Miralem eevi
2
, Damira
Kadi
3
,
Davorka Dautbegovi-
Stevanovi.
4

1
Department of Medical Biochemis-
try, Faculty of Medicine, University
of Sarajevo
2
Resident in Internal medicine, Clini-
cal Center University of Sarajevo
3
Department of Laboratory Diag-
nostics, Cantonal Hospital Zenica
4
Department of Internal Diseases,
Cantonal Hospital Zenica
Correspondence
Sabaheta Hasi, MD, Ph.D.
Department of Medical Biochemistry
University of Sarajevo, Faculty of
Medicine
ekalua 90, 71000 Sarajevo
Bosnia & Herzegovina
Phone: +387 33 22 64 72/134
Fax: +387 33 21 75 41
E-mail: sabaheta.hasic@mf.unsa.ba
ORIGINAL ARTICLE
C-Reactive Protein And Fibrinogen In
Type 2 Diabetes Mellitus*
ABSTRACT
Introduction. Chronic,low-grade inammation is important in the development and
progression of type 2 diabetes mellitus (T2DM). Indicators of increased inammatory activity
include elevated values of circulating acute phase proteins like C-reactive protein (CRP) and
brinogen. The aim of the study was to test sex-related differences in CRP and brinogen
blood levels in T2DM patients.
Patients and Methods. The cross-sectional study included 40 T2DM patients, both
sexes (19 males and 21 females), median age 70 (36-90) years. Patients were hospitalized
at the Clinic of Endocrinology, Clinical Center University of Sarajevo. The fasting glucose
levels, glycated haemoglobin, brinogen and CRP in the blood of T2DM patients were
determined by standard laboratory methods. The data were analysed by statistical software
SPSS 19.
Results. The median values of CRP and brinogen in blood were not statistically different
between female and male T2DM patients, although values had tendency to be higher in
female patients [17.30 mg/L (3.40-61.35) vs. 9.60 mg/L (3.50-28.90); p=0.573]; [5.70 g/L
(4.20-6.35) vs. 3.80 g/L (3.60-6.00); p=0.078]. A positive correlation between CRP and
brinogen was found in samples from female T2DM patients (rho=0.606;p<0.01).
Conclusion. Elevated CRP and brinogen indicate the presence of inammation in T2DM
patients. Female patients had higher values of both inammatory markers in blood in
comparison to males, but we did not prove statistically signicant sex-related differences.
KEY WORDS
Type 2 diabetes mellitus; inammation; C-reactive protein; brinogen.
DOI: 10.7251/SMD1302075H (Scr Med 2013;44:75-8)
Submitted: April 22, 2013
Accepted: September 15, 2013
One of important factors in the pathogenesis of type 2
diabetes mellitus (T2DM) is a state of subclinical chronic
inammation.
1
It is considered that inammation is a key
factor in insulin resistance.
2
Except for the disease develop-
ment, chronic low-grade inammation is important in the
progression of T2DM. Hyperglycemic condition and proin-
ammatory state in T2DM patients are responsible for the
development of a wide spectrum of atherosclerotic compli-
cations.
3
Indicators of increased inammatory activity are
elevated values of circulating acute phase proteins like C-
reactive protein (CRP) and brinogen.These proteins play
a signicant role in initiation, aggravation and progression
of atherosclerosis in diabetic patients.
4
The endothelial
dysfunction, promotion of foam cell formation, inhibition
of endothelial progenitor cell survival and differentiation,
activation of the complement system in atherosclerotic
plaque are major mechanisms of proatherosclerotic ac-
tion of CRP.
5-8
In addition, CRP further contributes to the
progression of atherosclerosis by stimulation of monocyte
interleukin-6 production.
9
There are several mechanisms
by which brinogen increases cardiovascular risk such
as stimulation of platelet aggregation, promotion of brin
formation and increase in plasma viscosity.
10,11
Sex-relat-
ed differences exist in CRP and brinogen blood values
among the healthy population.
12
Accordingly, our aim was
to examine if sex-related differences in CRP and brinogen
blood levels also exist in T2DM patients.
Patients and Methods
Patients. Forty (n=40) T2DM patients hospitalized at the
Clinic of Endocrinology, Clinical Center University of Sa-
rajevo were included in the study. Patients were divided in
sex-based groups: T2DM-males (n=19) and T2DM-females
(n=21). The median age of T2DM patients was 70 (36-90)
years. All data were taken from patients medical histories.
*
This paper was presented at the First congress on diabetes mel-
litus, Banja Luka, Republic of Srpska, Bosnia & Herzegovina,
March, 2013. (1 st Diabetology congress of Republic of Srpska,
21-24.03.2013.)
76
Scripta Medica
Clinical examinations and laboratory measure-
ments. Systolic and diastolic blood pressures were de-
termined by standard protocol using mercury manom-
eter. Body mass index (BMI) was calculated as weight in
kilograms divided by height in meters squared. Glucose
hexokinase method (Dimension RXL, Siemens, Munich,
Germany) was used for fasting blood glucose measure-
ment (reference range 3.3-6.1mmol/L). CRP and HbA1c
were analysed by immunoturbidimetric methods on the
Dimension Xpand Plus Analyzer (Siemens, Munich, Ger-
many). The CRP reference range was 0-5 mg/L and values
less than 6% for HbA1c were considered normal. Fibrino-
gen measurement was done using immunonephelometric
method using BN II nephelometer (Siemens, Munich, Ger-
many) (reference range 1.8-3.5 g/L).
Statistical analysis. Results of descriptive statistics are
presented by median with range from rst to third quar-
tile. Differences of parameters between two groups were
analysed using non-parametric Mann-Whitney U test be-
cause the criteria of normal data distribution were not sat-
ised. Spearmans correlation test was used to analyse the
association between studied parameters. For data analysis,
we used SPSS Statistics software version 19.0 (SPSS Inc,
Chicago, IL, USA). P values less than 0.05 were considered
statistically signicant.
Results
Characteristics of clinical and biochemical parameters of
type 2 diabetes mellitus patients are presented in Table 1.
There were no age-related differences between T2DM pa-
tients of both sexes. We found that type 2 diabetic patients
were overweight with a poor control of glycaemia. No sta-
tistically signicant differences were found with regard to
glucose and HbA1c levels, duration of disease and blood
pressure among men and women. Concentrations of CRP
Table 1. Clinical and biochemical parameters of type 2 diabetic patients
Parameters T2DM (n=40) T2DM-females (n=21) T2DM-males (n=19) P
Age (years) 70 (36-90) 70 (36-82) 69 (54-77) 0.520
BMI (kg/m2) 27.05 (23.85-29.67) 26.20 (22.80-29.40) 28.70 (24.30-29.70) 0.236
Disease duration (years) 9.5 (4-20) 10 (4-20) 9 (4-17) 0.810
STA (mmHg) 135(120-160) 140 (130-160) 130 (120-145) 0.196
DTA (mmHg) 80 (80-90) 80 (75-90) 80 (80-90) 0.872
FBG (mmol/L) 9.6 (7.8-14.5)
9.5 (7.70-15.90)
11.40 (8.0-14.50 )
0.810
HbA1c (%) 8.45 (7.15-9.15)
8.50 (7.20-9.10 )
7.90 (7.10-9.30)
0.851
CRP (mg/L) 16.5 (3.57-30.10 )
17.30 (3.40-61.35)
9.60 (3.50-28.90)
0.573
Fibrinogen (g/L) 4.82 (3.7-6.3 )
5.7(4.20-6.35)
3.80 (3.60-6.0 )
0.078
Abbreviations: T2DM-type 2 diabetes mellitus; BMI-body mass index; STA-systolic blood pressure; DTA-diastolic blood pressure; FBG-
fasting blood glucose;HbA1c-glycated haemoglobin; CRP-C-reactive protein; n-number of the patients included in the study; P-probabili-
ty;
-biochemical parameters which are out of the reference range.

