3-hydroxyisobutyric aciduria with a mild clinical course.
Explore the source record for details and available documents.
Fatty Acids, Volatile↗
Biomedical subjects
E Girardin
Publications and source records attributed to E Girardin.
Renal handling of carnitine in ill preterm and term neonates.
OBJECTIVE: To investigate the renal handling of carnitine in preterm and term ill neonates. METHODS: We studied the fractional tubular reabsorption of carnitine and the proximal renal tubular function of infants in the first week of life who were receiving very little or no carnitine in their diets. RESULTS: Mean plasma levels were low: total carnitine was 16.4 +/- 7.0 mumol/L, free carnitine was 9.2 +/- 5.0 mumol/L, and acylcarnitine was 7.2 +/- 4.1 mumol/L. The most premature group of neonates (gestation age, 26 to 31 weeks) had a fractional tubular reabsorption rate of free carnitine of 94.3% +/- 3.3%, which was lower than in the other two groups (98.1% +/- 2.4% for gestational age 32 to 36 weeks, p = 0.001; and 99.2% +/- 0.6% for gestational age 37 to 42 weeks, p = 0.002). In all patients the fractional tubular reabsorption of acylcarnitine was lower than that of free carnitine, indicating possible tubular secretion of acylcarnitine. It correlated with the total plasma carnitine levels (r = 0.53; p = 0.002). The fractional tubular reabsorption of free carnitine also correlated with gestational age (r = 0.60; p < 0.001). CONCLUSIONS: Ill neonates have a fractional tubular reabsorption rate of free carnitine within the normal range. It increases with gestational age, and has the same maturation rate as the other known indexes of proximal tubular function.
Carnitine↗
Cortical scintigraphy in the evaluation of renal parenchymal changes in children with pyelonephritis.
We designed a prospective study to evaluate the ability of dimercaptosuccinic acid cortical scintigraphy and ultrasonography to detect renal parenchymal lesions in children with pyelonephritis. One hundred eleven patients 1 week to 16 years of age (median 5.5 months) with a urine culture positive for pathogens were included in the study; cortical scintigraphy and ultrasonography were repeated in 25 children after a mean follow-up of 10.5 months. Cortical scintigraphy showed renal changes in 74 children (67%), and ultrasonography showed renal changes in 39 (35%) (p < 0.001); results of the two examinations were discordant in 49 patients (kappa = 0.19). Children more than 1 year of age had a higher incidence of renal lesions than did younger children (85% vs 66%; p = 0.04). The presence of inflammatory signs (erythrocyte sedimentation rate or C-reactive protein) had an 89% sensitivity and a 25% specificity in identifying renal lesions. Among children with renal changes, vesicoureteric reflux was present in 39%. At follow-up examination, 16 children (64%) had scars. Thus we found a high incidence of renal involvement in children with pyelonephritis. We found that cortical scintigraphy is more sensitive than ultrasonography in detecting renal changes, and we believe that it should be added to the initial examination of children with suspected pyelonephritis.
Adolescent↗
Early hemodynamic and renal effects of tumor necrosis factor alpha: role of thromboxane.
TNF alpha is an early mediator of endotoxemic shock. Its acute effect on renal hemodynamics is not known. In this study, the early hemodynamic and renal effects of TNF alpha were investigated in a rabbit model of shock, in which the measurement of the aortic blood flow before the bifurcation of the renal arteries allows one to differentiate between prerenal factors and hemodynamic renal response. Six groups of rabbits were studied, receiving either: (1) endotoxin, (2) endotoxin + thromboxane inhibitor Dazmegrel, (3) TNF alpha, (4) TNF alpha + Dazmegrel, (5) TNF alpha+indomethacin, or (6) placebo. Between 60 min and 3 hr after the injection, endotoxin induced a mean fall in arterial pressure of 32% (P < 0.01) and TNF alpha of 16% (P < 0.01). After endotoxin, the aortic blood flow decreased by 27% (P < 0.01) and after TNF alpha by 18% (P < 0.001). Both specific thromboxane inhibition and indomethacin abolished the TNF alpha central hemodynamic effect. The renal blood flow (-53%), the renal fraction of the aortic blood flow (-38%), and the glomerular filtration rate (-47%, P < 0.05) decreased 1 hr after endotoxin injection. In contrast, TNF alpha induced only a slight fall of the renal fraction of the aortic blood flow (-19%) after 2.5 hr. Glomerular filtration was not modified after TNF alpha injection most likely because of a 17% mean increase of filtration fraction in this group (P < 0.001). These data indicate that TNF alpha is implicated in the early hemodynamic changes of endotoxemic shock.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Cytokines and antagonists in septic shock].
