Biomedical subjects
Publications and source records attributed to D W Thomas.
The applicability of a hapten-antihapten sandwich technique incorporating a monoclonal antihapten bridge antibody to localisation of tissue antigen is described. The results show that the method is both versatile and selective and has the potential of being even more sensitive than currently used immunoperoxidase methods.
Random fecal alpha-1-antitrypsin concentration was measured in children with various gastrointestinal diseases and in normal subjects. One hundred fifteen subjects were evaluated: controls (39); chronic inflammatory bowel disease (20); chronic diarrhea (18); acute gastroenteritis (17); allergic gastroenteropathy (5); chronic pancreatic exocrine insufficiency (4); acute gastrointestinal bleeding (4); nonspecific colitis (4); celiac disease (3); and intestinal lymphangiectasia (1). Mean fecal-alpha-1-antitrypsin for the controls was 0.98 mg/g lyophilized stool. All children with celiac disease, allergic gastroenteropathy, lymphangiectasia, nonspecific colitis, acute gastrointestinal bleeding, and 19 of 20 patients with active chronic inflammatory bowel disease had fecal alpha-1-antitrypsin concentrations greater than 2.6 mg/g stool (mean of the controls + 2 SD). These disorders have all been previously documented to cause protein-losing enteropathy by 51Cr-labeled albumin excretion tests. The other study patients had normal fecal alpha-1-antitrypsin excretion when compared with controls. Serial fecal antitrypsin concentrations paralleled disease activity and clinical response to therapy. The results suggest that random fecal antitrypsin concentration is a valuable screening test for mucosal disorders associated with abnormal transmucosal serum protein loss.
Guinea pig T lymphocyte responses to a decapeptide antigen (NH1-Asp5-Ans6-Glu7-Glu8-Gly9-Phe10-Phe11-Ser12-Ala13-Arg14-OH) of human fibrinopeptide B (hFPB) were examined using various synthetic peptide analogues containing single residue substitutions. Each analogue was examined for antigenicity as determined by an in vitro proliferative responses of hFPN-immune strain 2 guinae pig T cells. In addition, both strain 2 and strain 13 animals were immunized with each analogue and immunogenicity assessed by in vitro T cell-proliferative responses with the homologous immunizing analogue and the parent peptide. Replacement of arginine14 with lysine formed an immunogenic analogue which showed no antigenic cross-reactivity with the native peptide in strain 2 T cell responses. In addition, substitution of arginine14 with blocked lysine again produced a unique immunogenic analogue that showed little or no antigenic identity with the intact lysine analogue or the native peptide. In similar fashion, substitution of resideu phenylalanie10 with tyrosine or Phe(4-NO2) created unique immunogenic analogues with little or no antigenic identity to the native peptide with strain 2 T cells. By contrast, replacement of phenylalanine11 with either tyrosine or Phe(4-NO2) resulted in analogues with a total loss of immunogenicity and antigenicity in strain 2 T cell responses. An analogue in which glutamic acid7,8 were replaced with glutamine retained a small degree of antigenicity with hFPB-immune T cells, but T cells from strain 2 animals immunized with the Gln analogue responded only marginally to the Gln analogue while producing good proliferative responses with the native peptide. On the other hand, an analogue in which asparatic acid5 was replaced with asparagine retained most of the antigenic identity with hFPB for strain 2 T cell responses. None of thee analogues were immunogenic for strain 13 guinea pigs. These observations are discussed with respect to the contribution of each substituted residue to T cell respones, mechanism of Ir gene function, and a model for T cell recognition of small peptide antigens.
Three hundred and seventy sedentary men aged 20-65 years enrolled in a physical training programme after a medical and fitness examination that included measurements of "classical" risk factors for coronary heart disease. Five years later re-examination showed (a) that on average the subjects had not changed significantly in weight, blood pressure, serum lipid concentrations, smoking habits, and physical working capacity; (b) that men who had remained active and therefore had a higher degree of fitness did not differ in risk factors from men who had returned to sedentary habits; and (c) that men who had improved substantially in fitness did not differ in risk factors from men whose fitness had not changed or had declined. Five years after the initial programme one-third of the men were continuing with regular vigorous exercise. These results do not support the view that classical risk factors for coronary heart disease improve with increased physical activity and fitness.
The incidental finding of hypercalcaemia during multi-channel screening was the initiating event in 33 (45 per cent) of 79 consecutive cases of surgically treated primary hyperparathyroidism. This subgroup was asymptomatic as defined. Although significant biochemical differences existed between symptomatic and asymptomatic cases, a range of metabolic indices of bone turnover fell postoperatively in almost all asymptomatic subjects, although initially abnormal in only 35 per cent. Achievement of normocalcaemia was significantly surgeon-dependent.
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Of 33 children with various cholestatic syndromes who were studies with sonography, 19 also had 131I rose bengal scintigraphy, and 12 also had 99mTc sulfur colloid scintigraphy. Patients were categorized into intra- or extrahepatic etiologies for their cholestasis. Of 19 children in the extrahepatic category, 17 had abnormal sonographic studies; two with biliary atresia appeared normal. All 14 patients in the intrahepatic category had normal sonographic studies. Rose bengal was most useful when demonstrating biliary patency. Some cases of biliary atresia with normal sonography and lack of rose bengal excretion into the intestinal tract could not be separated from cases of neonatal hepatitis using a similar combination of studies. Radiocolloid studies were less valuable than other examinations except when demonstrating diffuse hepatic reticuloendothelial dysfunction as found in two cases of congenital syphilitic hepatitis.
A new class of hepatobiliary imaging agents has become available--the N-substituted iminodiacetic acids. After intravenous administration, these compounds are quickly extracted by the hepatocytes and rapidly excreted into the biliary tree. By using a 99mTc label, sufficient activity may be given to allow excellent gamma-camera imaging, 99mTc-labeled p-isopropylacetanilido-iminodiacetic acid (PIPIDA) has been used in the evaluation of infants with biliary excretion disorders, including two infants with neonatal hepatitis, three with intrahepatic cholestatic jaundice, and 10 with biliary atresia. Follow-up evaluation of surgically created portoenterostomies has been performed as well. In comparison with the previously available agent (131I rose bengal), the marked reduction in radiation to the liver alone should predicate the use of 99mTc PIPIDA. In addition, the speed of handling of this agent by the liver and the vastly improved imaging statistics make 99mTc PIPIDA a desirable agent for the evaluation of biliary excretion disorders in infancy.
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Nalidixic acid may cause severe acidosis and we report a fatal case of lactic acidosis assocaited with nalidixic acid therapy. Studies in normal volunteers showed drug related impairment of lactate metabolism. We question whether the drug should be used in patients who may accumulate the drug or be predisposed to lactic acidosis.
The addition of amino acid supplements to peritoneal dialysis fluid has been studied in 8 patients with compromised renal function requiring peritoneal dialysis. By the addition of 10 ml of Vamin-glucose solution to each one litre of peritoneal dialysate, amino acid losses were curtailed, no significant alterations occurred in the plasma amino acid concentrations, there were no local complications and no infections were seen. This procedure is recommended as a safe, simple way of keeping a patient in positive amino acid balance during peritoneal dialysis.
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