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R Malka

Publications and source records attributed to R Malka.

10 recordsLinked to original sources

Cytokine production in human mixed leukocyte reactions performed in serum-free media.

The mixed leukocyte reaction (MLR) is an in vitro test commonly performed in a serum-containing medium (SCM), and used to study allorecognition and cellular immunity accompanied by cytokine release. We investigated the possibility of performing the MLR test in serum-free media (SFM) by comparing human leukocyte proliferation and cytokine release in MLRs performed in SFM and SCM. Of the four SFM tested, only Biotarget- was as effective as SCM in supporting leukocyte proliferation and IL-2 secretion. Both phenomena were observed only in allogeneic combinations. The levels of IL-1, IL-6, and TNFalpha in allogeneic MLR combinations in SFM were half those in SCM cultures; the kinetics of their release were the same. With the exception of IL-2, a high degree of spontaneous release of the other three cytokines analyzed was observed in responder cells, in irradiated stimulator cells, and in autologous combinations cultured in both SCM and SFM. It appears that unlike IL-2, the cytokines IL-1, IL-6, and TNFalpha are nonspecifically produced in MLR and cannot serve as sensitive indices of HLA disparity.

Culture Media, Serum-Free↗

Long-term use of tianeptine in 380 depressed patients.

Tianeptine is a new tricyclic compound whose principal action is to increase the reuptake of serotonin. In a multicentre trial in which 380 depressed patients were treated for one year, tianeptine produced a significant reduction in the MADRS scores from day 14, with a sustained reduction maintained for up to 12 months; other measures of efficacy (HRSA, HSCL, and CGI) also reflected the improvement. Only 11% of patients withdrew because of recurrence of depression and 2% because of side-effects, which were mainly drowsiness, irritability, and gastrointestinal disturbance. Apart from a minor reduction in heart rate, unaccompanied by any conduction changes, no clinically relevant changes in vital signs or laboratory tests were seen. Seven subjects who attempted suicide by tianeptine overdose had favourable outcomes, in spite of also taking other psychotropic drugs or alcohol. No evidence of tolerance or withdrawal symptoms was seen after treatment was stopped. These results suggest that tianeptine has the potential to provide safe antidepressant activity in both the acute and chronic phases of treatment.

Adolescent↗

Long-term administration of tianeptine in depressed patients after alcohol withdrawal.

Alcohol interferes with the central metabolism of the catecholamines and especially with indolamines (5-HT). Thus, the use of an antidepressant such as tianeptine, whose main neurochemical effect is to increase the reuptake of 5-HT, seems to be particularly indicated for the continued treatment of depressed patients after alcohol withdrawal. This study evaluated the therapeutic efficacy and acceptability during long-term administration of tianeptine in depressed patients (major depressive episode or dysthymic disorder) in a multicentre trial, after withdrawal from alcohol abuse or dependence. The results relate to 130 depressed patients, who abstained from alcohol and received treatment for a year. Only one patient dropped-out because of side-effects, and medication was interrupted in 5% of subjects because of alcoholic relapses. Prescribed in the long term, tianeptine did not produce orthostatic hypotension, changes in bodyweight, or alterations in the ECG. All changes found in haematological and biochemical investigations suggested an improvement in patients' physical state. This, and other studies, indicate that tianeptine appears to have the potential to be a safe antidepressant, which might be particularly useful in those patients who are susceptible to the side-effects of psychotropic drugs.

Adolescent↗

[Role of tianeptine in the prevention of depression relapse and recurrence. First estimations].

The potential activity of tianeptine in the prevention of depressive relapses or recurrences was evaluated in the course of a long-term multicenter study. Five hundred and ten patients were treated for a one-year period. During the first six months, 22 percent of patients responders to the treatment relapsed into depression or had a methodological equivalent of depressive relapse (a MADRS score equal to or higher than 25). This percentage of depressive relapses is comparable to those obtained with other antidepressants. After six months of treatment, 7 percent of patients with a stabilized recovery recurred into depression or had a methodological equivalent of depressive recurrence (a MADRS score equal to or higher than 25). An analysis compared this percentage with those obtained in the course of other studies. These percentages are classically more important. The role of diagnoses of depression was analysed. Percentages of depressive relapses and recurrences were also evaluated in the sub-sample of patients treated with tianeptine alone.

Adult↗

Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients.

