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Biomedical subjects

G Davies

Publications and source records attributed to G Davies.

At least 271 records · Page 15Linked to original sources

Changes in respiratory variables of grain handlers and civic workers during their initial months of employment.

The health effects of employment as a grain handler were studied by examining workers on two occasions, firstly, immediately before or soon after they were hired and again about two and a half months after they were employed. Over this time there was a substantial increase in the prevalence of cough, sputum, and eye irritation, accompanied by small pulmonary function changes suggestive of a restrictive ventilatory defect. No comparable changes in symptoms were observed over a similar number of months in grain handlers employed for an average of nine years or in control workers consisting of newly hired or long term civic outside labourers. The long term grain handlers, however, developed a similar change in their pulmonary function. These findings indicate the occurrence of a change in the health of grain elevator workers after a relatively brief duration of employment.

Adolescent↗

alpha-Adrenergic receptors and coronary spasm: an elusive link.

In 14 consecutive patients with variant angina we investigated the possible role of coronary alpha-adrenergic receptors in the genesis of coronary spasm. In eight patients, computerized, beat-by-beat analysis of the electrocardiogram recorded during continuous Holter monitoring failed to reveal any increase of heart rate and corrected QT interval (both indexes of cardiac sympathetic activation) in the period preceding the onset of ST segment changes in 197 episodes of ischemia caused by coronary spasm. In the same patients, analysis of the circadian distribution of ischemic episodes revealed a significantly higher incidence in the early morning hours, when sympathetic activity is at the lowest level. Twelve patients underwent serial provocative testing with cold pressor, phenylephrine, or norepinephrine infusion and administration of ergonovine maleate. Ergonovine consistently reproduced coronary spasm in all 12 patients, while results of cold pressor testing were positive in only one. Infusion of phenylephrine (eight patients) or norepinephrine after beta-blockade (four patients) failed to precipitate myocardial ischemia. In five patients infusion of phentolamine at the highest tolerated dose did not reduce significantly the number of ischemic attacks when compared with placebo. In contrast to results of previous reports, our data seem to rule out the hypothesis that an increase of sympathetic outflow to the heart plays an important role in the genesis of coronary spasm. We cannot, however, exclude the possibility of localized alpha-stimulation of epicardial arteries.

Adult↗

Myocardial ischemia during ergonovine testing: different susceptibility to coronary vasoconstriction in patients with exertional and variant angina.

Coronary spasm is an accepted cause of transient myocardial ischemia in patients with variant angina; more recently it has been suggested that dynamic stenoses could also play an important role in the pathophysiology of exertional angina. To test this hypothesis we submitted 31 patients with histories typical of exertional angina to ergonovine testing and compared the electrocardiographic and clinical responses to those observed in seven patients with variant angina. All underwent bicycle ergometric exercise testing and coronary angiographic examination. For all tests, ST segment shifts of 0.1 mV or greater were considered to be diagnostic of myocardial ischemia. In patients with exertional angina, exercise testing produced diagnostic ST segment depression in 21 (68%). Ergonovine testing produced diagnostic ST segment depression in nine (29%). All nine had positive exercise test results and two- or three-vessel disease, yet the test was negative in seven other patients with positive exercise test results and similar angiographic findings. Conversely, in the seven patients with variant angina, results of exercise testing were positive in five (ST segment depression in two, ST elevation in three), while ergonovine produced ST segment elevation in all seven. Coronary angiographic examination showed normal arteries in two, one-vessel disease in four, and three-vessel disease in one. Results of all ergonovine tests were positive at values of rate pressure product much lower than those observed during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The diagnosis of gallstones--a prospective comparison of oral cholecystography and real-time ultrasound.

A prospective study was made to compare the diagnostic value of ultrasound and oral cholecystography. 256 Patients were examined, 143 of whom were operated on. Ultrasound proved to have less chance of missing gallstones, whereas oral cholecystography showed a high percentage of false-positive results at first examination. Ultrasound is recommended as the method of choice for screening gallstones.

Cholecystography↗

Antibody response of nude (RNU/RNU) and hairy (RNU/+) rats to circulating cell surface components from human pancreatic cancer xenografts.

Homozygous nude rats (rnu/rnu) injected s.c. with 3 X 10(7) human pancreatic cancer cells from the GER cell line developed circulating antibody to GER cell surface, detected in a 125I binding assay against viable GER cells in vitro. Antibody titre rose with progressive xenograft growth. These antibodies showed no selectivity for GER cells when compared with a panel of other human cell lines. Heterozygous nude rats (rnu/+) immunised with serum from their GER xenograft-bearing nude relatives (rnu/rnu) also developed anti-GER cell surface antibodies. These antibodies showed some selectivity for GER and WAD (a second human pancreatic cancer cell line) when compared with other human cancer cells and lymphocytes. These findings show that some human pancreatic cancer cell surface components may persist independently in the circulation of xenograft bearing rnu/rnu rats despite the presence of antibody excess to other surface determinants from the same cells. It is suggested that differences in the relative immune competence of rnu/rnu and rnu/+ rats may offer a biological opportunity for enhancing the recognition of weak antigenic determinants which may have some useful selectivity for different types of human tumour cells.

Adenocarcinoma↗

Variables of pulmonary allergy and inflammation in grain elevator workers.

