Fifty years of medical specialisation: from foundation to fragmentation.

The past 50 years of medicine have been dominated by revolutions in biological sciences and clinical therapeutics. No less dramatic have been changes in our healthcare systems, with medical specialisation playing a leading role. The middle of the century saw the rapid development of the teaching hospital as the centre of professional education, collegiate identity, medical specialisation and clinical research. By contrast, the past 20 years have seen dramatic shifts in response to the demands of a more diverse community.

Success of a new health administration strategy. The patient-focused institute with a tripartite management.

As the result of the restructuring and decentralisation of the administration of St Vincent's Hospital, Sydney, I was Clinical Chief of a pilot "institute" for three years operating within a "patient-focused model" in hospital management. By the end of the trial, we had improved performance despite reductions in hospital and unit budgets.

Clinical representation in the development of casemix: measures and applications in Australia.

The Australian Casemix Clinical Committee coordinated the clinical evaluation of inpatient casemix classifications leading to the development of Australian national diagnosis-related groups 1, 2 and 3. It has provided and will continue to provide advice on clinical matters associated with casemix activities to the Commonwealth and State health authorities, public and private hospital associations, insurers and the clinical professions. In future, all clinicians will be expected to understand casemix, diagnosis-related groups and cost weights, especially those relevant to their speciality.

High density lipoproteins, genetic polymorphism for apo A-I and coronary artery disease.

HDL cholesterol and apolipoprotein A-I are associated with the development of coronary artery disease (CAD). The presence of a PstI site polymorphism adjacent to the gene encoding apo A-I (known as P2) has also been shown to be associated with CAD but this relationship is controversial. A case control study was conducted in an Australian population to re-examine whether the rare P2 allele is associated with CAD. Data were derived from 159 cases of angiographically confirmed CAD and 99 healthy controls. The proportion of CAD cases carrying the P2 allele did not differ significantly from controls (11% versus 9%). In a multiple logistic regression model controlling for the effects of age, country of birth, hypertension and hypotensive drugs, body mass index and lipid variables, the P2 allele failed to predict significantly the presence of CAD (odds ratio 1.83; 95% confidence interval 0.65-5.19).

Increased plasma beta-thromboglobulin in patients with coronary artery vein graft occlusion: response to low dose aspirin.

The therapeutic effect of aspirin on vein graft patency was studied in patients undergoing coronary artery bypass graft surgery. The study design enabled the prospective evaluation of the relation of platelet activation, as measured by plasma beta-thromboglobulin concentration, to subsequent coronary vein graft occlusion. Serial beta-thromboglobulin levels were measured in 105 patients randomized to receive aspirin (324 mg/day) or placebo beginning within 1 h after surgery. Graft patency was assessed angiographically at 1 week and 1 year after surgery. Of 49 patients receiving placebo, 17 (34.7%) had one or more graft occlusions, 6 early, 10 late and 1 with both early and late occlusion. Of 56 patients receiving aspirin, 7 (12.5%) had one or more occlusions, 3 early and 4 late (p less than 0.01). Preoperatively, the beta-thromboglobulin level in surgical patients (29 +/- 13.5 ng/ml) was significantly higher than that of 51 control subjects (22.6 +/- 11.1 ng/ml) (p less than 0.004). Plasma beta-thromboglobulin levels remained comparatively constant at 3 and 12 months after surgery in the 43 patients who had both samples available (p less than 0.001, r = 0.65). The reduction in beta-thromboglobulin concentration from the preoperative level to 12 months postoperatively was greater in the aspirin-treated group (p less than 0.001). Multivariate logistic regression analysis demonstrated a significant association between preoperative beta-thromboglobulin concentration and graft occlusion (p less than 0.02), and aspirin treatment was effective in preventing occlusion when adjusted for the preoperative beta-thromboglobulin level (p less than 0.005). Plasma beta-thromboglobulin concentrations are elevated in patients with coronary artery disease, suggesting ongoing platelet activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic guides in patients with idiopathic or ischemic dilated cardiomyopathy assessed for cardiac transplantation.