During septic shock, cytokines produced by host cells play an important role in the pathogenesis of hemodynamic involvement and cellular lesions. Recently, natural inhibitory substances able to neutralize the biological activity of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) were described. These inhibitory molecules are involved in the regulation of the production of these cytokines. Thus, an understanding of these mechanisms could lead to new treatments for septic shock. A review of the interactions of TNF alpha with macrophages, neutrophils and endothelium underlines the key role of TNF alpha in 3 important events of septic shock: neutrophil adherence to endothelium, capillary leak syndrome, and development of disseminated intravascular coagulopathy. In clinical studies, circulating TNF alpha concentrations were elevated and correlated with the severity of the disease. Soluble TNF receptors (TNF-sRI and TNF-sRII) neutralize the biological effect of TNF alpha. Their circulating levels are also increased in meningococcemia, but an imbalance between TNF alpha and TNF-sR was found at the beginning of the disease which could determine the severity of the shock in these patients. The IL-1 system is composed of IL-1 alpha and IL-1 beta, two forms of precursors, two distinct receptors, two soluble fragments of the extramembranous regions of these receptors, and a natural antagonist of IL-1 receptors (IL-1 ra) which could be secreted or remain intracellular. IL-1 ra improved the outcome in some experimental diseases (endotoxemic shock, cerebral malaria arthritis, graft-versus-host reaction). The treatment of septic shock with IL-1 ra is currently being assessed in phase I and II clinical studies. Blockade of cytokines by antibodies or naturally occurring inhibitory molecules could lead to new therapies for septic shock.
Cytokines↗
Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes.
Clinical or biochemical findings were reevaluated in 34 pediatric patients with primary renal tubular hypokalemic metabolic alkalosis. The patients were subdivided into two groups. Bartter syndrome (primary renal tubular hypokalemic metabolic alkalosis with normocalciuria or hypercalciuria) was diagnosed in 18 patients with molar urinary calcium/creatinine ratios greater than 0.20, and Gitelman syndrome (primary renal tubular hypokalemic metabolic alkalosis with magnesium deficiency and hypocalciuria) was diagnosed in 16 patients with molar urinary calcium/creatinine ratios less than or equal to 0.20 and plasma magnesium levels less than 0.75 mmol/L. Some clinically important differences between the groups were observed. Patients with Bartter syndrome were often born after pregnancies complicated by polyhydramnios (8/18) or premature delivery (7/18) and had short stature (11/18) or polyuria, polydipsia, and a tendency to dehydration (16/18) during infancy (12/18) or before school age (18/18). Patients with Gitelman syndrome had tetanic episodes (12/16) or short stature (3/16) at school age (14/16). We conclude that the Bartter and Gitelman syndromes represent two distinct variants of primary renal tubular hypokalemic metabolic alkalosis and are easily distinguished on the basis of urinary calcium levels.
Alkalosis↗
Serum and intracellular magnesium during normal pregnancy and in patients with pre-eclampsia.
OBJECTIVE: To determine the serum and lymphocyte magnesium concentrations during normal pregnancy and to compare the magnesium status in the third trimester of pregnancy between women with normal pregnancy and those with gestational hypertension (GH) or pre-eclampsia (PE). DESIGN: A prospective cross-sectional study followed by a prospective comparative study. SETTING: Department of Obstetrics and Gynecology, Department of Pediatrics and Genetics, Hôpital Cantonal Universitaire Genève, Switzerland. SUBJECTS: Seventy-one healthy pregnant women, with normal pregnancies between 6 and 38 weeks gestation. The second part included 43 women in the third trimester of pregnancy, 11 had GH, 11 had PE and 21 formed the comparison group of healthy normotensive women. MAIN OUTCOME MEASURES: Total serum and intralymphocytic Mg concentrations and urinary Mg excretion. RESULTS: There was a progressive reduction in total serum magnesium concentrations during normal pregnancy, thought to be partly due to haemodilution, because the decline in concentration of serum proteins paralleled that of Mg (P less than 0.001). In the three groups studied in the third trimester the serum Mg concentration was very similar in the GH and the comparison groups, but it was significantly higher in the PE group (P less than 0.01). The intralymphocytic Mg concentrations and the urinary Mg excretion were similar in all three groups. In five patients treated with MgSO4 there was a large increase in the serum Mg concentration and in the urinary Mg excretion. The intralymphocytic Mg concentration remained remarkably stable. CONCLUSIONS: Our data does not support the conclusion that Mg deficiency is the primary cause of pre-eclampsia.
