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Biomedical subjects

R Shiloh

Publications and source records attributed to R Shiloh.

17 recordsLinked to original sources
PubMed2002

Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia.

The beneficial effect of atypical antipsychotic drugs (APDs) in treatment-resistant schizophrenia patients has been attributed, mostly, to their relatively high serotonergic (5-HT)2 to dopaminergic (D)2 receptor blockade ratio. We hypothesized that a combination of typical APDs (D2 antagonists) and mianserin, a potent 5-HT2 antagonist, might also exert superior efficacy in this population. Eighteen inpatients with treatment-resistant schizophrenia who had an acute psychotic exacerbation of the disorder received, in a double-blind design, 30 mg/day mianserin (n = 9) or placebo (n = 9) in conjunction with typical neuroleptics [haloperidol (n = 9) or perphenazine (n = 9)]. Clinical status was evaluated before, during, and at the end of 6 weeks of combined treatment with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms and Hamilton Rating Scale for Depression. The typical APD/mianserin group exhibited significantly greater improvement in total BPRS scores (17.6% versus 5.5%; P= 0.03) and a trend towards greater improvement in SAPS scores (35.3% versus 13.0%; P = 0.07). Our study indicates that patients with chronic treatment-resistant schizophrenia who have an acute psychotic exacerbation ('acute-on-chronic') may benefit from the addition of a potent 5-HT2 blocker, such as mianserin, to typical antipsychotics. Our findings may further emphasize the contribution of enhanced 5-HT2 blockade to the 'atypicality' of the atypical APDs and to their greater efficacy in alleviating symptoms of chronic treatment-resistant schizophrenia.

Adult↗
PubMed2001

Stability of diagnosis: a 20-year retrospective cohort study of Israeli psychiatric adolescent inpatients.

Outcome according to diagnosis and stability of diagnosis were investigated in a follow-back study of 351 adolescents with various psychiatric disorders hospitalized in a closed psychiatric ward. The duration of follow-back was 15-19 years. All diagnoses were based on the ICD-9. Data were collected from the Health Ministry registry and, in the patients who could be located, by structured telephone interview. Special attention was directed at the diagnosis of transient adolescent psychosis (TAP) vs. schizophrenia and prognostic indicators of suicide. The results showed that the most stable diagnosis was anxiety disorder. The stability of the different diagnoses over time was greater between the second and last admission than between the first and last (for patients with three or more admissions). Number of hospitalizations correlated negatively with prognosis. TAP at second admission was an unstable diagnosis; 66% of these patients had a final diagnosis of schizophrenia. However, patients with a diagnosis of TAP at first admission had a higher predictive index score and a higher outcome score than schizophrenic patients. TAP appeared to be a valid diagnostic entity, distinguishable from schizophrenia in course, frequency of suicidal behaviour and social-occupational outcome. Suicide victims had a higher cumulative length of stay than age- and sex-matched non-suicidal patients. Fifty per cent of the suicide victims had a final diagnosis of schizophrenia, compared to 30 per cent for the whole sample. In conclusion, these findings indicate that TAP is associated with a relatively good prognosis and should probably be differentiated from schizophrenia. Further retrospective and prospective studies of adolescent psychiatric inpatients may help delineate the nature and course of psychosis and other psychopathology in this age group.

Adolescent↗
PubMed2001

Association between severity of schizophrenic symptoms and urinary retention.

A case is presented in which severe urinary retention (UR) occurred during an acute psychotic exacerbation of paranoid schizophrenia. The voiding dysfunction was apparent during continuous treatment with unchanged doses of haloperidol, and it completely resolved with the remission of the psychotic symptoms. A clear temporal correlation was evident between the patient's mental status, the Brief Psychiatric Rating Scale (BPRS) score and the degree of the UR as assessed by quantitatively measuring the total daily post-voiding urine residues. We could not relate the UR to any apparent general medical condition or to the haloperidol treatment. The presented data suggests that UR in schizophrenic patients might be the end-result of various psychosis-related mechanisms.

Acute Disease↗
PubMed2001

Absence of myoglobinuria in acute psychotic patients with marked elevation in serum creatine phosphokinase level.

Elevated levels of serum creatine phosphokinase, muscular type (CK(MM)) are caused primarily by diseased muscle fiber. Acute psychoses are often associated with a marked increase in serum CK(MM) levels, though the reason remains obscure. Since striated muscle damage is also associated with pigmenturia and myoglobinuria, we sought to determine whether the markedly high serum CK level of acute psychosis reflects skeletal muscle damage by evaluating urinary myoglobin in affected patients. Baseline serum CK was measured on admission in 713 consecutive acute psychotic inpatients (BPRS> or =40). Those showing a serum CK levels above 1000 IU/l on the first 2 days of hospitalization underwent urine collection for myoglobin testing. Patients with physical trauma or medical conditions known to cause CKemia were excluded. Twenty-five patients were eligible for the study. In no case did myoglobinuria or pigmenturia accompany the marked CKemia. There is an unexpected dissociation between the robust increase in the serum CK(MM) levels and the absence of myoglobinuria in acute psychosis. Our negative finding may indicate that the serum CK threshold for myoglobinuria is very high (above 10000 IU/l). Alternatively, psychosis-associated CKemia may be related to an unknown, nontraumatic, pathophysiological mechanism(s).

