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Biomedical subjects

C H Brown

Publications and source records attributed to C H Brown.

At least 127 records · Page 7Linked to original sources
PubMed1976

Defective platelet function following the administration of penicillin compounds.

Platelet function and blood coagulation were studied in five human volunteers receiving penicillin-G in incremental doses of 1.2--48 million U/day, in six volunteers receiving ampicillin in incremental doses of 60--300 mg/kg/day (4--20 g/day), and in six volunteers receiving methicillin in incremental doses of 60--300 mg/kg/day. Coagulation tests remained normal in all 17 volunteers. However, ADP-induced platelet aggregation became abnormal in every subject except one receiving ampicillin and one receiving methicillin. Defective aggregation occurred with predictability with the following doses: penicillin-G, 24 million U/day; ampicillin, 300 mg/kg/day; methicillin, 300 mg/kg/day. All volunteers given penicillin-G and all given ampicillin experienced dose-related prolongation of bleeding time which did not occur with methicillin. Striking prolongation of bleeding time occurred only with penicillin-G in doses of 48 million U/day. Other tests of platelet function including clot retraction, platelet factor 3 availability, and collagen-induced or epinephrine-induced aggregation remained normal during the administration of these drugs. Measurement of intracellular adenine nucleotides revealed that the ADP and ATP content of platelets was unaffected. It appears that at least one mechanism by which the penicillin compounds alter platelet behavior is by interfering with activation of these cells by ADP.

Adenosine Diphosphate↗
PubMed1976

Irradiation injury to the ureter and surgical tolerance. An experimental study.

An attempt was made to produce damage to the ureter of the dog with external irradiation in the high therapeutic ranges in the absence of surgery or cancer. No significant changes were apparent on excretory urography and only minimal changes were seen on histologic study. In another series of dogs, one ureter was reimplanted before the administration of maximal irradiation and the other ureter was reimplanted after the irradiation. The reimplanted ureter tolerated later irradiation very well. The postirradiated ureter tolerated similar surgery very poorly.

Animals↗
PubMed1975

Study of the effects of ticarcillin on blood coagulation and platelet function.

Ticarcillin is a new semisynthetic penicillin similar to carbenicillin. Since carbenicillin has been shown to inhibit platelet function to such an extent that bleeding may accompany its use, an investigation of the effects of ticarcillin on hemostasis was made. The drug was administered to 17 human volunteers for periods of 3 to 10 days in intravenous doses of 100, 200, or 300 mg/kg per day (7 to 21 g/day). Serial studies of blood coagulation and platelet function indicated that coagulation was unaffected by ticarcillin but that platelet function became defective in all subjects. Abnormal platelet function was evidenced by lengthening of bleeding time (17 of 17 volunteers), depressed adenosine diphosphate-induced platelet aggregation (17 of 17), defective collagen-induced aggregation (15 of 17), and abnormal epinephrine-induced aggregation (10 of 17). Prothrombin consumption, due to reduced platelet procoagulant activity, was significantly decreased with a dose of 300 mg/kg per day. Comparison of results from this study with those from an earlier carbenicillin study revealed that ticarcillin at 300 mg/kg per day produces the same defects in hemostasis as does carbenicillin at 300 mg/kg per day, but that lower doses (100 or 200 mg/kg per day) of ticarcillin result in only a mild defect in platelet function. If the effective dose of ticarcillin is proven to be lower than the doses of carbenicillin currently employed for treatment of certain gram-negative infections, bleeding should not be a frequent complication of ticarcillin administration, when the drug is given to patients with normal renal function.

Blood Coagulation↗
PubMed1975

Defective alpha-polymerization in the conversion of fibrinogen Baltimore to fibrin.

The subunit structure of fibrinogen Baltimore and fibrin formed from this inherited dysfibrinogenemia was analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The molecular weights of the alpha-, b- and gamma-chains of fibrinogen Baltimore were found to be identical to those of normal fibrinogen. Noncross-linked fibrin formed from both purified fibrinogen Baltimore as well as normal fibrinogen contained two alpha-monomers (alpha1 and alpha2). alpha2 was presumed to be alpha-monomer from which fibrinopeptide A had been released. The evolution of alpha2 during clotting of fibrinogen Baltimore was delayed and appeared to be quantitatively reduced when compared to normal. Crosslinked fibrin formed from fibrinogen Baltimore possessed an abnormal subunit structure. alpha-polymers were not generated in thrombin-induced, factor XIII-rich clots of fibrinogen Baltimore under conditions of pH and calcium concentration suitable for complete alpha-polymerization in normal fibrin. If clotting was carried out with calcium concentrations twice that required for normal clots or at pH 6.4, fibrin from fibrinogen Baltimore was completely cross-linked. These structural analyses of fibrin formed from fibrinogen Baltimore substantiate earlier findings that indicate a defect in the alpha-chain of this dysfibrinogenemia.

