Search

Successful public health initiatives require multi-sector collaboration. AVONet was a UK collaborative developed to provide evidence-based strategies for active ageing. This study explored the success of AVONet in the achievement of its objectives as perceived by all partners. A convergent parallel mixed-methods design was employed, utilizing a quantitative survey and qualitative semi-structured interviews. Data collection was undertaken in September 2010,18 months after establishing the collaborative and 6 months after funding had ceased. AVONet partners (n = 24) completed a 27-item survey. A sub-sample of four academics and four practitioners participated in semi-structured interviews. Quantitative and qualitative comparisons were made between academics' and practitioners' perceptions of success, potential for sustainability and satisfaction with structure and relationships. Participants perceived the AVONet collaborative positively. Significant between-group (academic v practitioner) differences in survey responses were observed for success (U = 19.5; p = 0.003) and structure (U = 125.5; p =0.001). Strong positive correlations were observed between success and structure and balance between information transfer and exchange (r =0.756; p<0.001). Interviews confirmed positive perceptions and perceived importance of the collaborative and highlighted the need for further integration and tangible outcomes for practitioners. Suggestions to enhance sustainability were provided, such as smaller working groups and local council-led governance. Perceived success in building a multi-sectoral collaborative can be achieved during a 10-month period, despite differing needs of contributors. For collaboratives developed as a result of external funding aimed primarily at facilitating research, involvement of practitioners at an early stage may help set more comprehensive goals, supportive communication strategies, and increase potential for sustainability. [ABSTRACT FROM AUTHOR]

There is ample evidence that host shifts in plant-feeding insects have been instrumental in generating the enormous diversity of insects. Changes in host use can cause host-associated differentiation ( HAD) among populations that may lead to reproductive isolation and eventual speciation. The importance of geography in facilitating this process remains controversial. We examined the geographic context of HAD in the wide-ranging generalist yucca moth Prodoxus decipiens. Previous work demonstrated HAD among sympatric moth populations feeding on two different Yucca species occurring on the barrier islands of North Carolina, USA. We assessed the genetic structure of P. decipiens across its entire geographic and host range to determine whether HAD is widespread in this generalist herbivore. Population genetic analyses of microsatellite and mt DNA sequence data across the entire range showed genetic structuring with respect to host use and geography. In particular, genetic differentiation was relatively strong between mainland populations and those on the barrier islands of North Carolina. Finer scale analyses, however, among sympatric populations using different host plant species only showed significant clustering based on host use for populations on the barrier islands. Mainland populations did not form population clusters based on host plant use. Reduced genetic diversity in the barrier island populations, especially on the derived host, suggests that founder effects may have been instrumental in facilitating HAD. In general, results suggest that the interplay of local adaptation, geography and demography can determine the tempo of HAD. We argue that future studies should include comprehensive surveys across a wide range of environmental and geographic conditions to elucidate the contribution of various processes to HAD. [ABSTRACT FROM AUTHOR]

Transoesophageal echocardiography (TOE) is a standard and indispensable technique in clinical practice. The present recommendations represent an update and extension of the recommendations published in 2001 by the Working Group on Echocardiography of the European Society of Cardiology. New developments covered include technical advances such as 3D transoesophageal echo as well as developing applications such as transoesophageal echo in aortic valve repair and in valvular interventions, as well as a full section on perioperative TOE. [ABSTRACT FROM AUTHOR]

Every perioperative transoesophageal echo (TEE) study should generate a written report. A verbal report may be given at the time of the study. Important findings must be included in the written report. Where the perioperative TEE findings are new, or have led to a change in operative surgery, postoperative care or in prognosis, it is essential that this information should be reported in writing and available as soon as possible after surgery. The ultrasound technology and methodology used to assess valve pathology, ventricular performance and any other derived information should be included to support any conclusions. This is particularly important in the case of new or unexpected findings. Particular attention should be attached to the echo findings following the completion of surgery. Every written report should include a written conclusion, which should be comprehensible to physicians who are not experts in echocardiography. [ABSTRACT FROM PUBLISHER]

Background Chronic stable angina is a common condition, but considerable differences exist in the likelihood of acute coronary events such as CHD death, non-fatal myocardial infarction (MI) and unstable angina between individual patients. Effective risk prediction is necessary for optimum management. The aim of this study was to identify clinical features and non-invasive test parameters associated with high risk of these coronary events in stable angina and compose a clinically useful model to predict adverse outcomes in this population.Methods Six hundred and eighty-two patients with stable angina and a positive exercise test (1mm ST depression) from the Total Ischaemic Burden European Trial (TIBET) study, were studied. Resting ECG, exercise tolerance testing and echocardiography were performed at baseline, off anti-anginal therapy. The patients were then randomised to treatment with atenolol, nifedipine or a combination of both. Clinical follow up continued for an average of 2 years (range 1–3 years).Results and conclusions Prior MI or prior CABG were the clinical parameters associated with adverse outcome in patients with stable angina and a positive exercise test. On the ECG, left ventricular hypertrophy was predictive, and on echocardiogram, increased left ventricular dimensions were predictive of adverse events. When combined with time to ischaemia on exercise testing in a simple clinically applicable table these factors could be used to predict of 2 year probability of events for an individual patient. [ABSTRACT FROM PUBLISHER]

