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Biomedical subjects

S Epstein

Publications and source records attributed to S Epstein.

At least 73 records · Page 4Linked to original sources
PubMed1996

Correlation of paroxysmal supraventricular tachycardia, atrial fibrillation, and sinus rhythm with incidences of new thromboembolic stroke in 1476 old-old patients.

The relationship between supraventricular tachycardia and the incidence of thromboembolic stroke has not been previously reported. We investigated in a prospective study the incidence of new thromboembolic stroke in 1476 patients, mean age 81 years, with atrial fibrillation, paroxysmal supraventricular tachycardia, or sinus rhythm detected by 24-hour ambulatory electrocardiograms. New thromboembolic stroke developed at 31-month follow-up in 87 of 201 patients (43%) with atrial fibrillation, at 43-month follow-up in 84 of 493 patients (17%) with paroxysmal supraventricular tachycardia, and at 45-month follow-up in 143 of 782 patients (18%) with sinus rhythm (p < 0.0001 comparing atrial fibrillation with paroxysmal supraventricular tachycardia or sinus rhythm). Kaplan-Meier survival curves showed a higher significance of thromboembolic stroke in patients with atrial fibrillation, compared to patients with paroxysmal supraventricular tachycardia or sinus rhythm (log-rank: p < 0.0001). Multivariate Cox regression model showed that independent significant predictors of thromboembolic stroke were: a) atrial fibrillation (relative risk = 3.31); b) prior thromboembolic stroke (relative risk = 2.85); c) sex (relative risk for women = 0.75); and d) age (relative risk = 1.02). These data show that atrial fibrillation is an independent predictor of thromboembolic stroke in elderly patients, and that paroxysmal supraventricular tachycardia is not associated with thromboembolic stroke.

Aged↗
PubMed1996

Short-term systemic insulin-like growth factor-1 is unable to prevent cyclosporin A-induced osteopenia in the rat.

Immunosuppression with cyclosporin A (CsA) is effective in a number of immune-mediated diseases and in preventing rejection following organ transplantation. We have repeatedly demonstrated that CsA in the rat model produces accelerated bone remodelling with net bone loss, best characterized in trabecular bone. IGF-I holds promise as a treatment for various osteopenic conditions. Although currently a subject of much controversy, various studies have suggested that in vivo it is anabolic to cortical as well as trabecular bone. The purpose of this study was, in part, to further characterize the effects of CsA and IGF-I on trabecular and cortical bone, and to see whether systemic IGF-I is able to modulate CsA's deleterious skeletal effects. Sixty 10 week-old, male, Sprague-Dawley rats were randomized to receive the following daily for 3 weeks: (1) CsA vehicle (veh) per os (po) + recombinant human (rh) IGF-1 veh subcutaneously (sc); (2) CsA 15 mg/kg po + rhIGF-I-veh; (3) CsA-veh + rhIGF-I 200 microg/kg sc; (4) CsA-veh + rhIGF-I 600 microg/kg sc; (5) CsA 15 mg/kg + rhIGF-I 200 microg/kg, and (6) CsA 15 mg/kg + rhIGF-I 600 microg/kg. Rats were weighed and venous blood was sampled serially for determination of glucose, ionized calcium (Ca2+), PTH, vitamin D, and osteocalcin. Following sacrifice on day 20, histomorphometry was performed on double calcein-labeled tibial metaphysis and diaphysis. All rats receiving CsA had elevated levels of blood glucose and osteocalcin by day 9 and vitamin D at day 20. PTH was similar in all groups, and Ca2+ was only raised in the CsA and CsA + IGF-I 200 microg/kg groups. Rats receiving IGF-I 200 microg/kg and IGF-I 600 microg/kg gained more weight than either vehicle- or CsA-treated animals, attesting to IGF-1's anabolic properties. CsA caused severe trabecular bone loss, not prevented by IGF-I; it even further increased the eroded surface. CsA and IGF-I had little effect on cortical bone volume or marrow area. IGF-I increased endocortical matrix synthesis, as evidenced by the increases in the percent endocortical osteoid perimeter, an effect negated by the addition of CsA. This experiment demonstrates that trabecular bone is more susceptible than cortical bone to the deleterious effects of CsA and indicates little role for IGF-1 in the pathophysiology or treatment of CsA-induced bone disease at the given doses and duration of treatment.