Cross-Sectional Studies↗
High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis.
Intrapulmonary activation of leukocytes and release of cellular mediators and enzymes are involved in the pathophysiology of the adult respiratory distress syndrome (ARDS). To investigate a possible role of local cytokines, we measured bronchoalveolar fluid (BALF) and plasma levels of tumor necrosis factor alpha (TNF-alpha) and its soluble inhibitors (sTNF-RI + RII), interleukin-1 beta (IL-1 beta), interferon-alpha (IFN-alpha), and granulocyte elastase in 14 patients at risk for ARDS and in 35 patients developing ARDS after trauma, sepsis, or shock. During clinical development of severe ARDS, BALF cytokines increased markedly: TNF-alpha from 116 +/- 36 to 10,731 +/- 5,048 pg/ml (mean +/- SEM), p = 0.001; sTNF-RI + RII from 3.7 +/- 1.4 to 24.6 +/- 2.6 ng/ml, p less than 0.05; and IL-1 beta from 7,746 +/- 5,551 to 42,255 +/- 19,176 pg/ml, p = 0.01. Plasma cytokines were not increased in most patients, nor were they correlated with the development or severity of ARDS. BALF elastase was higher in patients developing ARDS than in those at risk but not going into pulmonary failure (0.97 +/- 0.26 versus 0.28 +/- 0.13 U/ml, p = 0.026), and the highest values were observed in the early stages of severe ARDS (1.85 +/- 0.39 U/ml). BALF elastase levels correlated with IFN-alpha (r = 0.72, p less than 0.001). In conclusion, local release of TNF-alpha and IL-1 beta, possibly by pulmonary macrophages or other cells, and/or accumulation in the lung is associated with the development of ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchoalveolar Lavage Fluid↗
Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. The J5 Study Group.
The extracellular domain of tumour necrosis factor-alpha (TNF-alpha) receptors have inhibitory properties against TNF-alpha. The relative ratio between ligand and ligand inhibitors may influence the outcome of meningococcaemia. To test this hypothesis, levels of TNF-alpha and of each of the soluble inhibitory fragments originating from two distinct TNF-alpha receptors (sTNF-RI and sTNF-RII) were measured in sera of children with severe meningococcaemia. On admission to the hospital the levels of sTNF-RI, -RII and TNF-alpha were markedly increased and all three correlated with the outcome of the disease. A correlation was found between TNF-alpha and sTNF-RI (P less than 0.001 by Pearson rank correlation coefficient) or sTNF-RII (P = 0.012). For TNF-alpha concentrations below 500 pg/ml, the increase of TNF-alpha was proportional to that of sTNF-RI and RII; however, when TNF-alpha levels exceeded 500 pg/ml, sTNF-RI and RII concentrations did not increase proportionally. At admission, in patients with fatal outcome, the ratios TNF-alpha/sTNF-RI and -RII were higher than in survivors. During the first 6 hr, the kinetics of TNF-alpha, sTNF-RI and -RII were different. Naturally occurring TNF-alpha inhibitors may play an important role in modulating the biological activity of TNF-alpha in severe meningococcaemia.
Bacteremia↗
[Hypoglycemia induced by oral hypoglycemic agents. Records of the French Regional Pharmacovigilance Centers 1985-1990].
