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Biomedical subjects

C M Oakley

Publications and source records attributed to C M Oakley.

At least 37 records · Page 2Linked to original sources
PubMed1996

Myocardial beta adrenoceptor density in primary and secondary left ventricular hypertrophy.

OBJECTIVES: Myocardial beta-adrenoceptor density has been found to be reduced in hypertrophic cardiomyopathy, even when systolic function is preserved. Our purpose in the current study was to investigate whether beta-adrenoceptor down-regulation was unique to hypertrophic cardiomyopathy, or is also present in secondary myocardial hypertrophy. METHODS: Myocardial beta-adrenoceptor density was measured in 11 patients with hypertrophic cardiomyopathy, eight patients with left ventricular hypertrophy secondary to arterial hypertension or aortic valve disease and 18 normal control subjects, using positron emission tomography with 11C-CGP-12177 as the myocardial beta-adrenoceptor ligand. RESULTS: Reflecting the natural incidence of the conditions, the age of the hypertrophic cardiomyopathy patients was 37 (10) [mean (SD), range 20-51] years and that of the secondary hypertrophy patients 64 (18), [range 26-80] years; P < 0.01. The controls' ages were 50 (13), [range 21-65] years; however, since beta-adrenoceptor density is known to be influenced by age, the controls' data was split into groups matched to the hypertrophic cardiomyopathy and secondary hypertrophy patient sets. For the hypertrophic cardiomyopathy patients, mean left ventricular beta-adrenoceptor was 7.70 (1.86) pmol.g-1 compared to 10.17 (2.44) pmol.g-1 for a matched set of 15 controls; P < 0.01. In secondary left ventricular hypertrophy, beta-adrenoceptor was 6.35 (1.70) pmol.g-1 compared to 9.16 (2.00) pmol.g-1 for a matched set of 10 controls; P < 0.01. Plasma noradrenaline was 5.5 (2.2) nmol.l-1 in hypertrophic cardiomyopathy and 2.5 (1.0) nmol.l-1 for the matched controls; P < 0.01. The results for adrenaline were 2.2 (1.1) vs 0.4 (0.3) nmol.l-1 respectively; P < 0.001. For the secondary hypertrophy patients, the corresponding figures were 2.5 (1.2) vs 2.5 (1.0) nmol.l-1 for noradrenaline for patients and controls respectively (P = ns); and for adrenaline 0.2 (0.1) and 0.3 (0.2) nmol.l-1 respectively, P = ns. On multiple regression analysis, no relationships could be demonstrated amongst plasma catecholamines, beta-adrenoceptor, myocardial blood flow and echocardiographic E/A ratio and fractional shortening. CONCLUSION: Myocardial beta-adrenoceptor density appears to be comparably decreased in both primary and secondary left ventricular hypertrophy in the presence of preserved left ventricular systolic function.

Adult↗
PubMed1996

Valvular disease in pregnancy.

Previously asymptomatic mitral stenosis can lead to remarkably sudden development of life-threatening pulmonary edema in pregnancy and the patients, often immigrants from the developing world, may be unaware that they have heart disease. Diagnosis and treatment need to be rapid and effective. Left ventricular outflow tract obstruction may also lead to trouble in pregnancy with the development of angina and left ventricular failure. Regurgitant valve disease is much better tolerated in pregnancy than valvular stenosis, but mitral valve repair, usually feasible for nonrheumatic prolapsing mitral valves, should be carried out before pregnancy if regurgitation is severe. The treatment of women with Marfan's syndrome who already have aortic root widening but desire children remains very difficult, both with regard to the mother's safety and in relation to the dominant inheritance of the condition. Advice to women with artificial valves desiring pregnancy remains controversial, with continuation of warfarin increasingly favored over transfer to heparin in Europe. The use of bioprostheses in young women anticipating future pregnancy is also fading due to mounting evidence of accelerated deterioration of such bioprostheses during pregnancy.

Aortic Valve Stenosis↗
PubMed1996

Myocardial beta adrenoceptors and left ventricular function in hypertrophic cardiomyopathy.

