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Secondary prevention programmes can be effective in reducing morbidity and mortality from coronary heart disease (CHD). In particular, UK guidelines, including those from the Department of Health, emphasize physical activity. However, the effects of secondary prevention programmes with an exercise component are moderate and uptake is highly variable. In order to explore patients’ experiences of a pre-exercise screening and health coaching programme (involving one-to-one consultations to support exercise behaviour change), semi-structured telephone interviews were undertaken with 84 CHD patients recruited from primary care. The interviews focused on patients’ experiences of the intervention including referral and any recommendations for improvement. A thematic analysis of transcribed interviews showed that the majority of patients were positive about referral. However, patients also identified a number of barriers to attending and completing the programme, including a belief they were sufficiently active already, the existence of other health problems, feeling unsupported in community-based exercise classes and competing demands. Our findings highlight important issues around the choice of an appropriate point of intervention for programmes of this kind as well as the importance of appropriate patient selection, suggesting that the effectiveness of health coaching may be under-reported as a result of including patients who are not yet ready to change their behaviours. [ABSTRACT FROM PUBLISHER]

Aims To determine characteristics, outcomes, prognostic indicators and management of patients with acute coronary syndromes without ST elevation.Methods and Results A prospective registry was carried out with follow-up for 6 months after index hospital admission. A history of acute cardiac chest pain was required plus ECG changes consistent with myocardial ischaemia and/or prior evidence of coronary heart disease. Patients with ST elevation or those receiving thrombolytic therapy were excluded. A total of 1046 patients were enrolled from 56 U.K. hospitals. The mean age was 66±12 years and 39% were female. The rate of death or non-fatal myocardial infarction at 6 months was 12·2% and of death, new myocardial infarction, refractory angina or re-admission for unstable angina at 6 months was 30%. In a multivariate analysis, patients >70 years had a threefold risk of death or new myocardial infarction compared with those <60 years (P<0·01) and those with ST depression or bundle branch block on the ECG had a five-fold greater risk than those with normal ECG (P<0·001). Aspirin was given to 87% and heparin to 72% of patients in hospital. At 6 months 56% received no lipid-lowering therapy at all. The 6-month rate of coronary angiography was 27% and any revascularization 15%.Conclusions In this cohort there was a one in eight chance of death or myocardial infarction, and a one in three chance of death, new myocardial infarction, refractory angina or re-admission for unstable angina, over 6 months. Age and baseline ECG were useful markers of risk. Aspirin, heparin and statins were not given to about one-sixth, one-third and one-half respectively. Rates of angiography and revascularization appear low. A review of treatment strategies of unstable angina and myocardial infarction without ST elevation is warranted in the U.K. to ensure that patients are receiving optimum treatments to reduce mortality and morbidity. [ABSTRACT FROM PUBLISHER]

Previously the diagnosis of sex and cystic fibrosis status has been studied on single cells using the polymerase chain reaction (PCR). It has been suggested that allelic drop-out (PCR failure of one allele) and/or preferential amplification (hypo-amplification of one allele) may contribute to poor reliability and misdiagnosis, although this remains controversial as some reports suggest that allelic drop-out does not occur. We investigated an improved method of diagnosing sex and cystic fibrosis in single cells using a new technology (fluorescent PCR) to determine the base level of PCR artefacts (allelic drop-out and preferential amplification) which, in combination with improved sensitivity, should improve PCR reliability and accuracy. Fluorescent PCR gives high reliability (approximately 97%) and accuracy rates (approximately 97%) in somatic cells for both sex and cystic fibrosis diagnosis and its lower detection threshold allows allelic drop-out and preferential amplification to be easily distinguished. We also achieved high reliability and accuracy in diagnosing cystic fibrosis in human blastomeres. This study confirms earlier reports of both allelic drop-out and preferential amplification in single cell analysis. We demonstrate that both allelic drop-out and preferential amplification occur in somatic cells and suggest these are separate phenomena. Preferential amplification appeared common in single cell PCR while allelic drop-out apparently occurred at random in each allele. Preferential amplification was mainly amplification of the larger allele. We suggest that some inaccuracy/misdiagnosis may be due to both preferential amplification as well as allelic drop-out. Other findings were variability in drop-out between PCR and that amplification of signals from human blastomeres may be linked to embryo quality. We suggest that allelic drop-out is dependent on the number of cells within the sample. [ABSTRACT FROM AUTHOR]