Aims Despite advances in the treatment of acute coronary syndromes based on randomized trial data and published guidelines, the extent to which such treatments are applied in practice remains uncertain. Data from clinical trials derive from selected geographical areas and in highly selected populations of patients, and hence may not reflect the overall population. The aim of the study was to investigate variations in hospital management and outcome using unselected data collected in the prospective Global Registry of Acute Coronary Events (GRACE). Methods and Results The 95 hospitals in GRACE were organized into 18 population-based clusters in 14 countries. Information was recorded about patient management and outcome during hospitalization and after discharge. Data on treatments administered were analysed by baseline condition, hospital type, by the presence or absence of a catheterization laboratory, and by geographical region. Of 11543 patients, 44% had an admission diagnosis of unstable angina, 36% presented with myocardial infarction, 9% were admitted to rule out a myocardial infarction, 7% had chest pain and 4% were hospitalized for ‘other cardiac’ and ‘non-cardiac’ diagnoses. Of the total GRACE population 38% had a final diagnosis of unstable angina, 30% ST-segment elevation myocardial infarction, 25% non-ST-segment elevation myocardial infarction, and 7% of ‘other cardiac’ and ‘non-cardiac’ final diagnoses. The event rates for hospital death or reinfarction were six and 2% for non-ST-segment elevation myocardial infarction, seven and 3% for ST-segment elevation myocardial infarction, and 3% hospital death for unstable angina. The use of aspirin was similar across all hospital types and geographical regions. In contrast, the use of percutaneous coronary intervention and glycoprotein IIb/IIIa inhibitors was higher (P<0·0001) in teaching hospitals and hospitals with catheterization laboratories and was also higher in the United States. At discharge a higher percentage (P<0·0001) of patients received angiotensin-converting enzyme inhibitors in hospitals without catheterization laboratories. The use of statins was lower in non-teaching hospitals and in centres without a catheterization laboratory. Conclusions The GRACE study reveals substantial differences in the management of patients based on hospital type and geographical location. Further analyses will determine whether such variations translate into differences in longer term outcomes. GRACE provides a multinational reference for the implementation of therapies of proven efficacy. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. [ABSTRACT FROM PUBLISHER]

Aims To describe the clinical course of heart failure in a population-based sample of incident cases, and to identify factors predicting hospitalization and mortality.Methods and Results Three hundred and thirty-two incident cases were identified over 15 months; 208 inpatients and 124 outpatients. Thirty-eight inpatients died during the first hospital admission (case fatality 18%) leaving 294 at risk of subsequent hospitalization. Over an average follow-up of 19 months, 173 cases were hospitalized on 311 occasions. Two hundred and twenty-four (72%) of these admissions were unplanned, with 51% due to worsening heart failure. One hundred and ten cases died over the same period. Cases diagnosed as an inpatient had 26 more admissions for worsening heart failure per 100 cases during follow-up (95%CI 9 to 44) compared to cases diagnosed as an outpatient, and also a higher mortality (hazard ratio 3·1 (95%CI 1·9 to 5·1)). Age was the only factor associated with an increased risk of hospitalization for worsening heart failure, but age, functional class and serum creatinine were predictive of mortality.Conclusions New cases of heart failure are at high risk of subsequent hospitalization, especially during the first months after diagnosis. Whilst predicting which patients will be hospitalized is difficult, interventions designed to reduce hospitalizations for worsening heart failure should be targeted at elderly inpatients with a new diagnosis. Copyright 2001 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved [ABSTRACT FROM PUBLISHER]

The transcription factor for cyclic-AMP response element binding protein (CREB) has been implicated in long-term plasticity processes in vertebrate and invertebrate species. In the absence of the alpha/delta CREB isoforms, performance is impaired in long-term memory tasks and the long-term maintenance of long-term potentiation (LTP) is impaired in the hippocampus. However, it is not known whether CREB plays a role in neocortical plasticity. Antibodies to CREB revealed that CREB-immunoreactive nuclei are present in all cortical layers but are more numerous in layers II/III, where they composed at least two-thirds the total population of cells. CREB-immunopositive cells were therefore present and densest in the very cortical layers that exhibit experience-dependent plasticity at this age. In order to assess the role of CREB in neocortical plasticity, we studied the effect of vibrissae deprivation on receptive field plasticity in the barrel cortex of mutant mice lacking the alpha/delta isoforms of CREB. A single vibrissa was spared and others removed for 18 days. In wild-types this caused potentiation of the spared vibrissa response. However, in adult mutants (>6 months) spared vibrissa responses from homozygotes were potentiated less than in any adolescent animals or in adult wild-type littermates. Surround receptive field responses were abnormally large in homozygotes and failed to increase by the same amount as they did in wild-types. In contrast, the alpha/delta CREB mutation had no discernible effect on plasticity in cortical layers II/III of the younger adolescent age group (1-2 months), suggesting that different plasticity processes may operate at this age. Further tests showed that the beta isoform of CREB was up-regulated in the barrel cortex of the alpha/delta CREB knock-outs, suggesting that this subunit may have compensated partly for the loss of the alpha/delta isoforms. These studies suggest that CREB plays a role in experience-dependent plastic... [ABSTRACT FROM AUTHOR]

Background: More than 220,000 persons 65 years and older fracture a hip every year in the United States. Although hip fractures have been considered as a single, homogeneous condition, there are two major anatomic types of proximal femoral fractures: intertrochanteric and femoral neck. The present study's objective was to determine if the two types of hip fracture have different patient characteristics and sequelae.Methods: A prospective study of 923 elderly patients admitted to seven Baltimore hospitals for a hip fracture between 1984 and 1986.Results: Patients with intertrochanteric fractures were slightly older, sicker on hospital admission, had longer hospital stays, and were less likely at 2 months postfracture to have recovered activities of daily living than femoral neck fracture patients. Intertrochanteric fracture patients also had higher mortality rates at 2 and 6 months after fracturing. Long-term recovery (1 year) did not differ between fracture type.Conclusions: It appears that intertrochanteric fracture patients have intrinsic factors (older age, poor health) impacting upon their risk of fracture and ability to recover. Differences in patient characteristics and sequelae do exist between femoral neck and intertrochanteric hip fracture patients that impact upon recovery. [ABSTRACT FROM AUTHOR]

Background: Hip fracture in the aged is a major health problem, especially considering the increasing proportion of the elderly in the population. This study examines changes in circulating levels of hormones, which are purported to affect bone metabolism, in response to hip fracture in postmenopausal women.Methods: Patients consisted of women ages 65 and older who had surgery within 2 days of fracture. Serum samples were obtained at 3, 10, 60, 180, and 360 days postfracture. Healthy women without hip fractures from the same age range served as a control group (n = 17). Hormones were determined by radioimmunoassay. Subjects with fractures in the neck region of the femur (n = 78) were compared to subjects with fractures in the trochanteric region (n = 88).Results: Estrone concentration (47.6 +/- 5.7 pg/mL; mean +/- SEM) at 3 days postfracture was elevated (p < .001) compared to control levels of 20.7 +/- 4.6 pg/mL. By 2 months, levels had declined to control levels. Androstenedione and the adrenal hormones, DHEAS and cortisol, displayed similar responses. Parathyroid hormone (PTH) levels were not significantly different from the control concentration at 3 days following fracture, but increased (p < .001) during the year following fracture. Calcitonin concentrations were much higher (p < .001) 3 days postfracture (42.1 +/- 3.7 pg/mL) compared to controls without fracture (9.8 +/- 3 pg/mL). Except for testosterone, no differences could be attributed to fracture location. Only PTH, with concentrations higher in the older age groups (p < .001), showed an age-related response.Conclusions: Following hip fracture, there are some dramatic responses in hormones that purportedly are mechanistically important in bone metabolism. These changes include transient increases in steroid hormones, chronic elevations in calcitonin, and rising levels of PTH during the year after fracture. [ABSTRACT FROM AUTHOR]

