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Biomedical subjects

W A Brown

Publications and source records attributed to W A Brown.

At least 19 recordsLinked to original sources
PubMed1992

Mathematical models of complex dose-response relationships: implications for experimental design in psychopharmacologic research.

We develop a mathematical model to account for the complex relationship between drug dose and clinical response in psychopharmacologic research. The model specifies relationships among drug dose, drug bioavailability, pharmacokinetic factors, course moderators, clinical response and the heterogeneity of the disorder, and allows for the derivation of results that have implications for experimental design in psychopharmacologic research. These results form the basis for computer simulations which indicate that random assignment to two fixed doses is more powerful and less sensitive to heterogeneity than assignment to clinically determined doses. Fixed dose designs, however, tend to overestimate the magnitude of drug bioavailability-clinical response relationships. Clinically determined dose designs are useful in some experimental situations; their effectiveness is enhanced by systematically reducing the clinically determined dose. Larger dose reductions improve the ability to detect bioavailability-clinical response relationships.

Antipsychotic Agents↗
PubMed1992

Clinical features of depressed patients who do and do not improve with placebo.

The substantial placebo response in depression confounds treatment decisions and the assessment of new therapies. Improvement with placebo occurs infrequently in patients with chronic depression and in those with pituitary-adrenocortical hyperfunction, but other consistent predictors of placebo response have not been detected. We divided 241 moderately to severely depressed patients who had received placebo on a double-blind basis for 3 to 6 weeks into responders (greater than or equal to 50% improvement in Hamilton depression score, final Hamilton depression score less than or equal to 10), extreme nonresponders (less than 25% improvement), and partial responders (all others). Improvement with placebo was associated with a relatively short illness, a precipitating event, depression of only moderate global severity, and a good response to previous antidepressant treatment. These observations suggest that depressed patients who do and do not recover with placebo have different conditions that have not yet been fully characterized.

Adult↗
PubMed1992

Age and the dexamethasone suppression test: results from a broad unselected patient population.

We examined the relationship between age and postdexamethasone serum cortisol concentration in 676 psychiatric inpatients with a variety of DSM-III diagnoses. Regardless of diagnosis, patients 65 years and older had significantly higher nonsuppression rates than those below age 65 (64% vs. 34%). The correlation between age and cortisol level was moderate, but significant. Aging is associated with increasing nonsuppression rates to dexamethasone, and this change is augmented by an affective disorder diagnosis. Levels of nonsuppression and age-cortisol correlations vary depending on dose of dexamethasone, diagnosis, and gender.

Adolescent↗
PubMed1992

The determination of the steady-state pharmacokinetic profile of fluphenazine decanoate by gas chromatography/mass spectrometry detection.

This study uses the highly sensitive method of gas chromatography/mass spectrometry to compare the basic steady-state pharmacokinetic parameters of two fluphenazine decanoate formulations. Sixteen stable outpatients participated in a two-way crossover design study of the bioavailability of a new formulation of FPZ Dec, i.e., 10 mg/ml, to the standard 25 mg/ml formulation. When compared to a 1 ml injection of the standard formulation (25 mg/ml) over a two-week, steady-state period, we found bioequivalence as evidenced by similar mean areas under the curve (hrs x ng/ml). We did find that the injection volume of the same dose (2.5 ml of a 10 mg/ml formulation) results in a statistically significantly higher maximum serum level of parent fluphenazine. A tendency toward faster time to peak level was observed with the 10 mg/ml formulation but the difference was not statistically significant. Both of these differences are considered too small to be clinically significant. In a subgroup of 10 patients, pre-injection serum fluphenazine levels correlated significantly (Pearson r = 0.78, p < 0.05) with serum prolactin levels.

Adult↗
PubMed1992

Description of six new species of the genus Leptotrombidium from Mindanao Island and notes on the medically important genera of chiggers (Acari: Trombiculidae) of the Philippine Islands.

In the Philippine Islands, the genus Leptotrombidium currently consists of members of the subgenera Leptotrombidium and Trombiculindus. The following species are described as new: L. (L.) macacaphilus, L. (L.) longimedian, L. (L.) mindanensis, L. (L.) urogale, L. (L.) oculascutum, L. (T.) roseannleilaniae. The distribution of, and comments on, the known vectors of Rickettsia tsutsugamushi, L. (L.) deliense and L. (L.) fletcheri and the previously reported L. (L.) sandfordi, are given. Information on species of the potential scrub itch genera Blankaartia, Eutrombicula, and Schoengastia and a key to the genera and species of medically important trombiculids is provided.

