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M Epstein

Publications and source records attributed to M Epstein.

At least 145 records · Page 8Linked to original sources
PubMed1994

Calcium antagonists and the kidney.

During the past decade, attention has focused on the effects of calcium antagonists on renal function. Recent studies using diverse video microscopic techniques, including the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that calcium antagonists acutely antagonize pre-glomerular vasoconstriction. In contrast, most studies suggest that the efferent arteriole appears to be refractory to the vasodilatory effects of these agents. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics, including transplant-associated acute renal insufficiency and possibly cyclosporin nephrotoxicity. Evidence has accrued suggesting that calcium antagonists may also be protective against acute radiocontrast-induced nephrotoxicity. The renal hemodynamic and natriuretic effects of calcium antagonists command their use as antihypertensive agents in the management of essential hypertension, and transplant-associated hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Hypertension as a risk factor for progression of chronic renal disease.

The declining mortality due to coronary artery disease and stroke has been attributed in part to improved effectiveness and application of antihypertensive therapy, and successful identification and treatment of the population at risk. In striking contrast, end-stage renal disease (ESRD) attributed to hypertension has increased annually for the last decade and will probably worsen through the year 2000. Taken together, patients with diabetic nephropathy and those with hypertensive renal disease account for the majority of new cases annually. The reasons for the striking dissociation between the success with coronary artery disease and stroke on the one hand and the inability to lessen the incidence of ESRD remain to be clarified. Evidence reveals that all levels of untreated hypertension are associated with potentially declining renal function. Data from the Hypertension Detection and Follow-up Program and other studies suggest that antihypertensive treatment can prevent or retard development of progressive renal failure. No data are readily available on repeated measurement of glomerular filtration rate during prolonged treatment of mild hypertension in patients with normal or near-normal renal function. Although the importance of blood pressure control is implicit, a theoretical framework based on data derived from experimental animals suggests that angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists may exert specific renoprotective effects beyond those achieved by blood pressure reduction per se. The results of two recent long-term prospective studies support such a formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1993

Angiotensin-converting enzyme inhibitors and progression of nondiabetic chronic renal disease.

In recent years, considerable attention has focused on the possibility that some classes of antihypertensive agents may confer a greater renoprotective effect in retarding the progression of chronic renal insufficiency. Experimental studies in rats have demonstrated that the sustained increase in glomerular capillary pressure evoked in response to loss of renal mass produces a destructive sclerosing reaction. Administration of angiotensin-converting enzyme inhibitors decreases glomerular capillary pressure with a resultant reduction of glomerular sclerosis, suggesting that angiotensin-converting enzyme inhibitor therapy may protect the injured kidney from hemodynamically mediated glomerular damage. On the basis of these experimental observations, many studies have attempted to investigate whether angiotensin-converting enzyme inhibitors can slow the progression of chronic renal disease in humans. We surveyed the literature critically and concluded that, the data from animals notwithstanding, the majority of studies in humans have been nonrandomized, of too short duration, or confounded by investigative difficulties. Therefore, we cannot yet conclude that angiotensin-converting enzyme inhibitors modify the rate at which renal disease progresses in nondiabetic patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Successful delivery following myocardial ischemia during the second trimester of pregnancy.

Acute myocardial infarction during pregnancy is considered to be associated with approximately 50% mortality of both mother and fetus. However, there are not enough data regarding the role of acute myocardial ischemia. We present a 36-year-old, pregnant, white female who was admitted twice at 18 and 20 weeks of gestation with acute myocardial ischemia. Cardiac catheterization revealed 70-80% stenosis of the mid left anterior descending artery (LAD) with normal antegrade flow and very good retrograde filling of the LAD from distal collaterals of the right coronary artery. Therefore, due to angiographic suggestion of protected LAD territory, we recommended medical therapy and scheduled a vaginal delivery that was successfully completed without cardiovascular complications. A stress thallium test performed 6 months later was normal, supporting our clinical judgment. In conclusion, every case of a pregnant woman with coronary insufficiency should be treated according to individual coronary anatomy and blood supply to the territory of the diseased artery, and should not be based on the old data in the literature. The decision for revascularization prior to delivery versus medical therapy, or Caesarean section versus natural delivery, should be made by a team of a cardiologist and an obstetrician.

Acute Disease↗
PubMed1993

Calcium antagonists and the kidney: future therapeutic perspectives.

During the past decade, attention has focused on the effects of calcium antagonists on renal function. Recent studies using diverse videomicroscopic techniques including the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that calcium antagonists acutely antagonize preglomerular vasoconstriction. In contrast, most studies suggest that the efferent arteriole appears to be refractory to the vasodilatory effects of these agents. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics, including transplant-associated acute renal insufficiency and, possibly, cyclosporine nephrotoxicity. Evidence has accrued to suggest that calcium antagonists also may be protective against acute radiocontrast-induced nephrotoxicity. Finally, the renal hemodynamic and natriuretic effects of calcium antagonists commend their use as antihypertensive agents in the management of essential hypertension and transplant-associated hypertension.

Acute Kidney Injury↗
PubMed1993

Calcium antagonists and the kidney. Implications for renal protection.

