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Biomedical subjects

F H Epstein

Publications and source records attributed to F H Epstein.

At least 163 records · Page 9Linked to original sources
PubMed1984

Polyene toxicity in renal medulla: injury mediated by transport activity.

Polyene antibiotics such as amphotericin and nystatin increase membrane permeability and thus increase the amount of oxygen consumed in active electrolyte transport. In isolated perfused rat kidneys, the polyenes produced extensive injury to the medullary thick ascending limb, a segment of the nephron with limited oxygen supply. This damage was prevented if reabsorptive transport was inhibited by ouabain. Cell death under these circumstances thus appears to be mediated by increased oxygen demand for transport activity.

Amphotericin B↗
PubMed1984

Selective anoxic injury to thick ascending limb: an anginal syndrome of the renal medulla?

Cortico-medullary gradients of O2 availability within the renal parenchyma have been appreciated for some time, but not their pathophysiological significance. During isolated perfusion of the rat kidney with cell-free albumin-Ringer's medium, a specific anatomical lesion is consistently observed, confined to the medullary thick ascending limb of Henle's loop (mTAL), that progresses over 90 min from mitochondrial swelling to nuclear pyknosis and complete cellular disruption. The lesion is exaggerated by oxygen deprivation and ameliorated by increasing the oxygen content of the perfusion or by reducing the transport work of mTAL cells. Because of its anatomical location associated with a low O2 supply imposed by the medullary vascular system and its high rate of electrolyte transport, the mTAL appears to be exquisitely sensitive to O2 deprivation. The consequent anoxic lesion, resulting from an imbalance between O2 supply and demand, may have important implications for the understanding of ischemic renal injury.

Animals↗
PubMed1984

Transport activity modifies thick ascending limb damage in the isolated perfused kidney.

The thick ascending limb of Henle's loop ( TAL ) develops a specific and consistent structural lesion during perfusion of the isolated rat kidney that progresses from mitochondrial swelling at 15 min to complete cellular disruption at 90 min. Because it seemed possible that damage localized to this metabolically active portion of the nephron might be correlated with cellular transport, the histology of perfused kidneys was examined when transport activity in the TAL was varied. The fraction of TAL tubules showing severe damage (44 +/- 2% in kidneys perfused with glucose) was dramatically reduced by furosemide (7 +/- 2%; P less than 0.001). The lesion was eliminated by perfusion with ouabain or by preventing glomerular filtration. On the other hand, protection of TAL cells was not obtained with the proximal diuretic acetazolamide. These results suggest that the lesion of TAL cells that develops during perfusion of the isolated kidney is influenced by the work of cellular transport.

Acetazolamide↗
PubMed1984

Lessons from falling coronary heart disease mortality in the United States.

The marked decline in coronary heart disease mortality in the United States since the late 1960s is most likely due in large part to successful efforts at primary prevention, attributable in turn to improved eating habits, better control of blood pressure and a reduction in smoking. Another part of the decline can probably be explained by an improvement in prognosis. It remains to be established if there has been a reduction in morbidity as well as mortality. There are other countries which have experienced declines, though of a lesser degree, while several countries have recorded increases in coronary heart disease mortality. These downward and upward turns, in general, are likewise compatible with the theory that they are caused by corresponding favourable or unfavourable changes in life styles.

Adult↗
PubMed1984

Sensitivity of cAMP-stimulated salt secretion in shark rectal gland to "loop" diuretics.

The secretory response of isolated perfused shark rectal gland was characterized with respect to its inhibition by a chemically related series of 5-sulfamoylbenzoic acid derivatives and certain phenoxyacetic acid derivatives. Maximal fluid and salt secretion was elicited with dibutyryl adenosine 3',5'-cyclic monophosphate and theophylline. The potency series established for the 5-sulfamoylbenzoic acid compounds agreed well with the relative potencies previously established for these agents as inhibitors of Na+-K+-Cl- cotransport in the avian erythrocyte. The most potent compound tested (3-benzylamino-4-phenyl-5-sulfamoylbenzoic acid) had a 50% inhibitory concentration value of approximately 5 X 10(-7) M. This compound was approximately 10-fold more effective than bumetanide and 400-fold as inhibitory as furosemide in this system. Ethacrynic acid (EA; 10(-3) M) was a poor inhibitor of rectal gland secretion and was approximately equipotent with its saturated derivative, dihydro EA. In contrast, EA-L-cysteine was fully effective at 10(-4) M, although the EA-D-cysteine adduct was ineffective. These data also qualitatively agree with results obtained in the inhibition of avian erythrocyte Na+-K+-Cl- cotransport and suggest that the rectal gland possesses a serosally oriented "NaCl cotransport" system with pharmacological and perhaps physiological similarities to the Na+-K+-Cl-cotransporter found in erythrocyte and other cell membranes.

