0 Up votes0 Down votes

9 views8 pagesApr 01, 2011

© Attribution Non-Commercial (BY-NC)

PDF, TXT or read online from Scribd

Attribution Non-Commercial (BY-NC)

9 views

Attribution Non-Commercial (BY-NC)

- The Subtle Art of Not Giving a F*ck: A Counterintuitive Approach to Living a Good Life
- Sapiens: A Brief History of Humankind
- Hidden Figures: The American Dream and the Untold Story of the Black Women Mathematicians Who Helped Win the Space Race
- Shoe Dog: A Memoir by the Creator of Nike
- The Unwinding: An Inner History of the New America
- The Little Book of Hygge: Danish Secrets to Happy Living
- Never Split the Difference: Negotiating As If Your Life Depended On It
- Elon Musk: Tesla, SpaceX, and the Quest for a Fantastic Future
- Yes Please
- A Heartbreaking Work Of Staggering Genius: A Memoir Based on a True Story
- Grit: The Power of Passion and Perseverance
- Devil in the Grove: Thurgood Marshall, the Groveland Boys, and the Dawn of a New America
- The Emperor of All Maladies: A Biography of Cancer
- John Adams
- This Changes Everything: Capitalism vs. The Climate
- Team of Rivals: The Political Genius of Abraham Lincoln
- The Hard Thing About Hard Things: Building a Business When There Are No Easy Answers
- Principles: Life and Work
- Rise of ISIS: A Threat We Can't Ignore
- The World Is Flat 3.0: A Brief History of the Twenty-first Century

You are on page 1of 8

Rutgeerts

Am J Physiol Gastrointest Liver Physiol 275:169-175, 1998.

This article cites 15 articles, 4 of which you can access free at:

http://ajpgi.physiology.org/cgi/content/full/275/1/G169#BIBL

Methods for measurement of gastric motility

L. A. Szarka and M. Camilleri

Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296 (3): G461-G475.

[Abstract] [Full Text] [PDF]

[14C]erythromycin breath and urine test

W. P. D. Lemahieu, B. D. Maes, Y. Ghoos, P. Rutgeerts, K. Verbeke and Y. Vanrenterghem

Am J Physiol Gastrointest Liver Physiol, August 8, 2003; 285 (3): G470-G482.

[Abstract] [Full Text] [PDF]

Motilin agonists and dyspepsia: throwing out the baby with the bath water

M Camilleri, N J Talley and M Verlinden

Gut, October 1, 2002; 51 (4): 612-613.

[Full Text] [PDF]

Acute ingestion of a meal rich in n-3 polyunsaturated fatty acids results in rapid gastric

emptying in humans

M D. Robertson, K. G Jackson, B. A Fielding, L. M Morgan, C. M Williams and K. N Frayn

Am. J. Clinical Nutrition, July 1, 2002; 76 (1): 232-238.

[Abstract] [Full Text] [PDF]

on the following topics:

Biochemistry .. Octanoic Acid

Biophysics .. Metabolism

Physiology .. Digestion

Computer Science .. Mathematical Modeling

Updated information and services including high-resolution figures, can be found at:

http://ajpgi.physiology.org/cgi/content/full/275/1/G169

Additional material and information about AJP - Gastrointestinal and Liver Physiology can be found at:

http://www.the-aps.org/publications/ajpgi

AJP - Gastrointestinal and Liver Physiology publishes original articles pertaining to all aspects of research involving normal or

abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. It is published 12 times a year (monthly) by the

American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2005 by the American Physiological

Society. ISSN: 0193-1857, ESSN: 1522-1547. Visit our website at http://www.the-aps.org/.

Gastric emptying flow curves separated from carbon-labeled

octanoic acid breath test results

B. D. MAES,1 G. MYS,2 B. J. GEYPENS,1 P. EVENEPOEL,1

Y. F. GHOOS,1 AND P. J. RUTGEERTS1

1Department of Medicine, Division of Gastroenterology and Gastrointestinal Research Center,

Catholic University, Leuven B-3000, Belgium

Maes, B. D., G. Mys, B. J. Geypens, P. Evenepoel, and radioscintigraphic measurements taken simulta-

Y. F. Ghoos, and P. J. Rutgeerts. Gastric emptying flow neously in normal subjects and dyspeptic patients

curves separated from carbon-labeled octanoic acid breath allowed for highly accurate description of the gastric

test results. Am. J. Physiol. 275 (Gastrointest. Liver Physiol. emptying rate of a solid test meal (7, 16). With the use