OBJECTIVE: To assess the relation between left ventricular function and myocardial beta adrenoceptor density. METHODS: 17 patients with hypertrophic cardiomyopathy, six with and 11 without heart failure, were studied. Left ventricular function was assessed by echocardiography, and myocardial beta adrenoceptors by positron emission tomography. Patient data were compared with those obtained in normal controls. RESULTS: Myocardial beta adrenoceptor density in the 17 patients was 7.00 (SD 1.90) pmol/g v 11.50 (2.18) pmol/g in normal controls (P < 0.01). beta Adrenoceptor density in the six patients with left ventricular failure was 5.61 (0.88) pmol/g v 7.71 (1.86) pmol/g in the 11 patients with normal ventricular function (P < 0.05), and there was a significant correlation (r = 0.52; P < 0.05) between left ventricular fractional shortening and myocardial beta adrenoceptor density. A positive correlation (r = 0.51; P < 0.05) was also found between myocardial beta adrenoceptor density and the E/A transmitral flow ratio, an index of left ventricular diastolic function. CONCLUSIONS: There is myocardial beta adrenoceptor downregulation in patients with hypertrophic cardiomyopathy with or without signs of heart failure.

Adult↗
PubMed1995

The standard electrocardiogram as a screening test for hypertrophic cardiomyopathy.

Phenotypic heterogeneity in hypertrophic cardiomyopathy (HC) makes definitive diagnosis difficult, particularly during family screening. We studied the electrocardiogram (ECG) as a potential initial screening test in patients with HC. Using accepted diagnostic criteria, we examined the ECGs and echocardiograms of 159 patients with a confirmed clinical or genetic diagnosis of HC. An abnormal ECG was found in 154 patients (97%) while only 146 (92%) showed an abnormal echocardiogram. Of the former, 9 patients (6%) had normal echocardiograms and had been diagnosed on the basis of identification of a mutation in the beta myosin heavy chain gene (n = 8) or obligate carrier status (n = 1). Only 1 of these 9 patients was under age 20, the time at which hypertrophy is normally expressed on the echocardiogram. The remaining 5 patients (3%) without ECG abnormality consisted of 1 patient with an echocardiogram clearly diagnostic of HC and 4 clinically normal patients (aged 13, 24, 29, and 33 years) with normal echocardiograms who had been diagnosed by mutation identification (n = 3) or obligate carrier status (n = 1). Thus only these latter 4 patients (3%) would not have been diagnosed as having HC based on an abnormal ECG and/or abnormal echocardiogram. Screening relatives for HC by ECG criteria alone detects all those whom an echocardiogram will diagnose. While echocardiography aids in the specificity of HC diagnosis, the ECG, within the context of a family with a proven case of HC, is a more sensitive marker of the disease. It is therefore both a cost-effective and useful tool for screening those to proceed to echocardiography.

Adolescent↗
PubMed1995

Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance.

BACKGROUND: The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure (CHF) and is an independent predictor of peak exercise oxygen uptake. The pathophysiological basis for this remains unknown. The aim of this study was to partition DLCO into its membrane conductance (DM) and capillary blood volume components (Vc) and to assess if alveolar-capillary membrane function correlated with functional status, exercise capacity, and pulmonary vascular resistance. METHODS AND RESULTS: The classic Roughton and Forster method of measuring single-breath DLCO at varying alveolar oxygen concentrations was used to determine DM and Vc in 15 normal subjects and 50 patients with CHF. All performed symptom-limited maximal bicycle exercise tests with respiratory gas analysis; 15 CHF patients underwent right heart catheterization. DLCO was significantly reduced in CHF patients compared with normal subjects, predominantly because of a reduction in DM (7.0 +/- 2.6 versus 12.9 +/- 3.8 versus 20.0 +/- 6.1 mmol.min-1.kPa-1 in New York Heart Association class III, class II, and normal subjects, respectively, P < .0001), even when the reduction in lung volumes was accounted for by the division of DM by the effective alveolar volume. The Vc component of DLCO was not impaired. DM significantly correlated with maximal exercise oxygen uptake (r = .72, P < .0001) and inversely correlated with pulmonary vascular resistance (r = .65, P < .01) in CHF. CONCLUSIONS: Reduced alveolar-capillary membrane diffusing capacity is the major component of impaired pulmonary gas transfer in CHF, correlating with maximal exercise capacity and functional status. DM may be a useful marker for the alveolar-capillary barrier damage induced by raised pulmonary capillary pressure.

Blood-Air Barrier↗
PubMed1995

Renal response to candoxatrilat in patients with heart failure.

