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Biomedical subjects

J R Oster

Publications and source records attributed to J R Oster.

At least 19 recordsLinked to original sources

Low anion gap resulting from unexplained exposure to bromide in a patient with renal amyloidosis.

A patient with nephrotic syndrome secondary to renal amyloidosis was consistently observed to have serum anion gap levels as low as -1 mEq/L and averaging approximately 2 mEq/L. Neither multiple myeloma nor extreme hypertriglyceridemia was present, and the patient's serum albumin concentrations were not low enough to depress the anion gap to this degree. An increased serum bromide level (below the range expected to produce clinical toxicity) was the apparent cause of the low anion gap. The patient's parents, who live in the same apartment, also manifested low anion gaps and inexplicably elevated serum bromide levels. Despite detailed investigation, no environmental or pharmacologic source of bromide was uncovered. Although the source of the bromide in the present instance remains elusive, this report illustrates the necessity to measure serum bromide when a low anion gap cannot be explained by other factors, even when there is no history to suggest bromide exposure.

Acid-Base Equilibrium

Severe cerebral edema in a patient with anasarca and hypernatremia.

We describe a woman whose fatal post-liver transplantation cerebral edema was unexpected and of unusual pathogenesis. Her severe cerebral edema is of considerable pathophysiologic interest: 1) it developed in the setting of marked anasarca and persistent hypernatremia, and 2) although hepatic function was poor, it was not considered sufficiently deranged to induce cerebral edema. Furthermore, there was no histologic evidence of hepatic rejection or antemortem hepatic necrosis. We postulate that an impairment of the blood brain barrier in association with a degree of hepatic dysfunction insufficient by itself to cause cerebral edema permitted the brain interstitial fluid volume to increase pari passu with ECF expansion. Cytotoxic cerebral edema and vascular engorgement may also have contributed to a life-threatening increase in intracranial pressure.

Adult

Renal and electrolyte complications of congestive heart failure and effects of therapy with angiotensin-converting enzyme inhibitors.

Blood pressure declines in virtually all patients with severe congestive heart failure given an angiotensin-converting enzyme (ACE) inhibitor, but hypotension is of concern only if symptomatic. Acute renal insufficiency induced by an ACE inhibitor is due to reduced renal perfusion pressure together with blockade of angiotensin II-induced constriction of the efferent arteriole. Risk factors (or markers) for renal failure include hyponatremia, hypotension, volume contraction. Hyponatremia is an index of increased hemodynamic impairment, marked activation of the renin-angiotensin-aldosterone axis, and poor prognosis. Preventive measures for both ACE inhibitor-associated hypotension and renal insufficiency include withholding diuretics for a few days, initiating therapy with very small doses of ACE inhibitors, and cautious dose titration. Therapy for both hypotension and renal insufficiency involves increasing dietary sodium intake and reducing the dosage of, or temporarily discontinuing, the diuretic. The ACE inhibitor may have to be given at reduced dosage or discontinued for a time. If discontinuation is deemed necessary, administration of these survival-prolonging medications should be reinitiated after a brief respite whenever possible.

Acute Kidney Injury

Effect of hyperkalemia on insulin secretion.

The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68 +/- 0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p less than 0.05). We concluded that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.

Animals

Effect of hypertonic versus isotonic sodium bicarbonate on plasma potassium concentration in patients with end-stage renal disease.

The purpose of the study was to evaluate the potassium-lowering effect of hypertonic versus isotonic sodium bicarbonate (NaHCO3) in patients with end-stage renal disease (ESRD) receiving chronic maintenance hemodialysis. Immediately prior to dialysis, we infused isotonic (1.4%, 150 mEq/l) NaHCO3 in H2O (1 mEq/kg body weight over 2 h) to 10 patients with ESRD. Blood was drawn in heparinized tubes, without the use of a tourniquet, from the angioaccess for Na, K, pH, PCO2, HCO3, and osmolality at baseline (x 3) and after 10, 20, 40, 60, 90, 120, and 180 min of infusion. All patients were acidotic (HCO3 13-21 mEq/l, pH 7.25-7.38) prior to the study. In these patients, plasma HCO3 increased by an average of 3 mEq/l, and plasma K decreased by 0.35 mEq/l at 180 min. Plasma osmolality did not change. In 8 patients, a bolus of hypertonic (8.4%, 1,000 mEq/l) NaHCO3 (1 mEq/kg body weight over 5 min) tended to cause a transient increase in plasma HCO3, an increase in plasma osmolality, and minor changes in the K levels (an initial small and transient albeit significant decrease, followed by a tendency to increase). Finally, plasma K tended to increase in patients receiving infusions of either isotonic (n = 6) or hypertonic (n = 6) sodium chloride. Our data do not support the efficacy of the common practice of administering NaHCO3 for the emergency treatment of hyperkalemia in patients with ESRD receiving maintenance dialysis.

Bicarbonates

Tetany induced on separate occasions by administration of potassium and magnesium in a patient with hungry-bone syndrome.

