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Biomedical subjects

J Levin

Publications and source records attributed to J Levin.

At least 325 records · Page 18Linked to original sources

Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII.

The course and treatment of a life-threatening hemorrhagic episode in a patient with hemophilia A whose plasma contained a high concentration of an inhibitor of factor VIII activity is presented. The inhibitor of factor VIII was localized to the most anodal fractions of immunoglobulin G on electrophoresis, and was thus presumed to be an antibody directed against factor VIII. No therapeutic benefit occurred with infusions of massive amounts of fresh blood and factor VIII concentrates, or with a brief course of immunosuppressive therapy. Administration of standard and activated prothrombin complex concentrates resulted in reduction of the partial thromboplastin time to almost normal values and control of hemorrhage. Eight months later, another hemorrhagic episode occurred. Although a higher titer of inhibitor of factor VIII activity was still present in the patient's plasma, a beneficial therapeutic response was again achieved with standard prothrombin complex infusions.

Adult↗

Hemostasis.

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Arteries↗

Vascular disease.

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Amyloidosis↗

Thrombocytopenia.

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Alcoholism↗

Liver disease.

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Blood Coagulation↗

Relationships between thrombopoiesis and erythropoiesis: with studies of the effects of preparations of thrombopoietin and erythropoietin.

The effects of administration of partially purified human urinary erythropoietin and rabbit thrombopoietin, and of endogenously produced erythropoietin and thrombopoietin on both red cell and platelet production were examined in mice. Partially purified thrombopoietin was prepared from rabbit plasma by sequential fractionation with ammonium sulfate precipitation, and DEAE and Sephadex G-100 chromatography. Preparations of thrombopoietin and partially purified human urinary erythropoietin (NIH No. H-11-TaLSL) were administered subcutaneously to normal mice, and the rate of incorporation of selenomethionine-75 Se into platelets was measured as an index of thrombopoietic activity of the infused material. Erythropoietin and thrombopoietin were assayed for erythropoietic activity by measuring the rate of appearance of 59Fe in the red cells of posthypoxic polycythemic mice. Preparations containing thrombopoietin had barely measurable erythropoietic activity, and 7 units of partially purified erythropoietin had little thrombopoietic activity. When endogenous levels of erythropoietin were increased by hypoxia, platelet production was not enhanced. Similarly, increased levels of thrombopoietin, induced in response to thrombocytopenia produced by platelet antiserum, did not alter red cell production. These data suggest that physiologically increased levels of thrombopoietin do not stimulate erythropoiesis, and that physiologically increased levels of erythropoietn do not stimulate thrombopoiesis. However, currently available, partially purified preparations of erythropoietin and thrombopoietin may be capable of stimulating both platelet and red cell production if used in sufficient quantities.

Animals↗

The effects of hemorrhage, hypoxia, and a preparation of erythropoietin on thrombopoiesis.

The effects of hemorrhage, hypoxia, or a preparation of erythropoietin on platelet production were investigated by measuring incorporation of selenomethionine-75Se (75SeM) into the platelets of rabbits or mice. Rabbits that were bled daily for 5 days had a significant increase in the platelet count, 48 hours after cessation of hemmorrhage, that coincided with a threefold increase in isotope incorporation into platelets. Mice that were bled daily for 3 days also had significantly higher platelet counts and a 38 per cent increase in incorporation of isotope into platelets, 3 days after the last hemorrhage. Normal rabbits, injected with plasma from repeatedly bled, anemic, and moderately thrombocytopenic rabbits, had a 58 per cent greater maximum incorporation of 75SeM than did control animals. Mice exposed to hypoxia for 6 days had a mean platelet count 23 per cent lower than normal controls, but no change in incorporation of 75SeM into platelets. Plasma from hypoxic mice did not stimulate platelet production when injected into normal mice. A preparation of human urinary erythropoietin (15 to 30 U. per mouse or 30 to 120 U. per rabbit) significantly increased incorporation of isotope into the platelets of normal mice and rabbits. The results demonstrated that hemorrhage, but not hypoxia, is associated with increased thrombopoietic activity in plasma. However, large doses of preparations of human erythropoietin contained detectable thrombopoietic activity.

Animals↗

Effects of personal interactions and setting on subjective drug responses in small groups.

Subjective responses induced by secobarbital and meprobamate were evaluated in 4 X 4 controlled trials in small groups of healthy young adults over 4 months. Drug effects were mainly influenced by attitudes toward the project, personal interactions, and anticipations of the subjects. The effects of some of these factors were similar to, and at least as powerful as those which are usually considered characteristic of sedatives and stimulants. The same factors, however, did not apparently effect objective responses.

Analysis of Variance↗

Isolation and studies of the granules of the amebocytes of Limulus polyphemus, the horseshoe crab.