A significant side effect of aminoglycoside antibiotics is permanent hearing loss. This study was designed to determine the relative ototoxic liability of tobramycin, gentamicin, amikacin, and sisomicin. These drugs were given in daily subcutaneous dosages of 0, 50, 100, 150 or 200 mg/kg to guinea pigs for 4 weeks. Auditory damage was assessed by determining the Preyer pinna reflex, the ability of the cochlea to generate the AC cochlear potential and the number of sensory hair cells missing from the organ of Corti. Concentrations of antibiotic were determined in plasma and perilymph by a radioenzymatic assay. On an equal-dose basis the ototoxic liability of gentamicin was found to be similar to that of sisomicin, whereas the ototoxic liability of tobramycin was found to be similar to that of amikacin. Tobramycin and amikacin were less ototoxic than gentamicin and sisomicin. [ABSTRACT FROM PUBLISHER]

Aims(a) to assess short (1 year) and long-term (5 year) changes in left ventricular ejection fraction in patients with stable coronary disease with or without ECG evidence of transient ischaemia during daily life on routine therapy, and (b) to assess whether patients with recurrent transient ischaemic episodes have a particular propensity to gradual deterioration in left ventricular ejection fraction in the absence of infarction.Methods and ResultsOne hundred and forty eight patients (127 males; mean age 59 years), part of a natural history cohort of 172 patients who had undergone exercise testing, 48h ambulatory ST monitoring, and resting radionuclide ventriculography at baseline, and who had not suffered any intervening cardiac event, underwent repeat radionuclide ventriculography at 1 year follow-up on identical or very similar medications. Furthermore, 56 patients (50 males; mean age 65 years) of this cohort, who had ischaemia both on exercise testing and ambulatory monitoring at baseline (n=33), or no ischaemia on either test at baseline (n=23), and who had suffered no intervening event, underwent repeat exercise testing, ambulatory monitoring and radionuclide ventriculography at a mean of 61·8 months follow-up. In 38 of these 56 cases, long-term testing mirrored baseline testing in terms of presence or absence of ischaemia (both tests +, n=25; both tests −, n=13). At one year there was no change in left ventricular ejection fraction, either for the whole group (n=148; left ventricular ejection fraction 47=11·6%−47·13+11·07%,P=ns) or for subgroups with (n=62; left ventricular ejection fraction 48+12·1%–48·5+10·5%,P=ns) and without (n=86; left ventricular ejection fraction 46·2+10·4%–46·2+11·3%,P=ns) evidence of transient ischaemia at baseline. At 61 months, there was a small fall in mean left ventricular ejection fraction for the total study group (n=56; left ventricular ejection fraction 45·8+9·3%–42·1+8·8%,P<0·05); however, this fall was not significant for those patients with both baseline and 5 year evidence of transient ischaemia (n=25; left ventricular ejection fraction 44·9+8·7%–41·3+7·5%,P=0·056).ConclusionIn medically treated stable coronary patients who do not suffer any intervening cardiac event, recurrent transient (silent) ischaemic episodes do not, in themselves, lead to gradual deterioration in left ventricular systolic function over a 1–5 year period. [ABSTRACT FROM PUBLISHER]

Aims Platelet activation may be a determinant of thrombotic and restenotic complications following intracoronary stenting. In order to measure the effect of stenting on platelet activation antigen expression we used whole blood flow cytometry in 18 patients undergoing Palmaz–Schatz stenting (treated with full anticoagulation) and compared these with a group of 18 patients undergoing elective angioplasty. The effects of low molecular weight heparin and unfractionated heparin on platelet behaviour were also studied, both in vitro and in vivo to determine the contribution of prolonged heparin therapy to platelet activation following stenting.Methods and results Fibrinogen binding to activated GPIIb-IIIa, and surface expression of P-selectin, GPIb and GPIIb-IIIa antigens were measured in unstimulated peripheral blood samples (rest) and on stimulation with adenosine diphosphate (0·1–10μmol.l−1) and thrombin (0·02–0·16U.ml−1). No changes were seen in resting samples following angioplasty or stenting. Agonist responsiveness was unaltered after angioplasty, but in stented patients antigen expression in response to thrombin was significantly reduced (P≤0·04), whilst the adenosine diphosphate response was significantly increased (P=0·01). Similar effects were observed in patients with unstable angina treated with either low molecular weight heparin or unfractionated heparin in vivo. In vitro, both unfractionated and low molecular weight heparin inhibited thrombin-induced platelet activation, but stimulation of adenosine diphosphate responses was more marked with unfractionated than low molecular weight heparin.Conclusions There was a significant increase in platelet responsiveness to adenosine diphosphate following intra-coronary stenting in patients treated with conventional anticoagulants. This was probably a consequence of treatment with heparin. Activation of platelets by heparin may explain the increased rate of stent thrombosis in patients treated with anticoagulant therapy. Low molecular weight heparins stimulate platelets less than unfractionated heparin. [ABSTRACT FROM PUBLISHER]

Some 100 European cardiologists discussed calcium antagonists' role in the management of stable angina. Sixty-two percent of those involved used calcium antagonists rather than beta-blockers as first line therapy; 46% were prepared to use calcium antagonists in patients who had had a myocardial infarction more than 6 months previously. Only one tenth would use calcium antagonists in angina patients with left ventricular dysfunction. There was a broad preference for the use of heart rate-moderating calcium antagonists in most forms of stable angina. The discussions also underlined the diagnostic importance of angiography, exercise testing and lipid profile analysis. [ABSTRACT FROM PUBLISHER]

