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H J Verkade

Publications and source records attributed to H J Verkade.

At least 19 recordsLinked to original sources
PubMed2006

Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase.

Alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase (N-CDase) in the intestinal microvillar membrane are responsible for dietary sphingomyelin digestion. The activities of the enzymes require the presence of bile salt, and the enzymes can be released into the gut lumen in active forms by bile salts and trypsin. It is unclear to what extent that the intestinal presence of bile salts is critical for the intraluminal activity of these enzymes. We compared the activities of Alk-SMase, N-CDase, and other types of SMases in control and permanently bile diverted rats. In the intestinal tract of control rats, the activity of Alk-SMase was profoundly higher than those of acid and neutral SMases. Bile diversion reduced Alk-SMase activity by 85% in the small intestinal content, and by 68% in the faeces, but did not significantly change the activity in the intestinal mucosa. Western blot showed a marked reduction of the enzyme in the intestinal lumen but not mucosa. N-CDase activities both in the intestinal mucosa and content were reduced by bile diversion. Bile diversion also decreased aminopeptidase N activity in the content and increased that in the mucosa, but had no effects on that of alkaline phosphatase. In conclusion, the presence of bile salts is important for maintaining high intraluminal levels of Alk-SMase and N-CDase, two key enzymes for hydrolysis of sphingomyelin in the gut. We speculate that the sphingomyelin hydrolysis in cholestatic conditions is impaired not only by reduced hydrolytic activity but also by deficient dissociation of the enzymes from the membrane.

Amidohydrolases↗
PubMed2006

[Combined liver and kidney transplantation: indications and results at the University Medical Centre Groningen, 1994-2005].

UNLABELLED: OBJECTIVE. To describe the experience with combined liver and kidney transplantation at the University Medical Centre Groningen, The Netherlands. DESIGN. Retrospective. METHOD: Data were analysed from all patients who underwent combined liver and kidney transplantation in the University Medical Centre Groningen, in the period November 1994-December 2005. RESULTS: During the study period 582 orthotopic liver transplantations and 1026 isolated kidney transplantations were performed. 16 patients underwent combined liver and kidney transplantation: 4 were children (aged 17 months-16 years) and 12 were adults (aged 19-59 years). For all patients, both organs were obtained from the same post-mortem donor. Indications for combined liver and kidney transplantation were primary hyperoxaluria type I (n=6), polycystic liver and kidney disease (n=3) and unrelated liver and kidney failure (n=7). The 1- and 5-year survival rate was 88% (14/16), which was not significantly different from the results after isolated liver transplantation. Two patients died 11 days and 74 months after combined transplantation, due to complications from unsuccessful retransplantation of the liver for hepatic artery thrombosis and secondary biliary cirrhosis, respectively. A third patient died 51 days after combined transplantation due to sepsis. CONCLUSION: Combined liver and kidney transplantation was a life-saving intervention in this selected group of patients with combined liver and kidney failure. Patient survival was comparable to that of patients undergoing isolated liver transplantation.

Adolescent↗
PubMed2005

[Icterus prolongatus is a reason for laboratory investigation, also in breastfed neonates].

Three infants, a boy aged 4 months and two girls aged 3 months and 6 weeks, respectively, had jaundice while they were breastfed. Until then, the jaundice had been interpreted as an innocent consequence of the breastfeeding. In the two eldest patients, however, biliary atresia was diagnosed. A hepatoportoenterostomy was performed in the girl when she was 15 weeks old, but both ultimately underwent a liver transplantation with a good clinical outcome. In the youngest patient, the jaundice disappeared spontaneously and retrospectively was indeed probably associated with breastfeeding. Thorough physical examination and biochemical analyses (total and direct bilirubin, gamma-glutamyl-transferase) are important for the identification of neonatal cholestasis syndromes. Laboratory investigation is recommended in any neonate jaundiced after the age of 3 weeks to differentiate pathological neonatal cholestasis from prolonged jaundice related to breastfeeding.

Age Factors↗
PubMed2004

[Two sisters with progressive familial intrahepatic cholestasis].