Acute Disease↗
PubMed2001

Abnormal thermoregulation in drug-free male schizophrenia patients.

Schizophrenia patients may develop various thermoregulatory disturbances. We hypothesized that a standardized exercise-heat tolerance test [two 50-min bouts of walking a motor-driven treadmill at 40 degrees C (relative humidity=40%)] would reveal abnormal thermoregulation in drug-free schizophrenia patients. Six drug-free schizophrenia outpatients and seven healthy comparison subjects participated in this study. The schizophrenia patients exhibited significantly higher baseline and exertion-related rectal temperature. The relevance of these findings to the pathophysiology of schizophrenia-related thermoregulatory disorders is as yet unclear.

Adult↗
PubMed2001

Evaluation of the neurotoxic activity of typical and atypical neuroleptics: relevance to iatrogenic extrapyramidal symptoms.

Typical neuroleptic therapy often results in extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Recent reports reveal neurotoxic activity in some neuroleptics. We hypothesized that neurotoxicity might be implicated in EPS. This study aims to evaluate the neurotoxic activity of typical and atypical neuroleptics and to determine the possible role of neurotoxicity in neuroleptic-induced EPS. Perphenazine, haloperidol, clozapine, sulpiride, and risperidone (10-100 microM) were administered, either alone or combined with dopamine, to primary mouse neuronal or intact brain culture and to a human neuroblastoma (NB) cell line (SK-N-SH). Cell viability (measured by neutral red and alamar blue), DNA fragmentation (flow cytometry-NB) were determined. Neuroblastoma: perphenazine, clozapine, and haloperidol (100 microM) decreased viability by 87, 43, and 34% respectively. Sulpiride and risperidone were not toxic. At 10 microM, toxicity decreased markedly. Dopamine (125 microM) potentiated the perphenazine-induced toxicity. Flow cytometry of NB cells treated with perphenazine (2.5-40 microM) showed an increase (perphenazine 20 microM, 40 microM, 48 h) in fragmented DNA (74.7% and 95.0% vs. 8.7% in controls). Lower concentrations increased the G1 phase and decreased S phase in the cell cycle. In primary neurons, perphenazine, haloperidol, and clozapine, but not risperidone and sulpiride, induced a significant neurotoxic effect, which, in intact brain culture, was absent (haloperidol and clozapine) or lowered (perphenazine). Dopamine (0.5 mM) did not modify the effect of the drugs in the primary cultures. Neuroleptics possess differential neurotoxic activity with higher sensitivity of neoplasm tissue (NB compared to primary cultures). The order of toxicity was perphenazine > haloperidol = clozapine:sulpiride and risperidone were not toxic. Neurotoxicity is independent of dopamine and is associated with cell cycle arrest and apoptosis. With the exception of clozapine, neurotoxicity seems relevant to neuroleptic-induced EPS and TD.

Animals↗
PubMed2001

[Antidepressive effect of pyridoxine (vitamin B6) in neuroleptic-treated schizophrenic patients with co-morbid minor depression--preliminary open-label trial].

BACKGROUND: Minor depression is reported in 20-60% of schizophrenic patients during various stages of their disorders; impairing patients' compliance, response to treatment and worsening their overall prognosis. Various anti-depressive treatments have been proposed for such cases but response rates are usually poor. Pyridoxine (Vitamin B6) in essential for the proper metabolism of various neurotransmitters that are considered relevant to the pathophysiology of depression and/or schizophrenia and it has been reported beneficial in ameliorating depressive symptoms as part of major depression, premenstrual syndrome or 'Chinese restaurant syndrome'. We hypothesized that addition of pyridoxine to on-going neuroleptic treatment could improve minor depression in schizophrenic patients. METHOD: Nine schizophrenic patients with co-morbid minor depression participated in this study. All participants had a stable unchanged clinical state (changes in Brief Psychiatric Rating Scale (BPRS). Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative symptoms (SANS) scores < 5%) and all were maintained on unchanged doses of anti-psychotic drugs for at least 4 consecutive weeks prior to initiation of the study. Participants received, open-label, pyridoxine 150 mg/day in addition to their anti-psychotic treatment for 4 consecutive weeks. Mental status was evaluated before, during, and at the end of 4 weeks of pyridoxine administration using the BPRS, SAPS, SANS and HAM-D. RESULTS: Two of the nine patients (22%), characterized by higher initial HAM-D and SANS scores, and by older age and longer duration of illness, experienced marked improvements in depressive symptoms (23% and 28% decrease in HAM-D scores) following 4 weeks of pyridoxine administration. In one of these two, the improvement in depressive symptoms was accompanied by a parallel decrease in SANS Scores. CONCLUSION: A subgroup of schizophrenic patients with comorbid minor depression may benefit from pyridoxine addition to their on-going anti-psychotic treatment.