Animals↗
PubMed1984

Amino acids induce renal vasodilatation in isolated perfused kidney: coupling to oxidative metabolism.

Renal vasodilatation regularly accompanies protein feeding and amino acid infusions, but the mechanism is unknown. The effects of several different amino acids on renal hemodynamics were studied in the isolated rat kidney, perfused with glucose as the only other substrate. Addition of amino acids produced a dose-dependent, brisk, and sustained decrease in renal vascular resistance (by 5-35%) without change in glomerular filtration rate (GFR). The vasodilatation was associated with a parallel increase in O2 consumption (increases QO2). The effect was most marked with amino acids actively metabolized by the kidney, such as glutamine (at 2 mM), but was seen with most amino acids at 8 mM. The amino acid analogues alpha-aminobutyrate, taurine, and cycloleucine, cotransported with sodium but not metabolized, did not cause significant vasodilatation or increases QO2. Blocking active transport with ouabain blunted the amino acid-induced vasodilatation and increases QO2. Similar resistance to amino acids was produced by halting GFR with hyperoncotic medium. Restoration of GFR by increasing perfusion pressure in the presence of hyperoncotic medium reestablished amino acid-induced vasodilatation and increases QO2. Furosemide did not block the vasodilatory response. Inhibition of mitochondrial respiration by antimycin blocked both vasodilatation and increases QO2, but rotenone blockade could be bypassed by succinate or glutamine. Amino acids have a direct vasodilating action on isolated kidneys probably related to their role as metabolic substrates and linked to an increase in renal O2 consumption.

Amino Acids↗
PubMed1984

In vivo effect of volume expansion on rectal gland function. I. Humoral factors.

The spiny dogfish Squalus acanthias responds to volume expansion by increasing the rate of chloride secretion by its rectal gland. The response is elicited by intravascular infusion of either isotonic shark Ringer solution, a 1 M hypertonic sodium chloride solution, or an isotonic hyponatremic solution containing equal volumes of shark Ringer solution and 10% mannitol. The effect of volume expansion was evoked in explanted glands connected to a host fish only by the arterial supply, indicating that the response is mediated by a humoral factor. The explanted gland responded to theophylline (2.5 X 10(-3) M) and adenosine 3',5'-cyclic monophosphate (5 X 10(-4) M) by increasing the rate of secretion of chloride by an amount similar to that induced by volume expansion of the perfusing fish. Theophylline at concentrations (10(-6) to 5 X 10(-5) M) that are known to inhibit the effect of adenosine in isolated perfused glands failed to inhibit the effect of volume expansion on explanted glands. Somatostatin (4.5 X 10(-6) M), which inhibits the effect of vasoactive intestinal peptide (VIP) in the isolated perfused gland, completely prevented the secretory response to volume expansion in explanted glands. Volume expansion is a major stimulus for chloride secretion by the rectal gland. The effect is mediated by a humoral factor that appears to be VIP.

Animals↗
PubMed1984

In vivo effect of volume expansion on rectal gland function. II. Hemodynamic changes.

