Acknowledging the forgotten priority.
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Biomedical subjects
Publications and source records attributed to D M Boyle.
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High performance hydrophobic interaction chromatography has been used to separate progestin receptors (PRs) from human uterus and from the T47D human breast cancer cell line. Reproducible separations of high resolution were achieved using a TSK Phenyl-5PW column and a reverse salt gradient of 400 mM to 0 mM sodium sulfate in phosphate buffer, pH 7.4. Peaks of radioactivity exhibiting hydrophobic behaviour were isolated, as well as a smaller proportion of specific bound receptors located in the void volume fraction. No differences in retention times were observed between uterine and breast cell line samples. When the technique was used in conjunction with rapid vertical tube sucrose density gradient centrifugation, the 8S sedimenting PR from fresh, low-salt cytosol always eluted with a retention time of 24 min. The natural 4S receptor chromatographed as a single peak at 29 min while the 4S receptor species from high-salt cytosol appeared as two distinct peaks of radioactivity with retention times of 29 and 33 min. While specific binding was shown to occur in the void volume of the column, the origin of these receptors were indeterminate. These results would suggest that under these conditions the 8S receptor occurs as a single hydrophobic class of protein, whereas the data provides evidence that transformed 4S receptor may be proportioned into two unequal entities as a function of exposure to salt.
The Sixth Biennial Survey of Staffing in Cardiology was conducted in July 1990. This report summarises the data that were collected, together with the results of a survey of facilities in cardiology made in 1989. The total number of cardiologists in the United Kingdom, defined as individuals trained in the specialty and spending at least 40% of their time working in it, is now 323. Six individuals work part time only, making 320 whole time posts. This number has increased over the two years from 1988 to 1990 by 32, of which 23 work only in the specialty and nine as general physicians with a major interest in cardiology. The rate of increase in numbers over the past decade has been reasonably consistent with an average of approximately 4.4% per year. Thirty one districts in England and Wales still have no cardiologist and 13 other districts have little provision with an average of three (visiting) sessions each per week. The population in these 44 districts is 8.3 million. Scotland also has an inadequate distribution of service in the specialty. If recommendations for cardiac surgery and angioplasty made in the Fourth Report of a Joint Cardiology Committee of the Royal College of Physicians of London and the Royal College of Surgeons of England are to be met, we calculate that we need 63 more cardiologists in our major centres. To provide one cardiologist in every district hospital and two for larger districts would require 94 more specialists, making a total shortfall of 157 individuals. We have no excess of senior registrars to provide for a major expansion at consultant level. Time spent within the senior registrar (or academic equivalent) grade has tended steadily to decline and very few now reach the end of their contracts. The need for more individuals to pass through the senior registrar grade will be met in part by a planned reduction in the training period to three years. This will be inadequate, however, because projected retirements show that the number of consultant vacancies will increase sharply from 1997. We believe that additional senior registrar posts must be created if a serious shortfall in service provision by consultants is to be avoided. The provision of non-invasive facilities in cardiology is reasonable. The need for additional equipment for invasive cardiology has not been assessed. The number of physiological measurement technicians varies considerably between regions and is generally inadequate.
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A simple combined intravenous/intramuscular regimen is described for lignocaine administration in the early vulnerable stage of myocardial infarction. Plasma levels in the therapeutic range are attained. This allows adequate drug protection during transport to hospital when an intravenous regimen may be impractical or impossible.
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A double blind trial of practolol in coronary heart disease has been conducted for 2 years. In 298 patients with acute myocardial infarction there was no reduction in overall mortality. In a group with initial heart rate over 100 per minute mortality was significantly lowered up to 1 year. Of 484 patients with coronary heart disease treatment for 2 years did not produce a significant reduction in infarction or sudden death. Beta-adrenergic blocking drugs have been shown to reduce left ventricular work and to have an antiarrhythmic action. On these grounds they would seem theoretically to have a place in the management of acute myocardial infarction. Practolol is a cardio-selective beta-blocking agent with an intrinsic sympathomimetic action, but devoid of local anaesthetic effect. It has been found effective in post infarction arrhythmias (1). In early infarction it reduces the area of necrosis as measured by surface ST segment mapping (2).
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We measured the plasma concentrations of mexiletine in patients admitted to a hospital coronary care unit after the intramuscular injection (IMI) of 200, 300, 400, and 500 mg mexiletine. Mexiletine was rapidly absorbed and concentrations greater than 0.75 microgram/ml were achieved in some patients within 5 min of the injection. The maximum mean plasma concentration increased with 200, 300, and 400 mg but was lower after 500 mg than after 400 mg. After 400 mg mexiletine, plasma concentrations greater than 0.75 microgram/ml were achieved in at least seven of nine patients from 15 min to 2 h after administration. There were no local reactions to 200, 300, or 400 mg mexiletine, but local pain and tenderness occurred in three of nine patients after 500 mg. It was decided that 400 mg mexiletine would probably be the desired dose for intramuscular administration. In 14 patients given mexiletine 400 mg by IMI followed at 2 and 12 h by 360 mg by mouth the plasma concentration was in the therapeutic range (0.75-2.0 micrograms/ml) from 15 min to 24 h in at least 64% of patients. In 12 healthy volunteers the IMI of 400 mg mexiletine increased total creatinine kinase (CK), aspartate amino-transferase, and lactate dehydrogenase enzymes but CK-MB, LDi, and LDii concentration or LDi/LDii ratio were not outside the normal range. These studies indicate that mexiletine can be safely given to patients by IMI and that therapeutic plasma concentrations are achieved.