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Biomedical subjects

F R Rickles

Publications and source records attributed to F R Rickles.

108 records · Page 6Linked to original sources
PubMed1977

von Willebrand's disease and hemorrhagic telangiectasia: association of two complex disorders of hemostasis resulting in life-threatening hemorrhage.

The clinical and laboratory findings in a patient with uncontrolled gastrointestinal bleeding secondary to combined hemostatic defects (von Willebrand's disease and hemorrhagic telangiectasia) are described. Evidence for von Willebrand's disease was found in five family members, but no other affected relative was found to have hemorrhagic telangiectasia. Complete assestivity, factor VIII antigen and von Willebrand factor levels. The patient described also was evaluated for her response to transfusion utilizing these same measurements. Previous reports of the coexistence of hemostatic defects with hereditary hemorrhagic telangiectasia are reviewed. The importance of complete hemostatic evaluation of patients with mucocutaneous bleeding is stressed in light or current knowledge of the diagnostic specificity of available laboratory tests.

Blood Coagulation Tests↗
PubMed1977

Structural features of Salmonella typhimurium lipopolysaccharide required for activation of tissue factor in human mononuclear cells.

Activation of mononuclear cell tissue factor was examined utilizing lipopolysaccharides obtained from wild-type and both Rc and Re mutants of Salmonella typhimurium. Wild-type (smooth) lipopolysaccharide, galactose-deficient (Rc) lipopolysaccharide, heptose-deficient (Re) lipopolysaccharide, and lipid A preparations were all active in their ability to generate tissue factor activity in human mononuclear cells grown in tissue culture. Polymyxin B has been reported to prevent some of the lethal effects of endotoxin in vivo, and the drug reportedly binds to the 2-keto-3-deoxyoctulosonate-lipid A region of the lipopolysaccharide molecule. Polymyxin B was effective in inhibiting the tissue factor generating activity of wild-type lipopolysaccharide, Re lipopolysaccharide, and lipid A in a dose-dependent fashion. Treatment of lipid A preparations with mild alkali abolished the ability of these preparations to activate tissue factor in cells. Analogous to many of the other biologic properties of lipopolysaccharide, tissue factor activation in human mononuclear cells appears to depend upon the integrity of the lipid A portion of the molecule.

Cells, Cultured↗
PubMed1977

Tissue factor generation by human mononuclear cells: effects of endotoxin and dissociation of tissue factor generation from mitogenic response.

The effects of the presence of endotoxin in a mononuclear cell culture system have been assessed. Endotoxin was shown to be mitogenic for human peripheral blood lymphocytes and capable of stimulating the generation of tissue factor. Concentrations of endotoxin, found to contaminate many commercial mitogens and antigens, activated mononuclear cells in a time-dependent manner. Generation of tissue factor was detected in cultures harvested from 2 to 72 hours following stimulation with endotoxin. Dose-response curves relating concentrations of endotoxin to mononuclear cell stimulation were determined; as little as 0.001 microng/ml. of E. coli endotoxin was capable of stimulating the generation of tissue factor in the cell cultures. The mitogenic effect of endotoxin was modest, however, and appeared to be unrelated to the ability of endotoxin to active tissue factor. Inhibition of DNA synthesis in the cell cultures by cytosine arabinoside or nonlethal irradiation failed to impair the generation of tissue factor. Endotoxin contamination of various reagents used in cell culture was evaluated with the Limulus assay, which detected as little as 1 X 10(-4) microng/ml. of endotoxin. Endotoxin was detected in preparations of phytohemagglutinin, purified protein derivative of the tubercle bacillus, mumps vaccine, tetanus toxoid, concanavalin A, and pokeweed mitogen. Because of the broad implications of contamination by endotoxin of various reagents, we assessed the specificity of the Limulus assay for the detection of endotoxin in the lectin, concanavalin A, and determined that the reaction was specific for endotoxin. Contamination by endotoxin of mononuclear cell culture systems should be considered as a possible factor in the production of various biological effects attributed to some commonly used mitogens and antigens.

Cytarabine↗
PubMed1976

Thermal injury in von willebrand disease. Management of burn wound bleeding.

A 51-year-old woman sustained a 40% third-degree burn. After five grafting procedures that were unsuccessful due to uncontrolled bleeding, the diagnosis of von Willebrand disease was established. Skin grafting was subsequently accomplished without difficulty using cryoprecipitate as a source of antihemophilic factor (factor VIII). Serial clinical and laboratory investigations demonstrated that using the level of factor VIII procoagulant activity alone as an in vitro index of hemostasis was insufficient as a guide to the control of pathologic burn wound bleeding in this patient.

Blood Transfusion↗
PubMed1976

The effects of epinephrine infusion in patients with von Willebrand's disease.

Epinephrine infusion causes variable increases in the components of the Factor VIII (antihemophilic factor) complex in patients with von Willebrand's disease. The increase in antihemophilic factor procoagulant activity was greater than that of Factor VIII-related antigen and von Willebrand factor activity in two patients with von Willebrand's disease. Similar increases in the three individual factors were demonstrated in two other patients. A 4-10-fold increase in Factor VIII-related properties was identified in each of these individuals after infusion. One patient has been studied with very severe von Willebrand's disease; none of the Factor VIII-related properties increased despite two infusions of epinephrine. Bleeding times were normalized or remained normal in the two patients whose von Willebrand factor activity was greater than 25 U/100 ml. It remained prolonged in those three patients whose von Willebrand factor activity levels remained below that concentration. The increase in procoagulant activity was transient in all patients and t 1/2 values were estimated to be between 0.8 and 3.4 h.

Adult↗
PubMed1976

Procoagulant and platelet aggregating properties of antilymphocyte sera.

