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S R Hirsch

Publications and source records attributed to S R Hirsch.

At least 37 records · Page 2Linked to original sources
PubMed1995

Elevated platelet calcium mobilization and nitric oxide synthase activity may reflect abnormalities in schizophrenic brain.

Schizophrenia has a diverse nature of clinical symptoms and a number of hypotheses have been suggested to explain its aetiological basis. In this study we have examined two aspects of membrane function, receptor-activated calcium mobilization and calcium activated nitric oxide synthase activity in schizophrenic subjects. Thrombin induces mobilization of calcium ions from intracellular stores. The platelet response of drug naive schizophrenics was found to be significantly increased over a range of thrombin concentrations (0.01 to 0.60 U/ml) compared to control subjects. Possible involvement of nitric oxide (NO) in the aetiology of schizophrenia was investigated. NO has been functionally linked to both dopaminergic and glutamatergic systems both of which are strongly implicated in the biochemical pathology of schizophrenia. Nitric oxide synthase (NOS) activity was determined in platelets of controls, schizophrenic and panic disorder subjects. Enzyme activity was found to be significantly higher in platelets of drug naive schizophrenic subjects compared to controls, drug treated schizophrenics and panic disorder subjects. It is suggested that there is an imbalance of the calcium-induced L-arginine- nitric oxide pathway in platelets of schizophrenic subjects which may be modified by neuroleptic treatment. This imbalance may be mirrored in the central nervous system in particular at the NMDA receptor. It is possible that such a disturbance in the L-arginine-nitric oxide pathway may have pathological implications in the aetiology of schizophrenia.

Adult↗
PubMed1995

Depressive disorder due to craniopharyngioma.

Secondary causes of depression are legion, and must always be considered in patients presenting with features atypical of primary idiopathic depressive disorder. The case described is that of a middle-aged woman presenting initially with a major depressive disorder who was subsequently found to have a craniopharyngioma, leading to a revised diagnosis of mood disorder due to the tumour. Some features of the presentation might have led to earlier diagnosis had their localizing significance been recognized. Diencephalic lesions should always be considered in patients presenting with the hypersomnic-hyperphagic variant of depressive disorder.

Craniopharyngioma↗
PubMed1994

Population based study of fatigue and psychological distress.

OBJECTIVES: To determine the prevalence of fatigue in the general population and the factors associated with fatigue. DESIGN: Postal survey. SETTING: Six general practices in southern England. SUBJECTS: 31,651 men and women aged 18-45 years registered with the practices. MAIN OUTCOME MEASURES: Responses to the 12 item general health questionnaire and a fatigue questionnaire which included self reported measures of duration, severity, and causes of fatigue. RESULTS: 15,283 valid questionnaires were returned, giving a response rate of 48.3%, (64% after adjustment for inaccuracies in the practice registers). 2798 (18.3%) of respondents reported substantial fatigue lasting six months or longer. Fatigue and psychological morbidity were moderately correlated (r = 0.62). Women were more likely to complain of fatigue than men, even after adjustment for psychological distress. The commonest cited reasons for fatigue were psychosocial (40% of patients). Of 2798 patients with excessive tiredness, only 38 (1.4%) attributed this to the chronic fatigue syndrome. CONCLUSION: Fatigue is distributed as a continuous variable in the community and is closely associated with psychological morbidity.

Adolescent↗
PubMed1994

Elevated platelet phosphatidylinositol bisphosphate in mediated schizophrenics.

Levels of phosphatidyl inositol 4,5-bisphosphate (PIP2) have been measured in platelets from schizophrenic and healthy subjects by means of an immunoassay. Resting platelets from schizophrenic patients contained a significantly increased amount of PIP2 compared to controls. The agonist-stimulated hydrolysis of PIP2 in platelets from the schizophrenic group was also significantly greater than that in platelets from the control group. PIP2 plays an important role in cell signalling, and the observed abnormality may be reflected by an impairment in signal transduction via the inositol phospholipid pathway.

Adult↗
PubMed1994

Role of polyamines in the membrane pathology of schizophrenia. A study using fibroblasts from schizophrenic patients and normal controls.

The polyamines putrescine, spermine, and spermidine play a major role in the regulation of cell growth and differentiation, metabolic pathways, and on cell membrane functions in mammalian systems. It has recently been suggested that polyamines may be involved in the pathophysiology of schizophrenia. Moreover, several reports suggest that schizophrenia may be associated with a generalized cell membrane abnormality. In view of these findings, we measured polyamine levels in cultured skin fibroblasts from schizophrenic patients and normal control subjects. These was a significant increase in the levels of spermidine and in total polyamines in fibroblasts and spermine in the culture medium from schizophrenic patients. This preliminary report suggests that polyamines may play an important role in the membrane abnormalities that have been reported in schizophrenic patients.

