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Biomedical subjects

D N Sharpe

Publications and source records attributed to D N Sharpe.

At least 19 recordsLinked to original sources
PubMed1991

Treatment of primary hypercholesterolaemia with simvastatin. New Zealand multicentre evaluation.

OBJECTIVE: To assess the efficacy of simvastatin in a large patient cohort. DESIGN: In an open multicentre study, after a four week placebo phase, patients were treated with simvastatin for 24 weeks; a subgroup continued therapy for a further 24 weeks. Efficacy of simvastatin (a) with prolonged use over three years, and (b) in combination with bezafibrate was assessed in an open single site study. SETTING: Lipid or cardiology specialist hospital outpatient clinics. PATIENTS: For the open multicentre study, 228 patients with primary hypercholesterolaemia (total cholesterol level greater than 6.5 mmol/L) were recruited, of whom 224 met entry criteria and completed the study. Forty-seven of these patients continued therapy for one year. In the open single site study, 22 patients (with low density lipoprotein [LDL] cholesterol levels greater than 4.3 mmol/L) participated in studies of long term use (n = 9) or of combined therapy (n = 13). INTERVENTION: Therapy in the open multicentre study began with 10 mg of simvastatin per day, doubling to 20 mg after six weeks and then 40 mg after 12 weeks of therapy if total cholesterol levels persisted above 5.2 mmol/L. In the study of long term use, simvastatin (40 mg daily) was taken continuously over three years. In the study of combination therapy, bezafibrate (600 mg daily) was taken in addition to simvastatin (40 mg daily) for 10 months. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein concentrations. RESULTS: In the multicentre study, total plasma cholesterol levels were reduced by 32.8% from 9.11 +/- 1.84 (in mmol/L, mean +/- SD) to 6.12 +/- 1.25 (P less than 0.001), and LDL cholesterol levels by 41.4% from 6.90 +/- 1.92 to 4.04 +/- 0.31 (P less than 0.001). The effect of therapy was sustained in those patients continuing therapy to 48 weeks. The study of long term use found no significant attenuation of effect over three years of monotherapy. Combined simvastatin/bezafibrate therapy reduced the LDL cholesterol concentration by a further 19.9% (P less than 0.001) from levels achieved on simvastatin alone. CONCLUSIONS: Simvastatin is an effective, well tolerated lipid lowering drug, without significant attenuation of effect with prolonged use. Simvastatin plus bezafibrate appears to be a potentially useful drug combination.

Adult↗
PubMed1990

Endocarditis in the 80s in a general hospital in Auckland, New Zealand.

The clinical and investigative features of 102 episodes of infective endocarditis were analysed retrospectively. The most frequent presenting symptoms (malaise, fever, sweats, myalgia, weight loss) were non-specific. Fever, cardiac murmur, tachycardia, vascular phenomena and a change in mental state were the most common physical signs at admission. Anaemia was present in half the episodes and renal and liver dysfunction in about one-third. Streptococci (61) and staphylococci (31) were the causative organisms in all but 10 episodes. The commonest predisposing factors were underlying cardiac disease (52 per cent) and a preceding focus of infection (14.6 per cent). Left ventricular failure (33 per cent) and focal neurological disease (29 per cent) occurred frequently. Valvular surgery was performed in 20 episodes, with two in-hospital deaths. Overall hospital mortality was 27.5 per cent and death was most commonly neurological (11/28). A higher mortality was associated with elevated total white blood count, microscopic haematuria, renal or liver dysfunction at admission, S. aureus endocarditis, the development of left ventricular failure or focal neurological disease, age greater than or equal to 60 years and persistence of fever after one week of antibiotic therapy. The absence of both renal dysfunction at admission and subsequent microscopic haematuria identified a group with a very low hospital mortality (4.7 per cent). The three-year mortality of the entire group was 43.5 per cent.

Adult↗
PubMed1989

Effect of intravenous streptokinase as compared with that of tissue plasminogen activator on left ventricular function after first myocardial infarction.

