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Biomedical subjects

S Epstein

Publications and source records attributed to S Epstein.

At least 127 records · Page 7Linked to original sources

Evidence that cyclosporine G is less deleterious to rat bone in vivo than cyclosporine A.

We have previously shown that CsA administration to rats causes a high turnover bone loss with bone resorption exceeding bone formation. Similar findings have been reported in renal and cardiac transplantation patients administered CsA. Cyclosporine-G (CsG), a natural equipotent immunosuppressive analogue of CsA, has been shown to be less nephrotoxic than CsA. We therefore compared the effects of CsG and CsA on bone mineral metabolism. Sixty male Sprague-Dawley rats were divided into 3 equal groups as follows: group A (n = 20) was the control; group B (n = 20) received CsA 15 mg/kg by daily gavage; and group C received CsG 15 mg/kg by daily gavage for 28 days. Rats were bled weekly for measurement of circulating biochemical parameters of bone mineral metabolism and after sacrifice on day 28, the tibiae were removed for histomorphometric analysis. The tibial bone histomorphometry revealed that the percentage of bone volume was significantly reduced, and the osteoclast count increased in both the CsA and CsG group, but significantly less so in the CsG than the CsA group. Parameters reflecting bone formation in the CsG group were similar to controls but significantly different from the CsA group. Bone Gla protein levels in the CsA group were significantly increased compared with the control and CsG groups from day 14. Serum 1,25 dihydroxyvitamin D was increased significantly in the CsA group on days 14 and 28 compared with both control and CsG groups, and was significantly elevated in the CsG group compared with controls on the same days. We conclude that CsG is significantly less deleterious to bone mineral metabolism than CsA in the rat in vivo.

Animals↗

The role of general hospitals in the privatization of inpatient treatment for serious mental illness.

For almost three decades, many have regarded general hospital psychiatric units as the most appropriate setting for acute treatment of persons with serious mental illness who were once treated mostly in state hospitals. The extent to which this transfer has taken place and the differences between public and private general hospitals have been unclear. Using data from the 1988 National Mental Health Facilities Study and published data from the 1970s, the authors found that nearly half of all general hospitals providing psychiatric services treat persons with serious mental illness. Significant differences in case and payer mix were observed between public and private general hospitals, although these differences were smaller than in the 1970s. The findings suggest increased involvement by private general hospitals in treating patients reimbursed by public payers, but the findings also indicate that persons with serious mental illness and those using Medicaid are still more prevalent in public general hospitals than in private ones.

Community Mental Health Services↗

17 beta-estradiol prevents osteopenia in the oophorectomized rat treated with cyclosporin-A.

Cyclosporin-A (CsA) administered to the oophorectomized rat exaggerates the high turnover osteopenia associated with oophorectomy alone. This study investigated whether 17 beta-estradiol replacement could influence the development of osteopenia in the oophorectomized rat treated with CsA. Ninety female Sprague-Dawley rats, approximately 300 g in weight, were divided into 6 groups of 15 each and treated according to the following protocol: group A were sham operated (control), group B underwent oophorectomy (Ox), group C underwent Ox and received CsA (15 mg/kg, by daily gavage) for 28 days (Ox and CsA), group D underwent Ox and received CsA and a 0.1 mg 17 beta-estradiol pellet (EP) implanted sc (Ox, CsA, and EP), group E underwent Ox and received EP (Ox and EP), and group F, which was intact and nonoperated, received CsA (CsA). Rats were weighed and bled on days -7, 0, 7, 14, 21, and 28 for measurement of blood ionized calcium, bone Gla protein (BGP), 17 beta-estradiol, and PTH. Bone histomorphometry was determined after double tetracycline labeling. On day 28, serum 17 beta-estradiol was undetectable in groups B (Ox) and C (Ox and CsA), and similar to group A (control) in groups D (Ox, CsA, and EP), E (Ox and EP), and F (CsA). Oophorectomy resulted in a significant gain in weight in groups B (Ox) and C (Ox and CsA), which was prevented by 17 beta-estradiol in groups D (Ox, CsA, and EP) and E (Ox and EP). On day 28, serum BGP levels were higher in groups B (Ox; 73.58 +/- 3.63 ng/ml), C (Ox and CsA; 85.05 +/- 9.88), and F (CsA; 81.35 +/- 3.4) compared to group A (control; 46.07 +/- 5.52; P less than 0.05), while 17 beta-estradiol in groups D (Ox, CsA, and EP; 38.65 +/- 2.85) and E (Ox and EP; 41.89 +/- 1.89) prevented this rise (P = 0.01). BGP levels in group C (Ox and CsA) were higher on days 14 and 21 compared to group B (Ox). Groups D (Ox, CsA, and EP) and E (Ox and EP) had elevated blood ionized calcium levels from day 7 onward. Serum PTH levels were unchanged. Histomorphometric analyses of tibial metaphyses revealed increased parameters of bone formation and resorption, with significant loss of bone volume, in groups B (Ox; 12.03 +/- 1.40%) and C (Ox and CsA; 11.43 +/- 2.20) vs. group A (control; 24.36 +/- 2.37; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of an iron supplement on body iron status and aerobic capacity of young training women.