Adult↗
PubMed1994

Guns and me.

Explore the source record for details and available documents.

Adult↗
PubMed1994

Evaluation of nedocromil sodium 2% ophthalmic solution for the treatment of seasonal allergic conjunctivitis.

During peak ragweed season, 86 patients with seasonal allergic conjunctivitis participated in a 9-week, multicenter, double-masked, placebo-controlled, group-comparative study testing the efficacy and safety of bid nedocromil sodium, 2% ophthalmic solution. The clinical effectiveness of nedocromil sodium was measured by analyzing the means of patient daily symptom scores and eye examinations after 1, 3, 5, and 8 weeks of treatment. The use of nedocromil sodium during peak ragweed pollen season reduced symptom scores with statistically significant treatment differences as compared with the placebo for itchy eyes, tearing, overall eye condition, and symptom summary score. Clinician assessments also favored the use of nedocromil sodium as indicated by significant improvements in tearing, conjunctival injection, and conjunctival edema. No significant side effects were reported by the patients, allergists, or ophthalmologists. We conclude that nedocromil sodium, 2% ophthalmic solution, administered bid is more effective in the relief of symptoms of seasonal allergic conjunctivitis than placebo and causes no major side effects.

Adolescent↗
PubMed1993

Cerebral asymmetries and stimulus intensity relationships in EEG spectra of VEPs in unmedicated schizophrenic patients: relationships with Active and Withdrawn syndromes.

Active and Withdrawn syndromes in schizophrenia have been associated with different patterns of lateral asymmetry: higher left than right hemisphere activity in the Active syndrome and the opposite pattern in the Withdrawn syndrome. Here validation was explored with a power spectral analysis of the visual evoked potential recorded to flashes of five different intensities from primary sensory occipital cortex (O1, O2) and from temporal (T3, T4) cortex. Unmedicated schizophrenic patients were categorised as Active or Withdrawn syndrome by clinical ratings. Pattern of lateral asymmetry of electrodermal orienting responses was recorded and was found to be as predicted: larger on the left than right hand in the Active syndrome with the opposite pattern in the Withdrawn syndrome. Normal controls were also examined. At occipital placements the main results were in beta (18-22 Hz) in which (1), syndromes showed opposite asymmetry patterns consistent with predictions: higher power on the left in the Active syndrome and on the right in the Withdrawn syndrome and (2), there was an absence of normal stimulus intensity/beta power relations in the Withdrawn syndrome. The Active syndrome showed abnormal relations at the temporal location, reflected in high alpha activity (10-14 Hz), together with an abnormal asymmetry in 2-6 Hz activity in the direction of more slow wave activity in the right hemisphere, a lateral asymmetry consistent with the model. When compared with the controls the Withdrawn syndrome was dysfunctional at lower, sensory cortex, levels of processing while the Active syndrome was dysfunctional at higher, temporal cortex, stages of processing. Schizophrenic patients as a group were characterised by abnormal desynchronisation of left temporal activity.

Adult↗
PubMed1993

Pitfalls and problems of the long term use of neuroleptic drugs in schizophrenia.

Although acute and immediate extrapyramidal syndromes are common and, in the case of neuroleptic malignant syndrome, may have serious sequelae, the most important problem with psychotropic medication in schizophrenia remains the tardive movement disorders. These are increasingly recognised as being aetiologically as well as symptomatically heterogeneous. Although risk factors are being identified with greater clarity, there is little in the way of effective treatment. This suggests that clinicians must embark on long term neuroleptic treatment with vigilance. Clozapine alone has few extrapyramidal effects, and has been described in isolated instances as improving established movement disorders. However, haematological idiosyncrasies will preclude its use in all where compliance is uncertain. Its superior efficacy will hopefully give impetus to research into safer analogues.

Animals↗
PubMed1992

Schizophrenia, genetic retrenchment, and epidemiologic renaissance. The Sixth Biennial Winter Workshop on Schizophrenia, Badgastein, Austria, January 26-February 1, 1992.

