Gastric emptying flow curves separated from carbon-labeled
octanoic acid breath test results
B. D.
Maes1,
G.
Mys2,
B. J.
Geypens1,
P.
Evenepoel1,
Y. F.
Ghoos1, and
P. J.
Rutgeerts1
1 Department of Medicine,
Division of Gastroenterology and Gastrointestinal Research Center,
University Hospital Gasthuisberg, and
2 Department of Mathematics,
Catholic University, Leuven B-3000, Belgium
 |
ABSTRACT |
Recently, we developed the
[13/14C]octanoic
acid breath test to measure gastric emptying of solids. Although the
method has been validated extensively, absorption, metabolism, and
excretion of the label in the breath need to be corrected for. In this
study a mathematical model was developed that allows for
1) separation of the global
CO2 excretion after ingestion of
the labeled test meal into the emptying rate of the labeled test meal
from mouth to pylorus and the postgastric processing of absorption,
metabolism, and excretion of the label, and
2) numerical calculation of the half-emptying time and lag phase of the emptied meal. The model was
applied to the gastric emptying results obtained by simultaneous scintigraphic and breath test measurements. An excellent correlation was found between the gastric half-emptying time
(r = 0.98) and lag phase
(r = 0.85) determined
scintigraphically and via breath test. There was also a good agreement
between the two methods [mean values and confidence limits for
differences: t1/2 = 10 min (
20 to 41) and
tlag =
3
min (
39 to 34)]. Moreover, the separated gastric emptying
curves, lacking the influence of postgastric processing of the label,
showed real patterns of gastric outflow, which changes from moment to
moment.
breath test technology; mathematical models
 |
INTRODUCTION |
RECENTLY, WE DEVELOPED the
[13/14C]octanoic acid
breath test to measure gastric emptying of solids (7, 16). The
rationale of a breath test is based on the firm retention of
13/14C-labeled octanoic acid in
the solid phase of a test meal during mixing and grinding in the
stomach, followed by rapid absorption from the chyme entering into the
duodenum, an immediate and maximal oxidation in the liver to labeled
CO2, and a fast exhalation in breath. In vitro experiments showed that octanoic acid is firmly retained in a standard solid test meal in a gastric environment (7). It
has been known for a long time that octanoic acid, an eight-carbon
fatty acid found in dietary fats, is rapidly absorbed from the
intestine and carried to the liver via the portal venous system, where
it is rapidly and completely oxidized (1, 2, 4-6, 10-13,
17-20, 22, 25). Therefore gastric emptying of the meal, and not
the postgastric processing of the label, could be considered the
rate-limiting step in the rate of labeled
CO2 excretion in breath after
ingestion of a labeled solid test meal.
Mathematical analysis of CO2
excretion curves made it possible to exclude the influence of
endogenous CO2 production on the breath test results, and breath test and radioscintigraphic
measurements taken simultaneously in normal subjects and dyspeptic
patients allowed for highly accurate description of the gastric
emptying rate of a solid test meal (7, 16). With the use of a
regression model, we were able to calculate the half-emptying time and
lag phase, correcting for the postgastric processing of octanoic acid.
The aim of this study was to develop a separation model in which the
postgastric processing of octanoic acid could be mathematically separated from the CO2 excretion
curve after ingestion of a standard solid test meal to obtain real-time
gastric emptying curves. This approach of breath test curve analysis
has two potential benefits: 1)
physiologically meaningful gastric emptying parameters can be
calculated from breath test curves without correcting for postgastric processing of the label on a linear regression-estimated basis between
radioscintigraphy and breath tests, and
2) it allows for the evaluation of
gastric emptying rates, instead of amounts of emptied food, as a
function of time (flow curves). The classic multicompartmental
analysis, however, was not used due to the specific conditions
encountered in breath test technology. The multiple-chamber model is
difficult to apply in clinical 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 individual. Solution of the breath curve would
require the fitting of at least four exponential functions. This can
rarely be done convincingly with biological data, even if sampling
takes place over long periods of time. Also, it is not possible to
obtain a steady state of exchange between the different compartments (especially the slowly exchanging ones) during the 4-h period of breath
sampling. Moreover, when dose is not in the subsequently measured
compartment the rate constants for intercompartmental exchange cannot
be explicitly calculated from the multiexponential curve for tracer in
breath.
 |
RATIONALE FOR THE SEPARATION MODEL |
To elaborate the mathematical model, three functions were introduced to
describe three different processes.
