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Biomedical subjects

L Corash

Publications and source records attributed to L Corash.

At least 91 records · Page 5Linked to original sources
PubMed1982

Use of asplenic rabbits to demonstrate that platelet age and density are related.

An experimental model using asplenic rabbits injected with radioactive amino acids has been developed to examine the density distribution of newly released platelets. Platelets from asplenic rabbits had a larger mean volume and greater protein content than those from asplenic animals. Radiolabel, indicative of new platelets, is preferentially incorporated into the most dense platelets during the early postinjection period. Platelets of intermediate density also demonstrated augmented early label incorporation compared to the lightest cells, In contrast, during the late postinjection phase, there is preferential labeling of the least dense platelets. The specific radioactivity of heavy and light platelets rises to approximately equal levels, and falls abruptly, but the peak activities occur at distinctly separate times consistent with the concept of platelet density modification during platelet aging. Although platelet biologic properties are broadly distributed, these studies support the concept that on the average young platelets have an increased density and become less dense as they circulate.

Amino Acids↗
PubMed1981

Selective isolation of young erythrocytes for transfusion support of thalassemia major patients.

Transfusion-induced hemochromatosis remains a major therapeutic complication in the management of thalassemia major patients. Using available blood cell component separators, a system has been devised to selectively harvest young red cells from transfusion support of these subjects. Red cell units isolated by this method have an average estimated mean cell age of 30 days, compared to 60 days for unfractionated blood, and contain 80% of the hemoglobin content of standard red cell units. Radiochromium half-life for young cells measured in 7 asplenic thalassemia major patients averaged 47.4 days compared to 29.5 days for routine frozen red cells. The enhanced survival is not due to reticulocyte enrichment alone, but represents a true cohort of younger red cells. Although costly, this modality could theoretically halve the transfusion requirement in transfusion-dependent patients. When combined with modern iron chelator regimens, it may be possible to achieve consistently negative iron balance prior to the onset of hemochromatosis.

Cell Separation↗
PubMed1980

Blood lead concentrations in a remote Himalayan population.

The lead content in the air at the foothills of the Himalayas in Nepal was found to be negligible. The concentration of lead in the blood of 103 children and adults living in this region was found to average 3.4 micrograms per deciliter, a level substantially lower than that found in industrialized populations.

Adult↗
PubMed1980

Reduced chronic hemolysis during high-dose vitamin E administration in Mediterranean-type glucose-6-phosphate dehydrogenase deficiency.

The observation that high-dose oral vitamin E supplementation (800 IU per day) improved red-cell survival in two rare disorders associated with increased red-cell susceptibility to oxidative stress prompted a similar trial in 23 patients with Mediterranean glucose-6-phosphate dehydrogenase (G6PD) deficiency. Three months of vitamin E administration resulted in decreased chronic hemolysis as evidenced by improved red-cell life span (P less than 0.025), with an improvement in red-cell half-life from 22.9 +/- 0.7 days to 25.1 +/- 0.6 days (mean +/- S.E.M.), increased hemoglobin concentration (P less than 0.001), and decreased reticulocytosis (P less than 0.001) as compared with base-line values. Evaluation after one year of vitamin E administration demonstrated sustained improvement in all these indexes. Controlled clinical trials of vitamin E supplementation may be warranted to examine its efficacy in ameliorating acute hemolytic crises or in reducing morbidity from neonatal jaundice in this relatively common genetic disorder.

Administration, Oral↗
PubMed1980

Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome is an X-linked immunodeficiency disorder consisting of the triad of frequent infections, eczema, and profound thrombocytopenia. We evaluated the effects of splenectomy on hemostatic improvement and subsequent clinical course in 16 patients with the Wiskott-Aldrich syndrome. All 16 had an increase in platelet counts to at least 100,000 per cubic millimeter after splenectomy, with the mean increasing from 19,900 per cubic millimeter preoperatively to 262,700 per cubic millimeter after splenectomy. In addition, platelet size, which is characteristically small in this disease, also became normal. Survival after splenectomy correlated with the prophylactic use of antibiotics. Five of seven patients not taking prophylactic antibiotics died of sepis within 33 months of surgery. The mean survival of the nine patients maintained with prophylactic antibiotics, however, was at least 91.4 months, with six of these patients still alive an average of 11.0 years or more after splenectomy. Thus, splenectomy is a useful therapy for a major cause of morbidity and mortality in this complex syndrome.