Table 2. Gender related inammatory markers and parameters of the type 2 diabetic patients
Biochemical tests
T2DM patients
Females Males
CRP (mg/L)
Fibrinogen
(g/L)
CRP (mg/L)
Fibrinogen
(g/L)
FBG (mmol/L)
Rho 0.360 0.205 0.506 0.183
P 0.109 0.372 0.027 0.453
HbA1c (%)
Rho -0.120 -0.299 -0.143 -0.083
P 0.605 0.189 0.559 0.736
Fibrinogen (g/L)
Rho 0.606
-
-0.086
-
P 0.004 0.725
Abbreviations: T2DM-type 2 diabetes mellitus; CRP-C-reactive protein; FBG-fasting blood glucose; HbA1c-glycated haemoglobin;
Rho-Spearmans coefcient of correlation; p-probability.
correlation is signicant at 0.01 level. correlation is signicant at 0.05 level
77 Hasi, et al
and brinogen in blood were increased in both male and
female T2DM patients. The median blood values of CRP
and brinogen had tendency to be higher in female T2DM
compared to male patients, without statistical signicance.
Analyses of CRP and brinogen correlation and association
of inammatory markers with glycemic control parameters
in the blood of male and female patients are presented in
Table 2. Signicant positive correlation was found between
inammatory markers in females while glucose and CRP
correlated signicantly in male diabetic patients. The in-
signicant correlations were found between inammatory
markers and glycemic control parameters in female pa-
tients. In male T2DM patients, no signicant correlations
were observed between blood values of CRP and brinogen
and between brinogen and HbA1c (Table 2).
Discussion
Poorly controlled diabetes with elevated CRP and brino-
gen was found in the patients studied. Analysis of sex-re-
lated difference in achieving glycemic control has shown
that male patients had a higher glucose values than fe-
males. A poorer long-term glycemic control was noted in
female patients but sex-related differences were not statis-
tically different. A separate analysis of CRP and brinogen
in females and males has revealed a higher value in female
patients. Gender related differences in CRP and brinogen
were insignicant, but positive correlations between CRP
and brinogen values in females (p<0.01) and glucose and
CRP in males (P<0.05) were found. The mechanisms asso-
ciated with insulin resistance and accelerated atheroscle-
rosis development in patients with T2DM include impaired
vasodilatation, increased oxidative stress, low-grade in-
ammation and thrombus formation, just to name a few.
13
Inammation markers are indicators of risk for cardio-
vascular complications development in diabetic patients.
CRP and brinogen are hallmarks of the chronic inam-
mation and indicators of adipose dysfunction and insulin
resistance.
14
There are published data that the relative risk
for cardiovascular disease onset is more pronounced in
female diabetic patients compared to male.
15
Lakoski and
associates have shown a higher blood value of high sensi-
tivity CRP (hs-CRP) in women compared with men and
this gender difference was maintained across all ethnic
subgroups.
12
The results of Lai and associates and Ahonen
and coauthors studies have shown the existence of stronger
association of elevated hs-CRP concentration and meta-
bolic syndrome in women.
16,17
A higher circulating levels of
CRP in women are well established and can be related to
differences in visceral and subcutaneous fat and oestrogen
levels.
18,12,19,20
Study of Ili and associates have shown that
women with T2DM and clinically manifest coronary ar-
tery disease have more prominent lipid and inammatory
disorder and they are more susceptible for cardiovascular
complication development.
14
A reduced susceptibility to
plasmin degradation and increase of brinogen synthesis
rate are possible mechanisms of elevated brinogen in dia-
betic patients.
21
Study of Alzahrani and associates found
higher values of brinogen in female T2DM patients com-
pared to male patients. They have shown the existence of
variant type of clots with compromised brinolysis in fe-
male T2DM patients. There was gender specic association
between clotting parameters and cardiometabolic risk fac-
tors in this population.
22
The results obtained implicate the need for further evalu-
ation of gender difference in these markers by larger study
group and use of high sensitivity immunoassays. The nd-
ings in this study showed that the presence of elevated CRP
and brinogen indicates the existence of inammation in
T2DM patients as possible risk factors for complication de-
velopment. Female patients had tendency for higher values
of both inammatory markers in the blood, but the differ-
ences were not statistically signicant.
Authorship statement
SH takes full responsibility for the study design, the manuscript
writing and accuracy of the data analysis, M is responsible for
data collection, DK, DDS are responsible for data interpretation
and critical revision of the manuscript.
Financial disclosure
We declare that we have no conict of interest.
References
1. Badawi A, Klip A, Haddad P, et al. Type 2 diabetes mellitus and
inammation: Prospects for biomarkers of risk and nutritional
intervention. Diabetes Metab Syndr Obes 2010; 3:173-86.
2. Festa A, DAgostino R Jr, Howard G, Mykknen L, Tracy
RP, Haffner SM. Insulin Resistance Atherosclerosis Study
(IRAS) Chronic Subclinical Inammation as Part of the Insulin
Resistance Syndrome: The Insulin Resistance Atherosclerosis
Study (IRAS). Circulation 2000; 102(1): 42-7.
3. Maritim A, Sanders R, Watkins J. Diabetes, Oxidative stress,
and antioxidants. A review. J Biochem Mol Toxicol 2003; 17(1):
24-38.
4. Bosevski M, Bosevska G, Stojanovska M. Inuence of brinogen
and CRP on progression of peripheral arterial disease in type 2
diabetes: preliminary report. Cardiovasc Diabetol 2013; 12:29
doi: 10.1186/1475-2840-12-29.
5. Pasceri V, Willerson J, Yeh E. Direct proinammatory effect
of C-reactive protein on human endothelial cells. Circulation
2000; 102(18):2165-8.
6. Zwaka T, Hombach V, Torzewski J. C-reactive protein-mediated
low density lipoprotein uptake by macrophages: implications for
atherosclerosis. Circulation 2001;103(9):1194-7.
7. Verma S, Kuliszewski M, Li S, et al. C-reactive protein attenu-
ates endothelial progenitor cell survival, differentiation, and
function: further evidence of a mechanistic link between C-
78
Scripta Medica
reactive protein and cardiovascular disease. Circulation 2004;
109: 2058-67.
8. Torzewski J, Torzewski M, Bowyer D,et al. C-reactive protein
frequently colocalizes with the terminal complement complex
in the intima of early atherosclerotic lesions of human coronary
arteries. Arterioscler Thromb Vasc Biol 1998; 18:1386-92.
9. Blake GJ, Ridker PM. Inammatory biomarkers and cardiovas-
cular risk prediction. J Intern Med 2002; 252(4): 283-94.
10. Stec JJ, Silbershatz H, Toer GH, et al. Association of brinogen
with cardiovascular risk factors and cardiovascluar disease
the Framingham Offspring Population.Circulation 2000; 102
(14):1634-8.
11. Vanninen E, Laitinen J, Uusitupa M. Physical activity and
brinogen concentration in newly diagnosed NIDDM. Diabetes
Care 1994;17 (9):1031-8.
12. Lakoski SG, Cushman M, Criqui M, et al. Gender and C-reactive
protein: Data from the Multiethnic Study of Atherosclerosis
(MESA) cohort. Am Heart J 2006; 152 (3):593-8.
13. Laakso M. Cardiovascular disease in type 2 diabetes from
population to man to mechanisms: the Kelly West Award Lec-
ture 2008. Diabetes Care 2010; 33 (2): 442-9. doi: 10.2337/
dc09-0749.
14. Qasim AN, Budharaju V, Mehta NN, et al. Gender Differences in
the Association of C-Reactive Protein with Coronary Artery
Calcium in Type-2 Diabetes. Clin Endocrinol (Oxf) 2011;74 (1):
44-50. doi: 10.1111/j.1365-2265.2010.03879.x.
15. Ili D, Pei M, Savi T, Stankovic N, Djindji B. Gender-related
difference in inammatory and lipid parametres in patients
with type 2 diabetes mellitus. Acta Medica Medianae 2008; 47
(3): 39-43.
16. Lai MM, Li CI, Kardia SL,et al. Sex difference in the association
of metabolic syndrome with high sensitivity C-reactive protein
in a Taiwanese population. BMC Public Health 2010; 10: 429.
doi: 10.1186/1471-2458-10-429.
17. Ahonen T, Saltevo J, Laakso M, Kautiainen H, Kumpusalo E,
Vanhala M. Gender differences relating to metabolic syn-
drome and proinammation in Finnish subjects with elevated
blood pressure. Mediators Inamm 2009; 2009:959281. doi:
10.1155/2009/959281.
18. Khera A, McGuire DK, Murphy SA, et al. Race and gender dif-
ferences in C-reactive protein levels. J Am Coll Cardiol 2005; 46
(3):464-9.
19. Cartier A, Cote M, Lemieux I, et al. Sex differences in inamma-
tory markers: what is the contribution of visceral adiposity? Am
J Clin Nutr 2009; 89 (5):1307-14. doi: 10.3945/ajcn.2008.27030.
20. Kwok S, Canoy D, Ashton WD, et al. Increased C-reactive protein
levels in overweight and obese women taking exogenous hor-
mones: the United Kingdom Womens Heart Study (UKWHS).
Clin Endocrinol (Oxf) 2009; 71(5): 727-32. doi: 10.1111/j.1365-
2265.2009.03580.x.
21. Jain A, Gupta HL, Narayan S. Hyperbrinogenemia in patients
of diabetes mellitus in relation to glycemic control and urinary
albumin excretion rate. J Assoc Physicians India 2001; 49: 227-
30.
22. Alzahrani SH, Hess K, Price JF, et al. Gender-specic altera-
tions in brin structure function in type 2 diabetes: associations
with cardiometabolic and vascular markers. J Clin Endocrinol
Metab 2012; 97(12): E2282-7. doi: 10.1210/jc.2012-2128.
C-reaktivni protein i brinogen u tipu 2 diabetes
mellitus-a
APSTRAKT
Uvod. Hronina inamacija niskog stepena je znaajna za razvoj i progresiju tip 2 diabetes mellitus-a (T2DM). Pokazatelji
inamatorne aktivnosti su poviene vrijednosti proteina akutne faze u cirkulaciji kao to su C-reaktivni protein (CRP) i brinogen.
Cilj studije je bio ispitati postojanje spolnih razlika u vrijednostima CRP-a i brinogena u krvi pacijenata sa T2DM.
Metode. U presjenu studiju je ukljueno 40 pacijenata oboljelih od T2DM, oba spola (19 mukaraca, 21 ena), medijana
starosne dobi je bila 70 (36-90) godina. Pacijenti su bili hospitalizirani na Klinici za endokrinologiju, Klinikog centra Univerziteta
u Sarajevu. Standardnim laboratorijskim metodama su odreivani nivoi glukoze na tate, glikiranog hemoglobina, brinogena i
CRP-a. Podaci su statistiki obraeni sa SPSS 19. programom.
Rezultati. Medijane vrijednosti CRP-a i brinogena u krvi nisu bile statistiki znaajno razliite izmeu T2DM pacijenata enskog
i mukog spola, i ako je postojala tendenca viih vrijednosti kod ena u odnosu na mukarce. [17.30 (3.40-61.35) mg/l vs. 9.60
(3.50-28.90) mg/l; p=0.573]; [5.70 (4.20-6.35) g/l vs.3.80 (3.60-6.00) g/l; p=0.078]. Pozitivna korelacija je utvrena izmeu CRP-a
i brinogena kod T2DM pacijenata enskog spola (rho=0.606; p<0.01).
Zakljuak. Poviene vrijednosti CRP-a i brinogena ukazuju na prisutnu inamaciju kod pacijenata oboljelih od T2DM. Utvrene
su vie vrijednosti oba inamatorna markera u krvi pacijenata enskog spola, ali statistiki znaajne razlike nisu dokazane.
KLJUNE REI
Diabetes mellitus tip 2; upala; C-reaktivni protein; brinogen.
79
Scripta Medica
UDK 616.379-008.64
Damira Kadi,
Davorka Dautbegovi-
Stevanovi,
Sabaheta Hasi
Department of Laboratory Diag-
nostics and Department of Internal
Diseases, Cantonal Hospital Zenica,
Zenica, Bosnia & Hezegovina
Department of Medical Biochemis-
try, Faculty of Medicine, University
of Sarajevo, Sarajevo, Bosnia &
Herzegovina
Correspondence
Dr Damira Kadi
Department of Laboratory Diagnostics,
Cantonal Hospital Zenica
Crkvice 67, 72000 Zenica
Bosnia & Herzegovina
Phone: +387 32 405 133
Fax: +387 32 226 576
e-mail: damira.kadic@gmail.com
ORIGINAL ARTICLE
Function of -Cells and Insulin
Resistance in Long-Standing Type 2
Diabetes Mellitus*
ABSTRACT
Introduction. Every patient with type 2 diabetes mellitus secretes less insulin than
necessary for his/her level of insulin sensitivity, and many of them have some degree
of insulin resistance. The mix of insulin deciency and insulin resistance is different
for each patient and, in any patient, it may vary during the course of the disease. The
aim of our study was to examine the degree of -cells function and the presence of
insulin resistance in patients with a long-standing type 2 diabetes.
Methods. The study included 30 patients of both sexes (12 males, 18 females), with
the mean values of age 59 years (SD=7.88) and the disease duration of 10 years
(SD=5.36). The mean value of BMI was 31 kg/m (SD=4.74). The fasting glucose and
insulin concentrations and HbA1c in the blood were determined by the standard
laboratory methods. The percentages of functional -cells in the pancreas (HOMA-
%B), insulin sensitivity (HOMA-%S) and insulin resistance (HOMA-IR) were calculated
using a HOMA calculator v2.2. Then, the data were analyzed by statistical software
SPSS 19.
Results. The mean HbA1c was 10 % (SD=1.52) and FBG 12 mmol/L (SD=4.15). The
mean insulin was 13 mol/L (SD=6.11) and HOMA-%B 31 % (SD=18.99). The median
value of HOMA-%S was 49% (32.2-82.4) and HOMA-IR 2 (1.2-3.1). 87% of patients
had a HOMA-IR >1.
Conclusion. The highly reduced -cells function and the consequent insulin
deciency, usually combined with the moderate insulin resistance was determined in
the patients with a long-standing type 2 diabetes mellitus.
KEY WORDS
Type 2 diabetes mellitus; -cells function; insulin resistance.
DOI: 10.7251/SMD1302079K (Scr Med 2013;44:79-82)
Type 2 diabetes mellitus (T2DM) is the most common form
of diabetes and defects of both insulin action and insulin
secretion are usually present by the time of diagnosis. It is
progressive disorder of glucose metabolism with decreased
-cells function and insulin resistance as the dominant
factors in its genesis. The environmental factors, weight
gain and physical inactivity exacerbate metabolic abnor-
malities present in this disease. Every patient with T2DM
secretes less insulin than necessary for his/her level of in-
sulin sensitivity, and many of them have some degree of in-
sulin resistance. The mix of insulin deciency and insulin
resistance is different for each patient and, in any patient,
it may vary during the course of the disease. Multiple
causative factors such as genetic predisposition, insulin
resistance, increased insulin secretory demand, glucotox-
icity, lipotoxicity, impaired incretin release/action, amylin
accumulation and decreased -cell mass are implicated in
pancreatic b-cells impairment.
Insulin resistance, in pharmacological terms, can be de-
ned as a state in which the normal amounts of insulin
produce a subnormal biological response. It connotes
resistance to the effects of insulin on glucose uptake, me-
*
This paper was presented at the First congress on diabetes mel-
litus, Banja Luka, Republic of Srpska, Bosnia & Herzegovina,
March, 2013. (1 st Diabetology congress of Republic of Srpska,
21-24.03.2013.)
80
Scripta Medica
tabolism or storage. Insulin resistance is manifested by the
decreased insulin-stimulated glucose uptake in adipocytes
and skeletal muscles and impaired suppression of hepatic
glucose output.
5
The main causes of the insulin resistance
are genetic predisposition, obesity and physical inactiv-
ity.
6
The large amount of abdominal (visceral) fat, found
in obese people, is a source of bioactive mediators that di-
rectly contribute to insulin resistance and also affect lipid
proles, blood pressure and vascular inammation.
7-9
The fact that T2DM patients have different combinations of
-cells impairment and insulin resistance is well-known,
but we have investigated the characteristics of these disor-
ders in a long-standing, poorly controlled T2DM patients
treated only by peroral antidiabetics before hospitaliza-
tion in the Cantonal Hospital Zenica because of the insulin
therapy introduction. The assessment of -cells function
and insulin resistance in a long-standing T2DM patients,
as well as the assessment of HbA1c and obesity allows set-
ting of an appropriate glycemic target for T2DM patients.
The aim of our study was to examine the degree of -cells
function and the presence of insulin resistance in patients
with a long-standing type 2 diabetes.
Materials And Methods
Study subjects. The retrospective study was carried out
at the Cantonal Hospital Zenica. The data from medical re-
cords of 30 patients of both sexes (12 males, 18 females)
with the mean age of 59 years (SD=7.88) were analyzed.
The study included the patients with a long-standing
T2DM (disease duration more than 5 years) with the mean
duration of the disease of 10 years (SD=5.36), treated with
peroral antidiabetics. The patients were hospitalized from
August 2010 to October 2011 because of the insulin therapy
introduction. The body mass index (BMI), an estimate of
overall adiposity, was calculated as the weight in kilograms
divided by the height in meters squared. The mean value of
BMI was 31 kg/m (SD=4.74).
Laboratory data. After an overnight fast, the blood
samples were drawn for the measurement of fasting blood
glucose (FBG), insulin and glycated hemoglobin (HbA1c)
concentrations. The measurements were performed at the
Department of Laboratory Diagnostics, Cantonal Hospital
Zenica by the standard laboratory methods. Specically,
glucose concentrations were measured by enzymatic colo-
rimetric assay on Hitachi 912 (Roche, Basel, Switzerland),
insulin by chemiluminescentmicroparticle immunoassay
on Architect (Abbot, North Chicago, IL, USA) and HbA1c
by turbidimetric immunoassay for glycated hemoglobin/
modication of the alkaline hematin reaction for total
hemoglobin on Dimension (Siemens, Munich, Germany).
The percentages of functional -cells in pancreas (HOMA-
%B), insulin sensitivity (HOMA-%S) and insulin resistance
(HOMA-IR) were calculated using a Homeostatic Model
Assessment (HOMA) calculator v2.2. Original HOMA
1 model (rst described in 1985. by Matthews et al.) is a
structural mathematical model which allows values for in-
sulin sensitivity (which is reciprocal of insulin resistance)
and -cells function, expressed as a percentage of nor-
mal, to be obtained if fasting plasma glucose and insulin
concentrations are known. HOMA 2, currently solved
computer model, accounts the differences between hepatic
and peripheral insulin secretion or decreases in hepatic
glucose production for plasma glucose concentratins above
10 mmol/L, or renal glucose losses. The updated version
(1996) of HOMA model incorporates an estimate of proin-
sulin secretion into the model and allows the use of total or
specic insulin assays.
Statistical analysis. The obtained data were analyzed
by statistical software SPSS 19(SPSS Inc, Chicago, IL,
USA). The results of descriptive statistics were expressed
as the mean and standard deviation (SD) or median with
the range (25-75 percentile) depending on the data distri-
bution.
Results
The results of descriptive statistics are presented in tables
1. and 2. The mean FBG value was out of the reference
range (3.3-6.1 mmol/L). The mean HbA1c value was also
out of the reference range (4.8-6.0 %), as expected.
Statistical parameters
Mean SD Min Max Med Range
Age (years) 59 7.88 46 77 57 53.0-62.5
Disease duration (years) 10 5.36 5 23 10 5.0-15.0
BMI (kg/m) 31 4.74 21 38 32 26.8-34.3
HbA1c (%) 10.0 1.52 7.1 13.2 10.1 8.7-11.0
FBG (mmol/L) 12.4 4.15 5.5 20.4 11.4 9.4-16.5
Table 1. The Demographic, anthropometric and glycemic control parameters in 30 type 2 diabetic patients
Abbrevations: BMI-body mass index; HbA
1
c-glycated hemoglobin; FBG-fasting blood glucose; SD-standard deviation; Min-minimum
value in the group;Max- maximum value in the group; Med-median value; range- 25-75 percentile.
81 Kadi, et al
The mean blood insulin value was within the reference
range (3-17 mmol/L). The mean value of HOMA-%B was
highly reduced. The median value of HOMA-%S was re-
duced and according to that the median value of HOMA-IR
was increased moderately.
HOMA-IR values were elevated (HOMA-IR>1) in majority
of the patients (26 patients, 87%). Variety of combinations
of insulin deciency and insulin resistance were present.
Discussion
We examined the presence and the degree of -cells dis-
function and insulin resistance in the long-standing T2DM
patients. The obtained results revealed the normal insulin
level in relative terms. But, in absolute terms, such a level
was insufcient to maintain normoglycemia in T2DM pa-
tients.
Insulin secretion and action govern glucose homeostasis
through two feedback loops. A rise in glucose level stim-
ulates insulin secretion, which lowers plasma glucose,
but as a consequence, the sustained hyperinsulinemia
inhibits both insulin secretion and action.Finally, per-
sistent plasma glucose elevation (glukotoxicity) impairs
-cells function and leads to hepatic and muscle insulin
resistance.All the patients included in the study had a
highly reduced -cells function. We also found that major-
ity of the patients had the moderate insulin resistance.
Our results also show that the patients were poorly con-
trolled and obese. It has been found that obesity accompa-
nies 80 % of the diabetics in the Western world.It is even
featured in some subclassications of diabetes but is not
required for diabetes diagnosis.
The weakness of our study is the lack of possibility for
comparison of the obtained data with the data at the
time of setting the T2DM diagnosis. In spite of that, the
published data about initial disfunction show that the
progressive decline of -cells function exists in a long-
standing T2DM patients. It has been found that 50-75% of
the secretory capacity of the -cells is already lost by the
time fasting hyperglycemia develops.Once overt T2DM
is present, -cells function declines progressively with
time.According to United Kingdom Prospective Diabetes
Study (UKPDS), the average annual loss of -cells function
in untreated patients is 4%.
We have found a variety of combinations of insulin de-
ciency and insulin resistance in the T2DM patients includ-
ed in our study. Therefore, estimation of -cells function
and insulin resistance is important for making the medi-
cal decision that will lead to the adequate pharmacological
interventions (correction of oral therapy, introduction of
basal, combined or intensive insulin therapy ) combined
with diet and exercise. This approach may improve and
preserve -cells function before it reaches critically low
levels.
Authorship Statement
DK is responsible for the study design, the manuscript writing and
accuracy of the data analysis, DDS is responsible for the data col-
lection and critical revision of the manuscript, SH participated in
the data interpretation and critical revision of the manuscript.
Financial Disclosure
The authors declare no conict of interest.
References
1. Ismail-Beigi F. Pathogenesis and glycemic management of type
2 diabetes mellitus: a physiological approach. Arch Iran Med
2012;15(4):239-46.doi:012154/AIM.0014.
2. DeFronzo RA, Abdul-Ghani MA. Preservation of -cell Func-
tion: The Key to Diabetes Prevention. I ClinEndocrinolMetab
2011;96(8):2354-66. doi:10.1210/jc.2011-0246.
3. Ferrannini E. Insulin resistance versus insulin deciency in
non-insulin-dependent diabetes mellitus: problems and pros-
pects. Endocr Rev 1998;19(4):477-90.
4. Krentz AJ. Insulin resistance. BMJ 1996;313(7069):1385-9.
5. Kahn BB, Flier JS. Obesity and insulin resistance. JClin Invest
2000;106(4):473-81.
6. mire J. Obesity and metabolic insulin resistance. Medicus
2004;13(2):163-71.
Table 2. The insulin level and characteristics of Homeostatic Model Assessment in 30 type 2 diabetic patients
Statistical parameters
Mean SD Min Max Med Range
Insulin (mol/L) 12.8 6.11 2.6 24.9 12.0 7.7-18.1
HOMA-%B (%) 31 18.99 3.7 85.5 27 16.9-41.9
HOMA-%S(%) 59 36.74 2.4 142.9 49 32.2-82.4
HOMA-IR (1) 2.4 1.56 0.7 8.1 2.0 1.2-3.1
Abbrevations: HOMA-%B-percentage of functional -cells; HOMA-%S-percentage of insulin sensitivity; HOMA-IR-insulin resistance;
SD-standard deviation;Min-minimum value in the group;Max-maximum value in the group; Med- median value; range -25-75 percentile.
82
Scripta Medica
7. Meyer MR, Clegg DJ, Prossnitz ER, et al. Obesity, insulin
resistance and diabetes: Sex differences and role of oestrogen
receptors. ActaPhysiol(Oxf) 2011;203(1):259-69.doi:10.1111/
j1748-1716.2010.02237.x.
8. Mittelman SD, Van Citters GW, Kim SP, et al. Longitudinal
compensation for fat-induced insulin resistance includes re-
duced insulin clearance and enhanced -cell response. Diabetes
2000;49(12):2116-25.
9. Smiri-Duvnjak L. Pathophysiology of the metabolic syndrome.
Medicus 2004;13(2):151-61.
10. Dansuntornwong B, Chanprasertyothin S, Jongjaroenprasert W,
et al. The relation between parameters from homeostasis model
assessment and glycemic control in type 2 diabetes. J Med Assoc
Thai 2007;90(11):2284-90.
11. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA
modeling. Diabetes Care 2004;27:1487-95.
12. Abdul-GhaniMA.Type 2 Diabetes and the evolving paradigm in
glucose regulation. Am J Manag Care 2013;19(3):43-50.
13. BMI Classication.Global Database on Body Mass Index.
WHO.2006
14. Kahn SE. The importance of -cell failure in the development
and progression of type 2 diabetes. J ClinEndocrinolMetab
2001;86(9):4047-58.doi:10.1210/jc.86.9.4047
15. UK Prospective Diabetes Study Group.UK Prospective Diabetes
Study 16. Overwiev of 6 years therapy of type II diabetes: a
progressive disease. Diabetes 1995;44:1249-58.
Funkcija -elija i inzulinska rezistencija kod dugotrajnog
tip 2 diabetes mellitus-a
APSTRAKT
Uvod. Svaki pacijent sa tip 2 diabetes mellitus-om secernira manje inzulina nego to je potrebno za njegov/njen nivo inzulinske
senzitivnosti, a veina ih ima neki stepen inzulinske rezistencije. Mjeavina inzulinske decijencije i inzulinske rezistencije je
razliita kod svakog pacijenta, a kod bilo kojeg pacijenta moe varirati za vrijeme trajanja bolesti. Cilj ove studije je bio da ispita
stepen -elijske funkcije i prisustvo inzulinske rezistencije kod pacijenata sa dugotrajnim tip 2 dijabetesom.
Metode. Studija je ukljuivala 30 pacijenata oba pola (12 mukaraca, 18 ena) sa srednjim vrijednostima starosne dobi 59
godina (SD=7.88) i trajanja bolesti 10 godina (SD=5.36). Srednja vrijednost BMI je bila 31 kg/m (SD=4.74). Koncentracije glukoze
i inzulina natate i HbA1c u krvi su odreene koritenjem standardnih laboratorijskih metoda. Procenti funkcionalnih -elija
pankreasa (HOMA-%B), inzulinske senzitivnosti (HOMA-%S) i inzulinska rezistencija (HOMA-IR ) su izraunati koritenjem HOMA
kalkulatora v2.2. Dobiveni podaci su analizirani statistikim softverom SPSS 19.
Rezultati. Srednja vrijednost HbA1c je bila 10 % (SD=1.52), a FBG 12 mmol/L (SD=4.15). Srednja vrijednost insulina je bila 13
mol/L (SD=6.11), a HOMA-%B 31 % (SD=18.99). Medijana vrijednosti HOMA-%S je bila 49 % (32.2-82.4), a HOMA-IR 2 (1.2-3.1).
87% pacijenata je imalo HOMA-IR >1.
Zakljuak. Izrazito sniena -elijska funkcija i posljedina inzulinska decijencija, najee udruena sa umjerenom inzulinskom
rezistencijom je utvrena kod pacijenata sa dugotrajnim tip 2 diabetes mellitus-om.
KLJUNE REI
Tip 2 dijabetes melitus; funkcija -elija; rezistentnost na inzulin.
83
Scripta Medica
UDK 616.438-089.85
Golnaz Alemzadeh
1
,
Svjetlana Stoisavljevi-
atara
2
,
Gennadiy Voronov
1
,
Rajko Igi
1, 2
1
Department of Anesthesiology and
Pain Management, John H. Stroger
Hospital of Cook County, Chicago,
Illinois 60612;
2
Faculty of Medicine, University
of Banja Luka, 78000 Banja Luka,
Republic of Srpska, Bosnia and
Herzegovina.
Correspondence
Golnaz Alemzadeh, MD
John H. Stroger Hospital of Cook
County, Chicago, Illinois 60612, USA
email: golnazal@yahoo.com
ORIGINAL ARTICLE
Anesthesia Residents Have Limited
Knowledge of Biostatistics
ABSTRACT
We surveyed 27 anesthesiology residents to determine their basic understanding of
biostatistics. We wanted to see how well they could interpret statistical presentation
in biomedical literature and assess research outcomes. The questionnaire included
three sections: demographics of the participants, their knowledge of statistics
(21 questions) and their attitude and self reported condence about biostatistics.
Recognition of a meta-analysis was the highest scoring question (85% gave the
correct answer), and recognition of a case-control study scored the lowest (22%).
There was no effect of gender, the year of study, the number of years elapsed since
graduation at the medical school, or country in which the participants had attended
medical school (US or foreign schools). The only factor that increased the number
of correct answers signicantly was an additional course in biostatistics that two
participants had attended after graduation. Sixty six percent indicated they did not
understand all of the statistics they encountered in journal articles, but all of the
participants felt it was important to be able to understand the literature. We conclude
that most residents in this study lack the knowledge in biostatistics needed to
interpret results in medical publications. Most participants in this survey expressed
the desire to improve their knowledge on this subject, even though it would require
taking special courses in basic epidemiology, and statistics for the non-statistician
during their residency training.
KEY WORDS
Anesthesiology residents, knowledge biostatistics, survey, medical publications.
DOI: 10.7251/SMD1302083A (Scr Med 2013;44:83-5)
Accepted: July 15, 2013
Most biomedical and clinical studies involve the selection
of a small sample from a larger population (humans, ani-
mals, microorganisms, etc), from which the ndings can
be then extrapolated to the larger population with vary-
ing degrees of condence. Thus, it is important to under-
stand what each of the statistical tools can do and how to
use them properly. A basic understanding of statistics and
epidemiological principles related to experimental design,
methodology, data analysis, and interpretation of ndings
is also necessary to understand publications of evidence-
based medicine and the majority of clinical studies.
1
Be-
cause physicians depend on published literature to keep
current with medical information, they need to under-
stand statistical methods in order to interpret published
research outcomes appropriately.
Medical researchers in academic medicine need advanced
knowledge of these skills to plan and successfully conduct a
study and to analyze data acquired from clinical investiga-
tions. Thanks to Ronald Fisher (1890-1962), powerful statis-
tical methods have made a great impact on studies related to
health, and these methods continued to improve. Today we
can prepare a good study design, estimate adequate sample
size, and provide reliable analysis of the results.
2
Medical
researchers often seek help from a professional statistician
to solve complex statistical demands. However, simple ex-
perimental design and estimate of the essential sample size
is usually straightforward. Even when a statistician is readily
available, the investigator needs a basic knowledge of study
design, factors affecting sample size, and the appropriate
statistical test in order to obtain the best results. A well-in-
formed investigator will prepare a better research design and
make the proper statistical evaluation of the data collected.
One obstacle common to novice researchers is how to re-
port the data for publication in a journal. To help them de-
84
Scripta Medica
termine how to present their data, there are available sev-
eral useful papers on how to use standard deviation (SD) or
standard error of the mean (SEM, or SE), condence inter-
vals (CI) and other details, such as when to use particular
statistical tool.
3,4
A recent study
5
found that most residents in internal
medicine lack the knowledge of biostatistics needed to in-
terpret many of the results in published clinical research.
We questioned anesthesiology residents on their basic
understanding of biostatistics in order to identify specic
areas that should be included in the residency program
to prepare residents for this important lifelong learning
skill.
Methods
Twenty-seven residents in the department of Anesthe-
siology and Pain Management of the Stroger Hospital
of Cook County agreed to participate in this study. They
answered a questionnaire that included three sections:
the demographics of participants, their basic knowledge
of statistics (21 questions) and their attitude and self re-
ported condence about biostatistics. The participants in
this descriptive study had to complete the document in-
dividually under the conditions of a formal examination.
Knowledge scores were expressed as the percentage of cor-
rect answers. Missing answers were counted as incorrect
answers. All analyses of the data obtained were performed
with InStat software.
Results
All 27 participants (12 females and 15 males; 6 US and
21 foreign graduates) in our department completed their
questionnaires. The table shows the percentage score
for the twelve selected questions answered correctly.
Recognition of a meta-analysis was the highest scoring
question (85%), and the lowest score was in recogniz-
ing case-control study (22%). There was no effect of gen-
der, the year of study, the number of years elapsed since
graduation at the medical school, or country in which the
participants had attended medical school (US or foreign
schools). The only factor that increased the number of
correct answers significantly was an additional course
in biostatistics that was attended two participants after
graduation. Sixty-six percent indicated they did not un-
derstand all of the statistics they encountered in journal
articles, but all of them felt it was important to under-
stand the literature. Twenty of the participants stated
that they would like to devote time to additional study
of statistics, especially to understand the principles of
probability and research design.
Table: Correct answers for selected questions
Subject to identify,
recognize or interpret
Per cent of
correct answers
Continuous variable 48
Case-control study 22
Cohort study 63
Meta-analysis 85
P value 52
Purpose of double blinding 78
Purpose of randomization 56
Null hypothesis 59
t-test 37
Chi-square 48
Analysis of variance (ANOVA) 74
95% Condence interval 48
Discussion
The results of this survey show that anesthesia residents
need further education on the application and interpreta-
tion of basic epidemiological principles and biostatistics.
Similar ndings were obtained when we tested the resi-
dents of various other clinical disciplines (55 participants)
in Banja Luka with the same questionnaire translated in
Serbian (unpublished observation). The majority of the
residents in Banja Luka declared their interest in addition-
al study of statistics, especially in how to design a study
and how to estimate the number of patients to include. A
nice short paper on the latter topic was published recently
in the journal Radiology.
6
Lack of understanding of statistics can lead to erroneous
interpretations of research ndings as well as the inability
to critically assess published evidence. For those residents
who wish to participate in clinical research, knowledge of
statistics is essential. Not a single participant in our sur-
vey knew that statistical variability of the data (mean +/-
SD for n observations, for example: 48 +/- 8, n= 42) could
be presented as: 48, SD = 8, n = 42. This indicates that
the textbooks of statistics they have been using probably
do not include this recent change in statistical presenta-
tion.
3