1) The emptying rate of a labeled solid meal from mouth
to pylorus is given by M(t).
2) The rate of postgastric processing (absorption,
metabolism, and excretion in breath) of the label is given by
D(t).
3) The global process of
CO2 excretion after ingestion of a
labeled solid test meal is given by
T(t).
The aim of this study is to determine
M(t) given
T(t) and
D(t), which can both be measured,
and to describe the relation between the three functions. Therefore the
following assumptions were made. 1)
The meal is ingested at once, at time
0. This is not true, but the time of
ingestion was always restricted to 10 min, and time
0 was taken as the time of completion of the ingestion of the meal. 2)
T(t),
D(t), and
M(t) are piecewise continuous functions, not identical to zero and positive for each time
0. 3) The rate of metabolism of the label
[D(t)] is proportional to the rate of gastric emptying of the label
[M(t)]. This implies that the kinetics of metabolism of the label are independent of the
rate at which the label is emptied [no saturation of
D(t) as a function of
M(t)], or, stated differently,
that D(t) is invariant of
M(t).
We first demonstrate that, in theory, under the assumptions made above,
the separation model is a mathematically correct alternative to the
multicompartmental model to separate a function (i.e., gastric emptying
rate) from a global process when rate constants for intercompartmental
exchange cannot be explicitly calculated. We then demonstrate the
practical elaboration of deriving the gastric emptying rate from
labeled octanoic acid breath test curves and the proportionality of
D(t) to
M(t).
 |
DESIGN OF THE SEPARATION MODEL |
To simplify the rationale of the model,
T(t),
D(t), and
M(t) are not considered to be
continuous but are divided into discrete time intervals. The rate of
13/14CO2 excretion
during a certain time interval is the result of the accumulated effect
of parts that have left the stomach in the past intervals (Fig.
1). For example, the rate of label
recovered in breath during time
interval 3, called T3,
is the result of the part of the label that left the stomach in the
first time interval but was metabolized during the second time interval
(simplified: during the second passage in the liver), plus the part of
the label that left the stomach in the second time interval but that had already been metabolized during the first time interval
(simplified: the first passage in the liver). The addition of all
layers describes the total process
T(t), i.e., a
13/14CO2 excretion
curve after ingestion of a solid test meal. Mathematically it is
expressed as
or,
in general, as
|
(1)
|
By decreasing the length of the time intervals to zero, the formula
becomes a continuous function
|
(2)
|
The
relationship between the different rates as described in
equation 2 is mathematically known as
a convolution product. A number of properties can easily be derived
mathematically. However, these properties are not of interest in this
study, since it is not possible in general to find the inverse relation
between T and M, except for special classes of functions such as
ex. Such functions are used in
Fourier and in Laplace transforms, but these functions do not have the
form observed in our data. Therefore, we have used the discrete
formalism (Eq. 1) to derive a
discrete calculation in practice
or,
in general
|
(3)
|
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.

View larger version (34K):
[in this window]
[in a new window]
|
Fig. 1.
13/14CO2
excretion curve for gastric emptying of solids. Rate of
13/14CO2
excretion during a certain time interval is the result of the
cumulative effect of parts that have left the stomach in the past
intervals. Each layer shows how one excretion package of the label that
has left the stomach is excreted in breath as a function of time.
|
|
 |
ELABORATION OF THE MODEL |
Methods
Subjects and materials.
As functions of T(t), the
14CO2
excretion data obtained in the validation study comparing the
[14C]octanoic acid
breath test and the radioscintigraphic technique were used (7).