During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they alter dramatically the response of this preparation to vasoconstrictor agents. Our recent studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, demonstrated that the preferential augmentation of glomerular filtration rate observed in the isolated perfused kidney is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the renal hemodynamic effects of calcium antagonists commend their use in the management of essential hypertension.

Acute Kidney Injury↗
PubMed1993

Diagnosing sphingolipidoses in murine and human embryos.

The aim of this study was to diagnose lipid storage diseases in embryos at the preimplantation stage. Two parallel approaches were employed. Firstly, activities of several sphingolipid hydrolases were determined in extracts of murine embryos and also human oocytes and polyspermic embryos. Sensitive fluorescent or fluorogenic procedures provided indications that Tay-Sachs, Gaucher and Krabbe diseases might be diagnosed in one human blastomere, while for Niemann-Pick disease two might be required. Secondly, pyrene lipids were administered into murine embryos and their fluorescence was quantified by computerized imaging microscopy. As a model of Gaucher disease, the fluorescent substrate pyrene glucosylceramide was administered into murine embryos in the presence or absence of an inhibitor of the enzyme beta-glucosidase. Because of decreased degradation of the substrate in enzyme-inhibited cells, the fluorescence per blastomere was considerably greater relative to those which received no inhibitor. The results indicated that lipid storage diseases might be diagnosed in single human blastomeres at the preimplantation stage, obviating the need for pre-natal diagnosis and abortion of affected foetuses.

Animals↗
PubMed1993

Protein kinase C and calcium channel activation as determinants of renal vasoconstriction by angiotensin II and endothelin.

The mechanisms mediating renal microvascular constriction induced by angiotensin II (Ang II) and endothelin (ET) have not been fully established. In the present study, we have determined the effects of isradipine, a dihydropyridine calcium antagonist, on Ang II- or ET-induced constriction of afferent arterioles (AAs) and efferent arterioles (EAs) using the isolated perfused hydronephrotic kidney. Ang II (0.3 nmol/L) and ET (0.3 nmol/L) constricted AAs by 36 +/- 2% and 29 +/- 3%, respectively. Isradipine reversed AA constriction induced by both peptides. However, Ang II-induced AA constriction was more sensitive to isradipine than ET-induced constriction (half-maximal inhibitory concentration [IC50], 1.2 +/- 0.2 nmol/L [n = 12] versus 170 +/- 65 nmol/L [n = 19]; P < .01). The sensitivity of Ang II-induced AA constriction to isradipine was identical to that of KCI-induced AA constriction (IC50, 4.2 +/- 0.9 nmol/L; n = 12). Pretreatment with staurosporine (50 nmol/L), a protein kinase C inhibitor, enhanced the sensitivity of ET-induced AA constriction to isradipine (4.3 +/- 1.7 nmol/L, n = 14), rendering it identical to that of KCl-induced AA constriction. Ang II and ET decreased EA diameter by 26 +/- 2% (n = 12) and 12 +/- 2% (n = 8), respectively. In contrast to AA constriction, EA constriction induced by both peptides was relatively refractory to isradipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1993

Characterization of the renal microvascular actions of a new dopaminergic (DA1) agonist, YM435.

The renal vasculature is known to possess receptors for dopamine. The effects of dopamine and its mimetics on renal hemodynamics, however, have not been fully determined. In the present study, we have characterized the actions of the dopaminergic (DA1) agonist, YM435, on renal microvascular constriction induced by two dissimilar peptide vasoconstrictors, angiotensin II (AII) and endothelin (ET), in the isolated perfused hydronephrotic rat kidney. AII (0.3 nM) constricted afferent (AA) and efferent arterioles (EA) by 30 +/- 2% and 28 +/- 4%, respectively. ET (0.3 nM) preferentially constricted AA (37 +/- 2%) more than EA (18 +/- 2%). The subsequent administration of YM435 reversed the constrictor effects of AII or ET on both AA and EA in a dose-dependent manner. Although YM435 reversed AA and EA vasoconstriction induced by each peptide, the half-maximal inhibitory concentration for YM435 of ET-induced constriction exceeded that of AII (P < .001). Our findings constitute the first demonstration that YM435 is a potent vasodilator in the setting of either AII- or ET-induced AA and EA constriction. These results indicate that DA1 agonists reverse renal microvascular constriction mediated by AII and/or ET, and suggest that both AA and EA constitute the renal microvascular sites of action for DA1 agonists.

Angiotensin II↗
PubMed1993

Atrial natriuretic factor and liver disease.

