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Biomedical subjects

F Thuillier

Publications and source records attributed to F Thuillier.

At least 19 recordsLinked to original sources
PubMed2004

Net digestive absorption and adaptive hyperphagia in adult short bowel patients.

BACKGROUND AND AIMS: Intestinal adaptation after small bowel resection in humans is debated. We have quantified in adult short bowel (remnant small bowel length <2 m) patients oral intake and net digestive absorption and their evolution over time. PATIENTS AND METHODS: Oral intake and faecal output were studied over three days in 90 patients (39 and 51 without or with parenteral nutrition, respectively) and in 14 patients in early (<6 months) and late (>6 months) periods after digestive continuity. Nitrogen and fat output were measured using chemiluminescence and Van de Kamer techniques, respectively. RESULTS: In the whole group, 81% of patients had hyperphagia (spontaneous oral intake >1.5 x resting energy expenditure), independently and negatively related to fat absorption (p<0.01) and body mass index (p<0.001) but not braked by the presence of parenteral nutrition. Protein and fat absorption were related to small bowel length. We observed, in the late in comparison with the early period after digestive continuity: an increase in oral intake (1.6 v 2.3 resting energy expenditure), decrease in stool weight/oral intake ratio, no reduction in per cent fat absorption, and protein absorption improvement associated with a significant increase in the amount of protein absorbed (40 v 64 g/day; p<0.05), both being correlated with remnant small bowel length (p<0.01). CONCLUSIONS: This study confirms an adaptive hyperphagia in adult short bowel patients. Over time, hyperphagia and amount of protein absorbed increased, the latter being related to remnant small bowel length, indicating a behavioural adaptation that allows expression of intestinal absorptive adaptation.

Adaptation, Physiological↗
PubMed2000

Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans.

BACKGROUND & AIMS: No blood marker assessing the functional absorptive bowel length has been identified. Plasma citrulline, a nonprotein amino acid produced by intestinal mucosa, is one candidate. We tested this hypothesis in adult patients with the short-bowel syndrome, whose condition can lead to intestinal failure. METHODS: In 57 patients, after a minimal follow-up of 2 years subsequent to final digestive circuit modification, postabsorptive citrulline concentration was measured and parenteral nutrition dependence was used to define permanent (n = 37) and transient (n = 20) intestinal failure. Absorptive function, studied over a 3-day period, was evaluated by net digestive absorption for protein and fat (n = 51). Relations between quantitative values were assessed by linear regression analysis and cutoff citrulline threshold, for a diagnosis of intestinal failure by linear discriminant analysis. Cox model was used to compare citrulline threshold and anatomic variables of the short bowel as indicators of transient as opposed to permanent intestinal failure. RESULTS: In patients with short-bowel syndrome, citrulline levels were lower than in controls (n = 51): 20 +/- 13 vs. 40 +/- 10 micromol/L (mean +/- SD), respectively (P < 0.001). After multivariate analysis, citrullinemia was correlated to small bowel length (P < 0.0001, r = 0.86) and to net digestive absorption of fat, but to neither body mass index nor creatinine clearance. A 20-micromol/L threshold citrullinemia, (1) classified short bowel patients with permanent intestinal failure with high sensitivity (92%), specificity (90%), positive predictive value (95%), and negative value (86%); and (2) was a more reliable indicator (odds ratio, 20.0; 95% confidence interval, 1.9-206.1) than anatomic variables (odds ratio, 2.9; 95% confidence interval, 0. 5-15.8) to separate transient as opposed to permanent intestinal failure. CONCLUSIONS: In patients with short-bowel syndrome, postabsorptive plasma citrulline concentration is a marker of functional absorptive bowel length and, past the 2-year adaptive period, a powerful independent indicator allowing distinction of transient from permanent intestinal failure.

Absorption↗
PubMed2000

Duodenal vs. gastric administration of labeled leucine for the study of splanchnic metabolism in humans.

