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Biomedical subjects

S Gershon

Publications and source records attributed to S Gershon.

At least 19 recordsLinked to original sources
PubMed1990

Is the neuronal basis of Alzheimer's disease cholinergic or glutamatergic?

The hypothesis that the symptomatology of Alzheimer's disease is attributable to cholinergic dysfunction is supported by postmortem studies that have demonstrated reduced choline acetyltransferase (ChAT) activity across all areas of cerebral cortex and diminished numbers of perikarya in the basal forebrain nucleus basalis of Meynert. Biopsy studies of ChAT activity, choline uptake, and acetylcholine synthesis also suggest that cholinergic denervation occurs relatively early in the course of the disease, and in confirmation of postmortem data, correlates with the severity of cognitive impairment. An alternative hypothesis to explain the dementia of Alzheimer's disease is the glutamatergic hypothesis. This is based largely on postmortem evidence indicating reduced binding and uptake of D[3H]aspartate, as well as loss of a number of other putative markers, such as phosphate-activated glutaminase activity, glutamate concentration, and the number of pyramidal cell perikarya, with this latter change correlating with the severity of dementia. Short-comings of each hypothesis are discussed and the merits of single neuron hypotheses to explain the dementia of Alzheimer's disease are considered.

Alzheimer Disease↗
PubMed1990

Antipsychotics in the elderly.

Neuroleptics are commonly prescribed medications in the geriatric population and have a broader spectrum of indications than in younger patients. In spite of the frequent use of neuroleptics in elderly patients with organic brain syndromes, there are relatively few studies that use double-blind, placebo-controlled methodology. The results of these studies are conflicting; however, there is sufficient evidence that symptoms of agitation, behaviourial dyscontrol, and psychosis are often responsive to neuroleptic treatment. Elderly patients with schizophrenia or other psychotic disorders may also benefit from neuroleptic treatment. As there is a potential for overuse of these medications among the elderly, clear definition of checklist symptoms is imperative. Furthermore, periodic reduction of dose and possible discontinuation of the drug should be considered since many of the checklist symptoms in this age group are environmentally related and time-limited. There has so far been little evidence to support the use of one neuroleptic over another. Side-effect profiles suggest that low doses of the high potency agents are safer and better tolerated in the elderly. Both therapeutic effects and side effects should be assessed at regular intervals.

Aged↗
PubMed1990

Monosodium glutamate and tranylcypromine administration in healthy subjects.

The authors administered 400 to 1600 mg of monosodium glutamate and placebo to five healthy males while they were medication-free and again while they were receiving the monoamine oxidase inhibitor tranylcypromine, after having received the drug daily for at least 2 weeks. Monosodium glutamate produced no consistent changes in either blood pressure or heart rate in subjects receiving tranylcypromine. Spontaneous hypertensive episodes were observed in two subjects. These blood pressure increases also occurred with tranylcypromine alone and were unrelated to monosodium glutamate administration. Diet was not violated during these episodes.

Adult↗
PubMed1989

Correlation between brain-adrenal axis activation and cognitive impairment in Alzheimer's disease: is there a gender effect?

The present study evaluates the relationship between brain-adrenal axis activity and cognitive function in patients suffering from senile dementia of the Alzheimer's type (SDAT). Thirty-four subjects (20 females and 14 males) were assessed using the Global Deterioration Scale (GDS) and plasma cortisol levels after administration of 0.5 mg of dexamethasone. The results show a positive Spearman rank correlation between the GDS scores and postdexamethasone cortisol levels only in female subjects, but not in males. Different gender distributions might explain the contradictory results of previous investigations of the relationship between brain-adrenal axis activity and cognitive function in SDAT patients.

Aged↗
PubMed1989

Which atypical antipsychotics are identified by screening tests?