129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.

Adult↗

Role of drug therapies in the treatment of alcoholism: alcohol and anxiety--alcohol and depression.

Drug therapies are often used in therapeutic programs for alcoholics. This paper focuses on the use of psychotropic agents which can be used at different stages in the alcoholic disease process. It does not cover specific drug therapies for alcoholism (aversion, chemical restraint, dissuasion), nor nonspecific drug therapies (vitamins, magnesium) the interest and limits of which are well known. All types of psychotropic drugs, antianxiety drugs, antidepressants, thymoregulators, neuroleptics, and beta-blockers are used, with two main indications: (a) to prevent or to treat the withdrawal syndrome and (b) to diminish the psychopathological factors related to alcoholism (anxiety or depression, for example), in order to avoid pathological recourse to alcohol. Recently, attempts have been made to decrease the craving for alcohol in humans after detoxification. Although psychotropic drugs are often used in the management of alcoholics, such management is not limited to them, but also includes psychotherapy and social measures.

Alcoholism↗

[GABA and alcohol].

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Alcohol Drinking↗

[A controlled double-blind study of tetrabamate versus lorazepam and placebo in generalized anxiety].

The anxiolytic efficacy of tetrabamate was evaluated in a multicentric double-blind study versus lorazepam and placebo, in 269 patients with a generalized anxiety disorder according to DSM III-R criteria. The anxiolytic activity of tetrabamate (at 900 mg/day) was significantly superior than that of placebo from day 7 of treatment and equivalent to lorazepam efficacy (at 4.5 mg/day). In the tetrabamate group, 55.3% were considered as "good responders" (as defined by a HARS score reduction equal or superior to 50%), versus 51.3 and 32.9% respectively in the lorazepam and the placebo groups (chi-square = 9.63, p = 0.008). Sheehan's scales (parts 1 and 2), Norris visual analogue scales, CHESS 84, CHESS complement 82 for withdrawal evaluation, physician's overall evaluation of efficacy and tolerance, were also used to assess the clinical effects of tetrabamate. The data on these measures confirmed the anxiolytic efficacy of tetrabamate and showed some advantages in the tetrabamate group in comparison with the lorazepam group: a better global tolerance at the study end point (day 35), a greater efficacy on some anxiety somatic items and lesser frequency and severity of withdrawal symptoms during treatment tapering off.

Adult↗

[Long-term treatment using antidepressants. Tianeptine: methodology of a long-term study and preliminary results].

Numerous authors insist on the need for prolonged prescription of antidepressant drugs. Legislation develops and now requires long-term controls for psychotropic drugs. In order to assess long-term efficacy and safety of tianeptine, a clinical trial was undertaken with the objective of 100 patients completing one year of treatment. This multicentered study involves 157 psychiatrists all over France, under the responsibility of a national coordinator and 19 regional coordinators. The methodology is explained, as well as the various means that have been planned to set up the protocol, to follow the case reports and to analyse the results. The use of a central computer assisted monitoring and the organization of national and regional meetings with the investigators seem to take an important part in the management of the study. Preliminary results after 6 months of treatment for 478 patients are discussed. They confirm the prolonged efficacy and the safety of tianeptine. The effective contribution made by the logistic support should allow the study to reach its objectives. When completed, it should be a pilot study for further long-term studies with antidepressants.

Adult↗

[Anxiolytic efficacy and tolerance of tetrabamate in anxious patients abusing alcohol. Multicenter double-blind versus placebo study].

The anxiolytic efficacy of tetrabamate was evaluated in 68 out-patients presenting an anxiety state with alcohol abuse according to DSM III criteria. The study followed a double-blind placebo-controlled design with parallel groups and lasted for 21 days. Anxiety was evaluated by the Hamilton anxiety scale, Norris visual analog scales, and the Hopkins Symptom Check List, along with the investigator's assessment. Safety was evaluated in terms of somatic symptoms (CHESS 84) and the physician's overall evaluation. The anxiolytic activity of tetrabamate (three 300 mg tablets/day) was significantly greater than that of placebo from seventh day on. There were no statistically significant differences in safety profile between tetrabamate and placebo. Moreover, in the tetrabamate group the significantly greater improvement in the scores of somatic symptoms indicates that the compound caused no notable adverse effects and its activity on somatic complaints (psychopathologic and/or toxic).

Alcoholism↗