Granules were isolated from the cytoplasm of the amebocytes of Limulus polyphemus, the horseshoe crab, by disruption of cells obtained from blood which had been drawn into 2 mM propranolol. The granules subsequently were purified by centrifugation through a sucrose gradient that contained heparin. Extracts of the granules were prepared by freezing and thawing the granule preparations in distilled water. Transmission and scanning electron microscopy of the granules revealed round or ovoid particles. However, only one type of granule appeared to be present. The ultraviolet spectrum of the extract of amebocyte granules demonstrated a peak at 277 nm at pH 7.4, and a shift into two peaks of 281 nm and 290 nm at alkaline pH. Analytical ultracentrifugation revealed a pattern similar to that observed with lysates prepared from intact amebocytes. Polyacrylamide gel electrophoresis, in the presence of urea at pH 4.5, demonstrated patterns similar to those observed with amebocyte lysate. Extracts of the granules were gelled by bacterial endotoxin. The blood of the horseshoe crab contains only one type of cell, the amebocyte. Previous studies have shown that the blood coagulation mechanism of Limulus is contained entirely within amebocytes. The current studies suggest that the granules, which pack the cytoplasm of these cells, contain all of the factors required for the coagulation of blood, including the clottable protein. The intracellularly localized coagulation system is released from amebocytes when their granules rupture during cell aggregation.

Animals↗

Failure to demonstrate circulating endotoxin in malaria (38572).

The possibility that endotoxin or an endotoxin-like substance plays a role in malaria has been suggested by the clinical similarity between human malaria and the febrile reaction to endotoxins, as well as the occurrence of endotoxin tolerance in humans infected with malaria. However, endotoxin or endotoxin-like activity was not demonstrable, using the Limulus test, in the plasma of humans or monkeys infected with plasmodia. The data indicate that the febrile paroxysm of malarial infection is not associated with detectable levels of endotoxin in the blood.

Animals↗

Gallium-67-citrate scanning in primary cancer of the liver: diagnostic value in the presence of cirrhosis and relation to alpha-fetoprotein.

Gallium-67-citrate and 99mTc-sulfur colloid scans were performed in 38 South African blacks with primary hepatocellular cancer. Selective uptake of the radinuclide by the tumor occurred in 27 patients (70%). In 12 out of 18 patients with associated cirrhosis, 67Ga was concentrated in the defect or defects visible on the 99mTc-sulfur colloid scan, but in the remaining 6 cases (33%), the 2 scans were identical and the defects may have been attributed wrongly to cirrhosis. Alpha-fetoprotein (AFP) was detected by immunodiffusion in the serum of 26 patients. Twenty-one of these showed selective uptake of 67Ga by the tumor as compared with 6 out of 12 patients in whom this protein could not be detected. We were therefore unable to confirm a previous finding of a greater uptake of the of the radionuclide in AFP-negative primary liver cancer.

Fetal Proteins↗

Detection of endotoxemia with the Limulus test: preliminary studies in severely malnourished children.

Eighteen Peruvian children with protein-calorie malnutrition were studied to evaluate the usefulness of the limulus assay for endotoxin in detecting gram-negative sepsis. Nine of the children had at least one positive Limulus assay, and eight of this group had bacteriologic cultures indicative of gram-negative infection. Four of these nine children with positive Limulus assays died, whereas only one of the nine children with negative assays died. This preliminary study suggests the usefulness of the Limulus assay as an adjunct to bacteriologic cultures in the early detection of significant gram-negative infection in severely malnourished children.

Bacteria↗

The relationship of circulating endogenous endotoxin to hemorrhagic shock in the baboon.

Experiments were carried out to test the hypothesis that during hemorrhagic shock endotoxin enters the circulation from ischemic bowel by way of the portal venous system and is then associated with irreversibility of the hemorrhagic shock state. After placement of sampling catheters in the portal vein, right atrium, and aorta, 14 awake, restrained baboons were subjected to 1 hour of hemorrhagic shock at a mean arterial pressure (MAP) of 60 torr followed by a second hour at 40 torr MAP. Six animals were resuscitated with Ringers lactate and their shed blood; 8 were maintained hypotensive until death. Serial blood samples were analyzed for the presence of endotoxin. Endotoxemia was found infrequently, with no greater incidence (p > 0.6) in portal venous samples than in systemic blood, so these data were pooled for further analysis. Furthermore, endotoxemia was no more frequent (p > 0.6) late in shock than it was in early shock or during the baseline period. Autopsy showed no evidence of ischemic damage to the splanchnic viscera. It was concluded that spontaneous endogenous entotoxemia is not a common feature of hemorrhagic shock in baboons and is not related to the duration or degree of severity of hemorrhagic shock in this subhuman primate species.

Animals↗