A few months after birth two sisters aged 5 and 9 years had developed cholestasis and abnormal liver functions with symptoms including itching and jaundice. The younger sister also developed rickets and clotting disorders. On clinical, biochemical and immunohistopathological grounds the diagnosis of 'progressive familial intrahepatic cholestasis (PFIC) type 2' was made. Medical treatment was not succesfull in reducing symptoms. An ileocolonic bypass in the younger child was not effective. Subsequently, both patients underwent partial external biliary diversion (PEBD). Except for a period of intermittent itching in the younger child, both patients remained free of symptoms 2 years after PEBD. In cases where an early diagnosis is made, PEBD could delay or even prevent the necessity of liver transplantation.

Age Factors↗
PubMed2004

The value of prospective monitoring of Epstein-Barr virus DNA in blood samples of pediatric liver transplant recipients.

UNLABELLED: Post-transplant lymphoproliferative disease (PTLD) is one of the major causes of morbidity and mortality in transplantation patients. A primary Epstein-Barr virus (EBV) infection is a major risk factor for developing PTLD. The aim of this study was to determine circulating EBV DNA after liver transplantation in pediatric patients in relation to primary EBV infection and development of PTLD. EBV serology was performed before transplantation. Every 4 weeks after transplantation a competitive quantitative polymerase chain reaction (PCR) assay for EBV nuclear antigen-1 was performed in 13 patients. Patients were followed for development of a PTLD. Before transplantation four patients were EBV seropositive and nine patients were EBV seronegative. In one of the four patients who were EBV seropositive before transplantation, EBV DNA became detectable after transplantation, with a peak load of 3600 copies/mL. None of these four patients developed a PTLD. Eight of the nine patients who were EBV seronegative before transplantation developed positive EBV DNA samples. EBV DNA was first detected at a mean of 64 days after transplantation (range 38-89). The mean peak EBV DNA load was 79,700 copies/mL (3600-446,000). Two of these patients developed PTLD, but they could not be identified based on prior or concomitant EBV PCR results. CONCLUSIONS: In pediatric liver transplantation EBV DNA load is higher in patients with a primary infection than in patients who were EBV seropositive before transplantation. The EBV PCR cannot be used to identify individual patients who develop PTLD. However, elevated EBV DNA load can be used to detect a group of patients at increased risk for PTLD.

Adolescent↗
PubMed2003

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes.

AIM/HYPOTHESIS: Type I diabetes is associated with altered hepatic bile formation and increased intestinal cholesterol absorption. The aim of this study was to evaluate whether altered expression of the ATP-Binding Cassette half-transporters Abcg5 and Abcg8, recently implicated in control of both hepatobiliary cholesterol secretion and intestinal cholesterol absorption, contributes to changed cholesterol metabolism in experimental diabetes. METHODS: mRNA and protein expression of Abcg5 and Abcg8 were determined in the liver and intestine of rats with streptozotozin-induced diabetes and related to relevant metabolic parameters in plasma, liver and bile. RESULTS: Hepatic mRNA expression of both Abcg5 (-76%) and Abcg8 (-71%) was reduced in diabetic rats when compared to control rats. In spite of increased HDL cholesterol, considered a major source of biliary cholesterol, secretion of the sterol into bile relative to that of bile salts was reduced by 65% in diabetic animals. Intestinal mRNA expression of Abcg5 (-47%) and Abcg8 (-43%) as well as Abcg5 protein contents were also reduced in insulin-deficient animals. This was accompanied by a three- to four-fold increase in plasma beta-sitosterol and campesterol concentrations and by a doubling of the calculated apparent cholesterol absorption. These effects partially normalized upon insulin supplementation. CONCLUSION/INTERPRETATION: Our data indicate that effects of insulin-deficiency on bile composition and cholesterol absorption in rats are, at least partly, attributable to changes in hepatic and intestinal Abcg5 and Abcg8 expression.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2001

Postprandial chylomicron clearance rate in late teenagers with diabetes mellitus type 1.