We conclude that most residents in our study lack the
knowledge in biostatistics needed to interpret many results
in medical publications. Most of the participants expressed
their desire to improve their knowledge through courses
in basic epidemiology and statistics for the non-statistician
during residency training. Although there are many ex-
cellent books in statistics,
7,8
we presented short statistical
85 Alemzadeh, et al
courses for the residents and the novice authors in our hos-
pitals, both in Chicago and Banja Luka. We also included
a chapter on basic statistics in our textbook on biomedi-
cal writing and publishing.
9
In addition, universities, large
hospitals, and even medical journal editors could regularly
organize courses designed to provide training in planning
scientic research and statistics.
References
1. Greenhalgh T. How to read a paper. The basics of evidence-
based medicine. London, BMJ, 2006.
2. Goli D, krbi R, Voronov G. Reporting statistics in medicine.
Scr Med 2010;41:77.
3. Curran-Everett D, Benos DJ. Guidelines for reporting statistics
in journals published by the American Physiological Society. J
Appl Physiol 2004;97:457-9.
4. Stoisavljevi-atara S, Igi R. Statistical presentation of data in
biomedical publications. J BUON 2010;15:182-7.
5. Windish DM, Huot SJ, Gree ML. Medicine residents under-
standing of the biostatistics and results in the medical litera-
ture. JAMA 2007;298:1010-22.
6. Eng J. Sample size estimation: How many individuals should be
studied. Radiology 2003;227:309-13.
7. Myles PS and Gin T. Statistical methods for anesthesia and
intensive care. Edinburgh, Butterworth, 2000.
8. Swinscow TDV. Statistics at square one, ninth edition. London,
BMJ, 1999.
9. Igi R, Skrbi R. Kako se piu i publikuju biomedicinska nauna
saoptenja. Banja Luka/Laktai, Grafomark, 2012.
Specijalizanti iz anesteziologije nedovoljno poznaju
statisktiku
APSTRAKT
Anketirali smo 27 specijalizanata iz anesteziologije da ustanovimo osnovno razumevanje biostatistike. eleli smo da ustanovimo
kako oni interpretiraju statistike podatke u biomedicinskoj literaturi da bi procenili rezultate istraivanja. Upitnik je ukljuio tri
segmenta: demografske podatke o anketiranim, njihovo poznavanje statistike, (21 pitanje) i njihov interes za biostatistiku. Najvie
tanih odgovora je dato na prepoznavanje meta-analize (85%), a najmanje na casecontrol studije (22%). Na broj tanih odgovora
nije uticao pol ispitanika, broj godina nakon zavretka studija ili zemlju u kojoj su ispitanici zavrili medicinski fakultet. Jedini faktor
koji je poveao broj tanih odgovora bio je dodatni kurs biostatistike kod dva uesnika koji su ga pohaali nakon diplomiranja.
ezdeset est procenata uesnika navelo je da bi voleli da boljim poznavanjem mogu svatiti lanke iz literature. Zakljuili smo
da veina specijalizanata koje smo anketirali slabije poznaju biostatistiku neophodnu za interpretaciju medicinskih publikacija.
Veina uesnika je izrazila elju da unapredi svoje znanje iz te oblasti, ak ako to zahteva dodatni kurs iz osnova epidemiologije i
statistike potrebne ne/statistiaru za vreme specijalizacije.
KLJUNE REI
Specijalizanti anesteziologije, poznavanja biostatistike, anketa, medicinske publikacije.
86
Scripta Medica
UDK 616.711-007.5-053.5
Dragana Dzamic
1
,
Ivana Petronic
1,2
,
Dejan Nikolic
1
,
Dragana Cirovic
1,2
,
Tatjana Knezevic
1
,
Radivoj Brdar
2,3
1
Physical Medicine and Rehabilita-
tion, University Childrens Hospital,
Belgrade, Serbia
2
Faculty of Medicine, University of
Belgrade, Belgrade, Serbia
3
Pediatric Surgery, University Child-
rens Hospital, Belgrade, Serbia
Correspondence
Dragana Dzamic, MD, MSc
Sluba Fizikalne medicine i rehabili-
tacije, Univerzitetska deja klinika,
11000 Beograd, Serbia
email: denikol27@gmail.com
PRELIMINARY REPORT
Comparison of Conservative
Treatments for Children With
Idiopathic Scoliosis
ABSTRACT
Introduction. We evaluated the effectiveness of different methods of conservative
treatment modalities for the treatment of idiopathic scoliosis in children.
Patients and Methods. The study included 61 patients with scoliosis. The
modalities of physical treatment included exercise, exercise plus traction, exercise
plus mider, or a combination of exercise, traction and mider. We evaluated three
age groups: patients between 5 and 8 years of age (Group 1), those between 9 and
11 years of age (Group 2) and those between 12 and 14 years of age (Group 3).
The follow-up period was three months after the initial treatment, during which all
patients continued physical treatment. The outcome was categorized as improved,
unchanged or worsened.
Results and discussion. After three months of treatment the most frequent
outcome was unchanged (62% of all participants). Exercise was the treatment most
frequently applied (54% of the total group). We found no signicant difference in
treatment modes and treatment outcomes after three months (p>0.05). Exercise
alone was the most effective treatment for the youngest patients (Group 1). We also
noted that a combination of exercises and traction was most effective in patients
above 10 years of age; the majority of other patients showed either improvement or
unchanged outcomes in curve progression.
Conclusion. Patients with congenital scoliosis should be assessed individually
using a multidisciplinary approach. The rehabilitation program should be individually
prescribed, implemented daily and should include regular check-ups between three
and six months to assess spine curve progression.
KEY WORDS
Scoliosis, rehabilitation, children, age.
DOI: 10.7251/SMD1302086DZ (Scr Med 2013;44:86-9)
Accepted: August 15, 2013
Idiopahic scoliosis is dened as a three-dimensional de-
formity of the spine.
1
Age is an important determinant for
the progression of this deformity. Infantile scoliosis will
resolve spontaneously in about 80% of patients, while in
adolescents, scoliosis generally takes a benign course.
2

The conservative treatment for scoliosis, particularly in
children, consists of an exercise program with eventual
inclusion of traction and/or mider as needed. Currently,
physicians in different countries have different concepts
as to the need for physical therapy or surgery.
3,4
The ef-
fectiveness of exercise, particularly for reduction of curve
progression, pain onset and as treatments for scoliosis
pulmonary dysphunction, was noted previously.
5-7
A criti-
cal review of the complexisity of scoliosis treatment em-
phasized that the Cobb angle alone should not be the only
parameter for estimation of the need for surgery in these
patients.
8
The aim of our study was to evaluate the effectiveness of
different methods of conservative treatments for idiopath-
ic scoliosis in children.
Patients and Methods
Study groups. The study included 61 patients who were
referred to the University Childrens Hospital (UCH) for
treatment of scoliosis. The average age of the participants
87 Dami, et al
was 11.8 (SD = 2.1) years old. The patients were divided
into three groups according to age: Group 1 (5-8 years old);
Group 2 (9-11 years); Group 3 (12-14 years).
Diagnosis and treatment. Clinical and neurological ex-
aminations conrmed the diagnosis of scoliosis, and all
patients were followed by X-ray and imaging procedures.
Cobbs angle was used to establish the diagnosis of scoliosis
and to indicate recommendations for treatment. Accord-
ing to previous recommendations, a Cobbs angle above 10
0

was considered to be a scoliotic deformity.
9
All patients
were evaluated by board-certied physicians and pediatric
surgeons. Upon conrmation of the diagnosis of idiopathic
scoliosis, eligible participants between 5 and 14 years of age
were included in the physical therapy program. The physi-
cal treatment included: exercise, exercise plus traction,
exercise plus mider, and a combination of exercise, trac-
tion and mider. Mider was recommended for patients with
idiopathic scoliosis when the Cobbs angle was between
20
0
-45
0
or when Cobbs angle was between 20
0
-30,
0
with
5
0
progression between two consecutive measurements.
9

After considering the type, degree of the curve and the
ages of the participants, exercise was the most frequently
applied (33 patients, 54%), exercise and mider (2 patients,
3%), exercise and traction (10 patients, 16%), and combined
treatment (16 patients, 26%). We grouped patients accord-
ing to the age of onset of idiopathic scoliosis as described
above; the size of each group follows: Group 1 5 patients,
Group 2 11, Group 3 45. The physical treatment for each
group was continued regularly for three months. The en-
tire study group was then re-evaluated. The outcome for
each individual was categorized as improved, unchanged
or worsened.
The study was approved by our Institutional Review Board
and was carried out in accordance with good clinical prac-
tice. Prior to inclusion in the study, parents or legal guard-
ians were informed as to the study protocol, and informed
consent was obtained.
Statistical analysis. The chi-square test was used to
evaluate how each treatment mode inuenced the out-
come. We used Fishers test to evaluate treatment out-
comes between groups and accepted p<0.05 as indicative
of statistical signicance.
Results
After three months of treatment, the condition of 38 pa-
tients remained unchanged (62%) regardless of the mo-
dality of treatment applied (Table 1). Eight of 33 patients
who did exercise alone improved; six of those are from the
Group 3. Out of ten patients who had both the exercise and
traction program, two showed an improved condition.
However, six children from the same group developed a
Program Age groups*
Improved Unchanged Worsened
n n n
Exercise
Group 1 1 3 -
Group 2 1 6 -
Group 3 6 11 5
Total 8 20 5
Exercise &
Traction
Group 1 - 1 -
Group 2 - - -
Group 3 2 6 1
Total 2 7 1
Exercis &
Traction &
Mider
Group 1 - - -
Group 2 1 2 -
Group 3 2 8 3
Total 3 10 3
Table 2. Treatment outcomes of rehabilitation programs related to age
*Group 1 =5-8 years; Group 2 = 9-11 years; Group 3 = 12-14 years
Table 1. Effects of various thre months physical therapy pro-
grams for treatmen of scoliosis. The patients from all groups
are included.
Treatment
Improvement Unchanged Worsened
n n n
Exercise (n=33) 8 20 5
Exercise+mider
(n=2)
1 1 0
Exercise+traction
(n=10)
2 7 1
Exercise+traction
+mider (n=16)
3 10 3
Total 14 38 9
88
Scripta Medica
worsened condition. The combination of an exercise pro-
gram with traction and mider resulted in an improvement
of three children (Table 2). Of the two patients assigned
to treatment with both exercises and mider (Group 1 and
Group 2), one improved and the other experienced no
change in condition. There were no signicant differences
of the results obtained with different treatments in the de-
ned age groups.
Discussion
Our ndings indicate that that exercise is effective for all
patients who were diagnosed with idiopathic scoliosis,
while inclusion of other treatment modes, such as mider
or traction, does not necessarily inuence the outcome or
course of treatment. These results are consistent with pre-
vious ndings that exercise as physical therapy for patients
with scoliosis was more effective for prevention of curve
progression than other treatments.
10
However, it is impor-
tant to emphasize that further evaluation of the extent and
type of exercise is needed to establish the most effective
treatment for scoliosis. It was shown previously that an in-
dividual approach to the patients with individually adapt-
ed exercises is more effective than the usual physiotherapy
protocol.
11
Given the previous ndings on the effectiveness of exer-
cise, we believe that treatment could be improved by in-
dividual prescription of the type and extent of exercise. In
addition, each treatment program should be tailored to the
individual with scoliosis, depending upon more parame-
ters present at evaluation than by assessment of the Cobbs
angle alone.
Numerous published studies indicate that different mod-
ules of treatment are prescribed for different ages of pa-
tients with diagnosed idiopathic scoliosis.
8,12,13
Even though
we found no statistical signicance between the different
rehabilitation modes within the dened age groups, we
suggest that different modules of rehabilitation may inu-
ence, to some degree, the treatment outcome. We noted
that exercise in combination with traction was most ef-
fective in patients older than 9 years; curve progression in
the majority of those patients either improved or remained
unchanged. Aside from the effectiveness of exercise, these
slightly older patients may be more cooperative as to the
proper implementation of their therapy.
The small number of patients limited our study, so any fu-
ture study should include a larger number of participants.
Since we included only those patients with idiopathic sco-
liosis, additional investigations should also include other
types of scoliosis.
In conclusion, young patients with idiopathic scoliosis
should be assessed individually using a multidisciplinary
approach. Regardless of additional treatments, such as
mider or traction, exercise appears to be the most impor-
tant component in the conservative treatment of idiopathic
scoliosis. Each rehabilitation program should be individu-
ally prescribed, implemented daily and include regular
check-ups and timely follow-up until the termination of
skeletal growth.
Authors Contribution
DDarticle writing, critical revisions, therapy design; IPphysi-
cal examination, article writing, reference search; DN article
writing, methodological postulations, critical revisions; DC
therapy follow-up, literature search; TK methodological postula-
tions, critical interpretation of results; RB orthopedic examina-
tion, diagnostics.
Conict of interest
Authors declare no conict of interest.
Rerefences
1. Parent S, Newton PO, Wenger DR. Adolescent Idiopahhic: etiol-
ogy, anatomy, natural history, and bracing. Instr Course Lect
2005; 54:529-36.
2. Trobisch P, Suess O, Schwab F. Idiopathic scoliosis. Dtsch Arz-
tebl Int. 2010;107(49):875-83.
3. Hawes MC. The use of exercises in the treatment of scoliosis: an
evidence-based critical review of the literature. Pediatr Rehabil
2003;6:171-82.
4. Weiss HR, Negrini S, Hawes MC, et al. Physical exercises in the
treatment of idiopathic scoliosis at risk of brace treatment --
SOSORT consensus paper 2005. Scoliosis 2006;1:6.
5. Weiss HR, Bickert W. Improvement of the parameters of right-
heart stress evidenced by electrocardiographic examinations by
the in-patient rehabilitation program according to Schroth in
adult patients with scoliosis. Orthop Prax 1996; 32:4503.
6. Ferraro C, Masiero S, Venturin A. Effect of exercise therapy on
mild idiopathic scoliosis. Preliminary result. Europa Medico
Physica 1998;34:2531.
7. Negrini S, Antonini G, Carabalona R, et al. Physical exercises
as a treatment for adolescent idiopathic scoliosis. A systematic
review. Ped Rehab 2003;6:22735.
8. Weiss HR, Goodall D. The treatment of adolescent idiopathic
scoliosis (AIS) according to present evidence. A systematic
review. Eur J Phys Rehabil Med 2008;44:177-93.
9. Kim H, Kim HS, Moon ES, et al. Scoliosis Imaging: What radi-
ologists should know. RadioGraphics 2010;30:1823-42.
10. Romano M, Minozzi S, Bettany-Saltikov J, et al. Exercises for
adolescent idiopathic scoliosis. Cochrane Database Syst Rev
2012; 8:CD007837.
11. Negrini S, Zaina F, Romano M, et al. Specic exercises reduce
brace prescription in adolescent idiopathic scoliosis: a prospec-
tive controlled cohort study with worst-case analysis. J Rehabil
Med 2008;40:451-5.
12. Lincoln TL. Infantile idiopathic scoliosis. Am J Orthop (Belle
Mead NJ) 2007;36:586-90.
13. Morin C.Treatment of idiopathic scoliosis in children during the
growth period. Bull Acad Natl Med 1999;183:731-5.
89 Dami, et al
Poreenje konzervativnog tretmana kod dece sa
idiopatskom skoliozom
APSTRAKT
Uvod: Ispitivana je ekasnost razliitih metoda konzervativne terapije u tretmanu dece sa idiopatskom skoliozom.
Pacijenti i metode: Ispitivanjem je obuhvaeno 64 dece sa skoliozom. Vrste zikalne terapije koje su primenjivane su: vebe,
vebe sa trakcijom, vebe sa miderom ili kombinacija vebi, trakcije i midera. Praene su 3 uzrastne grupe: pacijenti izmeu 5-8
godina ivota (Grupa 1), izmeu 9-11 godina ivota (Grupa 2) i pacijenti izmeu 12-14 godina (Grupa 3). Period praenja je bio
3 meseca od poetka tretmana. Ishod konzervativne terapije je kategorisan kao: poboljanje, nepromenjeno stanje ili pogoranje.
Rezultati i diskusija: Posle 3 meseca od poetka terapije u 62% sluaja je dolo do poboljanja. Najee su primenjivane
vebe kao tip tretmana (54%). Nije naena znaajna razlika u ishodu tretmana u odnosu na tip terapije (p>0.05). Samo vebe su
najekasniji metod terapije u mlaoj grupi ispitanika (Grupa 1). Pokazano je da je kombinacija vebi i trakcija najekasnija metoda
u leenju dece preko10 godina ivota.
Zakljuak: Pacijente sa idiopatskom skoliozom treba individualno analizirati uz multidisciplinarni pristup. Rehabilitacioni program
treba biti individualno dizajniran i svakodnevno ga treba sprovoditi uz redovne kontrole izmeu 3 i 6 meseci.
KLJUNE REI
Skolioza, rehabilitacija, deca, uzrast.
90
Scripta Medica
Abayomi Akintorin,
Bozana Alexander,
Ahmad Abou Leila,
Jose Humanez,
James McPencow,
John. H. Stroger, Jr. Hospital of Cook
County, Chicago, IL
Correspondence
Abayomi Akintorin MD
pain management
John H. Stroger Jr. Hospital
Chicago,IL 60612
Email:
aakintorin@cookcountyhhs.org
CASE REPORT
Hemophilia AAcquired During
Coronary Artery Bypass Grafting
ABSTRACT
We report a challenging case of a rare cause of post operative bleeding that
occurred after the coronary artery by-pass graft procedure. We believe that acquired
hemophilia A was the main culprit. Patient post CABG developed nonsurgical
bleeding with new isolated PTT prolongation. Bleeding was resistant to conventional
therapy. Mixing studies didnt correct PTT, thus we ruled out factor deciencies.
Heparin effect was excluded by normal factor X levels. Patient received factor VIII
inhibitor bypass therapy after which corrected PTT and stopped bleeding. The triad
of acquired coagulopathy, noncorrectable PTT, and exclusion of heparin effect, make
acquired hemophilia A the most likely diagnosis.
KEY WORDS
Hemophilia A, CABG, factor VIII inhibitor, PTT, heparin.
DOI: 10.7251/SMD1302090A (Scr Med 2013;44:90-1)
Submitted: March 15, 2013
Accepted: April 18, 2013
UDK 616.151.5-07/-08
A 68-year-old, man with medical history of diabetes and
chronic hypertension presented for coronary artery bypass
grafting surgery. Patient had normal coagulation prole
prior to surgery. Initiation and weaning from cardiopul-
monary bypass (CPB) were uneventful with total CPB time
of 197 minutes. In the Intensive care unit (ICU) patient was
treated for retractable hypovolemia and increased chest
tube output. Patient was stabilized over night with the use
of blood products. Subsequently he underwent surgical ex-
ploration for continuous bleeding and coagulopathy. It was
noted that bleeding was from the soft tissues and not sur-
gically correctable. Coagulaton prole was characterized
by signicantly elevated PTT despite administration of
multiple blood products, including 17 units of FFP, 5 units
of cryoprecipitate, 15 units of platelets, 12 units of PRBCs
and 750 ml cell saver return. In addition, patient received
aminocaproic acid, DDAVP, Factor VII a, vitamin K and hy-
drocortisone. The patient returned to ICU with bleeding
rate of 1750ml/h and persistently elevated PTT>240 with
all other coagulation parameters essentially normal. Unre-
markable values of brinogen, heparin, PT, INR and plate-
lets were noted. Mixing studies showed correction of PT
with time but PTT remained elevated. These results could
be heparin effect (The factor Xa was normal and ruled out
heparin effect.) vs. true inhibitor (Figure 1). Hematology
service considered that this could be acquired hemophilia
Table 1. Medications associated with acquired Hemophilia A. Frequently, drug-induced anti-FVIII arises after hypersensitivity reactions
and remits shortly after withdrawing the offending drug. The pathophysiology of this phenomenon remains unknown. However, the strong im-
mune properties of both interferon (IFN) alpha and udarabine may explain the appearance of autoantibodies against FVIII and other immune
phenomena reported with their use.
1,
Antibiotics Anticonvulsants Miscelaneous
Penicillin Phenytoin Clopidogrel
Sulfonamides Methyldopa
Chloramphenicol Interferon alpha
Fludarabine
91
A with factor VIII inhibitor antibody. In the last effort they
recommended giving FEIBA (factor VIII inhibitor bypass-
ing agent) to counteract a possible inhibitor antibody to
FVIII. The next morning there was noted marked clinical
improvement. Chest tube output subsided, cardiac param-
eters improved and patient was weaned from hemody-
namic support. He was discharged to rehab facility with no
neurological sequel.
Discussion
Acquired hemophilia A is a rare bleeding diathesis caused
by antibodies directed against clotting factor VIII (FVIII).
It involves mostly soft tissues. Precipitating factors/condi-
tions associated with acquired hemophilia A are advanced
age, autoimmune conditions, malignancies, diabetes, cer-
tain viral infections, or postpartum. It may be associated
with the use of certain medications (Table 1). We present
a case where this immune deregulation developed during
open-heart surgery.
Acquired inhibitors against factor VIII, also termed acquired
hemophilia A, occur in non-hemophilic population with
an incidence of 1-4 per mil/year. Mortality rate, as severe
bleeding occur in up to 90% of cases, range from 8-22%.
2
The treatment priority is to arrest the acute bleeding and to
eradicate the factor VIII antibody.
3
Acute bleeding episodes
in patients with high-titer inhibitors can be treated using
human factor VIII bypassing agents, such as prothrombin
complex concentrates or recombinant activated factor VII.
References
1. Tiplady, CW, Hamilton PJ, Galloway MJ. Acquired haemophilia
complicating the remission of a patient with non-Hodgkins
lymphoma treated with udarabine. Clin Lab Haematol
2000;22:1635.
2. Franchini M, Lippi G. Acquired factor VIII inhibitors. Blood
2008;112:250-5.
3. Delgado J, Jiminez-Yuste V, Hernandez-Navarro F, Villar A.
Acquired hemophilia: review and meta-analysis focused on
therapy and prognostic factors. Br J Hematol 2003;121:21-35.
Figure 1. Elevated PTT initial work-up
Hemo lija A koja se pojavila u vreme koronarno-
arterijskog premotavanja
APSTRAKT
Prikazali smo rijedak uzrok koji je doveo do postoperativnog krverenja nakon premoavanja koronarne arterije (CABG).
Vjerujemo da je glavni uzrok tog krvarenja steena hemolija A. Nakon CABG procedure dolo je do krvarenja koje je praeno
prologiranim PTT (parcijalno tromboplastinsko vrijeme). Krvarenje je bilo otporno na konvencionalnu terapiju. Razliitim
ispitivanjima nije pokazano da PPT korigovano, stoga smo iskljuili njegovo pomanjkanje. Heparinski efekat je iskljuen jer je
nivo faktora X bio u granicama normale. Pacijent je primio faktor VIII inhibitor kao terapiju kod bypassa to je normalizolo PTT i
zaustavilo krvarenje. Trijada koja se sastoji od steene koagulopatije, nekorektabilane PTT i izostanak efekta heparina, upuuje
na to da je steena hemolija A najvjerovatnija dijagnoza.
KLJUNE REI
Hemophilia A, premoavanje koronarne arterije (CABG), inbitor faktora VIII, parcijalno tromboplastinsko vrijeme, heparin.
Akintorin, et al
92
Scripta Medica
Geeta Kutty
1
,
John E Yap
1
,
Shweta Gupta
2
,
Marin Sekosan
3
1
Department of Medicine,
2
Division of Hematology-Oncology,
3
Department of Pathology, John H
Stroger Jr. Hospital of Cook County,
1901 W Harrison St, Chicago, IL
60612, USA
Correspondence
Dr Marin Sekosan MD.
Department of Pathology, John H Stro-
ger Jr Hospital of Cook County, 1901 W
Harrison St, Lower Level, Chicago, IL
60612, USA.
Phone: +1 312 864 7546
Fax: +1 312 864 9002
Email: msekosan@cookcountyhhs.org
CASE REPORT
Advanced Esophageal Carcinoma
Expressing Human Chorionic
Gonadotropin (HCG-b)
ABSTRACT
Human Chorionic Gonadotropin (HCG; HCGb) is expressed by various solid
malignancies, including lung, pancreas, gastric and cervical cancers. Some previous
studies suggest that this indicates an adverse prognosis. However, most of these
studies evaluated HCGb expression by immunohistochemical methods, and the
clinical signicance of elevated levels of serum HCGb is not known. It may indicate
a particularly aggressive disease. This phenomenon has not yet been studied in
esophageal cancers. Here we present a case of a middle-aged woman with a poorly
differentiated esophageal carcinoma that expressed HCGb, and elevated levels of the
hormone appeared in her serum. These elevated serum levels were associated with
a very aggressive clinical course.
KEY WORDS
Esophageal cancer, Human chorionic gonadotropin, HCG
DOI: 10.7251/SMD1302092K (Scr Med 2013;44:92-4-26)
Submitted: August 23, 2013
UDK 616.149-008.331.1
A 46-year-old lady with a history of cholelithiasis pre-
sented with worsening, colicky epigastric and right upper
quadrant abdominal pain that had persisted for four to ve
months with no aggravating or relieving factors. She had
associated nausea, loss of appetite and a 40-pound weight
loss. She denied fevers, chills, vomiting, diarrhea, urinary
complaints or jaundice. She had regular but heavy men-
strual cycles and had four healthy children. Signicant
family history included ovarian cancer in her mother and
lymphoma in her sister. Our patient had never smoked, or
abused alcohol/drugs.
On physical examination, she was afebrile, pale but in no
distress, with a regular heart rate of 82/min and a respira-
tory rate of 18/min. Her blood pressure was 161/92 mmHg.
Systemic examination indicated normal lung, heart and
neurological functions. An abdominal exam revealed ten-
derness in the epigastrium and right upper quadrant with
no guarding or rigidity, no shifting dullness, no masses or
organomegaly and normal bowel sounds. Pelvic examina-
tion was normal.
Laboratory analysis showed normal serum electrolytes
and lipase, as well as normal renal and liver function.
Hemoglobin was 8.6 g/dL (normal = 11.7-14.9 g/dL) with
an MCV of 68/fL (normal = 81.8-96.9/fL). Serum ferri-
tin was 88.7 ng/ml (normal = 11-307 ng/ml) with a serum
iron of 9 mg/dL (45-182 mg /dL), low percent saturation
and a total iron binding capacity of 225 mg/dL (normal
250-425 mg/dL) consistent with anemia of inammation.
A urine pregnancy test was positive with an HCGb level
of 190 milli-International Units (mIU). A transvaginal
ultrasound showed multiple broids but no evidence of
uterine or tubal pregnancy. A spontaneous abortion was
suspected. However serial HCGb levels showed a plateau
with levels of 156 and 166 mIU, a nding that is incon-
sistent with spontaneous abortion. A CT scan of chest/
abdomen/pelvis showed irregular thickening of the distal
esophagus and gastric cavity with multiple liver metasta-
ses, predominantly in the left hepatic lobe with peri-por-
tal and retroperitoneal adenopathy. All tumor markers
CEA, CA 19-9, CA-125 and alpha-fetoprotein were nor-
mal. An esophago-gastro-duodenoscopy showed a large
ulcerated mass in the distal esophagus, extending to the
lesser curvature of the stomach. Biopsy indicated a poorly
differentiated carcinoma with some squamous differen-
tiation on immunohistochemistry. The tumor was also
stained for HCGb and was strongly positive, conrming
the ectopic secretion of HCGb by the tumor.
93
The patient had an esophageal stent placed, which was
then replaced with a jejunal feeding tube. She developed
post-operative wound infection, which was treated with
debridement and antibiotics. She was started on chemo-
therapy with cisplatin and 5-uorouracil for one cycle,
but as her tumor progressed, she experienced worsening
dysphagia and pain, and her functional status rapidly de-
clined. She enrolled in hospice services two months after
the initial diagnosis.
Discussion
Ectopic HCG (HCGb) secretion has been reported in sever-
al types of tumors, including cervical, gastric, pancreatic,
ovarian and lung cancers, and several studies indicate that
its expression is associated with a graver clinical outcome
as well. However, the prognostic signicance of ectopically
secreted serum levels of HCG in patients with esophageal
cancers remains unknown. We present a case of HCG-se-
creting esophageal carcinoma with a very aggressive clini-
cal course.
HCGb expression correlates with reduced tumor cell apop-
tosis, and increased expression may be involved as well in
tumor vascularization and dissemination in patients with
invasive cervical squamous carcinoma.
1
Moutzouris et al
showed that HCGb expression increased with tumor in-
vasiveness and that such tumors were relatively resistant
to treatment.
2
Others found that the a false positive urine
pregnancy test was neither sensitive nor specic enough to
be used as a tumor marker for lung and esophageal cancer.
3

