Unexpected decrease in cytogenetic biomarkers frequencies observed after increased exposure to organophosphorus pesticides in a production plant.
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Adult↗
Biomedical subjects
C Laurent
Publications and source records attributed to C Laurent.
An increased loading dose of ondansetron: a north european, double-blind randomised study in children, comparing 5 mg/m2 with 10 mg/m2.
A North European, randomised, double-blind study, comparing a loading-dose of ondansetron of 5 mg/m2 with 10 mg/m2, administered intravenously before highly emetogenic chemotherapy, was carried out in 187 chemotherapy-naïve children. In the first 24 h, both groups received further ondansetron intravenously at a dose of 5 mg/m2 8-hourly. Thereafter, ondansetron was given at an oral dose of 4 or 8 mg depending on the surface area of the child, three times a day and continued for at least 3 days after the last day of chemotherapy. There was no difference in the control of emesis between the two groups. Ondansetron provided good control of emesis and nausea on day 1 with 71-72% of patients experiencing two or fewer emetic episodes (complete or major responders) and 90-86% of patients reporting nausea as none or mild. There was also no difference in the efficacy of the treatment arms in the control of emesis and nausea on subsequent days of the study period. Both anti-emetic regimens were well-tolerated.
Adolescent↗
Spontaneous complete remission and recovery of donor haemopoiesis without GVHD after relapse and apparent marrow graft rejection in poor-prognosis myelodysplastic syndrome.
We report a patient with poor-prognosis myelodysplastic syndrome (MDS) after successful treatment of lymphoma, who was given an allogeneic BMT, engrafted and achieved complete remission, but later had a relapse of his MDS with complete disappearance of donor haemopoiesis. After two episodes of CMV pneumonia and continued prophylactic use of ganciclovir thereafter, he experienced a spontaneous complete disappearance of all signs of MDS, including myelofibrosis, and a complete return to donor haemopoiesis. This case is the first one to suggest a graft-versus-leukaemia effect (GVL) in MDS patients. It depicts the complex relationship between GVL, graft-versus-host disease (GVHD) and graft rejection. It could also constitute a clinical illustration of the possible antileukaemic effect of CMV infection and its treatment with ganciclovir.
Adult↗
A 15N-leucine-dilution method to measure endogenous contribution to luminal nitrogen in the human upper jejunum.
OBJECTIVE: This study was done to investigate whether an intraveinous infusion of 15N-leucine was accurate to differentiate between endogenous and exogenous nitrogen in the human jejunum after meal ingestion. SUBJECTS: Four healthy human volunteers equipped with an upper jejunal tube. INTERVENTIONS: The jejunal effluents were collected both under fasting conditions and after ingestion of 300g of yoghurt. The nitrogen, amino acid composition and 15N-leucine enrichment were determined in the digesta. RESULTS: During fasting, the jejunal flow rates (mmol/h) of both total nitrogen and amino acids were stable (6.9 +/- 2.7 and 1.88 +/- 0.79, respectively). After yoghurt ingestion, the flow rate of total nitrogen increased to 28.6 +/- 5.8mmol/h at 2h. The 15N-leucine enrichment in plasma reached a plateau at 4.3 mole % excess after one hour and did not vary significantly after meal ingestion. The 15N-leucine enrichment of the endogenous secretion (Ee) in the jejunum was fitted by the equation: Ee = 2.18[1 - 2.05 x exp( - 0.42 x t)]. After yoghurt ingestion, the enrichment in jejunal secretions decreased during the first 80 min. The endogenous nitrogen, calculated from the 15N-enrichment, significantly increased from 20 to 40min after meal ingestion compared to the basal value (P < 0.05). The estimation of the exogenous nitrogen and amino acid yield 300min after yoghurt ingestion indicated that 62 +/- 30% of the exogenous nitrogen and 75 +/- 12% of the amino acids were absorbed in the upper jejunum. CONCLUSIONS: The 15N-leucine-dilution method appears to be a convenient method to differentiate between the exogenous and endogenous contributions to nitrogen fluxes in the intestinal digesta of humans. It can be used in association with dietary protein labelling or in substitution when no labelled dietary proteins are available to compare the digestion as well as the absorption of meals at different levels of the intestine.
