Hyperprolinemia is a risk factor for schizoaffective disorder.

DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case-control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P=0.02, Odds ratio=4.6, 95% confidence interval 1.3-16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and we found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an intermediate phenotype associated with certain forms of psychosis.

Effect of enteral glutamine on leucine, phenylalanine and glutamine metabolism in hypercortisolemic subjects.

The effect of enteral Gln on protein and Gln metabolism was investigated during experimental hypercortisolemia. Four groups of subjects that had received corticosteroids and either enteral Gln (0.5 g x kg(-1) x day(-1) for 2 days) or isonitrogenous Ala-Gly were studied in a fasted or in a fed state. In either state, enteral Gln, compared with Ala-Gly, induced no statistically significant change in the endogenous rate of Leu appearance, an index of proteolysis, Leu oxidation, and nonoxidative Leu disposal, an index of protein synthesis, as studied by kinetics of [1-(13)C]Leu. Similar data were obtained from kinetics of [(2)H(5)]Phe, resulting in an unchanged protein balance in both cases. In contrast, enteral Gln significantly decreased the endogenous rate of Gln appearance and Gln de novo synthesis in the fed state (P < 0.05) as estimated by the kinetics of [(15)N]Gln. This decrease in Gln de novo synthesis induced by Gln could contribute to spare amino acids in hypercatabolic patients.

Low levels of glutathione in endoscopic biopsies of patients with Crohn's colitis: the role of malnutrition.

BACKGROUND AND AIMS: During active Crohn's disease, generation of free radicals is increased, and nutritional depletion is frequent. We investigated the glutathione concentration of the colonic mucosa in biopsies from patients with active Crohn's colitis depending on nutritional status. METHODS: Endoscopic biopsies were taken in 10 well-nourished control patients, and 18 patients with active Crohn's disease (11 well-nourished, seven malnourished with a recent weight loss > 10 %). Colonic biopsies were taken from healthy and inflamed mucosa and analysed for total glutathione concentration. RESULTS: Mucosal glutathione concentration (nmol/mg wet tissue) was lower in patients with active colitis both in diseased and healthy mucosa as compared with controls (1.89 +/- 0.39, 2.08 +/- 0.4 and 6.69 +/- 4. 94, respectively, P< 0.05). Mucosal glutathione was lower in healthy mucosa from malnourished versus well-nourished patients: 1.8 +/- 0.2 vs 2.3 +/- 0.37 (P= 0.02). CONCLUSIONS: Mucosal glutathione is markedly lower in active Crohn's colitis, even in healthy mucosa; glutathione depletion tends to be more severe in malnourished patients. Glutathione depletion may be related in part to malnutrition and contribute to a prolonged evolution of disease and could be a target for pharmacological and nutritional support.

Effects of an isotonic oral rehydration solution, enriched with glutamine, on fluid and sodium absorption in patients with a short-bowel.

AIM: To compare the effects of a standard oral rehydration solution with a polymeric glucose isotonic solution enriched with glutamine on water and sodium absorption in the short bowel. METHODS: Six patients with high jejunostomy were tested in a random order on 2 consecutive days with the standard solution (20 g/L glucose, 94 mmol/L sodium, 292 mOsm/kg osmolality) and a solution containing maltodextrins (18 g/L Glucidex 12; hydrolysis of 18 g of Glucidex 12 yields 20 g glucose) enriched with 14.6 g/L of glutamine (94 mmol/L sodium, 282 mOsm/kg osmolality). Solutions were administered via a naso-gastric tube at a rate of 2 mL/min. Jejunal effluent for each solution was collected during an 8-h period, after a 14-h equilibrium period. RESULTS: The net 8-h fluid absorption was not significantly different between the standard solution and the solution with glutamine (333 +/- 195 and 213 +/- 251 mL, respectively (mean +/- S.E.M.)). Net sodium absorption was higher for the standard solution than for the solution with glutamine (15 +/- 15 vs. 2 +/- 20 mmol, P < 0.05). The rate of glucose absorption was not different between the solutions. CONCLUSION: The replacement of glucose by maltodextrins and the addition of glutamine to the standard oral rehydration solution, without changing its sodium content or osmolality, results in a reduction of sodium absorption in the short-bowel syndrome.