A working formulation for the role of ANF in the sodium retention of cirrhosis is summarized in Figure 4. Sodium retention is initiated early in cirrhosis, either as a result of hepatic venous outflow block or of primary vasodilation. The consequent intravascular volume expansion causes increases in ANF levels. At this stage of disease, the rise in ANF level is sufficient to counterbalance the antinatriuretic influences. However, this occurs at the expense of an expanded intravascular volume with the potential for overflow ascites. With progression of disease, disruption of intrasinusoidal Starling forces and loss of volume from the vascular compartment into the peritoneal compartment occur. This underfilling of the circulation may attenuate further increases in plasma ANF and promotes the activation of antinatriuretic factors. At this later stage of disease, elevated levels of ANF are insufficient to counterbalance antinatriuretic influences. Thus the role of ANF in cirrhosis is primarily beneficial in that it successfully attenuates the antinatriuretic forces in the compensated stage. Raised ANF levels have two potential deleterious effects. First, ANF may exacerbate arterial vasodilation, leading to further sodium retention. The primacy of vasodilatation has been proposed as an alternate formulation to the overflow and underfill hypotheses. Second, Epstein et al. found higher basal ANF levels in cirrhotic patients with edema than in those patients without edema. ANF is known to reduce plasma volume in anephric animals and to increase the ultrafiltration coefficients of isolated capillaries. Therefore it is conceivable that in the clinical setting in which antinatriuretic factors limit the renal responsiveness to ANF but in which ANF levels are elevated (i.e., cirrhosis, congestive heart failure, primary kidney disease), ANF itself may contribute to edema formation at the level of the peripheral microcirculation. In general, ANF likely has no primary role in the sodium retention in cirrhosis. In early compensated cirrhosis, ANF may maintain sodium homeostasis despite the presence of mild antinatriuretic factors. In late ascitic cirrhosis renal resistance to ANF develops, rendering it ineffective.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Voluntary exercise and experimental mammary cancer.

The results of these studies indicate that voluntary activity suppresses the development of chemically and virally induced primary mammary tumors in rats and mice fed high-fat diets. These diets were chosen to mimic the current U.S. fat consumption of approximately 40% of calories as fat. It remains to be seen if activity exerts a similar suppressive effect on animals fed their customary low-fat diet (10% calories as fat). In general, the activity profiles of the female Fischer F-344 and Sprague-Dawley rat and the C3H/o mu j mouse exhibited a similar pattern with an early peak followed by a gradual plateau over time. The effects of activity on body fat composition showed a trend toward a decreased percent of body fat when compared to sedentary animals but a statistically significant decrease was found only in the F-344 female rat. In the DMBA model, carcinogen dose did alter outcome parameters. For example, time to first tumor was extended under low- but not high-DMBA conditions, and, conversely, tumor multiplicity was significantly decreased in the high- but not low-DMBA group. In the NMU model, an inverse association was found between the amount of activity and tumor incidence. A similar association was not found with the DMBA model. The reason for this is uncertain, but further analysis in terms of other parameters such as total tumor number may shed more light on this discrepancy. The suppressive effect of activity on the MMTV-induced mouse mammary tumor is of particular interest since it raises the possibility that activity may exert effects on the process of provirus insertion, and/or oncogene activation--an area of great potential promise in cancer prevention. Activity appeared to enhance the volume and to a lesser degree the number of metastatic foci in the lungs of F-344 retired breeders under high-fat but not medium-fat conditions. In addition, the most active animals in the high-fat group exhibited the greatest volume of metastases. These results, together with those in the NMU model, point to the critical importance of the quantity of voluntary activity an animal engages in and its relation to both primary and secondary cancer prevention. They imply that beyond a certain point of either frequency or intensity, the beneficial effect of exercise may be nullified by competing deleterious effects. The metastases study has also brought to light the importance of dietary fat as a potential intervening variable.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Breast cancer diagnosis and prognosis in women following augmentation with silicone gel-filled prostheses.

62 healthy women were studied mammographically before and after augmentation mammoplasty. Postaugmentation mammograms were done using both the implant compression and implant displacement technique. The amount of visualisable tissue was measured in all films before and after augmentation. We concluded: State-of-the-art film-screen mammography is extremely difficult to obtain in most patients augmented with silicone-gel-filled prostheses. On average, there is a decrease in measurable visualised breast tissue after augmentation mammoplasty with silicone-gel-filled prostheses. The area of mammographically measurable tissue is no different whether smooth or textured implants are used. Textured implants are less likely to form an early capsular contracture and are therefore preferred. However, the cancer-causing potential of polyurethane in humans is currently unknown. Anterior breast tissue is generally seen better with displacement mammography; posterior breast tissue with compression mammography. Better films are generally obtained when the implant is in the subpectoral position rather than subglandular. The more severe the capsular contracture, the poorer the mammogram. In addition 42 previously augmented patients developed breast carcinomas an average of 8.4 years after augmentation with silicone-gel-filled implants; 95% had palpable lesions (only 60% of which could be seen on mammography), 90% had infiltrating carcinomas, 45% had metastases to axillary nodes, and 7 patients have recurred, 5 of whom have died. We concluded: Augmented women who develop breast cancer are similar, in terms of tumour size and nodal positivity, to non-augmented breast cancer patients who present with palpable masses. When compared with non-augmented women whose breast cancers are found with screening mammography, augmented patients with breast cancer present with a higher percentage of invasive lesions and involved axillary lymph nodes, resulting in a poorer prognosis. The 40% false negative rate for mammography in this series is unduly high and alarming. Augmentation mammoplasty with silicone-gel-filled implants should be discouraged in women with a high risk of developing breast cancer.

Adult↗