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Biomedical subjects

M Epstein

Publications and source records attributed to M Epstein.

At least 109 records · Page 6Linked to original sources
PubMed1996

Monoclonal antibody-based methods for quantitation of hemoglobins: application to evaluating patients with sickle cell anemia treated with hydroxyurea.

High-titer monoclonal antibodies (mAb) were raised against chromatographically purified human hemoglobin (Hb) species. These mAb were specific for either Hb A, Hb F, Hb S or Hb C. Based on these antibodies, which were directly conjugated with either fluorochromes or an enzyme (horseradish peroxidase), we developed immunoassays for determining the Hb profile in the peripheral blood; an enzyme-linked immunosorbent assay (ELISA) for determining the absolute and relative quantities of various Hb species and one-step immunolabeling for fluorescence microscopic and flow cytometric analyses of the distribution of RBC with respect to their Hb types. We utilized these methods for monitoring the Hb F level and the percentage of Hb F-containing cells in patients with sickle cell anemia undergoing treatment with hydroxyurea.

Anemia, Sickle Cell↗
PubMed1996

Increased release of kaliuretic peptide during immersion-induced central hypervolemia in cirrhotic humans.

Kaliuretic peptide is a recently discovered potent stimulator of potassium and water excretion. Its role in modulating renal water handling in cirrhotic patients has not been defined. The responses of circulating kaliuretic peptide and atrial natriuretic factor in 8 cirrhotic subjects to water immersion were significantly greater (p < 0.05) than those of 7 healthy volunteers. With cessation of immersion, atrial natriuretic factor decreased within 30 min to preimmersion values, whereas kaliuretic peptide remained significantly elevated > 1 h, suggesting a slower clearance for kaliuretic peptide. The peak diuretic response to immersion corresponded in a temporal fashion to the peak circulating concentration of kaliuretic peptide, suggesting a possible physiological role of kaliuretic peptide in modulating volume homeostasis in cirrhotic humans.

Adult↗
PubMed1996

Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21-q32 and loss of the wild type allele in renal hamartomas.

Hereditary hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease (OMIM 145001) that has recently been mapped to chromosomal region 1q21-q32 (HRPT2). Here we report two families with HPT-JT syndrome in which adult renal hamartomas or cystic kidney disease were prominent associated features, possibly representing a new phenotypic variant of the HPT-JT syndrome. In the first family, renal lesions were present in five out of six affected individuals, whereas HPT and JT were seen in four and two cases, respectively. In the second family, JT was found in three of the five affected individuals and two affected members also exhibited polycystic kidney disease. The possibility of the latter cosegregating as a separate autosomal dominant gene can not be ruled out. A sex-dependent penetrance of primary HPT, resulting in predominantly male-affected cases was evident in the two families. Twenty microsatellite markers in the HRPT2 region were typed, in addition to markers in the multiple endocrine neoplasia (MEN) types 1 and 2 regions at 11q13 and 10q11. The disease in these two kindreds was linked to five markers in the 1q21-q32 region (logarithm-of-odds scores: 3.2-4.2), whereas linkage to the MEN1 and MEN2 regions was excluded. Meiotic recombinations detected in affected individuals placed the locus telomeric of D1S215, thus narrowing the HRPT2 region from > 60 to approximately 34 centimorgans. Loss of heterozygosity was studied in seven renal hamartomas from two affected individuals in the first family, as well as in a jaw tumor and a parathyroid tumor from the second family. All renal hamartomas showed loss of heterozygosity at the 1q21-q32 region. The losses invariably involved the wild type allele derived from the unaffected parent, suggesting the inactivation of a tumor suppressor gene in this region.

Adult↗
PubMed1996

Disparate effects of calcium antagonists on renal microcirculation.