However, another report indicated that elevated HCGb lev-
els in serum and urine correlated with established tumor
markers like CA 19-9 and carcinoembryonic antigen in pa-
tients with pancreatic and biliary cancers.
4

Most studies of HCG expression in invasive cancers have
been based on immunohistochemical analysis, yet the
practical role of this hormone in any tumor may differ de-
pending on the histological type. One study showed that
53% of patients with malignant gastric tumors had cells
that were immunohistochemically positive for HCG; the
positivity was more apparent in poorly differentiated tu-
mors than in well differentiated tumors and more common
in antral tumors than in other locations. This study did
not nd any prognostic signicance of HCG secretion by
the tumors.
5
Another immunohistochemical study of colon
cancers showed that patients with positive HCG had sig-
nicantly worse survival compared to those with negative
HCG production. The authors also found higher HCG posi-
tivity in patients with poorer tumor differentiation as well
as more advanced disease in those individuals who had
lymph node metastasis, peritoneal metastases and liver
metastasis than patients without metastases. HCG positiv-
ity also correlated signicantly with Dukes staging; Dukes
stage D tumors had signicantly higher rates of HCG ex-
pression compared to lower stages.
6
Others reported that
metastatic pancreatic adenocarcinomas had a >50% inci-
dence of HCG positivity and that HCG positive tumors had
statistically signicantly worse survival rates compared to
those that were negative for HCG.
7
HCGb secretion by esophageal carcinoma is rare, although
some investigators identied positive cells by immunohis-
tochemistry. Three cases of HCGb-secreting esophageal
squamous cell carcinoma were described by Birkenfeld et
al.
8
Immunohistochemical positivity was noted in 71% of
the 42 esophageal squamous cell cancers, along with sig-
nicantly greater positivity in tumors with lymph node
metastasis, but serum or urine levels were not reported.
9

The immunohistochemical expression of HCG in esopha-
geal cancers has been conrmed and the greater positivity
correlated with poorly differentiated squamous histology
in lymph node metastases, but no correlation with serum
levels of HCG has been reported.
10
HCG production is rare-
ly reported in esophageal adenocarcinomas, although one
immunohistochemical study reported HCGb positivity in
adenosquamous esophageal cancers in both well differ-
entiated and poorly differentiated squamous cell carcino-
mas.
11

Conclusion
Our patient had a rapidly deteriorating clinical course with
an aggressive HCGb-expressing, poorly differentiated
metastatic esophageal carcinoma. Our ndings conrm
previous studies of colon and pancreatic carcinomas that
suggest a poor outcome for patients with HCGb-secreting
tumors. Because there are, as yet, no studies that link el-
evated serum levels of HCG with prognosis in esophageal
cancers, further evaluation is needed to determine if HCG
secretion detected by serum analysis is a potential prog-
nostic marker for invasive esophageal cancers.
References
1. 1. Li D, Wen X, Ghali L, et al. hCG beta expression by cervi-
cal squamous carcinoma--in vivo histological association with
tumour invasion and apoptosis. Histopathology. 2008; 53(2):
147-55.
2. 2. Moutzouris G, Yannopoulos D, Barbatis C, Zaharof A, The-
odorou C. Is beta-human chorionic gonadotrophin production
by transitional cell carcinoma of the bladder a marker of aggres-
sive disease and resistance to radiotherapy? Br J Urol. 1993 Dec;
72(6): 907-9.
3. 3. DAgostino RS. Cole LA. Ponn RB. Stern H. Schwartz PE.
Urinary gonadotropin fragment measurements in patients with
lung and esophageal disease. J Surg Oncol 1992; 49(3): 147-50.
4. 4. Alfthan H. Haglund C. Roberts P. Stenman UH. Elevation
of free beta subunit of human choriogonadotropin and core
beta fragment of human choriogonadotropin in the serum and
urine of patients with malignant pancreatic and biliary disease.
Cancer Research 1992; 52(17): 4628-33.
5. 5. Yakeishi Y, Mori M, Enjoji M. Distribution of beta-human
chorionic gonadotropin-positive cells in noncancerous gastric
mucosa and in malignant gastric tumors. Cancer 1990; 66(4):
695-701
Kutty, et al
94
Scripta Medica
6. 6. Yamaguchi A, Ishida T, Nishimura G, et al. HUman chorionic
gonadotropin in colorectal cancer and its relationship to progno-
sis. Br J Cancer 1989; 60: 382-4.
7. 7. Syrigos KN, Fyssas I, Konstandoulakis MM, et al. Beta human
chorionic gonadotropin concentrations in serum of patients with
pancreatic adenocarcinoma. Gut 1998; 42(1): 88-91.
8. 8. Birkenfeld S, Noiman G, Krispin M, Schwartz S, Zakut H. The
incidence and signicance of serum hCG and CEA in patients
with gastrointestinal malignant tumors. Eur J Surg Oncol 1989;
15(2): 103-8
9. 9. Li DM, Li SS, Zhang YH, Zhang HJ, Gao DL, Wang YX.
Expression of human chorionic gonadotropin, CD44v6 and
CD44v4/5 in esophageal squamous cell carcinoma. Wor J Gas-
troenterol 2005; 11(47): 7401-4.
10. 10. Trias I, Campo E, Benasco C, Palacin A, Cardesa A. Human
chorionic gonadotropin in esophageal carcinomas. An immuno-
histochemical study. Pathol Res Practice 1991; 187(4): 503-7.
11. 11. Burg-Kurland CL, Purnell DM, Combs JW, Hillman EA, Har-
ris CC, Trump BF. Immunocytochemical evaluation of human
esophageal neoplasms and pre neoplastic lesions for b-choriogo-
nadotropin, placental lactogen, a-fetoprotein, carcinoembryonic
antigen and non-specic cross reacting antigen. Cancer Res
1986; 46: 2936-43.
12. 12. Yoshimura M, Nishimura R, Murotani A, et al. Assessment
of urinary beta-core fragment of human chorionic gonadotro-
pin as a new tumor marker of lung cancer. Cancer 1994 Jun
1;73(11):2745-52.
Pojava hemo lije A u vreme koronarno-arterijskog
premotavanja
APSTRAKT
Ekspresija humanog horionskog gonadotropina (HCG; HCGb) je ustanovljena u razliitim solidnim malignim tumorima, ukljuujui
plua, guterau, eludac i karcinom cerviksa. Neke predhodne studije sugeriu da ovo ukazuje na nepovoljnu prognozu.
Meutim, veina ovih studija je procjenjivala ekspresiju HCGb imunohistohemijskim metodama, dok je kliniki znaaj povienog
nivoa HCGb u serumu jo uvijek nepoznat, a moe ukazivati na posebno agresivnu bolest. Ovaj fenomen jo uvijek nije
prouavan kod raka jednjaka. Prikazali smo sluaj srednjovjene ene sa slabo diferenciranim karcinomom jednjaka, ekspresijom
HCGb i povienim nivoom hormona u serumu. Povien nivo ovog hormona bio je udruen sa veoma agresivnim klinikim tokom.
KLJUNE REI
Karcinom jednjaka, humani horionski gonadotropin, HCG.
95
Scripta Medica
Roberto Gianani
1
,
Sumul Gandhi
2
,
Jennifer Bero
1
1
Surgical Pathology Fellows, Univer-
sity of Illinois at Chicago and Stroger
Hospital of Cook County, Surgical
Pathology Fellowship Program,
Chicago Illinois.
2
Dermatopathology Fellow, Stroger
Hospital of Cook County, Chicago,
Illinois.
Correspodence
Jennifer Bero
Surgical Pathology Fellows
University of Illinois at Chicago,
Chicago, Illinois 60612 USA
IMAGES IN CLINICAL MEDICINE
Carcinosarcoma of the Uterus
Metastasizing to the Scalp
DOI: 10.7251/SMD1302095G (Scr Med 2013;44:95)
A 56 year old G12P6066 post menopausal woman present-
ed with progressive menorrhagia for three months and a
scalp lesion (Figure 1, A and B). On evaluation of an en-
dometrial biopsy a grade 2/3 endometrioid endometrial
carcinoma was identied. A subsequent CT scan revealed
a heterogeneous, enhancing soft tissue uterine mass.
Biopsy of the scalp lesion demonstrated a poorly differ-
entiated carcinoma with positive immunohistochemical
staining for CK7, EMA and focal positivity for ER and CA-
125. A similar prole was seen in the previously biopsied
endometrial lesion. Therefore metastasis of endometrial
carcinoma to the scalp could not be excluded.
A hysterectomy was subsequently performed. On gross
examination of the uterus, a 6.5 cm bulky, friable, exo-
phytic endometrial mass was identied. Myometrial in-
vasion was minimal. Microscopic examination revealed
a carcinosarcoma with high grade epithelial component
histologically similar to the scalp lesion (Figure 1, C and
D). Focal sarcomatous elements within the uterine tumor
were also present.
Carcinosarcomas of the uterus usually metastasize to the
lung or peritoneum and to date this is only the second re-
port in the english language literature of carcinosarcoma
of the uterus metastasizing to the scalp (1).
Reference
1. Hamarech WA, Subhraleena D, Cherian SV, Vence T. Uterine
Carcinosarcoma with scalp Metastasis: A rare presentation.
Intern Med 51: 131, 2012.
UDK 616.33-006.6
Figure 1. Morphologic and histologic presentation of the car-
cinosarcoma of the uterus metastazing to the scalp. A. CT
scan of the scalp; B. photograph of the scalp lesion; C. H&E stain
of the scalp lesion (20 x magnication); D. H&E stain of the uterine
tumor (20 x magnication).
A B
96
Scripta Medica
ivojin S. Jonjev,
Vladimir Torbica,
Jovan Raji
University in Novi Sad, Institute for
Cardiovascular Diseases of Vojvodi-
na, Clinic of Cardiovascular Surgery,
Novi Sad, Serbia
Correspodence
ivojin S. Jonjev, MD, PhD
Clinic of Cardiovascular Surgery
Put doktora Goldmana 4
21204 Sremska Kamenica, Serbia
E-mail: jonjevz@nscable.net
IMAGES IN CLINICAL MEDICINE
Mitral Valve Prolapse: Novel
Assessment With Real-Time 3D
Echocardiography
DOI: 10.7251/SMD1302096J (Scr Med 2013;44:96)
UDK 616.126.42-008.46-089
Mitral valve prolapse (MVP) is the most common cause of
mitral regurgitation and the most frequent reason for mi-
tral valve surgery in Europe. The most traditional method
for mitral valve evaluation has been two-dimensional (2D)
transthoracic echocardiography. However, soon after its de-
velopment, intraoperative transesophageal echocardiogra-
phy (TEE) became the preferable imaging method for both
the perioperative decision-making process and postoperative
evaluation after mitral valve surgery. Improved imaging mo-
dalities and implementation of real-time 3D TEE provided en
face views of the mitral valve from the left atrial perspective,
and this method soon became the new gold standard for the
diagnosis of MVP. Modern 3D echocardiographic imaging
provides three general modalities: volume rendered, biplane
or multi-plane, and color Doppler imaging. In this report, we
describe the clinical implications of three-dimensional (3D)
TEE in mitral valve reconstruction after MVP.
A 57-year-old Caucasian man was admitted to the hos-
pital with dyspnea due to undated mitral regurgitation.
Transthoracic echocardiography on admission revealed
severe mitral valve regurgitation due to mitral valve pro-
lapse. Coronary angiography demonstrated normal coro-
nary ndings. Intraoperative TEE was performed using a
General Electric Vivid E9 and a 6VT-D 5.0 MHz probe,
before and after cardiopulmonary bypass (CPB). Regular
2-dimensional (2D) TEE identied posterior mitral valve
cusp prolapse due to chord rupture but failed to reveal the
complete anatomy of the mitral valve. In contrast, the high
quality, real-time 3D TEE images provided accurate assess-
ment of valvular motion, precise location of the MVP, and
allowed adequate preoperative planning when reconstruc-
tion was being considered [Figures 1 and 2]. The patients
mitral valve was reconstructed by a standard quadrian-
gular resection between the P2/P3 section; a Blalock su-
ture of the resected area was done with T-Cron 4-0 poly-
lament suture. Reductive mitral valve annuloplasty was
performed by implantation of the semi-rigid ring #28. The
patient was discharged seven days after surgery without
complications.
Figure 1. Preoperative Real-Time 3D Transesophageal Echo-
cardiogram. The biplane image of mitral valve prolapse (a, b) shows
a set of two orthogonal planes. The left upper panel represents the
image at 0, and the left lower panel shows the image at 90. The
right panel (c) shows an en face view of the mitral valve from the left
atrial perspective obtained by the three-dimensional (3D) zoom tech-
nique. The arrow indicates the ail P2/P3 segment of the posterior
mitral leaet. LA = left atrium; LV = left ventricle.
Figure 2. Postoperative Real-Time 3D Transesophageal
Echocardiogram. Biplane images (a, b) show a competent
mitral valve with good leaflet coaptation. The right panel (c)
shows an en face view of the mitral valve from the left atrial
perspective obtained by the three-dimensional (3D) zoom
technique. The arrow indicates the implanted semi-rigid ring.
LA = left atrium; LV = left ventricle.
97
Scripta Medica
Nataa Stojakovi,
1
ivojin S. Jonjev,
2
Rajko Igi
1,3
1
Department of Pharmacology and
Clinical Pharmacology, Medical
Faculty, University of Banja Luka,
Republic of Srpska, Bosnia & Herze-
govina
2
Institute for Cardiovascular Dis-
eases of Vojvodina, Clinic of Cardio-
vascular Surgery, University of Novi
Sad, Serbia
3
Pain Management, John Stroger
Hospital, Chicago, Illinois, USA
Correspodence
Rajko Igi, M.D., Ph.D.
Pain Mangement
John Stroger Hospital of Cook
County, Chicago, IL 60612, USA
E-address: rigi@excite.com
SPECIAL ARTICLE-CLINICAL PRACTICE
Smoking Abstinence in Patients
Scheduled for Elective Surgery
ABSTRACT
Smokers have an increased risk of perioperative and postoperative complications,
including a higher incidence of airway and respiratory, cardiovascular events, and
impaired wound healing. This brief review will remind anesthesiologist and surgeons
that their preoperative smoking intervention for smoking cessation can be effective in
decreasing the incidence of complications. Preoperative smoking intervention, even if
it is both brief and intensive, may help to decrease this risk. The surgical event is the
important teachable moment that could translate, with proper smoking intervention,
into permanent smoking cessation.
KEY WORDS
Tobacco smoking, preoperative smoking intervention, smoking cessation, elective
surgery.
DOI: 10.7251/SMD1302097S (Scr Med 2013;44:97-9) Submitted: April 30, 2012
UDK 613.84:616-089
Cigarette smokers have an increased risk of perioperative
and postoperative complications, such as higher incidence
of airway and respiratory (e.g., reintubation, laryngo-
spasm, bronchospasm, and hypoventilation), cardiovas-
cular events, and impaired wound healing.
1,2
Preoperative
smoking intervention may be effective in decreasing the
incidence of such risk, and surgery may constitute a unique
opportunity for permanent smoking cessation. In this
short article, we present the reasons why the physicians,
anesthesiologists and surgeons should regularly perform
interventions for preoperative smoking cessation.
Background
Tobacco smoking has many effects on heart function and
circulation, both in the short and the long term.
1
Short/
term effects are mainly due to increased carbon monoxide
(CO) and nicotine in the blood. These substances persist as
long as 24 to 48 hours after smoking cessation. The harm-
ful action of carbon monoxide relates to the reduction by
3-12% of oxygen delivery to the tissues where CO binds
to the hemoglobin molecules instead of oxygen. Nicotine
stimulates the stress response to surgery, resulting in in-
creased blood pressure, pulse rate and systemic vascular
resistance, thus increasing the work of heart. It was re-
cently shown that nicotine replacement therapy (NRT)
causes a limited vasoactive effect only when administered
intravenously.
1
The long-term effects of smoking include
the development of generalized atherosclerotic changes in
the vasculature. Short-term effects of smoking are more
important in smokers who suffer from generalized athero-
sclerosis.
Smoking presents a higher risk of serious postoperative
complications, such as pneumonia and respiratory failure
due to impaired cilliary function, increased mucus pro-
duction, and the damage to immune responses within the
lung. Smoking can also cause impaired bone and surgical
wound healing, as a result of decreased immune function
and tissue oxygenation from vasoconstriction and car-
boxyhemoglobin formation.
3

