Biomedical subjects

J Greenhouse

Publications and source records attributed to J Greenhouse.

11 recordsLinked to original sources

PubMed2000

Effect of PMPA and PMEA on the kinetics of viral load in simian immunodeficiency virus-infected macaques.

In this study we compared the effect of postexposure treatment of the acyclic nucleoside analogs 9-(2-phosphonylmethoxyethyl)-adenine (PMEA) and 9-(2-phosphonylmethoxypropyl)-adenine (PMPA) on the kinetics of viral load in the blood and lymph nodes of rhesus macaques chronically infected with SIVmac251 for 18 weeks. Two of the four macaques treated with PMPA (20 mg/kg per day) for 28 consecutive days had demonstrable reductions in viral loads of 1.5 and 3 logs. Three of four macaques given the same dosing regimen of PMEA had viral load reductions ranging from 1.25 to 2.8 logs. Furthermore, treatment with either drug caused a reduction in virus burden in the lymph nodes by 2 weeks posttreatment. However, in both PMEA- and PMPA-treated animals, viral loads rebounded to day of treatment levels by 2 weeks after termination of treatment. The extent to which viral load was suppressed was similar for both drugs. In contrast, viral loads in three of four mock-treated animals remained persistently high throughout the study. This study has demonstrated that postexposure treatment with these acyclic nucleoside analogs could modulate the kinetics of viral load reduction in some animals.

Adenine↗

PubMed1996

Mixture models for eye-tracking data: a case study.

Heterogeneity in biomedical data is often a source of great scientific interest and mixture models provide a general framework for modelling the various types that arise in practice. Finite mixture models model discrete subgroups within populations while continuous mixture models inflate the variance to account for over-dispersed data. A potential problem with the application of finite mixture models in practice is that these models may drastically overestimate the number of component densities when there is a lack of model fit. This can have severe consequences, leading the data analyst to attach substantive interpretations to spurious subgroups. For this reason, we propose using the continuous mixture model as an alternative when fitting finite mixture models with an arbitrary number of components. In the context of an example examining a specific oculomotor component of eye-tracking dysfunction in schizophrenia, we demonstrate why the continuous mixture model provides a viable alternative to the finite mixture model for small sample sizes. We present methods for fitting and comparing both models using the parametric bootstrap and EM algorithm, and show that the distinction between the models decreases as the number of component densities in the finite mixture model increases.

Algorithms↗

PubMed1995

Cost utility analysis of maintenance treatment for recurrent depression.

This paper presents a cost-utility analysis of three maintenance treatments for recurrent depression: interpersonal therapy (IPT-M), imipramine drug therapy (Drug), and a combination of the two. We base our analysis on the results of the University of Pittsburgh's Controlled Clinical Trial of Maintenance Therapies for Recurrent Depression. We construct a Markovian state-transition model to incorporate clinical effectiveness into cost and quality-of-life impacts; we assign empirical values to the parameters of this model; and we then use Monte Carlo analysis to compare the relative cost effectiveness of the different maintenance treatments. For the patients who met the eligibility standards for the study, Drug maintenance treatment is cost-effective in the strongest sense of the term compared to either a placebo group or IPT-M: it both improves expected lifetime health (measured in quality-adjusted life years, or QALYs) and reduces direct medical costs. This is true even when relatively severe side effects of the drug are considered. Compared to the placebo group, IPT-M and the combination of IPT-M and Drug each improve expected lifetime health, although in neither case are expected direct medical costs reduced. Still, the cost of the resulting health improvements, under $5000/QALY, are very reasonable. A similar conclusion holds comparing Drug and IPT-M to IPT-M alone. All of the above conclusions are quite robust to sensitivity analyses.

Adult↗

PubMed1994

HIV-1 infection in pigtailed macaques.

