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Biomedical subjects

S Epstein

Publications and source records attributed to S Epstein.

At least 55 records · Page 3Linked to original sources
PubMed1997

Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions.

Chromosomal translocations of bcl-3 are associated with chronic B cell lymphocytic leukemias. Previously, we have shown that Bcl-3, a distinct member of the I kappa B family, may function as a positive regulator of NF-kappa B activity, although its physiologic roles remained unknown. To uncover these roles, we generated Bcl-3-deficient mice. Mutant mice, but not their littermate controls, succumb to T. gondii owing to failure to mount a protective T helper 1 immune response. Bcl-3-deficient mice are also impaired in germinal center reactions and T-dependent antibody responses to influenza virus. The results reveal critical roles for Bcl-3 in antigen-specific priming of T and B cells. Altered microarchitecture of secondary lymphoid organs in mutant mice, including partial loss of B cells, may underlie the immunologic defects. The implied role of Bcl-3 in maintaining B cells in wild-type mice may related to its oncogenic potential.

Animals↗
PubMed1997

Alendronate prevents cyclosporin A-induced osteopenia in the rat.

Post-transplantation bone disease is an increasingly recognized clinical entity whose etiology is multifactorial. The immunosuppressant agent cyclosporine-A (CsA) has repeatedly been shown experimentally to induce a high-turnover osteopenic state. Alendronate (Alen.) is a new generation bisphosphonate having far greater antiresorptive potency than previous bisphosphonates. It inhibits osteoclast resorption in vitro and in vivo without adversely affecting bone mineralization. This study was designed to investigate whether alendronate could prevent CsA-induced osteopenia in the rat. Forty-eight 8-month-old male Sprague Dawley rats were randomized into four groups to receive the following for 28 days: (1) CsA vehicle (veh.) p.o. daily and alendronate vehicle subcutaneously (s.c.) twice/week, (2) CsA 15 mg/kg p.o. daily and Alen. veh. s.c. twice/week, (3) Alen. 70 micrograms/kg s.c. twice/ week and CsA veh. p.o. daily, and (4) CsA 15 mg/kg p.o. daily and Alen. 70 micrograms/kg s.c. twice/week. Rats were weighed and bled and serum was assayed serially for calcium, PTH, 1,25(OH)2vit.D, and osteocalcin. Tibiae were removed following sacrifice on day 28, after double demeclocycline and calcein labeling, for histomorphometric analysis. Treated groups were compared to the vehicle-treated control. We confirmed previous findings that CsA produces elevated 1,25(OH)2 vitamin D and serum osteocalcin levels. Alendronate treatment by itself decreased osteocalcin by day 28 and resulted in a marginal decrease in serum total calcium on day 14. The histomorphometry findings reconfirmed that the administration of CsA induces a state of high-turnover osteopenia. Alendronate prevented CsA's adverse effects, particularly in maintaining trabecular bone volume, presumably by decreasing bone remodeling. Alendronate would seem to hold therapeutic promise in post-transplantation bone disease.

Administration, Oral↗
PubMed1997

Compromises produced by the dialectic between self-verification and self-enhancement.

Three studies of people's reactions to evaluative feedback demonstrated that the dialectic between self-enhancement and self-verification results in compromises between these 2 motives, as hypothesized in cognitive-experiential self-theory. The demonstration was facilitated by 2 procedural improvements: Enhancement and verification were established by calibrating evaluative feedback against self appraisals, and degree of enhancement and of verification were varied along a continuum, rather than categorically. There was also support for the hypotheses that processing in an intuitive-experiential mode favors enhancement and processing in an analytical-rational mode favors verification in the kinds of situations investigated.

Adolescent↗
PubMed1997

Competition, ownership, and access to hospital services. Evidence from psychiatric hospitals.