[Myocardial adaptation to ischemia. A study during repeated prolonged coronary occlusions in angioplasty]. / Adaptation du myocarde à l'ischémie. Etude au cours d'occlusions coronaires répétées et prolongées pour angioplastie.

Coronary angioplasty provides an ideal model for studying ischemic preconditioning in humans. Four coronary occlusions, each lasting 5.2 +/- 1.3 min, separated by 3 min of reperfusion, were performed during angioplasty of isolated stenosis of the left anterior descending artery of 18 patients with stable angina and normal left ventricular function. The ischaemia was evaluated and compared during the first and fourth coronary occlusion with the aid of clinical, electrocardiographic, echocardiographic and metabolic parameters. We analysed: 1) interval to chest pain and its intensity; 2) degree of ST change on the intracoronary electrocardiogram; 3) regional wall motion abnormalities on 2D echocardiography; 4) coefficient of myocardial lactate extraction. The results showed that during the fourth occlusion: chest pain occurred later (93 +/- 57 vs 60 +/- 49 s; p < 0.05) and ST elevation was less (0.69 +/- 0.5 vs 1.03 +/- 0.8; p < 0.05). During the fourth occlusion, there was a delay in appearance and a decrease in the regional wall motion abnormalities: anterior wall hypokinesia occurred later: 26 +/- 15 vs 19 +/- 19 s (p = 0.08). Akinesia observed in 10 patients out of 13 (77%) during the first occlusion, was only observed in 8 patients (62%) and dyskinesia, observed in 5 patients out of 13 (38%) during the first occlusion was not observed thereafter in any patient. The production lactate was less important during the fourth occlusion than during the first one: -3 +/- 17% vs -12 +/- 19% (p < 0.05). This study confirms that, in man, preconditioning allows myocardial adaptation to successive episodes of acute ischaemia.

Influence of antibiotics and food intake on liver glutathione and cytochrome P-450 in septic rats.

Experimental sepsis in rats induces a restriction in spontaneous food intake and a drop in liver glutathione, cytochrome P-450 (P-450) and aminopyrine demethylase (AD) activity. The present study was designed to assess the effects of antibiotics alone or when combined with food deprivation on these variables. Eighty-nine male Sprague-Dawley rats were assigned to six groups: control (C), acute infection (experimental pyelonephritis, I), acute infection with antibiotics and food given ad lib. (IA), control with antibiotics (CA), acute infection with antibiotics pair-fed to I (IAR), and sham-operated pair-fed to I (SR). Liver glutathione, P-450 and AD activities were reduced by 45.2, 79.8 and 41.2% respectively in group I. Glutathione and AD significantly increased only in those infected rats given antibiotics and allowed free access to food. P-450 did not normalize within the study period in infected rats receiving antibiotics and food repletion. The risk of drug hepatotoxicity in acute septic states is therefore closely related to the nutritional status. From this point of view, nutritional support is almost as important as treatment of infection.

Metabolic effects of propofol and flunitrazepam given for sedation after aortic surgery.

Sixteen patients who had undergone abdominal aortic surgery were allocated randomly to receive either propofol (total dose 3.2 (SEM 0.3) mg kg-1 h-1) or flunitrazepam (total dose 15 (2) micrograms kg-1 h-1) for 16 h after operation. Metabolic effects of sedation were assessed using a Deltatrac metabolic monitor. Initiation of sedation induced a 25% decrease in VO2 in both groups. The decrease was about 40% at 16 h. VO2 increased within 30 min after discontinuation of propofol and stabilized at values considerably less than the immediate postoperative value. A similar but slower increase was noted with flunitrazepam. While the propofol loading dose reduced the Buffington index and should therefore be avoided, no cardiovascular side effects were noted with the maintenance infusion. Weaning from ventilatory support was achieved within 15 (2) min and 264 (108) min after discontinuation of propofol and flunitrazepam, respectively.

Liver factors involved in drug metabolism in experimentally infected rats: deleterious effect of ornithine alpha-ketoisocaproate.

