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Biomedical subjects

W R Bell

Publications and source records attributed to W R Bell.

At least 145 records · Page 8Linked to original sources

Typhoid fever. Studies of blood coagulation, bacteremia, and endotoxemia.

Patients with typhoid fever were studied to determine whether disseminated intravascular coagulation (DIC), circulating bacteria, and endotoxemia were responsible for the signs and symptoms of their illnesses. Coagulation tests in 28 patients detected thrombocytopenia in 17, hypofibrinogenemia in nine, and elevated titers of fibrinogen-related antigens in 20. Repeated testing during convalescence showed a return toward normal values. Intestinal bleeding, however, did not correlate with abnormalities of coagulation tests. Thus, DIC occurred commonly but appeared to be a subclinical event in these patients. In 25 patients with positive blood cultures for Salmonella typhi, quantitative cultures detected from less than 10 to 9 x 10(2) bacteria/ml. Limulus tests for endotoxin in plasma were negative in all 21 patients tested. These results indicated that the concentrations of circulating bacteria and endotoxin in typhoid fever are lower than in other Gram-negative bacterial infections and suggested that circulating bacteria and endotoxin do not play a major role in the pathogenesis of typhoid fever.

Antigens↗

Isolation and insolubilisation of human F VIII by affinity chromatography.

A simple procedure has been developed for the isolation of coagulation factor VIII (F VIII) from plasma in a form which induces a monospecific antibody in rabbits. Amino acid precipitation from plasma was followed by gel filtration on Sepharose 4B and further purification was achieved by affinity chromatography on heparin-Sepharose. The material so isolated was identified by immunoelectrophoresis and lacked coagulant activity. The antiserum produced in rabbits inhibited F VIII coagulant activity and von Willebrand factor activity as measured by ristocetin platelet agglutination. The isolated IgG fraction insolubilised with CNBr-Sepharose 4B retained the ability to complex with F VIII. This complex possessed F VIII coagulant activity which could be removed in 0.6 M NaCl and dissociated in 8 M urea.

Amino Acids↗

The effects of ancrod, the coagulating enzyme from the venom of Malayan pit viper (A. rhodostoma) on prothrombin and fibrinogen metabolism and fibrinopeptide A release in man.

The action of ancrod on fibrinogen and prothrombin metabolism was studied in six healthy individuals by the use of 131I-fibrinogen and 125I-prothrombin and by measurement of blood levels of fibrinopeptide A. Two untreated healthy controls were studied at the same time. Rapid defibrinogenation occurred during the initial 3 hr ancrod infusion, and fibrinogen levels were maintained near zero throughout the study. Large quantities of non-thrombin-clottable TCA-precipitable 131I material could be demonstrated in the circulation, reaching a maximum 3 to 6 hr after ancrod infusion and clearing with a half-life of 6 hr. Gel filtration of 6 hr plasmas demonstrated the presence of complexes larger than fibrinogen, as well as degradation products of fibrinogen-fibrin. Prothrombin concentration and metabolism were unchanged by ancrod treatment. Fibrinopeptide A levels in the ancrod group were greather than 4,000 ng/ml during the initial defibrinogenation, declined to greater than 80 ng/ml, and then increased to high levels after 3 days. These studies provide explanations of previous observations concerning the specificity of ancrod and demonstrate that rapid clotting of fibrinogen and dissolution of fibrin can occur in vivo without recruitment of the classic coagulation mechanism.

Adult↗

Autotransfusion of shed mediastinal blood after cardiac surgery: a prospective study.

In a randomized prospective study of patients having cardiac surgery, autologous blood collected from mediastinal tubes was autotransfused preferentially in 63 patients (ATS), whereas 51 patients received bank blood for transfusion (control). Comparison of the two groups showed no significant difference in regard to age, sex, operations performed, or total postoperative bleeding (ATS 813 +/- 121 ml. per square meter versus control 711 +/- 93 ml. per square meter; N.S.) Although mean postoperative blood replacement was similar in the two groups (ATS 4.3 +/- 0.6 units per patient versus control 4.8 +/- 0.6 units per patient), requirements for transfusion of stored bank blood were reduced by 50 percent in the ATS group (ATS 2.4 +/- 0.3 units per patient versus control 4.8 +/- 0.6 units per patient; p less than 0.005). Coagulation studies demonstrated that this blood was defibrinogenated; yet it contains significantly more platelets and clotting factors than does bank blood. In this study, autotransfusion of shed mediastinal blood was safe and simple. It significantly reduced bank blood requirements and resulted in substantial financial savings for the patients and the hospital.

Blood Cell Count↗

Microscopic method for assaying F cell production: illustrative changes during infancy and in aplastic anemia.

Fetal hemoglobin (HbF)-bearing reticulocytes (F reticulocytes) can be detected in peripheral blood by a modification of the microscopic single-cell radial immunodiffusion method. Thereby otherwise inappreciable changes in HbF production can readily be recognized. F reticulocyte frequencies are reporducibly measurable whenever the product of whole blood HbF-bearing red cell (F cell) frequency and reticulocyte frequency is approximately 5 X 10(-4) or greater. Serial analyses of F reticulocytes and nonreticulocyte F cells (F erythrocytes) illustrate that (1) levels of F reticulocytes and F erythrocytes are persistently similar in normal adults with more than 6% F cells and thus cell survival times of F and non-F cells must be essentially the same, (2) changing levels of F reticulocytes can be sensitive predictors of later changes in mature F cell frequencies during infancy and in adults recovering from aplastic anemia, and (3) alterations in F reticulocyte frequency and the amount of HbF per F reticulocyte are discordant in some settings but concordant in others.