The purpose of the present study was to determine whether the cyclic variation of integratedbackscatter is measurable and quantifiable in all left ventricular walls and whether the information obtained using both parasternal and apical transducer positions can be used to identify changes in myocardial structure and contractility.The cyclic variation of integrated backscatter was measured from the parasternal long-axis, apical four-chamber and two-chamber views in 26 patients with idiopathic dilated cardiomyopathy(mean age 58 ± 9 years; ejection fraction 29 ± 10%) and compared with information obtained from 30 aged-matched healthy volunteers. For each subject, the cyclic variation of integrated backscatter was calculated from 16 predetermined regions-of-interest located within the myocardium of the basal and mid-segments of the left ventricle imaged from the long-axis view and also the basal mid and apical left ventricular segments imaged from the two apical views. The cyclic variation of integrated back-scatter was found to be present in 100% of the analysed regions-of-interest in healthy volunteers and in 87.5% of the analysed regions-of-interest in patients with idiopathic dilated cardiomyopathy. The mean value of cyclic variation of integrated backscatter, averaged from all regions-of-interest in the idiopathic dilated cardiomyopathy group, was significantly reduced compared to that in the healthy volunteers group (3.2 ± 2.5 dB [mean ± SD] vs 4 ± 2.9 dB, P<0.0001). Additionally, the healthy volunteers group demonstrated marked regional variability in the magnitude of cyclic variation of integrated backscatter which closely followed the regional changes in the contractile function of the normal heart. These regional differences in the magnitude of the cyclic variation of integrated backscatter were only partially retained in the idiopathic dilated cardiomyopathy group, and suggest that a multi-view approach of the recording of cyclic variation of integrated backscatter can be of value to differentiate normal from myopathic myocardium and to quantify regional differences in myocardial contractile performance throughout the left ventncular walls. [ABSTRACT FROM PUBLISHER]

Doppler myocardial imaging is a new cardiac ultrasound technique based on the principles of colour Doppler imaging which can determine myocardial velocities by detecting the changes of phase-shift of the ultrasound signal returning directly from the myocardium. To determine the normal range of transmural velocities in healthy hearts a prospective study was carried out involving 42 normal subjects (age from 21 to 78, mean 47±16 years). Using M-mode Doppler myocardial imaging the peak values of the mean velocity and velocity gradient across the left ventricular posterior wall were measured during standardized phases of the cardiac cycle. Peak mean velocities had the following values during the cardiac cycle: isovolumic contraction −1·3±1·2cm. s−1, early ventricular ejection 4·2±1·2cm. s−1, late ventricular ejection 1·8±1·1cm. s−1, isovolumic relaxation −2·0±0·8cm .s−1, rapid ventricular filling −6·6±2·2cm. s−1, atrial contraction −2·8±1·8cm. s−1, atrial relaxation 1·2±1·1cm. s−1. Peak velocity gradients were: isovolumic contraction 1·3±1·9 s−1, early ventricular contraction 4·7±1·9s−1, late ventricular contraction 1·1 ±1·0 s−1, isovolumic relaxation −0·6±0·5 s−1, rapid ventricular filling 6·1±3·4 s−1, atrial contraction 2·6±1·7 s−1, atrial relaxation 0·0±0·3 s−1. Linear regression analysis showed that with the increase of age, peak velocity gradient decreases during rapid ventricular filling (r=0·83; P<0·0001) and increases during atrial contraction (r=0·86; P<0·0001) while peak mean velocity increases only during atrial contraction (r=0·80, P<0·0001). Thus, there was no correlation between increasing age and systolic peak mean velocity and peak velocity gradient but both diastolic filling phases rapid ventricular filling and atrial contraction demonstrated age-related changes.In summary, this study has determined the age-related range of normal transmural myocardial velocities within the left ventricular posterior wall in healthy hearts during the cardiac cycle. We conclude that these measurements of peak mean velocities and peak velocity gradients, should form the baseline for subsequent Doppler myocardial imaging clinical studies on myocardial diseases processes. [ABSTRACT FROM PUBLISHER]

Objectives To determine the effects of atenolol, nifedipine and their combination on exercise parameters and ambulatory ischaemic activity in patients with mild chronic stable angina. Setting Multicentre, multinational study involving 608 patients from 69 centres in nine countries. Design Placebo washout followed by double-blind parallel-group study comparing atenolol 50 mg bd, nifedipine SR 20 mg bd, and their combination. Patients underwent maximal exercise testing using either a bicycle (n=289) or treadmill (n=319) and 48 h of ambulatory ST segment monitoring outside the hospital environment at the end of the placebo washout period and after 6 weeks of active therapy. Results Both medications alone and in combination caused significant improvements in exercise parameters and significant reductions in ischaemic activity during daily activities, when compared with placebo. There were, however, no significant differences between groups, for any of the measured ischaemic parameters although combination therapy resulted in a greater fall in resting systolic and diastolic blood pressure than either treatment alone. Conclusions In the management of mild chronic stable angina there appears to be little advantage gained from using combination therapy for ischaemia reduction. [ABSTRACT FROM PUBLISHER]

Objectives To study the relationship between presence or absence of ischaemic events on Holter monitoring and occurrence of a hard or hard+soft endpoint. Design A randomized double-blind parallel group study of atenolol, nifedipine and their combination, with ambulatory monitoring off-treatment and after 6 weeks of randomized treatment and prospective follow-up of 2 years on average. Setting Europe. Subjects 682 men and women with a diagnosis of chronic stable angina and who were not being considered for surgery. Main outcome Hard endpoints were cardiac death, nonfatal myocardial infarction and unstable angina; soft endpoints were coronary artery bypass surgery, coronary angioplasty and treatment failure. Results The study showed no evidence of an association between the presence, frequency or total duration of ischaemic events on Holter monitoring, either on or off treatment, and the main outcome measures. There was a non-significant trend to a lower rate of hard endpoints in the group receiving combination therapy. Compliance, as measured by withdrawal from trial medication, was clearly poorest in the nifedipine group with similar with drawal rates in the atenolol and combination therapy groups. Conclusion The recording of ischaemic events in 48 h Holter monitoring failed to predict hard or hard+soft endpoints in patients with chronic stable angina. [ABSTRACT FROM PUBLISHER]