Adolescent↗
PubMed1980

Intraoperative hemolysis. The initial manifestation of glucose-6-phosphate dehydrogenase deficiency.

Unexpected intraoperative hemolysis suggestive of a hemolytic transfusion reaction was the initial clinical manifestation of Mediterranean type glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in a 50-year-old Indian man. There was no evidence for immune mediated hemolysis since no unexpected RBC antibodies were found, and results of the direct antiglobulin test remained negative. Analysis of preoperative blood specimens demonstrated complete absence of G-6-PD activity. No etiologic agent clearly associated with G-6-PD hemolysis could be identified. Testing for G-6-PD deficiency should be considered when unexpected hemolysis occurs intraoperatively.

Glucosephosphate Dehydrogenase Deficiency↗
PubMed1980

Platelet heterogeneity: relevance to the use of platelets to study psychiatric disorders.

Laboratory workers in fields outside of hematology have shown increased interest in the platelet as an investigative model over the past decade. Simultaneously, primary knowledge about platelet biology has expanded rapidly. It is now clear that many of the platelet's specific properties may influence the collection and interpretation of platelet-related, experimental data. or example, platelet heterogeneity, with respect to physical and function character exerts a significant impact on platelet-related experiments. This report highlights some of the recent advances in the area, with specific emphasis on the area of platelet aging and its effect on the use of platelets as an investigative tool.

Blood Platelets↗
PubMed1980

Effect of magnesium deficiency on erythrocyte aging in rats.

Rats placed on a magnesium-deficient diet show decreased erythrocyte magnesium concentration, shortened erythrocyte survival, and erythrocyte membrane ultrastructure defects and become progressively anemic. Whether these pathologic processes are due to abnormal erythropoiesis or occur in the peripheral circulation is unknown. In the present study, magnesium and hemoglobin concentrations, reticulocyte count, erythrocyte pyrophosphatase, and pyruvate kinase activities were determined at weekly intervals for 6 weeks in whole blood and age-dependent erythrocyte fractions isolated from inbred Fisher rats fed a diet deficient in magnesium or the same diet with added magnesium. Freeze-fracture electron microscopic examinations were performed on age-dependent erythrocyte fractions to evaluate the membrane defect. The youngest red cells from magnesium-deficient rats were similar to those of control animals with respect to erythrocyte magnesium concentrations, pyrophosphatase activities, and membrane morphology. The older erythrocyte fractions from magnesium-deficient rats showed significant decreases in magnesium concentrations, pyrophosphatase activity, and the presence of membrane abnormalities. Thus, new erythrocytes produced in magnesium-deficient rats appear to be normal but rapidly develop biochemical and morphologic abnormalities with aging in a magnesium-deficient plasma environment.

Animals↗
PubMed1980

The molecular mechanism of the inherited phosphofructokinase deficiency associated with hemolysis and myopathy.

Normal human erythrocyte phosphofructokinase (ATP: D-fructose-6, P-1-phosphotransferase, EC 2.7.1.11; PFK) has recently been shown to consist of a heterogeneous mixture of five tetrameric isozymes: M4, M3L, M2L2, ML3, and L4 (M, muscle type; L, liver type). In the light of these findings, we have investigated the molecular basis of the inherited erythrocyte PFK deficiency associated with myopathy and hemolysis (Tarui disease). The propositus, a 31-yr-old male, suffered from muscle weakness and myoglobinuria on exertion. He showed mild erythrocytosis despite laboratory evidence of hemolysis. In his erythrocytes a metabolic crossover point was found at the level of PFK; 2,3-diphosphoglycerate (2,3-DPG) was also significantly reduced. The PFK from the patient's erythrocytes consisted exclusively of the L4 isozyme, and there was a complete absence of the other four. The leukocyte and platelet PFKs from the patient showed normal activities, chromatographic profiles, and precipitation with anti-M4 antibody. These studies provide direct evidence that in Tarui disease the M-type subunits are absent; but the liver- and platelet-type subunits of PFK are unaffected. The paradox of mild erythrocytosis despite hemolysis reflects the decreased production of 2,3-DPG.

