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Biomedical subjects

S Pollack

Publications and source records attributed to S Pollack.

At least 91 records · Page 5Linked to original sources
PubMed1994

The resampling method of statistical analysis.

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.

Adult↗
PubMed1994

Predictors of response to clozapine.

Clinical and biological measures were examined for their relationship to clinical response to clozapine. Associations were found between therapeutic response and the following variables: male gender, paranoid schizophrenia subtype diagnosis, older age at onset of illness, shorter duration of illness, higher levels of pretreatment acute EPS, low pretreatment CSF HVA/5-HIAA, greater decrease in prolactin (PRL) and increase in growth hormone (GH) response to apomorphine stimulation pretreatment and greater inhibition by clozapine treatment of PRL and GH response to apomorphine, and plasma clozapine levels above 350 ng/mL. These results are consistent with other investigators' findings and have practical and heuristic implications for the use of clozapine and understanding its mechanism of action.

Adult↗
PubMed1994

Clozapine and weight gain.

BACKGROUND: To investigate the association of clozapine treatment and weight gain, we studied short- and long-term weight gain, correlation of weight gain with treatment response, and risk factors for weight gain in 82 patients with chronic schizophrenia who received clozapine treatment for up to 90 months. METHOD: Weight values were obtained through retrospective chart review. Clozapine was titrated over an average of 3 to 5 weeks up to a dose of 500 to 600 mg/day. Psychopathology was assessed with the Brief Psychiatric Rating Scale and the Clinical Global Impressions scale. RESULTS: A clinically significant weight gain occurred mostly during the first 6 to 12 months, but continued well into the third year of treatment. Weight gain and treatment response were not correlated, and early weight gain was not a predictor of response. The cumulative incidence of patients becoming substantially overweight exceeded 50%. Being underweight at baseline correlated with maximum amount gained (p = .000), and being overweight at baseline correlated with percentage above ideal weight (p = .006). CONCLUSION: Treatment with clozapine is associated with a high incidence of substantial weight gain, posing a potential long-term health risk. Studies are needed of the underlying mechanisms of weight gain, as well as the treatment for this side effect.

Adult↗
PubMed1994

Cerebral morphometry and clozapine treatment in schizophrenia.

Studies of brain morphology in schizophrenia may be informative about basic pathophysiologic processes, provide clinically useful indicators of treatment response, and lead to the identification of markers for selective treatment effects. This paper reviews findings from magnetic resonance imaging studies of patients with schizophrenia conducted at Hillside Hospital, with special attention to (1) findings that have helped distinguish patients who respond well to typical neuroleptics from those who have gone on to trials of clozapine, (2) the capacity of morphological measures to predict clozapine treatment response, and (3) the possibility that selective hypertrophy of striatal structure may be caused by chronic treatment with typical neuroleptics, but not by clozapine.

Atrophy↗
PubMed1994

Clozapine, negative symptoms, and extrapyramidal side effects.

The importance of persistent negative symptoms in schizophrenia as a limiting factor in psychosocial and vocational rehabilitation has been increasingly emphasized. As a result, treatment trials and new drug development programs are focusing more attention on negative symptoms. Unfortunately, there is enormous phenomenological overlap between negative symptoms and neuroleptic-induced parkinsonism. We report data from a cohort of 56 clozapine-treated patients demonstrating significant correlations between measures of akinesia and anergia. Despite an average drug washout of over 2 weeks, the persistence of drug-induced parkinsonism can confound the assessment of therapeutic drug effects on negative symptoms.

Adolescent↗
PubMed1994

Clozapine dose in the United States and Europe: implications for therapeutic and adverse effects.

The report (1) provides an overview of clozapine doses used in trials conducted in Europe and the United States, (2) compares data on efficacy, and (3) compares side effects of clozapine from recent European and U.S. investigations. The reviewed European trials used a mean dose of 283.7 mg/day, while the mean dose in the U.S. studies was 444 mg/day. Even though the mean doses used in the United States are considerably higher than those used in Europe, the response rates for the two continents are strikingly similar. The main differences in a comparison of two samples evaluated in New York and Innsbruck were found in the prevalence of seizures (Innsbruck, 0%; United States, 7.1%) and confusion (Innsbruck, 0%; United States, 14%). Excitement was less prevalent in the U.S. study. The data presented appear to suggest that a lower dose of clozapine may be as effective as a higher dose in the management of treatment-resistant schizophrenic patients and may cause fewer side effects.

Akathisia, Drug-Induced↗
PubMed1994

The use of clozapine in neurologic disorders.

The advent of clozapine has marked a major advance in the treatment of schizophrenia because of its low incidence of extrapyramidal side effects and superior efficacy. Because of a relatively high incidence of agranulocytosis, approved indications for use are limited to treatment-refractory or neuroleptic-intolerant patients with schizophrenia. However, an emerging body of literature suggests that clozapine may be preferable to typical neuroleptics for treating psychosis in certain neurologic disorders. In addition, clozapine may have a place in the treatment of movement disorders that are caused by or are a result of the pharmacologic treatment of some neurologic illnesses. In general, clozapine doses used in these settings are lower than that for treating psychosis in schizophrenia. This article reviews the experience with clozapine in selected neurologic disorders.

Clinical Trials as Topic↗
PubMed1993

Azidothymidine (AZT)-induced siderosis.

Azidothymidine (AZT) interferes with heme synthesis. This should upregulate the synthesis of transferrin receptors and increase the amount of iron taken up by the cell. We found a 50% increase in the iron content of liver and a 20% increase in the iron content of macrophages in AZT-treated mice.

