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Biomedical subjects

D N Sharpe

Publications and source records attributed to D N Sharpe.

46 records · Page 3Linked to original sources

The noninvasive diagnosis of right ventricular infarction.

We evaluated scintigraphy and echocardiography for the diagnosis of right ventricular (RV) infarction. Of 26 patients with acute transmural myocardial infarction (MI), six with inferior MI had abnormal radionuclide uptake localized to the RV free wall on infarct scintigraphy or segmental akinesis of the RV free wall on gated radioangiography or both. These six patients with RV involvement (group I) were compared with the remaining nine with inferior MI (group II) and 11 with anterior MI (group III). RV/LV area ratios determined radioangiographically were significantly greater in group I than group II in diastole and systole. Echocardiographic RV enddiastolic dimension and RV/LV end-diastolic dimension ratio were significantly greater and RV stroke work index was significantly lower in group I than in group II. Predominant RV involvement in inferior MI may occur commonly. Anatomic and functional evidence of this diagnosis can be obtained noninvasively.

Echocardiography↗

The specificity of pyrophosphate myocardial scintigrams in patients with prior myocardial infarction: concise communication.

Fifty-five patients with old (9 days to 10 yr) transmural infarcts but with no evidence of recent infarction, were imaged with Tc-99m pyrophosphate. Discrete uptake was rare in the setting of an old infarct. Diffuse uptake was neither sensitive to, nor specific for, acute infarction. Prior infarction will rarely cause diagnostic error if the discrete pattern is required for a positive diagnosis.

Acute Disease↗

Percutaneous cardiac puncture in domestic pigs.

Blood sampling by percutaneous cardiac puncture was carried out in 69 domestic pigs. The procedure was shown to be safe and to produce reproducible data. The technique can be carried out without anaesthesia. Repeated sampling is possible over minutes, hours or days, and a wide range of sample volumes can be achieved by this technique.

Animals↗

Torulopsis glabrata endocarditis complicating aortic homograft valve treated with 5-fluorocytosine: case report with discussion of antifungal chemotherapy.

A case of Torulopsis glabrata endocarditis occurring in a patient 14 months after aortic homograft valve replacement is reported. The infection was not controlled by amphotericin B which led to progressive renal impairment. Re-operation was delayed by the development of multiple infarctions due to coronary emboli. The infection was subsequently eradicated by oral treatment with the newer antifungal agent, 5-fluorocytosine, but death of the patient eventually occurred from an arrhythmia related to the persisting myocardial failure consequent upon episodes of transmural infarction. Current evidence favours the use of early re-operation in all cases of endocarditis in addition to aggressive chemotherapy with a combined regime of amphotericin B and 5-fluorocytosine. Clinical pharmacology of 5-fluorocytosine is briefly discussed.

Amphotericin B↗

Treatment with digoxin and measurement of serum digoxin levels after myocardial infarction.

Forty-nine patients admitted to a Coronary Care Unit with myocardial infarction complicated by left ventricular failure, were treated with 1.75 mg Lanoxin over 36 hours. Serum digoxin levels were measured by radioimmunoassay at 8, 24, and 48 hours. No difference in serum levels was observed between those patients who received 'old' (reduced bioavailability) and those who received 'new' Lanoxin. Serum levels were significantly higher at 8 and 24 hours in those patients who received their first dose intramuscularly compared with those who received their first dose orally, irrespective of the bioavailability of the oral preparation used. No correlation was observed between serum digoxin levels and serum urea or creatinine during the 48-hour period of study. The incidence of arrhythmias is reported, but no conclusion can be drawn as to whether or not the glycoside contributed to this in any way. The use of digoxin in patients with acute myocardial infarction complicated by left ventricular failure is justifiable in the light of available evidence. However, in view of the possible predisposition of such patients to toxicity, lower serum levels than were achieved in many of our patients seem desirable and a modified dosage schedule is suggested.

Administration, Oral↗

Adverse effects associated with the newer inotropic agents.

The ideal inotropic agent should be available for both parenteral and oral administration and be potent and effective long term without significant adverse effects. In recent years, numerous new agents have been developed in an attempt to find a more potent, less toxic alternative to digoxin. beta-Agonists, while useful when given parenterally short term, appear to have their long term oral application limited by adverse effects and the development of tolerance. A number of other non-catecholamine agents, most of which have both inotropic and vasodilator actions, have also been studied. Adverse effects have been relatively frequent and occasionally severe. Of these newer agents none has yet been proven in clinical trials to be safe and effective in the long term.

Adrenergic beta-Agonists↗

The plasma and tissue turnover and distribution of two radio-iodine-labelled pig plasma low density lipoproteins.

