Defibrillators on Qantas aircraft.
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Aircraft↗
Biomedical subjects
M O'Rourke
Publications and source records attributed to M O'Rourke.
Hearing loss in adults with learning disabilities.
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Adult↗
Distal coronary-artery constriction in angina pectoris.
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Angina Pectoris↗
High-dose 24-hour infusion of 5-fluorouracil in metastatic prostate cancer. A phase II trial of the Piedmont Oncology Association.
Thirty-two patients with metastatic carcinoma of the prostate refractory to endocrine therapy were entered on trial. No patient entered in the study had prior chemotherapy. Patients were treated with 5-fluorouracil given at a dosage of 4 gm/m2 over a 24-hour period every 2 weeks. Of the 27 patients evaluable for response, there were no complete or partial remissions, but 9 (33%) had a stable disease. The 95% confidence interval for complete and partial response in this series (0 of 27 patients) is 0.0-12%. Myelosuppression and gastrointestinal toxicity was moderate. Two patients, however, experienced major but completely reversible neurotoxicity, including 1 with cerebellar ataxia and 1 with memory loss and stroke-like symptoms. These data indicate that high-dose fluorouracil used in this dosage and schedule is ineffective in the therapy of advanced carcinoma of the prostate.
Adenocarcinoma↗
Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and Chinese communities.
A comparative morphologic study of aortic changes with aging was conducted in different populations in an attempt to separate the effects of hypertension and atherosclerosis. Chinese and the occidental populations were chosen, as they are known to have a high prevalence of hypertension and atherosclerosis, respectively. Aortic tissue was collected from occidental (American and Australian) and Chinese populations from three geographic locations. Postmortem specimens were obtained from four fixed locations: ascending aorta (A), descending thoracic aorta (B), and abdominal aorta (suprarenal [C] and above the aortic bifurcation [D]). Histologic sections were used to measure aortic circumference, medial thickness, intimal thickness, and grade of atherosclerosis. Kidney sections were used to confirm the presence or absence of hypertension. A total of 302 cases (age range, 19 to 104 years; Male-to-female ration, 2:1) were studied: 112 Americans, 80 Australians, and 110 Chinese. Cases were divided into three age groups: 19 to 44; 45 to 64; and 65 years and older. The aortic circumference progressively decreased from sites A to D in all populations and age groups. The aortic circumference increased with age, and the increase was independent of the aortic location. When the populations were separated, however, the greater increase was at location A in the Chinese (P = .008) and locations D in the occidental (P = .13), a population contrast that was significant only in location A. Intimal thickness increased with advancing age and was maximal in the abdominal aorta. The population differences also were significant for intimal thickness and were significantly greater in the occidental population in B, C, and D locations, whereas for atherosclerosis significance was only seen in location D. Hypertension (as defined by the morphologic changes in the kidney) after adjusting for age, height, and weight resulted in no statistical significant effect on aortic circumference or on intimal thickness, but did show a significant increase in atherosclerosis score at locations B, C, and D. Also after adjusting for age, height, and weight, the Chinese had a significantly larger aortic circumference in location A compared with the occidental population, whereas in location D the occidentals with hypertension had a significantly larger circumference compared with Chinese, probably due to an interaction of atherosclerosis and hypertension. After similar adjustments, the medial thickness in locations A and C, the intimal thickness in B, C, and D, and atherosclerosis score in D were significantly greater in occidental than Chinese populations.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Arterial compliance and wave reflection.
Left ventricular "afterload" is the wall stress developed during systole by the ejecting ventricle. For any given ventricular conformation, this is given by the time course of pressure change in the left ventricle during ejection, and is approximated by the pressure measured in the ascending aorta. For a given flow ejection from the left ventricle, pressure generated in the ascending aorta is determined by the ascending aortic impedance. Impedance in turn is dependent on three properties of the systemic circulation--resistance, compliance and wave reflection. In conventional studies of left ventricular load and hypertension, attention is usually focussed entirely on peripheral resistance. Recent studies have shown a poor relationship between left ventricular mass and peripheral resistance, but a better relationship with compliance and indices of wave reflection. Hence compliance (or its inverse, aortic stiffness) and wave reflection must be considered in evaluating hypertension (especially "systolic hypertension") and the effects of drugs on ventricular load. Under ideal circumstances, as seen in youth, aortic compliance is high and wave reflection late, with the consequence that aortic systolic pressure is low and pressure is boosted throughout early diastole. With progressive aortic degeneration as seen with aging and in hypertension, systolic pressure in increased both directly by decreased compliance, and indirectly by early return of wave reflection. The effect of early wave reflection is not apparent from recordings of brachial systolic or diastolic pressure, but can be inferred from indirectly recorded carotid pressure, or from contour of the peripheral pressure wave.(ABSTRACT TRUNCATED AT 250 WORDS)
Arteries↗
Coupling between the left ventricle and arterial system in hypertension.