Animals↗
PubMed1993

In vivo modulation of natural killer cell activity by tamoxifen in patients with bilateral primary breast cancer.

Natural killer (NK) cell activity, the autologous mixed lymphocyte reaction (AMLR) and proportions of T cell subpopulations (CD3+/CD4+ and CD3+/CD8+) and NK cells (CD16+) were studied in 21 patients with bilateral primary breast cancer (BBC), 10 patients with single-breast cancer (SBC) and 20 healthy controls. All patients studied had no evidence of disease and had been off radiotherapy and/or chemotherapy for at least 1 year. Ten patients with BBC were also treated with tamoxifen. Patients with SBC had NK cell activity, AMLR responses and T cell subpopulations that were comparable to those of normal controls. In patients with BBC, a significant (P < 0.01) increase in NK activity compared to that in normal controls (42 +/- 13% versus 21 +/- 10%, effector-to-target cell ratio, 25:1) and a significant (P < 0.05) decrease in CD4+ T cell proportions (30 +/- 15% versus 49 +/- 13%) and absolute numbers (472 +/- 82/mm3 versus 953 +/- 131/mm3) were found. However, the proliferative response of BBC patients' T lymphocytes in AMLR was in the range of the normal controls. Lymphocytes derived from 10 BBC patients treated with tamoxifen exhibited NK cell activity that was comparable to that of normal controls and patients with SBC, and was significantly (P < 0.01) reduced compared to the pretreatment period. BBC patients who received tamoxifen also show a reduction in the proportion of CD4+ T cells and in AMLR proliferative responses, which decreased compared to levels in normal controls. Taken together, these results indicate that long-term tamoxifen treatment modulates immune responses in BBC patients.

Adult↗
PubMed1993

The dopamine-serotonin relationship in clozapine response.

The effects of clozapine on the dopamine and serotonin systems may underlie its atypical pharmacologic and clinical profile. To examine this hypothesis, we measured dopamine and serotonin plasma and cerebrospinal (CSF) metabolites and the relationship of these values to treatment response in 19 neuroleptic refractory and intolerant schizophrenic patients. Only a small change in the CSF and plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels was found. However, the pretreatment CSF HVA/5HIAA ratio and, to a lesser extent, the CSF HVA level predicted treatment response. These results suggest that the modest relationship between HVA and 5-HIAA and treatment response supports the involvement of both neurotransmitters in the pathophysiology of schizophrenia.

Adolescent↗
PubMed1993

Staff distress among haemophilia nurses.

To investigate the severity, sources, and means used to cope with the distress experienced by haemophilia nurses as a result of the widespread infection with Human Immunodeficiency Virus among haemophiliacs, we collected anonymous questionnaire data from all nurses in the Haemophilia Nursing Network Directory, compiled by the National Haemophilia Foundation in June, 1990. Questionnaires were returned by 136 of the 181 (75%) nurses in the sample. Over 50% of the sample gave distress responses to 15 of 44 statements. Areas associated with the greatest distress were: (1) Failure of patients to take steps to prevent transmission of HIV; (2) Fear of getting infected, and (3) the repeated loss experienced as patients died from infection. Nurses working with haemophiliacs for 11-15 years were particularly vulnerable to feelings of guilt for having participated in the treatment that resulted in HIV infection. Fear of contagion and distress from patient deaths were mutually exclusive ways of reacting to HIV in haemophiliacs. Looking for a new job was related to all major sources of distress. Interaction with peers was perceived as being the most useful source of emotional support.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Erythrocyte haemolysate interacts with ATP-Fe to form a complex containing iron, ATP and 13 800 MW polypeptide.

Iron first entering the reticulocyte is bound to ATP in the low MW cytosolic pool; some is also 'loosely bound' to haemoglobin, coeluting with haemoglobin from a molecular sieve column though not incorporated into haem. When haemolysate is mixed with ATP-Fe in vitro a similar high MW iron-containing complex is formed: the ATP-Fe interacts with a non-haemoglobin constituent of the haemolysate to form a high MW ATP-Fe complex in which the ratio of ATP:Fe (originally 6:1) is reversed, so that the complex contains more iron than ATP. The high MW ATP-Fe complex is formed even when ATP is in 150-fold molar excess and is formed without detectable hydrolysis of the ATP. The activity of haemolysate in forming the high MW ATP-Fe complex is not diminished by dialysis; all of the activity is recovered in the haemoglobin-containing fraction obtained from an Ultrogel AcA 44 column. The activity does not derive from haemoglobin since 85% of the activity is removed when haemoglobin is purified from haemolysate with DEAE-Sephadex. The chelatable iron pool of the cell probably includes both the high MW ATP-Fe complex and low MW ATP-Fe. Shunting of ATP-Fe to a high MW aggregate reduces the amount of iron present in the highly reactive low MW form and thus probably serves to limit the formation of cell damaging radicals.

Adenosine Triphosphate↗
PubMed1993

Polydipsia and tardive dyskinesia in chronic psychiatric patients--related disorders?

Dopamine supersensitivity, presumably playing a role in tardive dyskinesia, has been implicated in the unexplained polydipsia occurring in chronic psychiatric patients. To investigate this hypothesis, the authors compared laboratory measurements indicating the fluid status of 65 patients before and after the development of tardive dyskinesia. No evidence was found that patients who develop tardive dyskinesia concurrently develop abnormalities in fluid regulation.

Adolescent↗