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Biomedical subjects

S R Hirsch

Publications and source records attributed to S R Hirsch.

At least 55 records · Page 3Linked to original sources

Phenylacetic acid in CSF and serum in Indian schizophrenic patients.

1. It has been proposed that an increase in the concentration of the neuromodulator phenylethylamine at the post-synaptic dopamine receptor may be involved in the etiology of schizophrenia. If this increase is the case, a reduction in the CSF and/or serum concentrations of phenylacetic acid, its major metabolite, might be anticipated. 2. The authors have found in hospitalized Indian schizophrenic patients ingesting antipsychotic drugs, that the paranoid subgroup did indeed exhibit lower levels of unconjugated, conjugated and total phenylacetic acid in both serum and CSF.

Adult↗

Trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients: clinical and social outcome at two years.

OBJECTIVE: To evaluate a novel approach to the prophylaxis of schizophrenic relapse characterised by administration of brief courses of neuroleptic for the earliest non-psychotic signs of relapse (prodromal symptoms). DESIGN: Two year follow up of subjects randomised, double blind, to receive either active (control group) or placebo (intermittent group) depot neuroleptic medication. Both groups received brief courses of oral neuroleptic when prodromal symptoms or relapse occurred. SETTING: Psychiatric outpatient department, Charing Cross Hospital, London. SUBJECTS: 54 Stable patients in remission who met the American Psychiatric Association's DSM-III criteria for schizophrenia on the basis of case notes. MAIN OUTCOME MEASURES: Survival without relapse, survival without hospitalisation, point prevalence of extrapyramidal side effects and tardive dyskinesia, structured assessment of social functioning (social adjustment scale II), and frequency of prodromal symptoms. RESULTS: Of 19 relapses recorded over two years, 10 (53%) were preceded by non-psychotic prodromal signs. Survival rates for both relapse and hospitalisation were worse with intermittent treatment than continuous treatment over the two year follow up: 92% of controls and only 54% of patients given intermittent treatment survived the two year period without hospitalisation. Prolonged or frequent relapses as well as episodes of prodromal symptoms were more frequent with intermittent treatment. Lower scores for extrapyramidal side effects were recorded in the intermittent treatment group, but periodic assessments of social functioning failed to show any social advantages from this. CONCLUSION: The findings are at variance with a previous report of one year follow up in this cohort and attest to the superiority of continuous depot neuroleptic prophylaxis in preventing both psychotic and neurotic or dysphoric morbidity in schizophrenia.

Administration, Oral↗

The platelet polyphosphoinositide system in schizophrenia: the effects of neuroleptic treatment.

Signal transduction, mediated by the thrombin-stimulated polyphoshoinositide (PPI) turnover was studied in platelets from 44 schizophrenic patients and 33 healthy volunteers. The stimulated generation of inositol phosphates in the schizophrenic group was significantly greater than that in the control group. There was a lack of correlation between this augmented response and a variety of clinical parameters. The response in 9 drug-naive schizophrenic patients was not significantly different from that in controls. The response was significantly augmented in patients receiving neuroleptic treatment and in patients who had been off neuroleptics for at least 4 months. These results indicate that neuroleptic treatment may produce a long-term modification of signal transduction via the PPI system. Further studies are required to elucidate the exact nature of this modification and to explore the possibility that this effect of the neuroleptics may provide a novel approach to understanding the neurochemistry of schizophrenia and to monitoring the neuroleptic treatment.

Adult↗

A multicenter trial of nedocromil sodium, 1% nasal solution, compared with cromolyn sodium and placebo in ragweed seasonal allergic rhinitis.

This study was a double-blind, parallel-group study to evaluate a new medication, nedocromil sodium, 1%, in comparison with placebo and cromolyn sodium, 4%, for treatment of ragweed seasonal allergic rhinitis. Two hundred thirty-three patients (aged 12 to 65 years) from eight centers were randomized to treatment, one spray per nostril, four times daily, with nedocromil sodium, cromolyn sodium, or matched placebo (80, 76, and 77 patients, respectively). All patients had at least a 2-year history of ragweed seasonal allergic rhinitis. Treatment was for 8 weeks during the ragweed season, and daily pollen counts were used to identify the peak 3-week period. Clinic examinations were made before and after the 1-week baseline and after 1, 3, 5, and 8 weeks of treatment. Rhinitis symptoms were recorded each day by the patients. Nedocromil sodium was more effective than placebo (p less than 0.05) in relieving symptoms as recorded by the patients. Cromolyn sodium was also more effective than placebo, but the difference was not usually significant. Similarly, the active treatments were both better than placebo for clinical parameters measured at visits and for global opinions of treatment, and more rescue therapy was used by the placebo-treated group. There was no significant difference between the two active treatments, but the trend throughout was in favor of nedocromil sodium. Our findings demonstrated nedocromil sodium to be at least as effective as an established therapy (cromolyn sodium) in reducing symptoms of rhinitis during the peak ragweed pollen season.

Adolescent↗

Metabolic effects of combination glipizide and human proinsulin treatment in NIDDM.