The case is described of a 68-year-old man whose therapy induced tetany during each of two consecutive hospital admissions. On each occasion the patient had marked hypocalcemia and hypomagnesemia, presumably as a result of the hungry-bone syndrome associated with diffuse prostatic osteoblastic metastases. During the February 1991 admission, marked hypokalemia was the principal initial concern. It seems likely that the tetany associated with the administration of KCl, without sufficient calcium, resulted from attenuation of the protection against hypocalcemia-enhanced neuromuscular excitability conferred by coexisting hypokalemia. The admission in March 1991 was prompted by the finding (without symptoms) of very low levels of both serum Mg and serum Ca. Tetany occurred during the infusion of MgSO4, without calcium. An acute decrement in plasma ionized Ca resulting from complexing of Ca with sulfate ions together with augmented urinary excretion of Ca were likely pathogenic factors.

Aged

Use of centrally acting sympatholytic agents in the management of hypertension.

Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction.

Aged

The effect of acute metabolic acidosis on plasma cortisol, renin activity and aldosterone.

The effect of metabolic acidosis on the renin-aldosterone system remains unclear. In the present study anesthetized mongrel dogs (n = 19) were infused at similar rates with 0.45% NaCl (controls), HCl or NH4Cl (2.5mEq/kg) for 1--3 h. The induced metabolic acidosis in the two experimental groups was not associated with increases in plasma renin activity. Plasma cortisol (as a marker for ACTH secretion) and serum potassium concentration increased in both HCl- and NH4Cl-treated animals. Plasma aldosterone increased after 30 min in the HCl group and 60 min in the NH4Cl group and did not change in controls. These findings demonstrate that metabolic acidosis induced by HCl or NH4Cl is associated with increased aldosterone production without concomitant changes in plasma renin activity.

Acidosis

Effect of hemodialysis on myocardial function as assessed by postural stress testing.

Myocardial performance, measured by systolic time intervals during passive postural stress, was evaluated in patients with end-stage renal disease before and after a single hemodialysis and compared with that of normal volunteers. Predialysis, the patients displayed a sluggish hemodynamic response to sudden postural changes. With tilting to 90 degrees, the patients' heart rate did not increase adequately and left ventricular ejection time (LVET) decreased only slightly in comparison to that of controls. Postdialysis, however, the response to sudden postural change in terms of increases in heart rate, decreases in LVET and decreases in calculated ejection fraction, were indistinguishable from those of control subjects. Since pre-ejection periods were not different from those of controls at any time during the test, we were unable to demonstrate a definite abnormality of myocaridal function before or after dialysis. The marked hemodynamic improvement in response to upright tilting, noted postdialysis, can be best attributed to a dialysis-related reduction in cardiac preload.

Adult

Dose response to chlorthalidone in patients with mild hypertension. Efficacy of a lower dose.

A multicenter study of chlorthalidone was performed to determine the relative antihypertensive efficacy and side effects of doses lower than those usually recommended for therapy. After a 4-wk placebo control period 100 patients with mild hypertension were randomly assigned doubleblind to 12.5-, 25-, 50-, or 75-mg regimens of chlorthalidone or to placebo for 12 wk. The groups of patients taking 25, 50, and 75 mg had declines in blood pressure which were not significantly different from each other. Serum potassium decreased in the 50- and 75-mg groups but not significantly in the 25-mg group. We conclude that chlorthalidone, 25 mg daily, was at least as effective for hypertension as 50 and 75 mg with less perturbation of potassium. Use of smaller initial diuretic doses may provide equal efficacy with fewer side effects for many patients.

Adult

Relationship between blood pH and potassium and phosphorus during acute metabolic acidosis.

Metabolic acidosis is known to be associated with increased blood potassium and phosphorus concentrations but the influence of mineral versus nonmineral acids on these variables remains undefined. Therefore, we infused anesthetized mongrel dogs with 0.45% saline (controls), the mineral acids HCl and NH4Cl, and the nonmineral acids lactic, beta-hydroxybutyric and methyl malonic for 1-3 h. Administration of both mineral acids was associated with significant increases in plasma potassium. In contrast, infusion of the three monmineral acids did not result in increases in plasma potassium; in fact, the levels decreased initially in the majority of the dogs. Phosphorus concentrations were increased by lactic and beta-hydroxybutric acids, were unchanged by NH4Cl and HCl, and were decreased by methyl malonic acid. Although the mechanisms responsible for these changes remain to be elucidated, the findings indicate that short-duration infusion of mineral and nonmineral acids has substantially different effects on plasma concentrations of these predominantly intracellular ions.

Acidosis

Renin-aldosterone responsiveness in uncomplicated juvenile-type diabetes mellitus.

The changes in plasma renin activity (PRA) and plasma aldosterone concentration (PA) in response to dietary sodium restriction and upright posture were evaluated in 7 patients with juvenile-type, insulin-dependent, uncomplicated diabetes mellitus and in 5 healthy volunteers. All patients had normal blood pressure, 24-hour urine protein excretion and endogenous creatinine clearance. Renal sodium conservation and concentrating ability were grossly normal and 5 patients so tested, had normal renal acidification. PRA and PA were normal in every subject suggesting that abnormalities of the renin-aldosterone axis are late complications of diabetes mellitus usually associated with hypertension and nephropathy or neuropathy.

Adult