The prelmplantation diagnosis of a Hb-gtobin transgene in biopsied trophectoderm cells and blastomeres in embryos using a transgenic mouse model for the trait of human skkle-cefl anaemia has been undertaken. A sensitive procedure was developed for the amplification of the human β-globin gene sequence flanking the sickle mutation. Polymerase chain reaction (PCR) assays were undertaken on one to five biopsied trophectoderm cells and isolated blastomeres of the pre-implantation mouse embryo. After biopsy the blastocysts were cultured whilst the cells were analysed for the presence of the transgene, and a high proportion (82-91%) were viable as assessed by the presence of a blastocoele cavity within a 5-h period. The majority of the biopsied cultured blastocysts were frozen and used to confirm the diagnosis; 90 biopsied cultured blastocysts were transferred to pseudopregnant recipients and 34% established pregnancy. Material from day 13.5 post-coitum fetuses was also used to confirm the original diagnosis. The time (4–5 h) required to carry out the analysis obviates a need for extended culture or cryopreservation of the biopsied embryo. In individual experiments under optimal conditions, the presence of the transgene in biopsied cells was detected with 100% accuracy, and the PCR analysis was sensitive at the 1-cell level. The overall success rate of diagnosis and confirmation of the presence or absence of the human β-globin sequence in the biopsied embryo was 70%. Over the entire experimental period (14 months) DNA contamination from a variety of sources did occasionally occur; the methods used to overcome this problem are discussed. [ABSTRACT FROM PUBLISHER]

The preimplantation diagnosis of a HbSA-globin transgene in biopsied trophectoderm cells and blastomeres in embryos using a transgenic mouse model for the trait of human sickle-cell anaemia has been undertaken. A sensitive procedure was developed for the amplification of the human beta-globin gene sequence flanking the sickle mutation. Polymerase chain reaction (PCR) assays were undertaken on one to five biopsied trophectoderm cells and isolated blastomeres of the preimplantation mouse embryo. After biopsy the blastocysts were cultured whilst the cells were analysed for the presence of the transgene, and a high proportion (82-91%) were viable as assessed by the presence of a blastocoele cavity within a 5-h period. The majority of the biopsied cultured blastocysts were frozen and used to confirm the diagnosis; 90 biopsied cultured blastocysts were transferred to pseudopregnant recipients and 34% established pregnancy. Material from day 13.5 post-coitum fetuses was also used to confirm the original diagnosis. The time (4-5 h) required to carry out the analysis obviates a need for extended culture or cryopreservation of the biopsied embryo. In individual experiments under optimal conditions, the presence of the transgene in biopsied cells was detected with 100% accuracy, and the PCR analysis was sensitive at the 1-cell level. The overall success rate of diagnosis and confirmation of the presence or absence of the human beta-globin sequence in the biopsied embryo was 70%. Over the entire experimental period (14 months) DNA contamination from a variety of sources did occasionally occur; the methods used to overcome this problem are discussed. [ABSTRACT FROM AUTHOR]

Methods previously used for the biopsy of preimplantation mouse embryos have been applied to individual ‘spare’ human embryos. Early cleavage-stage human embryos have been cultured and individual blastomeres removed following zonae thinning or drilling. Embryos have also been cultured to the blastocyst stage for the biopsy of three to five trophectoderm cells. Both the biopsied embryo and the biopsied cells have been allowed to develop and/or grow . [ABSTRACT FROM PUBLISHER]

