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Biomedical subjects

M Meisner

Publications and source records attributed to M Meisner.

At least 19 recordsLinked to original sources

Blood volume determination using hydroxyethyl starch: a rapid and simple intravenous injection method.

OBJECTIVE: To develop and evaluate a new method for blood volume measurements using hydroxyethyl starch as a dilution marker. DESIGN: Laboratory and clinical investigation. SETTING: Neurosurgical operating rooms and anesthesiological laboratories of a university hospital. PATIENTS: Twelve patients who underwent a neurosurgical operation. INTERVENTIONS: Anesthesia and operations were carried out by physicians who were not involved in the study. In addition, blood samples were drawn from 50 volunteers. MEASUREMENTS AND MAIN RESULTS: Blood volume measurements by the hydroxyethyl starch method were validated in vivo by comparison with a conventional carbon monoxide technique. Patients were intravenously injected with hydroxyethyl starch (100 mL) and received simultaneously an injection of carbon monoxide (50 mL) into a closed-circuit ventilation system. Blood samples obtained before and 5 mins after injection were analyzed for carboxyhemoglobin and glucose plasma concentrations after acidic hydrolysis of hydroxyethyl starch. Blood volume was calculated from the difference between glucose concentrations measured after hydrolysis in the plasma, before and after the addition of hydroxyethyl starch. In vitro, the hydroxyethyl starch method had an error and a precision of approximately 2%. In vivo, simultaneous measurements of blood volume using hydroxyethyl starch and carbon monoxide demonstrated a high correlation (r2 = .96, p < .001) between these methods. The mean difference between the two methods relative to their average value was 1.0 +/- 3.5%; the bias was 52.3 mL, and the 95% confidence interval was -64.0 to +168.7 mL. CONCLUSIONS: Blood volume determination by the hydroxyethyl starch method is accurate and rapid and may enhance perioperative monitoring of fluid and blood therapy.

Adult

Estimating population size when duplicates are present.

Each of K mental health programmes reports the number of patients served in a year. The sum of these numbers, y, is an overcount because some patients are seen in more than one programme. Health care planners need to know the unduplicated number served by the mental health system. Thus, there is an unknown number, M, of distinct individuals who appear on one or more of K lists; some appear on multiple lists and the duplicates are not readily identifiable. Let X be the number of lists on which a randomly selected individual appears. When E(X) is known, y/E(X) is the natural estimator of M. We assume that we know the number of programmes, Xi, used by the ith individual in a random sample of recipients of service. Here, the intuitive estimator, Y/X has desirable statistical properties. We give confidence interval estimators for M. We apply the method to estimate the number of individuals served in 1991 by the mental health programmes in New York State.

Confidence Intervals

Statistical methods for cost-effectiveness analyses.

A statistical framework is presented for examining cost and effect data on competing interventions obtained from an RCT or from an observational study. Parameters of the join distribution of costs and effects or a regression function linking costs and effects are used to define cost-effectiveness (c-e) measures. Several new c-e measures are proposed that utilize the linkage between costs and effects on the patient level. These measures reflect perspectives that are different from those of the commonly used measures, such as the ratio of expected cost to expected effect, and they can lead to different relative rankings of the interventions. The cost-effectiveness of interventions are assessed statistically in a two stage procedure that first eliminates clearly inferior interventions. Members of the remaining admissible set are then rank ordered according to a c-e preference measure. Statistical techniques, particularly in the multivariate normal case, are given for several commonly used c-e measures. These techniques provide methods for obtaining confidence intervals, for testing the hypothesis of admissibility and for the equality of interventions, and for ranking interventions. The ideas are illustrated for a hypothetical clinical trial of antipsychotic agents for community-based persons with mental illness.

Antipsychotic Agents

Placebo washout in trials of antipsychotic drugs.

For antipsychotic phase 3 clinical trials, we compare the relative merits of a placebo washout period with an alternate design strategy using a low-dose antipsychotic treatment. Evaluations are made with respect to the achievement of specific clinical trial design goals including the effect on power for detecting between-treatment and within-treatment pre-post differences. The relative merits of these two designs are discussed separately for those patients who enter the initial leadin period after withdrawal from previous antipsychotic medication and for those not on medication immediately before that period.

Antipsychotic Agents

Effect of varying haloperidol plasma levels on negative symptoms in schizophrenia and schizoaffective disorder.

