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Biomedical subjects

M Tournier

Publications and source records attributed to M Tournier.

10 recordsLinked to original sources
PubMed2005

Prognostic impact of psychoactive substances use during hospitalization for intentional drug overdose.

OBJECTIVE: To assess whether current use of psychoactive substance(s) is a prognostic factor during hospitalization for intentional drug overdose (IDO). METHOD: Current intoxication with psychoactive substance(s) [cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)] was identified using toxicological urinalysis in 671 patients with IDO. An IDO was a priori defined as serious if associated with one of the following events: death, hospitalization in intensive care unit longer than 48 h, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. RESULTS: Subjects positive for toxicological assays were twice as likely to present with serious IDO (OR = 1.9, 95% CI: 1.3-2.8, P = 0.001), independently from a large range of confounding factors. The risk of serious IDO was especially marked in subjects using LSD, buprenorphine or opiates. CONCLUSION: Systematic investigation of substance use could be important to adapt medical management of subjects with IDO in general hospital, but also in primary care and psychiatric settings.

Adult↗
PubMed2003

Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study.

BACKGROUND: Epidemiological findings suggest that cannabis use is a risk factor for the emergence of psychosis, and that the induction of psychotic symptoms in the context of cannabis use may be associated with a pre-existing vulnerability for psychosis. This study investigated in a non-clinical population the interaction between cannabis use and psychosis vulnerability in their effects on psychotic experiences in daily life. METHOD: Subjects (N = 79) with high or low levels of cannabis use were selected among a sample of 685 undergraduate university students. Experience sampling method (ESM) was used to collect information on substance use and psychotic experiences in daily life. Vulnerability to develop psychosis was measured using a clinical interview assessing the level of psychotic symptoms. Statistical analyses were performed using multilevel linear random regression models. RESULTS: The acute effects of cannabis are modified by the subject's level of vulnerability for psychosis. Subjects with high vulnerability for psychosis are more likely to report unusual perceptions as well as feelings of thought influence than subjects with low vulnerability for psychosis, and they are less likely to experience enhanced feelings of pleasure associated with cannabis. There is no evidence that use of cannabis is increased following occurrence of psychotic experiences as would be expected by the self-medication model. CONCLUSION: Cannabis use interacts with psychosis vulnerability in their effects on experience of psychosis in daily life. The public health impact of the widespread use of cannabis may be considerable.

Adult↗
PubMed2003

Accuracy of self-report and toxicological assays to detect substance misuse disorders in parasuicide patients.

OBJECTIVE: To assess the accuracy of self-reported substance use and toxicological assays in subjects admitted for Intentional Drug Overdose (IDO), using as a reference diagnosis of substance use disorder. METHOD: Self-reported substance use was collected and toxicological assays were carried out in urine samples in 507 patients with IDO. A standardized psychiatric evaluation was performed in 100 randomly selected subjects. RESULTS: In routine practice, the emergency department staff did not investigate substance use in nearly one of two patients. Patients' statements and toxicological assays were more specific than sensitive, with lower scores for toxicological assays. Patients' statements made it possible to detect nearly 80% of subjects with substance use disorder. CONCLUSION: Identification of substance use disorder in subjects with IDO has strong clinical consequences regarding treatment and prevention of suicidal behaviour. Thus, emergency department staff should be made aware of the value of more systematically exploring self-reported substance use.

Adolescent↗
PubMed1999

4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties.

We have recently shown in vitro that 4-hydroxyisoleucine (4-OH-Ile), an amino acid extracted from fenugreek seeds, potentiates insulin secretion in a glucose-dependent manner. The present study was designed to investigate whether 4-OH-Ile could exert in vivo insulinotropic and antidiabetic properties. For this purpose, intravenous or oral glucose tolerance tests (IVGTTs and OGTTs, respectively) were performed not only in normal animals but also in a type II diabetes rat model. During IVGTT in normal rats or OGTT in normal dogs, 4-OH-Ile (18 mg/kg) improved glucose tolerance. The lactonic form of 4-OH-Ile was ineffective in normal rats. In non-insulin-dependent diabetic (NIDD) rats, a single intravenous administration of 4-OH-Ile (50 mg/kg) partially restored glucose-induced insulin response without affecting glucose tolerance; a 6-day subchronic administration of 4-OH-Ile (50 mg/kg, daily) reduced basal hyperglycemia, decreased basal insulinemia, and slightly, but significantly, improved glucose tolerance. In vitro, 4-OH-Ile (200 microM) potentiated glucose (16.7 mM)-induced insulin release from NIDD rat-isolated islets. So, the antidiabetic effects of 4-OH-Ile on NIDD rats result, at least in part, from a direct pancreatic B cell stimulation.