38): G169–G175, 1998.—Recently, we developed the

of a regression model, we were able to calculate the

[13/14C]octanoic acid breath test to measure gastric emptying

of solids. Although the method has been validated exten- half-emptying time and lag phase, correcting for the

sively, absorption, metabolism, and excretion of the label in postgastric processing of octanoic acid.

the breath need to be corrected for. In this study a mathemati- The aim of this study was to develop a separation

cal model was developed that allows for 1) separation of the model in which the postgastric processing of octanoic

acid could be mathematically separated from the CO2

global CO2 excretion after ingestion of the labeled test meal

into the emptying rate of the labeled test meal from mouth to excretion curve after ingestion of a standard solid test

pylorus and the postgastric processing of absorption, metabo- meal to obtain real-time gastric emptying curves. This

lism, and excretion of the label, and 2) numerical calculation approach of breath test curve analysis has two poten-

of the half-emptying time and lag phase of the emptied meal. tial benefits: 1) physiologically meaningful gastric emp-

The model was applied to the gastric emptying results

tying parameters can be calculated from breath test

obtained by simultaneous scintigraphic and breath test mea-

surements. An excellent correlation was found between the curves without correcting for postgastric processing of

gastric half-emptying time (r 5 0.98) and lag phase (r 5 0.85) the label on a linear regression-estimated basis be-

determined scintigraphically and via breath test. There was tween radioscintigraphy and breath tests, and 2) it

also a good agreement between the two methods [mean allows for the evaluation of gastric emptying rates,

values and confidence limits for differences: t½ 5 10 min (220 instead of amounts of emptied food, as a function of

to 41) and tlag 5 23 min (239 to 34)]. Moreover, the separated time (flow curves). The classic multicompartmental

gastric emptying curves, lacking the influence of postgastric analysis, however, was not used due to the specific

processing of the label, showed real patterns of gastric conditions encountered in breath test technology. The

outflow, which changes from moment to moment. multiple-chamber model is difficult to apply in clinical

breath test technology; mathematical models practice, because the dynamic exchange of CO2 with the

rapid and slow bicarbonate pool and the loss of label via

excretion in urine and feces and incorporation into bone

is difficult to estimate in humans, certainly in each

RECENTLY, WE DEVELOPED the [13/14C]octanoic acid breath individual. Solution of the breath curve would require

test to measure gastric emptying of solids (7, 16). The the fitting of at least four exponential functions. This

rationale of a breath test is based on the firm retention can rarely be done convincingly with biological data,

of 13/14C-labeled octanoic acid in the solid phase of a test even if sampling takes place over long periods of time.

meal during mixing and grinding in the stomach, Also, it is not possible to obtain a steady state of

followed by rapid absorption from the chyme entering exchange between the different compartments (espe-

into the duodenum, an immediate and maximal oxida- cially the slowly exchanging ones) during the 4-h period

tion in the liver to labeled CO2, and a fast exhalation in of breath sampling. Moreover, when dose is not in the

breath. In vitro experiments showed that octanoic acid subsequently measured compartment the rate con-

is firmly retained in a standard solid test meal in a stants for intercompartmental exchange cannot be

gastric environment (7). It has been known for a long explicitly calculated from the multiexponential curve

time that octanoic acid, an eight-carbon fatty acid for tracer in breath.

found in dietary fats, is rapidly absorbed from the

intestine and carried to the liver via the portal venous RATIONALE FOR THE SEPARATION MODEL

system, where it is rapidly and completely oxidized (1,

2, 4–6, 10–13, 17–20, 22, 25). Therefore gastric empty- To elaborate the mathematical model, three func-

ing of the meal, and not the postgastric processing of tions were introduced to describe three different pro-

the label, could be considered the rate-limiting step in cesses.

the rate of labeled CO2 excretion in breath after inges- 1) The emptying rate of a labeled solid meal from

tion of a labeled solid test meal. mouth to pylorus is given by M(t).

Mathematical analysis of CO2 excretion curves made 2) The rate of postgastric processing (absorption,

it possible to exclude the influence of endogenous CO2 metabolism, and excretion in breath) of the label is

production on the breath test results, and breath test given by D(t).