In an attempt to identify which parameters predict survival in advanced dilated cardiomyopathy, 232 patients presenting for assessment for cardiac transplantation were investigated and followed for 10 +/- 12 months (range 2 weeks to 5 years). Etiology of dilated cardiomyopathy included ischemic heart disease (33%), idiopathic (42%) and miscellaneous (25%). In each patient, 26 parameters were recorded. Whole group survival was 68% at 1 year, 56% at 2 years, 41% at 3 years and 25% at 4 years. On Cox multivariate regression analysis, 3 parameters predicted survival: New York Heart Association symptom class (p less than 0.0001), pulmonary capillary wedge pressure (p less than 0.008) and plasma atrial natriuretic factor level (p less than 0.002). On paired testing of actuarial survival curves, plasma noradrenaline also held predictive value (p less than 0.002), as did left ventricular ejection fraction less than or equal to 20% on radionuclide ventriculography (p = 0.007) and presence of greater than or equal to 4 beats of ventricular tachycardia on Holter monitoring (p = 0.007). Treatment with amiodarone did not appear to influence survival. Conventional determinants of prognosis in cardiomyopathy (symptom class, wedge pressure, nonsustained ventricular tachycardia and ejection fraction) do not alone always adequately differentiate survival in this group of high risk patients. More attention to plasma noradrenaline and to atrial natriuretic factor levels may give important additional information in the context of assessment of patients for transplantation.

Reproducibility of radionuclide left ventricular ejection fraction in patients awaiting cardiac transplantation.

Radionuclide-derived left ventricular ejection fraction (LVEF) is used to assess LV systolic function, to follow trends in the natural history of dilated cardiomyopathy, and to prioritize patients waiting for cardiac transplantation. Reproducibility of LVEF at extremely low levels has not, however, been reported. To assess the reproducibility of radionuclide LVEF at levels below 0.30 EF U, 17 highly symptomatic patients (NYHA Class III/IV) with dilated cardiomyopathy were studied on two occasions, 72 hours apart. Sequential scans were analyzed by two independent observers. Mean LVEF was 0.18 +/- 0.06 U (scan 1) and 0.17 +/- 0.06 U (scan 2). Interoperator reproducibility (SD) was 0.03 U (R = 0.76), interscan reproducibility (SD) was 0.03 U (R = 0.62), and overall reproducibility (SD) was 0.04 U (R = 0.50). The interobserver variation of 0.03 (actually 0.027) was just over one half that seen in normal volunteers (variation 0.05, n = 29) studied previously in this department. A change of greater than or equal to 0.08 U (2SD) in either direction is highly likely to represent a real change in LV function in those with LVEF less than or equal to 0.30 units, compared with the change of at least 0.10 units required in those with normal LV function. Lower interobserver and interscan reproducibility should be taken into account when interpreting sequential scans in patients with severe LV dysfunction.

The effects of adrenergic blockade on lipoproteins using the rat as an experimental model.

Adrenergic blocking drugs are known to have adverse effects on lipids and lipoproteins in man, although the mechanisms underlying these effects are unclear. In order to see whether the rat might be a suitable model to explore this issue, adrenergic blockers having differing properties with respect to receptor interaction were administered to rats orally over seven days, followed by measurement of plasma lipids and lipoproteins. Total plasma cholesterol was not significantly influenced by any of the drugs used, while triglycerides were reduced by 20% and 31% respectively with pindolol and prazosin. With respect to changes in HDL cholesterol, it was found that: (a) HDL cholesterol was significantly reduced by 8% during combined beta 1, beta 2 blockade with propranolol; (b) HDL cholesterol was not significantly changed during selective beta 1 blockade using atenolol, or during combined beta 1, beta 2 blockade and partial beta 2 stimulation using pindolol; and (c) HDL cholesterol was significantly increased during combined beta 1 blockade and beta 2 stimulation using celiprolol by 12%, or during alpha 1 blockade with prazosin by 8%. It appears that beta 2 receptor exposure or stimulation may be one of the key points in the interaction between adrenergic blockade and lipoprotein metabolism.

Timing of cardiac transplantation in idiopathic dilated cardiomyopathy.

