Biomedical subjects
Publications and source records attributed to C L Brown.
In our zeal to deal with alcohol and drug abuse, we may have a distorted picture of what the majority of college students actually think about alcohol and drug use. Students in this study done at a public university located in the Deep South report being generally intolerant of substance abuse.
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The epidermal-growth-factor receptor (EGF-r) and its ligands are involved in the control of proliferation of both normal and neoplastic thyroid epithelium. Autocrine stimulation of growth involving this receptor system has been identified in several types of human neoplasia and we were interested to determine whether it might occur in human thyroid tumours. We have therefore examined an archival series of thyroid tumours and non-neoplastic pathologies for expression of the EGF-r and 2 of its ligands, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF), using immunohistochemistry. We found evidence of expression of both the EGF-r and the TGF-alpha in the majority of thyroid tumours, with a trend to higher expression in more malignant neoplasms. We also found variable levels of expression of EGF-r and TGF-alpha in all cases of thyroiditis examined. We conclude that there is a potential autocrine loop involving the EGF-r system in both neoplastic and non-neoplastic conditions of the human thyroid.
The pathology of Coxsackie virus B4 (CVB4) infection in a murine model was investigated by in situ hybridisation using a biotinylated cDNA probe derived from CVB4. During the acute phase of infection virus RNA sequences were detected in the exocrine pancreas of 60% of mice infected with a pancreotropic variant of CVB4. A positive hybridisation signal was observed in other organs in some animals including the heart and liver of 1 mouse 28 days after infection. The cellular distribution of virus RNA sequences corresponded well with the histological findings in most tissues. Possible causes for failure of hybridisation in some infected pancreases are discussed in conjunction with potential application of the technique in human pancreas biopsy samples.
The gene for the alpha polypeptide chain (alpha s) of the heterotrimeric G protein Gs can be activated to the putative oncogene gsp by specific point mutations at codons 201 and 227. Such mutations have been reported in 40% of human growth hormone-secreting pituitary adenomas and in a single autonomously functioning thyroid adenoma. We examined an archival series of 45 differentiated human thyroid tumors by polymerase chain reaction amplification and oligonucleotide hybridization to identify point mutations at each of the affected codons. Successful amplification was achieved in 38 cases, and activating mutations were identified in 5 of 13 (38%) autonomously functioning adenomas, but in none of 16 nonfunctioning adenomas, six papillary carcinomas, or three follicular carcinomas. Our results confirm that the gsp oncogene is involved in the pathogenesis of autonomously functioning tumors but do not support a role in other thyroid tumors.
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Adverse effects of respirators have been the focus of considerable research over the past decade. Individual research projects have generally focused on one specific category of effects: ventilatory, respiratory control, work limitation, subjective discomfort, psychologic effects, thermal loading, and cardiovascular changes. Most were studied in experimental laboratory situations rather than in actual worksites. Very little attention has been given to compliance with use and actual effectiveness in preserving health. Inasmuch as many types of effects have been demonstrated, there is a need to carefully define which type(s) of effects is/are most important for respirator design selection and worker medical certification in particular situations. In general, respirators should be assessed for their effect on all relevant variables.
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Nurse executives who routinely feel overpowered in their work relationships are highly stressed. When high levels of stress are experienced regularly, ill health may be the outcome, resulting in negative consequences for both the nurse executive and the organization. Strategies are proposed for nurse executives to use in coping with consistent patterns of work-related overpowerment.
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The pharmacodynamic effects and acceptability of perindopril (4 mg daily) and hydrochlorothiazide (25 mg daily) given alone or in combination for 1 month were investigated in a double-blind, placebo controlled, parallel group study. The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups. Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide (11/7 mm Hg supine) given alone at these doses. The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure (24.5/12.6 mm Hg supine) taking into account the placebo response. The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide. The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group. Perindopril, whether given alone or in combination with hydrochlorothiazide, was well tolerated and produced no clinically significant change in routine haematology or serum biochemistry. The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction.
