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Biomedical subjects

M Halperin

Publications and source records attributed to M Halperin.

17 recordsLinked to original sources
PubMed1992

Chronic lactic acidosis in a patient with acquired immunodeficiency syndrome and mitochondrial myopathy: biochemical studies.

A 30-yr-old man with acquired immunodeficiency syndrome treated with zidovudine developed biopsy-proven mitochondrial myopathy. Chronic lactic acidosis (lactate, 10 +/- 1 mmol/L) persisted for more than 5 wk. Liver function tests were normal, but the concentration of lactose rose to 16.1 mmol/L when 500 mmol of ethanol was infused. The concentration of lactose rose by only 1.5 mmol/L with maximally tolerated exercise. If this mitochondrial lesion compromised flux through the electron transport system, increased turnover of ATP with exercise should have exacerbated the degree of lactic acidosis because of increased need to regenerate ATP via glycolysis. Two possible explanations will be discussed: first, there was both a rapid rate of production of lactic acid in affected muscles in conjunction and an equally rapid rate of removal by uninvolved organs. Second, there was a low net rate of production of lactic acid in involved muscles despite the exercise.

Acidosis, Lactic↗
PubMed1991

Moloney murine leukemia virus IN protein from disrupted virions binds and specifically cleaves its target sequence in vitro.

The integration of retroviral DNA plays an essential role in the viral life cycle. Previous studies of the Moloney murine leukemia virus (M-MuLV) have shown that viral integration is mediated by the integrase (IN) protein acting on the 13-bp inverted repeats that flank the linear viral DNA produced during reverse transcription. Prior studies have also shown that when the M-MuLV IN protein is produced in Escherichia coli it retains an ability to specifically associate with the viral inverted repeats (Krogstad and Champoux, 1990). In this study we present evidence that the IN protein present in detergent-disrupted virions is capable of specifically interacting with double-stranded oligonucleotides that correspond to the viral inverted repeats, and that this interaction may change after integration-related processing of the viral att sites. We further present evidence that, in vitro, detergent-disrupted virions are capable of specifically cleaving ds-IR oligonucleotides in an IN-dependent reaction that mimics the trimming step that precedes integration.

Animals↗
PubMed1991

Can oxygen consumption in blood in vitro be detected by a change in PCO2?

The PO2 measured in a sample of blood can be misleadingly low, owing to consumption of oxygen in vitro in patients with leukemia. The purpose of this study was to determine whether a rise in PCO2 in such blood could be a useful indication of consumption of oxygen in vitro. Because of the non-bocarbonate buffer capacity of blood and the carriage of CO2, mainly as bicarbonate, we reasoned that the rise in PCO2 would be too small to be helpful. Hence the quantitative relationship between the consumption of oxygen and the production of CO2 in blood was determined. Other reactions yielding CO2 (the titration of lactic acid) were monitored. Consumption of oxygen was stimulated in blood of normals in vitro by adding methylene blue (100 mumol/L); in addition, blood from four patients with leukemia was studied without additions. The rate of consumption of oxygen at 22 degrees C was linear over 60 min; the respiratory quotient was close to unity. The rise in PCO2 was small even when the fall in PO2 was 60 mmHg. We conclude that a rise in PCO2 is not a reliable way to diagnose consumption of oxygen in blood in vitro as patients may hyperventilate, making it very difficult to recognize a small rise in PCO2.

Adult↗
PubMed1990

Early methodological developments for clinical trials at the National Heart, Lung and Blood Institute.

The National Heart Institute, now known as the National Heart, Lung and Blood Institute (NHLBI), initiated its first multicentre randomized clinical trials of rheumatic fever and rheumatic heart disease in 1951. The modern era of multicentre trials began, however, when the Coronary Drug Project was initiated in the 1960s. This trial and subsequent NHLBI trials stimulated a wide variety of research on clinical trial methodology. This paper reviews early methodologic developments in four areas. First, an organizational structure for multicentre clinical trials was developed and codified in the 'Greenberg Report' in 1967. Second, design considerations related to patient risk, non-compliance, a lag in treatment effect, and changing risk were explored. The 'intention-to-treat' principle was implicit in these investigations. Thirdly, the concept of periodic review of accumulating data, recommended in the Greenberg report, stimulated research on methods for sequential analysis. Three statistical approaches were developed and investigation of their statistical properties continues today. These approaches are usually described as group sequential, stochastic curtailment, and Bayesian methods. Finally, comparison of treatments in longitudinal studies has been an increasing part of NHLBI research and methods have been developed for design and analysis of longitudinal studies.