Serum iron deficiency has a high incidence in female athletes. We investigated the effects of a daily oral iron supplement, (160 mg) administered during an intensive 7-week physical training programme, on body iron status, and the maximal aerobic capacity (VO2max) of 13 women (group A) compared to 15 who took a placebo (group B). The subjects were 19 years old. Blood samples were obtained before training began and on days 1, 7, 21 and 42 of training. They were analysed for packed cell volume (PVC) and for haemoglobin (Hb), 2,3-diphosphoglycerate (2,3-DPG), haptoglobin, iron and ferritin concentrations. The VO2max was measured on days 0, 21 and 42 of training. Following 21 days of training Hb, PCV and ferritin were significantly higher (P less than or equal to 0.01) in group A compared to group B. Over the training period Hb rose by 9.3% and 2.4% in groups A and B, respectively. At the end of training 66% of group B exhibited ferritin concentrations below 10 ng.ml-1, while none of group A had such low values. Mean VO2max of group A had increased by 7.5% following 21 days of training (P less than or equal to 0.01) and by 15.3% after 42 days. No appreciable increase in VO2max had occurred in group B by day 21 (significantly lower than VO2max of group A; P less than or equal to 0.05), however by day 42 it had increased by 14.3% (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Correlated Si isotope anomalies and large 13C enrichments in a family of exotic SiC grains.

A suite of morphologically distinctive silicon carbide (SiC) grains from the Orgueil and Murchison carbonaceous chondrite meteorites contains Si and C of highly anomalous isotopic composition. All of the SiC grains in this suite are characterized by a distinctive platy morphology and roughly developed hexagonal crystal forms that allow them to be distinguished from other types of SiC found in the host meteorites. The delta 29Si and delta 30Si values of individual SiC crystals deviate from those of normal solar material by more than 100%, while the delta 13C values range from 150 to 5200%. Isotopically normal C and Si are not found in any of these SiC crystals. The SiC grains belonging to this morphological suite are isotopically distinct from fine-grained SiC aggregates and other morphological types of SiC in unequilibrated meteorites. The 29Si/28Si and 30Si/28Si ratios of these platy grains are well correlated and define a linear array that does not pass through the composition of normal, solar Si. This behavior contrasts sharply with the diverse and poorly correlated Si isotopic compositions shown by the total SiC population. We suggest that the distinctive morphological characteristics and comparatively simple Si isotope systematics identify the platy SiC crystals as a genetically related family, formed around a single, isotopically heterogeneous presolar star or an association of related stars. The enrichments in 13C and the Si isotope systematics of the platy SiC are broadly consistent with theoretical models of nucleosynthesis in low-mass, carbon stars on the asymptotic giant branch. The Si isotope array most plausibly reflects mixing between 28Si-rich material, inherited from a previous generation of stars, and material enriched in 29Si and 30Si, produced in intershell regions by neutron capture during He-burning. 13C is also produced in intershell regions by proton reactions on 12C seed nuclei and is carried with s-process nuclei to the stellar envelope by convection which penetrates down to the He shell. The absence of a correlation between the Si and C isotopic compositions of the SiC suggests either episodic condensation of SiC, extending over several thermal pulses, in the atmosphere of a single star, or derivation of the SiC from several stars characterized by different rates of 13C production. In the multiple star scenario, the linear correlation of the 29Si/28Si and 30Si/28Si ratios among the platy SiC indicates that these stars evolved from a common Si seed composition under similar conditions of neutron-capture nucleosynthesis. The 29Si/30Si ratio of the SiC, inferred by us to be produced by neutron capture in the stellar interior, is distinct from values calculated from models of nucleosynthesis in AGB stars.

