A new "high purity" factor VIII concentrate for clinical use in haemophilia.
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Biomedical subjects
Publications and source records attributed to J Margolis.
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A simple microtechnique for carrying out partial thromboplastin time with kaolin tests with 2 microliter or less of test plasma is described. For single stage factor assays, less than 1 microliter of test solution may be used. Reagents and test plasma are loaded in sequence into a 10 microliter, long needle syringe and introduced into a micro test-tube immobilized in a water bath. The end-point is taken as a positive clearing of kaolin turbidity from the mixture while stirring. Correlation with normal techniques has been excellent.
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p-Aminobenzoic acid was fed to normal and alloxan-induced diabetic rats injected with [omega-14C]labeled and [2-14C]labeled fatty acids. The p-acetamidobenzoic acid that was excreted was hydrolyzed to yield acetate which was degraded. The distribution of 14C in the acetates formed when an [omega-14C]labeled fatty acid was injected was similar to that when a [2-14C]labeled fatty acid was injected. This contrasts with the finding that in acetates from 2-acetamido-4-phenylbutyric acid excreted when 2-amino-4-phenylbutyric acid was fed, there was a difference in the distributions of 14C, a difference attributable to omega-oxidation of the fatty acid. Acetylation of p-aminobenzoic acid is then concluded to occur in a different cellular environment than that of 2-amino-4-phenylbutyric acid, one in which omega-oxidation is not functional. When 2-amino-4-phenylbutyric acid was fed and [6-14C]palmitic acid injected, rather than [16-14C]palmitic acid, the distribution of 14C in acetate was the same as when [2-14C]palmitic acid was injected. This indicates that the dicarboxylic acid formed on omega-oxidation of palmitic acid does not undergo beta-oxidation to form succinyl-CoA. Thus, glucose is not formed via omega-oxidation of long-chain fatty acid.
Cryoprecipitate prepared by a rapid thawing technique was pooled in batches of 600--720 donor units and washed with ice-cold Tris-citrate-NaCl solution. After dissolving at 37 degrees C, it was adsorbed with Al(OH)3 and kaolin, and cleared by centrifugation. The supernatant, diluted with 5% dextrose was passed repeatedly through a bed of Celite, filtered through a 293 mm X 0.3 micrometer membrane disc and lyophilized. Typical composition was 15 U . ml-1 factor VII, and 40 mg . ml-1 protein with a yield of 300 U/l of starting plasma. The crude factor VIII concentrate was also a suitable material for preparation of high-purity factor VIII by controlled pore glass chromatography.
An improved one-stage method for accurate assays of factor VIII combines highly reproducible end points with elimination of temporal drift and of subjective factors involved in graphic analysis. Activated deficient plasma substrate (ADPS) is used as a single reagent for parallel tests. The assays can be performed manually or, with much greater precision, on an 8-channel coagulation meter of new design in which end points are recorded automatically and depend on an abrupt clearing of agitated cloudy suspensions. The coagulation time readings are reproducible to 0.5%. Factor VIII levels are read off a standard table or computed from a general equation which is readily programmable on a pocket calculator and is valid over a wide range of concentrations, including very low plasma levels.
Platelet function in vitro may be investigated in various ways. One of the accepted methods involves examination of platelet procoagulant release. Optimal conditions relating to maximal release have not been defined. Red cell stroma phospholipid can substitute for the platelet procoagulant in many in vitro tests (Quick et al., 1954, 1957; Margolis, 1961; Lovric & Margolis, 1964). Using a multiple channel coagulation meter, an assay system was developed for testing both red cell stroma and platelet procoagulants. Maximum procoagulant release was obtained by lysing in alkaline hypotonic solutions or by sonication. The system was tested in a one-stage kaolin-activated platelet-free plasma substrate, obtained from fresh pooled citrated plasma. With this method the amount of available procoagulant could be related to the numbers of red blood cells or platelets. The results indicated that one platelet provided procoagulant equivalent to that derived from 0.7 red cells. Procoagulant release was studied under various conditions and expressed in terms of stable (red cell) standard. Platelets subjected to hypotonic stress or factor 3 release (Hardisty test) were studied quantitatively. The addition of sulphinpyrazone (Anturan) had no observable effect on platelet release in this system.
Hypothermia is a grave prognostic finding in hepatic coma. Occasionally, it is found in patients whose conditions are stabilized clinically or are improving. When hypothermia occurs, the patients usually die within 24 to 48 hours. All of the patients described herein who eventually improved sufficiently to be discharged from the hospital achieved normal temperatures.
A case of palindromic rheumatism is presented in which the arthritic attacks usually were accompanied by an allergic vasculitis and dermatitis. Although this is not proof of the etiology, the constant association is suggestive of an allergic cause. A brief review of palindromic rheumatism in included.
An operational group is defined; how operational groups theory was applied at an ISSSTE clinic is described. It is underlined how operational groups promote change around the corerstone of a "task". The vicissitudes of an operational group with four psychiatrists who worked in community psychiatry at the ISSSTE, are described.
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