In youth and in health, a variety of factors combine to optimize coupling between the left ventricle and systemic circulation. In hypertension and with aging, optimal coupling is disturbed by increased arterial stiffness which increases systolic pressure through two different mechanisms. The first mechanism (reduced aortic compliance) is not directly affected by drugs, but the second (early wave reflection) is capable of modification by vasodilator therapy. Favourable effects of vasodilator agents may not be apparent when pressure is recorded conventionally in a peripheral artery but can be inferred from consideration of pressure wave contour. Recognition of these factors provides new strategies for dealing with hypertension and hypertensive heart failure in man.
Aging↗
ECG evidence of limited myocardial infarction following coronary occlusion treated by early intravenous rt-PA infusion.
Serial 12-lead surface electrocardiograms (ECGs) were analysed in 110 patients with first evolving myocardial infarction entered in a double-blind placebo-controlled trial of intravenous rt-PA within 2.5 h (mean 1.9 +/- 0.5 (SD)) of pain onset. ECG analysis was performed by two 'blinded' analysts. QRS scoring (by the modified Selvester method) was used as an index of myocardial necrosis. Patient results were analysed according to infarct location. There was no difference between the two treatment groups in ST-segment elevation or QRS score at entry or up to 24 h after symptom onset. However from 24 h, QRS score was lower in patients with anterior infarction given rt-PA than in those given placebo: 5.4 +/- 2.8 vs 7.7 +/- 4.1 (P = 0.02) at 48 h; 4.7 +/- 3.2 vs 8.0 +/- 4.0 (P = 0.01) at 4-10 days; and 4.6 +/- 3.9 vs 7.5 +/- 3.9 (P = 0.01) at 21 days. For patients with inferior infarction, rt-PA treatment also resulted in a lower QRS score although this was not significantly different from the score of the placebo group (P = 0.07). Comparison of QRS scores with ejection fraction measured from the contrast ventriculogram taken at 21 days showed a moderate correlation (r = 0.46) in patients with anterior infarction but a poor correlation in patients with inferior infarction. These ECG results indicate that in evolving anterior myocardial infarction, there is limitation of infarct size from early rt-PA infusion.
Double-Blind Method↗
Preventive strategies in management of acute myocardial infarction.
Recent studies on pathogenetic mechanisms, supplemented by findings in clinical trials point the way to a logical approach to acute evolving myocardial infarction. This is designed in the earliest stage to limit infarction through reduction in myocardial oxygen demands, improvement in collateral blood supply and dissolution of coronary thrombus, to prevent in a later stage coronary reocclusion through administration of antiplatelet agents, and then to prevent infarct expansion through reduction in ventricular wall tension throughout the period of repair. Application of such an approach holds the promise of reducing infarct size and all the complications of infarction, as well as short and long-term mortality. The approach is active and aggressive, and contrasts with the approach applied a decade ago, where infarction was accepted as inevitable and therapies were reserved for managing its complications.
Adrenergic beta-Antagonists↗
Arterial stiffness, systolic blood pressure, and logical treatment of arterial hypertension.