This study was designed to determine the effect of ornithine alpha-ketoisocaproate (O-KIC), a compound reducing muscle protein breakdown in physiological conditions, on liver factors involved in drug metabolism in rats with acute retrograde pyelonephritis. 91 rats were assigned to 7 groups differing in the level of food intake, induced infection, and the treatment by O-KIC (168 mg/kg bw/day). Rats were killed on the third day. O-KIC increased nitrogen balance and weight gain in controls, but not in malnourished infected or non-infected rats. Liver glutathione was significantly reduced by O-KIC in malnourished infected and non-infected rats. Though O-KIC induced a rise in liver microsomal proteins in control and infected animals, it decreased cytochrome P-450 in controls, and aminopyrine demethylase in both control and infected groups.

Liver glutathione and cytochrome P450 activity in experimental infection: study of the relative effects of infectious stress and malnutrition.

OBJECTIVE: To study the effects of infection and malnutrition on liver glutathione and cytochrome P450 (P450) in rats. DESIGN: Controlled experimental groups (12 groups). ANIMALS: Adult male Sprague-Dawley rats. INTERVENTIONS: Experimental endocarditis, pyelonephritis, or peritonitis were caused. Controls included free-fed rats and sham-operated rats, pair-fed to infected animals. Infection was verified by tissue culture. Rats were killed 3 days (acute infection) or 10 days (chronic infection, except endocarditis) after the induction of infection. RESULTS: Sham rats had lower liver weights, liver/body weight, and liver glutathione values than controls. Infected rats had larger liver weights and liver/body weight ratios and liver glutathione content than shams, and larger liver/body weight ratios than controls (acute infection). Infected rats had lower P450 values than both shams and controls. CONCLUSION: The malnutrition associated with infection caused decreased liver weight and glutathione content. Infection increased the liver weight, and liver glutathione content, but caused severe reduction in liver P450. If the same finding is true in infected patients, it could have consequences for the management of such patients.

Absorption and metabolic effects of enterally administered glutamine in humans.

To assess absorption and metabolic effects of enterally delivered glutamine, a total of 10 healthy subjects received perfusions of natural L-glutamine at graded infusion rates (ranging from 0 to 126 mmol/h; n = 2-8 subjects at each rate) along with a nonabsorbable marker (polyethylene glycol) through a double-lumen nasojejunal tube. Perfusions were administered after an overnight fast during three consecutive 1- or 2.5-h periods and in a randomized order. In eight subjects, continuous intravenous infusion of D-[6,6-2H2]glucose, L-[1-13C]leucine, and L-[15N]alanine was simultaneously performed. Glutamine was nearly quantitatively absorbed over the 30-cm study segment; estimated Km and Vmax of glutamine absorption were 2.48 and 2.32 mmol/min over the 30-cm study segment. Enteral glutamine administration induced 1) a dose-dependent increase in plasma glutamine level; 2) a rise in the plasma level and appearance rate (Ra) of alanine (from 191 +/- 42 to 213 +/- 51 mumols.kg-1.h-1, P less than 0.05, for 0 and 46.8-mmol/h glutamine infusion rates, respectively) and in plasma levels of glutamate, citrulline, aspartate, and urea; 3) a decline in plasma free fatty acid and glycerol levels; and 4) no change in leucine or glucose Ra. We conclude that glutamine is efficiently absorbed by human jejunum in vivo and may directly inhibit lipolysis, whereas it neither affects proteolysis nor glucose production in healthy postabsorptive humans.

[Hereditary hyperoxaluria or oxalosis. Apropos of a case]. / L'hyperoxalurie héréditaire ou oxalose. A propos d'un cas.

We report a case of primary oxalosis in a 12-year old girl. This unusual observation exemplifies two diagnostic pitfalls, i.e. false urinary tract infections and technical difficulties in accurately measuring oxalate urinary excretion. On the basis of this case and a review of the literature, we discuss diagnostic and therapeutic methods. Early diagnosis of the disease is important in order to monitor the patient and provide genetic counseling.

Comparison of the effects of continuous and cyclic nocturnal parenteral nutrition on energy expenditure and protein metabolism.