0193-1857/98 $5.00 Copyright r 1998 the American Physiological Society G169

G170 A SEPARATION MODEL FOR BREATH TEST ANALYSIS

3) The global process of CO2 excretion after inges- that had already been metabolized during the first time

tion of a labeled solid test meal is given by T(t). interval (simplified: the first passage in the liver). The

The aim of this study is to determine M(t) given T(t) addition of all layers describes the total process T(t),

and D(t), which can both be measured, and to describe i.e., a 13/14CO2 excretion curve after ingestion of a solid

the relation between the three functions. Therefore the test meal. Mathematically it is expressed as

following assumptions were made. 1) The meal is

ingested at once, at time 0. This is not true, but the time T2 5 M1D1

of ingestion was always restricted to 10 min, and time 0 T3 5 M1D2 1 M2D1

was taken as the time of completion of the ingestion of

the meal. 2) T(t), D(t), and M(t) are piecewise continu- T4 5 M1D3 1 M2D2 1 M3D1

ous functions, not identical to zero and positive for each

time $ 0. 3) The rate of metabolism of the label [D(t)] is T5 5 M1D4 1 M2D3 1 M3D2 1 M4D1

proportional to the rate of gastric emptying of the label or, in general, as

[M(t)]. This implies that the kinetics of metabolism of

n 21

the label are independent of the rate at which the label

is emptied [no saturation of D(t) as a function of M(t)], Tn 5 oD

i 51

n 2 i Mi (1)

or, stated differently, that D(t) is invariant of M(t).

We first demonstrate that, in theory, under the By decreasing the length of the time intervals to zero,

assumptions made above, the separation model is a the formula becomes a continuous function

mathematically correct alternative to the multicompart-

e D(t 2 t )M(t ) dt

t

mental model to separate a function (i.e., gastric empty- T(t) 5 0 0 0 (2)

ing rate) from a global process when rate constants for 0

intercompartmental exchange cannot be explicitly cal- The relationship between the different rates as de-

culated. We then demonstrate the practical elaboration scribed in equation 2 is mathematically known as a

of deriving the gastric emptying rate from labeled convolution product. A number of properties can easily

octanoic acid breath test curves and the proportionality be derived mathematically. However, these properties

of D(t) to M(t). are not of interest in this study, since it is not possible

DESIGN OF THE SEPARATION MODEL in general to find the inverse relation between T and M,

except for special classes of functions such as ex. Such

To simplify the rationale of the model, T(t), D(t), and functions are used in Fourier and in Laplace trans-

M(t) are not considered to be continuous but are divided forms, but these functions do not have the form ob-

into discrete time intervals. The rate of 13/14CO2 excre- served in our data. Therefore, we have used the discrete

tion during a certain time interval is the result of the formalism (Eq. 1) to derive a discrete calculation in

accumulated effect of parts that have left the stomach practice

in the past intervals (Fig. 1). For example, the rate of

label recovered in breath during time interval 3, called T2

M1 5

T3 , is the result of the part of the label that left the D1

stomach in the first time interval but was metabolized

during the second time interval (simplified: during the T3 2 D2M1

M2 5

second passage in the liver), plus the part of the label D1

that left the stomach in the second time interval but

T4 2 D3M1 2 D2M2

M3 5

D1

or, in general

i21

Ti 1 1 2 oD

j51

i 1 1 2 j Mj

Mi 5 (3)

D1

If T(t) and D(t) are known, M(t) can be separated from

the total process T(t) by decreasing the length of the

time intervals.

ELABORATION OF THE MODEL

Methods

Fig. 1.13/14CO

2 excretion curve for gastric emptying of solids. Rate of Subjects and materials. As functions of T(t), the

13/14CO excretion during a certain time interval is the result of the

14CO

2 excretion data obtained in the validation study

2

cumulative effect of parts that have left the stomach in the past

intervals. Each layer shows how one excretion package of the label comparing the [14C]octanoic acid breath test and the

that has left the stomach is excreted in breath as a function of time. radioscintigraphic technique were used (7). Briefly, in

A SEPARATION MODEL FOR BREATH TEST ANALYSIS G171

this study a standard solid test meal (250 kcal) consist- under the curve of 14CO2 in breath obtained during the

ing of one egg (labeled with 74 kBq of [14C]octanoic acid first hour after injection of each bolus of [14C]octanoic

and 110 MBq of 99mTc-labeled albumin colloid), two acid [using the formula for D(t)].

slices of bread, and 5 g of margarine was ingested by 16 The study protocol was approved by the ethics com-

healthy volunteers and 20 dyspeptic patients. Immedi- mittee of the University of Leuven. Informed consent

ately after ingestion of the meal, each subject was was obtained from all subjects.

seated between the two heads of a dual-headed gamma Measuring techniques and mathematics. 14CO2 in

camera equipped with parallel-hole low-energy collima- breath was collected by blowing through a pipette into

tors and interfaced to a computer. Scanning scinti- vials containing 2 ml of 1 M hyamine hydroxide and 2

graphic information was obtained every 10 min for up ml of ethanol together with one drop of thymolphtha-

to 1 h and every 15 min for another period of 1 h. lein solution. This amount of hyamine is neutralized by