Four exercise test protocols (Bruce, Balke, Ellestad and Steep) were compared in 16 patients with proven coronary artery disease in demonstrating the anti-anginal effects of sublingual glyceryl trinitrate in a randomization double-blind trial. Glyceryl trinitrate significantly improved the time, heart rate and rate pressure product to peak exercise, onset of angina and 1 mm ST segment depression in all four protocols (<0.05) (except rate pressure product to angina in the Balke protocol). The increase in exercise time was greatest for the Balke protocol at peak exercise (188.1±187.1) (mean±SD in s), at onset of angina (251.9±247.1) and at 1 mm ST depression (233.6±243.8), followed by the Steep and Bruce protocols, and was lowest for the Ellestad protocol 41.9±42.4, 96.5±65.8, 82.6±74.0, respectively. Increase in time to peak exercise with glyceryl trinitrate was significantly greater for the Balke protocol in comparison with the other three protocols and for the Bruce and Steep protocols when compared to the Ellestad protocol. Time to 1 mm ST depression with treatment was significantly greater on the Balke and Bruce protocols than the Ellestad protocol, and to onset of angina for the Balke compared to other three protocols. There were no significant differences between the Bruce and Steep protocols for any of the endpoints. The magnitude of treatment effect in the different protocols was accompanied by correspondingly greater inter-patient variability such that no protocol was more, or less, sensitive than another in detecting treatment effect. Changes in heart rate and rate pressure product with treatment were generally similar between the different protocols. In conclusion, a protocol with small and frequent increments (Balke), although able to show greater increase in exercise duration with glyceryl trinitrate than more aggressive protocols, is no more sensitive at detecting treatment effect. [ABSTRACT FROM PUBLISHER]

The significant reduction in cardiovascular morbidity and mortality following oestrogen replacement therapy in postmenopausal women is only partly explained by an improved lipid profile. Given acutely, oestradiol causes vasodilatation and increases coronary blood flow and, in large doses, improves treadmill performance in postmenopausal women with coronary artery disease. However, the significance of oestrogen-mediated vasodilatation is unknown since the acute effects of oestradiol in doses and preparations commonly used clinically have not been tested. The aim of this study was to evaluate the acute effects of conventional replacement therapy with 17 β-oestradiol on treadmill performance in 16 postmenopausal women with angina in a randomized, double-blind, placebo-controlled cross-over trial. Following baseline treadmill testing a transdermal oestrogen patch releasing 50 μg oestradiol. 24 h or matching placebo was applied and the exercise test repeated 24 h later. The patch was then removed. Seven to 14 days later the sequence was repeated using the alternative patch. The changes in time to angina, time to 1 mm ST segment depression and total exercise time for each treatment compared with the corresponding baseline test were calculated. Plasma 17 β-oestradiol increased with active therapy from 56±30pmol. l to 204±90pmol. l, indicating adequate replacement. Compared with their respective baseline exercise tests there were no differences between active and placebo patches for time to angina (active: 13±55 s vs placebo: 10±47 s), time to 1 mm ST segment depression (active: −30 ±52 s vs placebo: 24±71 s) or total exercise time (active: 14±45 s vs placebo: 13±35 s). Despite the recognized acute vasodilator action of larger doses of oestrogen, doses conventionally used in hormone replacement therapy had no acute effect on treadmill performance in this group of postmenopausal women with coronary artery disease. [ABSTRACT FROM PUBLISHER]

It has been reported that medically treated patients with stable angina and positive exercise test for ischaemia have an adverse 1–2 year outlook if they are shown also to have transient, and predominantly silent, ischaemic episodes detected by ambulatory ST segment monitoring during their daily activities: it has been suggested that this investigation could be used to identify patients more likely to benefit from early investigation and treatment. We assessed the long-term (up to 65 months) prognostic significance of transient iscliaemic episodes during daily activities in 172 patients routinely attending cardiac outpatients with medically treated stable angina who had undergone exercise testing and 48 h of ambulatory ST segment monitoring between February 1988 and August 1989 for this purpose. A positive exercise test for ischaemia was not a prerequisite for inclusion. One hundred and four patients (60.5%) had a positive exercise test for iscliaemia and 72 (42%) had transient ischaemia during daily activities (63 had both tests positive). Over a median 50-month follow-up period 54 patients suffered at least one cardiac event (primary event: cardiac death n=7; non-fatal myocardial infarction n=11; unstable angina n=18; elective CABGIPTCA n=18). Two further patients suffered non-cardiac death. Cardiac events, either objective (cardiac death or non-fatal myocardial infarction) or subjective (unstable angina or revascularisation) were no more likely to occur in those with transient ischaemia during daily life when compared with those without, at follow-up times up to 65 months. The detection of transient ischaemia during daily life is of limited practical clinical value in the management of ‘low risk’ medically treated patients with stable angina, and does not appear to help identify subgroups at increased risk of an adverse outcome at follow-up to more than 5 years. [ABSTRACT FROM PUBLISHER]

Therapeutic strategies for patients with unstable angina have been hampered by the difficulty in defining a homogenous cohort of patients, and identifying their risk for subsequent cardiovasular events. Despite the similarities in pathophysiological mechanisms between unstable angina and acute myocardial infarction, an analysis of recent trials of thrombolytic therapy in unstuble angina has failed to reveal evidence of improved clinical outcome. However, both aspirin and heparin have shown evidence of benefit and in order to test more specific andpotent thrombin inhibitors (for example hirudin) it is necessary to identify a cohort of patients with a high risk of subsequent cardiac events.This small scale pilot study set out to identify patients with unstable angina or non-Q wave infarction with a high risk of subsequent cardiac events and to undertake a feasibility study of two dose regimens of recombinant hirudin (HP W023). The impact on haemostatic parameters and the need for dose adjustment in order to achieve the target therapeutic range of activated partial thromboplastin time (aPTT) was also assessed. Firstly, the study revealed that it was possible to identify a high risk patient population (6143, 14% had sustained infarction; 10143, 23% required emergency or urgent revascularization and 11143, 26% elective revascularization). Secondly, it was possible to achieve stable antithrombin regimens with the two selected doses of hirudin (at least 78% of patients were within the target range at any of the time points). Haemostatic parameters were compared, but larger scale studies are required to establish safety, with a reliable estimate of the impact of hirudin on clinical events. [ABSTRACT FROM PUBLISHER]