OBJECTIVES: Our primary objective was to compare the effects of three different doses of candoxatrilat with the effects of placebo on urinary volume in patients with moderately severe heart failure. The effects of candoxatrilat on urinary composition, neuroendocrine indexes and renal hemodynamic function were also studied. BACKGROUND: Candoxatrilat, a neutral endopeptidase inhibitor, reduces degradation of atrial natriuretic peptide and provokes diuresis in patients with mild heart failure, but the renal effects have not been studied in patients with moderately severe heart failure in a placebo-controlled study. METHODS: In a double-blind crossover trial, the effects of intravenous boluses of saline vehicle (placebo) and 50, 100 and 200 mg of candoxatrilat were compared on separate days in 12 patients with heart failure. Urinary output and composition were measured for 8 h. Renal blood flow and glomerular filtration rate were determined by radionuclide techniques. Blood was withdrawn for the measurement of hormones before and 3 h after dosing. RESULTS: All doses of candoxatrilat increased urinary volume (e.g., [mean +/- SEM] 263 +/- 53 to 490 +/- 82 ml for saline solution and the 200-mg dose, respectively, p < 0.01) and sodium content (14 +/- 4 to 37 +/- 11 mmol, p < 0.001) in the 1st 4 h after dosing. Plasma atrial natriuretic peptide increased (140 +/- 26 to 279 +/- 37 pg/ml, p < 0.01), whereas aldosterone decreased (178 +/- 41 to 125 +/- 35 pg/ml, p < 0.01), and renin activity was unchanged (10 +/- 2 to 12 +/- 3 ng/ml per h). CONCLUSIONS: Candoxatrilat given acutely causes diuresis, even in patients with moderately severe heart failure.

Aged↗
PubMed1995

Magnitude of myocardial dysfunction is greater in painful than in painless myocardial ischemia: an exercise echocardiographic study.

OBJECTIVES: This study sought to assess the presence and extent of inducible myocardial dysfunction during painful and painless (silent) myocardial ischemia in a homogeneous patient cohort with coronary artery disease and no previous myocardial infarction. BACKGROUND: The functional significance of painless versus painful demand-driven ischemia remains controversial, with conflicting results in published reports regarding the amount of myocardium in jeopardy. METHODS: Exercise echocardiography was performed in 89 patients (mean [+/- SD] age 59.3 +/- 8.2 years) with significant coronary artery disease and positive exercise stress test results. Patients were taking no antianginal medications and were classified into painless and painful cohorts after the outcome of a symptom-limited treadmill exercise test. No patients had previous coronary artery bypass surgery. Images were acquired in digital format before and immediately after treadmill exercise testing. RESULTS: Fifty-eight patients had painful and 31 painless myocardial ischemia. Clinical and demographic characteristics as well as coronary artery anatomy were similar in both groups. Patients with painless ischemia achieved better exercise performance with greater exercise duration (p < 0.001) and higher maximal rate-blood pressure product (p < 0.001) than those with painful ischemia. New wall motion abnormalities were seen in 54 patients (93%) with painful versus 17 (55%) with painless ischemia (p < 0.001). Total ischemic score was greater in patients with painful than in those with painless ischemia (15.9 +/- 3.7 vs. 12 +/- 1.4, p < 0.001, respectively), with a greater number of ischemic myocardial segments in painful than in painless ischemia (101 [16%] vs. 21 [6%], p < 0.001, respectively). CONCLUSIONS: Patients with painless ischemia frequently have regional myocardial dysfunction on exertion detected by echocardiography, but painful episodes are accompanied by a greater magnitude of myocardial dysfunction.

Angina Pectoris↗
PubMed1995

The medical treatment of culture-negative infective endocarditis.

The most common cause for persistently negative blood cultures is the previous administration of antibiotics, but other causes include fastidious organisms (such as Brucella and Legionella), cell-dependent organisms (such as Chlamydia and Coxiella), fungi and a major immune reaction. Fastidious organisms may take up to 3 weeks to grow in optimal media. Abscess formation may take the organisms inaccessible. If the diagnosis is in doubt, echocardiography, and more specifically transoesophageal echocardiography, is invaluable. If the clinical diagnosis is made but cultures are unavailable or negative, treatment should be started without delay. The choice of antibiotic depends on the clinical setting. In general, penicillin and gentamicin are indicated for a subacute onset: flucloxacillin and gentamicin if the onset is acute. Intravenous drug abusers should receive vancomycin; those who have recently had a prosthetic valve inserted should receive vancomycin, together with rifampicin and gentamicin.