A delayed chylomicron (CM) clearance rate, a known risk factor for atherosclerosis, has been described in adults with diabetes type 1 (DM1). We determined the CM clearance rate in late teenagers with DM1, and the relationship between CM clearance rate and elevated plasma lipid concentrations in DM1 teenagers in poor metabolic control (as characterized by HbA(1c) percentage). Plasma lipids and CM clearance were determined in nine patients with DM1 (mean age +/- SD: 17.5 +/- 0.6 y) and four healthy controls (mean age +/- SD: 20.1 +/- 0.8 y), by measuring breath (13)CO(2), plasma triglyceride, retinyl palmitate, and (13)C-labeled oleic acid concentrations, after oral administration of a fat-rich meal together with vitamin A and (13)C-oleic acid. In patients with DM1, fasting triglyceride and cholesterol concentrations were positively correlated with HbA(1c) percentage (p < 0.05). Neither in DM1 patients, nor in controls, was an elevated triglyceride concentration (above 1.7 mmol/L) found. Yet, in 22% of DM1 patients, cholesterol concentration was above 5.2 mmol/L, but not in any of the controls. CM clearance rate in DM1 patients was similar to that in controls and did not significantly correlate with HbA(1c) percentage. Fasting lipid concentrations in DM1 patients were not significantly correlated with CM clearance rate. Present data indicate that elevated lipid concentrations in late teenagers with DM1 are not attributable to a delay in CM clearance rate. A delayed CM clearance rate at late teenager age is not a risk factor contributing to the increased risk for atherosclerosis in DM1.

Adolescent↗
PubMed2001

Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice.

Erythropoietic protoporphyria (EPP) is an inherited disorder of heme synthesis caused by deficiency of the mitochondrial enzyme ferrochelatase. EPP in humans is associated with liver disease, hypertriglyceridemia, and a low level of high density lipoprotein (HDL) cholesterol. To explore consequences of ferrochelatase deficiency in lipid metabolism, we have analyzed hepatic lipid content and plasma lipoprotein levels in chow-fed BALB/c mice homozygous ( fch/fch) or heterozygous ( fch/1) for a point mutation in the ferrochelatase gene and in wild-type controls (1/1). Livers of fch/fch mice show bile duct proliferation and biliary fibrosis, but bile formation is not impaired. The free cholesterol content of fch/fch livers is significantly increased when compared with fch/1 and 1/1 livers. Plasma cholesterol in fch/fch mice (9.9 +/- 6.4 mM) is elevated when compared with fch/1 and 1/1 mice (2.9 +/- 0.2 and 2.5 +/- 0.3 mM, respectively), because of an increased cholesterol content in the very low density lipoprotein-sized fractions, whereas HDL cholesterol is reduced. The ratio of cholesteryl ester to free cholesterol is 4.3 +/- 0.6, 3.3 +/- 0.3, and 0.3 +/- 0.1 in the plasma of 1/1, fch/1, and fch/fch mice, respectively. The latter is not due to reduced lecithin:cholesterol acyltransferase activity in plasma of fch/fch mice but to the presence of lipoprotein-X (Lp-X), a particle composed of bile-type lipids usually seen only in cholestatic conditions. Expression of mdr2, essential for biliary phospholipid/cholesterol secretion, is increased in fch/fch livers. In spite of this, biliary phospholipid/cholesterol secretion is reduced relative to that of bile salts. It is postulated that an inability of bile salts to stimulate lipid secretion adequately leads to formation of Lp-X in this noncholestatic condition. Distinct atherosclerotic lesions were found in aged fch/fch mice.Thus, ferrochelatase deficiency in mice leads to liver disease associated with altered hepatic lipid metabolism, a characteristic hyperlipidemia, and development of atherosclerosis.-Bloks, V. W., T. Plösch, H. van Goor, H. Roelofsen, J. Baller, R. Havinga, H. J. Verkade, A. van Tol, P. L. M. Jansen, and F. Kuipers. Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice. J. Lipid Res. 2001. 42: 41;-50.

Animals↗
PubMed2001

Measurement of parameters of cholic acid kinetics in plasma using a microscale stable isotope dilution technique: application to rodents and humans.

