Clozapine effects on neuroendocrine response to apomorphine challenge testing in chronic neuroleptic nonresponsive schizophrenia: preliminary findings.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Pollack.
Explore the source record for details and available documents.
Because of the abundance of the classical form of Kaposi sarcoma (CKS) among Jews and people of Mediterranean origin, studies have been conducted to find an association between CKS and HLA antigens. No conclusive results have been drawn, although in a number of these investigations an increased incidence of HLA-DR5 was reported. In our study 49 CKS patients of Jewish origin were serologically analyzed for HLA class I and class II antigens. We found no significant deviation in serologically defined HLA antigens frequencies between patients and 99 ethnically matched controls. However, a nonsignificant decrease in the frequencies of HLA-DR4, HLA-DR12, and the combination of DR4/DR11 was observed. Then we determined in these patients HLA-DRB1, HLA-DQA1, and DQB1 allelic polymorphism by oligotyping on PCR-amplified DNA. In this molecular analysis the only notable finding was a decreased frequency of the combination HLA-DQA1*0301/DQB1*0301, which appeared in one (2%) patient compared to 13 (13%) of the controls. However, the decrease was not statistically significant. On the basis of both serological and molecular analysis done on a relatively large group of CKS patients, we conclude that there is no significant linkage between HLA antigens and CKS in Jewish population.
OBJECTIVE: The purpose of this study was to determine if plasma clozapine levels were associated with treatment response. METHOD: To examine this question, neuroleptic nonresponsive patients with schizophrenia or schizoaffective disorder were given clozapine, which was titrated to 500 mg/day by day 14 of treatment, and the dose was held fixed at least through day 21. Subsequently, clozapine doses were adjusted as clinically indicated, up to a maximum of 900 mg/day. Plasma clozapine levels were obtained at weeks 3 and 6, and standard clinical ratings (Brief Psychiatric Rating Scale [BPRS] and Clinical Global Impression) were done at baseline and at weeks 3 and 6. RESULTS: Data from 45 subjects were analyzed. There were no correlations between plasma clozapine levels and change in BPRS scores at treatment weeks 3 and 6. However, when the subjects were classified as responders or nonresponders, therapeutic response was associated with clozapine blood levels above 350 ng/ml. CONCLUSIONS: This study suggest that clozapine blood levels are correlated with clinical response.
OBJECTIVE: This study sought to elucidate the relation of clinical, neuropsychological, and seizure variables to chronic and postictal psychoses in patients with temporal lobe epilepsy. METHOD: Forty-four patients with treatment-refractory temporal lobe epilepsy were given formal psychiatric evaluations; 29 patients had no psychiatric disorder or a nonpsychotic disorder, eight patients had postictal psychoses, and seven patients had chronic psychoses. Comparisons of clinical, neuropsychological, magnetic resonance imaging, and seizure variables were made between the nonpsychotic and the psychotic patients and, secondarily, between the patients with transient postictal psychoses and those with chronic psychoses. RESULTS: Bitemporal seizure foci, clustering of seizures, and absence of febrile convulsions were associated with both postictal psychoses and chronic psychoses. Younger age at onset of epilepsy and lower verbal and full-scale IQs differentiated the patients with chronic psychoses from those with postictal psychoses. CONCLUSIONS: Patients with temporal lobe epilepsy with chronic and postictal psychoses show similar profiles of clinical and seizure variables, suggesting shared etiologic factors. These factors may increase the propensity to develop psychotic symptoms, while other factors, such as time of onset of epilepsy and underlying neuropathology, may determine whether transient or chronic psychotic symptoms develop. Even among patients with treatment-refractory temporal lobe epilepsy, a specific subgroup of patients, characterized by bitemporal seizure foci, an absence of febrile convulsions, and a history of clustering of seizures, appears to be particularly prone to develop psychotic disorders. A process similar to secondary epileptogenesis may be involved in the development of the psychoses.