Adult↗
Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.
To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.
Animals↗
No evidence for linkage or association between the dopamine transporter gene and schizophrenia in a French population.
Pharmacological and clinical findings suggest that the dopamine transporter (DAT) gene may be involved in the genetic predisposition to schizophrenia. Linkage of a Taq I VNTR polymorphism in the DAT gene to schizophrenia was studied in multiplex schizophrenic families from Rouen, France (n = 10) and the Island of La Réunion (n = 21). Neither the lod score method nor nonparametric methods (the affected pedigree member method of Weeks and Lange [1988] and the sibling method of Green and Woodrow [1977]) provided any evidence for linkage. An association study, carried out within a group of 91 unrelated schizophrenic patients from Rouen and 91 matched control subjects, examined a 40 base-pair repeat polymorphism located in the 3' nontranslated end of the DAT mRNA. There was no significant difference in allelic or genotypic frequencies between the two groups. These results exclude any substantial involvement of the DAT gene in the pathogenesis of schizophrenia in the population studied.
Adult↗
Localization and quantity of hyaluronan in urogenital organs of male and female rats.
The histochemical distribution of hyaluronan was analysed in various urogenital organs of male and female (non-pregnant and pregnant) rats by use of a hyaluronan-binding protein and avidin biotin/peroxidase staining. Microwave-aided fixation was used to preserve the extracellular location of hyaluronan. The concentrations of hyaluronan in the different tissues were measured with a highly sensitive radio-assay. Hyaluronan accumulated predominantly in the connective tissue around smooth muscle fibres and in the subepithelial lamina propria. Abundant hyaluronan also occurred in perivascular and perineural connective tissue. In the female urogenital organs, hyaluronan content was high in the vagina and urinary bladder, and highest in the vagina during pregnancy. In the uterus, the surface epithelium of the endometrium stained intensely. In the ovary, the zona pellucida of the oocyte and the theca interna cell layer of the follicles and the follicular fluid of mature follicles exhibited prominent staining. The corpus luteum was devoid of hyaluronan, whereas enlarged corpora lutea of pregnancy exhibited weak, patchy staining. In male urogenital organs, staining for hyaluronan was absent from the testis and epididymis, whereas the erectile connective tissue of the penis stained intensely. The hyaluronan concentrations were high in penile tissue and urinary bladder, while testis, epididymis and the ductus deferens contained only little hyaluronan.
Animals↗
A rare allele of a microsatellite located in the tyrosine hydroxylase gene found in schizophrenic patients.
We investigated the frequency of a rare variant of a common microsatellite tetrarepeat allele in the tyrosine hydroxylase gene in 2 independent ethnic groups of schizophrenic patients and their matched controls. In a French population we found the rare variant allele in 5 of 94 (5%) unrelated chronic schizophrenic patients and in none of 145 unaffected controls, thus yielding a significant association (p < 0.01) between schizophrenia and the tyrosine hydroxylase gene. Similarly, in a replication study, we found the rare allele in 4 of 44 (9%) unrelated chronic schizophrenic patients and in none of 44 unaffected controls in a Tunisian population. Albeit the reason of this association is at the moment unknown, it is possible that this polymorphism in the tyrosine hydroxylase gene may be involved in the regulation of its activity.
Adult↗
Effect of acetate and propionate on fasting hepatic glucose production in humans.