OBJECTIVES: This article examines the impact of increasing competition among hospitals on access to inpatient services and preexisting differences in access between nonprofit and for-profit facilities. It tests theoretical propositions that suggest that nonprofit and for-profit hospitals will respond in different ways and to differing degrees to changing competitive pressures. METHODS: Drawing data from a 1987-88 national survey of psychiatric hospitals, the authors measured access in terms of the availability of different types of services and the provision of uncompensated care. The impact of hospital ownership, competition as well as the interaction of ownership and competition was assessed through a set of regression models, controlling for other characteristics of the hospital markets and local service system. RESULTS: Nonprofit psychiatric hospitals provide greater access than their for-profit counterparts under conditions of limited competition. Increased competition reduces the ownership-related differences in uncompensated care, but increases the differences for marginally profitable services. The market share of for-profit hospitals had an independent negative effect on access, holding constant the intensity of competition. CONCLUSIONS: The interaction of ownership and competition explains some seemingly inconsistent finding in the literature and points to the complexity of relying on ownership-based policies to protect access in an increasingly competitive health-care system.

Diagnosis-Related Groups↗
PubMed1997

This I have learned from over 40 years of personality research.

During the over 40 years in which I have conducted personality research, I have had a number of insights about the research process that I thought would be worth sharing: an awareness of the human side of science; lessons from the person-situation debate; lessons from comparing research on highly ego-involving natural events, such as sport parachuting, with laboratory analogues; the realization of what is wrong with the concept of the Freudian unconscious and what should be done to replace it and awareness of pervasive biases in the journal-reviewing process. Perhaps the one most general lesson I have learned is that the advancement of psychology as a cumulative, integrative science is hampered not so much by its conceptual complexity as by the difficulty of humankind to view itself objectively, with honesty, courage, and a willingness to surrender illusions.

Anxiety↗
PubMed1997

Activism, drug regulation, and the politics of therapeutic evaluation in the AIDS era: a case study of ddC and the 'surrogate markers' debate.

This paper presents an extended case study to demonstrate that the interpretation of clinical trials of antiviral AIDS drugs is significantly shaped by a widely dispersed allocation of scientific credibility. Specifically, the participation of AIDS activists in claims-making about AIDS trials and AIDS drugs complicates the politics of therapeutic evaluation, even as it challenges the monopolization of credibility by credentialed researchers. The paper tracks the social construction of belief about the efficacy of the combination therapy of AZT and ddC, between 1990 and 1995 in the United States. By intervening simultaneously in interpretative debates about the results of the clinical trials of this therapy and in methodological debates about how efficacy might best be measured in such trials, activists have helped to shape what is believed to be known about these drugs.

AIDS-Related Complex↗
PubMed1997

Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience.

PURPOSE: To determine the incidence of clinical cardiotoxicity from anthracycline chemotherapy in children with cancer and to identify associated risk factors. PATIENTS AND METHODS: The study population consisted of 6,493 children with cancer who had received anthracycline chemotherapy on Pediatric Oncology Group (POG) protocols from 1974 to 1990. Cardiotoxicity, defined as congestive heart failure not due to other causes, abnormal measurements of cardiac function that prompted discontinuation of therapy, or sudden death from presumed cardiac causes, was determined by a review of protocol records. RESULTS: Cardiotoxicity was confirmed in 106 patients (1.6%): 58 had congestive heart failure, 43 had changes in measures of cardiac function that prompted the discontinuation of therapy, and five died suddenly from presumed cardiac causes. In a multivariate analysis, factors that contributed to the relative risk (RR) of toxicity were a cumulative anthracycline dose > or = 550 mg/m2 of body-surface area (RR = 5.2), maximal dose > or = 50 mg/m2 (RR = 2.8), female sex (RR = 1.9), black race (RR = 1.7), presence of trisomy 21 (RR = 3.4), and exposure to amsacrine (RR = 2.6). Cardiotoxicity within 1 year after the completion of anthracycline treatment (early cardiotoxicity) represented 89.5% of all cases. CONCLUSION: Early clinical cardiotoxicity in children treated with anthracycline is rare. A high maximal dose, or cumulative dose of anthracycline, female sex, black race, presence of trisomy 21, and treatment with amsacrine increase the risk for anthracycline-associated cardiotoxicity.

