Biomedical subjects
Publications and source records attributed to K A Rickard.
The major problems currently facing haemophilia management in Australia relate to (1) a need for better co-ordination of our entire national effort for haemophilia therapy and (2) a need to improve the efficiency of our preparation of factor VII concentrates. If we could simply double or treble our factor VIII yields from the same volume of donor plasma many of our urgent treatment problems could be solved.
A drop counter-regulated fraction collector yields samples containing equal numbers of drops. Such fractions vary slightly in weight depending on experimental conditions such as surface tension. Provided that variables such as flow rate and eluate density remain constant, apparent surface tension may be estimated directly from the weights of eluate fractions obtained from gel filtration experiments. The detergents sodium cholate and sodium lauryl sulphate significantly decreased drop weights in this system. Following gel filtration on Sepharose 4B, sodium cholate eluted in the fractions containing low molecular weight material. It eluted in the same position when pre-mixed with human plasma. Normal plasma was found to contain two surface tension-reducing components with apparent molecular weights of 3-10(6) and 1-10(5). The apparent surface tension of whole human plasma was found to be time dependent and decreased as the flow rate was reduced.
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Fibrinolytic activity was determined from the rate of disappearance of turbidity in a suspension of heat-treated fibrin powder. Using this method for estimating residual fibrinolytic activity in mixtures of serum and plasmin, antiplasmin behaviors of specimens from patients with various clinical disorders were determined after long and short preincubation times. Slow-acting antiplasmins were found to be increased in a variety of conditions among these patients, while immediate acting antiplasmins were generally decreased, compared with those in specimens from a large pool of normal, healthy vounteers. Normal women taking oral contraceptives had consitently high levels of slow antiplasmins. Tests in vitro showed that the antifibrinolytic agents epsilon-aminocaproic acid, Trasylol and soybean trypsin inhibitor act only as fast antiplasmins.
Bone marrow samples from patients with megaloblastosis and iron deficiency have been assayed for their content of in vitro colony forming cells (CFC), and compared with a group of normal patients. The concentration of these cells was found to be significantly increased in the megaloblastic group, while their content in the iron deficient patients was slightly higher than the controls. An in vitro thymidine suicide procedures was utilised to assay the proportion of CFC in the S phase of the cycle. This was found to be increased in the megaloblastic group and only slightly increased in the iron deficient group. The findings in megaloblastosis seem to be consistent with the concept of impaired DNA synthesis. As the CFC monitors an early granulocytic progenitor these data suggest some impairment in DNA synthesis or an abnormal increase in amplification in this myeloid stem cell compartment. Such alterations in granulopoietic proliferation may contribute to the ineffective granulopoiesis of megaloblastosis and accordingly may be an important factor in the development of neutropenia sometimes associated with this condition. The slightly increased CFC concentration and altered cell cycle status found in iron deficiency suggest that iron is not a major requirement for granulopoiesis.
Plasma from a patient with early manifestations of disseminated lupus erythematosus, a prolonged partial thromboplastin time with kaolin, mildly prolonged prothrombin time, and a circulating inhibitor affecting the assay of several clotting factors was investigated. The most sensitive test for the inhibitor was found to be the Russell viper venom time without phospholipid. A decrease in phospholipid concentration as well as decreased sodium chloride levels both significantly enhanced the effect of the inhibitor in several coagulation tests. Of various phospholipid substitutes tested phosphatidyl ethanolamine was the most effective in partially correcting for the inhibitor. The inhibitor was not localized to the patient's platelets, which were also found to partially neutralize its effect. Since lupus erythematosus is sometimes accompanied by thrombocytopenia the coagulation disorder may be aggravated by such a deficiency of phospholipid. The inhibitor appears to act by preventing binding of phospholipid to the Xa/V/thromboplastin complex. It was characterized as a gamma globulin of mixed class.
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