Low-rate (6 ml/h) intragastric infusion of stable, isotope-labeled amino acids is commonly used to assess the splanchnic handling of amino acids in humans. However, when used in the postabsorptive state, this method yields unreliable plasma isotopic enrichments, with a coefficient of variation >10%. In this metabolic condition, we confirmed in six subjects that an intragastric infusion of L-[(2)H(3)]leucine at 6 ml/h yields an unreliable isotopic steady state in plasma amino acids with a coefficient of variation of 43 +/- 12% (mean +/- SD). In five additional subjects, we assessed the effects of 1) increasing the rate of delivery of a leucine tracer in an isotonic plasmalike solution at 240 ml/h into the gastric site, and 2) changing the site of infusion from gastric to duodenal with this same high rate of delivery. In contrast to the gastric route, and regardless of the rate of delivery, only the intraduodenal route allowed 1) isotopic plasma steady state (i.e., coefficients of variation were <10%: 5 +/- 3%), and 2) reproducible leucine extraction coefficients (22 +/- 5%). We conclude that an infusion site that bypasses the gastric emptying process, i.e., the duodenal route, along with delivery of a plasmalike solution, is necessary to reach isotopic steady state in plasma when labeled leucine is infused into the gastrointestinal tract in the postabsorptive state.

Adult↗
PubMed1999

Kinetics of serum tumor marker concentrations and usefulness in clinical monitoring.

Only a few markers have been instrumental in the diagnosis of cancer. In contrast, tumor markers play a critical role in the monitoring of patients. The patient's clinical status and response to treatment can be evaluated rapidly using the tumor marker half-life (t(1/2)) and the tumor marker doubling time (DT). This report reviews the interest of determining these kinetic parameters for prostate-specific antigen, human chorionic gonadotropin, alpha-fetoprotein, carcinoembryonic antigen, cancer antigen (CA) 125, and CA 15-3. A rise in tumor markers (DT) is a yardstick with which benign diseases can be distinguished from metastatic disease, and the DT can be used to assess the efficacy of treatments. A decline in the tumor marker concentration (t(1/2)) is a predictor of possible residual disease if the timing of blood sampling is soon after therapy. The discrepancies in results obtained by different groups may be attributable to the multiplicity of immunoassays, the intrinsic characteristics of each marker (e.g., antigen specificity, molecular heterogeneity, and associated forms), individual factors (e.g., nonspecific increases and renal and hepatic diseases) and methods used to calculate kinetics (e.g., exponential models and timing of blood sampling). This kinetic approach could be of interest to optimize patient management.

Biomarkers, Tumor↗
PubMed1998

Whole-body protein metabolism assessed by leucine and glutamine kinetics in adult patients with active celiac disease.

To assess the effect of increased renewal of intestinal epithelial cells on leucine and glutamine (Gln) turnover, 4-hour intravenous infusions of L-[1-(13)C]leucine and L-[2-(15)N]Gln were administered to five adult patients with active celiac disease in the postabsorptive state. There was a 35% increase in leucine flux (micromoles per kilogram per hour) in patients (117 +/- 17) compared with healthy controls (96 +/- 11, P < .03). Gln flux was increased by 13% in patients (377 +/- 35) versus controls (335 +/- 16, P < .04). These results suggest that active celiac disease, characterized by villous atrophy and crypt cell hyperplasia, is associated with a dramatic increase in whole-body protein breakdown as assessed by 13C-leucine, which may contribute per se to the protein malnutrition status of the patients. The increase in Gln utilization as assessed by L-[2-(15)N]Gln was moderate, but may have been offset due to the villose atrophy and ensuing reduced intestinal epithelial cell mass. The results are consistent with the concept that increased renewal of intestinal epithelial cells represents a sizable fraction of whole-body protein turnover and that Gln is an important fuel for epithelial intestinal cells in vivo.

Adult↗
PubMed1998

[6-mercaptopurine levels and study of blood lymphocyte subsets during azathioprine treatment of Crohn's disease].

