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Biomedical subjects

D A Kelly

Publications and source records attributed to D A Kelly.

At least 127 records · Page 7Linked to original sources

Fluorescence immunohistochemical detection of hypoxic cells in spheroids and tumours.

Polyclonal antibodies have been raised in rabbits to a haemocyanin adduct of a reductively-activated, fluorinated analogue of misonidazole. Fluorescence immunohistochemical studies show that the polyclonal antibodies bind to spheroid sections and tumour sections in patterns similar to those revealed by autoradiographic studies with a tritium-labelled derivative of the fluorinated misonidazole analogue.

Animals↗

Hemostasis in liver disease.

Patients with liver disease have a wide range of coagulation problems. Patients with parenchymal liver disease are likely to have reduced synthesis of proteins and inhibitors (Table 1), whereas dysfibrinogenemia and hyperplenism develop in cirrhosis. Patients with cholestasis without cirrhosis often have elevated levels of fibrinogen, Factors V and VIII, probably due to reduced clearance of proteins (Table 1). The hemostatic defects in liver disease are complex and multifactorial. They are often unpredictable and the mechanisms elusive. Developments in molecular genetics and immunology have shown that both qualitative and quantitative abnormalities of coagulation proteins and protein inhibitors contribute to the abnormalities in liver disease. Future research will certainly result in a better understanding of these defects and more effective therapy.

Adult↗

Increased severity and morbidity of acute hepatitis in drug abusers with simultaneously acquired hepatitis B and hepatitis D virus infections.

Hepatitis D virus (delta agent) markers were present in 111 (36%) of 308 intravenous drug abusers who were positive for hepatitis B surface antigen (HBsAg), 52 of these having hepatitis D virus antigenaemia. IgM antibody to hepatitis B core antigen (anti-HBc IgM) was present in 92 out of 95 subjects tested, indicating that hepatitis D virus and hepatitis B virus infections had been acquired simultaneously. Hepatitis D virus markers were present in three out of four patients with fulminant hepatitis, and in 80 of 223 (36%) with mild or moderate hepatitis compared with four of 29 (14%) of those who were asymptomatic. These proportional differences were significant (p less than 0.001). Hepatitis D virus markers were present in twice as many patients positive for anti-HBc IgM requiring admission to hospital with acute hepatitis compared with outpatients attending a drug treatment centre. Tests on one patient showed complete disappearance of HBsAg, but hepatitis D antigen (HDAg or delta antigen) and hepatitis B e antigen (HBeAg) were still present in serum samples. All five patients with chronic active hepatitis had hepatitis D antibody (anti-HD) compared with seven of 24 (29%) with chronic persistent hepatitis (p = 0.008). Blocking anti-HD persisted for long periods after simultaneous infections with hepatitis B virus and hepatitis D virus but at lower titres than in patients with chronic liver disease.

Acute Disease↗

Free-standing vaporizers. Another hazard.

A previously unreported hazard of free-standing 'Tec' type vaporizers relating to their positioning downstream of the oxygen flush is presented. Three Enfluratec Mark III vaporizers were studied; measurement of delivered enflurane concentration was performed at a flow rate of 8 litres/minute, during and after the application of the oxygen flush upstream of the vaporizer. The maximum difference between the dial setting and the measured vapour concentration occurred when a 5-second flush was applied to a vaporizer set at 0.2 volume %, the peak vapour concentration recorded being 2.3%. Other hazards of free-standing vaporizers are discussed and ways of avoiding these hazards considered.

Anesthesia, Inhalation↗

The effect of liver disease on factors V, VIII and protein C.