Briefly, in this study a standard solid test meal (250 kcal) consisting
of one egg (labeled with 74 kBq of [14C]octanoic acid and
110 MBq of 99mTc-labeled albumin
colloid), two slices of bread, and 5 g of margarine was ingested by 16 healthy volunteers and 20 dyspeptic patients. Immediately after
ingestion of the meal, each subject was seated between the two heads of
a dual-headed gamma camera equipped with parallel-hole low-energy
collimators and interfaced to a computer. Scanning scintigraphic
information was obtained every 10 min for up to 1 h and every 15 min
for another period of 1 h. Radioactivity remaining in the stomach at
each scanning period was expressed as a percentage of the activity
initially present. The gastric emptying rate so obtained was fitted by
the modified power exponential formula of Siegel et al. (24). The
half-emptying time
(t1/2 s) and lag phase
(tlag s)
were calculated according to that formula. Breath sampling for
14CO2
followed the same time schedule as the scintigraphic imaging technique
but continued for another 2 h of sampling, during which breath was
collected and measured in 15-min intervals. The results were expressed
as the percentage of 14C recovery
per hour and were further analyzed by nonlinear regression analysis to
calculate t1/2
and tlag. The
gastric emptying parameters of both techniques were compared by
correlation and linear regression analysis in this study.
To obtain the function D(t), 20 healthy subjects (10 women and 10 men, mean age 23 yr, range 18-28
yr) were examined. None of the subjects had a history of
gastrointestinal disease or surgery and none were taking medication.
After an overnight fast, a flexible tube was positioned in the second
part of the duodenum under radioscopic control. The
dynamics of
14CO2
appearance in breath were measured after intraduodenal administration of 74 kBq of
[14C]octanoic acid
sodium salt (DuPont NEN, Boston, MA), dissolved in 20 ml of water.
Breath samples were taken before and every 3 min during the first 30 min, every 5 min for the next 30 min, and every 15 min thereafter for
up to 4 h. The
14CO2
excretion curves were evaluated by
1) the
14CO2
peak excretion time, 2) the
14CO2
peak excretion, and 3) the
half-emptying time of the curve [using the formula for
D(t)].
To validate the invariance of D(t)
from M(t), six healthy volunteers (3 women, 3 men; age 18-24 yr) were studied. None of the subjects had
a history of gastrointestinal disease or surgery and none were taking
medication. After an overnight fast, a flexible tube was positioned in
the second part of the duodenum under radioscopic control, and 129.5 kBq of [14C]octanoic
acid sodium salt (supra) dissolved in 50 ml of water were injected into
the second part of the duodenum in a bolus at three different times: 74 kBq at time
0, 18.5 kBq (1/4 of the initial dose)
1 h later, and 37 kBq (1/2 of the initial dose) at 2 h. Breath samples
were taken every 5 min for 4 h. The kinetics of metabolism of each
bolus of [14C]octanoic
acid were evaluated by three parameters:
1) the time until peak excretion of
14CO2
in breath, 2) the maximal increase
of
14CO2
excretion after injection of each bolus, and
3) the increase in area under the
curve of
14CO2
in breath obtained during the first hour after injection of each bolus
of [14C]octanoic acid
[using the formula for
D(t)].
The study protocol was approved by the ethics committee of the
University of Leuven. Informed consent was obtained from all subjects.
Measuring techniques and mathematics.
14CO2
in breath was collected by blowing through a pipette into vials
containing 2 ml of 1 M hyamine hydroxide and 2 ml of ethanol together
with one drop of thymolphthalein solution. This amount of hyamine is
neutralized by 2 mM of CO2. The
end point of neutralization is indicated by decoloration of the
indicator. After decoloration, 10 ml of scintillation cocktail (Hionic
Fluor, Packard Instruments) were added and radioactivity was determined
by liquid scintillation spectrometry (Packard Tri-Carb liquid
scintillation spectrometer, model 3375; Packard Instruments, Downers
Grove, IL). CO2 production was
assumed to be 300 mmol per square meter of body surface per hour. Body
surface area was calculated by the weight-height formula of Haycock et
al. (9). The results were expressed as the percentage of
14C recovery per hour as a
function of time.