OBJECTIVES: Our aim was to study the relationships between clinical efficacy of azathioprine, 6-mercaptopurine pharmacokinetics and changes in peripheral blood lymphocyte subpopulations induced by azathioprine treatment in Crohn's disease. METHODS: Twenty-three patients were prospectively followed up for 1 year. Peripheral blood counts, total lymphocytes, CD3+, CD4+, CD8+, CD25+, CD16+CD56+, CD57+ and CD19+ lymphocyte subpopulations were carried out, using flow cytometry, during azathioprine treatment. Pharmacokinetic studies were performed at day 8 and month 3 by measuring 6-mercaptopurine plasma concentration after an oral dose of azathioprine (2 mg/kg). Results were compared in responders (no activity and no steroids) and non-responders. RESULTS: The decrease in peripheral blood leukocytes and neutrophils was significant after 1 month, reaching 49% and 48% of the pre-treatment values at 1 year; the one of lymphocytes was significant after 6 months and reached 41% at 1 year. Percentages of CD3+, CD4+, CD8+, CD57+, CD16+CD56+ and CD19+ lymphocytes remained unchanged whereas percentage of CD25+ lymphocytes increased from 10% to 28% (P < 0.01). There was a high inter and intraindividual variability of 6-mercaptopurine peak plasma concentration and area under the curve. No significant difference was found between responders (n = 14) and non responders (n = 7) for pharmacokinetic parameters and lymphocyte subpopulations; there was no correlation between lymphocyte subpopulation changes and 6-mercaptopurine pharmacokinetics. CONCLUSION: Monitoring of 6-mercaptopurine plasma concentration and blood lymphocyte subpopulations is of little value in Crohn's disease patients treated with azathioprine.

Adult↗
PubMed1997

Home parenteral nutrition and vitamin B12 status.

The vitamin B12 status of 20 subjects who were on home parenteral nutrition after surgical or functional small bowel resection and were given 1000 micrograms cyanocobalamin every 3 mo was studied by comparing their plasma vitamin B12, homocysteine (HS), and methylmalonic acid (MMA) concentrations. The plasma vitamin B12 concentration (median 145 pmol/L, 95% confidence interval: 123-217) was subnormal in four cases and borderline in four others. In the "4low B12" group, the concentrations of the markers of vitamin B12 deficiency were in the normal range; HS 10.7 mumol/L (8.0-12.3); and MMA, 0.15 mumol/L (0.09-0.19). References values were HS, 10.0 mumol/L (9.4-12.6); and MMA, 0.16 mumol/L (0.10-0.19). Thus, there were no metabolic signs of vitamin B12 deficiency in these subjects on parenteral nutrition, despite the fact that their plasma vitamin B12 levels were low. Analysis of individual data showed that the four patients with low circulating B12 had markers of intracellular vitamin B12 deficiency in the normal range.

Adult↗
PubMed1996

Assessment of insulin sensitivity in glucokinase-deficient subjects.

The chronic hyperglycaemia of glucokinase-deficient diabetes results from a glucose-sensing defect in pancreatic beta cells and abnormal hepatic glucose phosphorylation. We have evaluated the contribution of insulin resistance to this form of chronic hyperglycaemia. Insulin sensitivity, assessed by the homeostasis model assessment (HOMA) method in 35 kindreds with glucokinase mutations, was found to be significantly decreased in 125 glucokinase-deficient subjects as compared to 141 unaffected first-degree relatives. Logistic regression analysis showed that in glucokinase-deficient subjects a decrease in insulin sensitivity was associated with deterioration of the glucose tolerance status. A euglycaemic hyperinsulinaemic clamp was performed in 14 glucokinase-deficient subjects and 12 unrelated control subjects. In six patients and six control subjects the clamp was coupled to dideutero-glucose infusion to measure glucose turnover. Average glucose infusion rates (GIR) at 1 and 5 mU.kg body weight.min-1 insulin infusion rates were significantly lower in (the glucokinase-deficient) patients than in control subjects. Although heterogeneous results were observed, in 8 out of the 14 patients GIRs throughout the experiment were lower than 1 SD below the mean of the control subjects. Hepatic glucose production at 1 mU.kg body weight-1.min-1 insulin-infusion rate was significantly higher in patients than in control subjects. In conclusion, insulin resistance correlates with the deterioration of glucose tolerance and contributes to the hyperglycaemia of glucokinase-deficient diabetes. Taken together, our results are most consistent with insulin resistance being considered secondary to the chronic hyperglycaemia and/or hypoinsulinaemia of glucokinase-deficiency. Insulin resistance might also result from interactions between the unbalanced glucose metabolism and susceptibility gene(s) to low insulin sensitivity likely to be present in this population.

