ristocetin and Acute-Disease

The Fab-fragment of 6B4, a murine monoclonal antibody targeting the human platelet glycoprotein (GP) Ibalpha and blocking the binding of von Willebrand factor (VWF), is a powerful antithrombotic. In baboons, this was without side effects such as bleeding or thrombocytopenia. Recently, we developed a fully recombinant and humanized version of 6B4-Fab-fragment, h6B4-Fab, which maintains its inhibitory capacities in vitro and ex vivo after injection in baboons. We here investigated the antithrombotic properties, the effect on bleeding time and blood loss and initial pharmacokinetics of h6B4-Fab in baboons. The antithrombotic effect of h6B4-Fab on acute platelet-mediated thrombosis was studied in baboons where thrombus formation is induced at an injured and stenosed site of the femoral artery, allowing for cyclic flow reductions (CFRs) which are measured on an extracorporeal femoral arteriovenous shunt. Injection of 0.5 mg/kg h6B4-Fab significantly reduced the CFRs by 80%, whereas two extra injections, resulting in cumulative doses of 1.5 and 2.5 mg/kg, completely inhibited the CFRs. Platelet receptor occupancy, plasma concentrations and effects ex vivo were consistent with what was previously observed. Finally, minimal effects on bleeding time and blood loss, no spontaneous bleeding and no thrombocytopenia were observed. We therefore conclude that h6B4-Fab maintains the antithrombotic capacities of the murine 6B4-Fab, without causing side effects and therefore can be used for further development.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Bleeding Time; Blood Platelets; Constriction, Pathologic; Disease Models, Animal; Femoral Artery; Hemorrhage; Humans; Immunoglobulin Fab Fragments; Mice; Papio; Platelet Adhesiveness; Platelet Count; Platelet Glycoprotein GPIb-IX Complex; Regional Blood Flow; Ristocetin; Stress, Mechanical; Thrombocytopenia; Thrombosis

We have designed a simple test for the early diagnosis and treatment monitoring of thrombotic thrombocytopenic purpura (TTP). We examined plasma from 24 TTP patients and normal plasma using a cone and plate(let) analyser (CPA). Test plasma was mixed with citrated normal whole blood (group O) and subjected to flow at a shear rate of 1800/s. Mixing normal plasma (12.5, 25, 50 or 75 microl) with heterologous normal whole blood (final volume of 200 microl) resulted in a decrease of surface coverage (SC, maximally by 63%) and, to a lesser extent, of average size (AS, maximally by 37%) due to dilution of the blood sample. In contrast, mixing the same quantities of acute TTP plasma with normal blood yielded an increase in both SC (up to 125%) and AS (up to 130%). Increased SC and/or AS were detected in all 15 patients in acute phase and in three out of 14 patients in remission. Following repeated plasmapheresis, the enhanced platelet deposition in five patients with acute TTP returned to almost normal patterns. Mixing plasma from patients with other thrombocytopenic conditions in this way resulted in a decrease in both SC and AS, and did not differ from control subjects. In conclusion, the CPA is a simple and specific laboratory test that can be used for the diagnosis and monitoring of plasma exchange therapy in TTP.

Topics: Acute Disease; Humans; Infant, Newborn; Plasmapheresis; Platelet Adhesiveness; Platelet Aggregation; Platelet Function Tests; Purpura, Thrombotic Thrombocytopenic; Recurrence; Ristocetin; Sensitivity and Specificity

Topics: Acute Disease; Administration, Oral; Agranulocytosis; Evaluation Studies as Topic; Humans; Infection Control; Kanamycin; Leukemia; Neutropenia; Nystatin; Patient Isolators; Polymyxins; Radiation Injuries; Ristocetin

Topics: Acute Disease; Blood Platelets; Factor VIII; Humans; Ristocetin

Elective-differentiating solid nutrient media for simultaneous isolation of Vibrioes, Salmonella and Shigella were developed. Antibiotics active against grampostive microflora and dry bile salts inhibiting the growth of Proteus were used as the inhibitors of the growth of the accompanying microflora. The medium was lincomycin and the bile salts may be prepared in a dry form.

Topics: Acute Disease; Bacteria; Bacteriological Techniques; Bile Acids and Salts; Culture Media; Dagestan; Escherichia coli; Feces; Gastrointestinal Diseases; Humans; Hydrogen-Ion Concentration; Intestines; Lincomycin; Methicillin; Ristocetin; Salmonella; Shigella boydii; Shigella flexneri; Shigella sonnei; Vibrio

Topics: Acute Disease; Adenosine Diphosphate; Blood Cell Count; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Cell Survival; Epinephrine; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Phospholipids; Platelet Adhesiveness; Remission, Spontaneous; Ristocetin; Thrombocytopenia

Topics: Acute Disease; Adolescent; Adult; Anti-Bacterial Agents; Bacteria; Chloramphenicol; Chlortetracycline; Depression, Chemical; Enterococcus faecalis; Erythromycin; Erythromycin Ethylsuccinate; Female; Furazolidone; Humans; Male; Middle Aged; Neomycin; Nitrofurantoin; Oleandomycin; Oxytetracycline; Penicillin G; Penicillin Resistance; Penicillins; Pneumonia; Polymyxins; Ristocetin; Staphylococcus; Streptococcus; Streptomycin; Tetracycline; Urine