Adult↗

Coagulopathy with midtrimester induced abortion: association with hyperosmolar urea administration.

Coagulation changes, usually subclinical, have been reported in association with the induction of midtrimester abortion by the administration of intra-amniotic hypertonic sodium chloride, hyperosmolar urea, hyperosmolar urea plus prostaglandin F2alpha, and hyperosmolar ura or hypertonic glucose plus prostaglandin E2. In addition, clinically significant coagulopathy has been described in association with the administration of hypertonic sodium chloride. This study details a three-year experience involving 3,034 cases of midtrimester elective abortion and describes six cases of coagulopathy in association with the administration of hypertonic sodium chloride and two cases in association with the administration of hyperosmolar urea. The significance of these findings and etiologic considerations are discussed.

Abortifacient Agents↗

The clinical features of submassive and massive pulmonary emboli.

Clinical findings in 167 patients with angiographically established pulmonary emboli were analyzed in detail. The clinical symptoms and physical findings in this group were compared with the findings in 160 patients (diagnosis established by angiography) from an earlier similar study. The observations from this, the largest known group of patients with documented pulmonary emboli that has been studied and reported on, revealed that many of the "classic signs and symptoms" occurred infrequently. Most patients in this study had prognostic value. The data from this study demonstrate that no clinical findings are specific for the diagnosis of pulmonary emboli, but the absence of isolated frequently occurring signs and symptoms should mitigate against the presence of pulmonary emboli.

Angiography↗

False-negative test for fibrinogen--fibrin degradation products.

The tanned red cell hemagglutination inhibition immunoassay has proved to be a sensitive test for the measurement of fibrinogen-fibrin degradation products (FDP-fdp). The case of a patient who initially had a negative test for FDP-fdp due to the presence of an anti-D antibody and the use of O-positive tanned erythrocytes in the hemagglutination inhibition immunoassay is presented. When a control consisting of buffer substituted for the anti-fibrinogen antiserum, tanned erythrocytes and patient's serum is used, the agglutination due to incompatibility will be recognized. The irregular antibody can then be removed by absorption, and the titer for FDP-fdp can be accurately measured.

Adult↗

Fibrinogen synthesis in rabbits: effects of altered levels of circulating fibrinogen.

The effects of altered fibrinogen concentrations on fibrinogen synthesis in rabbits were evaluated by determining the rate of appearance of [75Se]selenomethionine (75SeM) in circulating fibrinogen. Fibrinogen levels were maintained at twice normal by infusion of homologous fibrinogen for either 1 or 6 days before the intravenous injection of 20 micronCi of 75SeM, and the rate of appearance of labeled fibrinogen was measured during the subsequent 24 h. In both groups, synthesis was unchanged. Five hours after induction of partial defibrinogenation by the infusion of bovine thrombin, fibrinogen synthesis was increased threefold. Stimulation was not attributable to decreased fibrinogen concentrations; synthesis was increased equally when levels were maintained above normal by infusion of fibrinogen before administration of thrombin. Heat-inactivated thrombin and diisopropylfluorophosphate-inactivated thrombin did not stimulate fibrinogen synthesis. Thrombin produced elevated titers of fibrinogen-fibrin degradation products (FDP-fdp). However, fibrinogen synthesis was not increased in rabbits that had received FDP-fdp from thrombin-treated donors. These data suggest that neither the fibrinogen concentration nor FDP-fdp influenced fibrinogen synthesis.

Animals↗

Stimulation of fibrinogen synthesis by thrombin in rabbits with ancrod-induced afibrinogenemia.

The effect of intravenous infusions of thrombin on fibrinogen synthesis was evaluated in rabbits rendered afibrinogenemic by ancrod. Fibrinogen production and catabolism were measured simultaneously with 75Se-labeled selenomethionine (75SeM) and with 125I-labeled fibrinogen injected 5, 12, 18, or 26 h after ancrod. In normal rabbits the infusion of ancrod (2 U/kg body mass during 1 h) did not alter fibrinogen synthesis nor did it affect the rate of fibrinogen catabolism measured during a period of 5-120 h after ancrod administration. Normal rabbits that received purified bovine thrombin (100 U/kg body mass during 1 h) exhibited a twofold stimulation of fibrinogen synthesis as measured by the incorporation of 75SeM injected 5 h after thrombin. Rabbits made afibrinogenemic by infusion of ancrod 5 h before thrombin also showed a twofold increase in fibrinogen synthesis, as did animals that received ancrod immediately after thrombin. These experiments show that ancrod alone has no effect on fibrinogen production, and that thrombin stimulates fibrinogen synthesis in afibrinogenemic rabbits to the same extent as in controls.

Afibrinogenemia↗

Heparin-induced coagulopathy.

Intravenous heparin, at doses of 3.0 U./gm of body weight, produced an intravascular coagulopathy in rats which was manifested by intestinal tract hemorrhage, a reduction in plasma fibrinogen concentration, a rise in fibrinogen-fibrin degradation products, and the absence of a rise in platelet count noted in the control animals. This coagulopathy could not be produced by conventional anticoagulant doses of heparin or the injection of large doses of heparin in the presence of protamine sulfate. Specific studies excluded hypoxemia, metabolic acidosis, and endotoxemia as possible etiologic factors. The coagulation abnormalities observed in this study differ from those produced by injection of other polyanionic substances but their precise pathogenesis is still uncertain.

Animals↗