Biomedical subjects
J G Kingham
Publications and source records attributed to J G Kingham.
Focal nodular hyperplasia of the liver.
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Dapsone and severe hypoalbuminaemia. A report of two cases.
Severe hypoalbuminaemia developed in two patients on long-term dapsone treatment for dermatitis herpetiformis. The patients had been treated with dapsone for 3 and 11 years before the syndrome developed and both recovered completely when dapsone was withdrawn. Albumin-turnover studies revealed a great increase in intravascular albumin catabolism and a modest decrease in synthesis.
Chlamydia, cytomegalovirus, and Yersinia in inflammatory bowel disease.
The relationship of three infectious agents, Chlamydia, cytomegalovirus, and Yersinia enterocolitica, to the aetiology, clinical course, and diagnosis of Crohn's disease was studied. There was no evidence of chlamydial infection in Crohn's disease and no indication either that cytomegalovirus alters the outcome of acute attacks or that infection with Y. enterocolitica is being misdiagnosed as Crohn's disease.
Vipoma: localisation by percutaneous transhepatic portal venous sampling.
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Hepatitis B in a hospital for the mentally subnormal in southern England.
The prevalence of hepatitis B viral (HBV) infection was assessed in 340 patients and 268 staff in a hospital for the mentally subnormal in Wessex. Hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg, e antigen (eAg), and antibody to eAg were used as markers of such infection. Forty patients and 10 staff had evidence of recent or current infection, while 149 patients and 50 staff had evidence of past infection. HBV markers were more common in mongols, epileptics, patients with cerebral palsy, and those of lower mental grades and reached a peak after 5-15 years of hospitalisation. eAg was detected in 12 out of 26 patients with HBsAg but in none of the four staff with HBsAg. Abnormal liver function values were found in 24 (60%) of the patients with recent or current HBV infection but in only 30 (19%) of those without HBV markers. Among the staff the prevalence of HBV markers correlated with the duration of employment and degree of contact with patients. Of those with recent or current infection, 4 (40%) had abnormal liver function values compared with 25 (12%) of those without HBV markers. Despite the high prevalence of markers clinically overt hepatitis B was rare.
Acid hydrolases in monocytes from patients with inflammatory bowel disease, chronic liver disease, and rheumatoid arthritis.
A sensitive technique was used to estimate two acid hydrolases--N-acetyl-beta-glucosaminidase (N.A.G.) and beta-glucuronidase (B.G.)--produced by peripheral-blood monocytes. Enzyme levels were measured after in-vitro incubation of monocytes with or without stimulation by zymosan and endotoxin. Compared with controls, enzyme production and release in inflammatory bowel disease, chronic liver disease, and rheumatoid arthritis were markedly raised. It is suggested that various stimuli, including immunological ones, may be responsible for the release of such enzymes from monocytes and that such release may be a factor in the production of the chronic inflammation seen in these disorders.
Selectivity of small intestinal exudate in celiac disease and Crohn's disease.
The small intestinal exudates of patients with protein-losing enteropathies produced by celiac disease or proximal jejunal Crohn's disease were compared with controls. The exudates in control subjects were highly selective, whereas those of the celiac and Crohn's disease subjects were relatively nonselective. It is believed that this loss of selectivity is secondary to basement membrane damage. An analogy is drawn with the renal lesion in nephrotic syndrome where basement membrane damage is associated with nonselective proteinuria.
Autoradiographic study of the permeability characteristics of the small intestine.
This autoradiographic study demonstrates the distribution of a range of small solutes and macromolecules in the mucosa of the guinea-pig small intestine after intracardiac injection. The substances investigated were: 14C-urea, 3H-mannose, 3H-inulin, and 125I polyvinylpyrrolidone (PVP). Small bowel biopsies were taken at intervals from one to 60 minutes after injection and the tissues processed for autoradiography. Light microscopic examination of the autoradiographs showed that the compartmental distribution depended on the molecular size of the substances being studied. Urea and mannose, as small solutes, were uniformly distributed throughout the intravascular, extravascular, and epithelial compartments. Inulin was evenly distributed in the vessel lumen and extravascular space but there was a considerable drop in concentration in the epithelium. PVP exhibited the most marked gradients, the concentration being greatest in the vascular lumina, lower in the extravascular space, least in the epithelium. Thus there appear to be two barriers to macromolecular passage which are freely permeable to small solutes: the capillary wall and the epithelium. At a light microscopical level it is not possible to observe whether the limiting membrane of each of these barriers is the cell plasmalemmal membrane or the basement membrane. The selectivity of the epithelial barrier is greater than that of the capillary barrier.
Treatment of HBsAg-positive chronic active hepatitis with human fibroblast interferon.
Two patients with HBsAg positive chronic active hepatitis have been treated with human fibroblast interferon 10(7) units daily for two weeks. Before treatment, both patients had high levels of hepatitis B surface antigen, core antibody, and DNA-binding antibody in the blood and one patient had a fourfold rise in serum AST. During treatment there was a striking fall in the core antibody titre and also in the DNA-binding antibody, which has been maintained for several months subsequently; in one patient the initially high AST level fell to normal. No significant adverse effects occurred, and these observations should encourage further trials of fibroblasts interferon in hepatitis B.
DNA-binding antibodies and hepatitis B markers in acute and chronic liver disease.
A Farr technique has been used to assay antibodies to double-stranded DNA in the serum of patients with acute and chronic liver disease and carriers of HBsAg from the United Kingdom and Iraq. These antibodies were found in all groups from both countries. The highest levels were found in chronic active hepatitis and cirrhosis. In the Iraqi patients there was a strongly positive correlation between DNA-binding antibody levels and the presence of hepatitis B markers but not with disease activity. In the patients from the United Kingdom there was little correlation with disease activity and none with autoantibodies. Ninety-five per cent of asymptomatic carriers of HBsAG had elevated DNA-binding antibodies. It is suggested that hepatitis B-specific DNA might be one trigger to DNA antibody formation, though in liver disease a variety of factors are clearly operative.
Interferon skin reactivity and pyrexial reactions.
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Small intestinal permeability. 1. Effects of ischaemia and exposure to acetyl salicylate.
Permeability of the small intestinal mucosa was estimated using a perfusion technique after either a period of ischaemia or exposure to acetyl salicylate. It was shown that these procedures increased the passive permeability of the mucosa to macromolecules while maintaining normal mucosal selectivity. Histologically, there was derangment of the epithelial cell layer of the villous tips without damage to the epithelial basement membrane or subepithelial structures. It is concluded that the epithelial cell layer is purely limiting with no selective function and that the role of selectivity must be ascribed to either or both of the other mucosal barriers, the capillary and the epithelial basement membrane.
Permeability of the small intestine after intra-arterial injection of histamine-type mediators and irradiation.
Permeability and selectivity of rabbit small intestine were estimated by a perfusion technique after intra-arterial injection of histamine-type mediators and intestinal irradiation. It was shown that the histamine-type mediators caused an increase in capillary permeability which produced an overall moderate increase in transmucosal permeability with a moderate loss of selectivity. Local intestinal irradiation caused a very marked increase in permeability and a profound loss of selectivity. It was felt that this was produced partly by an increase in capillary permeability but largely by damage to the epithelial basement membrane. It is concluded that the intestinal capillary endothelium is both rate-limiting and selective, though not to a major degree in either case. The epithelial basement membrane, however, appears to be both rate-limiting and markedly selective.
Watery diarrhoea and hypokalaemia associated with a phaeochromocytoma.
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