Intravascular volume expansion causes a 300% increase in the rate of fluid secretion from, and blood flow to, the in vivo rectal gland of the spiny dogfish Squalus acanthias. Similar increases are also observed in explanted rectal glands perfused through a catheter from the dorsal aorta of a volume-expanded dogfish. Stimulation of rectal gland secretion by volume expansion is not associated with a change in the ratio of chloride secreted to oxygen consumed by the rectal gland and the oxygen extraction ratio, suggesting that an increase in blood flow is necessary to support the increased rate of chloride secretion. Perfusion of the explanted gland with bumetanide (10(-4) M) completely inhibits the secretory response to volume expansion but does not prevent the increase in blood flow. Bumetanide also inhibits dibutyryl adenosine 3',5'-cyclic monophosphate- and theophylline-induced increases in chloride secretion but does not inhibit the hyperemic response. Somatostatin inhibits the secretory response of the explanted gland to volume expansion but does not prevent the increase in blood flow. Although an increase in blood flow is necessary to support the increased energy requirement of enhanced transport, the secretory response and the increase in blood flow appear to be independently regulated and mediated, at least in part, by humoral factors.

Animals↗
PubMed1984

Selective vulnerability of the medullary thick ascending limb to anoxia in the isolated perfused rat kidney.

A specific anatomical lesion sharply localized to the cells of the medullary thick ascending limbs (mTAL) and characterized by mitochondrial swelling progressing to nuclear pyknosis and cell death is elicited reproducibly in isolated rat kidneys perfused for 15 or 90 min with cell-free albumin-Ringer's medium gassed with 5% CO2, 95% O2 (O2 content, 1.5 vol/100 ml). The lesion, involving about half of mTALs, appears first in mTALs removed from vascular bundles and near the inner medulla, areas most likely to be anoxic. Hypoxic perfusion (O2 content 0.12 vol/100 ml) exaggerates the lesion, wiping out gradations of damage and extending it to all mTALs. O2-enriched perfusions using rat erythrocytes (O2 content 7.1 vol/100 ml) completely eliminates the lesion (unless gassed with carbon monoxide). Similarly, supplementation of the perfusion medium with a purified hemoglobin (O2 content 5.8 vol/100 ml) prevents mTAL injury. Perfusion with a fluorinated hydrocarbon blood substitute, Oxypherol (O2 content 4.3 vol/100 ml) also attenuates the lesion. These findings suggest that the mTAL is exquisitely susceptible to anoxic damage because of low O2 supply imposed by the medullary vascular system and the high rate of metabolism mandated by active reabsorption of sodium chloride. The vulnerability of the mTAL to anoxic injury could play a key role in the pathogenesis of ischemic renal injury.

Animals↗
PubMed1984

[Coronary heart diseases--epidemiology 1984].

Epidemiology is the basic science of preventive medicine, within the present context preventive cardiology. The thesis that premature coronary heart disease is preventable to a large extent is based on the concept of risk factors and the further thesis that there is a cause-and-effect relationship between these factors and the disease itself. The latter view has been more and more firmly supported during the past 30 years. Apart from the major risk factors serum lipids, blood pressure and smoking, a series of other factors play a role in the development and, particularly, the progression of coronary heart disease. The risk factors are determined to an appreciable degree by environmental influences and thus subject to change. The present state of knowledge with regard to living habits, including nutrition, in their effect on risk factors has been summarized, followed by a review of intervention studies which aim at documenting the effectiveness of preventive measures through changes in life style and by pharmaceutical means. The sum total of all scientific data; not only from epidemiological research but also clinical, experimental and pathological findings, lead to the conclusion that the application of preventive measures is indicated both for persons at high risk and the general population.

Blood Pressure↗
PubMed1984

Transport-dependent anoxic cell injury in the isolated perfused rat kidney.

The hypothesis that decrease in energy demand may prevent anoxic cell damage has been examined in the medullary thick ascending limb of isolated perfused rat kidneys exposed to oxygen deprivation. The effects of decreasing active reabsorptive transport in the medullary thick ascending limb were observed on the extensive damage regularly induced by hypoxic perfusion (gassed with no oxygen) or potassium cyanide. Anoxic injury was consistently attenuated or abolished if reabsorptive transport was decreased with ouabain or furosemide or by halting the glomerular filtration rate with the use of a hyperoncotic medium (nonfiltering kidney). Comparison of the injury generated by warm ischemia for identical time periods showed that complete ischemia does not reproduce the severe lesions seen during hypoxic perfusion. These results suggest that transport activity is a determining factor of anoxic cell death in the thick ascending limb of Henle's loop.