A stable isotope dilution method is described that allows measurement of cholic acid (CA) kinetics, that is, pool size, fractional turnover rate (FTR), and synthesis rate in mice, rats, and humans. Decay of administered [2,2,4,4-2H4]CA enrichment was measured in time in 50-microl plasma samples by gas-liquid chromatography/electron capture negative chemical ionization-mass spectrometry, applying the pentafluorobenzyl-trimethylsilyl derivative. The kinetic data expressed species-dependent differences. The CA pool sizes were 16.8 +/- 2.1, 10.6 +/- 1.2, and 2.4 +/- 0.7 micromol/100 g body weight for mice, rats, and humans, respectively. The FTR values were 0.44 +/- 0.03, 0.88 +/- 0.10, and 0.46 +/- 0.14 per day for mice, rats, and humans. The corresponding synthesis rates were 7.3 +/- 1.6, 9.3 +/- 0.1, and 1.0 +/- 0.2 micromol/100 g body weight per day. The human data agreed well with literature data obtained by conventional isotope dilution techniques. For rats and mice these are the first reported isotope dilution data. The method was validated by confirmation of isotopic equilibrium between biliary CA and plasma CA in the rat. Its applicability was demonstrated by the observation of increased CA FTR and CA synthesis rate in rats fed cholestyramine, which is known to increase fecal bile acid excretion. The presented stable isotope dilution method enables the determination of CA kinetic parameters in small plasma samples. The method can be applied in unanesthetized rodents with an intact enterohepatic circulation and may also be valuable when studying the development of human neonatal bile acid kinetics.

Adult↗
PubMed2000

Postprandial chylomicron formation and fat absorption in multidrug resistance gene 2 P-glycoprotein-deficient mice.

BACKGROUND & AIMS: It has been proposed that biliary phospholipids fulfill specific functions in the absorption of dietary fat from the intestine, but the physiological significance has not been established. The aim of this study was to evaluate the role of biliary phospholipids in dietary fat absorption in vivo by using mice homozygous or heterozygous for disruption of the Mdr2 gene (Mdr2((-/-)), Mdr2((+/-))) and control (Mdr2((+/+))) mice. Mdr2((-/-)) mice do not secrete phospholipids and cholesterol into bile, and bile salt secretion is not impaired. Mdr2((+/-)) mice show only impaired (-40%) phospholipid secretion. METHODS: Methods included an analysis of time dependency of intestinal uptake and plasma appearance of intragastrically administered (radiolabeled) triglycerides and measurement of 3-day fecal fat balance with low- and high-fat diets. RESULTS: Intragastric administration of olive oil resulted in a rapid increase in plasma triglycerides in Mdr2((+/+)) and Mdr2((+/-)) but not in Mdr2((-/-)) mice. The "postprandial response" of plasma triglycerides could be partially restored in Mdr2((-/-)) mice by intraduodenal infusion of whole rat bile. After intragastric [(3)H]triolein administration in Triton WR1339-pretreated animals, the appearance of (3)H-triglycerides in plasma was reduced by 70% in Mdr2((-/-)) compared with Mdr2((+/+)) mice, excluding accelerated lipolysis as the cause of defective triglyceride response in Mdr2((-/-)) mice. (3)H-triglycerides accumulated in enterocytes in Mdr2((-/-)) mice. Surprisingly, the efficacy of fat absorption as derived from balance studies was not affected and was only minimally affected in Mdr2((-/-)) mice fed low (14 energy percent)- and high (35 energy percent)-fat diets, respectively (all >95%). CONCLUSIONS: The results show that biliary lipid secretion is necessary for postprandial appearance in plasma of chylomicrons in vivo but not for quantitative absorption of dietary lipids.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Detection of impaired intestinal absorption of long-chain fatty acids: validation studies of a novel test in a rat model of fat malabsorption.