The culture of human preimplantation embryos from the 1-cell to the morula/blastocyst stage of development is not satisfactory at present. The success of various IVF laboratories ranges from 18 to 23%, therefore there is a requirement for improvement in the standard conditions used to culture the embryo. Using a limited number of ‘spare’ human embryos which were donated for research, in-vitro studies have been undertaken using various culture media. The results show that a significant improvement in viability is achieved using Ham's F-12 medium compared with other media presently used for culturing embryos. [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]

A multicentre epidemiological study to detect the prevalence of myocardial ischaemia in hypertensive left ventricular hypertrophy (LVH) was performed in 188 asymptomatic male hypertensives (131 treated). The mean age was 55 (range 40–82) years with blood pressure (BP) ≥160/100 mmHg or a systolic BP ≥ 180 mmHg. The participants were screened with echocardiography, and left ventricular hypertrophy (LVH), defined as LV mass index (LVMI) ≥ 130 g . m, was found in 127 (68%), of whom 95 were on antihypertensive treatment. Patients with LVH underwent a maximal bicycle ergometer exercise test and significant ST depression, indicating possible stress-induced ischaemia was found in 29 men (23%). These subjects were subjected to exercise thallium-201 scintigraphy, which was normal in 14 but showed reversible perfusion defects in 15. Thus, a high prevalence of LVH (70%) was detected in male hypertensives selected only on age and BP. In addition, although chest pain on exertion excluded patients from entry, a substantial portion had signs of ischaemia (23% on exercise ECG alone, and in 52% confirmed by thallium scan). The prevalence of these risk factors should be considered when evaluating hyper tensive patients. [ABSTRACT FROM PUBLISHER]

The analysis of genetic material is fundamental to many medical and scientific applications. One method that has been used extensively for detection or diagnosis of genetic material, especially for single-gene defects or sex, is the polymerase chain reaction (PCR). It is particularly useful when the amount of genetic material is very limited, or samples have been degraded or fixed. In recent years, sensitivity has increased so that even single copies of genes within a single cell can be detected. This article discusses some of the difficulties involved with single-cell PCR and introduces single-cell fluorescent PCR and its potential applications. The use of fluorescent PCR to reduce misdiagnosis is discussed in detail. [ABSTRACT FROM PUBLISHER]

Prenatal diagnosis (chorionic villus sampling (CVS) or amniocentesis) is performed at a relatively late stage of pregnancy (11-18 weeks). Such tests have significant disadvantages including increased risk of miscarriage and delay before results are known. Earlier prenatal diagnosis (< 11 weeks) has been discontinued because of the risk of fetal abnormalities. Recently fetal cells have been recovered from the coelomic cavity at 7-12 weeks gestation (coelocentesis). This study has established that highly sensitive fluorescent polymerase chain reaction (PCR) can provide rapid (4-5 h), reliable and accurate multiple genetic diagnoses (sexing and single-gene diagnosis) from coelomic cells. As prenatal diagnosis has a significant risk of contamination, we have also shown that coelomic cells can be simultaneously DNA fingerprinted to determine that contamination has not occurred. This earlier method of prenatal diagnosis would be very valuable, as it may overcome some problems of later conventional prenatal diagnosis and allow reassurance/treatment to be undertaken at a much earlier stage. Successful application of these techniques may supersede alternative methods of prenatal diagnosis. Although these techniques appear very promising, extensive clinical trials must be undertaken to determine safety of coelocentesis, diagnostic reliability and accuracy in a clinical setting. [ABSTRACT FROM AUTHOR]