Double-blind haloperidol was administered during two consecutive 3-week periods to 65 patients with acutely exacerbating schizophrenia or schizoaffective disorder. Two plasma levels were targeted. low (2 ng/mL) and moderate (10 ng/mL). The subjects were randomly assigned to four treatment sequences (low-low, low-moderate, moderate-moderate, or moderate-low). Data from 28 patients were available for the analyses of the second study period. In that period, decrease of plasma levels reduced mild but not severe negative symptoms. Thus, lowering of the plasma levels after the first 3 weeks of treatment may improve mild negative symptoms. Conversely, increasing the plasma levels may make mild negative symptoms worse.

Adult

Plasma haloperidol levels and clinical effects in schizophrenia and schizoaffective disorder.

BACKGROUND: Plasma haloperidol levels between 5 and 11 ng/mL may be clinically optimal for acutely exacerbated schizophrenia, but the evidence for this therapeutic window has been inconsistent. METHODS: Haloperidol was administered in a double-blind manner during two consecutive 3-week experimental periods to 65 patients with acutely exacerbated schizophrenia or schizoaffective disorder. Two plasma levels were targeted: "low" (2 ng/mL) and "moderate" (10 ng/mL). The subjects were randomly assigned to four treatment sequences (low-low, low-moderate, moderate-moderate, or moderate-low). RESULTS: In the first 3 weeks, the antipsychotic efficacy of haloperidol increased with plasma levels up to approximately 12 ng/mL. In the second 3 weeks, decrease of plasma levels reduced negative symptoms. CONCLUSION: For most patients, plasma levels not exceeding 12 ng/mL yield the best results in the first 3 weeks of treatment. Subsequent lowering of the plasma levels may improve negative symptoms.

Adult

Induction of nitric oxide synthase activity in phagocytic cells inhibited by tricyclodecan-9-yl-xanthogenate (D609).

1. The synthesis of nitric oxide (NO) by immune-stimulated murine phagocytic cells (J774) and the modulation of this synthesis by tricyclodecan-9-yl-xanthogenate (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), was investigated. D609 dose-dependently suppressed production of NO, as measured by the release of nitrite and nitrate, in response to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) in intact cultured cells with an IC50 of approximately 20 micrograms ml-1. D609 at 40 micrograms ml-1 completely abrogated immune-stimulated nitrite production. 2. The inhibitory effects of D609 on nitrite production were time-dependent and restricted to the first 18 h post-stimulation. D609 did not inhibit nitrite production in the cytosol of immune-stimulated phagocytes. 3. These findings indicate that the xanthogenate, D609, is a potent inhibitor of the induction of NO-synthase activity in immune-stimulated phagocytes. Furthermore, since D609 has been demonstrated to inhibit PC-PLC specifically, our findings suggest that the activation of this enzyme by LPS and IFN-gamma is a proximal step in the signal transduction of inducible NO-synthase in phagocytic cells.

Amino Acid Oxidoreductases

Simple designs and model-free tests for synergy.

Current statistical designs for studying whether two or more agents in combination act synergistically nearly always require the study of several doses of many dose ratios. The analysis is usually based on an assumed parametric model of the dose-response surface. In this paper, for both quantal and quantitative response variables, sufficient conditions are given for establishing synergy at a dose of the combination without the need to specify the model. This enables the use of simple designs with few doses even when there is sparse knowledge of the dose-response curves of the individual agents. The Min test, used for testing whether an identified treatment is best, may be used for testing synergy. Power issues are discussed.

Animals

A plant-capture method for estimating the size of a population from a single sample.

To estimate the size of a population a plant-capture method, an alternative to the classic capture-mark-recapture model, is presented. Known or marked individuals otherwise indistinguishable from the remainder of the population are planted followed by an effort to capture members from the augmented population. Maximum likelihood estimators and a confidence region together with the expected length of the confidence interval for the size of the population as a function of the number of plants are given. A methodology for comparing the cost efficiency of plant-capture to capture-recapture is developed. An application to counting the homeless is given.

Bias

Haloperidol blood levels and clinical effects.

