The control of quality and price of medical care through provision of a preselected panel of private practitioners.
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Biomedical subjects
Publications and source records attributed to M Epstein.
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Calcium-channel blockers (CCBs) have been used for the treatment of hypertension for more than 20 years, and recent clinical trials support the efficacy and safety of long-acting dihydropyridine (DHP) CCBs for a wide spectrum of hypertensive patients, including diabetic hypertensive patients. DHP CCBs are effective agents overall and are particularly effective when used in combination with other agents. Lercanidipine is a novel DHP CCB effective for the treatment of mild-to-moderate hypertension. Compared with other DHP CCBs, lercanidipine has a molecular design that imparts greater solubility within the arterial cellular membrane bilayer, membrane-controlled kinetics, and a high cholesterol tolerance factor. These favorable membrane-controlled kinetics impart a gradual onset of vasodilation and a long duration of action. Further, the unique pharmacokinetic and pharmacodynamic properties of lercanidipine appear to contribute to its efficacy and favorable safety profile. In clinical trials in the treatment of mild-to-moderate hypertension, lercanidipine was administered at a starting dose of 10 mg once daily, and increased to 20 mg once daily for nonresponders. Studies have shown that lercanidipine has a 24-hour antihypertensive effect and causes no significant increase in heart rate. Lercanidipine has been shown to be effective in a wide range of hypertensive patients, including mild-to-moderate hypertension, severe hypertension, the elderly, and those with isolated systolic hypertension. It is associated with a low rate of adverse events. Because of its efficacy and favorable safety profile, lercanidipine has the potential to improve blood pressure control in a wide range of patients, including those who have not responded to, or who have been unable to tolerate, other antihypertensive agents.
The pivotal role of potassium (K+) in cardiovascular disease and the importance of preserving potassium balance have become clinical hot points, particularly as relates to new and emerging cardioprotective and renoprotective therapies that promote potassium retention. Although clinicians may be aware of the critical nature of this relationship, quite frequently there is some uncertainty as to the best way to monitor potassium levels in the face of a host of pathologic states and/or accompanying drug therapies that affect serum levels and/or total body potassium balance. Moreover, guidelines for monitoring of serum potassium levels are at best tentative and oftentimes are translated according to the level of concern of the respective physician. To address these uncertainties, an expert group was convened that included representatives from multiple disciplines. They attempted to reach consensus on the importance of K+ in hypertension, stroke, and arrhythmias as well as practical issues on maintaining K+ balance and avoiding K+ depletion. Because of the complexity of this topic, issues of hyperkalemia will be addressed in a forthcoming manuscript.
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In summary, it is apparent that renal sodium retention in patients with advanced liver disease constitutes a fascinating constellation with numerous and diverse causes and an elusive pathophysiology. The dissociation between hyperaldosteronism and the attendant changes in renal sodium handling and the demonstration of an impairment in natriuretic hormone release despite the absence of overt signs of sodium retention underscore the complete nature of the derangement. It is likely that the development of sodium retention necessitates the participation of several hormonal and/or neural effectors, acting in concert. Additional insight into this fascinating problem must await further biochemical characterization of some of the mediators and a delineation of their pathophysiological role.
Several epidemiological and animal model studies suggest that consumption of olive oil, which is rich in the monounsaturated fatty acid, oleic acid (OA, C18:, n-9) may reduce the risk of breast cancer. There are however, a wide variety of olive oils in the marketplace with levels of OA ranging from a low of 50% to a high of 80% OA. The purpose of this rodent model study was to determine whether the level of OA in olive oil is a key determinant of its protective effects. We compared the inhibitory effects among three different types of olive oil containing 54, 70 and 80% OA and 20, 15 and 5% linoleic acid (LA), respectively, corn oil and a store bought olive oil, using the NMU-induced rat mammary tumor model. While little difference was found in total mammary tumor yields, a differential effect was found in the histological type of tumors formed. Olive oil containing 80% OA and 5% LA exhibited the lowest level of adenocarcinomas and the highest level of the more benign adenocarcinoma arising from within a fibroadenoma. While the reasons for this effect remain to be clarified, these results suggest that future studies on the health benefits of olive oil should take into account the type as well as the amount of olive oil.
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It has been proposed that the functional adaptations of surviving nephrons in advancing chronic renal failure (CRF) are not random but characterized by an excretory response which varies inversely with the number of surviving nephrons ('magnification phenomenon'). Because validation of this hypothesis in man is incomplete, we undertook to characterize the excretory response to acute volume expansion in patients with CRF. In normals, water immersion to the neck (NI) results in a redistribution of blood volume with preferential central hypervolemia (CV) in the absence of plasma compositional change. NI was utilized, therefore, to assess the response to acute CV. 13 patients with CRF (GFR = 3-65 ml/min) were studied twice while ingesting a constant diet (60-150 mEq Na/day): during a seated control study (C) and during 4 h of NI. FENa was constant during C. In contrast, during NI, there was a prompt and marked increase in FENa which markedly exceeded that of 29 normal subjects undergoing an identical study. In the CRF group the extent of the augmentation of FENa during immersion varied inversely with GFR (r = -0.54; p less than 0.05). These results provide evidence that the 'magnification phenomenon' subtends renal sodium handling in patients with CRF.
The newly described endothelium-dependent vasoactive substances, nitric oxide and endothelins, have been the subject of intense investigative interest and have been demonstrated to promote a wide array of autocrine and paracrine functions. Recent data highlight their emerging role as potential important mediators of renal failure in general, thus suggesting that they might also contribute to renal dysfunction in the setting of advanced hepatic disease. Most but not all investigators, have demonstrated that circulating ET-1 levels are elevated in patients with advanced liver disease, and some reports have suggested that the magnitude of the elevation correlates with the degree of renal dysfunction. Concomitantly, several investigators have demonstrated NO overproduction as assessed by elevated levels of NO2- and NO3- in patients with advanced liver disease. It has been suggested that serum nitrite/nitrate levels are highest in patients with functional renal failure (i.e., HRS) and that these levels correlate with the magnitude of endotoxemia. Although large voids in our knowledge remain, the available evidence suggest that a reset balance between vasoconstrictor and vasodilatory stimuli may contribute to the renal hemodynamic abnormalities that characterize the renal functional abnormalities of liver disease.