A distinctive feature of these workshops, in addition to those noted in the introductory overview, is the selection of a relatively isolated location for a 1-week period. This, together with a rich and varied program and an ethos of informality, encourages participants to discuss not only the work presented but also their unpublished work and their intuitions based on preliminary data and analyses. Such an interchange is of inestimable value to the schizophrenia research community. In scientific terms, a panel of concluding discussants (Drs Kendell, Torrey, and Waddington) were in some measure of agreement that genetics, particularly molecular genetics, appears to be experiencing a period of retrenchment, while epidemiology is experiencing something of a renaissance. Maternal influenza was a prominent theme, although the data were far from consistent. It was argued by Dr Wessely that risk for schizophrenia putatively attributable to maternal influenza might be 5% to 10% of all cases, indicating a modest effect. Eclectically, Dr Kendell believed the effect to be "real" but slight and fragile, it being sought against large aggregates that almost inevitably result in differing findings from differing countries or from different data bases within a given country. Gender differences were also among the more prominent themes, not just in an epidemiologic context but also in a variety of other studies. This points anew to disturbances in schizophrenia of factors that regulate, or are intimately associated with, sexual dimorphism in brain development. Abnormalities in cerebral asymmetry continue to pervade a variety of research findings and point further to neurodevelopmental anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1992

Inositol phospholipid turnover in platelets of schizophrenic patients.

Abnormalities in blood cell membrane phospholipid composition and metabolism from schizophrenic patients have been reported by many groups of investigators. Among membrane phospholipids, inositol phospholipids are of special importance as they are involved in transduction system that generates second messengers such as inositol trisphosphate and diacylglycerol. Our studies on platelet inositol phospholipid turnover suggest a significant increase in platelet phosphatidylinositol 4,5-bisphosphate levels, an increased production of inositol trisphosphate in neuroleptic-treated and neuroleptic-free schizophrenic patients platelets and a reduced calcium release by thrombin in neuroleptic-treated schizophrenic patients platelets. The enhanced production of inositol trisphosphate may be due to an increase in its precursor phosphatidylinositol 4,5-bisphosphate with an associated desensitisation of the intracellular inositol trisphosphate receptor by neuroleptics, which may explain the diminished calcium response to thrombin in schizophrenic patients platelets.

Adult↗
PubMed1992

The left medial temporal region and schizophrenia. A PET study.

Regional cerebral blood flow (rCBF) was measured in 30 schizophrenic patients with severe, persistent and stable symptoms using positron emission tomography (PET). Directed and non-directed correlational analysis of the relationship between psychopathology and rCBF was used to identify brain structures implicated in three behavioural subsyndromes of schizophrenia. Psychopathology and neurophysiology (rCBF) exhibited high correlations in the left medial temporal region, mesencephalic, thalamic and left striatal structures. The highest correlation was in the left parahippocampal region. A canonical analysis of the same data highlighted the left parahippocampal region and left striatum (globus pallidus) as sites which linked the behavioural subsyndromes in terms of shared rCBF correlates. Increasing severity of psychopathology was associated with increased rCBF in these regions. Disinhibition of left medial temporal lobe activity mediated by fronto-limbic connections is a possible explanation for these findings; however, the prefrontal component appears to be critically dependent on the behavioural subsyndrome.

Adult↗
PubMed1992

Inadequate treatment response to des-enkephalin-gamma-endorphin compared with thioridazine and placebo in schizophrenia.

The possibility of an involvement of peptidergic systems in schizophrenia has been under investigation for a number of years. Studies of the efficacy of des-tyr-gamma-endorphin were equivocal; more recent studies with des-enkephalin-gamma-endorphin have reported some activity but the peptide has only been investigated as an adjunct to neuroleptic medication, apart from one very small active reference comparator study. In the multicentre study reported here, 96 patients suffering from schizophrenia (DSM-III with a current exacerbation if chronic) were allocated randomly to double-blind treatment with either des-enkephalin-gamma-endorphin (DE-gamma-E) (Org 5878) 10 mg given as a once daily intramuscular injection for 4 weeks, thioridazine 400 mg orally in 2 divided doses or placebo using a double-dummy technique to preserve blindness. There was a significant advantage for thioridazine compared with placebo registered on all measures at weeks 3 and 4. There was no difference between DE-gamma-E and placebo. There was a significant difference between thioridazine and DE-gamma-E at weeks 3 and 4 registered on the MSS and at week 3 registered on the BPRS. The lack of efficacy of DE-gamma-E suggests that the theories that the endorphins have an important role in schizophrenia have to be revised. The need for well designed placebo controlled studies for assessing efficacy in schizophrenia is emphasized.

Adult↗
PubMed1992

Patterns of cerebral blood flow in schizophrenia.

Positron emission tomography was used to study the relationship between rCBF and symptom profiles in 30 schizophrenic patients. Factor analysis confirmed that the symptoms segregated into three syndromes--psychomotor poverty, disorganisation, and reality distortion--described previously. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in paralimbic and association cortex, and in related subcortical nuclei. The study confirmed predictions that psychomotor poverty and disorganisation are associated with altered perfusion at different loci in the pre-frontal cortex, and reality distortion with altered perfusion in the medial temporal lobe. The perfusion patterns suggest that the abnormalities of brain function underlying each of the three syndromes are not confined to single loci, but involve distributed neuronal networks.

Adult↗