Adolescent↗
PubMed1995

Energy and protein metabolism in malnutrition due to nonneoplastic gastrointestinal diseases.

Although a reduction in both energy expenditure and protein turnover has been demonstrated in starved volunteers, few metabolic data are available for patients in whom malnutrition is due to nonneoplastic gastrointestinal diseases. Chronically malnourished, unstressed adult patients with nonneoplastic gastrointestinal diseases (body mass index, 15.8 +/- 2.5 kg/m2, n = 13) and healthy control subjects (n = 10) were studied in the postabsorptive state using indirect calorimetry, as well as substrate fluxes of L[1-13C]leucine, L-[2-15N]glutamine (seven patients and six controls), and D[6,6-2H2]glucose (seven patients and eight controls). Resting energy expenditure (REE) expressed in kilocalories per 24 hours was significantly lower in patients than in controls; REE expressed per unit of fat-free mass (FFM) was not significantly different in both groups. Whole-body leucine turnover, oxidation, and nonoxidative disposal rates, based on either 13C-leucine or 13C-alpha-ketoisocaproic acid (KIC) enrichments, and glucose turnover rate were not significantly different between malnourished patients and controls. Moreover, glutamine turnover was increased by 28% in malnourished patients as compared with normal volunteers (429.8 +/- 86.8 v 334.9 +/- 15.9 mumol/kg/h, P = .02). These results suggest that hypometabolic adaptation, although previously documented in starved volunteers, is not operative during states of chronic malnutrition due to gastrointestinal disease. The increase in glutamine turnover rate might represent an adaptative mechanism to malnutrition for preservation of visceral mass or function.

Body Mass Index↗
PubMed1995

Intestinal transport and processing of immunoglobulin G in the neonatal and adult rat.

The proximal intestine of neonatal rats expresses a specific receptor (RFcn) that binds immunoglobulin G (IgG) and is no longer expressed after weaning. The aim of this study was to quantify and compare the intestinal transport and processing of IgG in intestinal fragments with or without RFcn, with the fluid-phase transport of horseradish peroxidase (HRP). The mucosal to serosal transport and degradation of IgG and HRP were measured in neonatal and adult rats in vitro in Ussing chambers. IgG transcytosis occurred without degradation in the proximal intestine of neonatal rats, where RFcn is expressed, up to a luminal concentration of 300 micrograms/ml. At higher mucosal IgG concentrations, a degradative pathway was also involved. The immunoreactive IgG fluxes across the proximal intestine of neonatal rats were higher than those observed in the distal neonatal intestine or those in the proximal and distal adult intestine. The rate of HRP transcytosis was higher than that of IgG but it involved a mainly degradative pathway. These results suggest that in the proximal intestine of the neonatal rat, where RFcn is expressed, the transcytotic rate for IgG is not increased, but the nondegradative transport of immunoreactive IgG is favored, especially at low luminal concentrations.

Aging↗
PubMed1994

Gastro-jejunal digestion of soya-bean-milk protein in humans.

