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M Halperin

Publications and source records attributed to M Halperin.

At least 55 records · Page 3Linked to original sources

Early stopping in the two-sample problem for bounded random variables.

In a fixed sample size clinical trial, the question often asked is whether the final outcome has been determined before the data has been completely collected. A particular situation occurs when the intake of subjects is slow relative to the time required for the outcome variable to be realized. We assume that the range of values the outcome variable may take can be specified in advance. We also assume that simple randomization has been used and thus, under the null hypothesis, Student's t test is a good approximation to the exact test involving the permutational distribution. In order to determine with partial data whether the outcome of the final test of hypothesis is already certain, certain nonlinear extremal problems with constraints must be solved. Analytic solutions may be expressed in the form of noniterative algorithms. Simulation studies suggest an approximation to the analytic solution. The results also provide a basis for assessing at the end of the trial, whether missing values are of consequence in the test of significance. An application based on an actual clinical trial is presented.

Clinical Trials as Topic↗

Elevation of the blood lactate concentration by alkali therapy without requiring additional lactic acid accumulation: theoretical considerations.

A patient presented with lactic acidosis and severe acidemia; sodium bicarbonate was administered to titrate the very large hydrogen ion load. Coincident with this therapy, the blood lactate concentration rose from 21 to 27 mmole/L. In order to evaluate whether this rise in lactate could have occurred without requiring additional net lactic acid production, the effect of the hydrogen ion concentration on lactate distribution was evaluated. Data obtained from animal studies support the established hypothesis that lactate is distributed like other weak organic acids at steady-state; hence, alkalemia should favor a shift of lactate from the intracellular fluid (ICF) to the extracellular fluid (ECF). The authors calculated that the blood lactate concentration could rise by 50% without requiring net lactic acid accumulation when the severe acidemia was corrected by alkali therapy. Thus, an increase in lactate concentration of the magnitude observed during alkali therapy need not indicate a worsening of the metabolic picture in lactic acidosis.

Alkalies↗

Effect of potassium on distal nephron hydrogen ion secretion in the dog.

The purpose of these investigations was to determine whether potassium might influence the DNHS and, if so, to gain insight into the mechanisms involved. Since DNHS is decreased by ECF volume expansion, dogs were studied in both normovolemic and ECF volume-expanded states. DNHS was assessed in vivo by examining the U-B PCO2. In dogs with an expanded ECF volume, the U-B PCO2 at comparable urine bicarbonate concentrations was almost 50% lower than in the normovolemic dogs. Despite hyperkalemia and kaluresis, the U-B PCO2 was minimally affected by potassium infusion in the dogs with an expanded ECF volume. In contrast, in the normovolemic dogs, the U-B PCO2 was much higher before potassium administration and it decreased after potassium infusion to levels comparable to those observed in the dogs with ECF volume expansion. The U-B PCO2 in the normovolemic dogs was inversely related to the rate of potassium excretion when this rate was less than 150 muEq/min. Amiloride, an agent that decreases the electrical gradient favoring DNHS, caused only a small fall in the U-B PCO2 in potassium-loaded dogs with either a normal or an expanded ECF volume. Although other explanations are possible, we favor the hypothesis that the secretion of potassium into the distal nephron led to a reduced rate of hydrogen ion secretion provided that there was a significant avidity for sodium reabsorption.

Absorption↗

A micromethod to measure ammonia.

We have described a simple technique for the measurement of picomoles or nanomoles of ammonium. Samples can be easily processed on the day of an experiment. analysis of 14C-glutamate can be done at a later date by an accurate sensitive and reliable method. We can readily process 50 samples per day. The sensitivity can be increased by using smaller volumes of ammonia-free solutions, prereacting endogenous ammonia with nonradioactive 2-oxoglutarate, and increasing the specific activity of 2-oxoglutarate. The volumes must, however, be very low so as not to diminish the ammonium concentration and thereby limit glutamate formation.

Ammonia↗

Correlations of plasma high-density lipoprotein cholesterol levels with other plasma lipid and lipoprotein concentrations.

We investigated the association of plasma high-density lipoprotein (HDL) cholesterol levels with levels of cholesterol in other plasma lipoprotein fractions (low-density [LDL], very low density [VLDL] and their sum) and with total plasma cholesterol and triglyceride levels in 3493 males and 3318 females in the Lipid Research Clinics (LRC) Prevalence Study. Correlation coefficients were calculated for each stratum of age, sex and hormone use using a logarithmic transformation. The correlations of log HDL cholesterol with the other lipid and lipoprotein fractions generally depended strongly on age and sex but not on use of gonadal hormones. In the 20-70-year range, the age dependence of each correlation coefficient was well described by a linear regression model. The weakly positive association between HDL and total cholesterol levels in adults and the marked negative association of HDL cholesterol with triglyceride and VLDL cholesterol levels in almost all strata are in good general agreement with the results of earlier studies.

Adolescent↗

Hyperchloremic metabolic acidosis in diabetes mellitus: a case report and discussion of pathophysiologic mechanisms.

A 21-year old woman with poorly controlled diabetes mellitus was examined for persistent hyperchloremic metabolic acidosis. There was no evidence of ingestion of hydrochloric acid or its equivalent. Gastrointestinal loss of bicarbonate was absent. Proximal tubular bicarbonate reabsorption and distal nephron hydrogen-ion secretion were normal. Ammonia and net acid excretions were high, and thus there was no obvious cause for this acidosis. Further study revealed a very large loss of beta-hydroxybutyrate in the urine that closely approximated net acid excretion. This loss of potential bicarbonate was the principal cause for the hyperchloremic metabolic acidosis. Phosphate, urate, and beta-hydroxybutyrate fractional excretions were all abnormally high. Generalized aminoaciduria was also present, but the renal handling of glucose and bicarbonate was normal. With improved control of her diabetes, the generalized aminoaciduria disappeared, the urine beta-hydroxybutyrate loss ceased, the fractional excretions of phosphate and urate approached normal, and the acidosis was rapidly corrected.

Adult↗

Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.

Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis.

Acetazolamide↗