The components of the factor VIII complex were estimated by immuno- and bioassays in 85 patients with liver disease. The plasma concentrations of the antigens were elevated in 65% (VIII:CAg) and in 76% (VIIIR:Ag) of patients while the biological activities were elevated in only 14% (VIII:C) and 15% (VIII:RiCof). There was no correlation with C-reactive protein, used as a measure of an acute phase reaction (X2 = 0.7; P = 0.1); or with severity of liver disease as judged by prothrombin ratio (P = 1.0) but highest values were observed in patients with cholestatic liver disease. Following parenteral vitamin K there was a significant fall in both the biological activity of VIIIC (36%) and of VIII:CAg (38%) in 13 vitamin K deficient patients (P less than 0.001) but no change in 23 vitamin K replete patients or in the VIIIR:Ag levels in either group. Factor V levels were lower in patients with parenchymal liver disease (0.54 +/- 0.1 units/ml, mean +/- SEM, n = 12; normal range 0.5-1.5 units/ml) than in patients with extrahepatic cholestasis who were vitamin K deficient (1.2 +/- 0.1 units/ml, P less than 0.0001). The levels of protein C antigen, the vitamin K dependent protease which inactivates factors VIII:C and V, was at the lower end of the range in both groups (0.7 +/- 0.1, mean +/- SEM, n = 18, normal range 0.74-1.4 units/ml). There was no significant change in either protein C antigen or factor V following vitamin K. The discrepancy between the biological activity of factor VIII and the antigen levels could represent accumulation of partially degraded factor VIII or production of a hypoactive form. There is no evidence that the reduction in VIIIC and VIII:CAg following vitamin K was mediated by protein C.

Adolescent↗

Occurrence of malignant hyperpyrexia in a patient with osteogenesis imperfecta.

Probable malignant hyperpyrexia (MH) developed and was successfully treated in a 20-yr-old man during anaesthesia for reduction of a fractured mandible. The sister of this patient had died after an anaesthetic at the age of 14 yr, but malignant hyperpyrexia was not suspected. Subsequent enquiries revealed that the patient and his sister both had osteogenesis imperfecta. This case illustrates the infrequently reported association of malignant hyperpyrexia with osteogenesis imperfecta, and the difficulties in obtaining an adequate personal and family history of previous anaesthetics.

Adolescent↗

Localization of factor VIIIC: antigen in guinea-pig tissues and isolated liver cell fractions.

Factor VIIIC:antigen (VIII:CAg) was estimated in guinea-pig tissues by an immunoradiometric assay using a human inhibitor antibody. In homogenized guinea-pig tissues, VIII:CAg was shown to be stable and to be predominantly located in the liver (9 +/- 1.2 units; mean +/- SEM, n = 8). Lesser amounts were detected in spleen (1.3 +/- 0.02 units), lung (0.6 +/- 0.07) and kidney (0.4 +/- 0.06). In isolated liver cell fractions separated by centrifugal elutriation VIII:CAg was mainly detected in the hepatocyte fraction (0.3 +/- 0.07 units/10(8) cells;mean +/- SEM, n = 5) and in lesser amounts in the endothelial (0.02 +/- 0.01 units/10(8) cells) and the Kupffer cell fractions (0.05 +/- 0.02 units/10(8) cells). The liver concentration of VIII:CAg was (0.17 +/- 0.02 units/g) which was 20% of the plasma concentration (0.96 +/- 0.01 units/ml, n = 8) suggesting that VIII:CAg may not be stored in the liver but is rapidly exported following synthesis.

Animals↗

Increased folate catabolism in mice with ascitic tumours.

Folate deficiency is reported in association with certain malignant tumours, and it has been suggested that this arises from increased folate turnover and catabolism in such circumstances. Using an experimental animal model to determine the rate of catabolism of [3H]pteroylglutamate (folic acid) by the quantitative estimation of the two urinary catabolites p-[3H]aminobenzoylglutamate and [3H]acetamidobenzoylglutamate, we have measured the rate of folate catabolism in mice with ascitic tumours. There was a significant increase in the rate of catabolism in the mice with tumours compared with controls over a 10 day period. This was associated with the accumulation of ascitic fluid and an increase in the number of tumour cells in the treated animals. The increase in catabolism appeared to be due to increased cell turnover of the tumour rather than an increase in cell mass, as the increase in mass of the tumour was negligible.

Animals↗