OBJECTIVE: Several studies have suggested that many patients with anxiety disorders present in nonpsychiatric medical settings such as primary care facilities, emergency services, and general practice. This study examined the prevalence of panic disorder and generalized anxiety disorder among patients admitted to the general emergency service at an urban medical center in Israel. METHODS: Four groups totaling 517 patients were assessed. The groups consisted of patients presenting with somatic complaints for whom no physical condition was diagnosed, patients with somatic complaints found to have a physical disorder, a group of nonpsychiatric consecutive admissions to the emergency service, and a group of referrals to the psychiatric emergency service. RESULTS: The prevalence of panic disorder and generalized anxiety disorder in the entire sample was 2.7 percent, which is comparable to the prevalence rates reported in various community studies. However, the prevalence among patients with somatic complaints but no physical disorder was 6.7 percent, significantly higher than in the nonpsychiatric comparison groups. The prevalence in the group of psychiatric referrals was 4.8 percent. CONCLUSIONS: A population at risk for higher prevalence of anxiety disorders can be identified among patients seen in an emergency service. Physicians in primary care settings and general emergency services should consider anxiety disorders in the differential diagnosis of patients with somatic complaints but without a diagnosis of physical disorder.
The authors review the current data on patterns of adolescent employment and examine the epidemiology of work-related injuries among adolescents in the U.S. They summarize the laws that have been created to protect adolescents against exploitation and injury in the workplace and the erosion of those measures that has occurred since 1980. Finally, the authors offer recommendations for the diagnosis and prevention of occupational injury among adolescents.
We present a comparison of the results from two studies of patients on clozapine. The American study (n = 84; Hillside Hospital, Glen Oaks, NY) and the European study (n = 63; Innsbruck University Clinics, Innsbruck, Austria) both examine efficacy and side effects in schizophrenic patients on this atypical neuroleptic. There is a very substantial difference in the dosing regimen used on both continents and this is reflected in the studies reported. A question with major clinical implications is whether the higher doses commonly used in the United States lead to a better outcome or a different profile of side effects. Outcome as a function of serum concentration will be examined. Results confirm a lower dose, lower clozapine blood level, and a lesser degree of side effects in the Austrian cohort when compared to the American sample. Surprisingly, the clinical efficacy of the lower dosing regimen was superior to the higher dose. Reasons for this anomaly are explored.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The Paramecium surface proteins (immobilization antigens) are expressed in a mutually exclusive manner; only one antigen is found on the cell surface at a time. Expression of these proteins is regulated in response to environmental cues such as temperature and pH. This regulation has been shown to be controlled at the level of mRNA abundance by transcriptional and post-transcriptional mechanisms. Here, we have studied the transcription and regulated expression of the immobilization antigen A gene in Paramecium tetraurelia by transforming an A-deficient strain, d12, with cloned portions of the A gene via microinjection. The A gene is approximately 8 kilobases (kb) long with the transcription start site at position -9 or -8 and the start of translation at position +1. Paramecia transformed with cloned DNA containing A-gene sequences beginning at position -264 and ending 63 base pairs (bp) past the gene's polyadenylation site show properly regulated expression of immobilization antigen A. Lines derived from paramecia transformed with a plasmid containing A-gene sequences starting at position -211, however, show markedly reduced A-gene mRNA levels, and rarely express the A antigen. Nevertheless, cells that do express the A protein exhibit mutual exclusion and normal responses to environmental stimuli. Thus, the 54 bp between -264 and -211, while important for transcription, are not involved in the control of mutual exclusion and responses to environmental changes. Further deletion to position -151 yields similar, but more extreme, results.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
In the last 10 years, Ethiopian Jews have immigrated to Israel in large numbers. Up to 1990 they came directly from their remote villages in northern Ethiopia and no HIV infection was detected in the several thousands that came. In contrast, 1.74% of approximately 14,000 new immigrant Ethiopians who arrived in 1991-92, after spending more than a year in Addis Ababa, were HIV positive. Several infants born in Israel following the latter immigration were found to be infected, whereas more than 2500 children born in Ethiopia were negative. Sexual transmission during their stay in Addis Ababa is thought to be the only route of infection, and therefore this is a newly infected population. Immunological studies revealed very low CD4 count in HIV-infected people. HIV-negative Ethiopian immigrants to Israel also have a lower CD4 count than the general Israeli population. Further studies are currently under way to look at the natural history of this particular HIV-infected group.
In 1991, more than 15,000 Ethiopian Jews immigrated to Israel after spending more than a year in Addis Ababa. They came from remote villages and had had no contact with modern medicine for centuries. About 2% of these new immigrants were found to be HIV positive. Their completely different background forced the Israeli government to develop a special educational program explaining about the modes of HIV infection and prevention measures. The staff participating in the program were mainly Ethiopian Jews who immigrated to Israel before 1990 and were employed as nurses or social workers. The goal of the study was to prevent the spread of the virus; thus the target population was those who were infected with HIV. As most of them were illiterate, posters with pictures were used to explain risk factors, and lectures were given explaining what a virus is and, especially, the "carrier state". Using this program the spread of HIV inside the Ethiopian community seems to have diminished.
