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Biomedical subjects

A G Fraser

Publications and source records attributed to A G Fraser.

At least 19 recordsLinked to original sources
PubMed2006

Report on the European Association of Echocardiography accreditations in echocardiography: December 2003-September 2006.

AIMS: The European Association of Echocardiography (EAE) launched its Accreditation scheme in echocardiography in December 2003. Currently there are accreditations in Adult Transthoracic Echocardiography and Transesophageal Echocardiography and an Accreditation in Echocardiography for Congenital Disease will be launched in December 2006. METHODS AND RESULTS: Over the past 3years 350 applicants have undertaken the written exams and 157 applicants have completed the process and achieved accreditation. This report summarises the accreditation process, the details of the numbers of applicants and their progress through the Accreditation scheme. This report also provides data about the performance of the written exam, its reliability and the effectiveness of the questions and data about the reproducibility of the log book marking system. CONCLUSION: Taken together this report provides evidence that the EAE Accreditation schemes have been effective in establishing a standard for echocardiographic practice and an accreditation that is effectively organised, reliable, robust and successful.

Accreditation↗
PubMed2006

The future of cardiovascular imaging and non-invasive diagnosis: a joint statement from the European Association of Echocardiography, the Working Groups on Cardiovascular Magnetic Resonance, Computers in Cardiology, and Nuclear Cardiology, of the European Society of Cardiology, the European Association of Nuclear Medicine, and the Association for European Paediatric Cardiology.

Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations, and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarises the principles that should guide developments in cardiovascular diagnostic services.

Biomedical Research↗
PubMed2006

Subclinical hypothyroidism, arterial stiffness, and myocardial reserve.

CONTEXT: Subclinical hypothyroidism (SCH) is associated with increased risk of cardiac disease; its impact on arterial function is less clear. OBJECTIVE: The objective of the study was the assessment of arterial and cardiac function. DESIGN: The study was a 6-month controlled observational study using pulse wave analysis and tissue Doppler dobutamine stress echocardiography. SETTING: The study was conducted at a thyroid clinic. PATIENTS: Nineteen female SCH patients with raised TSH, normal free T(4), and no cardiovascular disease [aged 49.2 +/- 3.8 yr; body mass index (BMI) 29.9 +/- 6.7 kg/m(2)] were recruited from the thyroid clinic, and 10 female controls (aged 50.2 +/- 3.4 yr; BMI 29.7 +/- 7.2 kg/m(2)) also participated in the study. INTERVENTIONS: Incremental doses of l-thyroxine were used. MAIN OUTCOME MEASURES: Indices of vascular stiffness and left ventricular echocardiographic function were measured. RESULTS: Baseline augmentation gradient was elevated in SCH, compared with controls [10.3 +/- 5.1 (sd) mm Hg vs. 8.0 +/- 4.2, P < 0.05]; when euthyroid (mean T(4) dose 114 mug/d), it fell to 8.8 +/- 5.3 mm Hg (P < 0.05). Heart rate-corrected augmentation index was 26.7 +/- 9.9 vs. 18.8 +/- 9.9% (P < 0.02), falling to 19.7 +/- 9.6% (P < 0.001) after treatment. Time of travel of the reflected wave was 139.3 +/- 11.7 msec, compared with 141.5 +/- 8.8 msec in controls (P < 0.05), increasing to 144.9 +/- 11.9 msec (P < 0.05). There were no differences in resting global, regional left ventricular function, or regional myocardial velocities during maximal dobutamine stress between SCH patients and controls, or in treated patients, compared with baseline. CONCLUSIONS: Arterial stiffness was increased in SCH and improved with l-thyroxine, which may be beneficial, whereas myocardial functional reserve was similar to controls and remained unaltered after treatment.

Arteries↗
PubMed2006

Acute effects of caffeine and tobacco on arterial function and wave travel.

BACKGROUND: Caffeine and tobacco consumption are risk factors for heart failure, but their effects remain controversial. It has been hypothesized that they cause alterations in arterial stiffness and arterial wave travel which may increase ventricular loading. In this study the authors examined the influence of these widely used stimulants on wave intensity and arterial stiffness parameters using carotid wave intensity analysis. MATERIALS AND METHODS: A new Doppler-based ultrasound method was used to measure the acute effects of caffeine and tobacco on wave intensity in the right common carotid artery. The measurements enabled changes in arterial stiffness parameters to be recorded. RESULTS: In 17 subjects compared with 10 controls, caffeine increased blood pressure, early systolic wave intensity and wave speed, but late-systolic wave intensity and mid-systolic reflections were unchanged. In 11 smokers studied before and after smoking one cigarette, blood pressure and arterial stiffness increased but wave intensity was unchanged. No changes were observed in the controls. CONCLUSIONS: Increased wave intensity during ejection after caffeine suggested sympathomimetic effects on the left ventricular function. Increased wave speed in the common carotid artery implied augmented central loading after caffeine, but the absence of measurable changes in local arterial stiffness in the carotid artery suggested more complex and regional effects. Cigarette smoking acutely increased local arterial stiffness in the common carotid artery. These changes can be detected using wave intensity analysis.