Two classes of pig plasma low density lipoprotein (LDL1 and LDL2) with different densities and molecular sizes were isolated by zonal ultracentrifugation and were further purified by flotation. The peptide component was iodinated with 125I, and the labelled lipoprotein was injected intravenously. 125I-LDL1 turnover studies were performed on 22 3-4 month old female Large White pigs, and 125I-LDL2 turnover studies on 4 similar pigs. A biological screening experiment confirmed that the shape of the plasma activity curve was not a function of protein denaturation. The pattern of radioactivity decline in plasma was not affected by the degree of LDL iodination. 125I-LDL1 turnover: The curve of plasma radioactivity plotted against time over the first 5 days after injection could be resolved into two exponentials. The plasma biological half-life (T 1/2) was calculated from the slower exponential predominant from the second day. The mean T 1/2 over 2-5 days was 22.9 hr (range 17.2-28.5 hr). Multicompartmental analysis of the plasma decay curve using an open mammillary model gave a mean fractional catabolic rate per day for LDL1 of 1.4 (range 0.9-1.9). The mean T 1/2 was 0.26-0.31 times and the fractional catabolic rate 3.0-3.9 times those values found in two studies on adult humans. The tissue distribution of 125I was analysed in a series of 20 animals killed from 1.0 to 33.8 days after 125I-LDL1 injection. Most tissue 125I (86-89%) was protein bound. An appropriate correction was made to the 125I counts for retained plasma in liver and spleen (using 131I-albumin); retained plasma in other tissues was negligible. Highest 125I tissue levels were found in the liver, supporting other evidence that the liver may be the major site of LDL1 catabolism. After 2.06 and 4.06 days the livers in two animals contained 1.6% and 0.7% respectively of the total injected 125I, equal to 33% and 54% of the total plasma 125I at those times. The skin contained about one-third to one-ninth the 125I in the liver at various times. Distribution in other organs was quantitatively minimal. Higher levels of radioactivity were found in the intima and inner media of the aorta than in the outer media. These results suggest that plasma LDL in the pig diffuses through the endothelial surface into the arterial wall. These findings are confirmed by autoradiography. 125I-LDL2 turnover: Parallel studies of plasma 125I-LDL2 turnover and tissue distribution were performed. The plasma biological decay curve was multi-exponential, suggesting that LDL2 metabolism is complex, and possibly more rapid than that of LDL1 (LDL2 is smaller and denser than LDL1). The tissue distribution of 125I-LDL2 in these pigs was very similar to that of 125I-LDL1. As LDL1 and LDL2 differ in the amount of lipid they contain, they may have different roles to play in lipid transport, and there may be interconversion of one into the other at different sites. This hypothesis remains conjectural.

Animals↗

The heart of the matter.

Coronary heart disease deaths have declined in New Zealand, as in other Western countries, during the past two decades. This is probably due to a combination of population lifestyle changes and improved treatment of the disease. However, the social class gradient for coronary disease has reversed and it is now more common in lower socio-economic groups who are increasingly disadvantaged in our community. Socioeconomic factors are powerful, primary determinants not only of coronary disease but also of many of the other health problems outlined in the New Zealand Health Charter. Policy making and health services delivery shape societal conditions essential for true health. These factors are considered in relation to the spectrum of human communication and the current transitional changes in our health system.

Arteriosclerosis↗

Nitroglycerin in a transdermal therapeutic system in chronic heart failure.

Nitroglycerin (NTG) in a transdermal therapeutic system (TTS) was evaluated in 16 patients with severe chronic heart failure. Eight patients were given NTG TTS with an in vivo release rate of 5 mg/24 h. No significant changes in heart rate or blood pressure were observed. Pulmonary capillary wedge (PCW) pressure was reduced significantly from a control value of 29 +/- 4 mm Hg to 17 +/- 2 mm Hg after 1 h (p less than 0.01), and significant reduction was maintained for 24 h. The system was then removed and PCW pressure rose to 27 +/- 2 mm Hg after 2 h. NTG TTS, 10 mg/24 h, was applied and PCW pressure was again reduced significantly. Significant reduction in systemic vascular resistance and increases in cardiac and stroke volume indices occurred on the first day at 4 h but were not maintained. In another eight patients, the haemodynamic effects of NTG TTS (5 mg/24 h), oral isosorbide dinitrate (20 mg), and topical NTG ointment (1 inch) were compared. Significant reductions in PCW pressure were achieved with each method of treatment, but no significant alterations in other haemodynamic measurements were observed. Haemodynamic reevaluation of 10 patients treated with NTG TTS for 3 months showed partial attenuation of the reduction in PCW pressure compared with the initial response.

Administration, Topical↗