All 98 cases of sulfonylurea-induced hypoglycemia reported by the 30 regional drug-monitoring centers between 1985 and 1990 were analyzed: 46 with gliclazide, 40 with glibenclamide, 5 with glipizide, 1 with glibornuride and 6 with first-generation sulfonylureas. These cases of hypoglycemia were often serious. The patients were 61% female and their mean age was 78.9 years. The average number of medications being taken was 3.4, but ranged up to 14. The risk factors were: reduced food intake (4.2%), renal failure (4.2%), prescription error (3.2%), voluntary or accidental overdose (5.2%), alcohol (1.1%), suspected drug interactions (50%), unknown (32.6%). The most frequent drug interactions involved miconazole (8 cases), angiotensin-converting enzyme inhibitors (9 cases), lipid-regulating agents (fibrates) (7 cases), co-trimoxazole (trimethoprim-sulfamethoxazole; 5 cases), metformin (4 cases), histamine H2-receptor antagonists (4 cases). The mechanisms of these interactions are discussed.
Administration, Oral↗
Pyridoxine-dependent seizures, clinical and therapeutic aspects.
Pyridoxine-dependency is a rare autosomal recessive disorder causing a severe seizure disorder of prenatal or neonatal onset, psychomotor retardation and death in untreated patients. Treatment requires life-long supplementation with pyridoxine (vitamin B6). The underlying defect is unknown, and there is no biological marker for the disease. Clinical diagnosis is often delayed and severe neurological sequelae are common. This article summarizes both clinical and therapeutic aspects.
Female↗
Glucocorticoid receptors in lymphocytes in anorexia nervosa.
OBJECTIVE: The aim was to explore the down-regulation of the glucocorticoid receptors during hypercortisolaemia in anorexia nervosa. DESIGN: Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were isolated for receptor binding studies. PATIENTS: Sixteen anorexic patients, aged 16-27 years, with a mean +/- SEM body mass index of 14.2 +/- 2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied. Six patients were reinvestigated after a significant weight gain. MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured with dexamethasone as ligand on lymphocytes. RESULTS: In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of glucocorticoid receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687 +/- 1750 vs 7347 +/- 1285 sites/cell; Kd: 7.7 +/- 2.4 vs 7.4 +/- 1.7 nM at 24 degrees C). After weight gain (14 +/- 2 to 16 +/- 2 kg/m2), receptor numbers were 8421 +/- 2126 (pre) and 9011 +/- 500 (post) sites/cell, which are not significantly different (P greater than 0.2); the Kd was unchanged (9.3 +/- 2.6 vs 9.2 +/- 2.4 nM). CONCLUSIONS Hypercortisolaemia does not down-regulate the lymphocyte glucocorticoid receptors in anorexia nervosa and a post-receptor defect might be involved in peripheral tissue resistance to the effects of glucocorticoid hormones in undernutrition.
Adolescent↗
Atrial natriuretic factor in patients with congenital heart disease: correlation with hemodynamic variables.
To investigate the alpha-atrial natriuretic factor in congenital cardiac malformations, three groups of children, aged 7 months to 16 years, with different hemodynamic situations were studied during routine cardiac catheterization. Twenty-one (group I) had tetralogy of Fallot, 24 (group II) had a left to right shunt with pulmonary hypertension and 12 (control group) had a minor cardiac lesion. Alpha-atrial natriuretic factor levels were determined by a radioimmunoassay on blood samples from the inferior vena cava, right atrium, pulmonary artery, left atrium and aorta. To evaluate the effect of an acute volume load, measurements of hormone and pressures were repeated after right ventriculography. Alpha-atrial natriuretic factor levels varied over a wide range in all groups and in all chambers investigated. Nevertheless, children with pulmonary hypertension had significantly higher levels of the hormone (p less than 0.01) and were well separated from the control group, but less well from those with tetralogy of Fallot. A 50% increase of alpha-atrial natriuretic factor from the inferior vena cava to the right atrium occurred in patients with shunt lesions with pulmonary hypertension and in patients with tetralogy of Fallot (p less than 0.001) and a further 30% increase from the right atrium to the pulmonary artery (p less than 0.05). After right ventriculography, a 100% to 200% increase of alpha-atrial natriuretic factor was observed in the total sample (p less than 0.001). A positive correlation was observed between right atrial mean pressure and right atrial alpha-atrial natriuretic factor (r = 0.63) and between pulmonary artery mean pressure and pulmonary artery alpha-atrial natriuretic factor (r = 0.61).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Cytokines and meningococcemia].
Explore the source record for details and available documents.
Animals↗
Tumour necrosis factor in neonatal listeriosis: a case report.