Astronomical Phenomena↗

Implanted 3He, 4He, and Xe in further studies of diamonds from Western Australia.

In measurements of the noble gases in additional samples of diamonds from the Argyle and Ellendale lamproites in Western Australia we have failed to encounter any neon-rich stones such as showed solar-like isotopic compositions in earlier work. No neon was detected above the relatively high blank levels in our glass apparatus. White and brown diamonds showed no differences in noble gas content, nor did samples segregated by the color of long-wave UF fluorescence. The rare gas patterns in the 1.2 Ga Argyle pipe are largely consistent with implanted 3He, 4He, and fissiogenic Xe from U/Th in the matrix rock in which the diamonds have been stored for so long. These implanted species are absent in diamonds from the much younger (approximately 20 Ma) Ellendale pipe. We give implantation formulae for several models of inhomogeneously distributed U/Th. Differences in 3He content between pipe and alluvial Argyle samples are consistent with expected cosmogenic production in the latter. An expanded data base for helium and carbon isotopic data on the same samples supports a negative [4He]-delta 13C correlation seen earlier in work from our group, but if the Argyle samples, which contain light carbon, are corrected for implanted 4He, the correlation is considerably weakened. We no longer see an earlier 3He/4He-delta 13C correlation.

Carbon Isotopes↗

Isotopic analyses of amino acids from the Murchison meteorite.

Previous isotopic analyses of the total amino acids of the Murchison meteorite showed these compounds to be substantially enriched in 2H, 13C, and 15N relative to terrestrial organic matter. These analyses have been repeated (2H, 13C) with inclusion of an ultrafiltration step to exclude the possibility that a fine particulate contaminant carried the isotopic excesses observed in the previous work. In addition, the meteorite amino acids were chromatographically separated to rule out the possibility that the isotopic enrichment of the meteorite extract could reside in basic compounds other than amino acids. The results indicate that the Murchison amino acids are truly isotopically unusual, that the isotopic excesses reside in at least several different amino acids, and that the isotopic contents of some of these amino acids reach values of about +40% (delta 13C) and +2500% (delta D). If it is assumed that the high deuterium content of the meteorite alpha-amino acids is a result of the synthesis of their molecular precursors by low temperature ion-molecule reactions in an interstellar cloud, their formation by aqueous phase Strecker reactions in the parent body is consistent with their general characteristics and with known parent body processes.

Amino Acids↗

Isotopic composition of hydrogen in insoluble organic matter from cherts.

Robert (1989) reported the presence of unusually enriched hydrogen in the insoluble HF-HCl residue extracted from two chert samples of Eocene and Pliocene ages. Since the presence of heavy hydrogen might be due to the incorporation of extraterrestrial materials, we desired to reexamine the same samples to isolate the D-rich components. Our experiments did not reveal any D-rich components, but the hydrogen isotope composition of the insoluble residue of the two chert samples was well within the range expected for terrestrial organic matter. We also describe a protocol that needs to be followed in the hydrogen isotope analysis of any insoluble organic matter.

