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Biomedical subjects

D Fitzgerald

Publications and source records attributed to D Fitzgerald.

51 records · Page 3Linked to original sources

Analyses of cancer incidence in black gold miners from Southern Africa (1964-79).

As an extension of an earlier study covering the 8-year period 1965-71 (t1), the incidence of cancer in black gold miners over a second 8-year period, 1972-79 (t2) has been investigated. The population again totalled 2.9 million man-years of employment, an average of 363,800 men per year. Of the 903 cancers found in t2, primary liver cancer accounted for 45.4%, oesophageal cancer 19.8%, cancer of the respiratory system 11.2% and bladder cancer 2.7%. Analysis of these 4 common cancers by country or region of origin of the miners confirms for the most part the patterns of incidence found in the earlier survey and consolidated rates are therefore presented for the full 16-year period, 1964-79 (t3). The spatial distribution of primary liver cancer within Mozambique and oesphageal cancer within Transkei have been investigated for the periods t1, t2 and t3 and temporal changes of rate have been examined by individual years from 1964 to 1979. The geographical gradient of incidence for cancer of the oesophagus in Transkei has become less marked during the second period of the survey and the crude incidence rate for primary liver cancer in gold miners from Mozambique has continued to drop throughout the period of the survey.

Africa, Southern

Essential role of calcium in cellular internalization of Pseudomonas toxin.

Pseudomonas exotoxin (PE) has been shown previously to enter mouse LM cells by receptor-mediated endocytosis, to block protein synthesis, and to cause cell death. The requirement for the divalent cation calcium in the binding and internalization of PE was examined. Biochemical studies showed that depletion of extracellular calcium with ethylene glycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid protected cells from the action of PE when the chelator was present during the internalization step. Extracellular calcium was not required for binding. We observed with immunoelectron microscopy that, in the cold, toxin bound to cell surfaces equally well in the presence or absence of chelator. In the presence of chelator, toxin was not cleared from the cell surface when cells were warmed to 37 degrees C. Replenishment of calcium (2 mM CaCl2), however, allowed normal rapid clearance of PE to occur. We suggest that internalization, but not binding, of PE by LM cells requires extracellular calcium.

ADP Ribose Transferases

Clinical pharmacology of tolmesoxide in refractory heart failure.

The haemodynamic effects and pharmacokinetics of single intravenous doses of tolmesoxide, a new vasodilator agent, were studied in 6 patients with severe cardiac failure secondary to ischaemic cardiomyopathy and refractory to conventional therapy. The mean (+ SEM) baseline cardiac index (CI) and pulmonary artery diastolic pressure (PADP) were 1.7 +0.11/min/m2 and 30.5 +4.1 mm Hg respectively. The mean % rise in CI was 78.8 +23.3 and the mean % fall in PADP was 35.2 +5.2. The mean half life of tolmesoxide in these patients was markedly prolonged at 15.6 +6.6h. Side effects were minimal - vomiting was seen in 1 patient. This agent warrants further study in the long term management of refractory cardiac failure.

Adult

Effect of beta-blockers on exercise double product (systolic blood pressure x heart rate).

1 The effect of single oral doses of six beta-receptor antagonists on exercise-induced changes in double product (systolic blood pressure x heart rate) were studied in 25 human volunteers. 2 Three doses of propranolol, nadolol, oxprenolol, pindolol, timolol and atenolol were selected for study on the basis of in vivo beta-blocking potency. 3 Although all beta-blockers studied reduced the double product response to exercise, the pharmacodynamics of this effect differed markedly. 4 Pharmacodynamic half-lives, estimated for the drug tested, were 39 h for nadolol, atenolol 21 h, timolol 15 h, oxprenolol 13 h, propranolol 11 and pindolol 8 h. 5 These results suggest that the clinical choice of a beta-blocker with the least problems of compliance can be made on the basis of pharmacodynamics as well as pharmacological profile.

Adolescent

Selective attention in fast and slow learners.