While smoking clearly increases the risk for perioperative
complications, recent publications suggest that even short
term preoperative smoking cessation can reduce the risk
of postoperative cardiovascular and pulmonary compli-
cations and improve post/surgical outcomes.
4,5
Evidence
from two trials indicates that interventions beginning four
to eight weeks before surgery with weekly counseling and
NRT, support smoking cessation and reduce complication
rates.
1,4,
Brief interventions support short-term smoking
cessation, but there is insufcient evidence to determine
whether they reduce complications. This may be due to the
98
Scripta Medica
longer period of pre-operative abstinence achieved when
interventions begin four to eight weeks before surgery.
Pre-and Post-operative Interventions
Brief or more intensive intervention, including both be-
havioral and pharmacological strategies, with or without
face-to-face contact, should be applied at least 48 hours be-
fore an elective surgical operation.
6,7
Despite evidence that
preoperative smoking cessation promotes favorable surgi-
cal outcomes, the clinical staff directly involved in peri-
operative care may not be adequately equipped to deliver
standardized cessation education. They may not be trained
to understand the challenges smokers encounter when at-
tempting to quit. Thus, a multidisciplinary approach with
physicians delegating smoking cessation counseling to
peer educators may prove more effective, especially in so-
cially disadvantaged populations.
Brief Intervention. The doctors should advise patients
according to the usual protocol: Asking about tobacco
history, Advising smoking cessation before surgery and
Presenting basic health information. Optimally, this AAP
advice also includes a written handout detailing the ma-
jor health benets to cessation (e.g., cardiovascular, lung
health, wound healing, and cancer risk reduction) and the
timeframe within which these benets occur.
Intensive Intervention. An intensive smoking cessa-
tion intervention may have a longer introductory session
with the opportunity to ask and respond to questions about
risks, benets and strategies. The intake nurse should refer
the patient to an educator who will assess smoking status
and offer individualized counseling. The health educator
should inform the anesthesiologist of the patient prefer-
ence (attempt to quit, cut back, or make no change at the
present time). For those patients who want to quit smok-
ing and who smoke six or more cigarettes a day, the anes-
thesiologist may prescribe medications (Table 1). For those
who smoke 6-9 cigarettes/day, a single medication should
be offered. For those who smoke 10 or more cigarettes per
day, the anesthesiologist may offer a combination of a long
acting agent (either bupropion or nicotine patches) with
a short acting nicotine replacement (lozenge). Bupropion
and/or nicotine patches
8
would be provided during the
entire preoperative period. The quit date should be coor-
dinated with the use of the medication. The patient may
be encouraged to sign a declaration of commitment not to
smoke preoperatively as a motivated reminder. This dec-
laration should be signed by both the patient and doctor
(anesthesiologist or surgeon) simultaneously.
Some patients are nervous immediately prior to and after
surgery and they often wish to smoke during that period.
Yet many of them are able to avoid smoking after anesthesia
and surgery with the support of an intervention. However,
a brief smoking intervention may not be powerful enough
to inuence heavy smokers; these highly dependent indi-
viduals may require more intensive intervention.
For patients who ceased to smoke preoperatively, the edu-
cator should focus on prevention of relapse in the postop-
erative phase. The educator should meet face-to-face with
participants during a postoperative surgical clinic ap-
pointment, generally within 1-2 weeks following surgery.
The counseling message must be tailored according to the
patients motivation and related to the behavioral change
achieved during the preoperative phase. Telephone coun-
seling may be scheduled following the postoperative clinic.
Millions of patients worldwide undergo surgery each year.
The rate of smoking in surgical patients is higher than
in the general population. Consistent and signicant im-
provement in preoperative quit rates and postoperative
morbidity has been achieved through interventions among
heterogeneous populations in the UK, Europe and Aus-
tralia. Several studies of intensive preoperative cessation
intervention indicate improved health both at the time of
surgery and during a 12-month postoperative period, as
well as decreased post-operative complications.
9-12
How-
ever, brief interventions failed to increase the long-term
cessation benets. The surgical event is the important
teachable moment that could translate into permanent
smoking cessation if adequate support is available from
clinical personnel. Perhaps even the hard-core smokers
need a doctors support to realize and benet from such an
opportunity.
Epilogue
Despite long lasting and intensive campaigns against to-
bacco use in many countries, including a successful cam-
paign of Yugoslav medical students,
13
cigarette smoking
remains one of the greatest public heath threats. It is an
Table 1. Pharmacologic interventions that assist smoking cessation during the preoperative period and/or during the initial
postoperative period.
Drug
*
Dose Duration Side effects
Nicotine patch 7-21 mg/day 8 weeks Erythema, pruritus
Nicotine lozenge two to eight lozenges of 2 mg/day 8 weeks Sore throat, heartburn
Bupropion (Zyban) 150 mg/day x 2 days, then 300 mg/day 8-12 weeks Insomnia, dry mouth, dizziness, rhinitis
*Some of these medications are not available in many developing countries.
99
Apstinencija od puenja kod pacijenata predvienih za
elektivne hirurke zahvate
APSTRAKT
U puaa postoji povean rizik od postoperativnih komplikacija, ukljuujui poveanu incidencu vazdunih i respiratornih, kao
i kardiovaskularnih dogaaja te usporenog zarastanja rana. Ovaj kratki lanak bi trebalo da podsjetiti anesteziologe i hirurge na
znaaj preoperativne intervencije u vezi sa prestankom puenja u smanjenju incidence komplikacija. Preoperativana intervencija
za prestanak puenja, makar kratka i intenzivna, moe doprinijeti smanjenju rizika. Operativni zahvat je vaan kljuni momenat
koji, uz prikladnu intervenciju, moe uiniti da pacijent trajno prestane da pui.
KLJUNE REI
Puenje duvana, preoperativna intervencija, prestanak puenja, elektivni hirurki zahvat.
especially prevalent heath problem in many developing
countries, including all of the Balkan states.

Approxi-
mately 70 percent of smokers annually express an interest
in quitting, but only about ve percent achieve sustained
cessation. Several systematic reviews report that simple,
one time advice from a physician during a routine consul-
tation increased the number of smokers who quit and did
not relapse for one year.
1
Published reviews also suggest
that advice from trained counselors were more effective in
increasing quit rates than a minimal intervention. Inter-
ventions aimed at changing smokers behavior should thus
be exploited before elective surgery.

Authorship statement
All authors contributed equally.
Financial disclosure
We declare that we have no conicts of interest.
References
1. Thomsen T, Villebro N, Mller AM. Interventions for pre-
operative smoking cessation. Cochrane Database of Sys-
tematic Reviews 2010, Issue 7. Art. No.: CD002294. DOI:
10.1002/14651858.CD002294.pub3.
2. Silverstein P. Smoking and wound healing. Am J Med
1992;93:22S-3S.
3. Turan A, Mascha EJ, Roberman D, et al. Smoking and Periop-
erative Outcomes. Anesthesiology 2011;114: 83746.
4. Moores LK. Smoking and postoperative pulmonary complica-
tions: an evidence-based review of the recent literature. Clin
Chest Med 2000; 21: 139-46.
5. Warner, DO. Tobacco Dependence in Surgical Patients. Curr
Opin Anaesthesiol. 2007;20(3):279-83.
6. Moores LK. Smoking and Postoperative Pulmonary Complica-
tions: An Evidence-based Review of the Recent Literature. Clin
Chest Med. 2000;21(1):139-46.
7. Mller AM, Villebro N, Pedersen T, Tnnesen H. Effect of preop-
erative smoking intervention on postoperative complications: a
randomised clinical trial. Lancet 2002;359(9301):114-7.
8. Tovey D, ed. Clinnical evidence concise. London, BMJ Publish-
ing Group, 2005
9. Sorensen LT, Karlsmark T, Gottrup F. LT Sorensen, T Karls-
mark, and F Gottrup, Abstinence from smoking reduces
incisional wound infection: a randomized controlled trial. Ann
Surg. 2003;238(1):1-5.
10. Lindstrm D, Sadr Azodi O, Wladis A, et al. Effects of a Periop-
erative Smoking Cessation Intervention on Postoperative Com-
plications: A Randomized Trial. Ann Surg. 2008;248(5):739-45.
doi: 10.1097/SLA.0b013e3181889d0d.
11. Sadr Azodi O, Lindstrm D, Adami J, et al. The efcacy of a
smoking cessation programme in patients undergoing elec-
tive surgery: a randomised clinical trial. Anaesthesia. 2009
Mar;64(3):259-65. doi: 10.1111/j.1365-2044.2008.05758.x.
12. Jha P, Ramasundarahettige C, Landsman V et al. 21
st
century
hazards of smoking and benets of cessation in the United
States. N Engl J Med 2013;368:341-50. doi: 10.1056/NEJM-
sa1211128.
13. Zizic-Borjanovic S, Jerinic M, Igic R. Twenty ve years of anti-
smoking movement started by medical students: some further
goals. J BUON 2007;12:181-4.
Stojakovi, et al
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LETTER TO THE EDITOR
Antimicrobial Consumption
DOI: 10.7251/SMD1302100S (Scr Med 2013;44:100)
Antibiotic use rates have declined dramatically since the
1990s,
1
in part because of more rational use of these drugs.
Judicious antibiotic usage is an important tool, both for
proper treatment of patients and avoidance of bacterial
resistance to antibiotics. Thus, national surveillance of an-
timicrobial consumption is needed to evaluate the quality
of antibiotic use.
2
The surveillance of outpatient antibiotic
use in the Republic of Srpska done this year by Markovi-
Pekovi
3
is an important indicator for the quality of local
outpatient medicine.
Results of the survey indicate that outpatient use of sys-
temic antibiotics in the Republic of Srpska, with approxi-
mate 19 DDD (Dened Daily Dose per 1000 inhabitants per
year), does not exceed that in 32 other European countries,
yet the European Surveillance of Antimicrobial Consump-
tion (ESAC) stated that such consumption should be fur-
ther reduced.
4
To reach this goal, it will be necessary to
involve the many national programs for family physicians
and others who work in primary care. In the article on an-
tibiotic use in the Republic of Srpska, the authors did not
mentioned if such instructions were organized. However,
they suggested that optimization of antibiotic use will be
obtained with strict compliance to the guidelines, and
education of professionals and public. It would be nice to
know how such education will be done.
It is a pity that the authors did not detail use of antimi-
crobials in various age groups, especially children. In re-
cent years, outpatient antibiotic utilization has tended to
decrease within this age group. For example, overall anti-
biotic prescriptions in France decreased by 57% between
2001 and 2010 in children aged 0 to 24 months, by 50% in
children aged 25 months to 6 years, and by 46% in children
older than 6 years of age.
5
In all of these groups, the great-
est reduction occurred in treatment for rhinopharingitis
(83%), and the lowest reduction was for otitis media, the
most common disease of childhood.

