Biomedical subjects
Publications and source records attributed to D Chalmers.
Electrophysiological investigations in a patient with progressive autonomic failure revealed selective damage to the somatic efferent innervation of the external urinary sphincter musculature, implying selective vulnerability of the motoneurons of Onuf's nucleus in the sacral cord. This vulnerability contrasts with the selective resistance of these motoneurons to degeneration in motor neuron disease.
1 The methodology and interim results of a post marketing surveillance of captopril, the first orally active angiotensin converting enzyme inhibitor are presented. 2 Utilising viewdata technology, details of hypertensive patients were entered directly into a mainframe computer. This allowed day to day monitoring of events; a facility not available with paper-based methods. 3 The design of the study allowed analysis of results including some details of efficacy, concomitant therapy, any disease symptoms and reasons for withdrawal. These factors could be categorised according to sex and age. 4 This preliminary report is based on the first 13,295 patients entered from July 1983 with follow-up until January 1985. The results of the study confirm the safety of captopril in the patients studied.
In 105 patient pairs, matched for sex, aged within a ten-year range and with closely similar coronary disease, the sensitivity and specificity of treadmill testing using the Bruce Protocol was compared to cycle ergometry using the 100 kpm/min (16 W/min) increment protocol, and found to be similar. The parameters of use were ST segment depression (sensitivity of 52% for treadmill and 61% for cycle), test angina (65% and 61%), significant work impairment (66% and 68%) and impaired blood pressure response (31% and 20%). The sensitivity was increased (treadmill to 84%, cycle to 89%) if the four parameters were grouped, and abnormality in any one of them was regarded as a positive test. The equivalent severity of coronary disease resulted in more severe work impairment on the cycle than on the treadmill. The mean work level of the treadmill group was 80%, and of the cycle group, 61% of their respective, nomographically predicted, normal values. The difference was similar for the zero, single and multivessel disease groups. This difference should be recognised when comparing the two techniques.
Four human, four hamster and three mouse established cell lines have been analysed for epoxide hydrolase activity, and these have been compared with activities of human and mouse tissue preparations. Activities expressed by the cell lines, using styrene oxide as substrate, varied between less than 0.005 and 0.44 nmol/min per mg total cellular protein. Human liver and human kidney expressed 12.2 nmol and 2.7 nmol/min per mg total protein respectively. Antibodies prepared against purified human- and mouse-liver epoxide hydrolase enzymes were used to characterize the enzyme in the cell lines. Antihuman antibody was able to inactivate and precipitate enzyme in human cell lines and partially inactivate and precipitate hamster enzymes. It was much less effective against mouse cell lines. Antimouse antibody was able to precipitate mouse enzymes and partially precipitate hamster enzymes but did not precipitate human enzymes. These data may reflect evolutionary divergence of the three species.
The association between specific reading disability and middle ear disease was investigated in a longitudinal study of 962 children followed from age 5 to 11. No significant differences were found in the prevalence of middle ear abnormalities between the reading disabled group (n = 49) and the remainder.
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Four acid hydrolases, acid phosphatase (AP), alpha-naphthyl acetate esterase (ANAE), beta-glucuronidase, and N-acetyl-beta-glucosaminidase, were determined cytochemically in peripheral blood lymphocytes from 50 patients with B and T chronic lymphocytic and prolymphocytic leukemias (CLL, PLL) and related disorders. Strong positive reactions were characteristic of the T-cell leukemias while the reactions were weak or negative in B-CLL and B-PLL. Differences in the cytochemical profile of T-CLL and T-PLL were noted. In both, beta-glucuronidase and N-acetyl-beta-glucosaminidase were positive; these enzymes are therefore good cytochemical markers of the chronic T-cell leukemias. AP and ANAE gave different results according to the disease process; AP was strong in T-CLL and variable in T-PLL, while ANAE was strongly positive in T-PLL, but weak or negative in T-CLL. The findings in T-CLL, a proliferation of T gamma lymphocytes, were similar to those of normal T gamma cells. In T-PLL, the findings did not relate to the membrane phenotype as defined by monoclonal antibodies.
Substance abuse profiles were compared among alcoholics, problem smokers, and overeaters. Fifteen scales were investigated under the rubrics of Motivation, Style (Craving, Loss of Control, and Drug Use) and Effects (Beneficial and Harmful). While all three samples were similar on the Motivation scales, Smokers differed substantially from Alcoholics and Overeaters on the Style scales and in terms of Emotional effects. Smoker were more similar to Alcoholics on perceived beneficial effects, and Alcoholics reported more severe harmful effects. Implications of the results for substance dependency theories and for treatment models were discussed.
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Barrett's oesophagus (BE) is a pre-malignant metaplastic tissue predisposing to oesophageal adenocarcinoma (EC), and gastro-oesophageal reflux is a risk factor for both conditions. Reflux of acid and bile can cause mucosal injury and initiate chronic inflammation. These processes can induce DNA damage, possibly via an oxidative stress mechanism, thus increasing the likelihood of progression from Barrett's metaplasia to dysplasia and finally carcinoma. The comet assay was optimized for the detection of DNA damage (strand breaks and alkali-labile sites) in oesophageal biopsies, including incorporation of the DNA repair enzyme Fapy-DNA glycosylase (Fpg). Fpg allows the detection of 8-hydroxy-2-deoxyguanosine (8-OHdG) sites, a known pro-mutagenic DNA lesion. BE patients were recruited from BE surveillance clinics and oesophageal biopsies collected at endoscopy. Comet analysis revealed significantly increased (p < 0.001) DNA damage in Barrett's epithelium compared with matched squamous epithelium, with median % tail DNA values of 25.1% (first to third quartile 21.7-29.6%) and 18.6% (first to third quartile 16.9-21.4%), respectively. The median % tail DNA was up to 70% higher in the matched BE tissue compared with squamous epithelium from the same patient. Fpg sensitive sites were demonstrated in both tissue types at similar levels. The raised level of DNA damage in the premalignant BE may contribute to the accumulation of genetic alterations occurring during progression to EC. Understanding these underlying mechanisms provides a basis for cancer prevention strategies in BE patients.
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