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Biomedical subjects

R P Brown

Publications and source records attributed to R P Brown.

At least 19 recordsLinked to original sources
PubMed1995

Chemical mixtures: current risk assessment methodologies and future directions.

Some of the most challenging problems that toxicologists confront are determining how biological effects of components in a complex mixture may interact, determining how these interactions affect the overall toxicity of the mixture, and determining how to incorporate this information into risk assessments of chemical mixtures. There has been considerable effort in this area since the publication of the U.S. Environmental Protection Agency's guidelines for risk assessment of chemical mixtures in 1986. This paper reviews the terminology used to describe chemical interactions and the methodologies that have been developed for conducting risk assessments of chemical mixtures. Particular attention is directed towards an examination of the applicability and validity of the methods for the assessment of risk posed by exposure to environmentally relevant concentrations of chemical mixtures. Limited, yet compelling, data are reviewed that suggest that for noncancer endpoints, adverse effects are unlikely to occur when the individual components in the mixture are present at levels well below their respective thresholds. Synergistic or antagonistic effects, not readily predicted from the mechanisms of action of the individual components, are possible when the mixture components are present at levels equal to or above their individual thresholds. Finally, synergistic carcinogenic effects have been observed in animal studies of mixtures, even at relatively low doses.

Animals↗
PubMed1992

Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients.

Serious suicidal behavior, affective disorders, and a variety of other psychopathologic behaviors and syndromes have been found to correlate with measures of the serotonin system. Clinical studies have employed a range of serotonin indexes, including the cerebrospinal fluid level of 5-hydroxyindoleacetic acid, the prolactin response to serotonin agonists, such as fenfluramine hydrochloride, and platelet serotonin-related proteins or serotonin content. Many of these indexes are correlated with suicidal behavior, but the interrelationship of these biologic measures has been uncertain. We studied the relationship of a series of serotonin indexes in patients in whom these measures were correlated with suicidal behavior. A positive correlation was found between cerebrospinal fluid 5-hydroxyindoleacetic acid and the maximal prolactin response to fenfluramine but not with platelet serotonin2 receptor indexes. The fenfluramine-stimulated maximal prolactin response correlated with platelet serotonin2 receptor number, particularly in older patients. We conclude that cerebrospinal fluid 5-hydroxyindoleacetic acid measurements cannot be replaced but can be complemented by less invasive procedures, such as a fenfluramine challenge test or platelet serotonin2 measures, in the study of the relationship of the serotonin system to psychiatric disorders.

Adult↗
PubMed1992

Knotting technique and suture materials.

Three groups of knots were examined using six no. 1 (metric 4) suture materials to identify the most effective and efficient knotting techniques. The three groups were the square or reef knot, the surgeon's knot and a double throw knot. Sequential single additional throws were added to these in order to determine when the strength of the knot reached the breaking force of the material, thus nullifying the need for additional throws. This strength was reached in all cases by a maximum of two additional throws. Suture materials examined were the non-absorbable monofilaments nylon and polypropylene, the absorbable monofilaments polyglyconate and polydioxanone and the braided materials polyglactin and polyglycolic acid, both coated. These were examined for their knot-holding capacity and breaking force to determine the best materials, which were polypropylene, polyglyconate and polyglycolic acid.

Suture Techniques↗
PubMed1992

Behavioral syndromes in Alzheimer's disease.

The Behavioral Syndromes Scale for Dementia (BSSD) is a new instrument that showed strong internal consistency and interrater reliability in an outpatient sample of 106 patients with probable Alzheimer's disease. Factor analysis provided support for a priori symptom groupings, particularly the syndromes of disinhibition and apathy-indifference. Dependency (87%), denial of illness (63%), and motor agitation (55%) were common, while sexual disinhibition (2.9%) and self-destructive behaviors (2.9%) were rare. Virtually all symptoms were predominantly minimal to mild in severity. Patients with longer illness duration were more apathetic. Disinhibited behaviors and apathy-indifference increased with greater severity of dementia. Catastrophic reactions, aggression, and agitation were associated with greater functional impairment. There was great heterogeneity in symptom presentation. In Alzheimer's disease, several behavioral changes might be direct manifestations of underlying brain pathology, rather than being solely secondary to cognitive impairment.