Attenuation of the increase in blood flow caused by acetylcholine in the peripheral vasculature and coronary circulation of patients with heart failure has been interpreted as an impairment of endothelium-dependent vasodilation. The aim of this study was to compare in man the effects of acetylcholine, which also has endothelium-independent actions, with substance P, which appears to be a pure endothelium-dependent vasodilator, on epicardial and resistance coronary arteries in patients with idiopathic dilated cardiomyopathy. The effects of intracoronary acetylcholine (101M and 10M) and substance P (5, 10 and 25 pmol. min) on epicardial coronary artery diameter and coronary blood flow velocity were measured with an intracoronary Doppler flow probe and quantitative coronary angiography in 11 patients with idiopathic dilated cardiomyopathy and 10 control subjects. Epicardial coronary artery diameter did not change with acetylcholine but increased significantly with substance P in both groups (cardiomyopathy patients: 3.3 ± 0.2 mm (mean ± SEM) at baseline vs 3.9 ± 0.2 mm with substance P 25 pmol. min, P<0.01, controls: 3.1± 0.2 mm at baseline vs 3.9 ± 0.3 mm with substance P 25 pmol. min, P<0.05). Coronary flow ratios with acetylcholine were lower in cardiomyopathy patients (10: 1.4± 0.1 vs 2.3 ± 0.4, P=0.05; 10M: 1.8 ± 0.2 vs 3.2 ± 0.5, P=0.05 vs controls). Coronary flow ratios with substance P 5, 10 and 25 pmol. min were 1.5 ± 0.1 vs 1.5± 0.1, l.8 ± 0.2 vs 2.2 ± 0.2 and 2.1 ±0.2 vs2.8 ± 0.3 (P=NS, cardiomyopathy patients vs controls respectively). Whereas epicardial coronary artery responses to acetylcholine and substance P are similar in patients with dilated cardiomyopathy and control subjects, the actions of acetylcholine and substance P on coronary resistance vessels differ. The impairment with acetylcholine has several components, related either to muscarinic receptorltransduction mechanisms or the production of other vasoactive compounds, rather than a simple inability of the vascular endothelium to cause vasodilation. [ABSTRACT FROM PUBLISHER]

The aim of this trial was to compare the efficacy of combination antithrombotic therapy with a prostacyclin-sparing aspirin plus anticoagulation versus conventional aspirin plus anticoagulation, when added to antianginal therapy, in patients with unstable angina or non-Q wave myocardial infarction already being treated with aspirin. In a double-blind (for the aspirin) study, 144 prior aspirin users were randomized; 72 patients received controiled-release, prostacyclin-sparing aspirin 75 mg daily plus anticoagulation (intravenous heparin followed by warfarin to maintain the international normalized ratio at 2−3), and 72 patients received conventional aspirin 75 mg daily plus the same anticoagulation. Controlled-release aspirin was formulated to preserve endothelial cell prostacyclin synthesis. Trial therapy was begun by 13.2 ± 12.3 h of qualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographic changes, myocardial infarction, or death, was analysed by intention to treat. At 12 weeks, events were [ABSTRACT FROM PUBLISHER]

Several theories have been proposed to explain the mechanism causing atheroma; these include endothelial cell injury, smooth muscle cell proliferation, lipid deposition and an abnormality of the vasa vasorum. Based on these hypotheses. new therapies aimed at causing regression or preventing the development of atheroma include heparin, calcium antagonists, beta-receptor antagonists, lipid lowering agents and drugs that manipulate platelets. [ABSTRACT FROM PUBLISHER]

This study was designed to examine the effects of nisoldipine (relative to placebo), a new dihydropyridine calcium entry blocking agent, in the treatment of silent ischaemia in conventional doses. A total of 409 patients with proven coronary artery disease were screened and of this 64 had at least six episodes or a total duration of 30 mm of ST segment depression (1 mm lasting at least 1 min) over 48 h. Fifty-two patients ultimately completed a randomized double-blind cross-over study comparing nisoldipine 5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and number of episodes of ST segment depression when compared to placebo on treatment with nisoldipine 5 mg twice a day and nisoldipine 10 mg daily. However, the confidence limits were wide and crossed the no-treatment effect line. In addition, the nisoldipine doses neither affected the circadian distribution of ischaemic episodes nor caused an alteration of the workload achieved either at peak exercise or at 1 mm ST segment depression measured 24 h after nidoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients with proven coronary artery disease is relatively uncommon, it accounts for approximately 16% of patients with positive exercise. In these patients nisoldipine, given as 5mg twice a day and 10 mg daily, showed no significant therapeutic effects, either on the frequency or severity of silent ischaemia. New formulations of slow release nisoldipine are consequently being developed so that a fuller 24 h therapeutic profile may be obtained. [ABSTRACT FROM PUBLISHER]

Background: Vital statistics underestimate the prevalence of perinatal and infant deaths. This is particularly significant when these parameters affect eligibility for international assistance for newly emerging nations.Objective: To determine the level of registration of livebirths, stillbirths and infant deaths in Jamaica.Methodology: Births, stillbirths and neonatal deaths identified during a cross-sectional study (1986); and infant deaths identified in six parishes (1993) were matched to vital registration documents filed with the Registrar General.Results: While 94% of livebirths were registered by one year of age (1986), only 13% of stillbirths (1986) and 25% of infant deaths (1993) were registered. Post neonatal deaths were more likely to be registered than early neonatal deaths. Frequently the birth was not registered when the infant died. Birth registration rates were highest in parishes with high rates of hospital deliveries (rs = 0.97, P < 0.001) where institutions notify the registrar of each birth. Hospital deaths, however, were less likely to be registered than community deaths as registrars are not automatically notified of these deaths.Conclusions: To improve vital registration, institutions should become registration centres for all vital events occurring there (births, stillbirths, deaths). Recommendations aimed at modernizing the vital registration system in Jamaica and other developing countries are also made. [ABSTRACT FROM AUTHOR]