Radioactivity remaining in the stomach at each scan- 2 mM of CO2. The end point of neutralization is

ning period was expressed as a percentage of the indicated by decoloration of the indicator. After decolor-

activity initially present. The gastric emptying rate so ation, 10 ml of scintillation cocktail (Hionic Fluor,

obtained was fitted by the modified power exponential Packard Instruments) were added and radioactivity

formula of Siegel et al. (24). The half-emptying time was determined by liquid scintillation spectrometry

(t1/2 s ) and lag phase (tlag s ) were calculated according to (Packard Tri-Carb liquid scintillation spectrometer,

that formula. Breath sampling for 14CO2 followed the model 3375; Packard Instruments, Downers Grove, IL).

same time schedule as the scintigraphic imaging tech- CO2 production was assumed to be 300 mmol per

nique but continued for another 2 h of sampling, during square meter of body surface per hour. Body surface

which breath was collected and measured in 15-min area was calculated by the weight-height formula of

intervals. The results were expressed as the percentage Haycock et al. (9). The results were expressed as the

of 14C recovery per hour and were further analyzed by percentage of 14C recovery per hour as a function of

nonlinear regression analysis to calculate t1/2 and tlag. time.

The gastric emptying parameters of both techniques

were compared by correlation and linear regression Application of the Model

analysis in this study. The function T(t) can be adequately described in both

To obtain the function D(t), 20 healthy subjects (10 healthy volunteers and subjects with abnormal gastric

women and 10 men, mean age 23 yr, range 18–28 yr) emptying rates (1) by two classes of function: atbe2ct or

were examined. None of the subjects had a history of mkbe2kt(1 2 e2kt )b 2 1, where t is time and a, b, c, m, k,

gastrointestinal disease or surgery and none were and b are regression-estimated constants.

taking medication. After an overnight fast, a flexible The mean 14CO2 excretion curve obtained in 20

tube was positioned in the second part of the duodenum healthy volunteers after intraduodenal administration

under radioscopic control. The dynamics of 14CO2 ap- of 74 kBq of [14C]octanoic acid served as the function

pearance in breath were measured after intraduodenal D(t). As far as the function D(t) is concerned, no class of

administration of 74 kBq of [14C]octanoic acid sodium functions exists. Accurate fitting of this curve is done by

salt (DuPont NEN, Boston, MA), dissolved in 20 ml of a combination of exponential and polynomial functions

water. Breath samples were taken before and every 3 b

min during the first 30 min, every 5 min for the next 30 I. Ascending slope: c(1 2 e2at )

min, and every 15 min thereafter for up to 4 h. The (f 1 g)

14CO excretion curves were evaluated by 1) the 14CO

2 2

II. Descending slope: e2dt

peak excretion time, 2) the 14CO2 peak excretion, and 3) III. Binding of I and II: h 1 it 1 jt 2 1 kt 3 1 lt 4

the half-emptying time of the curve [using the formula

for D(t)]. where t is time and a, b, c, d, f, g, h, i, j, k, and l are

To validate the invariance of D(t) from M(t), six regression-estimated constants.

healthy volunteers (3 women, 3 men; age 18–24 yr) Using these equations for T(t) and D(t), in Eq. 3 the

were studied. None of the subjects had a history of curve M(t) is obtained. Two gastric emptying param-

gastrointestinal disease or surgery and none were eters were calculated numerically from the individual

taking medication. After an overnight fast, a flexible curves M(t): 1) the gastric half-emptying time is calcu-

tube was positioned in the second part of the duodenum lated by solving the equation

under radioscopic control, and 129.5 kBq of [14C]octa-

e e

t1/2b `

noic acid sodium salt (supra) dissolved in 50 ml of water M(t ) dt 5 1⁄2 M(t ) dt

0 0

were injected into the second part of the duodenum in a

bolus at three different times: 74 kBq at time 0, 18.5 and 2) the lag phase (tlag b ), as defined by Siegel et al.

kBq (1/4 of the initial dose) 1 h later, and 37 kBq (1/2 of (24), which corresponds to the time of peak excretion in

the initial dose) at 2 h. Breath samples were taken the function M(t).