BACKGROUND: Classic fat balance studies detect fat malabsorption but do not discriminate between the potential causes of malabsorption, such as impaired intestinal lipolysis or reduced uptake of fatty acids. OBJECTIVE: We aimed to validate a novel test for the specific, sensitive detection of impaired intestinal uptake of long-chain unesterified fatty acids in an appropriate rat model of fat malabsorption. DESIGN: The absorption and appearance in plasma of [(13)C]palmitic acid were determined in control rats and in rats with fat malabsorption due either to chronic bile deficiency (permanent bile diversion) or to oral administration of the lipase inhibitor orlistat (200 mg/kg diet). [(13)C]Palmitic acid results were compared with the percentage absorption of ingested dietary fat determined by fat balance. RESULTS: Between 1 and 6 h after intraduodenal administration, plasma [(13)C]palmitate concentrations in control rats were 4-10-fold higher than in bile-deficient rats (P < 0.05) but were not significantly different between orlistat-supplemented rats and their controls. In control and bile-deficient rats, plasma [(13)C]palmitate concentrations allowed complete discrimination between normal (>92%) and reduced (<92%) fat absorption, whereas the percentage absorption of [(13)C]palmitate over 48 h appeared to be highly correlated with the percentage absorption of ingested dietary fat (r = 0.89, P < 0.001). CONCLUSIONS: The [(13)C]palmitic acid absorption test detects impaired intestinal absorption of long-chain fatty acids selectively and sensitively in a rat model of fat malabsorption due to bile deficiency. Our data strongly support the use of the [(13)C]palmitic acid absorption test for the diagnosis of clinical fat malabsorption syndromes.

Animals↗
PubMed2000

Intestinal absorption and postabsorptive metabolism of linoleic acid in rats with short-term bile duct ligation.

We investigated in bile duct-ligated (BDL) and sham-operated control rats whether the frequent presence of essential fatty acid deficiency in cholestatic liver disease could be related to linoleic acid malabsorption, altered linoleic acid metabolism, or both. In plasma of BDL rats, the triene-to-tetraene ratio, a biochemical marker for essential fatty acid deficiency, was increased compared with controls (0.024 +/- 0.004 vs. 0.013 +/- 0.001; P < 0.05). Net and percentage of dietary linoleic acid absorbed were decreased in BDL rats compared with control rats (1.50 +/- 0.16 mmol/day and 81.3 +/- 3.3% vs. 2.08 +/- 0.07 mmol/day and 99.2 +/- 0.1%, respectively; each P < 0.001). At 24 h after [(13)C]linoleic acid administration, BDL rats had a similar ratio of plasma [(13)C]arachidonic acid to plasma [(13)C]linoleic acid concentration compared with control rats. Delta(6)-Desaturase activity was not significantly different in hepatic microsomes from control or BDL rats. At 3 h after [(13)C]linoleic acid administration, plasma appearance of [(13)C]linoleic acid and cumulative expiration of (13)CO(2) were decreased in BDL rats, compared with controls (by 54% and 80%, respectively). The present data indicate that the impaired linoleic acid status in cholestatic liver disease is mainly due to decreased net absorption and not to quantitative alterations in postabsorptive metabolism.

Animals↗
PubMed1999

Biliary phospholipid secretion is not required for intestinal absorption and plasma status of linoleic acid in mice.

Biliary phospholipids have been hypothesized to be important for essential fatty acid homeostasis. We tested this hypothesis by investigating the intestinal absorption and the status of linoleic acid in mdr2 Pgp-deficient mice which secrete phospholipid-free bile. In mice homozygous (-/-) for disruption of the mdr2 gene and wild-type (+/+) mice, dietary linoleic acid absorption was determined by 72 h balance techniques. After enteral administration, [(13)C]-linoleic acid absorption was determined by measuring [(13)C]-linoleic acid concentrations in feces and in plasma. The status of linoleic acid was determined in plasma and in liver by calculating the molar percentage of linoleic acid and the triene:tetraene ratio. Although plasma concentration of [(13)C]-linoleic acid at 2 h after enteral administration was significantly lower in (-/-) compared to (+/+) mice (P</=0.05), net intestinal absorption of dietary linoleic acid or of [(13)C]-linoleic acid was similar in (+/+) and (-/-) mice. Molar percentage of linoleic acid and the triene:tetraene ratio were not different in whole plasma or in liver of (-/-) compared to (+/+) mice. Present data indicate that biliary phospholipids are involved in the rate of appearance in plasma of enterally administered linoleic acid, but are not required for net intestinal absorption or plasma status of linoleic acid.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Bile diversion in rats leads to a decreased plasma concentration of linoleic acid which is not due to decreased net intestinal absorption of dietary linoleic acid.

