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Biomedical subjects

S Epstein

Publications and source records attributed to S Epstein.

At least 145 records · Page 8Linked to original sources
PubMed1991

Salmon calcitonin prevents cyclosporin-A-induced high turnover bone loss.

Cyclosporin-A (CsA) has greatly influenced the outcome of organ transplantation and has also been effective in the treatment of many autoimmune diseases. Unfortunately, it has deleterious effects on bone remodelling, causing a high turnover bone loss, with bone resorption exceeding bone formation. Salmon calcitonin (SCtn) has been shown to inhibit bone resorption in high turnover states such as Paget's disease and postmenopausal osteoporosis. In an attempt to attenuate the high turnover bone remodelling caused by CsA alone, we studied the bone mineral effects of CsA in combination with SCtn in male Sprague-Dawley rats. Group A (n = 20) received vehicle as control, group B (n = 20) received CsA (15 mg/kg BW) by daily gavage and SCtn vehicle sc, group C (n = 20) received SCtn (1.3 IU/kg BW) daily sc and CsA vehicle, and group D (n = 20) received a combination of CsA and Ctn daily, as described above. Rats were bled weekly for determination of circulating biochemical bone parameters. Eight rats from each group were killed on day 14 (short term), and the remaining rats were killed on day 28 (long term). Tibiae were removed for bone histomorphometry after death, which revealed a reduction of trabecular bone volume and an increase in osteoclast number induced by CsA alone. These changes were significantly attenuated by the combination of CsA and SCtn to resemble the histomorphometry of the control group. The inhibition of osteoclast number by SCtn is the most plausible mechanism by which the combination therapy attenuates the high turnover bone loss induced by CsA alone.

Animals↗
PubMed1991

Psychiatrists' compliance with nonpsychiatric consultations: does compliance affect concordance?

Utilizing a systematic methodology (The Consultation-Liaison Outcome Evaluation System), the compliance of nonpsychiatric consultations within a general hospital psychiatric unit staffed by private practitioners was assessed. Thirty-one percent of the patients received such consultations and these patients had a longer length of stay than those without a consultation. Psychiatrists were generally compliant with both medication and diagnostic recommendations; but in only half the discharge summaries was the consultant's primary medical diagnosis fully reflected. The implications of these data are discussed.

Adult↗
PubMed1990

Effect of quinidine or procainamide versus no antiarrhythmic drug on sudden cardiac death, total cardiac death, and total death in elderly patients with heart disease and complex ventricular arrhythmias.

A prospective study correlated the effect of quinidine or procainamide versus no antiarrhythmic drug on sudden cardiac death, total cardiac death and total death in 406 elderly patients with heart disease and asymptomatic complex ventricular arrhythmias detected by 24-hour ambulatory electrocardiograms. Of 397 patients treated with quinidine, 184 (46%) developed adverse effects during the first 2 weeks of therapy and were given no further antiarrhythmic therapy. Of 9 patients treated with procainamide, 2 (22%) developed adverse effects during the first 2 weeks of therapy and were given no further antiarrhythmic therapy. Adverse effects developed during long-term therapy in 6 patients (2%) receiving quinidine and in 3 patients (33%) receiving procainamide. Mean follow-up was 24 +/- 15 months in both groups. Sudden cardiac death, total cardiac death and total death occurred in 21, 43 and 65% of patients receiving quinidine or procainamide, respectively, and in 23, 44 and 63% of patients receiving no antiarrhythmic drug, respectively (difference not significant). Survival by Kaplan-Meier analysis showed no significant difference between the 2 groups for sudden cardiac death, total cardiac death or total death through 4 years. Patients with abnormal left ventricular ejection fraction had a 3.4 times higher incidence of sudden cardiac death, a 2.4 times higher incidence of total cardiac death and a 1.4 times higher incidence of total death than patients with normal left ventricular ejection fraction. These data showed no significant difference in sudden cardiac death, total cardiac death or total death between patients treated with quinidine or procainamide or with no antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Alteration of vitamin D metabolism in Mexican-Americans.