Acids↗
PubMed1998

CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling.

The lymphocyte activation gene-3 (LAG-3) molecule is a T cell activation Ag closely related to CD4 at the gene and protein levels. We investigated whether LAG-3 itself may down-regulate the immune response by interfering with TCR signaling. The binding of Ab to the LAG-3 molecule followed by cross-linking (XL) inhibits cell proliferation and cytokine secretion in response to CD3XL on activated T cells. LAG-3XL-induced down-regulation is associated with functional unresponsiveness, as well as with high CD25 expression levels and reversion by exogenous IL-2. It is also associated with a down-modulation of CD3/TCR complex expression. At the biochemical level, LAG-3XL inhibits calcium response to CD3 stimulation. This inhibition is observed with different LAG-3- and CD3-specific mAbs on condition that the two receptors are cross-linked together. Finally, the capping of CD3 was shown to induce cocapping of LAG-3 molecules. Together, these results show that CD3/TCR complex-associated LAG-3 molecules can play an active role in negatively regulating the CD3/TCR activation pathway. They ultimately suggest that LAG-3 is an inhibitory receptor in activated T lymphocytes.

Antigens, CD↗
PubMed1998

LAG-3 does not define a specific mode of natural killing in human.

LAG-3 is a gene localized on the band p13 of human chromosome 12, close to the NK gene complex (NKC), expressed on activated NK cells and encoding a receptor for MHC class II molecules. Recently, LAG-3 has been proposed to define a specific mode of natural killing in mice. The putative role of LAG-3 on human natural killer cytotoxicity has been examined with specific monoclonal antibodies and a recombinant soluble form of LAG-3. Neither the antibodies, which are able to block the interaction with the ligand, nor the recombinant product, which has retained its binding capacity for MHC class II, had an effect on the natural killing of various target cells. Furthermore, in redirected killing assays, none of these antibodies were able to modulate either positively or negatively the cytotoxicity. Taken together, these data show that LAG-3 has no transducing activity involved in NK cytotoxicity, ruling out the existence of a specific mode of natural killing defined by this molecule in humans.

Antigens, CD↗
PubMed1995

CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins.

We analyzed CD4 major histocompatibility complex (MHC) class II interactions with CD4 and lymphocyte activation gene (LAG)-3 recombinant fusion proteins termed CD4Ig and LAG-3Ig. CD4Ig bound MHC class II molecules expressed on the cell surface only when used in the micromolar range. This weak CD4Ig binding was specific, since it was inhibited by anti-CD4 and anti-MHC class II mAb. LAG-3Ig bound MHC class II molecules with intermediate avidity (Kd = 60 nM at 37 degrees C). Using LAG-3Ig as a competitor in a CD4/MHC class II-dependent cellular adhesion assay, we showed that this recombinant molecule was able to block CD4/MHC class II interaction. In contrast, no inhibition was observed in a CD4/MHC class II-dependent T cell cytotoxicity assay. Together, these results suggest that co-engagement of the TcR with CD4 alters the CD4/MHC class II molecular interaction to become insensitive to LAG-3Ig competition.

Animals↗
PubMed1994

Lymphocyte-activation gene 3/major histocompatibility complex class II interaction modulates the antigenic response of CD4+ T lymphocytes.