Decreased bile secretion into the intestine has been associated with low plasma concentrations of essential fatty acids (EFA) in humans. We studied the mechanism behind this relationship by determining the status and absorption of the major dietary EFA, linoleic acid (LA), in control and 1-week bile-diverted rats. The absorption of LA was quantified by a balance method and by measuring plasma concentrations of [13C]LA after its intraduodenal administration. Absolute and relative concentrations of LA in plasma were decreased in bile-diverted rats (P<0.01 and P<0.001, respectively). Fecal excretion of LA was increased at least 20-fold in bile-diverted rats (0.72+/-0.11 vs. 0.03+/-0.00 mmol/day; P<0.0001). Due to increased chow ingestion by bile-diverted rats, net intestinal absorption of LA was similar between bile-diverted and control rats (1.96+/-0.14 vs. 1.91+/-0.07 mmol/day, respectively; P>0.05). After intraduodenal administration of [13C]LA, plasma concentrations were approximately 3-4-fold lower in bile-diverted rats for at least 6 h (P<0.001). Plasma concentrations of both [12C]arachidonic acid and [13C]arachidonic acid were increased in bile-diverted rats (P<0.05). We conclude that decreased plasma concentrations of LA in 1-week bile-diverted rats are not due to decreased net intestinal absorption of LA, but may be related to increased metabolism of LA.

Animals↗
PubMed1999

The unique acyl chain specificity of biliary phosphatidylcholines in mice is independent of their biosynthetic origin in the liver.

The liver synthesizes phosphatidylcholine (PC) de novo from choline via the CDP-choline pathway, and from phosphatidylethanolamine (PE) via the phosphatidylethanolamine N-methyltransferase (PEMT) pathway. Significant amounts of PC, which are highly specific in their acyl chain composition, are secreted into bile by the liver. To determine whether either of the 2 PC biosynthetic routes is sufficient to provide physiological PC concentrations in bile, or is responsible for the unique acyl chain composition of bile PC, we analyzed gallbladder bile composition in mice that synthesized PC either via the PEMT pathway (induced by feeding a choline-deficient diet) or the CDP-choline pathway (based on genetic PEMT-deficiency). The PC concentration in gallbladder bile of mice that synthesize PC mainly via the CDP-choline pathway was comparable with control mice that synthesize PC via both pathways, whereas it was reduced by approximately 40% in mice that synthesize PC via the PEMT pathway. The acyl chain composition of bile PC was similar irrespective of the active PC biosynthetic pathway in the liver. These data demonstrate that the CDP-choline pathway alone, but not the PEMT pathway alone, can account for physiological concentrations of PC in gallbladder bile. Moreover, the specificity of biliary PC fatty acyl composition is determined independently from the synthetic origin of PC.

Animals↗
PubMed1999

Validation in an animal model of the carbon 13-labeled mixed triglyceride breath test for the detection of intestinal fat malabsorption.

OBJECTIVE: To determine, in a rat model of fat malabsorption, the potency of the carbon 13-labeled mixed triglyceride ((13)C-MTG) breath test as a noninvasive, patient-friendly replacement for classic fat balance studies. STUDY DESIGN: Comparison of the percentage of fat absorption, detected by fat balance, with the (13)CO(2) recovery of the (13)C-MTG breath test in rats fed high-fat chow and varying amounts of the lipase inhibitor, orlistat (0, 50, 200, and 800 mg per kilogram of chow), for 5 days. RESULTS: On orlistat administration, total fat absorption decreased from 80.2% +/- 2.2% to 32.8% +/- 3.7% (mean +/- SEM, 0 mg and 800 mg of orlistat per kilogram of chow, respectively; P <.001). Correspondingly, breath (13)CO(2) recovery from (13)C-MTG at 6 hours decreased from 84.5% +/- 7.8% to 42.0% +/- 1.5% of the dose (0 mg and 800 mg of orlistat per kilogram of chow, respectively; P <.001). The 6-hour recovery of breath (13)CO(2) appeared to be highly correlated with the percentage of fat absorption (r = 0.88, P <.001). In rats with fat absorption higher than 70%, however, the coefficient of variation of the (13)C-MTG breath test was 3-fold larger than that of the fat balance. CONCLUSIONS: The (13)C-MTG breath test could potentially replace the fat balance method for comparing fat absorption efficacy between groups. Yet, a considerable interindividual variation of the (13)C-MTG breath test under conditions of relatively mild fat malabsorption does not support its application for diagnostic purposes in individuals.

Animals↗