Deuterium↗

Osteoporosis associated with rheumatoid arthritis: pathogenesis and management.

Rheumatoid arthritis is associated with both localized and generalized osteoporosis. Localized osteoporosis can be considered to be caused by local disease mechanisms, including the generation of factors from activation of the cytokine pathway. The etiology of generalized osteoporosis has been difficult to elucidate, particularly because of the lack of sensitive techniques to measure bone mineral density. The introduction of single- and dual-photon absorptiometry and quantitative computed tomography has allowed more accurate assessment of bone mineral density. In general, bone mineral density loss at appendicular sites does not correlate well with axial bone density loss. Corticosteroid treatment exaggerates the development of osteoporosis in up to 40% of patients with rheumatoid arthritis. Sex hormone status, physical activity, disease duration, and functional class are all significant predictors for the development of osteoporosis. Current therapy for prevention and treatment is based largely on theoretical considerations. Physical activity should be encouraged once acute joint inflammation has settled. Postmenopausal women and amenorrheic premenopausal women will benefit from cyclical estrogen replacement. Patients with low serum 1,25-dihydroxy vitamin D3 levels, and males with low serum testosterone levels, are candidates for replacement therapy with the appropriate hormones. In patients who are receiving corticosteroids the dose should be limited, and oral calcium supplements are of benefit. The use of the newer corticosteroid deflazacort, and disease-modifying immunosuppressive drugs, are discussed. Other therapeutic options which should be considered, although published trials are scarce, are calcitonin and the diphosphonates. Further studies are awaited concerning the optimum prevention and treatment of osteoporosis associated with rheumatoid arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

Delusions of disfigurement in a woman with acne rosacea.

A 36-year-old woman with newly diagnosed acne rosacea is presented. Her skin changes were noticeable only under closest scrutiny, but she quit her job, became despondent about her acne, and developed suicidal ideation. The diagnosis and treatment of this patient allow a broader discussion of the somatically focused patient whose ideation reaches delusional intensity.

Adult↗

Constructive thinking and coping with laboratory-induced stress.

In a laboratory stress test, poor constructive thinkers produced more negative affective and cognitive responses in all experimental periods and a greater increase in such responses in the stress period than did good constructive thinkers. The groups differed in physiological arousal in the recovery period but not in the stress period. Stressor-instigated negative thoughts and spontaneous negative thoughts produced different patterns of relations with variables measured in the laboratory and with symptoms reported in everyday life. Discriminating patterns of relations were found between measures of cognition and affect in the laboratory and self-reported emotional, physical, and behavioral symptoms in everyday life. The results help explain the relation between maladaptive automatic thinking, on the one hand, and elevated physiological arousal and emotional, physical, and behavioral symptoms, on the other.

Adaptation, Psychological↗

Cytotoxic activity of chimeric proteins composed of acidic fibroblast growth factor and Pseudomonas exotoxin on a variety of cell types.

Chimeric proteins composed of acidic fibroblast growth factor (acidic FGF) and several forms of Pseudomonas exotoxin (PE) that cannot bind to the PE receptor have been produced in Escherichia coli by expressing chimeric genes in which DNA encoding acidic FGF is fused to various mutant forms of PE. These acidic FGF-PE fusion proteins were found to be cytotoxic to a variety of tumor cell lines including hepatocellular (PLC/PRF/5 and HEPG2), prostatic (LNCaP), colon (HT29), and breast (MCF-7) carcinomas at concentrations of 1-70 ng/ml. The cytotoxic effects of acidic FGF-PE were FGF-receptor specific as demonstrated by competition with excess acidic FGF and by showing that acidic FGF-PE bound to the FGF receptor with the same affinity as acidic FGF. Furthermore, the cell-killing activity of acidic FGF-PE was toxin-mediated, as an acidic FGF-PE mutant, which does not possess ADP-ribosylation activity, failed to kill cells. These findings demonstrate that acidic FGF-PE is a potent cytotoxic molecule that can be targeted to FGF receptor-bearing cells. Because acidic FGF is a potent angiogenic molecule, cytotoxic acidic FGF-PE chimeras may have utility as anti-angiogenic agents. These molecules could be helpful in determining the functional role of FGF receptors in cellular processes.