Blood↗
PubMed1990

Enzyme-linked immunosorbent assay for distinguishing serological responses of lepromatous and tuberculoid leprosies to the 29/33-kilodalton doublet and 64-kilodalton antigens of Mycobacterium tuberculosis.

Immunoblot assays for the antibodies to Mycobacterium tuberculosis sonic extracts showed that all serum specimens of 40 lepromatous and of 28 tuberculoid leprosy patients reacted in a significant manner to 29/33-kilodalton (kDa) doublet and 64-kDa antigens, respectively. By using an enzyme-linked immunosorbent assay, we observed a significantly high immunoglobulin G antibody titer to the purified M. tuberculosis 29/33-kDa doublet and 64-kDa antigens in lepromatous and tuberculoid leprosy patients, respectively, as compared with normal subjects and tuberculosis patients. This enzyme-linked immunosorbent assay serology may be useful for distinguishing two polar types of leprosy and for diagnosing leprosy in general.

Antibodies, Bacterial↗
PubMed1989

Identification of mycobacterial antigens for "ELISA" serology in the diagnosis of leprosy and tuberculosis.

Using an immunoblotting assay (ImBA), several immuno-crossreactive antigenic components (ImCRAC-myc) have been identified in the whole sonicates of M. bovis-BCG, and M. tuberculosis (Mtb) and M. leprae (ML) whereby the sera of 100% lepromatous leprosy (L-Lep) reacted to 29/33 KD doublet and that of 100% tuberculoid leprosy (T-Lep) reacted to 64 KD bands. The antigens upon purification from Mtb Sonicates were used in a direct ELISA to measure antibody isotypes in the sera from L-Lep, T-Lep, healthy Lep. contacts (Lep. c), normal Dutch controls (N) and tuberculosis (TB) patients. A significantly high IgG titre to the doublet 29/33 KD and to 64 KD were observed among L-Lep and T-Lep patients respectively in comparison to sera from other groups of individuals. In certain cases of L-Lep patients, raised IgM titre to either or both to 29/33 KD doublet and 64 KD were also found. On the other hand, consistantly but significant high IgA-antibody titre to cell wall (CW), cytosol (cyt) and P90 fractions of Mtb distinguished clearly the TB patients from Lep groups, normals (NN) and Lep-c. It appeared that such antibody reactivity of TB sera might be directed to the groups of 58-60, 38-40, 18-20 and 14 KD antigens of mycobacteria e.g. Mtb. On the basis of the present observations we conclude that the measurement of class specific antibody response to the panel of these antigens could diagnose differentially between Lep, TB and NN/Lep-c among the population at large in an endemic area.

Antibodies, Bacterial↗
PubMed1989

Distribution-free confidence intervals for a parameter of Wilcoxon-Mann-Whitney type for ordered categories and progressive censoring.

Halperin, Gilbert, and Lachin (1987, Biometrics 43, 71-80) obtain confidence intervals for Pr(X less than Y) based on the two-sample Wilcoxon statistic for continuous data. Their approach is applied here to ordered categorical data and right-censored continuous data, using the generalization zeta = Pr(X less than Y) + 1/2Pr(X = Y) to account for ties. Deviations from nominal coverage probability for various sample sizes and values of zeta are obtained via simulation of either three or six ordered categories based on underlying Poisson or exponential distributions. The simulation results indicate that the proposed method performs quite well, and it is apparently superior to the approach of Hochberg (1981, Communications in Statistics--Theory and Methods A10, 1719-1732) for values of zeta far from 1/2.

Biometry↗
PubMed1978

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↗
PubMed1977

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↗