OBJECTIVE: Short chain fatty acids (SCFA, e.g. acetate and propionate) produced from bacterial colonic fermentation may be involved in the improvement of fasting glucose concentration observed with high dietary fibre diets. Because fasting blood glucose is related to hepatic glucose production, we have tested the effect of propionate and acetate on hepatic glucose production. SETTING: The study was carried out in the Clinical Research Center for Human Nutrition. SUBJECTS: Six healthy young volunteers. INTERVENTIONS: The subjects received, in a random order: acetate (12 mmol/h), or propionate (4 mmol/h), or acetate+propionate (12 mmol/h + 4 mmol/h), or an isotonic sodium salt solution (saline) in 3 h gastric infusions. Blood glucose and plasma insulin was monitored. Hepatic glucose production was measured with an isotopic method using [6,6-2H2] glucose. RESULTS: No changes were observed in blood glucose, plasma insulin concentrations or hepatic glucose production with any of the infused solutions. An increase in free fatty acid (FFA) plasma concentration related to the fasting state was observed with the saline solution, but not with the SCFA infusions (P < 0.05). There was also an increase in beta-hydroxybutyrate concentration with the saline and the acetate solutions, but not with the propionate or acetate+propionate solutions. CONCLUSIONS: SCFA, administered at a rate calculated on the basis of a continuous daily fermentation of 30 g dietary fibres, do not change hepatic glucose production or fasting blood glucose. Propionate and acetate decrease plasma FFA, and further studies are needed to explore this effect on glucose tolerance and insulin sensitivity.
Acetates↗
Genetic study of dopamine D1, D2, and D4 receptors in schizophrenia.
The goal of this study was to define precisely the involvement of the dopamine D1, D2, and D4 receptor genes in the etiology of schizophrenia. A linkage analysis using the lod score method was performed in 37 families originating from France (n = 14) and from the Island of La Réunion in the Indian Ocean (n = 23). No evidence of linkage between schizophrenia and genetic markers located at these loci was found. A simulation study was carried out to gauge the significance of these results. The conclusions of a nonparametric linkage test (i.e., the affected pedigree member method) were equally negative. For each genetic marker, an allelic association with the disease was also sought: 80 unrelated patients and 80 healthy control subjects were tested, and no significant association was found. These results, which are in agreement with those obtained by other groups, do not support the involvement of the dopamine D1, D2, and D4 receptor genes in the pathogenesis of schizophrenia.
Female↗
Pseudoautosomal region in schizophrenia: linkage analysis of seven loci by sib-pair and lod-score methods.
In a previous study, we reported a nonrandom segregation between schizophrenia and the pseudoautosomal locus DXYS14 in a sample of 33 sibships. That study has been extended by the addition of 16 new sibships from 16 different families. Data from six other loci of the pseudoautosomal region and of the immediately adjacent part of the X specific region have also been analyzed. Two methods of linkage analysis were used: the affected sibling pair (ASP) method and the lod-score method. Lod-score analyses were performed on the basis of three different models--A, B, and C--all shown to be consistent with the epidemiological data on schizophrenia. No clear evidence for linkage was obtained with any of these models. However, whatever the genetic model and the disease classification, maximum lod scores were positive with most of the markers, with the highest scores generally being obtained for the DXYS14 locus. When the ASP method was used, the earlier finding of nonrandom segregation between schizophrenia and the DXYS14 locus was still supported in this larger data set, at an increased level of statistical significance. Findings of ASP analyses were not significant for the other loci. Thus, findings obtained from analyses using the ASP method, but not the lod-score method, were consistent with the pseudoautosomal hypothesis for schizophrenia.
Family↗
Catecholamine metabolism and psychiatric or behavioral disorders.
A wealth of pharmacological data point to the involvement of catecholamine metabolism in a number of psychiatric and behavioral disorders. Furthermore, evidence points to many of these affective disorders having a moderate to large genetic component. These observations have provided the impetus to search for differences between individuals in the structure and regulatory elements of genes involved in catecholaminergic neurotransmission. The recent finding that a mutation in the structural gene for the enzyme monoamine oxidase A is associated, in several males of a large kindred, with borderline mental retardation and abnormal behavior is an important breakthrough in the field. Other promising results concern the tyrosine hydroxylase gene in manic depressive illness and the dopamine D2 receptor in alcoholism. These studies, their potential significance and difficulties in dealing with such complex disorders are discussed.
Alcoholism↗
Rate of [15N]leucine incorporation and determination of nitrogenous fractions from gastro-jejunal secretion in fasting humans.