Animals↗
PubMed1996

Combined flurbiprofen and cyclosporin-A does not attenuate bone loss and exaggerates renal impairment.

Cyclosporine (CsA) is a potent immunosuppressant that has revolutionized the success of organ transplantation. Flurbiprofen (FB), a propionic acid derivative NSAID, has been demonstrated in vivo to reduce osteoclast numbers in normal rats. The aim of this experiment was to determine whether addition of FB to CsA-treated rats could prevent the bone changes associated with CsA therapy. Forty-eight 10-12-week-old male Sprague-Dawley rats were randomized to receive, daily for 28 days: (1) CsA vehicle p.o. plus FB vehicle sc; (2) CsA (15 mg/kg) p.o. plus FB vehicle sc, (3) CsA vehicle p.o. plus FB (1.5 mg/kg) sc; and (4) CsA (15 mg/kg) p.o. plus FB (1.5 mg/kg) sc. Rats were weighed and venous blood sampled at baseline, 14 days, and 28 days for determination of glucose, Ca+2, BUN, creatinine, PTH, osteocalcin, and 1,25(OH)2 vitamin D. Tibiae were removed following killing, after double labeling for histomorphometry. Body mass was significantly lower than control in all rats receiving CsA on days 14 and 28 while blood glucose was only elevated in the CsA alone group. Day 28 BUN and creatinine were significantly elevated in the CsA group and the combination of CsA and FB revealed an exacerbation of this trend. Vitamin D and osteocalcin were consistently increased in the CsA and CsA/FB groups. Bone histomorphometry showed evidence of trabecular osteopenia in CsA and CsA/FB groups. CsA alone resulted in elevated bone turnover. FB was unable to prevent the trabecular bone loss induced by CsA therapy. This experiment indicates no role for FB as a therapeutic option in CsA-induced bone disease at the given doses and duration of treatment by virtue of its lack of bone sparing ability and adverse renal effects when the two drugs are administered concurrently.

Administration, Oral↗
PubMed1996

Individual differences in intuitive-experiential and analytical-rational thinking styles.

Two studies provide evidence for the reliability and validity of a new self-report measure of individual differences in intuitive-experiential and analytical-rational thinking based on cognitive-experiential self-theory (CEST). The Rational-Experiential Inventory (REI) was constructed to measure the 2 independent processing modes with a modified Need for Cognition Scale (NFC, J.T. Cacioppo & R.E. Petty, 1982) and a new scale, Faith in Intuition (FI). In Study 1, a factor analysis yielded 2 orthogonal factors corresponding to NFC and FI. Although heuristic processing was determined primarily by FI, NFC also contributed to heuristic responding, in line with CEST. The relation of FI and NFC to coping ability also was examined. In Study 2, the factor structure of the REI was replicated (N = 973). NFC and FI were differentially related to measures of personality, adjustment, achievement, and interpersonal relations.

Cognition↗
PubMed1996

T lymphocytes play a critical role in the development of cyclosporin A-induced osteopenia.

The T lymphocyte suppressor, cyclosporin A, has been shown to cause high turnover osteoporosis. We postulated that cyclosporin A may exert its effects via the T cell rather than direct activity on bone. In this study we administered cyclosporin A (15 mg/kg.day by gavage) to 11 10-week-old Rowett athymic nude rats and to 12 age-matched immunocompetent Sprague-Dawley rats. Placebo was administered to control groups (n = 12 for both). After 28 days of treatment, the Sprague-Dawley rats displayed high turnover bone loss, but the nude rats were largely unaffected by the drug. Sprague-Dawley treated rats had less than half the percent trabecular area of their controls as measured at the secondary spongiosa of the proximal tibial metaphysis (P < 0.001; strain by treatment, P = 0.007). The same pattern was evident for trabecular number, separation, and thickness (strain by treatment, P = 0.034, P = 0.001, and P = 0.021, respectively). Only the Sprague-Dawley rats had an elevated percent eroded perimeter and an elevated bone area referent bone formation rate (strain by treatment, P = 0.002 and P = 0.0003, respectively). Mass, glucose, ionized calcium, PTH, osteocalcin, 1,25-dihydroxyvitamin D, and creatinine all responded similarly to cyclosporin A regardless of strain. T Lymphocytes thus appear to be a prerequisite for the development of cyclosporin A-induced osteopenia.