Prof. dr Savo ibali
Emeritus Professor of infection diseases
Medicinski fakultet, Univerzitet u Tuzli
75000 Tuzla
Bosnia and Herzegovina
References
1. Greene SK, Kleinman KP, Lakoma MD, et al. Trends in anti-
biotic use in Massachusetts children, 2000-2009. Pediatrics.
2012;130:15-22.
2. Matuz M, Benko R, Hajdu E, Viola R, Soos G. Evaluation of am-
bulatory antibiotic use in Hungary using drug-specic quality
indicators. Orv Hetil 2013;154:947-56.
3. Markovi Pekovi V, Stoisavljevi-atara S, krbi R. Outpatient
utilization of systemic antibiotics in the republic of Srpska. Scr
Med 2013;44,8-13.
4. Adriaenssens N, Coenen S, Versporten A et al. European surveil-
lance of antimicrobial consumption (ESAC): quality appraisal of
antibiotic use in Europe. J Antimicrob Chemother 2011;66:S71-7.
5. Dommergues MA, Hentgen V. Decreased paediatric antibiotic
consumption in France between 2000 and 2010. Scand J Infect
Dis 2012;44:495-501.
UDK 615.322:665.528.292.94
101
Scripta Medica
Snjeana Popovi-Pejii
Klinika za unutranje bolesti -
odjeljenje Centar za dijabetes sa
endokrinologijom, KC Banja Luka,
12 beba bb, Banja Luka 78000,
Republika Srpska, Bosna i Herce-
govina
Correspondence
Snjeana Popovi-Pejii, prof. dr
Phone:++38751342552
Fax: ++38751342552
Email: snjezana.pejicic@kc-bl.com
CONTINUING MEDICAL EDUCATION
Questions and Answers
(Q & )
.
.
[This section includes short segments of texts from the published literature
or original texts. The main purpose is to provide questions and answers that
readers can use to improve their English.]
Scripta Medica
DOI: 10.7251/SMD1302101P (Scr Med 2013;44:101-4)
Questions
1. What type of stem cells has been applied in diabetes
therapy?
2. How is the population of cancer stem cells (CSCs) re-
cently dened?
3. Cells that produce and secrete antibodies are: I Plasma
cells, II T-cells, III B-cells.
a. I only
b. III only
c. I and II
d. II and III
e. I, II, and III
4. Which of the following may cause elevated white blood
cells?
a. Viral infection
b. Stress
c. Medication
d. Bacterial infection
e. All of the above
5. Which of the following describes a common use of an
adjuvant?
a. To diminish B-cell clone expansion and antibody syn-
thesis
b. To enhance the effect of a vaccine
c. To improve antibody deciencies
d. To inhibit translation of genes encoding numerous cy-
tokines
e. To treat inammatory diseases including autoimmune
disorders
6. A 2-month-old male infant presents with persistent
diarrhea, signs and symptoms of Pneumocystis carinii
pneumonia, and an oral fungal infection with Candida al-
bicans. His weight is in the 10
th
percentile. Test results for
HIV are negative by polymerase chain reaction. The most
likely cause of these ndings is
A. Grossly reduced levels of B-cells
B. An X-linked inheritance of HLA genes
C. Defective isotype switching
D. Defective T-cell function
E. Selective IgA deciency
7. Do you know the story of Viagra (sildenal citrate)?
8. A 25-year-old man fell out of a kayak and remained un-
derwater for approximately 5 min before being rescued. He
was immediately taken to the hospital and put on a ventila-
tor, but never regained consciousness. The next day he was
pronounced dead after an electroecephalogram did not
detect brain, and deep tendon reexes and a respiratory
drive were not found. At autopsy his brain was found to be
swollen, with side gyri, and narrow sulci. No gross area of
acute infarction was identied. A histologic section from
the Sommer sector of the hippocampus would most likely
reveal which of the following abnormalities?
A. Reactive gliosis
B. Red neurons
C. Tissue necrosis
D. Vacuolated oligodendrocytes
E. Vascular proliferation
9. What is the most common treatment for depression?
10. A 74-year-old male, a nonsmoker, complained of severe
nocturnal leg cramps. The patient also complained that
similar painful cramping occurred when he walked rap-
idly or jogged. Because some components of his lipid panel
exceeded the desirable range, and as he had a history of
myocardial infarction, his family physician prescribed
simvastatin (40 mg/day). The patient had taken this medi-
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cation for the past eight years. The painful nocturnal epi-
sodes started recently and affected either one or the other
leg.
Which of the following therapies one should try?
A. Reduce the dose of simvastatin to 10 mg/day
B. Stop simvastatin
C. Substitute pravastatin for simvastatin
D. Prescribe tablets of magnesium with vitamin B6
Answers
1. Advanced type 2 diabetes mellitus is associated with
signicant morbidity and mortality due to cardiovascular,
nervous, and renal complications. Attempts to cure diabe-
tes mellitus using islet transplantation have been success-
ful in providing a source for insulin secreting cells. How-
ever, limited donors, graft rejection, the need for continued
immune suppression, and exhaustion of the donor cell pool
prompted the search for a more sustained source of insulin
secreting cells.
Stem cell therapy is a promising alternative for islet trans-
plantation in type 2 diabetic patients who fail to control
hyperglycemia even with insulin injection. Autologous
stem cell transplantation may provide the best outcome
for those patients, since autologous cells are readily avail-
able and do not entail prolonged hospital stays or sustained
immunotoxic therapy. Among autologous adult stem cells,
mesenchymal stem cells (MSCs) therapy has been applied
with varying degrees of success in both animal models and
in clinical trials.
2. Many tumors consist of phenotypically and functionally
heterogeneous cancer cells. For many years, such hetero-
geneity was explained by the stochastic (clonal evolution)
model (Fig. 1a), which is based on the notion that all cancer
cells possess tumorigenic potential and can develop tumor
dependent on genetic and/or epigenetic changes.
However, more recent studies have suggested a new para-
digm, cancer stem cell model (Fig. 1b). Tumors show hier-
archy, with a subpopulation of cancer cells having a tumori-
genic potential much greater than that of other cancer cells.
This subpopulation of cells at the top of the hierarchy com-
prises cancer stem cells (CSCs), and tumors are thus thought
to manifest a hierarchical organizationconsisting of stem
cells, progenitors and differentiated cellssimilar to that
of normal tissues. A CSC has been dened as a cell within
a tumor that possess[es] the capacity to self-renew and to
cause the heterogeneous lineages of cancer cells that com-
prise the tumor. Similarly, the term tumor-initiating cell
has been used to describe a cell with the potential to initiate
a tumor. If this term is used to refer to the subpopulation of
cells within an established tumor that gives rise to a new
tumor when transplanted, then tumor-initiating cells are
essentially functionally equivalent to CSCs.
3. The correct answer is A.
Plasma cells produce antibodies against cell pathogens. B
cells are produced in the bone marrow and become plasma
cells. T cells are involved in cellular immunity, which is
mediated by thymus-derived lymphocytes.
4. The correct answer is E.
Elevated white blood cells or leukocytosis may be caused
by viral or bacterial infection, stress, medications (e.g.,
corticosteroids, certain antibiotics, and antiseizure drugs),
chronic bone marrow diseases, acute or chronic leukemia,
and tissue damage (e.g., burns).
5. The correct answer is B.
Adjuvants are commonly used to enhance the effect of a
vaccine. Adjuvant therapy is given in addition to a primary
treatment to nonspecically stimulate immune respons-
es, either directly or indirectly. Antibody deciencies are
sometimes treated with human immune globulin. Ant-in-
ammatory agents such as glucocorticoids can diminish B-
cell clone expansion and antibody synthesis and can also
inhibit translation of cytokine genes. Glucocorticoids are
also used to treat inammatory diseases.
6. The correct answer is D.
The fungal infection is highly suggestive of a T-cell defect.
Choices A, C, and E do not of themselves imply a deciency
in T-cell function. HLA genes are autosomal, not X-linked.
7. Scientists at Pzer reasoned that, if phosphodiesterase
inhibitors could be found, they might be useful drugs to
treat angina (chest pain) or hypertension. The phosphodi-
esterase (PDE) prevalent in vascular muscle is PDE 5, one
of at least nine different subtypes of PDE in human cells.
The search was on for substances that inhibit PDE 5, but
not the other prominent PDE types, and Viagra was found.
Viagra showed no signicant benets for angina or hyper-
tension, but some men in clinical trials reported penile
erection. Apparently, Viagra led to an increase in [cGMP{]
in penile vascular tissue, allowing vascular muscle relax-
ation, improved blood ow, and erection.
(This story is an example of a Program of drug design,
or Rational drug design, in which computer modeling of
enzyme-ligand interactions replaces much of the initial
chemical synthesis and clinical prescreening of potential
therapeutic agents. This way scientists are saving much
time and effort in drug development.)
8. The correct answer is B.
The microscopic changes produced by global hypoxia
are grouped into three categories. The earliest histologic
changes, occurring in the rst 24 h, include the formation
of red neurons (acute neuronal injury), characterized by
eosinophylia of the cytoplasm of the neurons, followed in
time by pyknosis and karryorrhexis. The Purkinje cells of
103
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104
Scripta Medica
the cerebellum and the pyramidal neurons of Sommer sec-
tor in the hippocampus are particularly sensitive to isch-
emic damage and are most likely to demonstrate these ear-
ly changes. The last two microscopic categories of global
hypoxic change are subacute changes, which occur at 24
h to 2 weeks, and repair, which occurs after 2 weeks. Sub-
acute changes include tissue necrosis, vascular prolifera-
tion, and reactive gliosis, while repair is characterized by
the removal of the necrotic tissue.
9. Medication is the most common treatment for mild to
moderate depression. For example, tricyclic antidepres-
sants, selective serotonin reuptake inhibitors (SSRIs),
monoamine oxidase inhibitors, reboxetine, or venlafaxine.
Three systematic reviews found no signicant difference in
outcomes with different kinds of antidepressant drug (tri-
cyclic antidepresants, SSRIs, or monoamine oxidase inhib-
itors). One systematic review found no signicant differ-
ence between tricyclic antidepressants and venlafaxine in
the population of people who responded over 1-12 months.
Another systematic review suggested that tricyclic antide-
pressants were more effective than monoamine oxidase
inhibitors in people with severe depressive disorders, but
may be less effective in atypical depressive disorders with
biological features such as increased sleep, and increased
appetite. A third systematic review found that tricyclic an-
tidepressants were associated with higher rates of adverse
effects than SSRIs, but the difference was small.
SSRIs are drugs that provide relief from some forms of de-
pression. By inhibiting reuptake of serotonin by serotonin
transporters, SSRIs prolong the activity of this transmit-
ter at synapses in the brain. SSIs include uoxetine (Pro-
zac, Flunirin), paroxetine (Paxil, Seroxat), and sertraline
(Zoloft).
One systematic review in people with moderate to se-
vere depressive disorder, many of whom were inpatients,
found that electroconvulsive therapy improved symptoms
over 1-6 weeks treatment compared with simulated elec-
troconvulsive therapy or antidepressant drugs. There is
consensus that electroconvulsive therapy should normal-
ly be reserved for people who cannot tolerate or have not
responded to antidepressant drug treatment, although it
may be useful when a rapid response is required.
[Depressive disorders are characterized by persistent low
mood, loss of interest and enjoyment, and reduced energy.
They often impair day-to-day functioning. Mild to moder-
ate depression is characterized by depressive symptoms
and some functional impairment. Resistant depression
is dened as an absence of clinical response to treatment
with a tricyclic antidepressant at a minimum dose of 150
mg daily of imipramineTofranil (or equivalent drug) for
4-6 weeks. Severe depression is characterized by addi-
tional agitation or psychomotor retardation with marked
somatic symptoms.]
10. The correct answer is C
Perhaps a combination of advanced age and atheroscle-
rotic changes created a predisposition for the simvastatin-
induced leg cramps. Pravastatin differs from simvastatin
in several ways. It is not metabolized by cytochrome P450
(CYP) 3A4 oxidases, and thus is not inuenced by CYP 3A4
inhibitors like simvastatin. Also, simvastatin is associated
with single-nucleotide polymorphisms located within the
SLCO1B1 gene on the chromosome 12 and established my-
opathy, while pravastatin lacks this association. These dif-
ferences may contribute to increased tolerance to pravas-
tatin in this particular case. Thus, simvastatin may be
substituted with pravastatin.
The dose of simvastatin of 10 mg/day or discontinuing
the drug may entirely eliminate the nocturnal leg cramps.
However, because there could be rebound effects related
to the vascular effects, it is better to prescribe substitute
simvastatin with another statin, such as pravastatin. Mag-
nesium, perhaps, could sometimes slightly reduce the sim-
vastatin-induced leg cramps.
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SPECIJALAN LANAK
Uslovi za ulazak biomedicinskog asopisa u MEDLINE
bazu biomedicinskih podataka
DOI: 10.7251/SMD1302110S (Scr Med 2013;44:110-1)
Medline je baza podataka koja sadri citate i apstrakte iz
preko 5000 biomedicinskih publikacija iz celog sveta.
1
U
tu bazu besplatno se ulazi putem PubMed sajta koji prua
citate lanaka i njihove apstrakte. Danas svi lekari, ali i
drugi strunjaci iz raznih zdravstvenih oblasti, redovno
pretrauju podatke u toj bazi podataka. Medline daje
naslove lanaka i apstrakte na engleskom jeziku, bez obzi-
ra na to da li su radovi publikovani na engleskom ili nekom
drugom jeziku.
Odluku o ulasku nekog asopisa u Medline donosi Odbor
za izbor (Literature Selection Technical Review Commit-
tee, LSTRC) koji imenuje director Nacionalne biblioteke
za medicinu u Vaingtonu (National Library of Medicine).
LSTRC svake godine razmatra molbe vie od 420 naslova
asopisa, a u bazu se ukljui manje od jedne treine.
asopisi koji izlaze tri ili vie puta godinje u tampanom
obliku, uz molbu i odgovore na s mnotvo pitanja, prilau
po jedan primerak etiri poslednja broja asopisa. asopisi
koji izlaze dva puta godinje (poput naeg asopisa, Scrip-
ta Medica) ili neredovno, prilau po jedan primerak, tri
poslednja tampana broja.
2
Propisi za asopise koji izlaze
samo elektronski drugaiji su.
Ocena asopisa
asopisi koji ne izlaze redovno, nemaju ansu da uu u
Medline. LSTRC procenjuje kvalitet asopisa na osnovu
brojnih parametara. Glavne od njih navodimo u nastavku.
1. Najvei deo asopisa mora da je posveen biomedicins-
kim temama.
2. Kvalitet lanaka je najvaniji pri izboru asopisa koji se
ukljuuje u Medline. Procenjuju se sledee odlike rado-
va u asopisu: validnost, vanost, originalnost i doprinos
datom podruju.
3. Kvalitet ureivanja radova treba da pokae objektivnost,
kredibilitet i kvalitet sadrine. Ta svojstva se procenjuju na
osnovu informacija o metodama selekcije lanaka koji se
publikuju, recenziranju (posebno uee spoljanjih re-
cenzenata), potovanju etikih normi, dokazu da su autori
dali izjave o nansijskom koniktu interesa, objavljivanju
eventualnih greaka (errata), davanjem anse da se objave
komentari italaca itd. Oglaavanje i komercijalni sponzori
ne bi smeli dovoditi u pitanje objektivnost publikacija.
4. Kvalitet produkcije asopisa (tampa, graka, izgled
asopisa, tampa na hartiji bez kiseline) takoe se razma-
tra.
5. Medline zahteva da su lanci u asopisu usmereni le-
karima, medicinskim tehniarima, stomatolozima, vet-
erinarima i svim profesionalcima koji obavljaju nauna
istraivanja ili se brinu o zdravlju. To su istraivai,
prakriari, edukatori, administratori ili studenti.
6. Vrste sadraja u asopisima koje Medline obuhvata
su sledee: originalna istraivanja, originalna klinika
zapaanja praena analizom i diskusijom; analiza lozof-
skih, etikih ili socijalnih aspekata zdravstva ili biomedi-
cinskih nauka; kritiki revijski lanci, opisi metoda ili pro-
cedura i prikazi sluajeva s diskusijom.
7. Za asopise na stranim jezicima vae isti (navedeni)
kriterijumi.
Naalost, uglavnom ogromna je veina od predloenih
asopisa uvrtena u Medline koji su na engleskom jeziku.
Najbolji je primer za to registrovan pre dve godine kada je
u jednoj turi procene, od svih prihvaenih koji izlaze na
engleskom, prihvaen samo jedan asopis koji izlazi na
stranom jeziku (portugalskom/engleskom).
Epilog
Kada je na asopis pre 2 godine odbijen, jer nije zado-
voljio kriterijume za ukljuivanje u Medline, redakcioni
odbor asopisa je doneo odluku da svi vani lanci izlaze
samo na engleskom, a razne informacije i dodatna uput-
stva autorima na srpskom. Osim toga uvedene su rubrike
Financial Disclosure, Authorship Statement, tampanje
na acid-free hartiji i neke druge novine. U januaru 2014.
godine (dve godine nakon prethodnog predloga), Scripta
Medica moe ponovo konkurisati da se asopis indeksira u
toj bazi podataka. Kvalitet objavljenih radova u poslednja
UDK 007:61]:004.65+050
111
Scripta Medica
tri broja bie i kritina odlika asopisa. Naalost, mali je
priliv kvalitetnih rukopisa dospevao u redakciju.
Pokuaji da se istraivanja u irem regionu Republike
Srpske podstaknu kursevima o publikovanju i nedavnim
izdavanjem knjige posveene istraivanju i biomedicins-
kom publikovanju
3
nisu tako brzo mogli podstai struno-
naunu aktivnost u naoj sredini. Sigurno je da e tek
kvalitetne doktorske studije i vee ulaganje u istraivanja
biti podsticaj boljim istraivanjima iz raznih biomedi-
cinskih disciplina koja e se u veem broju publikovati
kako u naem asopisu, tako i u raznim meunarodnim
asopisima. asopis Scripta Medica je tokom etiri go-
dine, od 2010. godine, zahvaljujui glavnom uredniku ak-
ademiku Rajku Igiu, pruio podsticaj nekolicini lokalnih
autora da razviju interesovanje za kvalitetnije istraivanje
i publikovanje.
Prof. dr Milan Skrobi
Prof. dr Stevan Trbojevi
Prof. dr Radoslav Gajanin
Reference
1. http://www.nlm.nih.gov/pubs/factsheets/factsheets.html
2. http://wwwcf.nlm.nih.gov/lstrc/lstrcform/med/index.html
3. Igi R, krbi R. Kako se piu i publikuju saoptenja o biomedi-
cinskim istraivanjima. Banja Luka/Laktai, Grafomark, 2012
112
Scripta Medica
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113
Scripta Medica
Volumen 69, Broj 12 VOJNOSANITETSKI PREGLED Strana 1015
P R I K A Z K N J I G E
Kako se pisu i publikuju saopstenja o biomedicinskim istrazivanjima
Autori:
Rajko Igi i Ranko Skrbi
Izdava:
GraIomark, Laktasi, Republika Srpska, BiH
Mesto i godina izdanja:
Banja Luka, Republika Srpska, BiH, 2012.
Stampa:
GraIomark, Laktasi, Republika Srpska, BiH
Tiraz:
1000
Povez:
Tvrdi; tabaci siveni koncem
ISBN 978-99955-57-64-5
Odavno se zna da u naunim i strunim krugovima vre-
dite onoliko koliko publikujete, odnosno onoliko koliko vas
rad, pretoen u publikacije, ima uticaja na oblast kojom se
bavite. Radi vee dostupnosti sirem krugu italaca, rezultati
naunog rada najese se objavljuju u Iormi lanka u nau-
nim asopisima. Pisanje naunih lanaka kreativan je posao
i zahteva dodatne napore, znanja i vestine, pa mnogima up-
ravo ovaj deo predstavlja najvei problem u Iinalizaciji nau-
noistrazivakog rada. Meutim, objavljivanje rezultata rada
ne podrazumeva samo pripremu rukopisa prema uputstvu od-
reenog asopisa, ve se odnosi i na komunikaciju sa redak-
cijom, odnosno urednistvom asopisa, a preko njih i sa re-
cenzentima, a nain i kvalitet te komunikacije, takoe, moze
da doprinese sto brzem i uspesnijem okonanju procesa pub-
likovanja.
Knjiga ,Kako se pisu i publikuju saopstenja o biomedi-
cinskim istrazivanjima' proI. dr Rajka Igia i proI. dr Ranka
Skrbia predstavlja svojevrsni vodi koji vas, korak po ko-
rak, vodi ka tom cilju. Kako se iz naslova knjige vidi, ona je
pisana za istrazivae iz oblasti biomedicinskih nauka, mada u
njoj korisne savete mogu nai autori i iz drugih naunih ob-
lasti jer metodologija pripreme naunog saopstenje je u
mnogim elementima jedinstvena, bez obzira na razlike u po-
jedinim naunim poljima. Iako je sadrzaj knjige uglavnom
usmeren ka autorima, korisne savete u njoj mogu nai i ure-
dnici/izdavai asopisa, recenzenti, ali i mentori master i do-
ktorskih teza, dakle svi oni koji uestvuju u realizaciji nau-
noistrazivakog rada.
Knjiga je podeljena u sedam poglavlja, iza kojih sledi