Studies were performed to investigate vitamin D metabolism in Mexican-Americans. Groups of 15 whites and 16 Mexican-Americans ranging in age from 18 to 41 years were evaluated. All of them were within 25% of their ideal body weight. Each of them was admitted to the Clinical Research Center of the University of Texas Health Science Center and placed on a daily diet estimated to contain 400 mg calcium and 900 mg phosphate. It was found that whereas serum vitamin D (1.8 +/- 0.5 versus 7.6 +/- 1.3 ng/ml, P less than 0.001) and serum 25-hydroxyvitamin D (9 +/- 1 versus 17 +/- 2 ng/ml, P less than 0.01) were significantly lower and serum 1,25-dihydroxyvitamin D (37 +/- 2 versus 28 +/- 2 pg/ml, P less than 0.001) was significantly higher in the Mexican-Americans than in the whites, serum calcium (9.1 +/- 0.1 versus 9.2 +/- 0.1 mg/dl), magnesium (1.84 +/- 0.07 versus 1.80 +/- 0.07 mEq/liter), and Gla protein (19 +/- 3 versus 21 +/- 2 ng/ml) were not different in the two groups. Urinary calcium (144 +/- 14 versus 124 +/- 16 mg/day), phosphate (672 +/- 51 versus 683 +/- 44 mg/day), sodium (110 +/- 8 versus 99 +/- 9 mEq/day), potassium (43 +/- 4 versus 49 +/- 3 mEq/day), and magnesium (7.3 +/- 0.7 versus 7.7 +/- 0.5 mEq/day) and creatinine clearance (173 +/- 14 versus 154 +/- 7 liters/day) were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Combined treatment with cyclosporin A and cortisone acetate minimizes the adverse bone effects of either agent alone.

Although cyclosporin A (CsA) and cortisone acetate (CRT) adversely affect bone, their combined effect on bone is unknown. Sprague Dawley rats were therefore administered either vehicle or CsA (7.5 mg/kg/day) by gavage and saline or CRT (2 mg/100 mg/day) by s.c. injection for 28 days. Group A received vehicle plus saline, group B CsA plus saline, group C vehicle plus CRT, and group D CsA/CRT. Serial bloods were sampled over a 28-day period for ionized calcium (Ca), PTH, 1,25 dihydroxyvitamin D (1,25(OH)2D), and bone gla protein (BGP osteocalcin) and tibia were examined on day 28 for histomorphometry. Results were compared with group A. Ca and PTH levels in groups B, C, and D were similar to those in group A during the study period. Group B had lower body weights, elevated levels of BGP, and an increase in 1,25(OH)2D. Group C developed weight loss and a decrease in BGP and 1,25(OH)2D. Group D had weight loss, BGP levels between those of group A and group C, and 1,25(OH)2D values similar to group A. Bone histomorphometry revealed high turnover osteopenia in group B and hyperostosis in group C with a decrease in bone formation and osteoclastlike cells. Combination therapy returned these to control values. In conclusion, the adverse effects of either CsA or CRT on bone in rats are minimized by combined therapy.

Animals↗
PubMed1990

Hyperostosis induced by the bisphosphonate (2-PEBP) in the oophorectomized rat.