Anti-Bacterial Agents↗
PubMed1995

Plasma neuro-endocrine activity in very elderly subjects and patients with and without heart failure.

Marked neuro-endocrine activation in patients with heart failure indicates a worse prognosis and a greater prognostic benefit from the use of ACE inhibitors. However, although the incidence of heart failure rises rapidly with age, relatively little is known about activation of the renin-angiotensin and sympathetic nervous system in patients with heart failure over the age of 75 years. This study was undertaken to investigate plasma concentrations of neurohormonal variables in elderly patients referred to the cardiac clinic with a presumptive, but unconfirmed, diagnosis of heart failure, and to compare these values to plasma concentrations found in age-matched normal subjects. Fifty patients referred with a diagnosis of heart failure were studied. All were receiving a diuretic but not an ACE inhibitor. Patients with renal, haematological and valve disease were excluded. Routine biochemistry and neurohormonal measurements were performed at their first visit, together with an electrocardiogram, chest X-ray and a full clinical examination by an experienced cardiologist. An echocardiogram and Doppler study was also performed and the diagnosis of heart failure either confirmed or refuted. Plasma concentrations of neuro-endocrine variables in healthy elderly subjects were similar to our normal laboratory range in younger subjects with the exception of atrial natriuretic peptide (ANP) (40 +/- 6 pg.ml-1, normal range < 40) and noradrenaline (5.7 +/- 0.7 nmol.l-1, normal range < 2.8). Impairment of left ventricular systolic function was confirmed in 38 of the 50 symptomatic patients (76%) and was associated with increases in plasma concentrations of active renin (58 +/- 8 IU.mol-1, P < 0.001 compared to healthy elderly subjects), angiotensin II (23 +/- 5 pg.ml-1, P < 0.008), noradrenaline (7.7 +/- 1.2 nmol.l-1, P < 0.01) and atrial natriuretic peptide (121 +/- 18 pg.ml-1, P < 0.002). Plasma concentrations were similar in normal subjects and those receiving treatment for heart failure but in whom the diagnosis was not confirmed. A weak relationship between plasma atrial natriuretic peptide (ANP) and left ventricular fractional shortening was demonstrated (r = -0.5, P < 0.001). Using an upper limit of ANP in the healthy elderly subjects of 62 pmol.ml-1 (mean + SD), plasma concentrations of ANP in the population with suspected heart failure had a sensitivity of 74% and specificity of 66% for the diagnosis of heart failure among elderly patients in the community or where access to echocardiography is limited. Left ventricular diastolic filling (assessed by Doppler) was abnormal in healthy elderly subjects and patients with heart failure, and appeared of limited value in the diagnosis of heart failure secondary to diastolic dysfunction. This study confirms that the renin-angiotensin system is activated in elderly patients with heart failure treated with diuretics. ANP may be helpful in diagnosing heart failure where it appears to have a complimentary role to echocardiography.

Aged↗
PubMed1995

Management of valvular stenosis.

The management of valvular stenosis has changed dramatically over the past 15 years, largely due to interventional cardiology. At the beginning of the 1980s, balloon valvuloplasty was thought by many to represent a definitive new treatment for calcific aortic stenosis in the elderly infirm. Before the end of the decade, this treatment had gone out of favor, but by that time we had learned that many of those same patients could undergo aortic valve replacement relatively safely and with excellent results. Unlike aortic stenosis, mitral stenosis is a disabling rather than a lethal disease, so the timing of intervention is much more difficult, particularly as there are treatment choices. Mortality, morbidity, and the possible bonus from proceeding earlier rather than later all need to be taken into consideration. Much to many people's surprise, mitral balloon valvuloplasty has grown and prospered, especially since the introduction of the Inoue balloon. It is the treatment of choice for young patients with mobile, noncalcified, stenosed valves, although still offering worthwhile palliation for older patients with higher echocardiographically determined valve scores. Echocardiography has gradually usurped cardiac catheterization for the assessment of valve stenosis and left ventricular function, but in patients with concomitant coronary disease that will be treated at the same time, the need for coronary angiography remains almost unchallenged.

Adolescent↗