every 5 min for 4 h. The kinetics of metabolism of each Statistics. The gastric half-emptying times and lag

bolus of [14C]octanoic acid were evaluated by three phases of the separated functions of M(t) were calcu-

parameters: 1) the time until peak excretion of 14CO2 in lated numerically after integration into M(t) as a

breath, 2) the maximal increase of 14CO2 excretion after function of time and were compared with the scinti-

injection of each bolus, and 3) the increase in area graphically determined half-emptying times and lag

G172 A SEPARATION MODEL FOR BREATH TEST ANALYSIS

each bolus injection of [14C]octanoic acid, peak excre-

tion in breath was reached at 10 6 0.83 min, with a

peak of 33.05 6 2.49% dose/h after the first bolus,

24.18 6 1.54% dose/h after the second bolus, and 28.61 6

2.03% dose/h after the third bolus. The increase in

14CO excretion 10 min after injection of the bolus was

2

33.05% (0.447% per injected kBq of activity) at 10 min,

8.18% (0.442%/kBq) at 70 min, and 16.59% (0.448%/

kBq) at 130 min. The area under the curve during the

first hour was 22.99 6 1.20% (0.31% per injected kBq of

activity) for the first injected bolus of 74 kBq, 7.17 6

0.47% (0.39%/kBq) for the second bolus of 18.5 kBq, and

10.64 6 05.4% (0.29%/kBq) for the third bolus of 37

kBq. The differences between the three boluses for the

three parameters (parameters 2 and 3 calculated per

Fig. 2. Dynamics of 14CO2 appearance in breath after intraduodenal kBq of activity) were statistically not significant.

administration of 74 kBq of [14C]octanoic acid in the second part of

the duodenum in 20 healthy volunteers (means 6 SE). Application of the Model

phases of the validation study (7), using correlation Figure 4 depicts the relationship between the three

analysis [SAS: PROC CORR (21)]. The two tests were functions T(t), M(t), and D(t) in two subjects after

further compared using the Bland and Altman proce- ingestion of a [14C]octanoic acid-labeled standard solid

dure (3). The three parameters for evaluation of the test meal. The first subject had a normal gastric

kinetics of metabolism of [14C]octanoic acid after intra- emptying rate with a scintigraphically determined

duodenal administration were compared for the three half-emptying time of 59 min (Fig. 4A): the rate of

boluses using the Mann-Whitney-Wilcoxon test (21). gastric emptying accelerates very quickly before reach-

ing a peak, followed by a gradual decline in the velocity

RESULTS of gastric emptying. The second subject had a delayed

gastric emptying rate with a scintigraphically deter-

Postgastric Processing of [14C]Octanoic Acid mined half-emptying time of 89 min (Fig. 4B); the

Figure 2 represents 14CO2 excretion as a function of acceleration and deceleration in the gastric emptying

time in 20 healthy subjects, after intraduodenal admin- rate is less pronounced and less steep. By analyzing the

istration of 74 kBq of [14C]octanoic acid (means 6 SE). gastric emptying data in this way, it was clear that

14CO appeared in the breath almost immediately, with

2

gastric emptying velocity changes from minute to

a peak excretion of 33.73 6 1.69% dose/h after 10.69 6 minute and never has a constant value.

0.77 min, followed by an exponential decrease of 14CO2 The separated gastric emptying function M(t) al-

activity in the breath. The half-excretion time of the lowed not only for evaluation of the real pattern of

curves was 67.5 6 1.37 min. emptying but also for the calculation of a half-emptying

time. The relationship between the gastric half-

Invariance of D(t) from M(t) emptying times determined scintigraphically and via

breath test in 16 healthy volunteers and 20 dyspeptic

In Fig. 3, the 14CO2 excretion as a function of time is

patients after ingestion of a dually labeled solid test

given in six subjects, after intraduodenal administra-

meal of 250 kcal is given in Fig. 5A. The correlation

coefficient between the two parameters was 0.98. Fig-

ure 5B gives the relationship between the lag phases

obtained by both techniques, defined as the point of

maximal gastric emptying rate according to the method

of Siegel et al. (24). The correlation coefficient was 0.85.

The Bland and Altman plots of gastric half-emptying

times and lag phases determined scintigraphically and

via breath test, given in Fig. 6, showed, first, an off-set

between both methods not significantly different from

zero, and second, no proportional differences between

the two methods [mean and confidence limits for differ-

ences between the methods: t1/2, 10 min (220 to 41) and

tlag, 23 min (239 to 34)].

