Biomedical subjects
G P Wyatt
Publications and source records attributed to G P Wyatt.
Human parvovirus infection revealing hereditary spherocytosis.
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Marfan's syndrome presenting as an intrapartum death.
A rare case of Marfan's syndrome presenting as an intrapartum death is described. Recognisable mitral valve lesions were present.
Food wastage in a burns unit.
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Pyogenic meningitis in chronic gastroenteritis and marasmus.
Pyogenic meningitis occurred in 6 infants in the course of chronic gastroenteritis, in 5 of whom a normal CSF had been recorded earlier in the illness. Clinical signs of meningitis were often absent. The problems of diagnosis and management and of possible predisposition to pneumococcal meningitis in children suffering from chronic gastroenteritis are discussed.
Bovine blood lead reference material.
A protocol is described for the preparation and characterization of bovine blood lead (Pb) reference material (RM). Adult bovine animals are orally dosed with Pb as Pb(NO3)2, and blood is collected directly from the jugular vein into 5-mL evacuated, low-Pb glass tubes containing EDTA as anticoagulant. The blood is cooled to 4 degrees C for 24 h and frozen and stored at -20 degrees C. Over 400 RMs were prepared and certified for reference values (RV) since the inception in 1974 of the Childhood Blood Lead Proficiency Testing Program. Five reference laboratories employing blood Pb methods of various principles were used to certify the RV, representing the true value, of 5 representative RMs containing 6.4-54.0 micrograms Pb/mL. Intertube homogeneity was verified by reference laboratories determining blood Pb in 20 tubes of 150 tubes collected from each of the 5 representative RMs. Intratube homogeneity was verified by an internal laboratory determining Pb in 12 consecutive 10-microL samples from 5 mL of blood in each of 3 representative RMs. Pb was unchanged in 37 bovine blood Pb RMs containing EDTA as anticoagulant after storage at -20 degrees C for 32-48 months.
In vitro chemopreventive efficacy screening using human keratinocytes and the in vivo data correlation.
Agents with potential cancer preventive activity were screened for efficacy in the Human Epidermal Cell (HEC) Assay. The HEC Assay measures inhibition of propane sultone-induced changes in the growth and/or differentiation in early passage keratinocyte cultures. The assay biomarkers were calcium tolerance, growth inhibition, and involucrin induction. The HEC Assay also provides information on the cytotoxicity of the agents following acute and chronic exposure. Agents were evaluated at non-toxic doses in the HEC Assay. The HEC Assay has been used to screen twenty-eight agents for chemopreventive efficacy. A positive response in one or more endpoints of the HEC Assay correlates 100% (16/16) with a positive response in one or more of the animal cancer prevention models (J. Cell. Biochem., 26S:29-53, 1996). The overall sensitivity for predicting efficacy in animals is 84%. The available data suggest that a positive assay response appears to be highly predictive of efficacy in vivo.
Differential growth response to exogenous calcium in normal and carcinogen-exposed primary human keratinocyte cell cultures.
The purpose of these studies was to examine an early carcinogen-induced change in primary human epithelial cell cultures and to attempt to reverse this change with retinoic acid. Primary cultures of human foreskin keratinocytes were prepared and exposed to the carcinogen, propane sultone. After each passage, a portion of cells were plated into medium containing increasing amounts of calcium. In a series of experiments it became evident that carcinogen exposed cells continued to grow in the presence of added calcium. Solvent control cell growth was decreased under such conditions. This new phenotype became apparent after the third subculture, but was pronounced after the fourth subculture. The addition of retinoic acid to the culture medium at each medium change reduced this effect and the keratinocytes grew more slowly, similar to control cells, in the presence of added calcium. The results suggest that carcinogen-exposed human keratinocytes acquire a resistance to calcium-induced differentiation or growth cessation and that retinoic acid can ameliorate this process. Although the mechanism of retinoic acid's inhibition remains unclear, these studies do provide a human cell model system which can be used to screen potential chemopreventive agents and for further mechanistic research.