Adolescent↗
PubMed1997

Short-term effects of growth hormone and insulin-like growth factor I on cancellous bone in rhesus macaque monkeys.

The purpose of our study was to determine the effects of GH and insulin-like growth factor I (IGF-I) administration singly and in combination on vertebral, tibial, and femoral bone in aged female monkeys as well as the various treatment effects on serum hormone levels and osteocalcin gene expression. Twenty-one ovulating female monkeys (rhesus macaque), aged 16-20 yr (5-6 kg), were divided into four groups to receive the following treatment for 7 weeks via Alzet pumps inserted sc: A, eluant (control group); B, recombinant human IGF-I (rhIGF-I; 120 micrograms/kg.day); C) rhGH (100 micrograms/kg.day); D, combination of rhIGF-I (120 micrograms/kg.day) and rhGH (100 micrograms/kg.day). Serum was assayed serially for glucose, IGF-I, GH, and IGF-binding protein-3 levels. All groups received double labeling with calcein. On the day of death, the primates' second lumbar vertebrae, tibiae, and femora were carefully dissected, fixed in 70% ethanol, and subjected to histomorphometric analysis. Ribonucleic acid was extracted from contralateral tibiae for the purpose of osteocalcin gene expression analysis. Serum glucose was unaffected by treatment. Serum GH was significantly elevated in groups C and D, whereas serum IGF-I and IGFBP-3 were only significantly increased in group D. Histomorphometric analysis showed no significant differences or trends for bone volume in any treatment group. Bone formation rate, surface and/or bone volume referent were significantly higher in both groups treated with GH (C and D) in tibia and femur, with a similar trend in vertebrae. The increase in bone formation rate was due mainly to a significant increase in mineral apposition rate, but there was also an increase in tibial mineralizing surface by GH by factorial analysis (P < 0.05). There were significant treatment effects on osteoid surface and osteoclastic surface in femur in the combination treatment group vs. the controls. Osteocalcin gene expression analysis supported an enhanced expression in both groups treated with GH. These findings are consistent with a short term effect of GH to increase bone remodeling and predominantly osteoblastic activity in the appendicular skeleton. In contrast, other than an isolated increase in osteoclastic surface in femoral bone, IGF-I, when administered alone, was unable to significantly influence bone formation or resorption activity in this short term study.

Animals↗
PubMed1997

The role of the T-lymphocyte in estrogen deficiency osteopenia.

Our laboratory has previously demonstrated that the T-lymphocyte is critical in the development of cyclosporin A-induced osteopenia in the rat model. A similar state of osteopenia is induced by estrogen depletion in the ovariectomized (OVX) rat, which is the animal model of postmenopausal bone loss. However, the role of the immune system, and particularly the T-lymphocyte, in estrogen deplete osteopenia has not been elucidated. We used the Rowett athymic nude rat as our model of T-lymphocyte deficiency. In this study, the experimental rats were divided into four groups as follows: (1) sham-operated Rowett heterozygous (rnu/+) euthymic rats (control group); (2) OVX Rowett heterozygous (rnu/+) euthymic rats; (3) sham-operated Rowett homozygous (rnu/rnu) athymic nude rats, which are T-lymphocyte deficient; and (4) ovariectomized Rowett homozygous (rnu/rnu) rats. Rats were weighed, and venous blood was taken in weeks 2, 4, and 6 for determination of serum osteocalcin. Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) was determined on the day of sacrifice. Following sacrifice, histomorphometry was performed on double-labeled proximal tibial metaphyses. Flow cytometric analysis of splenic mononu-clear cell isolates stained for OX19-positive (CD5) T-lymphocytes was performed. T-lymphocyte analysis revealed significant reductions in both athymic nude groups, while OVX euthymic rats demonstrated a diminished number of T-cells relative to their sham-operated counterparts. Histomorphometric data indicated that both OVX groups exhibited a significant loss of trabecular volume, with associated increases in indices for bone formation and resorption, with resorption likely outstripping formation, resulting in osteopenia. Serum osteocalcin was significantly elevated in the ovariectomized euthymic group throughout the experimental period compared with the control group (p < 0.01); it was elevated in the ovariectomized athymic group on week 4 only (p < 0.01 vs. control). It appears that the T-lymphocyte may not be an essential component in the pathogenesis of estrogen deficiency osteopenia. The contribution of circulating T-lymphocytes as well as other T-lymphocyte-rich organs needs to be explored further.