Animals↗
PubMed1995

Signal-averaged electrocardiography and ventricular tachycardia as predictors of mortality after acute myocardial infarction in elderly patients.

Signal-averaged electrocardiography and 24-hour ambulatory electrocardiographic monitoring were performed in 121 elderly patients > 6 months after acute myocardial infarction. All patients had asymptomatic complex ventricular arrhythmias and a left ventricular ejection fraction > or = 40%. Rates of sudden, cardiac, and total death were compared between groups with and without nonsustained ventricular tachycardia and between normal and abnormal signal-averaged electrocardiographic studies. The prevalence of an abnormal signal-averaged electrocardiographic study was 36%. Thirty-seven percent of the patients had nonsustained ventricular tachycardia, and the remaining patients had complex ventricular arrhythmias other than ventricular tachycardia. There were 27 sudden and 48 total cardiac deaths, and 66 deaths from all causes during a mean follow-up period of 30 months. Kaplan-Meier survival analysis showed a lower rate of sudden and cardiac death in the group without nonsustained ventricular tachycardia. Although there was a trend toward a lower rate of sudden death in patients with a normal signal-averaged electrocardiogram, there was no statistical difference in the rates of sudden, total cardiac, or total death between patients with normal or abnormal studies. The negative predictive value of having neither an abnormal signal-averaged electrocardiogram nor nonsustained ventricular tachycardia was 94% for sudden death. In elderly patients with complex ventricular arrhythmias and ejection fraction > or = 40% at least 6 months after an acute myocardial infarction, presence of nonsustained ventricular tachycardia predicted a higher rate of sudden and cardiac death. Signal-averaged electrocardiography alone was not predictive.

Aged↗
PubMed1995

Usefulness of an abnormal signal-averaged electrocardiogram for predicting cardiac death in elderly persons without heart disease.

We found an abnormal signal-averaged ECG in 7 of 51 elderly patients (14%) (mean age 83 years) without clinical evidence of heart disease, and in 1 of 25 volunteers (4%) (mean age 31 years range [17 to 47]) without clinical evidence of heart disease. The data from our prospective study indicate that at 43-month mean follow-up, elderly patients with an abnormal signal-averaged ECG but no clinical evidence of heart disease do not have an increased incidence of sudden cardiac death, total cardiac death, or total death.

Age Factors↗
PubMed1995

Azathioprine alone is bone sparing and does not alter cyclosporin A-induced osteopenia in the rat.

The immunosuppressant agent cyclosporin A (CsA) induces a high turnover osteopenic state, while the effect on bone of the antimetabolite azathioprine, a drug often used in conjunction with CsA in transplant patients, is less clear. This study was therefore designed to investigate the outcome of azathioprine administration, with reference to CsA, on bone mineral metabolism using the rat model. Four groups of 10-week-old male Sprague-Dawley rats (12 per group) were randomly allocated to receive by daily gavage for a 28-day period: (1) no treatment (control group); (2) azathioprine 1.5 mg/kg bw; (3) CsA 15 mg/kg bw; and (4) a combination of azathioprine and CsA, as described above. Rats were weighed and blood assayed serially for osteocalcin, ionized calcium, 1,25-dihydroxyvitamin D (1,25(OH)2VitD), and parathyroid hormone (PTH). Tibiae were removed following sacrifice on day 28 after double calcein labeling for histomorphometric analysis. Immunosuppressant groups were compared with nontreated control. We confirmed our previous findings that CsA induces a state of high turnover bone loss which is accompanied by a diminished gain in body weight (p < 0.01) and elevated serum osteocalcin (p < 0.001) and 1,25(OH)2VitD levels (p < 0.001). Azathioprine treatment alone did not alter ionized calcium, 1,25(OH)2VitD, or PTH levels. However, there was biochemical evidence of impaired osteoblastic activity as seen by decreased osteocalcin values on days 14 and 28 (p < 0.001). Azathioprine caused no loss of bone volume nor any deviation from the norm in mineral apposition rate, bone formation rate, or longitudinal bone growth. All three treatment groups showed an increased recruitment of osteoclasts to the bone surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Rapamycin: a bone sparing immunosuppressant?