Activities of Daily Living↗
PubMed1990

Regional cerebral blood flow in mood disorders. I. Comparison of major depressives and normal controls at rest.

We measured regional cerebral blood flow with the xenon 133 inhalation technique in 41 patients with major depressive disorder and 40 matched, normal controls during an eyes-closed, resting condition. The depressed group had a marked reduction in global cortical blood flow. To examine topographic abnormalities, traditional multivariate analyses were applied, as well as a new scaled subprofile model developed to identify abnormal functional neural networks in clinical samples. Both approaches indicated that the depressed sample had an abnormality in topographic distribution of blood flow, in addition to the global deficit. The scaled subprofile model identified the topographic abnormality as being due to flow reduction in the depressed patients in selective frontal, central, superior temporal, and anterior parietal regions. This pattern may reflect dysfunction in the parallel distributed cortical network involving frontal and temporoparietal polymodal association areas. The extent of this topographic abnormality, as revealed by the scaled subprofile model, was associated with both patient age and severity of depressive symptoms.

Adult↗
PubMed1990

Normalization of blunted lymphocyte beta-adrenergic responsivity in melancholic inpatients by a course of electroconvulsive therapy.

Electroconvulsive therapy has been reported to desensitize brain beta-adrenergic receptors in rodents, but this effect has not been studied in man. We examined the effect of a course of electroconvulsive therapy on lymphocyte beta-adrenergic responsivity in 19 inpatients with melancholia. Before treatment, beta-adrenergic cyclic adenosine monophosphate response to isoproterenol was significantly blunted in the patients compared with controls. Following a course of electroconvulsive therapy, beta-adrenergic responsivity increased such that patients no longer differed from controls. Thus, blunted lymphocyte beta-adrenergic responsivity is a state-dependent effect of melancholia that can be corrected by a therapeutic course of electroconvulsive therapy. The effect of electroconvulsive therapy on this beta-adrenergic system is in the opposite direction to that reported for rodent forebrain, where electroconvulsive therapy causes desensitization, and may reflect differences between peripheral and central effects, species differences, or disease effects.

Cyclic AMP↗
PubMed1990

Statistical issues in the identification of risk factors for suicidal behavior: the application of survival analysis.

Studies of suicide risk factors generally examine suicidal behavior as a dichotomous outcome. Survival analytic techniques are discussed in which the time until a suicide attempt from a specific point, such as prior attempt or onset of illness, is also examined. These procedures can incorporate information on those lost to followup or "censored." One survival analytic technique, Cox's proportional hazards model, is a particularly informative statistical technique for the study of suicidal risk factors because several covariates can be incorporated. Illustrative analyses estimate the significance of different risk factors, and demonstrate that there is a 32% increase in the relative risk of a suicide attempt associated with each prior attempt.

Adult↗
PubMed1990

CSF 5-HIAA and HVA concentrations in elderly depressed patients who attempted suicide.

CSF findings distinguished 12 elderly depressed patients who attempted suicide from nine depressed patients who did not and from seven normal control subjects. Psychosocial factors and measures of psychopathology did not differentiate suicidal from nonsuicidal patients. Biochemical factors may be important in evaluating suicide risk in the elderly.

Age Factors↗
PubMed1989

A pilot study of haloperidol treatment of psychosis and behavioral disturbance in Alzheimer's disease.

Nine outpatients meeting research criteria for probable Alzheimer's disease who had psychosis or behavioral disturbance participated in a single-blind, placebo-controlled pilot study. Oral haloperidol in doses of 1 to 5 mg daily improved target symptoms, confirmed by double-blind ratings of videotaped interviews. Patients could not be maintained on more than 4 mg of haloperidol daily due to the severity of extrapyramidal side effects. Modified Mini-Mental State scores worsened while taking haloperidol, with only partial recovery in the final 4-week placebo phase. Severe extrapyramidal side effects and decline in cognitive function may compromise the efficacy of commonly used doses of neuroleptic drugs in patients with Alzheimer's disease.