Animals↗
PubMed1997

The role of testosterone in cyclosporine-induced osteopenia.

Our laboratory has demonstrated that the immunosuppressants Cyclosporin A (CsA) and tacrolimus (FK506), in vivo in the rat, produce a high-turnover osteopenia. CsA is known to decrease serum testosterone (Test) levels both in the rat and in human transplant patients. Less is known of FK506's effect on androgens. CsA-induced hypogonadism may contribute to the aforementioned bone loss because hypogonadism itself is a risk factor for osteoporosis and fracture. The aim of this study was to assess serum androgen levels following CsA and FK506 therapy and to see wether Test replacement therapy, in the form of 28-day controlled release subcutaneous pellet implants, could prevent CsA-induced osteopenia. Two experiments were conducted. In experiment I, four groups of 6-month-old male Sprague-Dawley rats received the following: (A) CsA vehicle and placebo pellet, (B) Test 15 mg pellet and CsA vehicle, (C) CsA 10 mg/kg and placebo pellet, (D) Test 15 mg pellet and CsA 10 mg/kg. In experiment II, two groups of rats received (E) FK506 vehicle and (F) FK506 4 mg/kg. CsA, FK506, and vehicles were given for 28 days by daily oral gavage. The rats were weighted and bled on days 0, 14, and 28. All rats received double fluorescent labeling, and on day 28 the tibiae were removed for histomorphometry. Whole blood was assayed for CsA and FK506 levels. Serum was assayed for total and free Test as well as for osteocalcin (BGP), blood urea nitrogen (BUN), creatinine, and calcium. Whole blood monoclonal CsA levels measured by fluorescent immunoassay were in the therapeutic range, while a drug concentration profile showed good absorption of FK506. Those rats receiving Test and FK506 lost weight, while those receiving CsA remained constant. BUN was only marginally elevated in the CsA-treated groups on day 28 (p < 0.05), while creatinine was unchanged. On day 28, total and free Test was significantly reduced in the CsA-treated rats versus control (p < 0.05), while Test replacement therapy maintained total Test levels above vehicle (p < 0.01) and free Test levels similar to vehicle on day 28. FK506 did not lower total or free Test levels. BGP levels were significantly increased in the CsA (p < 0.01) and FK506 (p < 0.001) groups on day 28. BGP in the groups receiving Test alone and in combination with CsA remained similar to vehicle. Histomorphometry confirmed CsA- and FK506-induced high-turnover osteopenia. The Test alone group marignally increased bone formation. Test replacement failed to prevent the CsA-induced bone loss. In conclusion, immunosuppressive doses of CsA, but not FK506, lowers serum total and free Test. Hypoandrogenemia does not seem to be a major factor in CsA-induced osteopenia because bone loss occurs despite Test replacement.

Animals↗
PubMed1997

The determinants of dumping: a national study of economically motivated transfers involving mental health care.

OBJECTIVE: To examine the prevalence and determinants of economically motivated transfers (aka "dumping") from hospitals treating mental illness. DATA SOURCES: A composite data set constructed from three national random-sampled surveys conducted in 1988 and 1989: (1) of hospitals providing mental health care, (2) of community mental health centers, and (3) of psychiatrists. STUDY DESIGN: The study uses reports from administrators of community mental health centers (CMHCs) to assess the extent of patient dumping by hospitals. To assess the determinants of dumping, reported perceptions of dumping are regressed on variables describing the catchment area in terms of the proportion of for-profit hospitals, intensity of competition among hospitals, extent of utilization review, and capacity of the local treatment system, as well as competition among community mental health centers. To assess if dumping is motivated by factors distinct from those affecting other aspects of access, comparable regressions are estimated with ease of hospital admission as the dependent variables. PRINCIPAL FINDINGS: Economically motivated transfers of psychiatric patients were widespread in 1988: according to the reports of CMHC administrators, 64.7 percent of all hospitals providing inpatient mental health care engaged in transfers of this sort. The extent of dumping was higher in catchment areas with more competition among hospitals, more proprietary hospitals, and less inpatient capacity in the public sector. Dumping appeared to be more sensitive to capacity in the public sector but less sensitive to involvement by for-profit hospitals than were other measures of access to care. CONCLUSIONS: Economically motivated transfers of patients with mental illness were widespread in 1988 and likely have increased since that time, affecting the viability of the community mental health care system.