popis korisene literature, zatim deo Prilozi u kome su dati
veoma korisni primeri u vezi sa pripremom naunih publika-
cija (npr. primeri pojedinih vrsta naunih lanaka iz biome-
dicinskih asopisa, ukljuujui i prikaze knjiga, zatim lanci
posveeni publikovanju u recenziranim asopisima i nainu
pripreme projekta doktorske disertacije, pa primer teksta re-
cenzije naunog lanka i odgovora autora na primedbe i su-
gestije recenzenta, kao i primer molbe autoru lanka za doz-
volu da se deo njegovog rada koristi u knjizi) i, na kraju, ve-
oma bogat predmetni indeks, sa brojem stranice na kojoj se
odreeni pojam nalazi, sto znaajno olaksava korisenje
knjige. Pored toga, na poetku knjige dat je spisak slika i ta-
bela koji sadrze niz korisnih primera sa oznakom stranice na
kojoj se nalaze, sto dodatno pomaze u nalazenju potrebne in-
Iormacije.
U prvom poglavlju, ,Biomedicinske publikacije i izve-
staji', dat je kratak prikaz pojedinih vrsta publikacija koje se
najese sreu u oblasti biomedicine. Budui da su primeri
nekih od navedenih publikacija (npr. Pregledni lanak, Pis-
mo uredniku, Esej, Prikaz knjige) dati posle u sekciji Prilozi,
trebalo je ve na ovom mestu uputiti itaoca na njih jer bi na
taj nain, uz data objasnjenja, odmah i video kako ta vrsta
publikacije i izgleda.
Drugo poglavlje, pod naslovom ,Izbor teme za istrazi-
vanje', obrauje najvaznije aspekte planiranja naunog pro-
jekta, prikupljanja literature i, kao posebno znaajno, upu-
uje itaoca na to kako treba itati nauni lanak da bi iz nje-
114
Scripta Medica
Strana 1016 VOJNOSANITETSKI PREGLED Volumen 69, Broj 12
govog sadrzaja za sto krae vreme dosao do najveeg broja
relevantnih podataka.
Tree i etvrto poglavlje, ,Rukopis lanka o istraziva-
nju' i ,Priprema rukopisa', ine okosnicu cele knjige. U
njima je detaljno objasnjena struktura razliitih kategorija
naunih lanaka i naina kako bi ih trebalo koncipirati i napi-
sati sa brojnim primerima iz prakse, ukljuujui i razmatra-
nja jezika i stila rukopisa na srpskom i engleskom jeziku,
skraenica, upotrebe glagolskih vremena u naunom lanku,
transliteraciji irilinih slova u latinina, itd, tako da ove de-
love knjige s pravom mozemo nazvati `Bukvarom za pisanje
naunog lanka`. U njima se, takoe, razmatraju i pojedine
kategorije naunih lanaka, iji su primeri dati u sekciji
,Prilozi', ali, opet, autori su propustili priliku da to navedu u
tekstu i da, na taj nain, primerom pokazu kako taj lanak i
izgleda kada se objavi u biomedicinskom asopisu.
Poglavlje ,Ureivanje i publikovanje biomedicinskih
asopisa' namenjeno je, pre svega, urednicima i recenzenti-
ma, kao i izdavaima biomedicinskih asopisa, ali od znaaja
je i za autore jer im daje uvid u proces rada urednistva i na-
in na koji recenzenti procenjuju njihov rad.
Deo ovog poglavlja posveen je i radovima za sticanje
akademskog zvanja (stepen magistar ili, po novom, master, i
doktor nauka) sa objasnjenjima sto ti radovi treba da sadrze i
kako ih pripremiti, a, takoe, data su kratka uputstva o nainu
kako od doktorske disertacije pripremiti lanak za asopis. Dat
je osvrt i na pripremu apstrakta prezentacije na naunom sku-
pu, kao i na pripremu postera, sto moze da bude od koristi
mladim istrazivaima koji u poetku svoje karijere najese na
ovaj nain saopstavaju rezultate svojih istrazivanja.
Potpoglavlje ,Autorsko pravo, patentiranje i etika istra-
zivaa' u najkraim crtama donosi najosnovnije podatke u
vezi sa etikom u naunoistrazivakom radu, ukljuujui i eti-
ku u publikovanju. Iako su u uvodnoj rei autori naveli da
ovoj temi nisu posvetili veu paznju imajui u vidu da se da-
nas, u vreme Interneta i olaksane dostupnosti bazama naune
publicistike, mogue zloupotrebe u publikovanju naunih ra-
dova lako otkrivaju, misljenja sam da nasi autori, kojima je
ova knjiga i namenjena, jos uvek ne sagledavaju ovaj prob-
lem u pravom svetlu i da mu je trebalo posvetiti vise prostora
u knjizi. Naime, kao urednik ,Vojnosanitetskog pregleda'
vrlo esto sam svedok grubog krsenja etike publikovanja od
strane pojedinih autora. Najese se radi o sluajevima auto-
plagijarizma, kada autori svoj ranije objavljen rad u nekom
domaem asopisu, koji nije indeksiran u poznatim citatnim
bazama, neznatno prepravljen predaju kao potpuno novi rad
nasem asopisu. Iz razgovora sa nekima od njih, stie se uti-
sak da ponekad to ine zbog neznanja kada i u kom obimu
ve objavljene rezultate mogu koristiti u novom radu, a kada
ne. Nadam se da e u nekom od novih, dopunjenih izdanja
ove knjige, iji e tiraz, verujem, veoma brzo biti rasprodat,
autori i ovom problemu posvetiti vise paznje.
Poslednja dva poglavlja u ovoj knjizi posveena su kli-
nikim istrazivanjima i prikazu toksikoloskih rezultata na zi-
votinjama. Ukratko su navedene karakteristike pojedinih vr-
sta klinikih studija s osvrtom na statistiku obradu rezultata
tih studija i njihov prikaz u biomedicinskim publikacijama
(poglavlje ,Klinika istrazivanja') i opisano je na koji nain
se najese prikazuju rezultati istrazivanja u eksperimental-
noj toksikologiji (poglavlje ,Prikaz toksikoloskih rezultata
dobijenih na zivotinjama').
Do sada je na ovu temu na nasem govornom podruju
objavljeno tek nekoliko knjiga, ali ni izdaleka ne sadrze toli-
ko praktinih saveta i primera, kao ova knjiga. To ne treba da
udi, ako se ima u vidu da su njeni autori naunici i univer-
zitetski proIesori sa bogatim istrazivakim i publicistikim
opusom. ProIesor Igi je trenutno i glavni i odgovorni ured-
nik meunarodnog asopisa ,Scripta Medica', a, inae, poz-
nat je u naunim krugovima i kao organizator brojnih, veoma
uspesnih seminara na temu publikovanja u biomedicinskim
asopisima, na kojima mladim istrazivaima prenosi ogrom-
no znanje i iskustvo jednog plodnog istrazivaa, autora, re-
cenzenta, urednika i mentora.
Tekst koji je pisan lepim, ujednaenim i jasnim stilom,
tako da se knjiga ,lako' ita. Iako je ona prvenstveno name-
njena mladim istrazivaima koji ine prve korake u svetu na-
une publicistike, korisne podatke u njoj mogu nai svi koji
na bilo koji nain imaju veze sa publikovanjem naunih ra-
dova, ukljuujui i urednike biomedicinskih asopisa i njiho-
ve recenzente. Konano, knjigu bi trebalo da imaju i svi na-
stavnici koji predaju na Iakultetima iz medicinskog naunog
polja jer su mnogi od njih esto mentori mladim istrazivai-
ma, odnosno oni koji treba da ih uvedu u svet nauke i naune
publicistike.
proI. dr Silva Dobri
Vojnomedicinska akademija
Institut za naune inIormacije
(glavni i odgovorni urednik
,Vojnosanitetskog pregleda')
Zahvalnost za preuzimanje ovog lanka iz VSP dugujemo autoru, prof. dr Silvi Dobri i redakciji Vojno sanitetskog pregleda.
115
Scripta Medica
Uputstvo autorima za
pripremu rukopisa
Scripta Medica (SM) je internacionalni asopis Drutva doktora
Republike Srpske koji objavljuje originalne lanke (klinika, labo-
ratorijska i epidemioloka istraivanja), ali i lanke koji maju za cilj
da edukuju i obavijeste ljekare i strunjake drugih biomedicinskih
disciplina. SM, kao optiemedicinski asopis, daje prednost ru-
kopisima o originalnim klinikim istraivanjima. Na engleskom
jeziku asopis objavljuje originalne radove, pregledne lanke,
specijalne lanke, rjeavanje klinikog problema, prikaze slua-
jeva, slike iz klinike medicine, istorijske lanke i eseje. Samo na
srpskom se objavljuju prikazi knjiga, vijesti, izvjetaji sa naunih
skupova, krai edukativni i drugi lanci. asopis je svima, bez na-
knade, dostupan na internetu (www.scriptamedica.com).
Opta uputstva
1. Rukopis
Rukopis rada treba dostaviti u .DOC formatu (Microsoft Word,
Times New Roman font, veina slova 11 pt). Glavni naslov kucati
slovima veliine od 12 pt bold, a naslove poglavlja slovima od 11
pt bold. U tabelama koristiti slova veliine 10 pt, jednostruki
prored, a naslovi unutar tabela treba da su veliine 10 pt bold; za
glavni naslov tabele koristiti 12 pt bold; legende se ispisuju jed-
nostrukim proredom slovima od 11 pt. Illustracije se dostavljaju
u JPG ili TIFF formatu (300 dpi ili bolja rezolucija).
2. Za lijekove i hemikalije koristiti generike nazive. Za instru-
mente, aparate i ostale ureaje dati njihove nazive, a u zagradi
dati nnavesti proizvoaa i grad.
3. Brojeve koji su manji od deset u tekstu treba ispisati reima, a
za 10 i vie koristiti numeriku oznaku. Brojeve u tekstu i tabela-
ma treba navesti za vrednosti od koji su nainjene procentualne
vrednosti; iza srednje vrednosti stoji standardna devijacija (SD),
a iza medijana meukvartalni raspon (interquartile range, IQR).
4. Naslov slike treba da je veliine 10 pt bold; legende kucati jed-
nostrukim proredom, slovima veliine 10 pt.
5. Reference se u tekstu oznaavaju brojevima ispisanim super-
skriptom iza bilo kog znaka interpunkcije.
6. Jedinice mere, duine, teine i zapremine izraavaju se metri-
kim jedinicama (na primer, metarm, kilogramkg, litarl) ili
njihovim delovima. Temperaturu izraavati u stepenima Celzi-
jusa (
o
C); koliinu supstance u molima (mol), a pritisak u mili-
metrima ivinog stuba (mm Hg). Sve vrednosti hematolokih,
klinikih i biohemijskih merenja navoditi u metrikom sistemu
prema Meunarodnom sistemu mera (International System of
Units, SI units).
7. Skraenice koristiti samo za duge nazive, ukljuujui imena
hemijskih supstancija. Pun naziv dati kada se isti pojavi prvi put
u tekstu, ukoliko to nije standardna jedinica mere. Ako se skra-
enice koriste u Apstraktu, svaku treba objasniti kada se prvi put
pomene u tekstu. Za optepoznate skraenice, kao to su DNK,
SIDA, HIV, ATP, ADP, ne treba uvoditi pun naziv. U naslovu
lanka mogu se nai samo optepoznate skraenice.
8. Izjava o autorstvu. Da bi se istraiva kvalikovao za autora,
mora dati znaajan intelektualni doprinos studiji koja je osnova
za lanak (WAME.com, Policy StatementsAuthorship). Autor
mora uestvovati barem u jednoj aktivnosti u svakoj od tri sle-
dee kategorije:
a. postavljanje istraivakog pitanja, izrada koncepta i diza-
jna studije, prikupljanje i analiza podataka,
b. statistika analiza, interpretacija podataka, obezbeenje
sredstava za istraivanje, administartivna, tehnika ili
materijalna podrka, nadgledanje celokupnog toka istra-
ivanja,
c. pisanje prve verzije ili kritika revizija rukopisa.
Izuzetno autor moe biti istraiva koji je kao suspecijalista (na
primer biostatistiar, patolog ili epidemiolog) doprineo uskom
aspektu rada. Izjavu o autorstvu s navoenjem svog doprinosa
mora potpisati svaki autor (ako ih je dva ili vie). Izjava o autor-
stvu se objavljuje pod naslovom Doprinos autora, a sledi iza
Diskusije. Imena autora se u tom poglavlju ne ispisuju, ve samo
njihovi inicijali. Glavni (korespondirajui) autor je odgovoran za
integritet celokupnog rada. Neodgovorno je izostaviti istraivaa
koji je doprineo radu.
9. Izjava o sukobima interesa. Izjavu o deklaraciji potencijalnih
sukoba interesa daje i potpisuje svaki autor. (Videti uputstvo koje
je dato os strane Svetskog udruenja urednika medicinskih aso-
pisa, World Association of Medical Editors, WAME, www.wame.
org ili ICMJE uniform disclosure form for potential conicts of
interest, www.icmje.org.) Izjava ukljuuje sve nansijske aspek-
te (konsultacije, honorare, plaena putovanja na naune i druge
skupove, nansiranje od strane dravnih i privatnih institucija,
zarada od patenata, itd.) i navoenje organizacija koje imaju na-
sijski interes ili nansijski konikt s predmetom ili materijalima
o kojima se diskutuje u rukopisu. Ukoliko se rukopis prihvati u
tampu, urednici e diskutovati s autorima kako e takva infor-
macija biti saoptena itaocima u rubrici Konikti interesa.
10. Zahvalnost. U propratnom pismu, mora se navesti da su au-
tori dobili pisanu saglasnost od svih osoba koje se pominju u Za-
hvalnosti ili se citiraju kao lina saoptenja. Ovde se navodi i
nasijska pomo u obliku poklona opreme, supstancija ili lekova,
stipendije i sl.
11. Propratno pismo. Pismo se alje s rukopisom i sadri sledee
izjave:
a. rad nije ranije publikovan i nije istvremeno podnet za
objavljivanje u nekom drugom asopisu,
b. svi su autori proitali rukopis i odobrili ga i
c. pismena saglasnost ili dozvola je pribavljena od 1) svih
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Scripta Medica
osoba koje se pominju u poglavlju Zahvalnost, 2) od paci-
jenata ili dobrovoljaca koji su uestvovali u studiji i 3) od
etikog odbora ustanove za izvoenje studije na ljudima
(pacijenti i dobrovoljci) ili viim ivotinjama. [Saglasnost
Etikog odbora ustanove (Institutional Ethics Com-
mittee, IEC) za izvoenje studije je u skladu s Zahtevima
za izradu rukopisa koji se podnose medicinskim asopi-
sima (Uniform Requirements for Manuscripts Submitted
to Biomedical Journals, www.icmje.org).
Propratno pismo potpisuje korespondirajui autor.
12. Slanje rukopisa. Rukopis i sve priloge (propratno pismo, izja-
va o autorstvu i izjava o sukobu interesa) slati putem elektronske
pote na adresu editor@scriptamedica.com, najbolje u jednom
fajlu. U nazivu fajla treba da stoji i pezime autora s kojim
se vri korespodencija. Potpisani primerak propratnog pisma i
izjave mogu se slati putem faksa +387 (51) 329-100. Prijave ra-
dova koje nisu u skladu s navedenim instrukcijama nee se raz-
matrati.
13. Ureivaki proces. Rukopisi koji ispunjavaju osnovne uslove
za publikovanje, po proceni redakcije, uputie se recenzentima.
Autorima se preporuuje da predloe dva ili vie kvalikovanih
strunjaka iz odgovarajueg podruja koji bi mogli biti recenzen-
ti. Preduslov je da su kandidati publikovali najmanje pet laka u
asopisima koji su obuhvaeni MEDLINE bazom podataka. Sla-
nje rukopisa, korespodencija s urednicima i uvid u probni otisak
rada odvija se elektronskom potom.
14. Ocena rukopisa i revizije. Rukopisi koji su pogodni za slanje
recenzentima recenzirae dva recenzenta. Neki e rukopisi biti
prihvaeni bez potrebe da se revidiraju, a ako je nuna revizija,
glavni autor mora u pismu uredniku odgovoriti na svako pitanje,
kritiku, zahtev i sugestiju recenzenata i urednika. U novu verziju
rukopisa treba uneti odgovarajue izmene, a urednika asopisa
obavestiti ta je sve uraeno po preporukama. Sve izmene ru-
kopisa oznaiti drugom bojom slova i tu verziju rukopisa treba
poslati uredniku zajedno s pomenutim pismom u istom fajlu (iji
naziv opet ukljuuje i prezime korespondirajueg autora). SM
objavljuje oko 60% prispelih rukopisa.
15. Dodatne informacije mogu se nai ili dobiti od:
Drutvo doktora Republike Srpske
c/o Ms. Biljana Radii
Prvog krajikog korpusa 4/I
78000 Banja Luka, Republika Srpska
Bosnia i Herzegovina
Telefon i faks: +387-(51) 329-100
E-mail: drmrs@inecco.net
editor@scriptamedica.com
Specine instrukcije za pripremu rukopisa
Naslovna strana. Naslovna strana rukopisa sadri naslov
lanka, ime i prezime svakog autora (bez titula), naziv odeljenja,
ustanove i grada. Na toj stranici navodi se ime autora za korespo-
denciju (glavni autor) zajedno s adresom, brojem telefona i faksa
i e-adresom. Skraeni naslov s ne vie od 40 slova i praznih me-
sta takoe treba ovde navesti, a iza toga napisati koliki je broj rei
u rukopisu. Originalni lanci mogu sadravati do 2.500 rei, ne
raunajui reference i apstrakt. Za rukopise kontrolisanih klini-
kih istraivanja, autori e dobiti instrukcije od urednika.
Naslov treba da ukae na glavnu temu ili poruku lanka. Stan-
dardni naslov istraivakog lanka je fraza (ree reenica) koja
treba da je koncizna i precizna, informativna i deskriptivna.
Kada se u radu opisuje samo metod, naslov treba da ukae da li
je u pitanju nov metod ili unapreenje postojeeg.
Apstrakt i kljune rei. Za originalne radove apstrakt (do
250 rei) treba da ima sledeu strukturu: Uvod, Materijal i me-
tode, Rezultati i Zakljuak. U njemu treba navesti pitanje ili pro-
blem koji se u radu istrauje, metode koje su koriene, dobijene
rezultate i, na kraju, da se da odgovor da postavljeno pitanje. Za
ostale vrste lanaka apstrakt se pie u jednom pasusu. Svaki ap-
strakt treba da prui jasnu informaciju.
Ispod apstrakta, autori treba da navedu 36 kljunih rei ili
kratkih fraza prema terminima Medical Subject Headings
MeSH (www.nlm.nih.gov/mesh), na srpskom i engleskom jeziku.
Prevod apstrakta, tabela i naslova ilustracija na en-
gleski. Na posebnoj stranici priloiti naslov rada na engleskom
jeziku, imena i prezimena autora (bez titular) indeksirana broje-
vima, zvanini naziv ustanova na engleskom jeziku, structured
Abstract (Introduction, Methods, Results, Conclusion). Prevesti
nazive tabela, slika i celokupni tekst u njima. Treba se pridravati
jezikog standarda British English. [Radovi koji se u celini do-
stave na engleskom imaju prednost u objavljivanju. Uputstvo za
rukopise na engleskom dato je u Instructions for contributors.]
Uvod. U poglavlju Uvod, opisati razlog za istraivanje, dati svr-
hu studije ili objasniti zato je ona vana. Cilj istraivanja moe
biti u formi postavke, istraivakog pitanja ili hipoteze. Treba
samo citirati radove koji su relevantni.
Materijal i metode. Ovo poglavlje opisuje procedure pomou
kojih se izvodi studija; opis treba da omogui drugima, ako ele,
da studiju ponove. Ako je metod merenja poznat, treba ga citirati
i opisati s par reenica. Treba prikazati dizajn studije i navesti
koje su intervencije preduzimane, da li postoji saglasnost etikog
komiteta o eksperimentima na ljudima i viim ivotinjama, kako
je vrena randomizacija, koliko dugo su praeni uesnici, kako
su prikupljani podaci i kako je vrena statistika analiza poda-
taka. Treba denisati nezavisne i zavisne varijable. Za lekove i
hemikalije koristiti generike nazive, doze lekova i nain dava-
nja. Variabilnost izraziti pomou srednje vrednosti i standardne
devijacije (SD). Poto su SD i standardna greka srednje vredno-
sti (SE) pozitivni brojevi, Council of Science Editors preporuuje
eliminaciju znaka +/- sign; umesto njega SD, kao i SE, se daju
u zagradama. Na primer, sistolni krvni pritisak grupe zdravih
studenata iznosio je 129 mm Hg [SD = 6, n = 87]. Vrednost P
moe se koristiti da se odbaci nulta hipoteza, ali treba navesti
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Scripta Medica
procenu snage studije (power of the study) i statistiki test kori-
en u statistikoj analizi.
U revijskim (preglednim) lancima se opisuju metode kojima su
locirani, odabrani, pronaeni i sintetisani podaci. Te metode, ta-
koe, treba navesti u apstraktu.
Rezultati. Dobijene rezultate treba izloiti logikim tokom ko-
rienjem teksta, tabela i ilustracija. Sve ilustracije nose naziv
Slike (Figures). Taj deo rukopisa daje odgovor studije na po-
stavljeno istraivako pitanje. Ponekad je to najkrai tekstualni
deo rukopisa. Detalji se mogu prikazati u jednoj ili vie tabela i
slika. Ne ponavljati podatke iz tabela ili slika u tekstu. U tekstual-
nom delu treba samo naglasiti najvanije rezultate koji direktno
odgovaraju na pitanje iz Uvoda.
Tabele. Svaka tabela (4 tabele ili slike su dozvoljene) sa svojim
legendama treba da opie o emu je re; redosled im se numeri-
e arapskim brojevima u tekstu. Naslov treba da je iznad tabele,
a objanjenja, ukljuujui denicije skraenica, nalaze se ispod
tabele. Sve ovo pisati dvojezino (srpski i engleski). Tabele raditi
iskljuivo u programu Word (koristiti table-insert-table). U tabe-
li, u iste elije uneti tekst na srpskom i engleskom jeziku. (Nikako
ne praviti dve dabele na dva razliita jezika.)
Slike. Sve ilustracije (fotograje, grakoni, sheme) treba nu-
merisati arapskim brojevima redosledom njihovog pominjanja u
tekstu (maksimum 4 slike ili tabele su dozvoljene). Sve ilustracije
nose naziv Slike. Slova su tamna na beloj podlozi a veliina tre-
ba da je itjiva kada se tampanjem umanje. Originalne crtee,
EKG zapise i sl. treba skenirati sa barem 300 DPI (JPG ili TIF).
Legende za slike kucati s dvostrukim proredom na posebnom
listu oznaene Arapskim brojem koji odgovara slici. Simbole,
strelice, brojeve ili slova koji su na slici objasniti u legendi. In-
terna skala treba da se pojavi na mikrosnimku, a metodi bojenja
se opisuju u legendi. Tekst legende i sva objanjenja piu se dvo-
jezino.
Diskusija. Ukratko navesti glavni nalaz koji se odnosi na svrhu
istraivanja ili odgovor na istraivako pitanje koje je postavlje-
no u Uvodu. Zatim komparirati svoje nalaze s publikovanim ra-
dovima; osvrnuti se na ogranienja korienih metoda i navesti
implikacije svojih nalaza.
Zahvalnost. Navesti one koji su doprineli stvaranju rada, a
ne ispunjavaju merila za autorstvo, ako su osobe dale pismeni
pristanak za to. Finansijska i materijalna pomo se ovde takoe
navodi.
Doprinos autora. Ukoliko je rukopis pisalo dva ili vie autora,
svaki od njih opisuje doprinos radu (taka 8. ovog Uputstva).
Konikti interesa. Autori navode potencijalne konikte inte-
resa (taka 9. ovog Uputstva).
Reference. Ispravnost liste referenci je odgovornost autora.
Citirati lanke u tekstu rednim arapskim brojevima prema re-
dosledu navoenja u tekstu. Reference se ispisuju prema Van-
kuverskom stilubroj se u tekstu navodi u superskriptu, nakon
bilo kog znaka interpunkcije. Na primer, Vuli and colleagues.
12