Arterial stiffening is the principal cause of increasing systolic pressure with advancing years and in patients with arterial hypertension. It is associated with progressive arterial dilation and is due to degeneration of the arterial wall, probably as a consequence of repetitive cyclic stress; it increases systolic pressure directly by increasing amplitude of the pressure wave generated by a given flow impulse from the heart and indirectly by increasing wave velocity so that wave reflection from the periphery occurs earlier, augmenting pressure in late systole. The first mechanism affects pressure in both the central and peripheral arteries, the second predominantly in the central arteries. Change in brachial systolic pressure with age underestimates the rise in systolic pressure in the aorta and left ventricle. Arterial stiffness is reduced passively with reduction in arterial pressure. Drugs have little or no direct effect on arterial stiffness but can markedly reduce wave reflection. In patients with stiffened arteries, reduction in wave reflection decreases aortic systolic pressure augmentation. The decreased systolic pressure in central arteries brought about by this mechanism is not detected when systolic pressure is measured in a peripheral (brachial or radial) artery but can be inferred from change in contour of the pressure wave recorded in peripheral arteries.
Aging↗
In vitro fertilisation and allied techniques. The initial experiences of the first Irish service.
Since 1986 in vitro fertilisation and allied techniques have formed a part of the fertility service at St. James's Hospital. By June 1988 using routine methodology, IVF or GIFT has been attempted at least once in 94 women with a further 17 having one repeat procedure and 4 two repeat procedures performed. Although embryos were cultured from 54% of oocytes in which fertilisation was attempted, no pregnancies were achieved during that period with IVF. Ten pregnancies had occurred during a GIFT cycle (9 at first attempt, 16%) 60% of these are on-going. Also continuing were pregnancies where ovulation induction was abandoned on day 8 (1) and where conception occurred spontaneously whilst on the waiting list for the procedure (8) and in untreated cycles following the procedure (4) (16%). Seventy percent of patients who failed the first time expressed a wish to try again.
Female↗
Noninvasive determination of age-related changes in the human arterial pulse.
Arterial pressure waves were recorded noninvasively from the carotid, radial, femoral, or all three of these arteries of 1,005 normal subjects, aged 2-91 years, using a new transcutaneous tonometer containing a high fidelity Millar micromanometer. Waves were ensemble-averaged into age-decade groups. Characteristic changes were noted with increasing age. In all sites, pulse amplitude increased with advancing age (carotid, 91.3%; radial 67.5%; femoral, 50.1% from first to eighth decade), diastolic decay steepened, and diastolic waves became less prominent. In the carotid pulse, there was, in youth, a second peak on the downstroke of the waves in late systole. After the third decade, this second peak rose with age to merge with and dominate the initial rise. In the radial pulse, a late systolic wave was also apparent, but this occurred later; with age, this second peak rose but not above the initial rise in early systole, even at the eighth decade. In the femoral artery, there was a single systolic wave at all ages. Aging changes in the arterial pulse are explicable on the basis of both an increase in arterial stiffness with increased pulse-wave velocity and progressively earlier wave reflection. These two factors may be separated and effects of the latter measured from pressure wave-contour analysis using an "augmentation index," determined by a computer algorithm developed from invasive pressure and flow data. Changes in peak pressure in the central (carotid) artery show increasing cardiac afterload with increasing age in a normal population; this can account for the cardiac hypertrophy that occurs with advancing age (even as other organs atrophy) and the predisposition to cardiac failure in the elderly. Identification of mechanisms responsible offers a new approach to reduction of left ventricular afterload.
Aging↗
Arterial dilation and reduced wave reflection. Benefit of dilevalol in hypertension.
We compared dilevalol (an isomer of labetalol), 200-400 mg daily, against atenolol, 50-100 mg daily, in a double-blind, crossover, placebo-controlled trial with respect to effects on arterial distensibility (measured as pulse wave velocity [PWV]) and wave reflection (assessed from carotid pressure wave contour). Twelve patients of mean age 58 years (range 44-73 years) with essential hypertension (supine diastolic blood pressure 95-114 mm Hg) took active therapy for 12 weeks, separated by a 2-4 week placebo period. Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe. PWV was measured between carotid and femoral arteries (aortic PWV), carotid and radial arteries (arm PWV), and femoral and pedal arteries (leg PWV). Early wave reflection was calculated from the ratio of the height of the peak of the carotid wave above its shoulder to the pulse pressure and was expressed as an augmentation index. Both drugs were equally effective in reducing brachial sphygmomanometric pressure and PWV in all three regions (active vs. placebo, p less than 0.001), but there was no significant difference between the two active therapies. However, the augmentation index (averaged during the treatment period) was significantly lower with dilevalol (19%) than with atenolol (28%, p less than 0.01), corresponding to a greater decrease of 5-8 mm Hg in carotid systolic pressure compared with the brachial artery. Although both drugs were equally effective in reducing arterial distensibility, the vasodilating action of dilevalol gave added benefit in reducing wave reflection, presumably through its vasodilatory effect on peripheral conduit arteries.