Ten anti-human lymphocyte sera in clinical use at six transplant centers and five anti-nonhuman lymphocyte sera were studied for their procoagulant and platelet-aggregating properties. This investigation was initiated following the observation of a clinical episode of renal artery thrombosis, associated with the use of one of the sera in a patient who had received a cadaveric renal transplant. The procoagulant from this serum shortened the clotting times of individual samples deficient, respectively, in factors XII, XI IX, X VIII, and VII. Esterolytic activity, demonstrated on the substrate benzoylarginine ethyl ester, was completely inhibited by phenylmethylsulfonyl fluoride, but coagulant activity was variably affected. The platelet-aggregating activity (PAA) has been identified as a complement-fixing gamma G antibody that was absorbed from the antilymphocyte serum (ALS) with human spleen lymphocytes. Five of the ten anti-human lymphocyte sera showed varying procoagulant activity (PCA), and six sera demonstrated PAA. Three sera contained both activities. The presence of both PCA and PAA in the same preparation may predispose patients to thrombotic events, particularly if administered intravenously. Sera should be screened for PCA and PAA prior to clinical use, and sera with these properties should be used with caution.

Animals↗
PubMed1973

Tissue factor activity in lymphocyte cultures from normal individuals and patients with hemophilia A.

The procoagulant material of lymphocytes has been characterized as tissue factor. Lymphocytes stimulated with phytohemagglutinin or the purified protein derivative of the tubercle bacillus developed procoagulant activity with incubation in tissue culture. While this material corrected the prolonged clotting time of factor VIII (AHF) deficient plasma, we have shown, utilizing a sensitive radioimmunoassay, that no AHF antigen was present in the cell cultures. Further, we have demonstrated this material to be tissue factor by coagulation techniques and immunological cross-reactivity. The published data regarding factor VIII synthesis is reviewed in light of these observations and comments are made regarding the role of the lymphocyte procoagulant.

Animals↗
PubMed1973

Quantitative assay of a plasma factor deficient in von Willebrand's disease that is necessary for platelet aggregation. Relationship to factor VIII procoagulant activity and antigen content.

In a previous paper, we showed that the abnormality of ristocetin-induced platelet aggregation in platelet-rich plasma in 10 patients with von Willebrand's disease could be corrected by a factor in normal plasma that was present in the same fractions as factor VIII procoagulant activity (antihemophilic factor, AHF, VIII(AHF)) when prepared by chromatography on Bio-Gel 5 M (Bio-Rad Laboratories, Richmond, Calif.). This observation suggests that patients with this disorder are deficient in a plasma factor, associated with the factor VIII molecule, that is necessary for normal platelet function. In the present paper, we describe, an assay for this factor, the von Willebrand factor (VIII(VWF)), based on the observation that a log-log relationship exists between the amount of ristocetin-induced aggregation of washed, normal platelets and the concentration of normal plasma present in the test system. We assayed the activity of VIII(VWF) as well as antihemophilic factor procoagulant activity (VIII(AHF)) and factor VIII antigen (VIII(AGN)) in 15 patients with von Willebrand's disease and 20 normal subjects. A highly significant correlation (r approximately 0.80) between VIII(VWF) and both VIII(AHF) was found in normal subjects and in patients with von Willebrand's disease. This finding, in addition to the observation that agarose gel chromatography fractions that have VIII(AHF) procoagulant activity also have VIII(VWF) activity, strongly suggests that the von Willebrand factor is associated with the factor VIII molecule. VIII(VWF) in normal plasma was not inhibited by human anti-VIII, and VIII(VWF) levels were normal in hemophilic plasma. Thus, the VIII(VWF) site on the factor VIII molecule appears to be different from that determining VIII(AHF). Finally, the activity of VIII(VWF) appeared to correlate better with the bleeding time than either VIII(AHF) or VIII(AGN). This suggests that VIII(VWF) assayed in this study may be the "anti-bleeding factor" that is deficient in von Willebrand's disease. These findings are consistent with a decreased synthesis of the factor VIII molecule in von Willebrand's disease and suggest the possibility of additional abnormalities of the site on the molecule that determines the activity of VIII(VWF).

Adult↗
PubMedDate not supplied

Production of modified crosslinked cell-free hemoglobin for human use: the role of quantitative determination of endotoxin contamination.

In vivo toxicity remains a major barrier to the successful use of cell-free hemoglobin (Hb) as an oxygen carrier in humans. Bacterial endotoxin (lipopolysaccharide, LPS) is known to contribute to the in vivo toxicity of Hb preparations, and the prevention of LPS contamination is a critical aspect of the effort to create an efficacious Hb blood substitute. Limulus amebocyte lysate assays for endotoxin were performed on multiple Hb samples from 26 independent production runs for the preparation of human crosslinked cell-free hemoglobin (alpha alpha Hb). High levels of LPS contamination (1- > 100 ng/mL) of alpha alpha Hb solutions were detected in multiple samples during many of the initial production runs. It was observed that LPS contamination of alpha alpha Hb solutions could occur at any step during the production sequence. Substantial enhancement by alpha alpha Hb of the biologic effects of LPS was demonstrated by two independent assays for endotoxin (the Limulus amebocyte lysate test and a mononuclear cell procoagulant assay), whereas LPS biologic activity was only slightly increased by human serum albumin and substantially diminished by IgG. These results suggest that the prevention of LPS-related toxicities in vivo may be more important to the clinical use of Hb solutions than to the use of other intravenous protein products. Therefore, it was encouraging to note that, with the careful monitoring for LPS in the production facility and in multiple samples during cell-free Hb production, sources of LPS contamination were recognized and the appropriate sites were made endotoxin-free.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