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Biomedical subjects

S J Machin

Publications and source records attributed to S J Machin.

215 records · Page 12Linked to original sources
PubMed1981

The effect of clinical prostacyclin infusions in advanced arterial disease on platelet function and plasma 6-keto PGF1 alpha levels.

We have infused synthetic prostacyclin (PGI2) continuously for approximately 72 h at the maximum tolerated dose (ranging from 5 to 60 ng/kg/min) into nine patients with advanced arterial disease. Prior to the infusion seven out of nine patients had spontaneous platelet aggregation and five out of six patients tested had an abnormal circulating platelet aggregate ratio. During the infusion only one patient still had spontaneous aggregation and all the abnormal circulating platelet aggregate ratios returned to the normal range. However, none of the patients showed any suppression of ADP induced aggregation. The level of exogenous PGI2 required in vitro prior to the infusion to completely inhibit ADP induced aggregation was 5-10 ng/ml in three of the four patients tested. Ten healthy adults showed complete inhibition with 1 ng/ml of PGI2. It appears that the platelets of some patients with arterial disease are more resistant to the anti-aggregating properties of PGI2. Plasma 6-keto PGF1 alpha levels, measured by radioimmunoassay, were within the normal range (100-381 pg/ml) in all but one of the patients prior to the infusion. During the infusion plasma 6-keto PGF1 alpha levels rose proportionally to the infusion dose. After stopping the infusion 6-keto PGF1 alpha levels declined according to an exponential process with a half life of 18-29 min, prolonged to 47 min in one patient who was anuric. The linear increase in 6-keto PGF1 alpha levels suggests this as a useful indicator of increased circulating PGI2.

Adult↗
PubMed1981

Familial bleeding tendency with partial platelet thromboxane synthetase deficiency: reorientation of cyclic endoperoxide metabolism.

Three family members from three successive generations presented with a moderate bleeding tendency and a functional platelet defect. They had absent aggregation with arachidonic acid (0.6--3 microM), reversible aggregation with ADP (4 microgram) and cyclic endoperoxide analogues, single wave aggregation only with adrenaline (5.4 microgram) and a prolonged template bleeding time (> min). Malondialdehyde formation was reduced after N-ethylmaleimide stimulation (2--6 nmol/10(9) platelets; control values 8--12 nmol) and serum thromboxane B2 values were reduced (33--101 ng/ml; control values 200--700 ng/ml). When the platelets were incubated with [3H]arachidonic acid the final metabolite of the lipoxygenase pathway (HETE) was produced in normal amounts but the production of thromboxane B2 and HHT was decreased whereas prostaglandin F2a, and E2 and probably D2 were increased. Evidence for enhanced production of prostaglandin D2 was also provided by the rise in the patient's platelet cyclic AMP levels following stimulation with arachidonic acid. The patient's washed platelets stimulated the production of 6-keto PGF 1a by aspirin-pretreated cultured bovine endothelial cells. The plasma levels of 6-keto PGF1a (439--703 pg/ml; normal 181 +/- 46 pg/ml) were raised. The decreased production of thromboxane B2, HHT and malondialdehyde and increased formation of prostaglandin F2a, E2, D2 and of 6-keto PGF1a are compatible with a partial platelet thromboxane synthetase deficiency and reorientation of cyclic endoperoxide metabolism. The markedly prolonged bleeding time would result not only from reduced formation of thromboxane A2 but also from increased production of the aggregation inhibiting prostaglandins PGI2 and PGD2.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1980

Factor X deficiency in the neonatal period.

An infant with a severe deficiency of factor X presened in the neonatal period with uncontrollable bleeding from heel prick sites, spontaneous bruising, and haematoma. The deficiency was controlled by infusions of dried human factors II, IX, and X concentrate; the half-life of the infused factor X material is only 18 hours. Despite prophylactic weekly infusions of factor X concentrate, the child developed a fatal intracerebral haemorrhage when only 4 months old. Coagulation studies on both parents and the elder sister showed no obvious coagulation abnormality.

Factor X Deficiency↗
PubMed1980

Reduced prostacyclin activity in systemic lupus erythematosus.

When fresh rabbit aorta is incubated with plasma, prostacyclin, a potent inhibitor of platelet aggregation, is normally released. Plasma obtained from 2 patients with systemic lupus erythematosus (SLE) inhibited prostacyclin activity, while plasma from 22 other patients with SLE and 40 normal control subjects showed normal activity. Absence of prostacyclin activity did not appear to correlate with the clinical severity of the underlying disease. The possible association of this finding and the presence of thrombotic lesions in both patients is discussed.

Adult↗
PubMed1980

Congenital combined factor VII and factor VIII deficiency.

