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Biomedical subjects

R Donaldson

Publications and source records attributed to R Donaldson.

At least 19 recordsLinked to original sources
PubMed1997

Increased frequency of P-glycoprotein gene amplification in colchicine-resistant Rat-1 clones transformed by v-src.

A rat fibroblast cell line (Rat-1) carrying a temperature-sensitive mutation of v-src was used to determine whether inducible cellular transformation altered the ability of cells to amplify the p-glycoprotein gene in response to colchicine selection. Transformed and nontransformed Rat-1 fibroblasts selected under 4 times the LD50 generated the same number of colchicine-resistant colonies. We next examined colchicine-resistant colonies derived from transformed cells and compared them to colchicine-resistant colonies derived from nontransformed cells. When Rat-1 cells were selected at 35 degrees C (transforming temperature), 7 out of 7 clones exhibited a 3- to 5-fold p-glycoprotein gene amplification. These results contrasted to those found at the nontransforming temperature (40 degrees C); none of the 8 colchicine-resistant clones examined had amplified the p-glycoprotein gene. Thus in Rat-1 cells carrying a temperature-sensitive v-src gene, p-glycoprotein gene amplification was observed at a high frequency only in transformed clones selected at the temperature permissive for v-src activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Influence of angiotensin converting enzyme inhibition on exercise performance and clinical symptoms in chronic heart failure: a multicentre, double-blind, placebo-controlled trial.

One hundred and seven patients with chronic heart failure (NYHA class II to IV) stabilized on digitalis and/or diuretics, recruited from 11 centres were randomized into a double-blind, placebo-controlled study to assess the effect of 12 weeks of cilazapril therapy on exercise tolerance and clinical status. Thirty-five patients were randomized to placebo and 72 to cilazapril at a starting dose of 1 mg daily; titration to cilazapril 2.5 mg at week 4 and 5 mg at week 8 (or matching placebo) was carried out in patients who did not improve clinically. Demographic characteristics, including exercise test duration increased from 402 s (+/- 17 SEM) at baseline to 462 s (+/- 19 SEM) at week 12 for the cilazapril group (+15%) and from 405 s (+/- 23 SEM) at baseline to 408 s (+/- 30 SEM) at week 12 in patients on placebo (+1%) (P < 0.001). In the placebo group, patients able to exercise for more than 6 min at baseline showed an increase in exercise duration at week 12 while those able to exercise for up to 6 min at baseline showed a decrease (P = ns). In contrast, cilazapril-treated patients showed an increase in exercise tolerance regardless of baseline exercise test duration; patients with the most impaired exercise tolerance at baseline showed a greater improvement than patients with mildly impaired baseline exercise tolerance (P < 0.05 vs placebo). NYHA class improved by at least one grade in 51% of the cilazapril group vs 32% in the placebo group (P = ns). At the end of the trial, 15% of the patients were non-responders on cilazapril vs 41% on placebo (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Making your own videotapes for patient instruction.

Producing your own videotapes can be both fun and clinically helpful. They are extremely effective for patient instruction and for obtaining informed consent. This article discusses the production, presentation, and effective use of videotapes in office practice.

Humans↗
PubMed1986

Use of monophasic action potential recordings during routine coronary-artery bypass surgery as an index of localised myocardial ischaemia.

In 8 patients undergoing routine coronary-artery bypass surgery, monophasic action potentials (MAPs) were measured by means of a hand-held pressure contact electrode to provide an index of local ischaemic changes. 4 patients received left internal mammary anastomoses (LIMA), and there were a total of 27 saphenous vein grafts (SVG). After completion of all grafts blood-flow to the myocardium was reduced for 90 s by means of different permutations of SVG and LIMA occlusion, either on or off bypass. In all patients MAPs indicated typical ischaemic changes. The high sensitivity of the method enables the study to be completed quickly and without hazard to the patient. The technique provides a new means to assess local ischaemia, the viability of specific areas of myocardium, and the efficiency of individual grafts during surgery.

Action Potentials↗
PubMed1986

The diagnosis of aortic root abscess by cross-sectional echocardiography.

Aortic root abscess is frequently a lethal complication of infective endocarditis. Early diagnosis of this complication is of paramount importance because antibiotic therapy is often ineffective and early surgery is probably the treatment of choice. We have compared the diagnostic accuracy of cross-sectional echocardiography with operative findings in the diagnosis of aortic root abscess. Aortic root abscess was diagnosed in nine of 129 patients with infective endocarditis at the National Heart Hospital between 1983 and 1985. Cross-sectional echocardiography demonstrated the presence and location of the aortic root abscess in eight cases; in the ninth case a small abscess was missed. In two other cases, a large abscess was visualised, but abscesses of between 2 mm and 4 mm were missed; the extent and size of large aortic abscesses tended to be underestimated. Echocardiography should be an integral part of the investigation of patients with aortic valve infective endocarditis.

Abscess↗
PubMed1985

d-Sotalol: a new potent class III anti-arrhythmic agent.