To prevent the high turnover bone remodeling associated with acute estrogen deficiency, the bisphosphonate [2-(2-pyridinyl) ethylidene-BP] (2-PEBP) was administered to oophorectomized (OX) rats. Three groups of 15 rats each (250 g) were studied. Group (Gp) A was sham operated, Gp B was OX, and Gp C received 2-PEBP (1.72 mg/kg/day) intraperitoneally for 3 days commencing 4 days postoophorectomy. Oophorectomy was confirmed with serum estradiol measurements. Blood samples were collected on days -7, 0, 7, 14, 21, and 28 for ionized calcium (Ca2+), PTH, and serum bone gla protein (BGP). Rats received tetracycline for bone histomorphometric labeling. All results were compared to Gp A. Body weight increased significantly in Gps B and C (P less than 0.005 by day 28). There was no significant difference in Ca2+, and PTH levels in Gps B and C were similar to Gp A. BGP levels were significantly higher on day 28 in Gp B (P less than 0.05). In Gp C, BGP levels were significantly decreased on days 7, 21, and 28 (P less than 0.03). Gp B revealed increased bone turnover without loss of bone volume (BV/TV). BV/TV was significantly increased in Gp C despite a decrease in parameters of bone formation and normal osteoclast number. In conclusion, 2-PEBP in the OX rat inhibited bone resorption more than formation with resultant hyperostosis. Serum BGP appeared to be a good marker of the changes observed on bone histomorphometry.

Animals↗
PubMed1990

The effect of high-dose salmon calcitonin on bone mineral metabolism in the normal rat.

The paucity of information on the effect of long-term high-dose salmon calcitonin administration on normal bone mineral metabolism and histology prompted an investigation of the influence of high-dose synthetic calcitonin in the rat. Serum ionized calcium, osteocalcin or BGP (bone gla protein), and immunoreactive PTH were measured serially during calcitonin administration and bone histomorphometry analyzed at 6 weeks (after sacrifice). Daily injections of salmon calcitonin, 0.4 IU/100 g (group B) and 2 IU/100 g (group C), resulted in significant hypocalcemia at 4 hours for both experimental groups (P less than 0.004). Serum iPTH was significantly higher over the study period for both groups administered calcitonin. Serum BGP levels were significantly lower than controls during the study in group C (P less than 0.002) and to a lesser extent in group B (P less than 0.05). In group C, bone histomorphometry revealed increased resorption (osteoclast count), decreased trabecular bone volume, and decreased double-labeled tetracycline surface (bone formation). In group B an increase in osteoclast count but no alteration in bone formation was observed. To assess the role of PTH in the above findings, high-dose calcitonin was administered to parathyroidectomized rats. All of the above changes in bone histomorphometry were not observed in this group of animals. In conclusion, high doses of calcitonin promote hypocalcemia, secondary hyperparathyroidism, and osteoclastosis in the normal rat in a dose-dependent manner with very high-dose calcitonin impairing bone formation.

Animals↗
PubMed1990

1,25 Dihydroxyvitamin D3 modifies cyclosporine-induced bone loss.

We have previously shown that cyclosporin A (CsA) produces high bone remodeling with resorption exceeding formation and loss of bone volume in the rat. This may have important clinical implications where CsA is widely used in organ transplantation. 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is a bone mineralizing hormone which also has immune modifying properties. Consequently, we studied the effect of combined CsA and 1,25(OH)2D3 administration over 28 days in four groups of rats. Group A received vehicle (n = 10), group B CsA (15 mg/kg) (n = 10) alone, group C 1,25(OH)2D3 plus CsA (n = 15), and group D 1,25(OH)2D3 alone (20 ng/100 g) (n = 15). Rats were bled periodically at day 0, 7, 14, and 28 and Ca, parathyroid hormone (PTH), 1,25(OH)2D, osteocalcin (bone Gla-protein, BGP), BUN, and creatinine were measured. Rats were sacrificed on day 28 and bones were examined histomorphometrically. Compared to controls, CsA resulted in significant elevation of BGP and a transient increase in 1,25(OH)2D with excess bone remodeling and loss of bone volume. 1,25(OH)2D3 administration produced hypercalcemia, a significant rise in BGP, with suppression of PTH and increased osteoid volume. Combined therapy prevented the loss of bone volume probably due to increased osteoid tissue and enhanced osteoblast activity. Renal dysfunction, a side-affect of CsA, was not a factor. In conclusion, 1,25(OH)2D3 combined with CsA restores bone volume which is accompanied by increases in serum calcium and BGP.