The aim of this study was to quantify the nitrogen fraction flow rates in gastro-jejunal secretions in fasting humans and to determine the [15N]leucine incorporation into the secreted proteins. A double lumen intestinal perfusion method was used in 5 healthy volunteers. Plasma and gastro-jejunal juices were collected during a 15-h intravenous [15N]leucine infusion. Total, soluble and insoluble nitrogen, amino acids and [15N]leucine enrichment were measured. The total nitrogen flow rate was 7.2 +/- 1.9 mmol.h-1 and 58% was ethanol soluble. The amino-acid composition remained constant and glycine was the most abundant. The plasma [15N]leucine enrichment at the isotopic plateau was 4.8 +/- 0.9 mol% excess. The [15N]leucine enrichment in the intestinal chyme increased asymptotically to reach a plateau after 5 h. The [15N]leucine enrichment at the plateau and the fractional synthesis rate of secreted proteins were 1.6 +/- 0.5 mol% excess and 21.5 +/- 3.3%.h-1, respectively. These results show that the composition of the basal gastro-jejunal secretion is very stable. A part of this secretion is composed of proteins with rapid synthesis rates.
Adult↗
No major role for the dopamine D2 receptor Ser-->Cys311 mutation in schizophrenia.
A new structural polymorphism (Ser311/Cys311) in the dopamine D2 receptor (DRD2) gene has recently been reported to be associated with schizophrenia, particularly in patients with a positive family history of schizophrenia (Arinimi et al., 1994). However these findings remain controversial (Asherson et al., 1994; Nanko et al., 1994; Nöthen et al., 1994; Shaikh et al., 1994). Thus we investigated the role of the Cys311 mutation in schizophrenia using both association and family studies. First, we screened for the Cys311 mutation in 113 unrelated Caucasian schizophrenics (mean age 42 +/- 0.6; 34 females and 79 males) including 25 familial cases, and 184 unrelated controls (mean age 49 +/- 0.5, 74 females and 110 males) free of any psychiatric disorders. Diagnoses were ascertained according to DSM-III criteria (Campion et al., 1994). All patients and controls were native to the area of Rouen.
Alleles↗
Homozygosity at the dopamine D3 receptor locus is not associated with schizophrenia.
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Alleles↗
Localization of hyaluronan in the human endolymphatic sac. A study using the affinity hyaluronan binding protein.
This study was undertaken with the aim of localizing hyaluronan (hyaluronic acid, HYA) in tissue sections of the human endolymphatic sac by use of a hyaluronan-binding affinity protein and the avidin-biotin/peroxidase staining procedure. Five human endolymphatic sacs were removed during surgery for acoustic neuroma. After microwave-aided fixation and decalcification, paraffin-embedded sections were prepared by routine histological methods. HYA was detected in some of the intraluminal substance as well as in parts of the epithelial lining, mainly in the rugose portions of the endolymphatic sac. HYA was observed intracellularly in epithelial cells. It was also found in the subepithelial tissue near the epithelia and close to the bony aqueduct. The distribution of HYA was uneven at all locations. The finding of HYA within the human endolymphatic sac may imply that this substance has important functions in the control of inner ear fluid homeostasis.
Affinity Labels↗
[Prevention of macroangiopathy of type 2 diabetes in clinical practice].
The increase in cardio-vascular morbidity of people with Type 2 diabetes is due to the frequent association of Type 2 diabetes with classical risk factors but also to diabetes per se, whatever the mechanisms involved. From a clinical point of view, it is important to stop smoking, with a great benefit, to treat hypertension with other drugs than diuretics or beta-blockers and to treat dyslipidaemia. The lipid abnormalities often improve with the only glycaemic control. In all cases, the normalisation of HbA1c is a very important therapeutic goal, by diet, exercise, oral hypoglycaemic drugs or insulin if necessary. The treatment will be especially useful in high risk patients, i.e. patients with coronary heart disease, patients with albuminuria, patients with more than 3 risk factors associated with diabetes and/or with high glycaemic levels.
Antihypertensive Agents↗
Over-worked and under-valued.
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Burnout, Professional↗