Kada se citiraju dve reference, one se odvajaju zarezom, bez raz-
maka. Tri ili vie referenci u nizu se razdvaja crtom (na primer,
3-6
). Reference koje se eventualno citiraju u tabelama i slikama
dobijaju redni broj prema mestu gde se ove ilustracije postave u
tekstu. Za citiranje prema Vankuverskom stilu, videti Uniform
Requirements for Manuscripts Submitted to Biomedical Jour-
nals; to su pravila koja su data od strane Meunarodnog komi-
teta urednika medicinskih asopisa (International Committee of
Medical Journal Editors; www.icmje.org). Ako referenca sadri
est autora ili manje, treba navesti sve autore prezimenom, raz-
mak, inicijali, zarez. Ako u pitanju sedam ili vie autora, navode
se prva tri i sledi et al. U nastavku su primeri navoenja nekih
publikacija, a za ostale uputstvo je na internet stranici: (www.
nlm.nih.gov/bsd/uniform_requirements.html).
De Lacey G, Record C, Wade J. How accurate are quotations
and references in medical journals. BMJ 1985;291:884-6.
International Committee of Medical Journal Editors. Uniform
requirements for manuscripts submitted to biomedical jour-
nals. Croat Med J 2003;44:770-83.
Huth EJ. How to write and publish papers in the medical sci-
ences. Philadelphia: ISI Press, 1982.
Davidovi L, Markovi M, oli M, et al. Treatment of tra-
umatic rupture of the thoracic aorta. Srp Arh Celok Lek
2008;136:498-504.
Curtis MJ, Shattock MJ. The role of the manuscript assessor.
In: Hall GM, ed. How to write a paper. London: BMJ Publishi-
ng Group; 1994:89-95.
Electronic publications (ove citate treba izbegavati):
International Society of Scientometrics and Informatics Web
site. Available at: http://www.issi-society.info (accessed Mar-
ch 20, 2012).
Lock SP. Journalology: are the quotes needed? CBE Views.
1989:1257-9. Available at: http://gareld.libraryupenn. edu/
essays/v13po19y1990.pdf (accessed Dec 25, 2011).
Revijski lanci
Revijski lanci se piu po narudbi redakcije, na ne vie od 2,500
rei, ne raunajui reference i apstrakt. Uz rukopis se mogu pro-
iti 4 tabele ili ilustracije. Broj referenci je ogranien na 50.
Prikaz bolesnika
Prikazi bolesnika verovatno e biti publikovani ako se u njima
opie sledee: nuspojave (tetne ili korisne) ili interakcije leko-
va koje od ranije nisu poznate; nov, neoekivan ili neoban tok
bolesti; uzrona veza izmeu dve bolesti koja ranije nije bila opa-
ena; prikaz, dijagnoza i/ili leenje novih bolesti ili bolesti koje
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Scripta Medica
se naglo ire; ranije nepoznata veza izmeu dve bolesti ili raznih
simptoma; neoekivan dogaaj u toku bolesti ili leenja pacijen-
ta; ranije nepoznata bolest. SM ne objavljuje prikaze bolesnika
koji slue samo u edukativne svrhe (da se opie ono to je po-
znato, a to su mnogi zaboravili). SM nerado objavljuje prikaze
bolesnika koji spadaju u kategoriju retkih sluajeva.
Prikaz bolesnika (manje od 750 rei) ukljuuje sledee: naslov
(na engleskom i srpskom), prikaz bolesnika sa diskusijom (mo-
gue je priloiti do 3 ilustracije), do 6 referenci i nestrukturisan
apstakt na engleskom i srpskom (do 100 rei). Naslov treba da
je kratak kako bi olakao elektronsko pretraivanje. Prikaz bo-
lesnika sadri kratke anamnestike podatke, ziki pregled i
glavne nalaze svih pretraga, opis leenja, koje su opcije za leenje
razmatrane, ishod leenja. Diskusija ukljuuje izjavu da li je u
pitanju neobina dijagnoza, prognoza, terapija ili tetna pojava,
da li su u literaturi opisani slini sluajevi, ta je neobino kod
prikazanog bolesnika, ta bi se u slinim sluajevima moglo dru-
gaije uraditi.
Prikaz bolesnika moe imati najvie 5 autora. Veoma kratke pri-
kaze bolesnika (bez ilustracija) primamo kao Pisma uredniku.
Autori moraju pribaviti pisani pristanak bolesnika da se lanak o
njemu moe objaviti; ako pristanak ne moe da potpie bolesnik,
pristanak treba traiti od roditelja ili staratelja. U propratnom
pismu treba navesti da je takav dokumenat pribavljen. Izjavu o
doprinosu autora (ukoliko ih je dva ili vie) i izjavu o koniktima
interesa moraju potpisati autori.
U propratnom pismu, autori treba da ukau po emu njihov pri-
kaz bolesnika doprinosi medicinskoj literaturi. Prilozi koji ne sa-
dre tu informaciju vratie se autorima bez ocene rukopisa.
Slike iz klinike medicine
Urednici e razmatrati originalne, jasne i interesantne slike koje
ukazuju na novije ili klasine klinike odlike koje su praene tek-
stom (uz najvie 3 reference) na ne vie od 200 rei. To saoptenje
mogu pisati najvie dva autora. Autori moraju dobiti pismenu sa-
glasnost od pacijenta, bliskog roaka ili staratelja. U propratnom
pismu treba navesti da je takava saglasnost pribavljena. Izjavu
izjavu o koniktima interesa moraju potpisati autori.
Reavanje klikog problema
Reavanje razliitih klinikih problema, ukljuujui klinike
studije, treba da sadri sledee delove: Apstrakt (na srpskom i
engleskom), Uvod, Metode ili Prikaz(e) bolesnika, Diskusija, Re-
ference (do 20). Apstrakt se pie u jednom pasusu (nestrukturi-
sano) na do 150 rei. Ovaj tip rukopisa ne sme imati vie od 1400
rei, ne raunajui reference, tabele i ilustracije. Autori moraju
dobiti pismenu saglasnost od pacijenta, bliskog roaka ili stara-
telja. U propratnom pismu treba navesti da je takav dokumenat
pribavljen. Izjavu o doprinosu autora (ukoliko ih je dva ili vie) i
izjavu o koniktima interesa moraju potpisati autori.
Pisma uredniku
Kada se pismo odnosi na nedavno objavljen lanak u ovom asopi-
su, ono moe imati do 250 rei, ne raunajui refernce. Sva pisma
treba da su kratka i konkretna. Ne vie od 5 referenci moe se pri-
loiti, ali ne lustracije ili tabele. Izjavu o koniktima interesa mo-
raju potpisati autori. Urednici imaju pravo da skrate svako pismo.
Uvodnici
Uvodnike pie urednik ili strunjaci po pozivu. Cilj im je da se
ukae na lanke koji su objavljeni u asopisu ili da se izraze opta
i aktuelna gledita.
Specijalni lanci
Specijalni alanci sadre do 1500 rei. Posveeni su nekom medi-
cinskom problemu, istorijskoj perspektivi, edukaciji, demograji
ili savremenim temama. Do 15 referenci i 2 tabele ili ilustracije
su dozvoljene. Nestrukturisan apstrakt (do 150 rei) na srpskom
i engleskom se prilae uz tekst specijalnog lanka. Izjavu o kon-
iktu interesa moraju potpisati autori.
Saoptenje za novinare. Autore interesantnih i vanih
lanaka redakcija e zamoliti da napiu tzv. press release
saoptenje za novinare. Taj tekst pomae da se poruka ispravno
prenese irokoj javnosti. Ni autor ni novinari ne treba da
distribuiraju podatke iz nepublikovanih lanaka sve dok ne
proe embargo asopisa za sredstva javnog informisanja, tj. dok
se asopis ne publikuje.
Saoptenje za novinare obino sadri 150 do 250 rei kojima se
iznosi glavna poruka. Reenice treba da su kratke, a rei razum-
ljive. Laiku treminologiju treba koristiti kad god je mogue, a
tehnike termine i uobiajene strune skraenice treba objasniti
kada se koriste prvi put. Takoe, jasnije je umesto procenata ko-
ristiti aproksimacije. Na primer, za 9% bolje je navesti jedan
od deset ili za 55% vie od polovine. Na kraju ovih saoptenja
treba navesti ime, adresu, telefon i e-adresu glavnog ili starijeg
istraivaa. Ukoliko je vie autora potpisalo lanak, mogue
je da bilo koji bude izabran za komuniciranje s medijima za
masovno informisanje. Kada urednik Scripta Medica proceni,
asopis moe organizovati konferenciju za novinare kako bi bili
predstavljeni zanimljivi lanci. Na konferencji e se distribui-
rati press release odabranih lanaka, a autor e odgovarati na
pitanja novinara.
Slanje rukopisa
-Rukopis, tabele, slike i propratno pismo i izjave treba
slati elektronskom potom, editor@scriptamedica.com,
kad god je mogue sve u jednom fajlu koji u nazivu
sadri prezime korespondirajueg autora.
Propratno pismo i izjave se mogu skenirati i slati elek-
tronski. Izuzetno se ti materijali mogu poslati faksom
+387 (51) 329-100.
Da se izbegnu kanjenja, preporuujemo autorima da
sve potpisane dokumente poalju zajeno s rukopisom.
POTPISI
- PROPRATNO PISMO
- IZJAVA O AUTORSTVU
- IZJAVA O KONFLIKTIMA INTERESA
119
Scripta Medica
Instructions For
Contributors
Scripta Medica (SM) is a peer-reviewed international jour-
nal published under the auspices of the Medical Society of the
Republic of Srpska. The journal publishes original biomedical
studies, including those addressing ethical and social issues. As
a general medical journal, SM gives preference to clinically ori-
ented studies over those on experimental animals. It publishes
peer-reviewed original research papers, case reports, review ar-
ticles, essays, special articles, clinical problem-solving, images
in clinical medicine only in English. Book reviews and news are
published only in Serbian. The full text of SM is available, free of
charge, online at www.scriptamedica.com.
General instructions
1. Manuscripts should be submitted in the .DOC format (Micro-
soft Word), using the Times New Roman font. The text should
be single spaced 11 point. The main heading should be 12 point
bold. Subheadings should be 11 point bold. Tables must be 10
point, single spaced; headings within tables should be 10 point
bold; the main table heading should be 12 point bold; legends
should be single spaced in 11 point. Illustrations can be submit-
ted in either JPG or TIFF format (300 dpi or higher resolution).
2. Drugs and chemicals should be indicated by generic names.
Instruments, apparatus or other devices are indicated by trade
names, with the producers name and place of production indi-
cated in brackets.
3. Numbers in text and tables should be provided if expressed
as %; means should be accompanied by SDs, and medians by
interquartile range (IQR). In text, use following rule: spell out
numbers up to ten and then use numerical designation for 10 and
above.
4. All images must have minimum resolution of 300 dpi. The
main gure heading should be 10 point bold; legends should be
single spaced 10 point.
5. References should be indicated in the text sequentially in the
Vancouver numbering style, as superscripted number after any
punctuation mark.
6. Units of measure, length, height, weight and volume are to be
expressed in metric units (e.g., meterm, kilogramkg, literl)
or subunits. Temperature should be in degrees Celsius (
o
C); quan-
tities of substances are given in moles (mol), and blood pressure is
expressed as millimeters of mercury (mm Hg). All values of hema-
tological, clinical and biochemical measurements use the metric
system according to the International System of Units (SI units).
7. Abbreviations may be used for very long names, including those
of chemical compounds. The full name should be given when
rst mentioned in the text unless it is a standard unit of mea-
sure. If abbreviations are to be used in the Abstract, each should
be explained when rst mentioned in the text. Well-known ab-
breviations, such as DNA, AIDS, HIV, ADP, ATP etc, need not be
introduced by the full name. Titles should include abbreviations
only when the abbreviation is universally accepted.
8. Authorship statement. To qualify for authorship, one must
made substantial intellectual contributions to the study on
which the article is based (WAME.com, Policy StatementsAu-
thorship). The author should participate at least in one of these
three categories:
a. research question, conception and design, data acquisi-
tion and analysis,
b. statistical analysis, interpretation of data, provision of
funding, technical or material support, overall supervi-
sion of the project.
c. drafting or critical revision of the manuscript.
In some research projects may participate experts (such as bio-
statisticians or epidemiologists) that may not be equally familiar
with all aspects of the work (for example, some clinical variables
or laboratory measurements), but they may be qualied as the
authors. A statement acknowledging contribution to the manu-
script should be signed by all the authors. It will be published in
the section Author Contributions. The corresponding author is
responsible for the integrity of the work as a whole. It is dishon-
est to omit mention investigator who had important engagement
with some aspects of the work.
9. Financial disclosure. A disclosure statement declaring any
potential conict of interest must be signed by each author.
(See the policy statement on conict of interest issued by the
World Association of Medical Editors, WAME, www.wame.org
or ICMJE uniform disclosure form for potential conicts of in-
terest, www.icmje.org.) This disclosure includes all afliations
or nancial involvement (e.g., employment, consulting fee or
honorarium, gifts, stock ownership or options, travel/accomo-
dations expenses, grants or patents received or pending, and
royalties) with any organization having a nancial interest in or
nancial conict with the subject matter or materials discussed
in the manuscript. This information will be held in condence
while the paper is under review. If the manuscript is accepted
for publication, the editors will discuss with the author how
such information is communicated to the reader in the section
Conicts of interest.
10. Acknowledgment statement. The cover letter must state that
the authors obtained written permission from all individuals
named in an Acknowledgment or cited as personal communica-
tions.
11. Consent statement and permission obtained by the institu-
tional ethics committee (IEC). A cover letter should state that
written informed consent was obtained from all subjects (pa-
tients and volunteers) included in the study, and that the study
was approved by the IEC.
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Scripta Medica
The majority of these instructions are in accordance with Uni-
form Requirements for Manuscripts Submitted to Biomedical
Journals (www.icmje.org).
12. Cover letter. The letter accompanying the submission should
include the following:
a. A statement that the paper has not been previously pub-
lished, nor is it concurrently submitted to any other jour-
nal,
b. A statement that the manuscript has been read and ap-
proved by all authors.
c. Assertion that written acknowledgments, consent state-
ments and/or permission by the institutional ethics com-
mittee were obtained.
This letter should be signed by corresponding author.
13. Submission of manuscripts. Manuscripts and all enclosures
(cover letter, authorship statement and nancial disclosures)
should be sent by e-mail to editor@scriptamedica.com, pref-
erably in one le. Signed copies of the cover letter and various
statements may be faxed to +387 (51) 329-100. Submissions that
do not comply with these instructions will be returned, unread.
14. Editorial process. Manuscripts deemed suitable for publica-
tion by in-house assessment will be reviewed by two or more out-
side experts. Contributors are encouraged to provide names of
two or more qualied reviewers with experience in the subject of
the submitted manuscript, but this is not mandatory. Page proofs
of accepted articles will be sent to the corresponding author, and
the corrected proofs should be returned within three days. The
entire process, from the initial submission of the manuscript
to the nal review, including the sending and receiving of page
proofs, can be completed online.
15. Review procedure. Manuscripts suitable for peer review will
be sent to two outside reviewers. Some manuscripts may be
accepted without revision, but if revision is required, the cor-
responding author must address each question, criticism and
suggestion from the reviewers and editor. These topics can be
addressed in a letter to the editor along with a revised manu-
script. The acceptance rate for SM is around 60%.
16. For further information, please contact us at the following ad-
dress:
Drutvo doktora Republike Srpske
c/o Ms. Biljana Radii
Prvog krajikog korpusa 4/I
78000 Banja Luka, Republic of Srpska, Bosnia & Herzegovina
Phone & Fax: +387-(51) 329-100
E-mail: drmrs@inecco.net
editor@scriptamedica.com
Specic instructions for a manuscript
Title page. The title page of the manuscript contains the title
of the article, the full name of each author (without titles), and
the departments and institutions of the author(s) in the order
they are listed. The title page must also include the name of the
corresponding author, (along with address, phone and fax num-
bers and e-mail address) to which the work should be attributed.
A short running title should have no more than 40 characters,
including spaces. The word count should be indicated as well.
Original articles may have up to 2.500 words, excluding refer-
ences and abstract.
The title should identify the main topic or the message of the pa-
per. The standard title of a research paper is a phrase (rarely a
sentence) that identies the topic of the paper; it should be con-
cise and precise, informative and descriptive.
The title of a descriptive paper should include the necessary
description, function, purpose, animal species or population.
When a method is described, the title should indicate whether it
is new or improved.
Abstract and key words. Structured abstracts should be in-
cluded in papers that report original research. Abstracts are lim-
ited to 250 words in four labeled paragraphs: Introduction, Mate-
rials and Methods, Results, and Conclusion. The abstract should
state concisely the question that was asked or the objectives of
the study, the methods that were used, the results obtained, and
adequately answer the question posed in the introduction. The
abstract should provide pertinent information when read alone.
Below the abstract, authors should provide 3-6 key words or
short phrases, according to terms from the Medical Subject
HeadingsMeSH (www.nlm.nih.gov/mesh).
Introduction. Generally, this section provides the motivation
for the paper (i.e., what is missing or unknown in the research
literature at this time), an overview of the scientic theory or
conceptual models on which the research was based, and the
purpose of the study and why it is important. Cite only relevant
references.
Materials and methods. This section accurately describes
the procedures used to carry out the study; it should be com-
plete enough to permit others to replicate the study. Describe
the methodological design, subjects, data sources, data collec-
tion methods, and any statistical and analytical procedures.
These ve parts may not be needed in all papers. Short papers
may include these details in different paragraphs, but titled
subsections may be used in longer papers. The Methods section
should describe how the research was structured, how subjects
or groups of subjects (dened by sex, age, and other character-
istics) and how the subjects were chosen and assigned to these
groups. Identify all drugs and chemicals by generic names, exact
drug dosages and routes of administration. Variability should be
expressed in terms of means and standard deviations (SD). Be-
cause SD and SEM are positive numbers, we recommend elimi-
nation of a +/- sign; instead, the SD may be given in brackets. For
example, systolic blood pressure in group of healthy students
was 129 mm Hg [SD = 6, n = 87]. A p-value can be used to dis-
121
Scripta Medica
prove the null hypothesis, but the authors should also give an
estimate of the power of the study and state the exact tests used
for statistical analysis.
Results. This section presents ndings in logical sequence us-
ing the text, tables and illustrations. This section should show
how the results of the study answer the research question. This
may be shortest part of the entire paper. Details may be present-
ed concisely in one or more tables or gures. Do not repeat the
data presented in tables or illustrations in the text. Emphasize or
summarize only important observations and how these answer
the question posed in the introduction.
Tables. Each table (4 tables or gures are permitted) with its
legends, should be self-explanatory and numbered in Arabic nu-
merals in order of their mention in the text. The title should be
typed above the table, and any explanatory text, including deni-
tions of abbreviations, is placed below the table.
Illustrations (Figures). All gures (photographs, graphs, or
schemes) should be numbered with Arabic numerals in the order
of their mention in the text (a maximum of 4 gures or tables
may be submitted). All lettering should be dark against a white
background and of sufcient size to be legible when reduced for
publication. Do not send original artwork, x-ray lms, or ECG
tracings but rather photographs of such material. Images need
to be at least 300 DPI (JPG or TIF les). Figure legends should
be typed double-spaced on a separate page with Arabic numer-
als corresponding to the gure. All symbols, arrows, numbers,
or letters should be explained in the legend. An internal scale
should appear on photomicrographs, and methods of staining
should be described in the legend.
Discussion. Briey state the principal nding that relates to
the purpose or research question posed in the Introduction and
follow with an interpretation of the results obtained. Compare
your ndings with work reported previously by others. Discuss
the implications of your ndings and their limitations with re-
spect to the methods used.
Acknowledgments. List all persons as well as nancial and
material supporters who helped to realize the project, even if
they did not meet the criteria for authorship.
References. The reference list is the responsibility of the au-
thors. List all the papers or other sources cited in describing pre-
vious or related research. Cite references in the text sequentially
in the Vancouver numbering style, as superscripted number after
any punctuation mark. For example: as reported by Vuli and
colleagues.
12
When two references are cited, they should be sepa-
rated by comma, with no space. Three or more consequtive refer-
ences are given as a range with an en rule. References in tables
and gures should be in numerical order according to where the
item is cited in the text. For citations according to the Vancou-
ver style, see Uniform Requirements for Manuscripts Submitted
to Biomedical Journals; this source gives the rules and formats
established by the International Committee of Medical Journal
Editors (www.icmje.org). If there are six authors or fewer, list
all six by last name, space, initials, comma. If there are seven or
more, list the rst three in the same way, followed by et al. For a
book, list the editors and the publisher, the city of publication,
and year of publication. For a chapter or section of a book, give
the authors and title of the section, and the page numbes. For
online material, please cite the URL and the date you accessed
the website.. Online journal articles can be cited using the DOI
number. Do not put references within the Abstract section. All
titles should be in English (the name of the original language
should appear in brackets). See examples below that conform to
the Uniform Requirements for Manuscripts Submitted to Bio-
medical Journals:
De Lacey G, Record C, Wade J. How accurate are quotations
and references in medical journals. BMJ 1985; 291:884-6.
International Committee of Medical Journal Editors. Uniform
requirements for manuscripts submitted to biomedical jour-
nals. Croat Med J 2003; 44:770-83.
Huth EJ. How to write and publish papers in the medical sci-
ences. Philadelphia: ISI Press, 1982.
Davidovi L, Markovi M, oli M, et al. Treatment of trau-
matic rupture of the thoracic aorta. Srp Arh Celok Lek 2008;
136: 498-504.
Curtis MJ, Shattock MJ. The role of the manuscript assessor.
In: Hall GM, ed. How to write a paper. London: BMJ Publish-
ing Group; 1994: 89-95.
Electronic publications:
International Society of Scientometrics and Informatics Web
site. Available at: http://www.issi-society.info Accessed March
20, 2012.
Lock SP. Journalology: are the quotes needed? CBE Views.
1989:1257-9. Available at: http://gareld.libraryupenn. edu/
essays/v13po19y1990.pdf. Accessed April 25, 2012.
Review article
Review articles are written by individuals who have studied a
particular subject or area extensively, and who are considered
experts. For these reviews, the word count may not exceed 2.500
words, excluding references and abstract. The manuscript may
have up to 4 tables or illustrations, and as many as 50 references.
Case report
Case reports are most likely to be published if they describe
any of the following: an unreported drug side effects (adverse
or benecial), drug interactions; a new, unexpected, or unusual
manifestation of a disease; previously unsuspected causal as-
sociation between two diseases; presentations, diagnosis and/
or management of new and emerging diseases; an unexpected
association between diseases or symptoms; an unexpected event
122
Scripta Medica
in the course of observing or treating a patient, ndings that shed
new light on the possible pathogenesis of a disease or an adverse
effect; a previously unknown disease. Scripta Medica does not
publish instructive case reports, that is, presentations that make
important teaching point of what is already well known but often
forgotten.
Case reports (no longer than 750 words) should include the fol-
lowing: title, case presentation (including up to three illustra-
tions) and discussion, references (up to six), and an unstructured
abstract in English or Serbian. The abstract may be a single para-
graph containing no more than 100 words, and followed by key
words. Title should facilitate retrieval with electronic searching.
Case presentation should include the history, examination and
investigations adequately, description of treatments, state have
all available therapeutic options been considered, and are out-
comes related to treatments. Discussion includes following: state
does the case have an unusual diagnosis, prognosis, therapy or
harm; report of a literature review of other similar cases and
is this different; explain rationale for reporting the case; what
is unusual about the case; could things be done differently in a
similar case?
Case reports may have as many as ve authors. A very short case,
a novel use of equipment, or new information about a particular
disease can be submitted as a Letter to the Editor. Consent for
publication must be obtained from the patients involved; if this
is not possible, permission from a close relative or guardian must
be obtained before submission.
Authors should indicate in a cover letter how the case report con-
tributes to the medical literature. Submissions that do not include
this information will be returned to authors prior to peer review.
For all case reports, informed written consent is required; the
cover letter should state that consent was obtained. Authorship
statement and nancial disclosure should be presented.
Images in clinical medicine
The editors will consider original, clear and interesting images
that depict novel or classic clinical pictures submitted along
with a descriptive paragraph of up to 200 words. The report may
include two authors and three references. The authors must ob-
tain a signed, informed consent from the patient or from a close
relative or guardian. The cover letter from the corresponding au-
thor should state that written consent was obtained.
Clinical problem-solving
Solutions for various clinical problems, including certain clini-
cal studies, should include the following sections: Abstract, In-
troduction, Methods or Case(s) Presentation, up to four tables
or illustrations, Discussion, References (maximum 20). The
unstructured Abstract must be in English and be limited to 150
words, and followed by key words. This type of communication
should not exceed 1400 words in all, including references and
tables. Authors must obtain signed informed consent directly
from the patients involved or from a close relative or guardian
before submission. The cover letter should note that consent was
obtained. Authorship statement and nancial disclosure should
be presented.
Letter to the editor
If the letter refers to a recent journal article, it should not exceed
250 words, excluding references. All letters should be brief and
to the point with no more than ve reference citations. Figures
or tables are not permitted in this format. Financial disclosure
should be presented.
Editorial
Editorials are solicited by the editor to provide perspective on
articles published in the journal and/or to express the general
policies or opinions of the Editorial Board.
Special article
Special articles of 1500 words or less may be devoted to any
medical problem, historic perspective, education, demography,
or contemporary issues. Up to 15 references may be cited, and the
piece may contain 2 tables or illustrations. An unstructured ab-
stract in English (150 words or less) should accompany a specic
article. Finacial disclosure should be presented.
Press Release. The authors of a particularly interesting or
signicant articles may be asked by the editor of the Scripta
Medica, or directly by the media, to write a press release, a text
that will help spread the message to wide audience. Neither
authors nor journalists should distribute unpublished reports
until the journals media embargo has expired.
Press release should be between 150 and 250 words long and
covey the main message in short sentences and understandable
terms. Lay terminology should be used whenever possible, and
technical words and abbreviations should be explained when
rst used. For lay readers and listeners approximations are pref-
erable to percentages when reporting data. For example, 9% be-
comes nearly one in ten, and 55% becomes more than half.
The press release should contain the name address, telephone,
and e-address of the primary or senior author, but if there are
multiple authors, one could be selected to talk to the media.
When appropriate, Scripta Medica may organize a press confer-
ence to present interesting articles. The authors cwill be invited,
and the press releases will be distributed.
SUBMISSION OF PAPERS
- Manuscripts, tables and gures should be emailed to
editor@scriptamedica.com, whenever it is possible, all
in one le.
Signed cover letter and the statements can be scanned
and submitted electronically together with previous
materials or faxed to +387 (51) 329-100.
To minimize delays, we advise that you prepare signed
copies of all statements before submitting the manuscript.
SIGNATURES
- Cover letter
- Authorship statement
- Financial disclosure statement

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-biochemical parameters which are out of the reference range.

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