Application of the Model
The function T(t) can be adequately
described in both healthy volunteers and subjects with abnormal gastric
emptying rates (1) by two classes of function:
atbe
or
mk
e
(1
e
)
1,
where t is time and
a, b,
c, m,
k, and
are regression-estimated constants.
The mean
14CO2
excretion curve obtained in 20 healthy volunteers after intraduodenal
administration of 74 kBq of
[14C]octanoic acid
served as the function D(t). As far
as the function D(t) is concerned,
no class of functions exists. Accurate fitting of this curve is done by
a combination of exponential and polynomial functions
where
t is time and
a, b,
c,
d, f,
g, h,
i, j,
k, and l are
regression-estimated constants.
Using these equations for T(t) and
D(t), in Eq. 3 the curve M(t) is
obtained. Two gastric emptying parameters were calculated numerically
from the individual curves M(t):
1) the gastric half-emptying time is
calculated by solving the equation
and
2) the lag phase
(tlag b),
as defined by Siegel et al. (24), which corresponds to the time of peak
excretion in the function M(t).
Statistics.
The gastric half-emptying times and lag phases of the separated
functions of M(t) were calculated
numerically after integration into
M(t) as a function of time and were
compared with the scintigraphically determined half-emptying times and
lag phases of the validation study (7), using correlation analysis
[SAS: PROC CORR (21)]. The two tests were further compared
using the Bland and Altman procedure (3). The three parameters for
evaluation of the kinetics of metabolism of
[14C]octanoic
acid after intraduodenal administration were compared for the
three boluses using the Mann-Whitney-Wilcoxon test (21).
 |
RESULTS |
Postgastric Processing of
[14C]Octanoic Acid
Figure 2 represents
14CO2
excretion as a function of time in 20 healthy subjects, after
intraduodenal administration of 74 kBq of
[14C]octanoic acid
(means ± SE).
14CO2
appeared in the breath almost immediately, with a peak excretion of
33.73 ± 1.69% dose/h after 10.69 ± 0.77 min, followed by an exponential decrease of
14CO2
activity in the breath. The half-excretion time of the curves was 67.5 ± 1.37 min.

View larger version (17K):
[in this window]
[in a new window]
|
Fig. 2.
Dynamics of
14CO2
appearance in breath after intraduodenal administration of 74 kBq of
[14C]octanoic acid in
the second part of the duodenum in 20 healthy volunteers (means ± SE).
|
|
Invariance of D(t) from
M(t)
In Fig. 3, the
14CO2
excretion as a function of time is given in six subjects, after
intraduodenal administration of three different boluses of
[14C]octanoic acid. At
each bolus injection of
[14C]octanoic acid,
peak excretion in breath was reached at 10 ± 0.83 min, with a peak
of 33.05 ± 2.49% dose/h after the first bolus, 24.18 ± 1.54% dose/h after the second bolus, and 28.61 ± 2.03% dose/h after the third bolus. The increase in
14CO2
excretion 10 min after injection of the bolus was 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 ± 1.20% (0.31% per injected kBq of
activity) for the first injected bolus of 74 kBq, 7.17 ± 0.47%
(0.39%/kBq) for the second bolus of 18.5 kBq, and 10.64 ± 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
kBq of activity) were statistically not significant.

View larger version (18K):
[in this window]
[in a new window]
|
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 duodenum at 0, 1, and 2 h, respectively, in
6 healthy volunteers (means ± SE).
|
|
Application of the Model
Figure 4 depicts the relationship between
the three functions T(t),
M(t), and
D(t) in two subjects after ingestion
of a [14C]octanoic
acid-labeled standard solid test meal. The first subject had a normal
gastric emptying rate with a scintigraphically determined half-emptying
time of 59 min (Fig. 4A): the rate
of gastric emptying accelerates very quickly before reaching a peak,
followed by a gradual decline in the velocity of gastric emptying. The
second subject had a delayed gastric emptying rate with a
scintigraphically determined half-emptying time of 89 min (Fig.
4B); the acceleration and
deceleration in the gastric emptying rate is less pronounced and less
steep. By analyzing the gastric emptying data in this way, it was clear
that gastric emptying velocity changes from minute to minute and never
has a constant value.