Adult↗
PubMed1980

Disseminated intravascular coagulation: diagnostic and therapeutic considerations.

Disseminated intravascular coagulation, although an uncommon diagnosis on a general medical service, is one of the most common, acquired disorders of coagulation. With more aggressive therapy of critically ill patients it is also a diagnosis which is increasing in frequency. Recent advances in our understanding of the underlying causes for DIC and its pathophysiology have led to the establishment of diagnostic criteria and guidelines for the management of patients. Hemorrhage and thrombosis are the major criteria for initiation of therapy, and heparin is the most efficacious approach when correction of underlying causes is inadequate. Frequent monitoring of patients on heparin therapy can improve the benefit-to-risk ratio for this disorder.

Adult↗
PubMed1978

Monoamine oxidase activity in different density gradient fractions of human platelets.

Monoamine oxidase (MAO) activity measured in human platelets is reportedly altered by such drugs as epinephrine, lithium carbonate, and imipramine, and also reduced in a number of clinical disorders. To evaluate whether MAO activity might differ in platelet subpopulations, density gradient centrifugation with arabino-galactan was used to prepare four platelet fractions that differed in weight and volume. MAO activity in the lightest and smallest platelet subpopulation was approximately one-half that in the heaviest and largest subpopulation. Because platelet weight and size are thought to be related to platelet age, it is possible that some drug effects on platelet MAO activity might represent changes in platelet turnover. Factors other than platelet turnover rates may contribute to individual differences in platelet MAO activity, however, since one group of individuals with markedly reduced platelet MAO activity exhibited no shift in the proportion of lighter versus heavier platelets nor in the relative amount of MAO activity in each density gradient subfraction.

Blood Platelets↗
PubMed1978

Separation of younger red cells with improved survival in vivo: an approach to chronic transfusion therapy.

Transfusion of donor blood containing predominantly younger red cells with prolonged survival in vivo could significantly reduce the iron overload of patients requiring chronic transfusion. Age-dependent separation of red cells can be obtained by buoyant density centrifugation on isotonic solutions of arabino-galactane. By this technique, rabbit red cells were separated on a single layer of arabino-galactane and the appropriate fraction, after being labeled with (51)Cr, was reinfused into the donor. The survival in vivo was calculated by a mathematical model which corrects for both (51)Cr elution and random loss. There was a significant difference in survival in vivo between the light young red cells and the heavy old red cells. The potential survival in vivo of the 50% lightest red cells was 56 days, compared to 28 days for the heaviest red cells. Arabino-galactane appeared to be devoid of acute toxicity and of strong antigenicity and it did not appear to adhere to the red cell stroma. These data extrapolated to humans indicate that it may be feasible and advantageous to use red cells fractionated by this technique for transfusion. The 50% lightest human red cells can be expected to have a mean survival of 88 days, compared with 60 days for unfractionated blood. Transfusion of young red cells could significantly reduce the iron overload for patients requiring chronic transfusion, by avoiding infusion of the oldest red cells, which contribute equally to iron overload yet offer only transient survival in vivo.

Animals↗
PubMed1978

Demonstration of the outer surface of freeze-etched normal human platelets: correlation with buoyant density.

The external surface of the normal human platelet shows clusters of spherical particles in a reticular pattern with smooth and regular surface membrane in adjacent areas. Labelling with cationic ferritin demonstrates a diffuse distribution of ferritin particles which stop at the fracture face of the intramembranous surface. The intramembranous surface is not labelled. Previously discrepant observations on the plasma membrane surface are probably due to different techniques of platelet preparation for freeze-etch electron microscopy. Density-dependent platelet sub-populations do not differ with respect to the ultrastructural features of their external surface and intramembranous portions of the plasma membrane. Based upon the relationship between platelet density and age, it appears that the ultrastructure of the normal platelet plasma membrane does not change with in vivo ageing.

Blood Platelets↗