ADP Ribose Transferases↗

Ego defensive styles and alexithymia: a discriminant validation study.

Fifty-six mildly depressed psychiatric outpatients were evaluated for alexithymia measured by the Toronto Alexithymia Scale. Each subject also completed a Defensive Style Questionnaire that assessed the maturity of their ego defenses. Alexithymia was strongly associated with immature ego defenses, but not with depression. The data suggests that alexithymia and such primitive defensive operations are separate phenomena. These findings empirically support earlier observations regarding the nature of alexithymia.

Adult↗

A national study of psychiatric hospital care.

BACKGROUND: The delivery system for psychiatric inpatient services in the United States has changed dramatically over the past 30 years, undergoing a marked privatization. METHOD: To assess the effect of changes in ownership and types of inpatient settings on the structure of the mental health services system, the authors surveyed a national sample of nonfederal mental health facilities in 1988. RESULTS: Comparing their data to those of earlier surveys, they found that a decline in the number of patients per staff occurred in most settings over the last decade, suggesting that this aspect of quality of care may have improved. They observed important ownership-related differences in 1988 in diagnostic mix (e.g., more schizophrenia treated in public facilities than in private ones) and in payer source (e.g., more third-party revenues in public facilities than occurred in the past). CONCLUSIONS: There was a significant interaction between ownership form and type of facility, suggesting that the type of inpatient setting, ownership, and the relation between the two should be considered in assessing the impact of privatization on the accessibility of health care available for the mentally ill. The authors found that the increase in private psychiatric hospitals has widened the availability and choice of treatment facilities for those with private funding sources (especially children and adolescents) but has not had a similar effect in increasing sources of care for the seriously mentally ill dependent upon public financing.

Adolescent↗

Cyclosporin-A increases synthesis of 1,25-dihydroxyvitamin D3 in the rat and mouse.

We have previously observed elevated serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] levels in male rats treated with oral cyclosporin-A (CsA). This elevation was independent of changes in PTH, ionized calcium, or phosphate. This paper investigates the potential sources and mechanisms for this increase in both rats and mice. Kidney homogenates from rats treated for 14 days with (15 mg/kg) had a significant increase in 25-hydroxyvitamin D (25OHD)-24-hydroxylase (24-hydroxylase) activity (149 +/- 20 vs. 89 +/- 16 fmol/mg.min; P less than 0.05), but nonsignificant increases in 25OHD-1 alpha-hydroxylase (1 alpha-hydroxylase) activity compared to controls. Kidney homogenates from C57b16J mice after the administration of 30-50 mg/kg CsA for 3 days revealed a linear dose-related increase in renal 1 alpha-hydroxylase (r = 0.96; P less than 0.05), which became significant with doses of 30 mg/kg CsA or more (P less than 0.05). To investigate the source of this 1,25-(OH)2D production, serum 1,25-(OH)2D was measured before and 48 h after bilateral nephrectomy in rats receiving CsA for 16 days. The percent decrease in serum 1,25-(OH)2D values was not significantly different in CsA-treated and untreated rats (33.9 +/- 4.9% vs. 47.5 +/- 4.9%), indicating little or no contribution from nonrenal sources. Studies of MCRs and production rates (PRs) revealed that the elevated 1,25-(OH)2D values were due to enhanced production and not altered clearance (PR, 12.4 +/- 1.2 vs. 19.1 +/- 1.9 fmol/mg.min; P less than 0.01). CsA increases 1 alpha-hydroxylase activity and produces significant elevations in serum 1,25-(OH)2D levels in both rats and mice. This increase may have an impact on bone mineral metabolism and immune modulation in postorgan transplantation patients.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