View larger version (18K):
[in this window]
[in a new window]

View larger version (17K):
[in this window]
[in a new window]
|
Fig. 4.
14CO2
excretion [T(t)],
postgastric processing
[D(t)], and gastric
emptying [M(t)] after
ingestion of a
[14C]octanoic
acid-labeled standard test meal in a subject with normal gastric
emptying
(t1/2 s = 59 min; A) and a subject with delayed gastric emptying
(t1/2 s = 89 min; B) (% dose per hour as a function of time).
Scintigraphic data are shown at bottom (% retention as a function of
time).
|
|
The separated gastric emptying function
M(t) allowed not only for evaluation
of the real pattern of emptying but also for the calculation of a
half-emptying time. The relationship between the gastric half-emptying
times determined scintigraphically and via breath test in 16 healthy
volunteers and 20 dyspeptic patients after ingestion of a dually
labeled solid test meal of 250 kcal is given in Fig.
5A. The
correlation coefficient between the two parameters was 0.98. Figure
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 differences
between the methods:
t1/2, 10 min
(
20 to 41) and
tlag,
3
min (
39 to 34)].

View larger version (11K):
[in this window]
[in a new window]
|
Fig. 5.
Scintigraphically determined gastric 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.
|
|

View larger version (13K):
[in this window]
[in a new window]
|
Fig. 6.
Bland and Altman plots of
t1/2 s and
t1/2 b
(A) and
tlag s and
tlag b
(B). Individual differences between test results are
plotted against averages of individual test results of both tests
(solid and dashed lines, mean difference ± 2 standard
deviations).
|
|
 |
DISCUSSION |
This study aimed to develop a mathematical model to separate one
physiological function from breath test results. All breath tests are
based on the administration of a substrate with a functional group
containing a carbon atom with either the radioactive
(14C) or the stable
(13C) isotope of carbon. The
functional group is enzymatically cleaved during passage through the
gastrointestinal tract, during its absorption, or in subsequent
metabolic processes. After cleavage of the target bond, the cleaved
portion undergoes further metabolism to
14CO2
or
13CO2,
which mixes with the bicarbonate pool of blood and is finally expired
in the breath. In this way,
14/13CO2
excretion is a reflection of the total amount or kinetic properties of
the enzyme studied, given that this enzyme relates to the rate-limiting step in the whole process.
By applying this mathematical model to the
[13/14C]octanoic
acid breath test to measure gastric emptying of solids, we were able to
demonstrate that postgastric processing of
[13/14C]octanoic acid
until
13/14CO2
exhalation occurs very rapidly, with minimal intersubject variability.
This is due to very rapid absorption from the small intestine, quick
transport to the liver [no mucosal esterification, no
incorporation in chylomicrons (10, 18-19)], and a ready and almost complete oxidation to
13/14CO2
in the liver [no requirement for carnitine to cross the double mitochondrial membrane (4, 22)]. Therefore, gastric emptying of
the meal can be considered the rate-limiting step in
13/14CO2
excretion after ingestion of a
[13/14C]octanoic
acid-labeled solid meal. Also, an average function can be used to
describe the "postgastric processing" of octanoic acid.
Metabolism of octanoic acid remains unaltered not only in healthy
volunteers but also in other circumstances, as has been shown for
insulin-dependent diabetes mellitus (14) or after administration of
octreotide (15).
The assumption of invariance of postgastric processing of
[13/14C]octanoic acid
from the rate of emptying from the stomach was fulfilled in this study.
Hence all other assumptions made were also fulfilled and the separation
model could be applied by "subtracting" the shape of the
postgastric processing curve on each moment from the global
13/14CO2
excretion curves after ingestion of a labeled meal, in a continuous way
and according to the amount of label that has left the stomach at that
moment.
The results obtained with the separation model are excellent. The model
allows gastric half-emptying time and lag phase to be calculated very
accurately and it also provides a method to evaluate patterns of
gastric emptying velocity or flow, which changes from minute to minute.