Adult↗
PubMed2000

Acute antipsychotic drug administration lowers body temperature in drug-free male schizophrenic patients.

We examined, in a controlled design, potential alterations in body temperature of male schizophrenic patients following acute antipsychotic drug (APD) administration. Fourteen drug-free (study group) and seven schizophrenic patients maintained on APDs (comparison group) initiated or received higher dose of their APD, respectively, for 27 days. Initial body temperature was 0.36 degrees C higher in the study group (P=0.01) and decreased within 24 h to values comparable to that of the comparison group (all within normal range).

Adolescent↗
PubMed2000

Heat intolerance in patients with chronic schizophrenia maintained with antipsychotic drugs.

OBJECTIVE: Schizophrenia may be associated with hyperthermic syndromes such as febrile catatonia, neuroleptic malignant syndrome, and heatstroke. The authors hypothesized that an exercise-heat tolerance test would disclose abnormal thermoregulation in schizophrenic patients. METHOD: Seven male schizophrenic outpatients in remission maintained on depot antipsychotic treatment and eight healthy comparison subjects completed a heat tolerance test that consisted of two 50-minute bouts of walking a motor-driven treadmill at 40xC (relative humidity=40%). RESULTS: A significantly higher rise in rectal and skin temperatures was observed in the patient group. No differences in heart rate, blood pressure, or perspiration were detected. CONCLUSIONS: Schizophrenic patients maintained on antipsychotic drugs exhibit impaired heat tolerance. Possible explanations are a reduced ability to convey heat from the body's core to the periphery with or without excessive heat production. The hyperthermic response to the heat tolerance test may reflect a dysfunction associated with schizophrenia, a neuroleptic-induced side effect, or both.

Adult↗
PubMed1997

Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study.

BACKGROUND: We hypothesised that a combined regimen of clozapine, a relatively weak D2-dopaminergic antagonist, and sulpiride, a selective D2 blocker, would demonstrate a greater antipsychotic efficacy by enhancing the D2 blockade of clozapine. METHOD: Twenty-eight people with schizophrenia, previously unresponsive to typical antipsychotics and only partially responsive to current treatment with clozapine, received, double-blind, 600 mg/day sulpiride or placebo, in addition to an ongoing clozapine treatment. The clinical status was evaluated before, during, and at the end of 10 weeks of sulpiride addition using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, and Hamilton Rating Scale for Depression. RESULTS: The clozapine-sulpiride group exhibited substantially greater and significant improvements in positive and negative psychotic symptoms. About half of them, characterised by a younger age and lower baseline SAPS scores, had a mean reduction of 42.4 and 50.4% in their BPRS and SAPS scores, respectively. CONCLUSIONS: A subgroup of patients with chronic schizophrenia may substantially benefit from sulpiride addition to clozapine.

Adult↗
PubMed1996

Low-dose imipramine for thioridazine-induced male orgasmic disorder.

Male orgasmic disorder is commonly encountered among patients treated with thioridazine. This side effect interferes significantly with sexual satisfaction. In this pilot study, eight male schizophrenic patients who complained of orgasmic disorder, compatible with probable retrograde ejaculation during thioridazine treatment, were given concomitant low-dose imipramine (25-50 mg at bedtime). Four of the eight reported complete resumption of their previous ejaculatory function, and in one patient there was a partial, but substantial, improvement. Three patients noted no change. It appears that imipramine might be beneficial for some patients with thioridazine-induced male orgasmic disorder.

Adult↗
PubMed1995

Catatonia as an unusual presentation of posttraumatic stress disorder.

A patient with posttraumatic stress disorder (PTSD) had several episodes of catatonia in the past 44 years. These episodes were characterized by a sudden onset of intense excitement, mild pyrexia, often moderate elevation of serum creatinine phosphokinase and the development of a full catatonic state. We could not relate the symptomatology exhibited to any one of the accepted etiologies of catatonia. We assume, following careful evaluation of the clinical picture, and thorough biochemical and imaging work-up, that in this case the catatonic states represented an overwhelming psychic response to associated traumatic recollections, bringing to extreme the avoidance, numbness and motor responses usually encountered in PTSD.

Aged↗
PubMed1984

6,7,4'-Trihydroxyisoflavan: a potent and selective inhibitor of 5-lipoxygenase in human and porcine peripheral blood leukocytes.

The effect of 6,7,4'-trihydroxyisoflavan on human platelet 12-lipoxygenase and human and porcine PMNL 5-lipoxygenase activities has been studied. 6,7,4'-Trihydroxyisoflavan was found to inhibit 5-lipoxygenase more strongly than 12-lipoxygenase; its concentration for 50% inhibition (IC50) was 1.6 microM for human and porcine 5-lipoxygenase and 22 microM for human platelet 12-lipoxygenase. Inhibition of microsomal cyclooxygenase from ram seminal vesicles is exhibited at much higher concentrations of 6,7,4'-trihydroxyisoflavan (IC50 = 200 microM).

Animals↗