Seventy-nine patients with idiopathic dilated cardiomyopathy were assessed and followed up to evaluate 9 variables that might predict duration of survival after assessment for cardiac transplantation. Patients with ischemic heart disease, alcoholic and peripartum cardiomyopathy were excluded. There were 38 deaths (48%) during the 18-month (mean) follow-up. Patients underwent determination of left ventricular ejection fraction by radionuclide scan, echocardiography, cardiac catheterization and myocardial biopsy. Only left ventricular ejection fraction determined by radionuclide study correlated significantly with time to death in nonsurvivors (r = 0.38, p less than 0.05). Multivariant analysis and Cox multivariate regression analysis revealed that the single consistent determinant of prognosis was radionuclide-determined ejection fraction. It was an excellent predictor of survival to 3 months (p less than 0.0001) and a reasonable predictor of survival to 6 months (p less than 0.05). There was no variable that efficiently predicted survival for any period greater than 6 months. In 15 of 70 patients (21% of the entire group), clinical status and radionuclide ejection fraction improved after assessment but only one of these had an ejection fraction less than or equal to 0.10. No patient with a radionuclide ejection fraction greater than or equal to 0.20 died within 6 months of assessment. For those with ejection fraction between 0.11 and 0.19, survival after cardiac transplantation exceeded that of the natural history of their disease; this suggests that transplantation should be undertaken within 6 to 12 months of assessment. Left ventricular ejection fraction less than or equal to 0.10 predicts an extremely poor prognosis (6-month survival was 17%) and such patients should be transplanted with minimal delay.

Risk of infective endocarditis in mitral valve prolapse with and without precordial systolic murmurs.

The risk of infective endocarditis (IE) associated with a systolic murmur in patients with mitral valve prolapse (MVP) was investigated in a case-control study. The case group comprised all patients with MVP (n = 19) from a series of 136 consecutive adult admissions for IE. Three matched control subjects were chosen for each case from a series of 144 MVP patients without IE. Seventeen of the 19 cases (89%) had documented evidence of systolic murmurs existing before the IE episode; systolic murmurs were documented in 25 of the 57 control subjects (47%). The data indicate a significant increase in the risk of IE in MVP patients with a systolic murmur (p less than 0.01). The absolute probability of IE developing in a patient with MVP and a murmur was estimated to be approximately 1 in 1,400 per year; this was 35 times greater than the probability in a patient with MVP without a murmur. The results suggest that by restricting prophylaxis to MVP patients with a systolic murmur, cover would be provided for almost 90% of those with MVP in whom IE would be likely to develop.

Coronary artery bypass graft failure--an autoimmune phenomenon?

Plasma anticardiolipin antibody (ACA) was measured in 83 patients having coronary artery bypass graft surgery and results were correlated with the incidence of early (1-2 weeks) and late (12 months) graft occlusion, as judged by angiography. There was an association between preoperative ACA level and the incidence of late graft occlusion in relation to both number of patients with an occlusion and number of distal anastomoses occluded. 8 of 15 patients (53.3%) whose maximum ACA level exceeded 4 SD of the mean of controls had a late graft occlusion. When the ACA titre was 2-4, 0-2, or less than 0 SD above the mean of the controls, the occlusion rates were 3 of 13 (23.1%), 3 of 33 (9.1%), and 1 of 15 (6.7%), respectively (p less than 0.03). The incidence of a postoperative rise in ACA level was higher in patients who had had a myocardial infarction in the past than in those with a history of angina only (chi 2 = 4.08, p less than 0.05). This observation supports the notion that one mechanism of ACA production is an immune response to myocardial injury. These results raise the further possibility that the ACA, or related antiphospholipid antibodies, may play a part in progressive coronary vessel disease.

The prevalence of arrhythmias in hypertrophic cardiomyopathy: role of ambulatory monitoring and signal-averaged electrocardiography.

Hypertrophic cardiomyopathy (HCM) is associated with a high incidence of supraventricular and ventricular arrhythmias. The presence of ventricular tachycardia (VT) in patients with HCM has been associated with a high risk of sudden death. Forty-seven patients with HCM (31 male, 16 female, mean age 47 years) underwent continuous 24-hour ambulatory electrocardiographic (ECG) monitoring. High grade ventricular arrhythmias (modified Lown class 3, 4a, 4b) were found in 20 patients (43%) with VT in 11 (24%). In each case the arrhythmia was asymptomatic. Supraventricular arrhythmias were detected in 16 patients (34%). Signal-averaged electrocardiography in 27 patients showed late potentials in three of 11 patients with repetitive ventricular arrhythmias and was negative in 15 of 16 patients without these arrhythmias. In conclusion, asymptomatic high grade ventricular and supraventricular arrhythmias are common in HCM and are readily detected with continuous electrocardiographic monitoring. Signal-averaged ECG has low sensitivity for the detection of subclinical VT in patients with HCM.