In 1990, Schulze-Delrieu (23) pointed out that radioscintigraphic
gastric emptying results, expressed as a percentage of the initial
amount still remaining in the stomach, represent cumulative data (i.e.,
mathematical integration of a velocity curve, or "distance"
rather than "velocity") and that "gastric emptying rates
determined in this way do not allow any conclusions regarding the rate
or pattern of actual gastric outflow and identical emptying rates may
hide major differences in flow pattern." A gastric emptying flow
curve can be obtained from radioscintigraphic data by taking the first
derivative of the measured curve. However, mathematical derivation is
less stable than mathematical integration. This leads to inaccuracies
for calculation of kinetic parameters such as the lag phase, as defined by Siegel (24), since it is mathematically easier to determine the peak
of a flow curve than to determine the point of inflection of a
cumulative curve. This could be the explanation for a less good
correlation of the lag phases of both techniques in this study.
On the other hand, the separation model has it limits. By using fitting
curves for the actual measured data of
13/14CO2
excretion, the transpyloric flow is smoothed to a general flow curve
and does not display the gushes of chyme leaving the stomach in a
pulsatile way.
The separation model presented has a theoretical advantage compared
with the classical multiple chamber model (8), in that it makes fewer
assumptions. It makes no assumptions about laws governing the flow
stream of the label. Moreover, the multiple chamber model is difficult
to apply in clinical practice, as discussed in the introduction. The
use of the curve D(t), representing
the postgastric processing of the label, in separating
M(t) out of T(t) and
D(t) is an appropriate solution to
these problems because D(t) is shown
to be proportional to M(t).
In conclusion, an accurate mathematical model was developed to separate
gastric emptying flow curves from
13/14CO2
excretion curves obtained after ingestion of a
[13/14C]octanoic
acid-labeled solid test meal, thereby also excluding the influence of
endogenous CO2 production on
breath test results. The model also has attractive prospects for other
(breath) tests to separate a specific gastrointestinal function, e.g.,
separation of the process of intraluminal lipolysis out of the data of
a mixed triglyceride breath test and separation of the assimilation of
carbohydrates from gastric emptying of the given test meal.
 |
FOOTNOTES |
Address for reprint requests: P. J. Rutgeerts, Dept. of Medicine
and Medical Research, University Hospital Gasthuisberg, B-3000 Leuven,
Belgium.
Received 16 December 1996; accepted in final form 4 March 1998.
 |
REFERENCES |
1.
Bach, A. C.,
and
V. K. Babayan.
Medium-chain triglycerides: an update.
Am. J. Clin. Nutr.
36:
950-962,
1982[Abstract].
2.
Bach, A. C.,
T. Phan,
and
P. Métais.
Effect of the fatty acid composition of ingested fats on rat liver intermediary metabolism.
Horm. Metab. Res.
8:
375-379,
1976[Medline].
3.
Bland, J. M.,
and
D. G. Altman.
Statistical methods for assessing agreement between two methods of clinical measurement.
Lancet
I:
307-310,
1986.
4.
Bremer, J.
Carnitine and its role in fatty acid metabolism.
Trends Biochem. Sci.
2:
207-209,
1980.
5.
Clark, B. J.,
and
F. M. House.
Medium-chain triglyceride oil ketogenic diets in the treatment of childhood epilepsy.
J. Hum. Nutr. Diet.
32:
111-116,
1978.
6.
Clark, S. B.,
and
P. Holt.
Inhibition of steady-state intestinal absorption of long-chain triglyceride by medium-chain triglyceride in the unanesthetized rat.
J. Clin. Invest.
48:
2235-2243,
1969[Medline].
7.
Ghoos, Y. F.,
B. D. Maes,
B. J. Geypens,
G. Mys,
M. I. Hiele,
P. J. Rutgeerts,
and
G. Vantrappen.
Measurement of gastric emptying rate of solids by means of a carbon labelled octanoic acid breath test.
Gastroenterology
104:
1640-1647,
1993[Medline].
8.
Gladtke, E.,
and
H. M. von Hattingberg.
Pharmakokinetik. New York: Springer Verlag, 1977.