Animals↗
PubMed1990

Impact-induced devolatilization and hydrogen isotopic fractionation of serpentine: implications for planetary accretion.

The degree of impact-induced devolatilization of nonporous serpentine, porous serpentine, and deuterium-enriched serpentine was investigated using two independent experimental methods, the gas recovery method and the solid recovery method, yielding consistent results. The gas recovery method enables determination of the chemical and hydrogen isotopic composition of the recovered gases. Experiments on deuterium-enriched serpentine unambiguously identify the samples as the source of the recovered gases, as opposed to other possible contaminants. For shock pressures near incipient devolatilization (Pinitial = 5.0 GPa), the hydrogen isotopic composition of the evolved gas is similar to that of the starting material. For higher shock pressures the bulk evolved gas is significantly lower in deuterium than the starting material. There is also significant reduction of H2O to H2 in gases recovered at higher shock pressures, probably caused by reaction of evolved H2O with the metal gas recovery fixture. The hydrogen isotopic fractionation between the evolved gas and the residual solid indicates nonequilibrium, kinetic control of gas-solid isotopic ratios. In contrast, gaseous H2O-H2 isotopic fractionation suggests high temperature (800-1300 K) isotopic equilibrium between the gaseous species, indicating initiation of devolatilization at sites of greater than average energy deposition (i.e., shear bands). Impact-induced hydrogen isotopic fractionation of hydrous silicates during accretion can affect the distribution of hydrogen isotopes of planetary bodies during accretion, leaving the interiors enriched in deuterium. The significance of this process for planetary development depends on the models used for extrapolation of the observed isotopic fractionation to devolatilizations greater than those investigated experimentally and assumptions about timing and rates of protoatmosphere loss, frequency of multiple impacts, and rates of gas-solid or gas-melt isotopic re-equilibration. A simple model indicates that substantial planetary interior enrichments of D/H relative to that of the incident material can result from impact-induced hydrogen fractionation during accretion.

Asbestos, Serpentine↗
PubMed1990

The response of circulating parameters of bone mineral metabolism to ethanol- and EDTA-induced hypocalcemia in the rat.

The mechanism of the acute hypocalcemia that follows acute ethanol administration has not been established. Measurements of parathyroid hormone (PTH) performed during this hypocalcemia reveal conflicting results. We compared the response of ionized calcium (Ca2+), immunoreactive PTH and bone Gla protein (BGP) after ethanol- and EDTA-induced hypocalcemia. 103 male Sprague Dawley rats each weighing approximately 300 g received ethanol and 100 rats of similar weight received EDTA. In each of these studies the animals were divided into experimental and control groups. The ethanol-treated rats received ethanol, 2 g/kg body weight, by ip injection and the EDTA-treated rats received 100 mg EDTA/kg body weight by im injection. Controls received normal saline by the corresponding route of administration. Rats were sacrificed at 0, 30, 60, 90, 180 and 360 min for the measurement of the above parameters. In both experimental groups Ca2+ levels were significantly reduced to the same degree by 30 min with return to control values by 360 min. There was no significant difference in immunoreactive PTH, and BGP between control and ethanol-treated groups. In the EDTA-treated rats, however, PTH values were significantly increased at 30 (P less than 0.005) and BGP at 60 and 90 minutes (P less than 0.005) vs. control. Therefore acute ethanol administration appears to blunt the PTH response to hypocalcemia. A direct inhibitory effect of ethanol on osteoblast function ie BGP production cannot be excluded. In addition, PTH may stimulate BGP.

Animals↗
PubMed1990

Influence of increased metabolic rate on [13C]bicarbonate washout kinetics.