A newborn with fatal neonatal listeriosis developed septic shock, neutropenia, thrombocytopenia and profound hypoxaemia due to severe pulmonary hypertension. Tumour necrosis factor alpha, interleukin-1-beta and interferon-gamma serum concentrations were markedly elevated, suggesting the participation of these cytokines in the aetiopathogenesis of shock induced by Listeria monocytogenes in the neonate.
Amoxicillin↗
Relation between tumor necrosis factor-alpha and granulocyte elastase-alpha 1-proteinase inhibitor complexes in the plasma of patients with cystic fibrosis.
Patients with cystic fibrosis suffer from a chronic, progressively destructive bronchitis characterized by colonization of the airways by Pseudomonas aeruginosa. Cell wall lipopolysaccharides from P. aeruginosa may stimulate secretion of cytokines such as tumor necrosis factor alpha (TNF alpha) by monocytes/macrophages. We found elevated levels of TNF alpha (150 +/- 60 pg/ml), interleukin-1 alpha (144 +/- 205 pg/ml), and interleukin-1 beta (62 +/- 100 pg/ml) in plasma from 25 patients with cystic fibrosis. In patients with less advanced disease, elevated plasma levels of TNF alpha correlated with high levels of complexes between neutrophil elastase and alpha 1-proteinase inhibitor, suggesting that TNF alpha may be a mediator of neutrophil degranulation. TNF alpha, by its chemotactic effect on neutrophils, may also contribute to the massive influx of neutrophils into and around the bronchial tree. Our findings raise the questions whether in patients with cystic fibrosis TNF alpha acts as cachectin and whether it mediates the anorexia that often results in weight loss.
Adolescent↗
Effect of low dose dopamine on hemodynamic and renal function in children.
The purpose of the study was to investigate the effect of low doses of dopamine in children. Fourteen cases were studied after open heart surgery. Cardiac output and renal parameters were determined under baseline conditions and under continuous infusion of dopamine 2.5 and 5 micrograms/kg/min. During the control period cardiac index was 2.62 +/- 0.19 L/min/m2, renal plasma flow was decreased at 269 +/- 41 mL/min/1.73 m2, GFR was 86.6 +/- 9.2 mL/min/1.73 m2, and filtration fraction was elevated at 37.1 +/- 1.9%. Plasma concentration of aldosterone correlated with the filtration fraction. At 5 micrograms/kg/min dopamine increased significantly cardiac output, renal plasma flow, and to a lesser extent GFR, thus decreasing the filtration fraction. At 2.5 micrograms/kg/min dopamine, increased renal plasma flow only in patients older than 5 y and had no effect on the other parameters. The increase of cardiac output in response to dopamine was abolished by propranolol pretreatment. By contrast, the hemodynamic renal response to dopamine was not altered by beta-blockade. These results indicate that 5 micrograms/kg/min of dopamine could prevent renal failure after open heart surgery in children by increasing renal blood flow and attenuating renal compensatory mechanisms.
Adolescent↗
Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura.
Because of the possible involvement of cytokines in gram-negative septicemia, we investigated serum levels of tumor necrosis factor alpha, interleukin-1 beta, alpha interferon, and gamma interferon in children with gram-negative sepsis and purpura fulminans. We studied 55 patients (ages, 1 month to 19 years) with a clinical diagnosis of sepsis and purpuric lesions who were in shock or had three or more other biologic risk factors. The mortality rate was correlated with the number of risk factors present on admission to the hospital (P = 0.03). Tumor necrosis factor alpha was elevated in 91 percent of the 35 patients tested, interleukin-1 in 21 percent of the 33 patients tested, and gamma interferon in 19 percent of the 32 tested. Alpha interferon levels were within normal limits in the 32 patients tested. Serum levels of tumor necrosis factor alpha were positively correlated with the number of risk factors (P less than 0.05) and negatively correlated with blood fibrinogen levels (P = 0.01). Tumor necrosis factor alpha, interleukin-1, and gamma interferon were significantly higher in patients who died than in the survivors. Alpha interferon levels were similar in the two groups. Serum concentrations of both interleukin-1 and gamma interferon were correlated with concentrations of tumor necrosis factor alpha. These data provide evidence that serum levels of tumor necrosis factor alpha, interleukin-1, and gamma interferon correlate with the severity of meningococcemia in children. The findings may have implications for new therapeutic approaches.
Adolescent↗