[Calcified bullet thrombus of the inferior vena cava and left renal vein in an adult]. / Une calcification de la veine cave inférieure et de la veine rénale gauche chez l'adulte.

Calcifications are rarely located within the inferior vena cava and the renal veins. The etiology is poorly understood and the prognosis is uncertain. We report a case in a 55-year-old man.

[Endocarditis due to Coxiella burnetti despite the absence of obvious exposure]. / Endocardite à Coxiella burnetti en l'absence d'exposition évidente.

Q fever is an ubiquitous zoonotic disease caused by Coxiella burnetti, an intracellular Gram negative bacteria. It may present as an acute or a chronic disease course. Endocarditis due to Coxiella burnetti represents 1 to 5% of all infectious endocarditis. We report a 41-year-old man without obvious exposure history, who presented with a Q fever endocarditis.

Selenoprotein P, rather than glutathione peroxidase, as a potential marker of septic shock and related syndromes.

BACKGROUND/AIMS: Oxidative stress is involved in sepsis-related endothelium dysfunction. Selenoprotein-P (Sel-P), the main plasma selenoprotein, may have high antioxidant potential, and binds to endothelium. We hypothesize that, in septic shock, and similar syndromes such as systemic inflammatory response syndrome (SIRS), Sel-P binds massively to endothelium, causing a drop in Sel-P plasma concentration. METHODS: Plasma Se, Sel-P and albumin concentrations, and glutathione peroxidase (GPx) activity were measured in patients with septic shock and SIRS with organ failure (S group, n = 7 and n = 3, respectively) admitted to the intensive care unit (ICU) and compared to non-SIRS patients (NS group, n = 11) and healthy volunteers (HV group, n = 7). RESULTS: On ICU admission, plasma Sel-P concentrations were 70% lower in the S group than in the other groups [15 (10-26) vs. 44 (29-71) and 50 (45-53) nmol/l] and were lower in nonsurviving septic-shock patients. GPx activity did not differ between groups. Sel-P was significantly lower before ICU death in the 3 deceased patients of the S group (septic shock) than in the 3 patients of the non-SIRS group. CONCLUSIONS: Early decrease in Sel-P plasma concentrations was specifically observed in septic shock and was similar in SIRS patients whereas GPx activity remained unchanged. Further studies are needed to determine whether Sel-P can be an early marker of septic shock linked to microvascular injury.

[PSA kinetics after radiotherapy]. / Cinétique de PSA après radiothérapie.

The prostate specific antigen (PSA) is the best marker of the prostate cancer today although not very specific of this pathology. The dynamic interpretation of this marker always has to prevail over that of overtaking a threshold. After radiotherapy, PSA can decrease after a mean interval of one to two years to a value less than 1 microg/L (predictive of recurrence-free survival). Biochemical recurrence after radiotherapy is defined by an increase of PSA by 2 microg/L or more above the PSA nadir, whether or not it is associated with endocrine therapy. The time of appearance of the recurrence and the PSA doubling time after total radiotherapy have a diagnostic value on the nature of the site of recurrence, local or metastatic.

[PSA kinetics after total prostatectomy]. / Cinétique du PSA après prostatectomie totale.

The prostate specific antigen (PSA) is the best marker of the prostate cancer today although not very specific of this pathology. The dynamic interpretation of this marker always has to prevail over that of overtaking a threshold. With the lack of residual cancer, PSA becomes undetectable by the first month after total prostatectomy: less than 0.1 microg/L. The type of diminution mono- or biphasic of the marker depends on the chronology of the takings. Faced with residual cancer, PSA either does not become undetectable or increases after an initial undetectable period. A recurrence is defined by a value of PSA higher than 0.2 microg/L and confirmed on two successive assays. The time of appearance of the recurrence and the PSA doubling time after total prostatectomy have, with the initial clinical stage and the Gleason score, a diagnostic value on the nature of the site of recurrence, local or metastatic.

[Nephelometry or turbidimetry for the determination of albumin, ApoA, CRP, haptoglobin, IgM and transthyretin: which choice?]. / Turbidimétrie ou néphélémétrie: quel choix pour les dosages de l'albumine, l'ApoA, la CRP, l'haptoglobine, l'IgM et la transthyrétine?

Nephelometry, which is considered as the reference method for serum proteins determination requires a specific equipment. The majority of protein determinations are therefore carried out on biochemistry automats using turbidimetry. The objective of a CNBH group (Collège national de biochimie des hôpitaux) was to compare nephelometry and turbidimetry for 7 automats: 2 nephelometers, the BN Prospec (Dade-Behring) and Immage (Beckman-Coulter) and 5 biochemistry systems using turbidimetry, the Integra and Modular (Roche Diagnostics), the LX20 (Beckman-Coulter), RXL (Dade-Behring) and AU (Olympus). The study was based on the determination of sera collections (albumin, ApoA, CRP, haptoglobin, IgM, transthyretin) of 140 samples each: 110 limpid samples and 30 samples called HLI (hemolytic, lipemic or icteric). Fifteen hospitals took part to this work. An ANOVA analysis on limpid samples and quality control sera concluded to an "automat" effect for the 6 tested proteins but did not show a "method" effect, (i.e. nephelometry versus turbidimetry). On the other hand, the transferability of the results was expected to be better and an effort on the choice of the antibodies and the standardization procedures should be made.

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.

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.

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.

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.

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.

[6-mercaptopurine levels and study of blood lymphocyte subsets during azathioprine treatment of Crohn's disease]. / Dosage de la 6-mercaptopurine et étude des sous-populations lymphocytaires sanguines au cours du traitement par l'azathioprine dans la malaide de Crohn.

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.

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.

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.

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.

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.

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.

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.