Immunosuppressant therpay is associated with osteoporosis both clinically, post-transplantation, and experimentally. In rats, cyclosporin A (CsA) and FK506 induce a state of high turnover rapid bone loss. After 14 days of administration in immunosuppressive doses, the more recently discovered immunosuppressant, rapamycin, resulted in no change of cancellous bone volume. A longer study over 28 days has now been carried out; contrasting the new drug with CsA and FK506. Sixty, 10-week-old Sprague-Dawley rats were randomly divided into five groups of 12 rats each. The first group served as an aging control. The remaining four groups received, by daily gavage, a combined vehicle placebo, CsA 15 mg/kg, FK506 5 mg/kg, and rapamycin 2.5 mg/kg, respectively. CsA- and FK506-treated rats, but not those treated with rapamycin, demonstrated high turnover osteoporosis with raised serum 1,25(OH)2D (p < 0.05) and elevated serum osteocalcin (p < 0.05). The trabecular bone area was decreased by 66% (p < 0.01) in the CsA group and 56% (p < 0.05) in the FK506-treated group compared with the control animals. The CsA- and the rapamycin-treated groups failed to gain weight and developed severe hyperglycemia (> 20 mmol/l, p < 0.001) by day 14 but which largely resolved by day 28. Unlike the groups treated with CsA and FK506, rapamycin-treated rats had no loss of trabecular bone volume but there was increased modeling and remodeling and a decreased longitudinal growth rate. Rapamycin may thus confer a distinct advantage over the established immunosuppressants in not reducing bone volume in the short term.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Bone mineral metabolism in T lymphocyte-deficient and -replete strains of rat.

The immune and skeletal systems are known to interact. We have repeatedly shown that in contrast to in vitro data, the administration of T lymphocyte immunosuppressants, such as cyclosporin A, leads to an increase in bone resorption and a high turnover osteopenia. The purpose of this study was to characterize the bone metabolism of the T lymphocyte deficient Rowett athymic homozygous (rnu/rnu) nude rat. We wished to determine whether these rats share the bone abnormalities of cyclosporin A-treated rats. Eleven 10-week-old Sprague-Dawley rats and 12 similarly aged nude rats were studied over a 4-week period. Metaphyseal cancellous bone histomorphometry was similar in the two groups of rats and only differed with regard to percentage eroded perimeter (lower in nude rats, p = 0.0008) and longitudinal growth rate (49% lower in nude rats, p < 0.001). The nude rats had less body mass (p < 0.001) but nevertheless gained the same percentage of their body weight over the study period. The athymic rats had lower levels of serum, 1,25-dihydroxyvitamin D (p < 0.014) and serum osteocalcin(p < 0.009), and at the age of 14 weeks the nude rats had lower concentrations of serum creatinine (p = 0.001) and blood ionized calcium (p = 0.0002), yet serum PTH was similar throughout. RNA isolated from the contralateral tibias revealed that the nude group had lower steady-state levels of osteocalcin mRNA despite similar rates of bone formation. In its entirety, the data suggest that T cell deficiency per se is not necessarily associated with high turnover osteopenia.

Animals↗
PubMed1995

Amylin increases bone volume but cannot ameliorate diabetic osteopenia.