Although cyclic nocturnal total parenteral nutrition is a widely used technique, its metabolic consequences have not been fully investigated. During two successive 7-day periods, 12 patients received randomly either standard continuous (infusion 24 hr/day) or cyclic (infusion between 5 pm and 9 am) total parenteral nutrition (TPN). Calorie and nitrogen intakes were identical during both periods. Energy expenditure was investigated by indirect calorimetry and showed practically no difference between continuous standard (1383 +/- 41 kcal/day-1) and cyclic total parenteral nutrition (1428 +/- 46 kcal/day-1). However, in the cyclic regimen, when compared with continuous infusion, energy expenditure was higher between 5 pm and 9 am and lower between 9 am and 5 pm. At the end of the noninfusion period, the 24-hr profile of the nonprotein respiratory quotient showed a slight decrease in patients receiving the cyclic infusion, in contrast with the stability of the quotient in the standard regimen. However, the nitrogen balance and variations in nutritional status did not differ significantly. In conclusion cyclic TPN is efficient for achieving a positive energy and nitrogen balance and in addition it induces a metabolic profile closer to physiological conditions.

Angina pectoris with angiographically normal coronary arteries: a clinical, hemodynamic, and metabolic study.

Seventy-six patients with anginalike chest pain (ALCP) and angiographically normal coronary arteries (NCA) had a study of the myocardial metabolism at rest and during maximal atrial pacing. The results were compared with pain characteristics, electrocardiogram, left ventricular, and coronary hemodynamic data. Coronary blood flow (CBF) was measured by continuous thermodilution. At maximal paced heart rate, the study of the myocardial metabolism distinguished two groups: (1) a first group of 50 patients whose lactate extraction coefficient was equal to or exceeded 9% and was considered as normal (Gr. I, K greater than or equal to 9%); (2) a second group of 26 patients whose lactate extraction coefficient was below 9% (Gr. II, K less than 9%), significant of myocardial ischemia. In group I (K greater than or equal to 9%), chest pain was usually atypical (typical in only 25% of cases) and rapid atrial pacing most often caused neither pain nor ECG changes. The hemodynamic and angiographic study showed minor alterations of the left ventricular cavity in 50% of cases. In group II (K less than 9%), chest pain was typical in 50% of the patients and maximal atrial pacing most often caused chest pain (85%) and ST-segment depression (80%). In almost every case, the left ventricular and the coronary angiograms were normal. Only in this group, which had clinical, electrical, and metabolic signs of myocardial ischemia, could the diagnosis of angina pectoris with angiographically normal coronary arteries be upheld.(ABSTRACT TRUNCATED AT 250 WORDS)

[Angina pectoris with normal coronary arteries: clinical, hemodynamic and metabolic study]. / L'angine e poitrine avec artères coronaires normales: étude clinique, hémodynamique et métabolique.

Sixty patients without organic heart disease presenting with chest pain suggestive of angina pectoris and angiographically normal coronary arteries underwent clinical, hemodynamic and metabolic investigation. The study of myocardial lactate metabolism during atrial pacing (168 +/- 14 bpm) allowed identification of two groups: --40 patients with a normal coefficient of lactate extraction (K greater than or equal to 9 per cent); --20 patients with a pathologically low coefficient of lactate extraction (K less than 9 per cent) reflecting myocardial ischemia. In the first group, chest pain was often atypical (75 per cent of cases). Hemodynamic investigation showed minor abnormalities of the left ventricle in 48 per cent of cases. The diagnosis of angina was rejected in these patients. In the second group, the majority of patients developed chest pain (85 per cent of cases) at the maximal heart rate with significant ST depression (80 per cent of cases). The chest pain was typical of angina pectoris in 50 per cent of cases. Hemodynamic and angiographic investigation of the left ventricle was completely normal in nearly all cases. Only these patients with clinical, electrocardiographic and metabolic signs of myocardial ischemia can be considered as having angina with normal coronary arteries. Although studies of myocardial lactate metabolism and other signs of myocardial ischemia distinguish clearly between these two groups of patients, the coronary hemodynamics were similar. Resting coronary flow, its increase for the same myocardial oxygen demands and coronary resistances were comparable in both groups, and not significantly different from the values obtained in a control group of patients without coronary artery disease or chest pain. These results confirm that about 30 per cent of patients investigated for chest pain suggestive of angina pectoris who have angiographically normal coronary arteries, develop signs of myocardial ischemia during atrial pacing. The physiopathological explanation remains unclear as coronary hemodynamics have been found to be normal.