Biomedical subjects
Publications and source records attributed to D G de Silva.
A six week old baby girl from a closed Malay community in Hambantota presented with gradually increasing oedema since two weeks of age. She was oedematous, with gross non selective proteinuria, hypoproteinaemia and hypercholesterolaemaia. Congenital nephrotic syndrome is extremely rare and has not been reported previously in Sri Lanka.
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Serum interleukin 6 (IL-6) and tumour necrosis factor (TNF) were measured in children with dysentery during an epidemic caused by Shigella dysenteriae 1. IL-6 and TNF were also measured in fresh stool filtrates from children with acute gastroenteritis. The median serum IL-6 concentration was raised significantly in the children with complications (haemolytic uraemic syndrome, leukemoid reaction, thrombocytopenia, thrombocytosis, and severe colitis lasting more than one week) during the first week (n = 18, 9-7728 pg/ml; median 107) and in the second week (n = 13, 5-312 pg/ml; median 77), compared with convalescent sera (n = 10, < 3-85 pg/ml; median 39; p < 0.02 and < 0.05 respectively). The median IL-6 concentration during the first week was significantly higher in the group with complicated disease than in those with no complications (n = 8, < 3-37 pg/ml; median 5; p < 0.001). Although serum TNF concentrations were significantly raised in the complicated group during the first and second weeks of the illness and in the uncomplicated group compared with convalescence, there was no significant difference in the TNF concentrations between the complicated and uncomplicated groups. IL-6 was detectable in stool filtrates from eight of 13 children with S dysenteriae 1 infection and four of eight children with S flexneri infection. It was not detectable in Cryptosporidia, rotavirus, or adenovirus infections, those with pathogen-negative acute diarrhoea or controls. Seven of 13 children with S dysenteriae 1 and three of nine children with S flexneri infections had TNF detectable in stools. None of the children with Salmonella, Cryptosporidia, rotavirus of children with pathogen-negative diarrhoea and controls had detectable TNF in stool filtrates. It is postulated that the local and generalised vasculitis observed in shigellosis may be related to a direct effect of Shiga toxin on endothelial cells or caused by cytokine production stimulated by endotoxin, or both.
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We report three patients with fulminant hepatic failure following sepsis managed by exchange transfusion. The literature on the role of infection in the pathogenesis of fulminant liver failure and of exchange transfusions in its management is reviewed.
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A total of 192 samples of serum from 113 Sri Lankan patients with clinical dysentery was examined for antibodies of the IgM class to the lipopolysaccharides (LPSs) of Shigella dysenteriae-1 and Escherichia coli O157:H7. By means of ELISA and immunoblotting, 59 patients were found to have serum antibodies to the LPS of S. dysenteriae-1 only. Four samples from one patient were found to contain serum antibodies to the LPSs of both S. dysenteriae-1 and E. coli O157:H7. Antibodies to the LPS of S. dysenteriae-1 were also detected in 16 samples from 25 children, from Sri Lanka, with no previous history of dysentery; one of these children also had antibodies to the LPS of E. coli O157:H7. Analysis of 16 samples from apparently healthy children in the U.K. showed that only one serum contained antibodies to the LPS of S. dysenteriae-1. This patient had a history of recent travel to Pakistan. The isolation of S. dysenteriae-1 remains the preferred test for the diagnosis of bacillary dysentery. The use of serology as a means of providing evidence of infection with S. dysenteriae-1, however may prove to be a useful adjunct to cultural techniques but needs to be validated in an area where this organism is endemic.