DISCUSSION

Fig. 3. 14CO2 appearance in breath after intraduodenal administration

of 74, 18.5, and 37 kBq of [14C]octanoic acid in the second part of the duo- This study aimed to develop a mathematical model to

denum at 0, 1, and 2 h, respectively, in 6 healthy volunteers (means 6 SE). separate one physiological function from breath test

A SEPARATION MODEL FOR BREATH TEST ANALYSIS G173

Fig. 4. 14CO2 excretion [T(t)], postgastric process-

ing [D(t)], and gastric emptying [M(t)] after inges-

tion of a [14C]octanoic acid-labeled standard test

meal in a subject with normal gastric emptying

(t1/2 s 5 59 min; A) and a subject with delayed

gastric emptying (t1/2 s 5 89 min; B) (% dose per

hour as a function of time). Scintigraphic data are

shown at bottom (% retention as a function of

time).

results. All breath tests are based on the administra- By applying this mathematical model to the

tion of a substrate with a functional group containing a [13/14C]octanoic acid breath test to measure gastric

carbon atom with either the radioactive (14C) or the emptying of solids, we were able to demonstrate that

stable (13C) isotope of carbon. The functional group is postgastric processing of [13/14C]octanoic acid until

enzymatically cleaved during passage through the gas- 13/14CO exhalation occurs very rapidly, with minimal

2

trointestinal tract, during its absorption, or in subse- intersubject variability. This is due to very rapid absorp-

quent metabolic processes. After cleavage of the target tion from the small intestine, quick transport to the

bond, the cleaved portion undergoes further metabo- liver [no mucosal esterification, no incorporation in

lism to 14CO2 or 13CO2, which mixes with the bicarbon- chylomicrons (10, 18–19)], and a ready and almost

ate pool of blood and is finally expired in the breath. In complete oxidation to 13/14CO2 in the liver [no require-

this way, 14/13CO2 excretion is a reflection of the total ment for carnitine to cross the double mitochondrial

amount or kinetic properties of the enzyme studied, membrane (4, 22)]. Therefore, gastric emptying of the

given that this enzyme relates to the rate-limiting step meal can be considered the rate-limiting step in 13/14CO2

in the whole process. excretion after ingestion of a [13/14C]octanoic acid-

G174 A SEPARATION MODEL FOR BREATH TEST ANALYSIS

tric half-emptying time (t1/2 s ) (A) and lag

phase (tlag s ) (B) vs. gastric half-emptying

time and lag phase determined via breath

test (t1/2 b and tlag b ), using the separation

model.

labeled solid meal. Also, an average function can be major differences in flow pattern.’’ A gastric emptying

used to describe the ‘‘postgastric processing’’ of octanoic flow curve can be obtained from radioscintigraphic data

acid. Metabolism of octanoic acid remains unaltered by taking the first derivative of the measured curve.

not only in healthy volunteers but also in other circum- However, mathematical derivation is less stable than

stances, as has been shown for insulin-dependent diabe- mathematical integration. This leads to inaccuracies

tes mellitus (14) or after administration of octreotide for calculation of kinetic parameters such as the lag

(15). phase, as defined by Siegel (24), since it is mathemati-

The assumption of invariance of postgastric process- cally easier to determine the peak of a flow curve than

ing of [13/14C]octanoic acid from the rate of emptying to determine the point of inflection of a cumulative

from the stomach was fulfilled in this study. Hence all curve. This could be the explanation for a less good

other assumptions made were also fulfilled and the correlation of the lag phases of both techniques in this

separation model could be applied by ‘‘subtracting’’ the study.

shape of the postgastric processing curve on each On the other hand, the separation model has it

moment from the global 13/14CO2 excretion curves after limits. By using fitting curves for the actual measured

ingestion of a labeled meal, in a continuous way and data of 13/14CO2 excretion, the transpyloric flow is

according to the amount of label that has left the smoothed to a general flow curve and does not display

stomach at that moment. the gushes of chyme leaving the stomach in a pulsatile

The results obtained with the separation model are way.

excellent. The model allows gastric half-emptying time The separation model presented has a theoretical

and lag phase to be calculated very accurately and it advantage compared with the classical multiple cham-

also provides a method to evaluate patterns of gastric ber model (8), in that it makes fewer assumptions. It

emptying velocity or flow, which changes from minute makes no assumptions about laws governing the flow

to minute. In 1990, Schulze-Delrieu (23) pointed out stream of the label. Moreover, the multiple chamber

that radioscintigraphic gastric emptying results, ex- model is difficult to apply in clinical practice, as dis-

pressed as a percentage of the initial amount still cussed in the introduction. The use of the curve D(t),

remaining in the stomach, represent cumulative data representing the postgastric processing of the label, in

(i.e., mathematical integration of a velocity curve, or separating M(t) out of T(t) and D(t) is an appropriate

‘‘distance’’ rather than ‘‘velocity’’) and that ‘‘gastric solution to these problems because D(t) is shown to be

emptying rates determined in this way do not allow any proportional to M(t).

conclusions regarding the rate or pattern of actual In conclusion, an accurate mathematical model was

gastric outflow and identical emptying rates may hide developed to separate gastric emptying flow curves

and t1/2 b (A) and tlag s and tlag b (B).