Intracavitary recording of monophasic action potentials (MAP) is a sensitive means of detecting the electrophysiological effects of early or subendocardial ischaemia. The effects of nitroglycerin (NTG) on the MAP was evaluated during pacing-induced angina in seven patients with localised, reversible ischaemia. Recordings from the ischaemic zone demonstrated a decrease in MAP amplitude and an abnormal rate-corrected shortening of MAP repolartisation. The “control” right ventricular MAP showed only the expected rate-dependent decrease in duration throughout the pacing stress test. The ischaemic MAP were unchanged following the intracoronary administration of NTG (100 μg). In contrast, intravenous NTG (200 to 300 μg) produced a normalisation of MAP amplitude and duration in spite of continuous pacing at the angina-provoking rate. These changes were preceded by a fall in aortic pressure (from mean 123/84 to 96/62) and subsequent lowering of the rate-pressure product.The major beneficial effects of NTG on the early electrical changes of pacing-induced ischaemia are thus related to decreased oxygen demand due to reduction in cardiac preload. [ABSTRACT FROM PUBLISHER]

N-acetyl-β-glucosaminidase (EC 3.2.1.30, recommended name β-N-Acetylglucosamini-dase) was found to be a constituent of human cardiac lysosomes. β-glucuronidase was also found in this tissue, while lysozyme, an enzyme present in leucocyte lysosomes, was not detectable in the heart. The activities of both N-acetyl-β-glucosaminidase and β-glucuronidase were elevated in plasma during the first 24 h after the onset of chest pain in patients with acute myocardial infarction and the peak levels of N-acetyl-β-glucosaminidase correlated well with those of creatine kinase. N-acetyl-β-glucosaminidase showed a further rise in plasma activity which gave a peak at 72 h after the onset of chest pain and this was accompanied by a rise in lysozyme activity. It is suggested that lysosome disruption caused by myocardial cell necrosis was responsible for the initial rise in plasma lysosomal enzyme activity and that the subsequent inflammatory reaction gave rise to the second peak. [ABSTRACT FROM PUBLISHER]

Ten patients with proven single-vessel coronary artery disease and a positive exercise test for ischaemia were investigated to establish the importance and therapeutic implications of dynamic coronary stenosis in such patients. All patients interrupted their anti-anginal therapy and undertook serial exercise testing in an attempt to identify variability in the ischaemic threshold. Ergonovine testing was performed in nine patients and all underwent 48 h of ambulatory ST segment monitoring while treatment was discontinued. Patients then entered a randomized double-blind study of atenolol and nifedipine; treadmill exercise testing and 48 h of ambulatory ST segment monitoring were performed at the end of each treatment phase. Six (60%) patients showed evidence of variability in coronary vasomotor tone, four of whom developed significant ST segment changes during administration of ergonovine; a further two had >30% variability in time to onset of ischaemia during serial treadmill exercise testing. Atenolol significantly increased the time to ischaemia on exercise testing, both in the group as a whole and in the subgroup with evidence of altered vasomotor tone when compared with no therapy, and led to a non-significant reduction in the frequency and duration of ischaemia during the patients' daily lives. Nifedipine, conversely, did not significantly increase time to ischaemia on exercise testing or reduce the frequency or duration of ambulatory ischaemia in either the whole group or the subgroup. With evidence of altered vasomotor tone when compared to no therapy however it was beneficial in terms of reduction in chest pain and requirement for glyceryl trinitrate during daily life. Evidence suggesting alterations in coronary vasomotor tone is common in patients with single-vessel coronary artery disease; however, beta-blockade appears effective in the treatment of ischaemia in these patients, and does not appear to aggravate the ischaemic situation. [ABSTRACT FROM PUBLISHER]

This study was designed to examine the relationships between dose of Wellcome two-chain recombinant tissue type-plasminogen activator (BWrt-PA) and coronary patency and fibrinolytic parameters in acute myocardial infarction (AMI). In an open randomized study, patients with AMI (determined by ECG) and symptoms of less than 4 h duration without contraindications for fibrinoly tic therapy were treated with rt-PA in nominal doses of 20 (7.7 MU), 50 (14.8–29.6 MU) or 1OOmg (29.6–48.2 MU) administered over 90 min followed by intravenous heparin. Coronary patency was determined by coronary arteriography of the infarct-related artery and haematological parameters (fibrinogen, plasminogen, a-antiplasmin and fibrin (ogen) degradation products) measured at 90 min. Coronary patency increased in a dose-related manner to 53% (95% C.I. 37–69%) in the 100 mg/90 min group. Logistic regression demonstrated a relationship between dose (in MU kg) and coronary patency. Fibrinogen at 90 m was reduced to 74 (61.5–86.4%) of the pooled plasma standard in the nominal 100 mg group. Patients with a higher predosefibrinogen had higher reductions of fibrinogen. Serious bleeding occurred in three (3%) patients, and no intracranial bleeds were reported. B W rt-PA produces dose-related patency of the coronary arteries with moderate, dose-related reduction in fibrinogen. [ABSTRACT FROM PUBLISHER]

A possible role for adjuvant therapy following thrombolysis exists in the context of reperfusion injury and post-ischaemic dysfunction, or so-called ‘stunned myocardium’. The question that arises is whether the extent of myocardial stunning, or the ultimate extent of necrosis, can be reduced by preventing reperfusion injury and the impairement of reflow. Essential to any attempted intervention is an understanding of the mechanism underlying myocardial damage following ischaemia and reperfusion. Certain mediators responsible for injury and repair have been identrfied, and their effects modified in experimental preparations; the role of complement, in particular, is central to these phenomena. Lysis of coronary artery thrombus is only the initiator of a sequence of events involving vascular endothelium and an intravascular response to tissue injury. The challenge is whether reperfusion injury may be modified and whether such intervention will favourably alter clinical outcome. [ABSTRACT FROM PUBLISHER]

Labetalol, a combined alpha-and beta-receptor antagonist, was compared with nifedipine in a placebocontrolled, randomized doubled-blind cross over study (four week treatment periods ) of 11 normotensive patients with stable exertional angina pectoris. Standard recomended doses of both drugs (labetalol 200–400 mg twice daily, nifedipine 10–20 mg three times daily) were used. Angina frequency was similar during the placebo washout period and treatment with the two drugs. The duration of treadmill exercise to angina, ischaemia (>1 mm ST segment depression), and end of exercise was increased by both labealol and nifedipine when compared with placebo, but there was no difference between the drugs. Ambulatory ST segment monitoring demonstrated that the frequency, duration and magnitude of ST segment depression, whether painful or silent, were unaffected by either drug. Labetalol is an effective agent in improving exercise tolerance in normotensive patients with stable exertional angina pectoris, with an efficacy similar to that of nifedipine. [ABSTRACT FROM PUBLISHER]