Aqueous extracts of the aerial parts of Melothria maderasptana and the leaves of Osbeckia octandra have been compared with (+)-3-cyanidanol with regard to their abilities to alleviate carbon tetrachloride (CCl4)-induced liver dysfunction in albino rats by comparing the abilities of these drugs to protect the liver against CCl4-mediated alterations in the liver histopathology and serum levels of aspartate aminotransferase (GOT), alkaline amino-transferase (GPT), and alkaline phosphatase. In both pretreatment and post-treatment (administration of drugs before or after CCl4 treatment) experiments, the most marked rate of recovery of the liver was exhibited by the group of rats treated with Melothria maderaspatana extract. Although the protection offered by (+)-3-cyanidanol and Osbeckia octandra appears to be comparable in post-treatment, Osbeckia was significantly more effective in pre-treatment. From the overall results obtained it appears that the aqueous extracts of Melothria maderaspatana and Osbeckia octandra are both as potent or in some instances (in pretreatment experiments) more potent than (+)-3-cyanidanol. Of the two plants tested under the present experimental conditions used, Melothria maderaspatana appears to be marginally more effective than Osbeckia octandra in protecting the liver against CCl4-induced alterations.
Children with mixed helminthic infections between the ages of 2 and 14 years, from a slum area, were treated with two regimes of albendazole. A majority of children had moderate to heavy infections with Trichuris trichiura (greater than 70%) and Ascaris lumbricoides (greater than 84%). Children treated with a single 400 mg dose of albendazole showed a very good response in ascariasis with 100% cure rate irrespective of the severity of infection. In Trichuriasis (n = 40), a cure rate of 50% was observed in mild infections, but only a reduction in the egg counts of 60% and 57% respectively were observed in moderate and heavy infections. Only 10 patients with Necator americanus infections were treated with the single dose, and the cure rate in mild infections was satisfactory (86%), with an overall egg reduction rate of 95%. In 47 children included in the multiple dose regime (200 mg daily x 3 days), the cure rates in trichuriasis were, 82%, 66%, and 37% respectively in mild, moderate, and heavy infections. The egg reduction rate was 98% in all degrees of infection in trichuriasis. The cure rate in ascariasis, with the multiple dose regime was similar to that of the single dose, with 100% egg reduction, irrespective of the severity of infection.
Effects of pH on second-order rate constants, k (25 degrees C), have been determined for the [Fe(CN)6]3- and [Co(phen)3]3+ oxidations of ferrocytochrome c-551 from Pseudomonas aeruginosa, Pseudomonas stutzeri, and Azotobacter vinelandii. For each oxidant similar directional trends are observed. With [Fe(CN)6]3-, rate constants over the pH 4-9.5 range first decrease, and then increase to plateau pH approximately equal to 9 k values of 0.96.10(5), 4.4.10(5) and 1.05.10(5) M-1.s-1, respectively. With [Co(phen)3]3+, rate constants increase in two separate well-defined stages from pH 2.5-9.5 to plateau pH approximately equal to 9 k values of 1.35.10(5), 3.6.10(5) and 1.37.10(5) M-1.s-1, respectively. From these trends, and consistent with previous NMR studies, protein pKa values of 7.16, 8.00 and 6.67, respectively, for the three reduced cytochromes c-551 are assigned to the buried propionic acid at position 7 on the haem ring. Since at pH greater than 6 the trends with pH for both [Fe(CN)6]3- and [Co(phen)3]3+ are in the same direction, it is concluded that this deprotonation results in a decrease in protein reduction potential. At pH less than 6, the trends with [Co(phen)3]3+ and [Fe(CN)6]3- are in opposite directions. Well defined pKa values of 3.6, 3.80 and 3.80 for P. aeruginosa, P. stutzeri and A. vinelandii, respectively, are observed with [Co(phen)3]3+ as oxidant. Upper limits only of pKa values less than 5.0, less than 4.1 and less than 4.5, respectively, are observed with [Fe(CN)6]3- as oxidant, which may or may not be the same as those observed for [Co(phen)3]3+. These latter pKa values are assigned to carboxylate residues at or near to the binding site(s). It is noted that charged residues are invariant on the front face (incorporating the exposed haem edge) of all three cytochromes c-551, and that there are only two carboxylates. One possibility is that the locality including both carboxylates defined by residues Asp-19, Lys-21, Lys-28 and Asp/Glu-29, serves as a binding site for both 3+ and 3- oxidants.
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