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Biomedical subjects

G I Ingram

Publications and source records attributed to G I Ingram.

At least 37 records · Page 2Linked to original sources

Factor-VIII activity and antigen, platelet count and biochemical changes after adrenoceptor stimulation.

Adrenaline, isoprenaline and salbutamol were administered by intravenous infusion to human subjects. Isoprenaline was covered with practolol in an attempt to reduce the unpleasantness of the circulatory effects. Changes were recorded in pulse rate and blood pressure, and in blood levels of factors V, VIII, X, XI, and XII, platelet count, lactate, pyruvate, potassium and free fatty acids. Factor VIII was studied by clotting assays, by reactions with two rabbit antisera and two human antibodies, and by desulphated agarose chromatography. At the rate at which they were adiminstered, all three drugs increased the pulse rate by 20-40 beats/min. Factor VIII rose c. 2.5 X with adrenaline but only c. 1.5 X with isoprenaline and salbutamol; but other clotting factors did not alter. Chromatography provided no evidence of a change in the size of the molecule carrying factor-VIII clotting activity. The rate of clearance of the heightened plasma activity could not be shown to differ from that of "ordinary" factor VIII infused into haemophiliacs. The platelet count rose after adrenaline, fell after salbutamol and did not change significantly after isoprenaline. Among the biochemical responses, the only significant difference between the drugs was that lactate rose after adrenaline and salbutamol but did not change after isoprenaline. The rise in factor-VIII clotting activity after adrenaline is considered to represent a real increase in blood concentration, presumably by release of additional factor VIII from stores. The evidence suggests that this could be classified as a beta2 effect; and that the quantity which can be released is unrelated to the current plasma level. The rise in platelet count produced by adrenaline may be the resultant of an alpha-mediated rise due to contraction of the exchangeable splenic pool and a beta2-mediated fall, the alpha effect predominating.

Adult↗

The prothrombin time test: effect of varying citrate concentration.

Blood samples from 12 normal subjects and 46 patients on oral anticoagulants were divided so that each was anticoagulated with four concentrations of trisodium citrate solution in the range 0.09-0.15 M, 9 vol blood being added to 1 vol citrate solution in each case. Citrated blood haematocrit and plasma prothrombin time was measured on each subsample; 0.025 M CaCl2-solution was used for recalcification throughout. Three laboratories participated, each using a different prothrombin-time technique.

Anticoagulants↗

Four heparin preparations: anti-Xa potentiating effect of heparin after subcutaneous injection.

Four different heparin preparations--sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m.w. 9,000) and high molecular weight sodium heparin (mean m.w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i.u./ml) at 3-4 hours after the injection. With sodium heparin (m.w. 15,000) the highest values (0.135 i.u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0.072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 i. u./ml at 3-4 hours after injection). These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.

Calcium↗

Immunoradiometric assay of factor VIII related antigen, with observations in 32 patients with von Willebrand's disease.

A solid phase non-competitive immunoradiometric assay (IRMA) has been developed which allows measurement of factor VIII related antigen (VIIIR:AG) levels in normal plasma as low as 2.5 x 10(-4) U/ml. The assay is based on the extraction of VIIIR:AG from test plasma by means of polystrene tubes coated with a specific unlabelled anti-VIIIR:AG rabbit antiserum and subsequent labelling of the extracted antigen with 125I-labelled anti-VIIIR:AG rabbit IgG.

Antibody Specificity↗

Bleeding from self-administration of phenindione: a detailed case study.

A young woman presented with a 2 year history of a severe bleeding disorder and marked deficiencies in all four vitamin-K-dependent factors. Metabolic studies with tracer doses of tritium-labelled vitamin K1 suggested that the patient might be taking an oral anticoagulant; and subsequently her plasma was found to contain a substance identical to phenindione in its spectrophotometric and chromatographic properties. The half-disappearance times of factors II, IX, X were measured after the administration of a concentrate of these factors and were found to conform with published figures. The concentrate controlled the patient's excessive bruising and prolonged skin and gingival bleeding. It would therefore seem that factor VII may not be essential in reversal of the bleeding disorder induced by anticoagulant overdose.

Adult↗

Heterozygous and homozygous factor XI defect in consanguineous family.

A woman with symptoms of prolonged post-traumatic bleeding was found to have a severe defect of factor XI, and was thought to be homozygously affected. Both her parents, who were first cousins, and all her three children, though asymptomatic, showed a moderate defect and appeared to be heterozygous. Both her parents' factor XI levels were about twice those in her children, and this was thought to be an age effect.

Age Factors↗

A computer program for the analysis of parallel-line bioassays of clotting factors.

An interactive computer program for the analysis of clotting factor assays is described. The program provides potency estimates against a standard, and will compare the observed and expected responses of a treated patient. Tests for validity of curve fitting are provided, with a number of optional transforms. If asked, the program will provide the user with a list of valid commands at any given step, and will identify certain errors in input.

Blood Coagulation Factors↗