The activation requirements for antigen-dependent proliferation of CD4+ T cells are well documented, while the events leading to the inactivation phase are poorly understood. Here, we tested the hypothesis that the lymphocyte-activation gene 3 (LAG-3), a second major histocompatibility complex (MHC) class II ligand, plays a regulatory role in CD4+ T lymphocyte activation. CD4+ class II-restricted T cell clones were stimulated by their relevant antigen (hemagglutinin peptide or diphteria toxoid) and antigen-presenting cells with or without anti-LAG-3 monoclonal antibody (mAb). Kinetic studies were performed to monitor different activation parameters, including the measurement of thymidine incorporation, expression of activation antigens and cytokine secretion. Results showed that the time course from the initial time points up to the peak time point was not modified in the presence of anti-LAG-3 mAb. However, addition of these antibodies, either as whole IgG or as Fab fragments, led to increased thymidine incorporation values for late time points and, hence, to a shift in the decreasing proliferation curve. We also showed that expression of activation antigens, such as CD25, was higher in the presence of anti-LAG-3 mAb, and that cytokine concentrations, i.e. of interferon-gamma or interleukin-4, were higher in the corresponding culture supernatants. In addition, we tested whether the effects of anti-LAG-3 mAb were limited to antigen-dependent, MHC class II-restricted responses. The proliferative responses of CD4+ T cell clones following stimulation with either interleukin-2, mitogens, a combination of anti-CD2 mAb, immobilized anti-CD3 or anti-T cell receptor mAb were not altered by anti-LAG-3 mAb. The allogeneic proliferative response of a CD8+ T cell clone was also not affected. Overall, the present analysis reveals a modulating effect of anti-LAG-3 mAb, mediated specifically on antigen-dependent, MHC class II-restricted responses of CD4+ T cell lines. These results support the view that LAG-3/MHC class II interaction down-regulates antigen-dependent stimulation of CD4+ T lymphocytes.

Antigens, CD↗
PubMedDate not supplied

[A case of Parkinsonian syndrome, cognitive impairment and hyperammonemia induced by divalproate sodium prescribed for bipolar disorder].

Several cases of Parkinsonian syndrome, cognitive impairment or hyperammonemia induced by sodium valproate have been described in the literature. We report the first case presenting an association of the three adverse effects occurring with divalproate sodium prescribed for bipolar disorder: a 58-year-old man with a history of bipolar type I disorder presented with Parkinsonian syndrome and cognitive impairment of insidious onset. This patient had been treated for several years with lithium carbonate, with a successful effect on mood swings, but with distressing adverse effects such as hand tremor and diarrhoea. Lithium therapy was progressively withdrawn while sodium divalproate was initiated. Associated medications, unchanged for several years, were amisulpride (daily dose: 100 mg), liothyronine, ciprofibrate and benfluorex. The patient was treated with sodium divalproate for seven months (daily dose: 1,000 mg), and with trihexyphenidyle for one month for extrapyramidal symptoms. At hospital admission, he presented with temporal disorientation, slowed thinking, severe anterograde memory deficits, and Parkinsonian syndrome. The minimal mental state (MMS) score was 16 (maximum: 30). The patient was anxious but did no present with mood symptoms. He also developed hyperammonemia (124 micromol/liter, normal range: 15 to 60 micromol/liter) without signs or biochemical evidence of hepatic failure. Valproate concentrations were within the therapeutic ranges (79 mg/l, normal range: 50 to 100 mg/l). The CT-scan showed cerebral and cerebellar atrophy with enlarged ventricles. The electroencephalogram showed generalized slowing waves. All the symptoms resolved within one month after the withdrawal of divalproate: the extrapyramidal hypertonia resolved, the MMS score was 29. The CT-scan and the electroencephalogram returned to normal. The divalproate was replaced by lithium. After a one-year follow-up, the cognitive and neurological symptomatology did not reappear at the exception of the pre-existing hand tremor. The pathophysiology of valproate induced hyperammonemic encephalopathy remains unclear. A possible mechanism is neuronal toxicity induced by increased intracellular concentrations of glutamate and ammonium in astrocytes. Indeed, these abnormal intracellular concentrations increase the intracellular osmolarity and thus induce rise in intracranial pressure and cerebral oedema. Reversible dementia could be due to a direct toxic effect of valproate on the central nervous system or to an indirect effect mediated through valproate-induced hyperammonemia. It has been suggested that the occurrence of extrapyramidal syndrome could be explained by a disturbance in the GABAergic pathways inducing reversible dopamine inhibition. A drug adverse reaction should always be considered when a patient treated with valproate presents with extrapyramidal symptoms and cognitive disorders even when valproate concentrations are within standard therapeutic ranges.

Antipsychotic Agents↗