9.
Haycock, G.,
G. Schwartz,
and
D. Wisotsky.
Geometric method for measuring body surface area: a height-weight formula validated in infants, children and adults.
J. Pediatr.
93:
62-66,
1978[Medline].
10.
Iber, F.
Relative rates of metabolism of MCT, LCT and ethanol in man.
In: Mittelkettige Trigkyceride in der Diät, edited by H. Kaunitz,
K. Lang,
and W. Fekl. Berlin: Z. Ernährungswiss, 1974, vol. 17, p. 9-16.
11.
Kritchevsky, D.,
and
S. A. Tepper.
Influence of medium-chain triglycerides on cholesterol metabolism in rats.
J. Nutr.
86:
67-72,
1965.
12.
Leveille, G. A.,
R. S. Pardini,
and
J. A. Tillotson.
Influence of medium chain triglycerides on lipid metabolism in rat.
Lipids
2:
287-294,
1967.
13.
Lossow, W. J.,
and
I. L. Chaikoff.
Carbohydrate sparing of fatty acid oxidation.
Arch. Biochem. Biophys.
57:
23,
1955.
14.
Maes, B. D.
Measurement of Gastric Emptying Using Dynamic 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 and liquids in normal healthy volunteers.
Aliment. Pharmacol. Ther.
9:
11-18,
1995[Medline].
16.
Maes, B. D.,
Y. F. Ghoos,
B. J. Geypens,
G. Mys,
M. I. Hiele,
P. J. Rutgeerts,
and
G. Vantrappen.
The combined 13C-glycine/14C-octanoic acid breath test: a double carbon labelled breath test to monitor gastric emptying rate of liquids and solids.
J. Nucl. Med.
35:
824-831,
1994[Abstract].
17.
McGarry, J. D.,
and
D. W. Foster.
Regulation of hepatic fatty acid oxidation and ketone body production.
Annu. Rev. Biochem.
49:
395-420,
1980[Medline].
18.
Mishkin, S.,
L. Stein,
Z. Gatmaitan,
and
I. M. Arias.
The binding of fatty acids to cytoplasmatic proteins: binding to Z protein in liver and other tissues of the rat.
Biochem. Biophys. Res. Commun.
47:
997-1003,
1972[Medline].
19.
Ockner, R. K.,
J. A. Manning,
R. B. Poppenhausen,
and
W. K. Ho.
A binding protein for fatty acids in cytosol of intestinal mucosa, liver, myocardium and other tissues.
Science
177:
56-58,
1972[Medline].
20.
Osumi, T.,
and
T. Hashimoto.
Acyl-CoA oxidase of rat liver: a new enzyme for fatty acid oxidation.
Biochem. Biophys. Res. Commun.
83:
479-485,
1978[Medline].
21.
SAS/STAT User's Guide ((1st ed.), version 6.03). Raleigh, NC: SAS Institute, 1988.
22.
Scheig, R.
Hepatic metabolism of medium chain fatty acids.
In: Medium Chain Triglycerides, edited by J. R. Senior. Philadelphia, PA: University of Pennsylvania, 1968, p. 39-49.
23.
Schulze-Delrieu, K.
The load to length principle in the inhibition of gastric emptying by intestinal feedback.
Gastroenterology
98:
1387-1388,
1990[Medline].
24.
Siegel, J. A.,
J. L. Urbain,
L. P. Adler,
N. D. Charkes,
A. H. Maurer,
B. Krevsky,
L. C. Knight,
R. S. Fisher,
and
L. S. Malmud.
Biphasic nature of gastric emptying.
Gut
29:
85-89,
1988[Abstract].
25.
Wu-Rideout, M. Y. C.,
C. Elson,
and
E. Shrago.
The role of fatty acid binding protein on the metabolism of fatty acids in isolated rat hepatocytes.
Biochem. Biophys. Res. Commun.
71:
809-816,
1976[Medline].
Am J Physiol Gastroint Liver Physiol 275(1):G169-G175
0002-9513/98 $5.00
Copyright © 1998 the American Physiological Society