This study explored the relationships between plasma levels and the clinical effects of haloperidol in 176 acutely exacerbated schizophrenic or schizoaffective patients. After a single-blind placebo period of 1 week (period 1), they entered the double-blind period 2 randomly assigned to one of three plasma levels of haloperidol: low (2 to 13 ng/mL), medium (13.1 to 24 ng/mL), or high (24.1 to 35 ng/mL). Patients whose conditions did not improve in period 2 continued on one of the three haloperidol levels (period 3). Periods 2 and 3 lasted 6 weeks each. Only minor differences in clinical responses were noted among the three levels of haloperidol. These results imply that low or moderate doses of neuroleptics are appropriate for many acutely psychotic patients.

Acute Disease

Control for environmental risk factors in assessing genetic effects on disease familial aggregation.

A probabilistic model was developed to assess the impact of two independent dichotomous familial risk factors on familial aggregation of a disorder in pairs of relatives where one member was ascertained as a proband or index subject (i.e., a case or control). Under this model, one risk factor is of primary interest (i.e., a susceptibility gene), while the effect of the other is to be controlled (i.e., an environmental risk factor). Familial aggregation was examined within strata defined by the status of proband and relative with respect to the environmental factor. The findings suggest that for proband-relative pairs, under both the additive and multiplicative models, an environmental factor can be controlled in the analysis based solely on the status of the proband. If the relation between the genetic and environmental factors is neither additive nor multiplicative, however, the analysis must take account of environmental risk factors in both proband and relative.

Bias

Haloperidol blood levels and effects in schizophrenia and schizoaffective disorder: a progress report.

To test the hypothesis of a "therapeutic window," we have randomly assigned acutely exacerbating schizophrenic or schizoaffective patients to one of three plasma levels of haloperidol (HAL): 2-13, 13.1-24, or 24.1-35 ng/ml. Patients who did not improve after 6 weeks of this treatment were randomly assigned to one of the three haloperidol levels for another 6 weeks. The improvement was defined as at least 50 percent reduction of the Brief Psychiatric Rating Scale (BPRS) total score. The results obtained in 111 patients do not support any consistent relationship between plasma level of haloperidol and clinical improvement. Patients in the high haloperidol plasma range tended to have more side effects. These results suggest that the haloperidol doses used in clinical practice may be higher than necessary.

Adult

Predicting assaultiveness in psychiatric inpatients: a pilot study.

A sample of 87 psychiatric inpatients known to have been assaultive while in the hospital was contrasted with a matched group of nonviolent patients to identify the personal risk factors that distinguished the two groups. Data were collected using a personal history interview, a neurological examination, and an electroencephalogram. The four risk factors identified--neurological abnormality, history of violent crime, history of violent suicide attempts, and deviant family environment in childhood--were used to develop a statistical model predicting which subjects in a sample of newly admitted patients would become assaultive during the first three months after admission. The predicted classification of patients was found to be significantly related to subsequent assaultive behavior.

Adolescent

Combining multivariate bioassays.

Linear multivariate theory is applied to the problem of combining several multivariate bioassays. Results are an asymptotic test of the hypothesis of a common log relative potency; the maximum likelihood estimator of the common log relative potency; and an exact and asymptotic confidence interval estimator for log relative potency.

Analysis of Variance

Optimal crossover designs in the presence of carryover effects.

Under either the random patient-effect model with sequence effects or the fixed patient-effect model, the usual two-period, two-treatment crossover design, AB,BA, cannot be used to estimate the contrast between direct treatment effects when unequal carryover effects are present. If baseline observations are available, the design AB,BA can validly be used to estimate a treatment contrast. However, the design AB,BA,AA,BB with baseline observations is more efficient. In fact, we show that this design is optimal whether or not baseline observations are available. For experiments with more than two periods, universally optimal designs are found for both models, with and without carryover effects. It is shown that uncertainty about the presence of carryover effects is of little or no consequence, and the addition of baseline observations is of little or no added value for designs with three or more periods; however, if the experiment is limited to only two periods the investigator pays a heavy penalty.

Clinical Trials as Topic

Matched-pairs study of reserpine use and breast cancer.

This paper reports on an analysis of psychiatric population. 55 female patients with breast cancer were matched with non-cancer patients on age, year of admission, psychiatric diagnosis, race, and religion. Reserpine use was examined for yearly use by each year preceding the diagnosis of breast cancer, by cumulative yearly use, and by other defined time periods. Regardless of the definition of reserpine user, there were no significant increased relative risks of breast cancer for those women on reserpine. There was a fairly low proportion of patients from each group who were on the drug in any given year, and a fairly wide range of total dosage received. Over half of the women used reserpine at some time during their hospital stay.

Aged