Four pigtailed macaques were inoculated with autologous cells expressing low levels of human immunodeficiency virus type 1 (HIV-1). During the first 10 weeks, infectious virus was recovered from peripheral blood mononuclear cells (PBMCs) and lymph nodes from three of the animals. Subsequently, HIV-1 DNA was frequently detected in uncultured PBMCs from all three animals, and virus was isolated from one of them at weeks 38 and 61. The fourth animal, which was rechallenged at week 10 with cell-free virus isolated from one of the others, never became virus isolation positive, but harbored HIV-1 proviral genomes. These virus infections were accompanied by the development of varied HIV-1-specific humoral immune responses. Antibodies to gp160 were first apparent at week 8 in the three initially infected animals and persisted. The animal from whom virus was isolated at late times also developed persisting antibodies to HIV-1 p24 and gp120. Antibodies to gp120 and gp160 became apparent in the rechallenged animal at 1 week following reinoculation, but they waned with time. In vivo passage of the virus was attempted at week 6. One recipient pigtailed macaque and one recipient cynomolgus monkey failed to become detectably infected following transfusion of virus-positive blood and lymph node cells. The long-term presence of HIV-1-specific antibodies and proviral genomes in these animals, and the recovery of infectious virus more than 1 year following inoculation, are indicative of persistent infection, and confirm previous reports that pigtailed macaques are susceptible to HIV-1.

Animals↗

PubMed1993

Etomidate anesthesia increases seizure duration during ECT. A retrospective study.

We reviewed charts of 28 consecutive depressed psychiatric inpatients who had received electroconvulsive therapy (ECT). As a preliminary investigation, we compared the effects of thiopental and etomidate anesthesia on seizure duration. Etomidate, a nonbarbiturate, has been shown to enhance seizure activity in other contexts. The mean age of our sample was 64 years. Because each patient received both etomidate and thiopental at various sessions during their course of ECT, each patient served as his or her own control. The mean proportion of etomidate sessions per patient was 54%. Mean seizure durations were significantly longer (p < 0.001) for the etomidate sessions as compared with the thiopental sessions. In contrast to some prior reports we found that the use of etomidate anesthesia in our sample of 28 consecutive inpatients enhanced seizure duration in ECT. Although controversial, some have advocated that longer seizure times will enhance effectiveness of ECT. We could not compare the anesthetic agents' clinical efficacy in relieving depression due to the retrospective nature of our study.

Adult↗

PubMed1990

Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals.

CD4+ T cells of patients with AIDS exhibit a qualitative defect in their ability to respond to soluble antigen while their responses to mitogens remain normal. CD4+ T cells can be broadly divided phenotypically into "naive" [CD45RA+ (2H4+)] and "memory" [CD29+ (4B4+) or CD45RO+ (UCHL1+)] cell subpopulations, which represent distinct maturation stages. To determine the human immunodeficiency virus type 1 (HIV-1) infectability of memory and naive CD4+ T-cell subsets in vitro and to determine the in vivo preference of HIV-1 in these subpopulations, we obtained highly purified CD4+ T-cell subsets from normal and HIV-1-infected individuals and studied them by viral cultivation, quantitative polymerase chain reaction, and functional assays. Polymerase chain reaction studies demonstrated that the memory cell subset of CD4+ T cells is preferentially infected (4- to 10-fold more than naive T cells) by HIV-1 in vitro, and these memory cells are the principal reservoir for HIV-1 within CD4+ T cells obtained from infected individuals. Functional abnormalities attributable to CD4+ T cells in HIV-infected individuals (failure to respond in vitro to soluble antigen or to anti-CD3 monoclonal antibodies) were shown to reside primarily within these memory cells. Thus, the present study suggests that the selective functional defects present in the memory CD4+ T-cell subset of HIV-infected individuals may be a direct result of the preferential infection and consequently greater viral burden within these cells.

Antigens, CD↗

PubMed1989

Graves' disease: an analysis of thyroid hormone levels and hyperthyroid signs and symptoms.