Blood Coagulation Disorders↗
PubMed1975

Inhibitory stimulus control following errorless discrimination learning.

Three generalization procedures were used to investigate inhibitory stimulus control following discrimination learning with few errors. Three groups of pigeons acquired a discrimination between a green stimulus (the positive stimulus) and a vertical or horizontal line (the negative stimulus) through differential autoshaping followed by multiple schedule presentation of the two stimuli with gradually increasing stimulus durations. Genereralization testing was along a line-tilt continuum. For one group, the test involved a resistance-to-reinforcement procedure in which responses to all line tilts were reinforced on a variable-interval schedule. For a second group, also tested with the resistance-to-reinforcement procedure, the lines were superimposed on the green field that formerly served as the positive stimulus. A third group was tested in extinction with the combined stimuli. Control groups had no discrimination training but responding to green was nondifferentially reinforced. The control subjects responded more to all line tilts during testing than did the comparable experimental subjects, indicating that the negative stimulus had become an inhibitory stimulus. Both resistance-to-reinforcement groups revealed inhibitory gradients around the negative stimulus, but the gradient for the extinction group was relatively flat. These data are consistent with others that modify Terrace's early conclusion concerning the failure of inhibition to develop during errorless training.

Journal Article↗
PubMed1975

Evaluation of a microcrystalline bovine collagen hemostatic agent in canine solid viscera injury using abdominal impedance plethysmography.

Bioelectric impedance as a sensitive noninvasive technique for detecting and monitoring changes in compartmental body fluid volume was used to compare the efficacy of two hemostatic agents in controlling postoperative abdominal bleeding following surgically induced solid viscera injury. Gelatin foam-oxidized cellulose sponge and bovine MCHH were both effective topical hemostatic agents. It appears that MCCH has certain advantages over conventional agents.

Abdominal Injuries↗
PubMed1975

Morphological, biochemical, and functional changes in human platelets subjected to shear stress.

Thromboembolic complications associated with cardiovascular prostheses are thought to result from activation of coagulation factors or platelets by surface contact and/or by certain physical forces generated at the interface between the foreign material and blood. Studies of the effects on human platelets of one of these physical forces, shear stress, were made. A rotational viscometer was used to apply graded levels of shear stress to platelet-rich plasma. Very low shear stress (50 dynes per square centimeter) resulted in the liberation of small amounts of ATP, ADP, and serotonin and subsequent platelet aggregation. Stresses of 100 dynes per square centimeter or more resulted in the appearance in plasma of nonstorage nucleotides, indicating cell lysis, and shear stresses of 250 dynes per square centimeter or more resulted in the fragmentation of platelets. Shear-induced platelet aggregation was partially reversible but only those samples subjected to low levels of shear stress recovered their ability to aggregate to the subsequent addition of ADP. These studies indicate that platelets are extremely sensitive to shear stress and raise the possibility that thrombus formation and/or accelerated platelet turnover in patients with rheumatic valvular disease or who possess artificial heart valves or other cardiac prosthetic devices could result from the effects of this physical force on circulating platelets.

Adenosine Diphosphate↗
PubMed1975

Rheological properties of fibrin clots. Effects of fibrinogen concentration, Factor XIII deficiency, and Factor XIII inhibition.

The effect of fibrinogen concentration, Factor XIII deficiency, and Factor XIII inhibition, utilizing hydroxylamine, on the formation of clot structure in vitro was studied in human platelet-free plasma systems. Rheological and biochemical techniques were employed to relate changes in clot elasticity and viscosity to clot structure formation following recalcification of citrate anticoagulated samples. Classical theories of linear viscoelasticity for swollen crosslinked materials were shown to give an excellent estimate of the number of covalent crosslinks per fibrin monomer, which is directly attainable from rheological data. SDS gel electrophoresis was utilized to show qualitatively that decreases in maximum clot elasticity, at constant fibrinogen concentration, are directly related to a decrease in Factor XIII-mediated intermolecular crosslinking. The use of the technique to investigate both kinetic and equilibrium crosslinking (or structure formation) abnormalities in plasma systems is discussed.

Blood Coagulation↗