Isometric exercise and cold pressor stimulation have been proposed as alternatives to dynamic exercise in the evaluation of patients with coronary heart disease. We evaluated all three, by gated radionuclide ventriculo-graphy, in 13 male controls and 44 male patients with coronary heart disease. In controls, mean left ventricular ejection fraction did not change during isometric exercise or cold pressor stimulation (64±2 to 63±2 and 63 ± 3) but fell significantly in patients (56±1 to 53±I and 53±1, both P < 0·001). During dynamic exercise, mean left ventricular ejection fraction rose in controls (64±2 to 84±2, P<0·001) but did not change in patients (56±1 to 56 ±2). There was considerable overlap between the groups in the left ventricular ejection fraction response to isometric exercise and cold pressor stimulation; only dynamic exercise discriminated between them. Isometric exercise and cold pressor stimulation are of little value in the diagnosis of coronary heart disease by radionuclide ventriculography. [ABSTRACT FROM PUBLISHER]

We studied 34 patients with proven coronary heart disease to determine whether the presence or absence of angina pectoris during exercise testing was associated with greater disease, ST segment depression or fall in left ventricular ejection fraction. Angina pectoris was the limiting symptom in 19 and fatigue/breathlessness in 15 patients. Exercise time [421(31) vs. 455(64) s], ST depression [1.4(0.3) vs. 1.1(0.3)mm], fall in left ventricular ejection fraction [13(2) vs. 12(2)] and coronary score and fall in left ventricular ejection fraction [15(2) vs. 8(3), P < 0.02]. The degree of ST segment depression correlated with the coronary score (r = 0.6) and fall in left ventricular ejection fraction (r = 0.5).ST segment depression but not angina pectoris during exercise predicted the extent of disease and its functional consequences. [ABSTRACT FROM PUBLISHER]

First pass radionuclide ventriculography was performed with gold 195m in a sequential evaluation of left ventricular ejection fraction during cold pressor stimulation. We studied 10 normal controls, 10 patients with angina pectoris who had proven coronary artery disease and normal left ventricular function during contrast angiography and 10 patients with dilated cardiomyopathy with normal coronary arteries and impaired left ventricular function at contrast angiography. Mean resting ejection fraction was similar in controls and patients with coronary heart disease (57 ± 2 vs 58 ± 3) but was significantly lower in the cardiomyopathic subjects (27 ± 4, P < 0.001). After 30 seconds cold pressor stimulation, mean left ventricular ejection fraction fell in the normal controls (57 ± 2 to 52 ± 2, P <0.05) but was unchanged in those with coronary heart disease and dilated cardiomyopathy (58 ± 3 to 55 ± 3 and 27 ± 4 to 24 ± 4, both NS). No further significant change occurred after 2.5 minutes stimulation (53 ± 1, 58 ± 3 and 23 ± 3, respectively). There was no difference in the pattern of left ventricular ejection fraction response between the groups. Six controls, 4 patients with coronary heart disease and 4 patients with dilated cardiomyopathy had a significant fall in left ventricular ejection fraction and 4, 5 and 6, respectively, developed a new or further deterioration in regional wall motion. Thus neither changes in regional wall motion nor left ventricular ejection fraction response distinguished either patient group from the normal controls. We do not recommend cold pressor stimulation as a diagnostic test for coronary heart disease. [ABSTRACT FROM PUBLISHER]

We investigated, by radionuclide ventriculography, left ventricular function in 10 fit elderly men and in 11 young volunteers. During exercise in the young subjects left ventricular ejection fraction (LVEF) rose from 63±3 to 73±1 (P < 0·005) and end systolic volume (ESV) fell from 48±6 to 38±5 ml (P <0±0·005) but were unchanged in the elderly (57±3 to 55±3 and 57±6 to 64±7 ml, respectively (NS). End diastolic volume (EDV) did not change in either group, stroke volume rose significantly only in the younger subjects, cardiac output rose in both groups but less in the elderly (5±0·5 to 12±1 vs 6±0·5 to 18±1 1 min−1). We conclude that this data lend support to the hypothesis that increasing age is associated with reduced left ventricular contractile performance. [ABSTRACT FROM PUBLISHER]