In order to determine how soya-bean proteins are digested and metabolized in the human intestine before colonic bacterial fermentation and to estimate their true digestibility, the gastro-jejunal behaviour of soya-bean proteins in water and in two other forms (a concentrated soya-bean-protein solution (isolate) and a drink composed of crude soya-bean proteins (soymilk)) was studied in humans. Experiments were carried out in eight healthy volunteers using a double-lumen steady-state intestinal perfusion method with polyethyleneglycol (PEG) as a non-absorbable volume marker. Gastric emptying and N and electrolyte contents of the jejunal digesta were analysed. Gastric half-emptying time (min) of the liquid phase after water ingestion (12.59 (SE 0.12)) was shorter (P < 0.05) than those for soymilk (37.74 (SE 11.57)) and isolate (36.52 (SE 11.23)). Electrolytic balances showed that for all meals, Na+, Cl- and K+ were secreted when Ca2+ was efficiently absorbed from the jejunal lumen. Gastro-jejunal N absorption for isolate and soymilk were 63 and 49% respectively, and were not significantly different from one another; after water ingestion, endogenous N was estimated to be 21 mmol. An estimate of the exogenous:endogenous values for the effluents was obtained from the amino acid compositions of soymilk and effluents after water or soymilk ingestion, indicating that 70% of the total N was exogenous and 30% endogenous. Under these conditions the endogenous fraction represented 31 mmol after soymilk ingestion and the gastro-jejunal N balance indicated that 54% of the soymilk was absorbed. This finding indicates that the true gastrojejunal digestibility of soya-bean proteins is similar to that of milk proteins.

Adult↗
PubMed1994

Intestinal nitrogen and electrolyte movements following fermented milk ingestion in man.

The present study focuses on the digestion and absorption of milk and fermented milk (FM) reflected by gastro-ileal N and electrolyte movements in six healthy volunteers. The N and electrolyte content of the intestinal effluents were analysed both at the beginning of the jejunum and in the distal ileum. The gastric half-emptying time of the liquid phase was significantly (P < 0.05) shorter for milk (35 (SE 2) min) than for FM (60 (SE 2) min). The N balance showed that 58 and 50% of ingested proteins, milk and FM respectively were absorbed between the stomach and the proximal jejunum and that 91 and 90% respectively were absorbed between the stomach and the terminal ileum in 240 min. Evaluation of mineral absorption indicated that 44 and 67% of Ca was absorbed in the duodenum after milk and FM ingestion respectively, and 41 and 11% of Ca disappeared between the jejunum and the ileum respectively. With regards to N and Ca intestinal availability, the present study confirms that FM products represent an interesting source of N as well as minerals for man. This confers on FM a beneficial effect compared with milk especially for lactase (EC 3.2.1.108)-deficient subjects and children with persistent diarrhoea.

Adult↗
PubMed1994

Glutamine metabolism in healthy adult men: response to enteral and intravenous feeding.

To assess the effect of feeding on glutamine kinetics, six healthy men received 4-h intravenous infusions of L-[2-15N]glutamine and L-[1-13C]leucine on 3 separate days: 1) in the postabsorptive state, 2) over the course of an 8-h nasogastric infusion of a small peptide-based nutrient mixture, and 3) during an 8-h isonitrogenous, isoenergetic intravenous infusion (1.5 g amino acid.kg-1.d-1; 130 kJ.kg-1.d-1, or 31 kcal.kg-1.d-1; 58% carbohydrate and 42% fat). Regardless of the route, nutrition increased leucine appearance rate (Ra) and oxidation, stimulated protein synthesis, and improved leucine balance; apparent rates of protein breakdown decreased during enteral nutrition only. Glutamine Ra increased 16.8% (NS) and 26.2% (P < 0.01) with parenteral and enteral feeding, respectively, over postabsorptive values. The present findings are consistent with a major role of glutamine in interorgan nitrogen transport in the fed state and further suggest that increased availability of precursors may stimulate glutamine synthesis de novo, and enteral infusion of peptide-bound amino acids may be an effective route to provide free glutamine to the rest of the body.

Adult↗
PubMed1992

Gastroileal nitrogen and electrolyte movements after bovine milk ingestion in humans.

Gastric emptying and flow rates of nitrogen and electrolytes (Na+, K+, Cl-, Mg2+, Ca2+) were studied in humans after bovine milk ingestion. With water as the control, intestinal effluents were collected after meal ingestion at the beginning of the jejunum or in the distal ileum. The flow rate of the effluent peaked in the first 40-min period after meal ingestion and returned to the initial amount within 100 min. After water ingestion the quantity of nitrogen recovered in the digesta remained unchanged both in the jejunum and in the ileum during the test period. After milk ingestion the nitrogen concentration in the jejunal digesta peaked in the first 20 min. Forty-two percent of milk nitrogen was absorbed before the jejunum and 93% was absorbed before the end of the ileum. These results showed that for the completion of the absorption of dietary proteins such as milk proteins, the lower part of the intestine is necessary.