Although calcium antagonists reduce systemic blood pressure, the effects of calcium antagonists on renal preglomerular and postglomerular microcirculation have been suggested to differ. In the present study we examined the vasodilator action of dihydropyridine-type calcium antagonists, including nifedipine, nicardipine, amlodipine, and efonidipine, on afferent and efferent arterioles during angiotensin II (A-II)- and norepinephrine (NE)-induced renal vasoconstriction. Isolated perfused hydronephrotic kidneys were used to directly visualize renal microcirculatory response to calcium antagonists. Both A-II and NE caused marked vasoconstriction of afferent (A-II, 27 +/- 2% decrement; NE, 28 +/- 2% decrement) and efferent arterioles (A-II, 25 +/- 4% decrement; NE, 22 +/- 2% decrement). The subsequent addition of nifedipine, nicardipine, and amlodipine reversed the afferent arteriolar vasoconstriction in a dose-dependent manner, and elicited complete vasodilation at 10(-6) M. In contrast, efferent arteriolar vasoconstriction was relatively refractory to the dilator action of these calcium antagonists; maximal dilation observed at 10(-6) M was 21 +/- 1% (A-II) and 22 +/- 3% (NE) for nifedipine, 25 +/- 3% (A-II) and 20 +/- 6% (NE) for nicardipine, and 39 +/- 6% (A-II) and 37 +/- 3% (NE) for amlodipine. In striking contrast, efonidipine dilated not only afferent arterioles, but also efferent arterioles in a dose-dependent manner. At 10(-6) M, efonidipine completely inhibited the afferent (A-II, 89 +/- 7% reversal; NE, 99 +/- 8% reversal) and efferent arteriolar vasoconstriction (A-II, 93 +/- 4% reversal; NE, 87 +/- 9% reversal). These findings clearly demonstrate that calcium antagonists dilate the afferent arteriole. Unlike the effects on the afferent arteriole, efferent arteriolar responsiveness to calcium antagonists differ, depending on the type of calcium antagonist. The efonidipine-induced efferent arteriolar vasodilation is probably not related to voltageoperated calcium channels, and may act, in concert with blood pressure lowering effect, to ameliorate glomerular capillary hypertension.

Angiotensin II↗
PubMed1996

Aging and the kidney.

A host of abnormalities of renal structure and function accompanies advancing age. An appreciation of methodologic considerations, including population selection, that might confound the assessment of the effects of aging on renal function has prompted a recent reappraisal. Earlier studies assessed the effects of aging by utilizing cross-sectional studies and institutionalized elderly subjects, with their attendant drawbacks. Recent longitudinal studies have utilized appropriate patient cohorts, selected for lock of renal disease, including potential kidney transplant donors. These studies indicate that the morphological and functional changes of aging tend to be less marked than previously thought. The common denominator of these functional changes is a diminution in renal reserve, along with constraints on the kidney's ability to respond appropriately to challenges of either excesses or deficits. Although these alterations are unlikely to be of major clinical consequence under everyday conditions, they attain clinical significance when residual renal function is challenged by the superimposition of an acute illness. Finally, it should be emphasized that elderly patients frequently suffer from comorbid conditions, such as hypertension and heart disease, that may be additive to the changes of aging, thereby amplifying these abnormalities.

Adolescent↗
PubMed1996

The benefits of ACE inhibitors and calcium antagonists in slowing progressive renal failure: focus on fixed-dose combination antihypertensive therapy.

During the past two decades, major investigative interest has been focused on the determinants of chronic renal disease and interventions to retard the inexorable progression to end-stage renal disease. Recent studies have provided a theoretic framework for anticipating that angiotensin-converting enzyme (ACE) inhibitors, and possibly calcium antagonists, may preferentially retard the progression of renal disease. Whereas the majority of available clinical trials have assessed the effects of ACE inhibitors in patients with insulin-dependent diabetes mellitus (IDDM), there are relatively few long-term studies that have evaluated the renal protective effects of ACE inhibitors and calcium antagonists in patients with nondiabetic renal disease. Although clinical trials have been initiated using both of these drug classes as monotherapy, theoretical considerations suggest that fixed-dose combinations of an ACE inhibitor and a calcium antagonist might be appealing as renal protective agents. Several lines of evidence suggest that the renal microcirculatory effects of coadministration of both agents should be complementary. Similarly, recent observations suggest that the two classes may act in a complementary manner to countervail pathogenetic mechanisms at the level of the mesangium. A recent study in type II diabetic patients demonstrated that combination therapy with an ACE inhibitor and a calcium antagonist induced the greatest reduction in proteinuria, and reduced the rate of decline in glomerular filtration rate (GFR) more than did either agent alone at the same level of blood pressure reduction. Based on such considerations, recent randomized prospective studies have been initiated to compare the renal protective effects of combination calcium antagonist-ACE inhibitor therapy versus monotherapy with agents of either of these two antihypertensive classes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Phase I trial of interleukin 2 in combination with the soluble tumor necrosis factor receptor p75 IgG chimera.