64 children aged 8 yr. were trained on a tactile simultaneous discrimination task. Selective attention was measured in terms of percentage contact time per trial to the relevant dimension. Inter- and intra-couplings per trial were also recorded. Multivariate analyses were carried out to examine the role of component factor scores, obtained from a component curve analysis of the percentage touching time per trial, and selected cognitive variables in differentiating between the fast and slow learner groups. Percentage touching time factor scores and a memory factor were significant, but there was no significant difference between the groups in the number of couplings made. As learning progressed the number of inter- and intra-couplings decreased.

Aptitude

Analyzing infants vision: evaluating progress.

This paper is a further report outlining and analyzing the data from the first 271 infants and toddlers seen at the Infants' Vision Clinic of the Optometric Center of New York during its first two years of operation. The data investigated this paper concerns the evaluation of the progress made by those children who returned to the clinic for continuing visual care.

Child, Preschool

Pharmacokinetics of isosorbide dinitrate after intravenous infusion in human subjects.

Plasma concentrations of isosorbide dinitrate have been measured after intravenous infusion of drug at a rate of 5.0 mg h-1 for 150 min and after single equal oral doses of 12.5 mg of drug in solution to two normal human subjects. During the infusion, uneven plateau concentrations were approached after 30 min. The calculated average steady-state plasma levels were 258 ng ml-1 and 514 ng ml-1 in the two subjects respectively. The half-life of elimination of isosorbide dinitrate after termination of the infusion was 9--10 min. After oral doses, peak plasma levels of 26.6 ng ml-1 and 12.7 ng ml-1 occurred at 10 min and 20 min in the two subjects respectively. The terminal half-life of drug after the oral doses was much longer than the elimination half-life (about 10 min), and was associated with the absorption phase. Fairly good agreement was obtained between the observed concentrations and those predicted by a one-compartment open model. The systemic availability of isosorbide dinitrate after the oral doses was up to only 3 per cent of the equal doses infused, indicating that presystemic elimination processes accounted for very large proportions of the oral doses. The systemic clearances of drug after infusion of 0.32 l min-1 and 0.16 l min-1 were unexpectedly low for a drug of reported high liver extraction ratio.

Adult

Age-related reduction of baroreflex tachycardia without loss of beta-adrenoceptor-mediated tachycardia in Sprague-Dawley rats.

We examined baroreflex function and cardiac responsiveness in young (3-7 months) and old (21-24 months) Sprague-Dawley rats. Nitroprusside was more effective in lowering diastolic blood pressure (DBP) in old than in young conscious animals, but there was no such difference in anaesthetised animals. In conscious animals, the slope of the regression line for the fall in DBP produced by nitroprusside against the resultant tachycardia was significantly steeper for young animals, so that a given fall in DBP produced a greater rise in heart rate in young animals. In anaesthetised or pithed animals, the tachycardia produced by isoprenaline, noradrenaline, and single-pulse electrical stimulation did not differ between young and old animals. Hence, we have evidence that baroreflex sensitivity is reduced in aged rats, but that this is not due to a decreased responsiveness of the heart.

Aging

Baroreflex function in elderly hypertensives.

Baroreflex function was assessed in elderly hypertensive patients and compared with that observed in young hypertensives and young normotensives. Mean arterial pressure was reduced by 20% using intravenous nitroprusside infusion in 10 elderly hypertensive patients (older than 65 years and diastolic pressures over 95 mm Hg), in 10 young hypertensives (under 60 years and diastolic pressures over 95 mm Hg), and in seven young normotensive subjects (under 60 years and diastolic pressures under 95 mm Hg). Elderly subjects demonstrated greater sensitivity (p less than 0.005) and greater variability of response (p less than 0.025) to nitroprusside than either young group. There was no significant difference between the slight heart rate increases observed in the supine position in the three groups. However, in the erect position, heart rate increases were significantly less in the elderly hypertensive group than in the young hypertensive group (p less than 0.01) or the young normotensive group (p less than 0.005). Furthermore, the slope of the regression line relating change in blood pressure with change in R-R interval was less for the elderly patients than for the young hypertensives (p less than 0.05) or the young normotensives (p less than 0.025). We conclude that the heart rate component of the baroreflex is impaired in elderly hypertensives, and anticipate that the clinical response to antihypertensive drugs will be altered.

Adult