The effects of 3 mo of treatment with a combination of glipizide and human proinsulin were studied in a small group of closely monitored patients. The patients had non-insulin-dependent diabetes mellitus (NIDDM) and poor glucose regulation, despite maximal sulfonylurea therapy. This was a randomized double-blind placebo-controlled trial in which there were three treatment groups who received either 20 mg glipizide given 30 min before breakfast and dinner and human proinsulin given subcutaneously at bedtime (n = 5), glipizide and human proinsulin placebo (n = 5), or glipizide placebo and human proinsulin (n = 5). Glycemic regulation was assessed by measurements of 24-h plasma glucose profiles and glycosylated hemoglobin. Our observations demonstrate that the combination of glipizide plus human proinsulin was more effective than either agent alone in controlling overall glycemia in patients with NIDDM. The data support the concept of use of an agent during the day that has its major effects postprandially and another agent at bedtime that is relatively hepatospecific.

Administration, Oral↗

Trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients: clinical outcome at one year.

A study was conducted to investigate a novel approach to the prophylaxis of schizophrenic relapse. The treatment strategy comprised brief intermittent courses of neuroleptic agents begun as soon as non-psychotic symptoms believed to be early signs of relapse appeared. Fifty four stable, remitted outpatients meeting the American Psychiatric Association's DSM-III criteria for schizophrenia were randomised double blind to receive brief intermittent treatment with either active or placebo depot neuroleptic injections. Only three patients given placebo injections and two controls were admitted to hospital during one year of follow up. Eight (30%) of the patients given placebo injections and only 2 (7%) of the controls, however, had a recurrence of schizophrenic symptoms. Patients given placebo injections experienced fewer extrapyramidal side effects and showed a trend towards a reduction in tardive dyskinesia. Dysphoric and neurotic symptoms were identified before eight out of 11 relapses, and these symptoms were more frequent in patients given placebo depot injections. These results suggest a viable but not necessarily better alternative to continuous oral or depot treatment for less ill, chronic, stabilised schizophrenics based on the early treatment of putative prodromal symptoms of relapse.

Adult↗

Recommendations for the use of residential air-cleaning devices in the treatment of allergic respiratory diseases.

In an attempt to recommend standards for room air-cleaning devices, a committee reviewed (1) the types and performance characteristics of available domestic air-cleaning devices, (2) the available data on concentrations of allergens in the indoor air, and (3) the studies that have examined the health effects of the use of indoor air-cleaning devices. Absense of adequate data on the clinical relevance of indoor ambient allergen levels, as well as the effect of air-cleaning devices on these levels, plus a general lack of health effects by these devices in published double-blind studies precluded any firm recommendations for their use. It was clear, however, that use of room air-cleaning devices in the absence of other forms of environmental control was not reasonable.

Air↗

Criteria for evaluating improvement in schizophrenia in psychopharmacological research (with special reference to gamma endorphin fragments).

A review of treatment trials with DT gamma E revealed widely discrepant results. Relevant variables were the variety of measures employed for monitoring psychotic symptoms, and the different criteria used to judge the degree of improvement. The authors suggest a uniform outcome criterion for early trials of new treatments, which would generate more consistent and comparable results between studies, and give a stronger indication of the value of the treatment under test. When the data from the various treatment trials of DT gamma E were reanalysed, applying a uniform outcome criterion of improvement of a change of 80% or more on rating-scale score, the results were more consistent than would have been suspected from the original reports.

Clinical Trials as Topic↗

The effects of some polyamines on putative behavioural indices of mesolimbic versus striatal dopaminergic function.

The presence of polyamines in the brain, together with the previous reports of a structural similarity with neuroleptics, has led to the hypothesis that polyamines may have a modulatory role in the control of cerebral dopamine function. In this study, the effects of two polyamines, spermine and spermidine, were therefore tested on indices of dopamine-mediated behaviour in rats and mice. Spermine and spermidine caused a dose-dependent inhibition of mouse spontaneous climbing behaviour and wheel running at doses between 5 and 40 mg/kg IP but failed to cause catalepsy in the rat or to antagonise the stereotyped behaviour induced by apomorphine. When polyamines were given by intracerebral injection a similar regional selectivity was seen. Both spermine and spermidine (5-20 micrograms) when given bilaterally into the nucleus accumbens inhibited the hyperactivity caused by amphetamine injected into the same nucleus. However, when injected into the rat corpus striatum, neither polyamine was able to initiate any asymmetry or circling either spontaneously or after apomorphine injection IP. These results indicated a selective action of polyamines on mesolimbic dopamine behaviour. Possible implications for the understanding of psychosis and future work are suggested.

Amphetamine↗

Does short term placebo treatment of chronic schizophrenia produce long term harm?

A randomised double blind placebo controlled trial is the most reliable method of assessing putative new developments in medical treatment. In schizophrenia, however, some clinicians believe that relapse contributes to long term deterioration and therefore that patients exposed to either placebo or an inactive new treatment may be put at a disadvantage in the long run if the trial leads to an additional relapse. A seven year follow up of patients included in a randomised placebo controlled trial of fluphenazine decanoate, in which 66% of the group given placebo relapsed compared with 8% of those who received the active drug, permitted examination of any long term adverse consequences in those patients who had received placebo. Seventy six (94%) of the 81 patients in the original trial were followed up. At the end of the follow up period there were no consistent or important differences in any measure of clinical or social outcome between the patients who had received placebo and those who had received the active drug. This negative finding has implications for the debate on the risk of placebo controlled trials of maintenance treatment in chronic schizophrenia.

Chronic Disease↗