Our purpose was to determine the effective biological dose and/or maximum tolerated dose of recombinant human tumor necrosis factor receptor:IgG chimera (rhuTNFR:Fc; Immunex, Seattle, WA) in combination with interleukin 2 (IL-2) with regard to reduction in IL-2 toxicity and modulation of biological effects of high-dose IL-2 administration. Twenty-four patients with metastatic cancer were treated with escalating doses of rhuTNFR:Fc at 1, 1, 5, 10, and 20 mg/m2 i.v. on days 1 and 15 (dose levels 1-5) or 10, 20, and 30 mg/m2 days 1 and 15 plus 50% dose on days 3, 5, 17, and 19 (dose levels 6-8) prior to IL-2 at doses of 300,000 IU/kg (dose level 1) and 600,000 IU/kg (dose levels 2-8) i.v. every 8 h on days 1-5 and 15-19. The t1/2 of rhuTNFR in patients receiving IL-2 was 72 h. The median number of IL-2 doses was 24, and central nervous system, skin, and cardiac arrhythmias were the major dose-limiting toxicities. TNF bioactivity was inhibited, and the polymorphonuclear leukocyte chemotactic defect normally seen with IL-2 was not observed. Increases in C-reactive protein, IL-6, IL-8, and IL-1 receptor antagonist levels were partially suppressed relative to historical controls, whereas peripheral blood mononuclear cell phenotypes, urinary nitrate, endothelial adhesion molecule expression in skin biopsies, and cellular infiltrates in tumor biopsies were consistent with findings in patients treated with IL-2 alone. Four patients developed thyroid dysfunction. There were five responses: two complete responses (both melanoma) and three partial responses (response rate, 21%). rhuTNFR:Fc may modulate the toxicity and some of the biological effects of IL-2 while preserving antitumor activity. Dose level 6 (10 mg/m2 on days 1 and 15, and 5 mg/m2 on days 3, 5, 17, and 19) has been chosen for a randomized, double-blind, placebo-controlled trial of IL-2 with and without rhuTNFR:Fc.

Adult↗
PubMed1995

Renal sodium retention in liver disease.

In many patients with cirrhosis, salt retention eventually culminates in ascites and edema. The pathogenesis probably involves several hormonal and neural effectors acting in concert. When conservative therapy with diet and diuretics fails to mobilize fluid, options for more intensive treatment include large-volume paracentesis and the transjugular intrahepatic portosystemic shunt.

Diet, Sodium-Restricted↗
PubMed1995

Non-visualized left anterior descending artery revealed on selective conus artery catheterization.

Cardiac catheterization of a man with severe angina and anterior ischemia on exercise testing with perfusion imaging demonstrated normal anterior wall motion resting left ventriculography, but failed to visualize the left anterior descending (LAD) or conus artery on left and right coronary angiography. Selective contrast injection of a large conus artery originating from a separate ostium in the right aortic sinus demonstrated extensive collateral circulation to an LAD occluded at its origin from the left main coronary artery, thus providing essential information for subsequent patient management.

Aged↗
PubMed1995

Evolving concepts in the management of hypertension.

Currently, a plethora of antihypertensive medications exists. One concern about the long-term use of many of these agents is that adverse effects may offset their benefits. Despite the availability of many newer agents, blood pressure continues to be inadequately controlled in the majority of treated hypertensive patients, and many still remain at higher risk of premature death than the general population. More than 60% of treated hypertensive patients fail to attain blood pressures of < 140/90 mmHg. The major factors that permit a rational choice of medication include demographic considerations such as race and age, coexisting disease, safety, patient acceptance (quality of life), potential drug interactions, and additional salutary effects. The role of nondiuretic monotherapy is an integral component of this discussion. Preliminary data indicate that the use of calcium-channel blockers, converting-enzyme inhibitors, and AII-receptor antagonists constitutes excellent therapy in many patients. The effects of medication on the metabolic and lipid profiles are also considered.

Angiotensin II↗