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 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.

[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.

[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.

[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.

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.

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.

Effect of fat-emulsion phospholipids on serum lipoprotein profile during 1 mo of cyclic total parenteral nutrition.

Changes in serum lipoprotein determined by selective precipitation were investigated in 11 adult patients during 1 mo of parenteral nutrition. Patients were divided into two groups that received a similar nutrient regimen except for Intralipid (IL) phospholipid, which was higher in group A (10% IL, n = 5) than in group B (20% IL, n = 6), 139 +/- 15 vs 71 +/- 0.5 mg.kg-1.d-1 (P less than 0.01). Lipoprotein X (LPX) detected soon after IL infusions were started reached its highest concentrations in group A. LPX concentrations correlated with phospholipid intakes on days 7 and 15 but not on day 29. Significant increases in the cholesterol and phospholipid content of low-density-lipoprotein-very-low-density-lipoprotein fractions were observed only in group A. It is suggested that these changes were induced by the twofold-higher intake of phospholipids in group A. With regard to the possible involvement of LPX in lipid overloading of the reticuloendothelial system and hepatocytes, administration of 20% IL seems preferable to 10% IL.

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.

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.

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.

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.

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.

Selenium status prior to and during one month total parenteral nutrition in gastroenterological patients: A randomised study of two dosages of Se supplementation.

13 consecutive adult gastroenterological patients with non-malignant disease who were candidates for total parenteral nutrition (TPN), and who had mild protein-energy malnutrition (82 +/- 3% of ideal body weight, serum albumin 32 +/- 2 g/l, mean +/- SEM) were found to have, prior to TPN, a Selenium level 50% less than controls (p < 0.001) as assayed by Se and glutathione peroxidase (GSHPx) in plasma and erythrocytes. Compared with other trace metals and minerals, eg, Mn, Zn and Cu, depletion of Selenium was the most marked in this population. Patients were randomised to be supplemented with either 100 or 200 microg/d of sodium-selenite, equal to 32 microg (0.4 micromol) or 64 microg (0.8 micromol) of selenium, in two cross-over periods of TPN, each of two weeks. In this short term study, significant increases in the four measurements of Se status (p < 0.05) were seen in all patients, but there was no difference between those receiving the high or low dose of the element. GSHPx in plasma was normalised within 1 month whereas the increase seen in the erythrocyte pool was consistent with a 4-month half-life. Pooled Se values for patients and controls showed logarithmic correlations between Se and GSHPx in erythrocytes (p < 0.001) and plasma (p < 0.01). Changes in GSHPx provided further evidence of Se depletion in our patients. This study suggests that malnourished gastroenterological patients receiving TPN require Se supplements and that 100 microg (0.4 micromol)/d of sodium-selenite is adequate for most patients since there was no additional benefit from the higher dose of 200 microg (0.8 micromol).

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.

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.

[D-lactic acidosis and encephalopathy in short-bowel syndrome occurring during antibiotic treatment]. / Acidose D lactique et encéphalopathie au cours d'un syndrome du grêle court à l'occasion d'un traitement antibiotique.

A 24 year-old patient with a short-bowel syndrome receiving home parenteral nutrition in addition to oral feeding for 32 months was treated by oral trimethoprim-sulfamethoxazole for urinary tract infection. Three days later, he developed neurologic disorders associated with severe hyperchloremic acidosis and high plasma level of D-lactate. This is a rare complication of intestinal malabsorption due to small bowel by-pass or extensive resection due to transient alteration of intestinal microflora induced by the oral antibiotic treatment. Diagnosis requires a high indice of suspicion.

[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.

[Lipoprotein (a)]. / La lipoprotéine (a).

Lp(a) or pre-beta 1-lipoprotein or Sinking pre-beta LP (SPB) is a special LP. Its very high density (1050 to 1120) means that it can be extracted from LDL and HDL. In common with the LDL, it possesses apo B and a similar size. It is characterized by the presence of specific apoproteins, non-immunoreactive albumin and a carbohydrate chain rich in sialic acid. Its transmission is hereditary; there is a major locus transmitted by autosomal dominant inheritance. Another hypothesis suggests that it is transmitted autosomally according to a polygenic mechanism for 75 p. cent of the molecule with superimposition of non-genetic elements for the rest. Lp(a) is not a product of Lp(b) metabolism; it is not transformed into any other LP and it does not exchange its apoproteins. Its synthesis is constant over time and its function is not yet known. Its assay depends on the antigenicity of the specific determinants of the apo Lp(a). Only radio-immunoassay is able to give values for any sample size especially for levels of less than 50 to 80 mg/l (respective limits of the EID and IDR techniques). It appears that a high Lp(a) level could constitute an additional risk to developing coronary heart disease and the limit beyond which this risk exists could be 300 mg/l in normolipidaemic subjects. The in vitro binding of LP to glycoaminoglycanes (GAG) could be a model for studying LP binding in vivo. It has been seen that, by the intermediary of a low concentration of Ca++ ions, the reactivity of Lp(a) to GAG was selective.

[Assay of serum selenium by atomic absorption spectrophotometry. Value in the biological diagnosis of nonobstructive cardiomyopathies]. / Dosage du sélénium sérique par spectrophotométrie d'absorption atomique. Intérêt dans le diagnostic biologique des cardiomyopathies non obstructives.

The authors present a technique of direct assay of serum selenium by atomic absorption spectrophotometry, using electrothermal atomization in a graphite oven. The initial results of the assays performed in patients with non-obstructive cardiomyopathies (NOCM) reveal a decrease in the serum selenium level. This element could therefore represent a laboratory marker for these diseases.