In a double-blind trial comparing two thrombolytic agents as treatment for acute myocardial infarction, we randomized 270 consecutive patients an average (+/- SD) of 2.5 +/- 0.6 hours after the onset of chest pain from a first myocardial infarction--135 to receive intravenous streptokinase (1.5 million units over 30 minutes) and 135 to receive intravenous recombinant tissue plasminogen activator (rt-PA) (100 mg over three hours). The primary end point was left ventricular function as assessed by cineangiography performed three weeks after infarction. The effects of the two agents on left ventricular function were similar. The ejection fraction was identical (58 +/- 12 percent) in both groups. The end-systolic volume was 61 +/- 29 ml in the streptokinase group and 66 +/- 31 ml in the rt-PA group (P not significant). Patency rates at three weeks for the infarct-related artery were also similar (75 percent in the streptokinase group and 76 percent in the rt-PA group). Reinfarction rates at 30 days were the same (5 percent) in both groups. One patient had a fatal intracerebral hemorrhage 13 hours after receiving rt-PA, and another had a fatal cerebellar hemorrhage 21 hours after receiving rt-PA for reinfarction nine days after treatment with streptokinase. An intention-to-treat analysis revealed that mortality at 30 days was 3.7 percent in the rt-PA group as compared with 7.4 percent in the streptokinase group (P greater than 0.2). Follow-up for a mean of 9.0 months revealed no significant difference in survival; we observed 12 deaths (8.9 percent) in the streptokinase group and 8 deaths (5.9 percent) in the rt-PA group (P = 0.34). We conclude that rt-PA and streptokinase, in the doses given, have similar effects on left ventricular function after a first myocardial infarction. Because of the small number of deaths, it is not possible to determine whether their effects on mortality are similar.

Double-Blind Method↗
PubMed1989

Effect of reducing atrial pressure on atrial natriuretic factor and vasoactive hormones in congestive heart failure secondary to ischemic and nonischemic dilated cardiomyopathy.

The effect of an acute and sustained reduction in atrial pressure on atrial natriuretic factor (ANF) and vasoactive hormone secretion was studied in 9 patients with congestive heart failure (CHF). Intravenous nitroglycerin was titrated to reduce the pulmonary artery wedge pressure by 30 to 50% and maintain this reduction for 4 hours. After 60 minutes of nitroglycerin administration, the mean decrement in wedge pressure was 10.0 +/- 1.7 (standard error) mm Hg (35%) and plasma ANF was 65.3 +/- 13.9 pmol/liter (35%). The initial decrease, sustained reduction and later increase in plasma ANF levels closely paralleled the changes in pulmonary arterial wedge (r = 0.94, p less than 0.0001) and right atrial pressures (r = 0.91, p less than 0.0001) during and immediately after the nitroglycerin infusion. Plasma aldosterone and cortisol levels increased during the first 2 hours of the nitroglycerin infusion, but there was little change in plasma norepinephrine or plasma renin activity. Although levels were elevated in CHF, plasma ANF still responded rapidly to changes in atrial pressure. A sustained reduction in pressure produced a sustained reduction in ANF levels. These findings provide further support for a regulatory role of ANF, even in chronic CHF.

Aged↗
PubMed1988

Patent foramen ovale in young stroke patients.

The prevalence of patent foramen ovale in patients presenting with non-haemorrhagic stroke or transient ischaemic attacks under the age of 40 years was determined by contrast echocardiography. Studies were performed at rest and with a Valsalva manoeuvre in 40 stroke patients and in an age and sex matched control group. Right-to-left shunting was found in 20 (50%) of the stroke patients and 6 (15%) of the controls (p less than 0.001). Paradoxical embolism through a patent foramen ovale may be an under-recognised cause of stroke in young adults.

Acute Disease↗
PubMed1986

Has the long term prognosis following myocardial infarction improved?