Activities of Daily Living↗
PubMed1989

A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor.

Monoamine oxidase (MAO) inhibitors are effective antidepressants whose use is limited because of unwanted side effects and the possibility of a tyramine-induced hypertensive crisis (cheese reaction). (-)-Deprenyl (the official nonproprietary name for this substance is selegiline), a selective MAO type B inhibitor, may be safer and have fewer side effects, but its antidepressant efficacy is uncertain. A double-blind placebo-controlled study was carried out in depressed outpatients who were treated with (-)-deprenyl in an MAO type B selective dose range and at a higher nonselective dose range. (-)-Deprenyl did not have a statistically significant antidepressant effect after three weeks of treatment at doses of 10 mg/d. However, after six weeks and at higher doses (averaging about 30 mg/d for the second three weeks), (-)-deprenyl was superior to placebo in antidepressant effect with a positive response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton Depression Rating Scale mean score vs 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with (-)-deprenyl was no greater than with placebo. It was concluded that (-)-deprenyl is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of nonselective MAO inhibitors.

Adult↗
PubMed1988

Blunted beta-adrenergic responsivity of peripheral blood mononuclear cells in endogenous depression. Isoproterenol dose-response studies.

Previous studies of peripheral blood mononuclear cells isolated from drug-free, hospitalized patients with endogenous major depression have demonstrated a diminished adenosine 3',5'-monophosphate (cyclic AMP) response to single concentrations of isoproterenol as compared with that obtained from normal control subjects. We now report results of isoproterenol dose-response studies that indicate lower basal levels of cyclic AMP as well as diminished cyclic AMP levels in response to isoproterenol stimulation at concentrations ranging from 10(-10) to 10(-5) mol/L in drug-free, hospitalized patients with endogenous depression. The major factor responsible for the diminished cyclic AMP production in the depressed patients was a loss of receptor sites capable of cyclic AMP production. Taken together with our previously reported finding that beta-adrenergic antagonist binding was normal in peripheral blood mononuclear cells obtained from depressed patients, the results of the dose-response studies suggest a loss of receptor function (desensitization) rather than a diminished number of receptor binding sites (down-regulation) as the underlying mechanism. Potential explanations for beta-adrenergic desensitization and its implications for the catecholamine hypothesis of depressive disorders are discussed.

Adult↗
PubMed1988

Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables.

In an attempt to determine the relative contributions to adrenocortical hyperactivity in depression of agitation, delusions, and melancholic subtype, we measured cortisol levels before and after dexamethasone in 93 unipolar major depressed inpatients. Stepwise multiple regression showed that agitation predicted 22% of the variance in a.m. cortisol level after dexamethasone. Addition of the variables melancholia and delusionality to the regression model accounted for 27% and 34%, respectively, of the variance in the same cortisol variable. Age, illness severity, and weight loss added no further significant predictive value. Age, weight loss, and illness severity did affect cortisol levels when examined separately from the other variables. Rate of nonsuppression on the dexamethasone suppression test (DST) differed between the nonmelancholic major depressive group and any other group with melancholia. These results suggest why some discrepancies may exist between studies of the DST in delusional depression and indicate that agitation merits careful assessment in future studies of DST response.

Adrenal Cortex↗
PubMed1987

Seizures with neuroleptics and antidepressants.

Seizures remain among the most serious side effects of psychotropic drugs. The authors review the literature associating neuroleptic and antidepressant medications with seizures, discussing the relative "seizurogenicity" of different medications, risk factors for seizures, and drugs of choice for high-risk patients. Case histories are presented. Available evidence suggests that molindone, fluphenazine, and haloperidol are among the least seizurogenic neuroleptics and that doxepin, monoamine oxidase inhibitors, or electroconvulsive therapy may be safest in treating the depressed patient at risk for seizures.

Adult↗