The c-erbB-1 and c-erbB-2 proto-oncogenes are frequently activated by gene amplification and overexpression in a variety of human cancers. In an analysis of a large series of benign and malignant thyroid tumours, no abnormalities of structure or expression of either of c-erbB-1 or c-erbB-2 were found. Activation of these oncogenes is not a necessary event in neoplasia of this epithelial system.
Nucleolar organiser regions (NORs) were counted in the nuclei of both epithelial and stromal cells in cases of endometrial hyperplasia and carcinoma. The scores for each case were expressed as a ratio. No significant difference was found between the ratios for cystic hyperplasia and hyperplasia with architectural atypia, confirming the view that these are morphological variants of the same benign hyperplastic process. The ratios for hyperplasia with cytological atypia and adenocarcinoma differed significantly from the benign hyperplasias. This adds support to the view that hyperplasia with cytological atypia should be considered a neoplastic condition.
Twenty-nine patients with primary hyperparathyroidism underwent double-tracer subtraction scanning after injection of 201Tl as thallous chloride for thyroid and parathyroid images followed by 99mtechnetium as sodium pertechnetate for thyroid images prior to surgical exploration of the neck. The operative findings were correlated with the scans. All 23 adenomas (100%) and 13 of 18 (72%) hyperplastic glands were correctly localized. The ability of the scan to identify abnormal parathyroids was determined by the gland mass rather than whether the tissue was adenomatous or hyperplastic as all 32 (100%) abnormal glands weighing more than 180 mg were successfully localized in contrast to four of nine (44%) glands weighing less than 180 mg. An additional technique, in which emission tomography was carried out after subtraction scintigraphy, was used on 11 patients in the series. In all 11, the site of a single abnormal gland was predicted by the conventional subtraction scan: in nine of these patients, emission tomography provided additional localization of the gland in the anteroposterior plane.
Thirty-nine free-ranging raccoons (Procyon lotor) in an endemic rabies area of Pennsylvania (USA) were vaccinated with a single intramuscular inoculation of commercial inactivated rabies virus vaccine, 17 June to 23 August 1987. Paired serum samples, pre- and postvaccination, were obtained from eight raccoons and were analyzed in vitro for rabies virus neutralizing antibody using a modified rapid fluorescent focus inhibition test. Seven of eight (88%) recaptured raccoons demonstrated seroconversion within 15 to 26 days of vaccination. At 1 yr postvaccination, three vaccinated raccoons were recaptured and challenged in captivity with street rabies virus, resulting in the death of two of three vaccinates and five of five unvaccinated control raccoons.
Twenty-one adult raccoons (Procyon lotor) were radio-marked on each of two areas in Centre County, Pennsylvania from 17 June to 23 August 1987. Raccoons on Area 1 were vaccinated with a commercial inactivated rabies virus vaccine administered intramuscularly, whereas on Area 2 raccoons were not vaccinated. Survival rates were estimated for three periods: pre-season (23 August to 23 October 1987), harvest season (24 October 1987 to 23 January 1988) and post-season (24 January to 26 March 1988). Kaplan-Meier survival rates (+/- SE) were 1.00 +/- 0.00 for both areas during the pre- and post-season periods. Survival rates during the harvest period were 0.67 +/- 0.11 and 0.69 +/- 0.11 for Area 1 and Area 2, respectively. Survival rates between the two areas were not different (P = 0.929). During 23 August 1987 to 26 March 1988, rabies was not an apparent factor in raccoon survival. Conclusions regarding timing an oral rabies vaccination campaign based upon occurrence of rabies-related mortalities could not be presented because of the lack of obvious rabies mortality. However, our findings, combined with information about immunization, vaccine distribution, and peak periods of raccoon rabies, suggest a late winter or early spring vaccination period would be optimum for reducing the number of raccoons susceptible to rabies.
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