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Biomedical subjects

B Lerer

Publications and source records attributed to B Lerer.

At least 163 records · Page 9Linked to original sources

A controlled trial of phenelzine in posttraumatic stress disorder.

Thirteen patients meeting DSM-III criteria for posttraumatic stress disorder participated in a random-assignment, double-blind crossover trial comparing phenelzine (45-75 mg/day) and placebo. Ten patients completed at least 4 weeks of each treatment phase. Clinical response to phenelzine did not differ from placebo, and overall improvement by the end of the study could not be attributed to the active drug. The findings are discussed in the light of preliminary reports suggesting that phenelzine may be an effective treatment for posttraumatic stress disorder.

Adult↗

Lithium modulation of second messenger signal amplification in man: inhibition of phosphatidylinositol-specific phospholipase C and adenylate cyclase activity.

The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.

Adenylyl Cyclase Inhibitors↗

Cyclic AMP second-messenger signal amplification in depression.

Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.

Adult↗

Post-partum psychosis in adult GM2 gangliosidosis. A case report.

Adult hexosaminidase A deficiency is a form of GM2 gangliosidosis with autosomal recessive inheritance. Only 35 cases (mostly among Ashkenazic Jews) have been reported worldwide. Symptoms include, in a third of the cases, psychosis. A 27-year-old sufferer with no prior psychiatric history, developed a post-partum psychosis, with affective and hebephrenic components, 3 days following her first delivery. She responded to lithium within 10 days of initiating treatment; the full episode lasted 1 month. We conclude that lithium is the preferred treatment for psychosis in such adult patients, especially in light of possible long-term neurological deterioration caused by phenothiazines. Ashkenazic Jews with atypical neurological syndromes presenting with psychosis should be tested for hexosaminidase A deficiency.

Adult↗

Isoelectric focusing of human platelet phospholipase C: evidence for multimolecular forms.

Polyacrylamide gel isoelectric focusing was employed to characterize phospholipase C activity in the supernatant fraction after disruption of human platelets. Three bands of enzyme activity were detected on focused gels: a major band of activity (B) and two additional bands (A,C) were consistently identified. The isoelectric points of the three bands were in the range of pH 7.5-8.0. Phospholipase C activity was assayed using both phosphatidylinositol and phosphatidylinositol-4-monophosphate. The prominent B band was active against both substrates and no evidence for substrate preference towards phosphoinositides was obtained. These data suggest that isozyme forms of cystolic phospholipase C are present in human platelet supernatant and suggest the possibility of functional and structural differentiation of the various forms of the enzyme.

Animals↗

Posttraumatic stress disorder in Israeli combat veterans. Effect of phenelzine treatment.

Twenty-five Israeli combat veterans fulfilling DSM-III criteria for posttraumatic stress disorder (PTSD) participated in an open, prospective trial of phenelzine sulfate administration (median daily dose, 60 mg; range, 30 to 90 mg); three patients withdrew early due to side effects. Treatment was continued for at least four weeks in 22 cases and thereafter for as long as it was felt to be of benefit. Therapeutic efficacy was rated using a new PTSD scale, the Hamilton Depression Scale, and the Hamilton Anxiety Scale administered at four weekly intervals. Six patients completed four to eight weeks of phenelzine treatment; seven patients, nine to 13 weeks; and nine patients, 14 to 18 weeks. Comparison of mean prediscontinuation scores with pretreatment ratings showed, at best, only small (23% to 38%) differences (on the PTSD and Hamilton Anxiety scales) in the group treated for nine to 13 weeks. Two patients with a concurrent diagnosis of panic disorder and two with a concurrent diagnosis of dysthymic disorder were the most improved symptomatically but fell short of clinically significant remission. Although statistically significant improvement was observed on seven of the 12 items of the PTSD scale, sleep disturbance was the only symptom showing a clinically impressive change. These results only partially support previous positive reports of phenelzine treatment of PTSD.

Adult↗

Remote and recent memory in long-hospitalized chronic schizophrenics.

This study shows that chronic, long-hospitalized schizophrenics perform (tested by the Famous Events Questionnaire) at a higher level on remote memory than they do on word list recall. A post hoc, matched-tasks check suggested that this finding was not due to differences in the discriminating power of the tasks. Relative to normals, patients showed no differential performance on the three time periods (1973/74, 1979/80, 1984) represented in the remote memory questionnaire, thus giving no evidence for an amnesic gradient. The findings are discussed in relation to amnesia and dementia hypotheses in chronic schizophrenia.

Adolescent↗

Conditioned avoidance acquisition and extinction following repeated electroconvulsive shock: strain effect and response to vasopressin.

Male albino rats (Sabra strain) were exposed to electroconvulsive shock (ECS) once daily for periods ranging from 1 to 13 days, and proactive effects on conditioned avoidance response (CAR) acquisition and extinction were studied. CAR acquisition was intact following both single and repeated ECS, but extinction was accelerated by multiple ECS administration. These findings resembled the effect of repeated ECS on anterograde memory function in humans and confirmed previous observations based on a passive avoidance paradigm. However, extinction was not accelerated in a different rat strain (LC2). Parallel open field activity measures suggested that these findings were not related to ECS-induced alterations in locomotor activity. Administration of arginine vasopressin prior to each ECS, or following acquisition sessions, as well as 1-desamino-8-D-arginine vasopressin administration following acquisition sessions, did not ameliorate ECS-induced deficits in the Sabra rats. Differences between the present paradigm of ECS administration and those in which positive effects of vasopressin and other neuropeptides have been reported are discussed. The potential research applications of a rodent model of ECS-induced memory impairment that parallels deficits encountered in the clinical context are considered.

Animals↗

Performance of chronic schizophrenics on matched word and design recall tasks.