Adolescent↗
PubMed1996

Association of average heart rate on 24-hour ambulatory electrocardiograms with incidence of new coronary events at 48-month follow-up in 1,311 patients (mean age 81 years) with heart disease and sinus rhythm.

A prospective study performed in 1,311 men and women, mean age 81 years, with heart disease and sinus rhythm showed at 48-month follow-up that male sex, increasing age, and average 24-hour heart rate measured from 24-hour ambulatory electrocardiograms were independent risk factors for new coronary events. There was a 1.14 times higher chance of developing new coronary events for an increment of 5 beats/min of heart rate after controlling the confounding effect of other risk factors.

Age Distribution↗
PubMed1996

Raloxifene analog (LY117018 HCL) ameliorates cyclosporin A-induced osteopenia in oophorectomized rats.

Cyclosporin A (CsA) administered to the oophorectomized (Ox) rat exacerbates the high turnover osteopenia associated with estrogen deficiency. 17 beta-estradiol replacement therapy prevent this bone loss. The aim of this study was to see whether an estrogen-like compound, Raloxifene analog (LY117018 HCL, Ral) could likewise ameliorate CsA-induced osteopenia in the Ox rat. Sixty 6-month-old Sprague-Dawley rats, divided into five groups, underwent oophorectomy. One group acted as a basal group and the others received either vehicle (group B), CsA 15 mg/kg/day (group C), Ral 3 mg/kg/day (group D), or CsA 15 mg/kg/day and Ral 3 mg/kg/day (group E) for 28 days by gavage. A sixth sham operated group of 12 rats received vehicle only (group A). Rats were weighed and bled on days 0, 14, and 28 for measurement of ionized calcium, glucose, osteocalcin (BGP), 17 beta-estradiol, and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Tibiae were removed on day 28 for bone histomorphometry after double tetracycline and calcein labeling. Oophorectomy caused a significant gain in weight in groups B and C which was prevented by Ral in groups D and E. Randomized blood glucose levels and 1,25(OH)2D3 levels were elevated in both CsA-treated groups. Blood ionized calcium levels were lower in vehicle (group B) compared with sham (group A) on day 28. Ox (group B) had significantly higher serum BGP levels compared with sham-operated rats. Serum BGP levels were further elevated in group C compared with vehicle and were lowered in both Ral-treated groups to vehicle levels by day 28. Bone histomorphometry revealed a high turnover osteopenia with increased parameters of bone formation and resorption and loss of cancellous bone volume postoophorectomy (group B). CsA (group C) exacerbated the effects of oophorectomy. Ral (group D) completely prevented the high turnover osteopenia caused by oophorectomy and was able to attenuate substantially the effects of CsA in the Ox rat (group E). Ral therapy ameliorated CsA-induced osteopenia in the Ox rat and might prove a useful agent in preventing bone loss in postmenopausal women receiving CsA.

Animals↗
PubMed1996

Osteoporosis in pregnancy.

Osteoporosis has long been described in pregnant women who developed vertebral fractures in the last trimester or shortly after delivery without underlying disorders. However, this condition appears to be relatively rare and the clinical features, associated metabolic abnormalities and a pathological mechanism have not been fully established. This paper reviews available data on osteoporosis and pregnancy and briefly discusses the relationship between pregnancy and bone mass, calcium homeostasis, systemic skeletal hormones and local factors to help explain the pathophysiology of this unique disorder.

Adult↗