Coronary heart disease mortality in New Zealand has declined by 25% in the 15 years since 1968. One possible explanation for this decline is lower case-fatality rates resulting from improvements in the management of myocardial infarction. This paper tests this hypothesis by examining trends in three year survival following a definite myocardial infarction for the population aged 35-69 in Auckland. The data were obtained from two methodologically identical population-based registers of myocardial infarction compiled in Auckland in 1974 and 1981. The three year survival rates were 59% and 65% for the two time periods respectively and this difference did not reach statistical significance. However, as the survival curves appear to be diverging, there may have been a small improvement in long term outcome after myocardial infarction.

Actuarial Analysis↗
PubMed1984

Myocardial infarction and sudden death in Auckland.

A population-based register of definite myocardial infarction and sudden death was established in Auckland for the twelve months from 1 March 1981. Data were collected on 905 myocardial infarctions and 300 sudden deaths that occurred in people under the age of 70 years. The age standardised event rates were more than three times higher in men than in women. The rates of myocardial infarction were comparable in Maoris and non-Maoris but the sudden death rate was almost three times higher in Maoris than in the other ethnic groups. The age standardised 28 day myocardial infarction case fatality rates were 27% and 21% for men and women respectively. Overall, 42% of patients who reached hospital were transported by a life support unit, and 59% of patients who reached a coronary care unit did so within four hours of onset.

Adult↗
PubMed1984

Prevention of ventricular fibrillation during acute myocardial infarction by intravenous propranolol.

A trial of intravenous followed by oral propranolol, started within 4 h of onset of suspected myocardial infarction and continued over 27 h, was carried out in 735 patients; 364 received propranolol, 371 were controls. Ventricular fibrillation during the first 48 h after entry to the trial occurred in 2 treated patients and in 14 controls (p = 0.006). Rates of hospital mortality, complications other than ventricular fibrillation, and progression from threatened to completed infarction did not differ between treated and control patients. Ventricular fibrillation was not apparently prevented by prior beta-blocker treatment, which was not a reason for exclusion from the trial. This intravenous/oral propranolol regimen seems to prevent ventricular fibrillation due to evolving myocardial infarction.

Administration, Oral↗
PubMed1984

Trends in survival after myocardial infarction in New Zealand, 1974-81.

Coronary heart disease mortality in New Zealand has declined by 20% in the 13 years since 1968. One possible explanation for this decline is lower case-fatality rates resulting from improvements in the management of myocardial infarction. This paper tests this hypothesis by examining trends in 1-year survival following a definite myocardial infarction for the population aged 35-69 in Auckland. The data were obtained from two methodologically identical population-based registers of myocardial infarction compiled in 1974 and 1981 in Auckland. In both periods the 1-year crude case-fatality rate was 30% and the pattern of survival over 1 year was similar. These data suggest that factors other than the improved care of myocardial infarction patients are responsible for the decline in coronary heart disease mortality rates in New Zealand.

Adrenergic beta-Antagonists↗
PubMed1984

Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study.

A number of studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure treated with angiotensin converting-enzyme inhibitors. The long-term efficacy of the oral long-acting converting-enzyme inhibitor enalapril remains to be established in controlled studies. We evaluated this drug in 36 patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapy. After baseline assessment of symptoms, exercise capacity, and results of echocardiographic examination and right heart catheterization, patients were randomly assigned to treatment with 5 mg enalapril twice daily (n = 18) or placebo (n = 18) in a double-blind fashion. The two groups had similar clinical, echocardiographic, and hemodynamic characteristics before treatment. After 3 months of treatment, the enalapril group showed a significant improvement as judged by subjective patient impression, functional class, and exercise duration (9.3 +/- 5.7 vs 17.6 +/- 5.6 min; p less than .001). Diuretic dosage was reduced in six patients and increased in one patient, one patient had died and another had been withdrawn from the study. In the placebo group there was no significant change with respect to patient impression, functional class, or exercise duration; diuretic dosage was increased in seven patients and four patients had died. Echocardiographic left ventricular dimensions were significantly reduced and left ventricular shortening fraction significantly increased in the enalapril group but were unchanged in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