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Biomedical subjects

R Rodvien

Publications and source records attributed to R Rodvien.

35 records · Page 2Linked to original sources

In vitro assessment of interaction of blood with model surfaces.

An in vitro system for the assessment of blood compatibility of artificial surfaces is described. Anticoagulated human whole blood was pumped through columns of beads and then analyzed for evidence of platelet retention and the release of platelet constitutents. Platelets were retained on the columns by adhesion to the beads and by aggregation. Experiments were conducted with PVAc, PC, PMA and PS beads to provide data on the reproducibility of the system and the effects of anticoagulants and RBC concentration on platelet adhesion and release. The system is versatile, inexpensive, reproducibile, and also suitable for studies of the effects of pharmacologic agents and other aspects of platelet-artificial surface interaction.

Anticoagulants

Impairment by heparin of primary haemostasis and platelet [14C]5-hydroxytryptamine release.

Heparin was administered to 34 normal subjects by intravenous injection (100 mu/kg) and the template bleeding time was significantly increased both 10 min and 120 min following injection. Before heparin the bleeding time was 5-3 +/- 1.0 min (mean +/- 1 SD); 10 min after injection it was 9.8 +/- 5.6 min (P less than 0.001); and 120 min after injection it was 7.2 +/- 3.9 min (P less than 0.001). Increases in the bleeding time were unrelated to changes in platelet count, and independent of heparin's effect on plasma coagulation. In blood drawn 10 min and 120 min following heparin injection, there was significantly less [14C]5-HT released from platelet-rich plasma (PRP) in response to collagen, 0.41 mM epinephrine and 8 micron ADP, although in vitro addition of heparin (0.1 mu/ml, 0.5 mu/ml and 2.5 mu/ml) to baseline PRP of three subjects did not depress [14C]5-HT release. Our experiments suggest that intravenous administration of a therapeutic dose of heparin can cause a significant reversible inpairment of platelet haemostatic properties, possibly by an indirect mechanism.

Adult

Colchicine toxicity: a multisystem disease.

A 23-year-old black man survived a life-threatening multisystem disturbance resulting from a large single dose of colchicine administered intraurethrally for condyloma acuminata. Gastroenteritis and probable pancreatitis rapidly evolved into severe respiratory failure, marked neuromuscular problems, alopecia, and complete bone marrow aplasia. Within two months he had completely recovered. This patient demonstrates that colchicine should be used with extreme caution, if at all, for the therapy of condyloma acuminata.

Adult

Effects of matrix contact during gel filtration of human platelets in plasma.

When gel filtration is used to transfer platelets from plasma into an established environment, alterations in platelet characteristics may result from the change in environment or from the effects of platelet contact with the gel matrix. To approach the problem of evaluating the relative contributions from these sources, a Sepharose 2B matrix was employed and platelets transferred from citrate anticoagulated PRP into autologous PPP to yield plasma-GFP. Platelet recoveries averaged 93%. PRP: plasma-GFP pairs were found to be indistinguishable with respect to: morphology; ADP, thrombin or collagen-induced aggregation response; uptake of 5-hydroxytryptamine (5-HT) or adenosine; and thrombin or collagen-induced release of accumulated 5-HT or adenosine. Pairs are distinguishable by prostaglandin E2 synthesis assayed immediately after filtration.

Adenosine

Cyclic AMP in human blood platelets: relation to platelet prostaglandin synthesis induced by centrifugation or surface contact.

Exposure of blood platelets to physical stimuli such as centrifugation, filtration through Sepharose gel, or stirring with particulate material leads to production of prostaglandins E2 and F2alpha and to a reduction in cAMP. These effects resemble those produced by ADP, epinephrine, collagen, and thrombin in association with the platelet release reaction but are less effectively inhibited by aspirin.

Adenosine Diphosphate

Role of platelets in hemostasis and thrombosis.

Platelets interact with the coagulation factors in a complex way to arrest bleeding or generate thrombi. Recently, the platelet's relationship to endothelial alteration and atheroma production has received renewed attention. At present, tests of platelet function better define "hypocoagulable" rather than "hypercoagulable" states.

Blood Coagulation

The effect of somatostatin on coagulation and platelet function in man.

Preliminary evidence has suggested that somatostatin might interfere with platelet function in the baboon. Because this agent is currently being administered experimentally to human beings, we studied its effect on coagulation and platelet function in man. In five subjects, a four-hour infusion of somatostatin (500 micrograms per hour) had no definite effect on platelet count, leukocyte count, hematocrit, platelet adhesiveness and aggregation, bleeding time, partial thromboplastin time, prothrombin time, and fibrinogen levels. A similar infusion for 18 hours in three subjects was likewise without effect. These studies indicate that somatostatin does not affect coagulation and platelet function in man and that its prolonged administration lacks ostensible toxicity.

Adenosine Diphosphate

Platelets, hemostasis, and thromboembolism during treatment of acute respiratory insufficiency with extracorporeal membrane oxygenation.

Twenty-eight patients were supported with long-term extracorporeal membrane oxygenation as a treatment for acute respiratory insufficiency. Clinical, laboratory, and autopsy data concerning platelets, hemostasis, and thromboembolic disease are presented for the periods during and after bypass. During bypass, a "foreign-surface coagulopathy" was encountered which consisted of abnormal bleeding plus frequent, generalized, small and large vessel thromboembolic events. The abnormal bleeding is attributed to heparin, thrombocytopenia, and a qualitative platelet defect. Possible causes of the thromboembolic events including disseminated intravascular coagulation are also discussed, and speculations are offered concerning clinical management and directions for future investigation.

Adolescent

The structure of spleen in experimentally induced iron deficiency anemia.

Splenic ultrastructure was studied in experimentally induced severe iron deficiency in rabbits. Fragmentation and phagocytosis of blood cells, particularly red cells and platelets, were observed in the red pulp. Mitochondrial changes similar to those previously described in other sideropenic tissues were noted in the lympholytes and reticular cells of both the red and white pulp. The most striking findings were the changes associated with the membranous structures and endoplasmic reticulum. These changes were similar to those characteristically associated with lipid peroxidation. Glutathione peroxidase was shown to be deficient in the red cells of these sideropenic animals. The morphologic changes observed may be explained on the basis of lipid peroxidation of membranes, and it is suggested that iron deficiency results in "deficiency" of enzymes normally responsible for the protection of tissues against peroxidation injury. Increased susceptibility to peroxides may lead to peroxidation injury of membranous structures and morphologic changes described herein.

Anemia, Hypochromic

Effect of hemin on the synthesis of hemoglobin and other proteins in mammalian cells.

The initiation of globin synthesis in intact reticulocytes and in reticulocyte lysates is maintained by the addition of hemin. The specificity of this effect has been studied to determine whether it is restricted to hemoglobin and erythroid cells. In intact reticulocytes, hemin (500 muM) enhances the synthesis of carbonic anhydrase as well as of hemoglobin. Similar enhancement of protein synthesis is observed on addition of hemin (500 muM) to intact Krebs II ascites tumor cells, in cell-free extracts of these cells, added hemin (50 muM) increases endogenous protein synthesis and the translation of exogenous rabbit globin messenger RNA. These results provide evidence that the effect of hemin is not restricted to globin, and they suggest that hemin may enhance protein synthesis in at least some nonerythroid cells.

Alanine