Adult↗
PubMed1992

Urinary excretion of iodide and fluoride from supplemented food grade salt.

Iodide and fluoride supplemented food grade salt (NaCl) is a common source of these two micronutrients. In a pilot study, we investigated whether increased intake of NaCl supplemented with iodide (I-) and fluoride (F-) results in their higher bioavailability. Twelve healthy adult human volunteers ingested increasing quantities (1, 3, 6 and 9 g) of NaCl with usual diet over 8 days. Sodium (Na+), I- and F- were measured in 24 hour urine specimen. During the 4 day basal period when no additional NaCl was ingested, ingestion of NaCl calculated from urinary Na+ concentration and diuresis was 8.25 +/- 0.67 g/24 h. During the same period 0.11 +/- 0.01 and 0.61 +/- 0.04 mg of I- and F- respectively were excreted in the urine per 24 h. Increased ingestion of supplemented NaCl resulted in higher urinary excretion of sodium while urinary creatinine remained stable. 92% of I- and 40% of F- contained in the additional amount of NaCl ingested were excreted in the urine. These results indicate that with increased ingestion of supplemented (I- and F-) NaCl, almost the totality of I- is excreted in the urine while fluoride is either incompletely absorbed or retained by the body to a higher extent. I- and F- supplemented NaCl is, therefore, an effective vehicle to provide these micronutrients when ingested with diet.

Adolescent↗
PubMed1991

Digestion of bovine milk proteins in patients with a high jejunostomy.

Digestion of milk proteins was studied in short-bowel patients. After ingestion of water, purified beta-lactoglobulin (beta-Ig), or skim milk, effluents were collected at the stoma. The flow rate of the effluent peaked in the first 30-min period after ingestion and returned to the basal value within the first 60 min. After milk ingestion 1) the nitrogen concentration of effluents peaked in the first 30 min, 2) SDS-polyacrylamide gel electrophoresis and Western blot indicated the presence of beta-Ig and alpha-lactalbumin (alpha-lac) in jejunal effluents but only during the first 30 min whereas caseins were detected during the initial 1-2 h effluents, and 3) immunoenzymo metric assay indicated that 64% and 44% of the beta-Ig and alpha-lac, respectively, were recovered in an intact antigenic form. Results indicate that the digestion of milk proteins in humans differs quantitatively. Digestion appeared partially incomplete in the upper jejunum, suggesting the importance of the ileum for completion of digestion.

Blotting, Western↗
PubMed1990

Antibiotic-lock technique is an effective treatment of bacterial catheter-related sepsis during parenteral nutrition.

Catheter-related sepsis is one of the most frequent and troublesome complications of parenteral nutrition. In a 2-year survey of 19 home parenteral nutrition patients, with a total of 25.2 years of cyclic nocturnal parenteral nutrition, the annual incidence of catheter-related sepsis was 1.27, of which 84% were due to bacterial catheter infection without any cutaneous focus. These 27 episodes were treated by a daily, 2 ml injection of antibiotic-saline solution, mainly amikacin, locked for 12 h per day within the infected catheter for 15 (7-20) days. On admission the parenteral nutrition was halted for 2 days and the catheter hub was changed. In 7 cases, an average of 3 days (2-5) of systemic antibiotic therapy was given in addition to the 2-week antibiotic-lock. Control of catheter-sepsis was achieved in 93% of the 27 episodes and parenteral nutrition was resumed using the same catheter with only one episode of recurrent sepsis. The present data confirm our preliminary report of the efficacy of the antibiotic-lock technique for the control of bacterial catheter-related sepsis. This treatment offers the advantage over current therapies of avoiding repeated catheter change and 2-6 weeks of systemic antibiotic therapy.

Journal Article↗