This paper describes two family members who have a combined hereditary deficiency of factors VII and VIII. The propositus, a 16-year-old male, presented with recurrent gastrointestinal bleeding. He and his mother had moderate defects of factors VII and VIII. The propositus received factor VIII cover, during and after a laparatomy. The possible hereditary transmission pattern of the combined defect is discussed.

Adolescent↗
PubMed1980

The bleeding patient.

The author has commented on the more frequently encountered acquired haemostatic defects and briefly outlined the relevant routine laboratory investigations that should be performed and their clinical significance. It is important that any replacement therapy with plasma, coagulation factor preparations and concentrates, and platelet infusions should be given promptly and their effectiveness assessed at regular intervals (Urbaniak and Cash, 1977). One's approach to the bleeding patient should be a combination of clinical assessment and interpretation of laboratory data, thus allowing an effective flexible policy to be followed.

Blood Coagulation↗
PubMed1979

Incidence of allo-immunization and allergic reactions to cryoprecipitate in haemophilia.

38 haemophiliacs who had received frequent cryoprecipitate infusions, were investigated for the presence of antibodies directed against red cell, HLA, Gm, Inv and platelet-specific antigens. 15 had detectable antibodies against one or more antigen systems. 11 experienced allergic reactions following infusions of cryoprecipitate. There was no correlation between allergic reactions and the presence of detectable antibodies.

Adolescent↗
PubMed1970

Changes in the antibody status of a population following epidemic infection by influenza virus A2-Hong Kong-1-68.

The haemagglutinin of influenza virus A2/Hong Kong/1/68 was shown to be markedly different from that of previously isolated A2 virus strains. No haemagglutination-inhibiting (HI) antibody to A2/Hong Kong/1/68 virus was detected in serum specimens collected in 1966 from persons aged 60 years or less. In contrast, HI antibody tests with 270 sera collected in 1968 indicated that 9.6% had demonstrable HI antibody at low titres, and 35.2% of 454 postepidemic (1969) sera had demonstrable HI antibody at relatively high titres. Most sera from persons aged 80 years and more collected in 1968 and 1969 had demonstrable HI antibody to influenza virus A2/Hong Kong/1/68. No HI antibody to the Hong Kong virus was detected in pre-epidemic sera from children aged 6 months to 3 years, whereas 32% of postepidemic sera had HI antibody. The acquisition of HI antibody to A2/Hong Kong/1/68 was not accompanied by an increase in the incidence or titres of HI antibody to heterotypic A2 influenza viruses. For sera from children aged 4-11 years, an increase of HI titre to heterotypic A2 influenza was found.

Adolescent↗
PubMedDate not supplied

Accidental envenoming by a Gaboon viper (Bitis gabonica): the haemostatic disturbances observed and investigation of in vitro haemostatic properties of whole venom.

We report the successful treatment of envenoming by the Gaboon viper (Bitis gabonica) and include results of in vitro investigations of the haemostatic properties of the whole venom. The patient was admitted to casualty soon after the bite with chest tightness, dizziness, nausea and swelling at the site of the bite and was treated immediately with polyspecific antivenom, hydrocortisone, chlorpheniramine and antibiotics. Results of haemostatic investigations were essentially normal on admission but on day 3 the thrombin time became prolonged and was associated with significant hypofibrinogenaemia and elevated D-dimers. Factors V and VIII, antithrombin III and protein C levels and platelet number were not significantly reduced. The haemostatic disturbances persisted for more than 24 h despite treatment with blood products (16 units of cryoprecipitate, 2 units of fresh frozen plasma and 6 units of platelet concentrate). Resolution of the abnormalities occurred only after administration of a further dose of antivenom. The period of hypofibrinogenaemia occurred at a time when venom antigen was undetectable in plasma by enzyme-linked immunosorbent assay. Studies in vitro with whole venom and a panel of amidolytic substrates commonly employed for measurement of haemostatic proteins revealed significant activity of venom with substrates sensitive to kallikrein and plasmin. The venom inhibited washed platelet aggregation induced by collagen, thrombin, arachidonic acid and the calcium ionophore A23187 in a dose-dependent manner.

Adult↗
PubMedDate not supplied

Acute sensorineural deafness in Lassa fever.

A prospective audiometric evaluation of 69 hospitalized febrile patients in Sierra Leone, West Africa, revealed a sensorineural hearing deficit (SNHD) in 14 (29%) of 49 confirmed cases of Lassa fever and in 0 of 20 febrile controls. An SNHD was present in nine (17.6%) of 51 people who had evidence of previous Lassa virus infection. Twenty-six of 32 local residents who had previously sustained a sudden deafness had antibody titers to Lassa virus of 16 or greater, compared with six of 32 matched controls. Lassa fever is associated with an incidence of SNHD, which considerably exceeds that previously reported with any other postnatally acquired infection, and accounts for a prevalence of virus-related hearing impairment in the eastern province of Sierra Leone that is greater than that reported from anywhere else in the world.

Acute Disease↗