Individual differences between test re-

sults are plotted against averages of

individual test results of both tests

(solid and dashed lines, mean differ-

ence 6 2 standard deviations).

A SEPARATION MODEL FOR BREATH TEST ANALYSIS G175

from 13/14CO2 excretion curves obtained after ingestion Kaunitz, K. Lang, and W. Fekl. Berlin: Z. Ernährungswiss, 1974,

of a [13/14C]octanoic acid-labeled solid test meal, thereby vol. 17, p. 9–16.

11. Kritchevsky, D., and S. A. Tepper. Influence of medium-chain

also excluding the influence of endogenous CO2 produc- triglycerides on cholesterol metabolism in rats. J. Nutr. 86:

tion on breath test results. The model also has attrac- 67–72, 1965.

tive prospects for other (breath) tests to separate a 12. Leveille, G. A., R. S. Pardini, and J. A. Tillotson. Influence of

specific gastrointestinal function, e.g., separation of the medium chain triglycerides on lipid metabolism in rat. Lipids 2:

287–294, 1967.

process of intraluminal lipolysis out of the data of a 13. Lossow, W. J., and I. L. Chaikoff. Carbohydrate sparing of

mixed triglyceride breath test and separation of the fatty acid oxidation. Arch. Biochem. Biophys. 57: 23, 1955.

assimilation of carbohydrates from gastric emptying of 14. Maes, B. D. Measurement of Gastric Emptying Using Dynamic

the given test meal. Breath Analysis, edited by B. Maes. Leuven, Belgium: Acco, 1994.

15. Maes, B. D., Y. F. Ghoos, B. J. Geypens, M. I. Hiele, and P. J.

Rutgeerts. Influence of octreotide on gastric emptying of solids

Address for reprint requests: P. J. Rutgeerts, Dept. of Medicine and liquids in normal healthy volunteers. Aliment. Pharmacol.

and Medical Research, University Hospital Gasthuisberg, B-3000 Ther. 9: 11–18, 1995.

Leuven, Belgium. 16. Maes, B. D., Y. F. Ghoos, B. J. Geypens, G. Mys, M. I. Hiele,

Received 16 December 1996; accepted in final form 4 March 1998. P. J. Rutgeerts, and G. Vantrappen. The combined 13C-glycine/

14C-octanoic acid breath test: a double carbon labelled breath test

Med. 35: 824–831, 1994.

REFERENCES

17. McGarry, J. D., and D. W. Foster. Regulation of hepatic fatty

1. Bach, A. C., and V. K. Babayan. Medium-chain triglycerides: acid oxidation and ketone body production. Annu. Rev. Biochem.

an update. Am. J. Clin. Nutr. 36: 950–962, 1982. 49: 395–420, 1980.

2. Bach, A. C., T. Phan, and P. Métais. Effect of the fatty acid 18. Mishkin, S., L. Stein, Z. Gatmaitan, and I. M. Arias. The

composition of ingested fats on rat liver intermediary metabo- binding of fatty acids to cytoplasmatic proteins: binding to Z

lism. Horm. Metab. Res. 8: 375–379, 1976. protein in liver and other tissues of the rat. Biochem. Biophys.

3. Bland, J. M., and D. G. Altman. Statistical methods for Res. Commun. 47: 997–1003, 1972.

assessing agreement between two methods of clinical measure- 19. Ockner, R. K., J. A. Manning, R. B. Poppenhausen, and

ment. Lancet I: 307–310, 1986. W. K. Ho. A binding protein for fatty acids in cytosol of intestinal

4. Bremer, J. Carnitine and its role in fatty acid metabolism. mucosa, liver, myocardium and other tissues. Science 177: 56–

Trends Biochem. Sci. 2: 207–209, 1980. 58, 1972.

5. Clark, B. J., and F. M. House. Medium-chain triglyceride oil 20. Osumi, T., and T. Hashimoto. Acyl-CoA oxidase of rat liver: a

ketogenic diets in the treatment of childhood epilepsy. J. Hum. new enzyme for fatty acid oxidation. Biochem. Biophys. Res.