Animals↗
PubMed1984

How useful is a family history of hypertension as a predictor of future hypertension?

A hypothetical model for predicting hypertension is discussed. Assuming that being in the top quintiles of the blood pressure distribution at adolescence and/or having a family history of hypertension, the estimated risk for developing hypertension as an adult could be 37% in a population with a prevalence of hypertension on 20%. Using the blood pressure level in adolescence and/or positive family history of hypertension as a predictive "test", the sensitivity of this "test" is 65% and the specificity 73%.

Adolescent↗
PubMed1983

Survival after cardiopulmonary resuscitation in the hospital.

Little is known about prognostic factors that determine outcomes after in-hospital cardiopulmonary resuscitation. We studied prospectively 294 consecutive patients who were resuscitated in a university teaching hospital. Forty-one patients (14 per cent) were discharged from the hospital; three quarters of them were still alive six months later. A multivariate analysis revealed that pneumonia, hypotension, renal failure, cancer, and a homebound life style before hospitalization were significantly associated with in-hospital mortality (P less than 0.05). None of the 58 patients with pneumonia and none of the 179 in whom resuscitation took longer than 30 minutes survived to be discharged. On the other hand, fully 42 per cent of the patients who survived for 24 hours after resuscitation left the hospital. At the time of discharge from the hospital and again six months later, 93 per cent of the survivors were mentally intact. Although depression was generally present at the time of discharge, it tended to resolve subsequently. However, all patients reported some decrease in functional capacity, often attributed to fear. This persisted at six months after discharge. Age alone did not appear to influence the prognosis for survival after cardiopulmonary resuscitation or the adjustment to chronic illness after discharge from the hospital.

Adolescent↗
PubMed1983

Ouabain binding in rectal gland of Squalus acanthias.

In an attempt to examine the mechanisms of activation of (Na, K)-ATPase when epithelial transport is stimulated, the binding of ouabain to rectal gland tissue was measured before and after stimulation with dibutyryl cAMP and theophylline. Stimulation significantly altered the characteristics of ouabain binding to slices of Squalus acanthias rectal gland and to isolated rectal gland cells, accelerating the rate of binding and increasing the amount of ouabain bound at equilibrium when low concentrations of ouabain (10(-9) to 10(-7) M) were present in the medium. Scatchard plots of ouabain binding were nonlinear, suggesting at least two classes of binding sites, one of higher and one of lower affinity. Stimulation with cAMP and theophylline appeared to increase the affinity of the high-affinity site. Ouabain binding was increased by cAMP and theophylline even in the presence of furosemide (10(-4) M) or bumetanide (10(-5) M), and when Li+ was substituted for Na+, or NO3- for Cl- -maneuvers known to inhibit rectal gland secretion. The changes in ouabain binding induced by cAMP and theophylline do not appear, therefore, to be secondary to secretory activity but may reflect a change in the configuration, environment or location of existing enzyme so as to enhance its activity. Stimulation of ouabain binding cannot be demonstrated in whole homogenates of rectal gland, indicating that intact cells are necessary for the cyclic AMP-induced increase in ouabain binding to become manifest.

Animals↗
PubMed1983

[Results of recent intervention studies on prevention of heart disease and their significance for Switzerland].

Recently published intervention studies and their implications for Switzerland. Recently published results of large scale intervention studies (Multiple Risk Factor Intervention Trial, MRFIT, and European Intervention Study, World Health Organization European Collaborative Group) seem to question, according to some observers, the basis of population oriented cardiovascular prevention. As the National Research Program 1A "Prevention of Cardiovascular Disease in Switzerland" was based on the same assumptions regarding the relationship of risk factors and cardiovascular disease, the authors discussed the implication of the two studies for Switzerland. A detailed analysis of the European Intervention Study shows, that in spite of the overall non-significant mortality reduction of 8% there were important differences between participating countries, With significant differences in Belgium and Italy, both with innovative health education programs. MRFIT shows an important reduction of risk factors also in the control group, indicating a beneficial effect of "usual care" by practising physicians. Together with the recent recommendations of a WHO expert committee the authors conclude, that the two studies do not invalidate the principles of cardiovascular prevention.

Adult↗