Amylin is normally secreted in a regulated fashion by the pancreatic beta-cells in parallel with insulin and has been reported to have bone-conserving properties. Type I diabetes mellitus results in a low-turnover osteopenia in the presence of decreased amylin, which is in contrast to type II diabetes where less bone loss, in the presence of high amylin levels, occurs. We investigated the effects of amylin on bone mineral metabolism in normal and diabetic (streptozotocin-induced) rats, in order to ascertain whether amylin would modify the streptozotocin-induced diabetic osteopenia. Ten-week-old male Sprague-Dawley rats were randomized as follows: group A (n = 18) received normal saline; group B (n = 18) received amylin; group C, diabetic rats (n = 23), received normal saline; and group D, diabetic rats (n = 23), received amylin. Amylin (100 pmol/100 g b.w.) was administered by a daily subcutaneous injection. Double calcein-labeled tibiae were removed for histomorphometric analysis followed sacrifice on day 19. Results showed no difference in blood ionized calcium between groups. Blood glucose remained above 600 mg/dl in the diabetic animals and was not affected by the administration of amylin. Serum osteocalcin, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), and 1,25 dihydroxyvitamin D [1,25(OH)2D] were significantly lower in the diabetic rats compared with control group A by day 19. Amylin produced higher levels of serum osteocalcin in group B on day 9 (P < 0.05) compared with controls but returned to control values (group A) by day 19; no such change occurred in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1995

A new rapid and reproducible homologous immunoradiometric assay for amino-terminal parathyroid hormone in the rat.

Measurement of parathyroid hormone (PTH) in the rat is most often performed with competitive ligand radioimmunoassays (RIA) utilizing heterologous antibodies. We report here the validation of a newly developed homologous immunoradiometric assay (IRMA) for rat PTH. Two different goat antibodies to the amino-terminal sequence of rat PTH are utilized; one is immobilized onto plastic beads to capture the PTH molecules and the other is radiolabeled for detection. To test this new IRMA, 30 Sprague-Dawley rats were randomized into three treatment groups to receive by intraperitoneal injection: (1) saline 1 ml/kg (control); (2) calcium chloride 40 mg/kg (hypercalcemic); and (3) EDTA 300 mg/kg (hypocalcemic). Blood samples were taken at 0, 30, 60, 180, and 300 minutes after administration of the assigned treatment for measurement of ionized calcium (Ca2+) and serum PTH. Most of the variance in PTH levels was found to be due to changes in Ca2+ (r2 = 0.780, P < 0.0001). There was also a close temporal relationship between the two, with the highest levels of PTH occurring at the same measured time points as the lowest Ca2+, and vice versa. The measured detection limit of the IRMA was 3 pg/ml with intra- and interassay coefficients of variation of 1.74% and 3.07%, respectively. Serial dilutions with pooled rat serum, synthetic rat PTH-(1-34), and synthetic human PTH-(1-34) showed good parallelism with increased specificity for the pooled and synthetic PTH, despite a degree of crossreactivity with hPTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Blood lactate concentration following exercise: effects of heat exposure and of active recovery in heat-acclimatized subjects.

The purpose of this study was to examine the effect of ambient heat on the decrease in blood lactate concentration ([LA]bl) during passive and during active recovery. Ten trained men performed six 1-min bouts of exercise at 100% VO2peak on a cycle ergometer, with 1-min rest between the bouts. Each subject exercised twice in thermoneutral (22 degrees C, 40% RH, TN), and twice in hot (35 degrees C, 30% RH, H) conditions. Exercise was followed by either 40 min of passive recovery (sitting) or by 20 min active recovery (cycling at 35% VO2peak) and 20 min passive recovery, named thereafter, 'active recovery'. Capillary blood lactate was measured before, 1 min after, and every 5 min during recovery. Heart rate (HR), rectal and skin temperatures (Tre, Tsk) were monitored continuously. VO2 was measured prior to exercise, during the last exercise bout, the first 10 min of recovery, and periodically thereafter. Post-exercise [LA]bl was similar in all treatments (13.5 +/- 1.8, 13.0 +/- 1.3, 14.8 +/- 4.1, 13.3 +/- 2.6 mmol.l-1 for TN-active, TN-passive, H-active and H-passive, respectively). [LA]bl was significantly lower during active, compared to passive recovery in both, TN and H conditions. Environmental heart did not independently affect [LA]bl during passive or active recovery. Exercise resulted in an elevation in Tre in all treatments, with a significantly higher Tre during active recovery in H compared to the other sessions. Likewise, no differences in HR and in VO2 were observed between H and TN conditions during active nor during passive recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