We have compared the effect of a new drug d-sotalol which has minimal beta-blocking action with the parent (beta-blocking) compound dl-sotalol on monophasic action potential (MAP) duration in open-chested dogs. In seven experiments d-sotalol was administered in intravenous bolus doses of 1.5, 3 and 6 mg/kg given at 10 min intervals. In a further seven experiments dl-sotalol was administered using the same dosage regimen. The animals were anaesthetized with chloralose and urethane. Atrioventricular block was created by injection of the bundle of His with 0.1 ml of 40% formalin in order to ensure capture by ventricular pacing. After prior beta-blockade with propranolol (0.25 mg/kg), simultaneous epicardial and endocardial MAP were recorded at paced heart rates of 100 and 150 beats/min after each bolus injection. d-Sotalol and dl-sotalol showed similar prolongation of MAP duration (measured at 90% repolarization) in both endocardial and epicardial recording at both paced heart rates. These results show that the dextro-isomer of sotalol possesses similar class III action to the parent compound and that this action is homogeneous with respect to left ventricular endocardium and epicardium at heart rates of 100 beats/min and 150 beats/min over a wide dose range. d-Sotalol may be a useful anti-arrhythmic agent in man.

Action Potentials↗
PubMed1985

Prevalence and clinical significance of aortic valve prolapse.

The prevalence and clinical significance of aortic valve prolapse were determined prospectively in 2000 consecutive patients undergoing routine clinical cross sectional echocardiography. Two hundred and twelve patients were excluded because the aortic cusps were not adequately visualised. Aortic valve prolapse was defined as downward displacement of cuspal material below a line joining the points of attachment of the aortic valve leaflets. Twenty four cases of aortic valve prolapse (1.2%) were identified. The patients were aged 12-64 years and nine were women. All had underlying valvar heart disease and the commonest lesion (in 11 cases) was prolapse of the larger cusp in bicuspid valves. Aortic valve prolapse was seen in four patients with mitral valve prolapse (two with severe regurgitation), one of whom had marfanoid aortic root dilatation. The remaining examples of aortic prolapse were seen in patients with various disorders including one with pulmonary atresia, two with aortic root disease (one with dissection and one with idiopathic dilatation), and one case of severe mitral regurgitation. Valves destroyed by infective endocarditis were seen in two cases. Aortic valve prolapse may be detected in various cardiac disorders and does not imply the presence of aortic regurgitation, but when bicuspid aortic valves are present it may well be important in producing such regurgitation. Although aortic valve prolapse may be associated with severe forms of mitral valve prolapse, these patients rarely have aortic regurgitation.

Adolescent↗
PubMed1984

Class III action of beta-blocking agents.

We have studied the effect of the intravenous administration of the following drugs on ventricular refractoriness in 35 experiments in open chested beagle dogs: atenolol 0.2 mg X kg-1; nadolol 0.05 mg X kg-1; oxprenolol 0.2 mg X kg-1; pindolol 0.04 mg X kg-1; propranolol 0.2 mg X kg-1; sotalol 0.6 mg X kg-1 and timolol 0.1 mg X kg-1. The animals were anaesthetised with chloralose and urethane. Measurements were made of left ventricular epicardial monophasic action potentials (MAP) (n = 35) and the left ventricular paced evoked response (PER) (n = 25) at a fixed paced cycle length of between 220 and 310 ms. The animals were initially beta-blocked with iv pindolol or propranolol and the drug under study then administered iv 10 min later. The results were as follows: (control and post drug administration) MAP: nadolol 151 +/- 12 SD to 172 +/- 13 SD (p less than 0.001); oxprenolol 153 +/- 21 to 178 +/- 20 (p less than 0.001); sotalol 153 +/- 19 to 176 +/- 20 (p less than 0.001); atenolol 152 +/- 25 to 153 +/- 23 (NS); pindolol 149 +/- 11 to 152 +/- 10 (NS); propranolol 152 +/- 26 to 155 +/- 26 (NS); timolol 144 +/- 23 to 144 +/- 21 (NS). PER: nadolol 172 +/- 14 to 190 +/- 20 (p less than 0.001); oxprenolol 164 +/- 16 to 188 +/- 15 (p less than 0.001); propranolol 166 +/- 22 to 173 +/- 18 (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1980

Exercise testing after beta-blockade: improved specificity and predictive value in detecting coronary heart disease.

The value of exercise testing in detecting myocardial ischaemia resulting from coronary atheroma remains controversial. In order to increase the reliability of exercise testing, all its components (asymptomatic, haemodynamic, and electrocardiographic) have been scrutinised. In this study, concerned only with the electrocardiographic response to exercise, the incorporation of beta-blockade into the standard exercise procedure has improved specificity and predictive value without affecting sensitivity. Fifty patients with anginal pain and 50 asymptomatic subjects with an abnormal electrocardiogram were investigated by exercise testing before and after beta-blockade (oxprenolol). All subjects had coronary arteriograms and left ventriculograms, and the results of exercise testing were related to the presence or absence of obstructive coronary artery disease. Possible causes of false positive exercise tests were eliminated by echocardiography. Though beta-blockade was unreliable in distinguishing ischaemic from non-ischaemic resting electrocardiograms, it eliminated all the false positive electrocardiographic responses to exercise in both groups and did not abolish any of the true positive electrocardiographic responses. Thus, specificity and predictive value were improved without reduction in sensitivity. This technique may not necessarily be applicable to other groups of patients or to a random population, but the results of this study suggest it will be a useful additional routine procedure in the investigation of coronary heart disease.

Adolescent↗