Patient selection for cardiac transplantation.

Since February 1984, 27 isotopic cardiac transplants have been performed in 25 patients. These 25 patients were from a pool of 45 patients who were accepted into the Programme. Sixteen patients have died awaiting a transplant, and four patients are presently on the waiting list. All patients accepted for cardiac transplantation were NYHA Class IV. There were 136 referrals during this period for cardiac transplantation, and 14 referrals for heart-lung transplantation. The commonest reason for non-acceptance into the Programme is that patients were considered not to be ill enough and to have a prognosis of more than six months. Patient selection is a key factor in ensuring a successful outcome with cardiac transplantation.

Reduction in plasma cholesterol and increase in biliary cholesterol by a diet rich in n-3 fatty acids in the rat.

Cholesterol and lipoprotein metabolism were investigated in a group of rats fed a fish oil-supplemented diet, a rich source of n-3 fatty acids. For comparison purposes, other groups of rats were fed either safflower oil (n-6 fatty acids) or coconut oil (saturated fatty acids). Diets were isocaloric and contained identical amounts of cholesterol. Rats fed fish oils for 2 weeks showed a 35% lower plasma cholesterol level than rats fed safflower oil, who in turn showed a 14% lower plasma cholesterol level than those fed coconut oil. The fall in plasma cholesterol level with fish oils was associated with significant falls in low density and high density lipoprotein cholesterol levels, but with no significant change in the ratio of low density to high density lipoprotein cholesterol. The fatty acid compositions of plasma, hepatic, and biliary lipids showed relative enrichment with n-3 fatty acids, reflecting the composition of the diet. The fish oil diet increased the basal secretion rate of cholesterol into bile, but the bile acid secretion rate remained unchanged. It is suggested that n-3 fatty acids reduce the plasma cholesterol level in rats by increasing the transfer of cholesterol into bile.

On the effects of dietary n-3 fatty acids (Maxepa) on plasma lipids and lipoproteins in patients with hyperlipidaemia.

An encapsulated preparation of fish oil (Maxepa) was administered to hyperlipidaemic patients in order to establish the responsiveness of the common lipid phenotypes to dietary supplementation with n-3 fatty acids. 13 patients took 6 g/day of fish oil and 12 patients took 16 g/day in a randomized, double-blind crossover study, whereby each subject took fish oil for 3 months and matching placebo for 3 months. The study was conducted against a background diet restricted in saturated fat and cholesterol. In Types IIa and IIb hyperlipoproteinaemia there was no substantial fall in plasma cholesterol concentration. Plasma triglyceride concentrations were reduced significantly in Types IIb and IV (28% and 41% respective reductions). In a separate study using 16 g/day of fish oil in patients with Type V hyperlipoproteinaemia, plasma triglycerides were reduced by 58% and plasma cholesterol concentration by 34%. The change in plasma triglyceride concentration was significantly correlated with the basal triglyceride level (r = -0.94), and was dose-related (33% fall on 6 g/day and 58% fall on 16 g/day). The fall in plasma triglyceride concentration was accompanied by a significant reduction in the concentration of very low-density lipoprotein cholesterol (-42%), a significant rise in low density lipoprotein cholesterol (+7%), and a significant rise in high-density lipoprotein cholesterol concentration (+6%), there being no significant change in the ratio of low density to high density lipoprotein cholesterol. There were changes in the fatty acid composition of plasma and platelet lipids which reflected dietary supplementation with n-3 fatty acids, notably an increase in the proportion of eicosapentaenoic and docosahexaenoic acids which occurred in a dose-dependent fashion. Despite these changes there was no significant variation in the bleeding time, platelet count or blood viscosity during the treatment.

Diagnosis and management of acute myocarditis aided by serial myocardial biopsy.

Two cases in which right ventricular endomyocardial biopsy established a definitive pathologic diagnosis of acute myocarditis are presented. Both patients presented with severe left ventricular dysfunction, atrial flutter and an intraventricular conduction defect. Immunofluorescent and immunoperoxidase examination of the biopsy specimens suggested a humoral immune mechanism in one case and a cell-mediated immune mechanism in the other. Substantial improvement in cardiac function followed treatment with prednisolone and azathioprine in both cases. Significant regression of the myocardial inflammatory changes was documented by a further endomyocardial biopsy in each case following clinical improvement.