Animals↗
PubMed1992

Side effects and the "blindability" of clinical drug trials.

A novel, simple approach to retrospective assessment of "blindability" was applied to data on outpatients in a controlled, double-blind clinical comparison of a putative antidepressant, etoperidone, and placebo. A "blind" evaluator proved capable of discriminating between the active drug and placebo on the basis of reported side effects alone, raising questions about the true blindness of the study.

Ambulatory Care↗
PubMed1992

Are patients who are intolerant to one SSRI intolerant to another?

One hundred patients with major depression who had discontinued fluoxetine because of side effects were enrolled in a multicenter, open, 8-week study of sertraline. After a washout period of at least 3 weeks following fluoxetine discontinuation and an additional 1-week, single-blind, placebo washout period, patients began treatment with 50 mg sertraline once daily. Based on the clinician's judgment of patient response, doses were titrated upward if necessary. The maximum daily dose of sertraline was 200 mg. Depressive symptoms and adverse events were assessed weekly. An interim analysis was conducted of the first 93 patients who completed the study. Of 91 evaluable patients, 69 sertraline-treated patients (75.8%) experienced significant improvement in depression. Only 8 of 93 patients (8.6%) discontinued sertraline because of side effects.

1-Naphthylamine↗
PubMed1992

Preliminary observations of the effect of methamphetamine in decomposing tissues on the development rate of Parasarcophaga ruficornis (Diptera: Sarcophagidae) and implications of this effect on the estimations of postmortem intervals.

Larvae of Parasarcophaga ruficornis (Fabricius) (Diptera: Sarcophagidae) were reared on tissues from rabbits administered different dosages of methamphetamine to study the effects of this drug on development of this species. The rabbits were given 37.5, 71.4, and 142.9 mg of methamphetamine via ear vein infusion. From Hours 30 to 60, larvae feeding on tissues from rabbits receiving 71.4 and 142.9 mg of methamphetamine developed more rapidly than larvae from the control colony and those feeding on tissues from the rabbit receiving 37.5 mg of methamphetamine. The time required for pupariation was significantly greater for colonies fed on tissues from methamphetamine-dosed rabbits than for the control. These differences were sufficient to alter postmortem interval estimates based on larval development by up to 18 h and estimates based on puparial development by up to 48 h. The presence of methamphetamine or amphetamine could not be detected in Diptera larvae in this experiment using radioimmunoassay techniques, as there was a nonspecific reaction, resulting in a false positive.

Amphetamine↗
PubMed1991

Effect of heroin in decomposing tissues on the development rate of Boettcherisca peregrina (Diptera, Sarcophagidae) and implications of this effect on estimation of postmortem intervals using arthropod development patterns.

Larvae of the flesh fly Boettcherisca peregrina (Robineau-Desvoidy) were reared on the tissues of rabbits to study the effects of heroin on the development rates of this species. The rabbits were given 6, 12, 18, and 24 mg of heroin by cardiac puncture. From Hours 18 to 96, larvae feeding on tissues containing heroin (as morphine) developed more rapidly than those feeding on tissues from the control. The time required for pupation was significantly greater for colonies fed on tissues from heroin-dosed rabbits than for the control colony. The differences observed in the rates of development were sufficient to alter postmortem interval estimates based on larval development by up to 29 h and estimates based on pupal development by 18 to 38 h.

Animals↗
PubMed1991

Fluoxetine in the treatment of late luteal phase dysphoric disorder.

BACKGROUND: Despite many associations between late luteal phase dysphoric disorder (LLPDD) and major depression, there have been no placebo-controlled trials of an antidepressant in this disorder. METHOD: The authors conducted a double-blind, randomized, placebo-controlled trial of fluoxetine in the treatment of LLPDD. The diagnosis of LLPDD was based on daily, prospective self-rating forms that subjects completed over two menstrual cycles. Subjects with other psychiatric disorders, determined by the Schedule for Affective Disorders and Schizophrenia interview, were excluded from the study. Women who continued to meet criteria for LLPDD after a single-blind trial of placebo were randomly assigned to treatment for two menstrual cycles with either fluoxetine 20 mg/day (N = 10) or placebo (N = 10). RESULTS: Nine of the 10 subjects receiving fluoxetine responded to treatment, whereas only 2 of the 10 receiving placebo did (p less than .0003). Symptoms decreased significantly in all 10 LLPDD diagnostic categories in the fluoxetine-treated group. All subjects taking fluoxetine elected to continue with this treatment after completion of the study. CONCLUSIONS: These results suggest that fluoxetine is an effective and well-tolerated treatment for LLPDD.