Nutr. Diet. 32: 111–116, 1978. Commun. 83: 479–485, 1978.

6. Clark, S. B., and P. Holt. Inhibition of steady-state intestinal 21. SAS/STAT User’s Guide (1st ed.), version 6.03. Raleigh, NC:

absorption of long-chain triglyceride by medium-chain triglycer- SAS Institute, 1988.

ide in the unanesthetized rat. J. Clin. Invest. 48: 2235–2243, 22. Scheig, R. Hepatic metabolism of medium chain fatty acids. In:

1969. Medium Chain Triglycerides, edited by J. R. Senior. Philadel-

7. Ghoos, Y. F., B. D. Maes, B. J. Geypens, G. Mys, M. I. Hiele, phia, PA: University of Pennsylvania, 1968, p. 39–49.

P. J. Rutgeerts, and G. Vantrappen. Measurement of gastric 23. Schulze-Delrieu, K. The load to length principle in the inhibi-

emptying rate of solids by means of a carbon labelled octanoic tion of gastric emptying by intestinal feedback. Gastroenterology

acid breath test. Gastroenterology 104: 1640–1647, 1993. 98: 1387–1388, 1990.

8. Gladtke, E., and H. M. von Hattingberg. Pharmakokinetik. 24. Siegel, J. A., J. L. Urbain, L. P. Adler, N. D. Charkes, A. H.

New York: Springer Verlag, 1977. Maurer, B. Krevsky, L. C. Knight, R. S. Fisher, and L. S.

9. Haycock, G., G. Schwartz, and D. Wisotsky. Geometric Malmud. Biphasic nature of gastric emptying. Gut 29: 85–89,

method for measuring body surface area: a height-weight for- 1988.

mula validated in infants, children and adults. J. Pediatr. 93: 25. Wu-Rideout, M. Y. C., C. Elson, and E. Shrago. The role of

62–66, 1978. fatty acid binding protein on the metabolism of fatty acids in

10. Iber, F. Relative rates of metabolism of MCT, LCT and ethanol in isolated rat hepatocytes. Biochem. Biophys. Res. Commun. 71:

man. In: Mittelkettige Trigkyceride in der Diät, edited by H. 809–816, 1976.

- Janaki Lenin ColumnsUploaded byராஜேஷ் 'பலவேஷம்'
- Conf Tested Assemblies Iec 61439Uploaded bymumi87
- Transmission and System Operation Business GroupUploaded bySujan Singh
- BoqUploaded bystrawderson
- ivbtUploaded byapi-295561999
- National SymbolsUploaded byCamille Lopez
- Science and the Limits of Knowledge (EPUB): A Free Excerpt from “Dialogue with a Nonbeliever (About Science and the Limits of Knowledge, the Big Bang and Evolution, Ancient Christianity and Modern Heterodoxy),” Second EditionUploaded byBogdan-John Vasiliu
- Benefit of HappinessUploaded byAtika Deviani W
- chapter 06.docUploaded bykrpeters1
- 33994616 Labor1 Digest Part4Uploaded byMavic Morales
- TechnicalreportNI43 101 EnglishUploaded byJulius Enock Mandusu
- Livro Receitas Vegetarianas 100 SugestõesUploaded bymjoseyoga
- Chemical and Physical Properties of the ZSM-5 Substitutional SerieUploaded byW00W
- TUBE Survey QuestionsUploaded byanonymous00000
- Afib Simplified Guidelines Treatment chart UCM_324032.pdfUploaded byLakshay Tyagi
- Rijke TubeUploaded bysubha_aero
- Energy Efficient motors.pdfUploaded byAnoop Mathew
- CancerUploaded bytheintrov
- Progress test_03.pdfUploaded byfabrini
- Cardiac ArrhytmiasUploaded byboblish
- plan noticesUploaded byapi-252555369
- Trees of Somalia: A field guide for development workersUploaded byOxfam
- TOA 1Uploaded byRukia Kuchiki
- Corrosion Under InsulationUploaded bybountymani
- @Loop & InsightsUploaded bystandab
- Manual for Preparations of Fruts and Vegetables for MarketUploaded bylastoutrider
- Performance Appraisal StandardsUploaded byAnnie Sarah
- jrsocmed00038-0059aUploaded byYustiamka Permana
- Sausagey Santa - Carlton Mellick IIIUploaded byLeonardo Rodriguez
- groupxUploaded byOrnela Barisone

## Much more than documents.

Discover everything Scribd has to offer, including books and audiobooks from major publishers.

Cancel anytime.