Matched word and design recall tasks were constructed and used to assess the performance of chronic schizophrenics on neuroleptics alone and on both neuroleptic and anticholinergic drugs. The two groups of patients performed at an equally low level on both tasks, without evidence for a differential deficit. The tasks did, however, evoke a differential deficit in clustering performance for designs as opposed to words. Although clustering, which is based on recall, is not necessarily as well matched for words and designs as recall itself, this result suggests a lateralized dysfunction in brain structures related to use of mnemonic organization at retrieval.

Adult↗

Differential effects of chronic administration of desipramine on the cyclic AMP response in cortical slices and membranes in the rat.

Chronic administration of desipramine resulted in a significant decrease in the degree of stimulation of production of cyclic AMP by noradrenaline, isoproterenol and forskolin in slices of the cerebral cortex of the rat. In preparations of membranes from similarly treated animals, GppNHp- and forskolin-stimulated adenylate cyclase activity was increased, while isoproterenol-, manganese- and sodium fluoride-stimulated activity was unchanged. It is concluded that chronic administration of desipramine exerts effects on the adenylate cyclase system additional to its action on beta-adrenergic receptors, possibly by modifying the catalytic or guanyl nucleotide binding units of the enzyme.

Adenylyl Cyclases↗

Effect of lithium in vitro and after chronic treatment on human platelet adenylate cyclase activity: postreceptor modification of second messenger signal amplification.

LiCl in vitro markedly inhibits forskolin-stimulated human platelet adenylate cyclase activity by competing competitively with Mg2+ for a site on the catalytic subunit. The sensitivity of platelet membrane adenylate cyclase to lithium inhibition for individual manic patients was determined by the Dixon plot procedure: marked individual differences in sensitivity to lithium were observed pretreatment (0.66 mM-3.15 mM LiCl). After 3 weeks of continuous treatment with lithium in vivo a significant decrease in adenylate cyclase affinity for lithium was observed (pretreatment average Ki = 1.38 +/- 0.92 mM vs. treatment average Ki = 2.98 +/- 1.35 mM LiCl, n = 10). The clinical implications of these findings relating to chronic lithium exposure are discussed.

Adenylyl Cyclase Inhibitors↗

Effects of single and repeated electroconvulsive shock administration on inositol phosphate accumulation in rat brain slices.

Accumulation of inositol-1-phosphate after labeling with [3H]inositol and stimulation with noradrenaline, carbachol, and serotonin was measured in rat cortical, caudate nucleus, and hippocampal slices. The response to noradrenaline was significantly increased in cortical slices from animals that had received either a single electroconvulsive shock (ECS) or a series of 10 daily ECS but was unchanged in caudate nucleus or hippocampal slices. The response to carbachol, a muscarinic cholinergic agonist, was unchanged in cortical or caudate nucleus slices but was significantly reduced in hippocampal slices from animals that had received chronic ECS. The response to serotonin in cortical slices was not affected by the treatment. The results are correlated with changes in receptor number, which have been demonstrated to occur after administration of ECS.

Animals↗

Cyclic AMP signal transduction in posttraumatic stress disorder.

Cyclic adenosine 3',5'-monophosphate (cAMP) signal transduction was examined in lymphocytes and platelets obtained from patients with posttraumatic stress disorder. Intact lymphocytes from the posttraumatic patients (N = 10) showed significantly lower basal, isoproterenol-, and forskolin-stimulated cAMP levels than those from 10 healthy control subjects. In platelet membrane preparations, basal, forskolin-, aluminum chloride plus sodium fluoride-, and prostaglandin E1-stimulated adenylate cyclase activity levels were all significantly lower in the posttraumatic group than in the control group. The authors discuss the potential role of their findings as a biological marker for posttraumatic stress disorder.

Adenylyl Cyclases↗

Facilitation of ECT by caffeine pretreatment.

In this study, eight patients participated in a standardized protocol to assess the effects of caffeine on seizures in ECT. Caffeine sodium benzoate (500-2000 mg) was administered intravenously 10 minutes before ECT, and seizure duration was compared with that of a previous treatment unmodified by caffeine. Seizure duration was significantly increased during ECTs preceded by caffeine. Three other patients given caffeine when seizures of adequate duration could no longer be elicited at maximal stimulus levels experienced longer seizures. Administration of caffeine was not associated with significant cardiovascular or other (including cognitive) adverse effects.

Benzoates↗

Carbamazepine versus lithium in mania: a double-blind study.

Thirty-four manic patients were randomly assigned to treatment with carbamazepine or lithium. Clinical response was rated over 4 weeks. Twenty-eight patients, 14 in each group, completed the full protocol. Serum levels for both drugs were within the accepted therapeutic range. The overall response to treatment was not significantly different between the two groups. Comparison of individual Clinical Global Impressions, Brief Psychiatric Rating Scale, and Beigel-Murphy Manic State Rating Scale change scores showed a more consistent level of improvement across patients in the lithium-treated group compared to a minority of good responders in the carbamazepine-treated group. The findings suggest that carbamazepine has antimanic potential in specific bipolar patients whose clinical characteristics remain to be clearly defined.

Adult↗

Bereavement in combat.

Despite the obvious fact that loss and bereavement are an integral part of the war experience, surprisingly little has been written about bereavement and grief in combat. This article discusses reasons for the resistance to the concepts of loss and bereavement in military psychiatry, distinctive aspects of combat bereavement, factors that impede appropriate grieving in war, and, with the aid of case vignettes, the varieties of bereavement states seen in combat situations. The authors conclude that the clinical phenomena of grief run like a connecting thread through the various presentations of combat-related psychiatric syndromes, including post-traumatic stress disorders, and that more research in this area is called for.

Adult↗