The value of ambulatory ST-segment monitoring in the detection of underlying coronary artery disease was investigated in one hundred consecutive patients who underwent exercise testing and coronary arteriography for chest pain. Forty-seven also had thallium-201 radioisotope imaging performed Six of the 26 patients with normal coronary arteries and 52 of the 74 patients with significant coronary artery disease had ST-segment changes during 48 h of ambulatory monitoring (sensitivity 77%). In comparison, the sensitivity of conventional exercise testing was 73% and specificity was 81%. Previous myocardial infarction did not influence the results, but patients with poor left ventricular function more often had absence of ambulatory ST-segment changes. Three-vessel coronary artery disease was detected more efficiently (sensitivity 80%), compared with single vessel disease (sensitivity 50%). Thallium scintigraphy demonstrated defects of uptake in nine patients without ambulatory ST-segment changes (sensitivity 82%, specificity 71%). The majority of these patients had small inferior or posterior defects in thallium uptake Only one patient with ambulatory ST-segment changes had normal coronary arteries and demonstrable spasm. Thus, ambulatory ST-segment monitoring is as valuable as stress testing in the detection of coronary artery disease and in addition helps detect patients with coronary spasm and normal coronary arteries. [ABSTRACT FROM PUBLISHER]

Ventricular arrhythmias are a frequent cause of sudden death in patients with coronary artery disease. The incidence and relationship of ventricular tachycardia to periods of myocardial ischaemia in these patients has not been fully investigated. Ambulatory ST-segment monitoring was performed in 100 consecutive patients with chest pain, of whom 74 had significant coronary artery disease. Recordings were analysedfor ST-segment changes and episodes of ventricular tachycardia (>3 beats, rate> 100 beats min). None of the 26 patients with normal coronary arteries, one of the 22 patients (4.5%) with single vessel disease, one of the 22 patients (4.5%) with double vessel disease and four of the 30 patients (13%) with triple vessel disease, had episodes of non-sustained ventricular tachycardia. Four of these six patients had episodes of reversible ST-segment change but ventricular tachycardia was related to these episodes in only two patients. These two patients had multiple episodes of tachycardia which occurred after the onset of ST-segment change and terminated before the ST-segment returned to baseline; they occurred in clusters with a mean of 12 episodes in each cluster. ST-segment change did not follow episodes of ventricular tachycardia in any patient. The number of ventricular complexes in each episode varied between three and 24 beats and were uniform in three of the six patients. The mean heart rate before the onset of tachycardia was 79 ±8 beats per minute and the rate of tachycardia had a mean of 170±34 beats a minute. Less than 10% of the episodes had a prematurity index of less than 1. Thus, although ventricular tachycardia was infrequently associated with periods of ischaemia, when this didoccur, the episodes were multiple and frequent. [ABSTRACT FROM PUBLISHER]

Treatment of both stable and unstable angina depends on initially defining the pathophysiological mechanisms. The goal of treatment is to prevent the development of angina pectoris and possibly also to improve the prognosis, β-blockade is effective in treating effort-related angina, as are calcium antagonists, which are also effective in treating coronary spasm. Combination therapy may be synergistic, but evidence to support this is controversial. In unstable angina the main goal of treatment is the prevention of myocardial infarction and death. While calcium antagonists have not been shown to improve the prognosis, there is more evidence to support the use of β-blockers, particularly in combination with a calcium antagonist. Aspirin and possibly heparin should be considered as routine treatment. [ABSTRACT FROM PUBLISHER]

We report the successful management and 2 year follow up of a young patient with Q fever endocarditis on a congenitally bicuspid aortic valve complicated by extensive abscess formation in the aortic valve ring and interventricular septum. Aortic root abscess formation complicating Q fever endocarditis has been reported in only one previous patient. Serological tests may thus be indicated in patients with aortic abscesses. Despite extensive aortic and intramyocardial abscess formation it proved possible to control the progression of disease by open drainage of the abscess and aortic valve replacement. Although the requirement for aortic root replacement was anticipated in this patient, it has not been required. [ABSTRACT FROM PUBLISHER]

In this article we discuss the place of ambulatory ST-segment monitoring in the investigation of the patient following coronary angioplasty. Particular attention is focused on the relationship between the results of exercise testing (the standard technique in the evaluation of the post-angioplasty patient) and ambulatory ST-segment monitoring, in order to assess whether ST-segment monitoring might contribute further information in the identification of residual or recurrent ischaemia. [ABSTRACT FROM PUBLISHER]

The effects of isosorbide dinitrate on acute myocardial ischaemia were studied in 19 patients during coronary angioplasty. The duration of balloon inflation to the onset of ST segment depression was increased by the administration of intracoronary isosorbide dinitrate from (mean ± SEM) 13 ± 2 to 20 ± 2s (48%) (P < 0·01) and the duration to 1 mm ST segment depression increased form 23 ± 2 to 29 ± 3s (28%) (P < 0·01). Systolic blood pressure fellfrom 118 ± 3 to 111 ± 4 mmHg but there was no change in intracoronary distal occlusion pressure. Thus during coronary occlusion isosorbide dinitrate prolongs the time to the onset of myocardial ischaemia. [ABSTRACT FROM PUBLISHER]

The physiological effects of dynamic exercise, isometric exercise and pacing differ. In general, dynamic exercise is the preferred means of increasing myocardial oxygen demand; this can be undertaken on either a treadmill or a bicycle. ST-segment changes may be measured using many different lead systems. Although down-slowing ST-segment depression is the most specific electrocardiographic sign of myocardial ischaemia, 1 mm planar ST-segment depression has been found to provide the most sensitive evidence of myocardial ischaemia without undue loss of specificity. R wave analysis has not been widely accepted as a helpful addition to ST-segment measurement in detecting the presence of coronary artery disease. It has been suggested that the use of the ST/heart rate slope accurately predicts not only the presence of the coronary artery disease, but also its severity in terms of one, two and three vessel disease. We and others have been unable to confirm this finding. [ABSTRACT FROM PUBLISHER]