Adult↗
Systolic blood pressure: arterial compliance and early wave reflection, and their modification by antihypertensive therapy.
Arterial stiffness (the inverse of compliance) is the major determinant of left ventricular and central aortic peak systolic pressure. Recent prospective epidemiological studies (MRFIT, Framingham) have confirmed the importance of systolic (rather than diastolic) pressure in the development of cardiac failure and stroke, and in all-cause mortality. Arteries stiffen in hypertension and with increasing age. Arterial stiffening increases systolic pressure by two mechanisms. The first is by causing a higher pressure to be generated at the peak of ventricular ejection (through increase in aortic characteristic impedance), and the second is by causing a secondary rise attributable to early return of wave reflection from peripheral sites (through an increase in arterial pulse wave velocity). ACE inhibitors, and also nitrates, decrease arterial stiffness. They also dilate peripheral conduit arteries; this reduces wave reflection. These drugs thus reduce systolic pressure in central arteries not only by reducing arterial stiffness but also by reducing inappropriately early wave reflection. Quantitatively, the latter action seems to be more important than the former. Neither action is seen with beta-blocking agents. These beneficial actions on central systolic pressure are not always apparent when pressure is measured in a peripheral artery such as the brachial or radial. This is because the reflected wave constitutes the peak of the pressure wave in central arteries but is usually just an undulation on the downstroke of the wave in peripheral arteries. Hence sphygmomanometric recordings underestimate reduction in central systolic pressure and in left ventricular load brought about by ACE inhibitors and by nitrates.
Antihypertensive Agents↗
What is the arterial pressure?
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Blood Pressure Determination↗
Limitation of myocardial infarction by early infusion of recombinant tissue-type plasminogen activator.
In a double-blind randomized trial involving five Sydney hospitals and the city ambulance paramedical service, 145 patients with a first evolving myocardial infarction and with onset of pain less than 2.5 (mean 1.9 +/- 0.5 [SD]) hr previously were allocated to intravenous infusion of 100 mg recombinant tissue-type plasminogen activator (rt-PA) or placebo over 3 hr. The groups at entry were similar. At assessment 21 days later, left ventricular ejection fraction measured both by contrast and radionuclide ventriculography was higher in the rt-PA compared with the placebo group (61 +/- 13%, n = 64, vs 54 +/- 14%, n = 62, contrast, 2p = .006; 52 +/- 13%, n = 66, vs 48 +/- 13%, n = 62 isotope, 2p = .08). This indicates limitation of myocardial infarction by rt-PA.
Adult↗
Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man.
Effects of sublingual glyceryl trinitrate (GTN) were studied in ten patients without heart failure during diagnostic cardiac catheterisation following angiography. GTN caused substantial reduction in peak left ventricular and aortic pressure (19 mmHg) with lesser reduction in mean aortic pressure (9 mmHg) and no change in diastolic aortic pressure. Reduction in stroke volume (by 15%), associated with fall in left ventricular end diastolic pressure (by 4 mmHg) was insufficient to explain the marked (17 mmHg - 34%) reduction in pulse pressure. Decrease in pulse pressure was associated with loss of the late systolic peak on both the aortic and left ventricular pressure wave. This peak is caused by pulse wave reflection. GTN caused no change in peripheral resistance or in indices of aortic compliance (characteristic impedance, total arterial compliance) but was associated with reduction in fluctuations of both modulus and phase of aortic impedance. All these changes in pressure waves and in impedance spectra are explicable on the basis of decreased peripheral wave reflection. This can be attributed to the known vasodilatory effect of GTN on the peripheral arteries. Simulation of arterial vasodilatation in a multi-branched model of the systemic arterial system confirmed this interpretation. Dilatation of peripheral arteries explains in part the beneficial effects of GTN in adult man.
Adult↗
Acute obstructive suppurative cholangitis.
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Acute Disease↗