PURPOSE: Assessment of disease severity for patients with hyperthyroidism involves clinical evaluation and laboratory testing. To determine if there is a correlation between symptoms and thyroid function test results, we prospectively studied hyperthyroid patients using a standardized symptom rating scale and serum thyroid function parameters. PATIENTS AND METHODS: We examined 25 patients with untreated, newly diagnosed Graves' disease using the Hyperthyroid Symptom Scale (HSS) and serum levels of thyroxine (T4), triiodothyronine (T3) relative insulin area (RIA), and estimates of free thyroxine index (FTI). In addition, we compared thyroid hormone levels with standard measures of depression and anxiety in these patients. RESULTS: When regression analyses controlling for age were performed, none of these symptom ratings were associated with FTI or T3 RIA. The HSS was correlated with goiter size and anxiety ratings and was inversely correlated with age. CONCLUSION: The present study suggests that there is no relationship between the clinical assessment of disease severity and serum levels of thyroid hormone in untreated Graves' disease.

Adult↗

PubMed1988

Psychiatric and neuropsychological response to propranolol in Graves' disease.

We describe the endocrine, psychiatric, and neuropsychological assessments of 10 untreated, newly diagnosed Graves' disease subjects who were studied longitudinally at three stages: hyperthyroid (stage 1), after 2 weeks of propranolol treatment (stage 2), and after 6 months of antithyroid treatment (stage 3). Major depression, generalized anxiety disorder, and hypomania were diagnosed at stage 1. Elevations on psychiatric symptom rating scales and in motor activity monitoring at stage 1 were significantly decreased at stage 2 and again at stage 3. Psychiatric improvements paralleled improvements in endocrine symptoms. Neuropsychological improvements were noted on the more challenging memory and attention tasks at stage 3, whereas propranolol treatment was not associated with changes on attention tests. Results are discussed in relation to catecholamine-thyroid hormone interactions, in particular, the beta-adrenergic system.

Adult↗

PubMed1988

A psychiatric and neuropsychological study of patients with untreated Graves' disease.

We studied 13 untreated Graves' disease subjects in a clinical research unit using endocrine, psychiatric, and neuropsychological assessments. We used SADS interviews, RDC, standardized symptom rating scales, and motor activity monitoring to update earlier studies and quantified psychiatric symptoms to elucidate any correlations between endocrine and psychiatric status. Nine of 13 subjects had major depression, 8/13 had generalized anxiety disorder, and 3/13 were hypomanic. Anxiety levels were much higher than in other hospitalized medical patients. Using a broad battery of neuropsychological testing, we found mild deficits in attention, memory, and complex problem solving that were consistent with previous studies of hyperthyroid patients. The severity of psychiatric symptoms could easily result in an inappropriate referral to a psychiatrist prior to the diagnosis of hyperthyroidism. The relationship between psychiatric symptoms and possible CNS effects of excess levels of thyroid hormone is discussed.

Adult↗

PubMed1988

A symptom rating scale for delirium.

The authors present a 10-item clinician-rated symptom rating scale for delirium. Compared to demented, schizophrenic, and normal control groups, 20 delirious subjects scored significantly higher on the scale, which quantitates multiple parameters affected by delirium. The scale can be used alone or in conjunction with an electroencephalogram and bedside cognitive tests to assess the delirious subject.

Adult↗

PubMedDate not supplied

Plasma norepinephrine variations with dietary sodium intake.

Plasma catecholamine and renin activity levels were measured across a range of dietary sodium intakes (10--300 mEq/day) in 20 normal male volunteers. Supine plasma norepinephrine levels presented a triphasic pattern in relation to urine sodium, whereas epinephrine levels were not significantly altered by sodium intake, and renin showed the well-known hyperbolic relationship to urine sodium excretion. Highest supine norepinephrine values occurred at low salt intakes, the lowest when sodium excretion was between 100 and 180 mEq/day, and intermediate when sodium excretion was greater than 180 mEq/day. These findings show that sodium intake is an important consideration in the interpretation of plasma norepinephrine levels.

Adult↗