Adult↗
PubMed1990

Prolactin shifts after neuroleptic withdrawal.

Neuroleptic-induced alterations in serum prolactin levels may have important clinical implications. Twenty-two stable schizophrenic patients, taken off medication over a 3-week period, were followed for 40 weeks or until the neuroleptic was reinstituted. Serum prolactin levels were measured during neuroleptic treatment and during the neuroleptic-free period. When serum prolactin levels were plotted over time, 55% of the subjects showed shifting prolactin levels in the shape of a "V" (i.e., a fall in prolactin level preceding an increase in the level) in the early weeks following withdrawal. Subjects with the "V" shape had significantly lower prolactin levels during neuroleptic treatment than those without the "V" shape. The pathophysiological significance of the prolactin "V" pattern is uncertain. It is consistent, however, with transient dopaminergic hyperactivity following neuroleptic withdrawal.

Adult↗
PubMed1990

The dexamethasone suppression test and completed suicide.

The present study was undertaken to further explore the relationship between the dexamethasone suppression test (DST) and suicide. Depressed inpatients who had undergone the DST at index admission and later committed suicide (n = 13) were matched for age, gender, diagnosis, and type of DST (1 mg, 2 mg) with depressed inpatients from the same hospital and study time period to form 2 groups: a suicide attempter group (n = 25) and a nonattempter group (n = 28). The suicide completers group had significantly higher 1600 postdexamethasone cortisol levels than the suicide attempters group and a significantly higher 1600 rate of DST nonsuppression compared with the suicide attempter + nonattempter combined group. Although the rate of DST nonsuppression did not differ between the suicide attempter and nonattempter groups, serious attempters had significantly higher 1600 cortisol levels and a statistically higher proportion of patients who completed suicide than nonserious attempters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Simultaneous monitoring of force, acceleration and electromyogram during computer-controlled infusion of atracurium in sheep.

Five sheep were anaesthetised with sodium thiopentone, nitrous oxide and oxygen, and the lungs ventilated artificially. A computer-controlled infusion of atracurium employing feedback from isometric force measurement was set to maintain 15, 50 and 85% depth of neuromuscular block. Each was held constant for 30 minutes, while isometric force and electromyogram were measured on the left forelimb and acceleration on the right. The acceleration transducer records at the three levels of block were practically identical with those from force measurements: mean differences (SD) between simultaneous measurements being 3.6 (5.4)%. EMG value was 10.1 (12.0)% different from force measurement. Correlation between simultaneous force and either acceleration or EMG was excellent (r = 0.986 and 0.938 respectively). In clinical practice all three techniques measure block comparably. In the sheep forelimb, EMG was a less reliable method of measuring block.

Animals↗
PubMed1990

Fluoxetine in the treatment of premenstrual syndrome.

Despite many associations between premenstrual syndrome (PMS) and major depression, there have been no placebo-controlled trials of an antidepressant in this disorder. We conducted a double-blind, randomized, placebo-controlled trial of fluoxetine in the treatment of severe PMS. The diagnosis of PMS was made using daily, prospective, self-rating forms over two menstrual cycles. Women who continued to meet criteria for PMS after a single-blind trial of placebo during one menstrual cycle were randomly assigned to treatment for two menstrual cycles with either fluoxetine at 20 mg/day (n = 9) or placebo (n = 6). Eight of the 9 subjects receiving fluoxetine responded to treatment, whereas only 1 of the 6 receiving placebo responded (p less than .025). All subjects on fluoxetine elected to continue with this treatment after completion of the study. These preliminary results suggest that fluoxetine is an effective and well-tolerated treatment for severe PMS.

Adult↗
PubMed1989

Neuroleptic nonresponse and affective symptoms: a 2-year prospective study of schizophrenic outpatients.

For 2 years we assessed clinical state, and plasma neuroleptic and prolactin levels every 6 months in 105 male schizophrenic outpatients. The patients took a variety of neuroleptics at clinically determined doses. Those who had psychotic symptoms at 50% or more of their visits had higher neuroleptic doses, more tardive dyskinesia, and more affective symptoms than the other patients. These groups were not, however, significantly different in their age of onset, years of education, duration of illness, duration of neuroleptic exposure, or negative symptoms.

Adult↗