The purpose of this study was to examine possible mechanisms of the obstructive and restrictive ventilatory defects of grain elevator workers. We found that grain handlers whose skin tests were positive to grain or fungal antigens had no excess of respiratory symptoms or pulmonary function abnormalities. Also, those having a possible work-related respiratory problem showed no response to inhalation challenge tests with grain dust extract. In addition, grain handlers exhibited neither an increase in positive serum precipitin tests with fungal antigens nor abnormal serum levels of C3 and C4, C-reactive protein, rheumatoid factor or antinuclear factor. However, their serum a1-antitrypsin level was elevated. The latter finding may be indicative of a pulmonary inflammatory process, but we have found no clear indication of a type 1 or 3 allergic state in grain elevator workers.

Adult↗

Factors influencing R wave amplitude in patients with ischaemic heart disease.

R wave amplitude changes during exercise have been ascribed to alteration in left ventricular volume and their measurement advocated for the improved diagnosis of coronary disease. The reproducibility of exercise QRS changes and their relation to ST segment depression, respiratory pattern, and left ventricular volume during ischaemia were studied in 10 patients with angina and coronary disease. QRS amplitude was measured in a 16 lead precordial map during three identical exercise tests in each patient and left ventricular volume assessed continuously using gated blood pool imaging with a single scintillation probe during manoeuvres to provoke ischaemia. During exercise, QRS amplitude increased or remained unchanged in four patients and fell in six patients in a consistent manner for each patient. R wave amplitude was not affected by changes in respiratory pattern. R wave amplitude did not alter in 33 of 39 episodes of left ventricular volume increase (mean 32%) or decrease (mean 36%) in end-diastolic counts. These findings suggest that precordial R wave changes during ischaemia are not determined primarily by alteration in left ventricular volume or the respiratory pattern. Though reproducible in each patient and following a definite relation to ST segment depression, the variable directional response during exercise suggest that R wave amplitude changes have little diagnostic value.

Adult↗

Platelet-derived growth factor promotes proliferation of erythropoietic progenitor cells in vitro.

To investigate serum requirements for optimal erythropoiesis in vitro, we studied the response of erythroid progenitor cell proliferation in culture to platelet-derived growth factor (PDGF). Human bone marrow cells cultured with platelet-poor plasma-derived serum (PDS) form fewer erythroid colonies than do cells cultured with human whole blood serum or fetal calf serum (P less than 0.05). Treatment of washed platelets with thrombin releases a low molecular weight (less than 100,000) factor that enhances colony growth. This secreted factor appears to be PDGF, based upon the ability of partially purified and electrophoretically pure PDGF to restore colony-forming capacity of PDS-containing cultures to 70-96% of the level found in control cultures with whole blood serum or fetal calf serum. Enhancement of colony growth by PDGF was noted only in marrow cultures supplemented with erythropoietin and PDS. Presence of bioactive erythropoietin in PDGF preparations was excluded by assay in hypertransfused, polycythemic mice, and in fasted rats. Although PDGF stimulates erythroid burst formation in marrow cultures containing optimal concentrations of burst-promoting activity (BPA), it does not influence proliferation of circulating erythroid bursts, regardless of BPA concentration added to culture. We conclude that PDGF is a serum determinant of optimal erythroid progenitor cell proliferation in marrow culture. The activity of PDGF is distinct from that of the apparent erythroid specific growth factors erythropoietin and BPA.

Animals↗

Pharmacokinetics of meptazinol in man following repeated intramuscular administration.

A study was performed in 6 healthy volunteers to determine whether 50 mg intramuscular doses of meptazinol repeated four hourly for 24 h would lead to accumulation of the drug. The first dose of meptazinol was rapidly absorbed with a subsequent mean (+/- SD) elimination half-life of 1.6 +/- 0.33 h. This value was unaffected by the administration of intermediate doses. There was no significant accumulation of the drug; 95% of the steady-state plasma concentration was achieved after a mean (+/- SD) of 1.9 +/- 0.39 and 99% after a mean (+/- SD) of 2.9 +/- 0.63 doses. These findings are consistent with the theoretical prediction for a rapidly absorbed drug with a plasma elimination half-life of 1.6 h. No clinically relevant changes were seen in pulse blood pressure, haematological or biochemical screens. Reported side effects were of a subjective and minor nature.

Adult↗

Growth of human digestive-tumour xenografts in athymic nude rats.

The athymic nude rat rnu/rnu has been established as an in vivo model for the acceptance of human digestive-tumour xenografts. We report the successful xenografting of 7/12 (58%) primary explants from patients with digestive cancer. Successful xenografting also occurred in 21/25 (84%) pancreatic tumours derived from a pancreatic exocrine adenocarcinoma (GER) maintained in cell culture; 2 of those have been successfully passaged in nude rats. The simultaneous implantation of these tumours into nude mice led to an almost identical take rate. Passage of one colonic and one pancreatic xenograft from nude rats into nude mice, and transplantation back into nude rats, increased the take rates. The critical period for the establishment of primary tumour growth was usually 28-42 days. The xenografts maintained histological and cytological characteristics of the primary explants or of the original tumour from which the cell line derived. The karyotype of the cell line was also maintained in the solid tumour. Three murine tumours were successfully grown as xenografts. Despite their immunoincompetence, the rats in this study showed no increased morbidity or mortality when kept in conventional conditions, compared with animals housed in isolators. The athymic nude rat will become a valuable complementary tool to the nude mouse for the establishment and maintenance of human digestive tumours and for surgical and serial serological studies.

Adenocarcinoma↗