The effect of changes in metabolic rate on the dynamics of CO2 exchange among its various compartments in the human body is not well understood. We examined CO2 dynamics in six healthy male subjects using an intravenous bolus of [13C]bicarbonate. Subjects were studied while resting, during light exercise [50% of the lactate threshold (LT), 3-4 times resting O2 uptake (VO2)], and during moderate exercise (95% of the LT, 6 times resting VO2). The sum of three exponential terms well described the washout of 13CO2 in exhaled breath both at rest and during each exercise level despite substantial increases in metabolic rate accompanying the exercise studies. Average recovery of 13C label rose from 67% during rest to 80% during light and moderate exercise (P less than 0.01). The estimate of CO2 elimination (VCO2) calculated from the washout parameters and corrected for recovery was in very good agreement with the VCO2 directly measured simultaneously breath by breath (r = 0.993, SE for VCO2 = 0.079 l/min). By use of a three-compartment mammillary model, the quantity of CO2 in the central pool (Q1) doubled from rest to light exercise (233 +/- 60 to 479 +/- 76 mmol, P less than 0.01) but did not change further with moderate exercise (458 +/- 74 mmol). Rate constants for exchange between pools and for irreversible loss from the system tended to increase with metabolic rate, but there was large variation in the responses. We conclude that the compartmental dynamics of CO2 transport and storage are very sensitive to changes in metabolic rate induced by exercise.

Adult↗
PubMed1990

Oral [13C]bicarbonate measurement of CO2 stores and dynamics in children and adults.

During exercise, less additional CO2 is stored per kilogram body weight in children than in adults, suggesting that children have a smaller capacity to store metabolically produced CO2. To examine this, tracer doses of [13C]bicarbonate were administered orally to 10 children (8-12 yr) and 12 adults (25-40 yr) at rest. Washout of 13CO2 in breath was analyzed to estimate recovery of tracer, mean residence time (MRT), and size of CO2 stores. CO2 production (VCO2) was also measured breath by breath using gas exchange techniques. Recovery did not differ significantly between children [73 +/- 13% (SD)] and adults (71 +/- 9%). MRT was shorter in children (42 +/- 7 min) compared with adults (66 +/- 15 min, P less than 0.001). VCO2 per kilogram was higher in the children (5.4 +/- 0.9 ml.min-1.kg-1) compared with adults (3.1 +/- 0.5, P less than 0.0001). Tracer estimate of CO2 production was correlated to VCO2 (r = 0.86, P less than 0.0001) and when corrected for mean recovery accurately predicted the VCO2 to within 3 +/- 14%. There was no difference in the estimate of resting CO2 stores between children (222 +/- 52 ml CO2/kg) and adults (203 +/- 42 ml CO2/kg). We conclude that orally administered [13C]bicarbonate can be used to assess CO2 transport dynamics. The data do not support the hypothesis of lower CO2 stores under resting conditions in children.

Adult↗
PubMed1990

Usefulness of echocardiographic left ventricular hypertrophy and silent ischemia in predicting new cardiac events in elderly patients with systemic hypertension or coronary artery disease.

The authors performed a prospective study to correlate echocardiographic left ventricular hypertrophy (LVH) and silent ischemia (SI) detected by twenty-four-hour ambulatory electrocardiographic monitoring with new cardiac events in 355 patients, mean age eighty-two +/- eight years, with systemic hypertension or coronary artery disease (CAD). Cardiac events included myocardial infarction, primary ventricular fibrillation, or sudden cardiac death. Mean follow-up was thirty-one +/- seven months (range twelve to forty). Cardiac events occurred in 28 of 147 patients (19%) without LVH or SI (A), in 56 of 113 patients (50%) with LVH and no SI (B), in 16 of 29 patients (55%) with SI and no LVH (C), and in 52 of 66 patients (79%) with LVH and SI (D). Significant p values were p less than 0.001 comparing D with A, D with B, C with A, and B with A; and p less than 0.02 comparing D with C. These data indicate that echocardiographic LVH and SI detected by ambulatory electrocardiographic monitoring are independent risk factors for new cardiac events in elderly patients with systemic hypertension or CAD.

Aged↗