Only two tests were specific for antipsychotic potential. All effective antipsychotics blocked pharmacologically induced locomotion and affected firing in the mesolimbic DA neurons. The remaining single- (Table 1) and repeated- (Table 2) dose tests identified the atypical antipsychotics. Clozapine, thioridazine, sulpiride, tiospirone, and molindone were atypical in both types of study. Pimozide, pipamperone, aceperon, methylperon, and clotiapine were atypical in single-dose studies, clopenthixol in repeated-dose studies. Since the biochemical abnormality causing psychoses is unknown, it may be that current methods of screening for new antipsychotics are inadequate and possibly inappropriate. If a neurotransmitter other than DA is the primary cause, then totally new tests may be needed. Present tests, especially those involving behavioral paradigms, may continue to select out compounds that cause EPS side-effects. New methods such as positron emission tomography scanning and other brain-imaging techniques hold the promise of studying specific types and subtypes of receptors in the living human brain. The recent discovery of chromosomal abnormalities in psychotic illness may provide new insights into the biochemical causes of such disorders and lead to completely new compounds that will be both safer and more effective. In the meantime we plan to review the literature on the clinical use of the compounds identified as atypical in this article and to develop research protocols to assess their efficacy in treatment-resistant psychoses and intractable conditions such as tardive dyskinesia.

Animals↗
PubMed1989

Serotonergic anxiolytics in the treatment of panic disorder: a controlled study with buspirone.

The efficacy of buspirone for panic disorder was tested in 60 patients who met Diagnostic and Statistical Manual of Mental Disorders (3rd ed.) criteria for panic disorder or agoraphobia with panic attacks. Patients were randomly assigned to treatment with buspirone (mean dose 29.5 mg/day), imipramine (mean dose 140 mg/day), or placebo, and treated for 8 weeks after a 4- to 7-day placebo lead-in period. Patients with 4 or fewer attacks per month and those without attacks at the baseline visit were excluded from panic frequency comparisons. Both buspirone and imipramine tended to be better than placebo on total number of panic attacks, global psychopathology, and the Hamilton Anxiety rating scale, but end point differences among treatments were not statistically significant. At the end of the study, 25% of the buspirone patients were panic-free, as were 7% of the imipramine patients and 14% of the placebo patients; again, these differences were not statistically significant. The results of this study were inconclusive, partly because of the relatively small number of patients (10-11) completing the study in each treatment group, and partly because of a robust placebo response in this population. Possible reasons for this high placebo response are discussed, as well as suggestions for changes in study design for future studies.

Adult↗
PubMed1988

Antipsychotic drugs in schizophrenia: current issues.

In the 1950s antipsychotic antidopaminergic drugs were introduced as the pharmacological treatment of schizophrenia. In the last 35 years a large fund of knowledge has been acquired about these drugs. Still, a number of issues regarding them require further addressing. We have reviewed the literature on some of these issues, focusing on those factors that the previous studies have resolved inadequately. The issue of optimal dosages of antipsychotics in schizophrenia has been analyzed from the perspective of the dose requirements during "rapid tranquilization", "in acute psychotic phases of schizophrenia", "in chronically hospitalized psychotic schizophrenic patients" and during "maintenance phases of schizophrenia". We have briefly discussed the different methodologies available for measuring neuroleptic levels in plasma, their methodological weaknesses and strengths and some of the larger studies done with chlorpromazine, haloperidol and fluphenazine to establish correlations between levels, treatment response, oral dosages and side-effects. The theoretically fascinating concept of supersensitivity psychosis has been reviewed and the theoretical and practical weaknesses that exist in most of the papers that have claimed validity for this concept are presented. The article also reviews the preclinical, postmortem and clinical research that demonstrates the presence of site selectivity for dopamine receptors in the newer atypical neuroleptics. Finally, the article briefly reviews the current status of some unorthodox clinical strategies, that may be potentially applicable in managing schizophrenic disorders.

Animals↗
PubMed1987

A controlled clinical trial of tiaspirone in schizophrenia.

