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Biomedical subjects

M Meisner

Publications and source records attributed to M Meisner.

At least 19 recordsLinked to original sources
PubMed1998

Postoperative plasma concentrations of procalcitonin after different types of surgery.

OBJECTIVE: Procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations were measured after different types of surgery to analyze a possible postoperative induction of procalcitonin (PCT), which might interfere with the diagnosis of bacterial infection or sepsis by PCT. DESIGN: PCT and CRP plasma levels as well as clinical symptoms of infection were prospectively registered preoperatively and 5 days postoperatively. SETTING: University hospital, in-patient postoperative care. PATIENTS: Hundred thirty patients were followed up; 117 patients with a normal postoperative course were statistically analyzed. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PCT concentrations were moderately increased above the normal range in 32 % of patients after minor and aseptic surgery, in 59 % after cardiac and thoracic surgery, and in 95 % of patients after surgery of the intestine. In patients with an abnormal postoperative course, PCT was increased in 12 of 13 patients. CRP was increased in almost all patients. CONCLUSIONS: Postoperative induction of PCT largely depends on the type of surgery. Intestinal surgery and major operations more often increase PCT, whereas it is normal in the majority of patients after minor and primarily aseptic surgery. PCT can thus be used postoperatively for diagnostic means only when the range of PCT concentrations during the normal course of a certain type of surgery is considered and concentrations are followed up.

Bacterial Infections↗
PubMed1998

Modulation of mouse endotoxin shock by inhibition of phosphatidylcholine-specific phospholipase C.

During Gram-negative bacterial infections, lipopolysaccharide (LPS) interacts with monocyte/macrophage receptors, resulting in a host defense response. Activation of intracellular signal transduction pathways implicating various protein kinase and phospholipases is crucial in activating the transcription of genes encoding proinflammatory cytokines and inducible nitric oxide synthase (iNOS). In this article, we demonstrate that in mouse, endotoxin shock activation of phosphatidylcholine-specific phospholipase C (PC-PLC) plays a major role in controlling the inflammatory response. Inhibition of PC-PLC by the specific inhibitor tricyclodecan-9-yl-xanthogenate (D609) before LPS reduced the release of interleukin-1 beta, interleukin-6 and nitric oxide (NO) in vivo. In contrast, tumor necrosis factor-alpha serum levels were not altered by the pretreatment with D609. Consequently, survival from endotoxin shock of D609-treated animals was significantly improved compared with control animals (45% vs. 20%). Thus, inhibition of PC-PLC can reduce the inflammatory response to LPS and may serve as a novel approach to therapy of sepsis.

Animals↗
PubMed1997

Classification of the effectiveness of combination treatments.

According to FDA regulations, a combination drug is not efficacious unless each component contributes to the claimed effects. For a univariate endpoint, this implies that the combination at specific doses must be superior to each of its components at the same doses. More demanding is the property of synergy, in which the effect of the combination must be superior to the effect expected based on those of its components. If it is equal to those effects, it is additive, and if it is inferior, it is antagonistic. We give regions in the combination dose plane where these concepts are well defined. If the effect of the combination is greater than the greatest effect achievable by any of its components it is therapeutically synergistic. A combination can be antagonistic, yet its components can still contribute to the claimed effects. If it is additive, synergistic or therapeutically synergistic, its components must contribute to the claimed effects. We relate these concepts and provide designs and sequential procedures for determining whether a combination is therapeutically synergistic, synergistic, additive, antagonistic and contributing or antagonistic and non-contributing.

Animals↗
PubMed1997

Estimating the size of a population from a single sample: methodology and practical issues.

In contrast to classical capture recapture methods, the single-sample method of Laska, Meisner, and Siegel (1988) (LMS) enables estimation of the size of a population, N*, on the basis of a single survey. For example, it may be desired to estimate the unduplicated number of individuals served by a mental health center during the last year on the basis of a 1-week sample. The time since each of the sampled individuals last engaged in the activity that defines the population is ascertained. The LMS estimator of N* and its unbiasedness property are motivated in a simple way, and an improved LMS estimator is introduced if additional information is available. An empirical assessment of the procedure is made using mental health service data for which the true population size is known. The performance of the extended LMS estimator is a substantial improvement over the standard LMS estimator.

Bias↗
PubMed1997

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↗
PubMed1997

History of violent behaviour and schizophrenia in different cultures. Analyses based on the WHO study on Determinants of Outcome of Severe Mental Disorders.

BACKGROUND: Information on patterns and correlates of the violent behaviour of individuals with schizophrenia is largely limited to populations in developed countries. Data from a World Health Organization epidemiological study of schizophrenia and related disorders, the Determinants of Outcome of Severe Mental Disorders (DOSMD), presented an opportunity to study patterns of violence across multinational settings. METHOD: Centres in 10 countries participated in the DOSMD study. An incidence sample of 1017 patients with schizophrenia who had their first-in-lifetime contact with a helping agency as a result of their psychotic symptoms was obtained. Data were available on their history of violent behaviour, substance use, and demographics. RESULTS: The occurrence rate of assault in the entire cohort was 20.6 per hundred, but the rate was three times higher in the developing countries (31.5 per hundred) than in developed countries (10.5 per hundred). History of assault was associated with positive symptoms, such as excitement and auditory hallucinations, and with serious alcohol problems. CONCLUSIONS: The cultural context and the specific characteristics of the disease in individuals with schizophrenia may interactively affect rates of violent behaviour.

Adolescent↗
PubMed1997

Procalcitonin--influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations.

In this study we have analysed the influence of temperature and time of storage and of repeated freezing on procalcitonin plasma concentrations ex vivo. We have also analysed the difference of procalcitonin concentrations in arterial or venous blood samples and the influence of different anticoagulation techniques on procalcitonin concentrations (serum, EDTA-, lithium-heparin- or citrate plasma). At room temperature (25 degrees C) a loss of procalcitonin plasma concentrations of 6.4% +/- 2.6% (mean, 2 standard error of the mean) after 3 hours (4.6% +/- 5.2% at 4 degrees C) and 12.3% +/- 3.1% after 24 hours occurred (6.3% +/- 5.0% at 4 degrees C, n = 17 each). Comparing the procalcitonin concentrations of blood samples with different anticoagulants (n = 24 each), there was only a significant difference between procalcitonin concentrations in heparinized plasma and serum (+ 7.6%, difference of the mean). There was no significant influence of the blood sampling technique (arterial or venous line) and of repeated freezing/thawing cycles (up to 3 times) on the procalcitonin concentrations measured. Although the difference of sampling and storage of the blood on procalcitonin concentrations is not significant, multiple factors may act synergistically on the result of procalcitonin measurement. To keep variations of ex vivo conditions as minimal as possible, a standardized technique of anticoagulation, time and temperature of storage is recommended, e.g. the use of EDTA-plasma and storage at room temperature, when samples are measured within 4 hours after blood drawing.

Anticoagulants↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

A risk-based prospective payment system that integrates patient, hospital and national costs.

We suggest that a desirable form for prospective payment for inpatient care is hospital average cost plus a linear combination of individual patient and national average cost. When the coefficients are chosen to minimize mean squared error loss between payment and costs, the payment has efficiency and access incentives. The coefficient multiplying patient costs is a hospital specific measure of financial risk of the patient. Access is promoted since providers receive higher reimbursements for risky, high cost patients. Historical cost data can be used to obtain estimates of payment parameters. The method is applied to Medicare data on psychiatric inpatients.

Costs and Cost Analysis↗