Cardiovascular and ventilatory responses to electrically induced dynamic exercise were investigated in eight healthy young males with afferent neural influence from the legs blocked by epidural anaesthesia (25 ml 2% lidocaine) at L3-L4. This caused cutaneous sensory anaesthesia below T8-T9 and complete paralysis of the legs. Cycling was performed for 22.7 +/- 2.7 min (mean, SE) (fatigue) and oxygen uptake (VO2) increased to 1.90 +/- 0.13 1 min-1. Compared with voluntary exercise at the same VO2, increases in heart rate (HR) (135 +/- 7 vs. 130 +/- 9 beats min-1) and cardiac output (16.9 +/- 1.1 vs. 17.3 +/- 0.91 min-1) were similar, and ventilation (54 +/- 5 vs. 45 +/- 41 min-1) was higher (P < 0.05). In contrast, the rise in mean arterial blood pressure during voluntary exercise (93 +/- 4 (rest) to 119 +/- 4 mmHg (exercise)) was not manifest during electrically induced exercise with epidural anaesthesia [93 +/- 3 (rest) to 95 +/- 5 mmHg (exercise)]. As there is ample evidence for similar cardiovascular and ventilatory responses to electrically induced and voluntary exercise (Strange et al. 1993), the present results support the fact that the neural input from working muscle is crucial for the normal blood pressure response to exercise. Other haemodynamic and/or humoral mechanisms must operate in a decisive manner in the control of HR, CO and VE during dynamic exercise with large muscle groups.
A series of depressed patients had monoamine metabolites measured in cerebrospinal fluid (CSF) and urine. We wished to see if CSF or urinary measures were more strongly associated with suicidal behavior in depression. Using a variety of graphical and analytic statistical approaches we found that the urinary measures of dopamine metabolism had the strongest association with suicide attempts in depression. These surprising results suggest that selected peripheral correlates of monoaminergic neurotransmission deserve further study in suicidal behavior.
OBJECTIVE: This study addressed the unique clinical properties attributed to the atypical antipsychotic clozapine, including its efficacy in patients with treatment-refractory psychosis and against negative symptoms, its lack of acute extrapyramidal side effects, and the longer time course of its therapeutic effects. METHOD: The clinical responses of 84 schizophrenic inpatients (66 with treatment-refractory illness and 18 who were intolerant of antipsychotic treatment) were examined. After all previous antipsychotic medications had been withdrawn, the patients were treated with clozapine according to a standardized titration and dosage schedule. Patients who tolerated and responded to treatment were discharged and maintained on a regimen of clozapine for up to 52 weeks. Patients were evaluated for behavioral response and side effects after weeks 3, 6, 12, 26, 39, and 52 of treatment. RESULTS: Fifty percent of the patients with treatment-refractory illness and 76% of the treatment-intolerant patients responded to clozapine in up to 52 weeks. The optimal period for a trial of clozapine appeared to be 12-24 weeks. Clozapine exhibited therapeutic effects on negative symptoms, but these were not clearly independent of its effects on positive symptoms and extrapyramidal side effects. Several variables, including early age at onset of illness and female gender, were found to be predictors of poor response to treatment. Predictors of good response included the presence of extrapyramidal side effects during previous treatment with classic neuroleptics and a diagnosis of paranoid schizophrenia. CONCLUSIONS: These findings have important implications for the use of clozapine and our understanding of the pathophysiology of treatment-resistant schizophrenia.
Some non-statisticians occasionally use improper statistical methodology due to a lack of appreciation for the model assumptions that underlie a particular technique. The resampling method is a recent attempt to solve statistical problems with a minimum of assumptions. In essence, resampling involves an intuitive approach to inferential statistics that obviates the need for the mathematically derived sampling distribution. The resampling approach takes advantage of readily accessible high-speed computers to do a computationally intensive Monte Carlo experiment on the available data. The resampling approach liberates the user from imposing assumptions that are sometimes dubious. It also directs one away from a black-box attitude toward statistical analysis and instead forces the user to consider the purpose of the inferential process. A particularly user-friendly implementation of resampling methods that addresses some of the problems faced by non-statisticians is found in a simple, yet powerful, computer program called "Resampling Stats," version 3.13.
Explore the source record for details and available documents.