The antipsychotic efficacy of tiaspirone, a new atypical antipsychotic agent, was compared to standard neuroleptics, in a single-blind cross-over study. Nine actively psychotic schizophrenic patients entered the study and 6 completed it. Significant overall improvement, on BPRS and CGI ratings, occurred by week 4, on both--tiaspirone and standard neuroleptics. There were no significant differences between tiaspirone and standard neuroleptics, in their antipsychotic efficacy. In keeping with the preclinical profile of tiaspirone, no extrapyramidal symptoms (EPS) were observed with tiaspirone. Two patients showed EPS on standard neuroleptics. Five of the 6 patients showed mild transient elevation of liver enzymes while on tiaspirone. Liver enzymes returned to normal within 3 weeks of discontinuation of tiaspirone. Tiaspirone appears to be a promising new antipsychotic agent that may be clinically effective without causing extrapyramidal syndromes.

Adult↗
PubMed1987

Pre-infusion heart rates and laboratory-induced panic anxiety.

Resting and pre-infusion heart rates recorded in 66 panic disorder patients revealed no significant differences between panickers and nonpanickers. There was also no significant difference in pre-fusion heart rates between either lactate or isoproterenol panickers and placebo nonpanickers. There was neither a sensitizing nor a desensitizing effect of laboratory-induced panic attacks on subsequent pre-infusion heart rates.

Adolescent↗
PubMed1987

Sleep and depression.

Manifestations of sleep disturbances can potentially serve as external criteria for the diagnosis of specific subtypes of major depressive disorder (MDD). Depressed patients generally experience disturbances of sleep continuity and rapid eye movement (REM) sleep. Disturbances in nonrapid eye movement (NREM) sleep (stages III and IV) also occur. Characteristic of primary sleep disturbance in many depressed patients are shortened REM latency periods and instabilities in NREM sleep identified by increases in the number of stage shifts, decreases in the duration of stage III and IV sleep, and a shift towards lighter sleep stages (sleep efficiency disturbances). Treatment modalities for these sleep disturbances include sleep deprivation therapy and antidepressant therapy. Sleep deprivation alone has been only moderately successful, while antidepressant therapy usually results in symptomatic improvement. To restore normative sleep, REM sleep periods and stage III and IV sleep must be returned to normal. Trazodone therapy has been shown to reduce the frequency of arousals, the severity of drowsiness, and the duration of REM sleep, and increase restorative slow wave sleep and stage III and IV NREM sleep.

Depressive Disorder↗
PubMed1987

Thyroid hormone levels in panic disorder.

A history of thyroid dysfunction has been reported in patients with phobic disorders. There is also evidence of a blunted TSH response to TRH stimulation in patients with panic disorder. In this study, values of T3, T4 and T7 were compared between 26 patients with panic attacks and 20 normal controls. Patients were diagnosed according to DSM-III criteria and those with a clinical history of thyroid dysfunction were excluded. Patients were not on any medication when the blood samples were drawn. The mean values of T3, T4 and T7 did not significantly differ between the two groups, suggesting no evidence of hypo or hyperthyroidism; however, the variance of distribution of T3, T4 and T7 values was significantly different between the two groups (Fmax values for T3: 2.55, p value less than 0.05; T4: 3.15, p value less than 0.01; T7: 2.55, p value less than 0.05).

Adult↗
PubMed1987

Tiaspirone in schizophrenia.

It was predicted that tiaspirone, a novel compound, would benefit schizophrenic patients since in animal experiments it is a potent dopamine blocker. Following a placebo washout period of 1 to 2 weeks, 14 patients were treated for 28 days with the drug in a single-blind, dose ranging trial. GAS, NOSIE, and BPRS scores all showed significant improvement. No serious adverse effects were found. The absence of extrapyramidal symptoms was particularly encouraging since 10 of the 14 subjects had previously had them on other neuroleptics. Tiaspirone may represent a step forward in the search for a safer antipsychotic.

Adolescent↗