Adult↗
PubMed2005

Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine.

BACKGROUND: Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as azathioprine and 6-mercaptopurine (6-MP). Studies examining lymphoma risk in IBD patients treated with these medications have been underpowered and have yielded conflicting conclusions. AIMS: The purpose of this meta-analysis was to provide a more precise estimate of the relative risk of lymphoma among IBD patients treated with azathioprine or 6-MP. METHODS: Studies were included if they were English language, full article, cohort studies specifically designed to evaluate cancer as an adverse outcome of treatment with azathioprine or 6-MP. Pooled standardised incidence ratios were calculated to estimate the relative risk of lymphoma associated with therapy. Heterogeneity was assessed using Poisson regression. Sensitivity analyses examined the influence of individual studies on risk estimate and heterogeneity statistics. RESULTS: Six studies were identified that met our inclusion criteria. When the data were combined across all studies, the pooled relative risk was 4.18 (95% confidence interval 2.07-7.51; 11 observed cases, 2.63 expected). Sensitivity analysis showed that exclusion of any one study had a relatively small effect on the pooled relative risk estimate (range 3.49-5.21) but excluding either the study with the highest or lowest estimated relative risk eliminated the statistically significant heterogeneity. CONCLUSIONS: Our data suggest an approximate fourfold increased risk of lymphoma in IBD patients treated with azathioprine/6-MP. The increased risk of lymphoma could be a result of the medications, the severity of the underlying disease, or a combination of the two.

Azathioprine↗
PubMed2005

Strain rate imaging after dynamic stress provides objective evidence of persistent regional myocardial dysfunction in ischaemic myocardium: regional stunning identified?

OBJECTIVE: To investigate whether persistent ischaemic dysfunction of the myocardium after dynamic stress can be diagnosed from changes in ultrasonic strain rate and strain. DESIGN: Prospective observational study, with age matched controls. SETTING: University hospital. PATIENTS AND METHODS: 26 patients (23 men, mean (SD) age 58.9 (8.1) years) with coronary artery disease but no infarction and 12 controls (9 men, aged 56.1 (8.8) years) with normal coronary arteriography and negative exercise test underwent treadmill exercise (Bruce protocol). Tissue Doppler echocardiography was performed at baseline, at peak exercise, and at intervals up to one hour. Systolic and diastolic velocity, strain, and strain rate were recorded in the basal anterior segment of 16 patients with proximal left anterior descending coronary artery disease. RESULTS: Patients developed ischaemia, since they experienced angina, exercised for less time, and reached a lower workload than the control group, and had ST segment depression (-2.4 mm). Myocardial systolic velocity immediately after exercise increased by 31% and strain rate fell by 25% compared with increases of 92% and 62%, respectively, in the control group (p < 0.05). During recovery, myocardial systolic velocity and strain rate normalised quickly, whereas systolic strain remained depressed at 30 and 60 minutes after exercise, by 21% and 23%, respectively, compared with baseline (p < 0.05 versus controls). Myocardial diastolic velocities and strain rate normalised but early diastolic strain remained depressed by 32% compared with controls for 60 minutes (p < 0.05). Strain during atrial contraction was abnormal for 30 minutes. CONCLUSIONS: Myocardial strain shows regional post-ischaemic dysfunction in systole and diastole and may become a useful diagnostic tool in patients presenting with chest pain with a normal ECG.

Blood Flow Velocity↗
PubMed2004

Genome-wide RNAi identifies p53-dependent and -independent regulators of germ cell apoptosis in C. elegans.

We used genome-wide RNA interference (RNAi) to identify genes that affect apoptosis in the C. elegans germ line. RNAi-mediated knockdown of 21 genes caused a moderate to strong increase in germ cell death. Genetic epistasis studies with these RNAi candidates showed that a large subset (16/21) requires p53 to activate germ cell apoptosis. Apoptosis following knockdown of the genes in the p53-dependent class also depended on a functional DNA damage response pathway, suggesting that these genes might function in DNA repair or to maintain genome integrity. As apoptotic pathways are conserved, orthologues of the worm germline apoptosis genes presented here could be involved in the maintenance of genomic stability, p53 activation, and fertility in mammals.

Animals↗
PubMed2003

Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography: optimal diagnostic models using off-line tissue Doppler in the MYDISE study.

AIMS: To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. METHODS AND RESULTS: We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiver-operator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). CONCLUSION: Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age.

Adult↗
PubMed2003

Helicobacter pylori, Chlamydia pneumoniae and myocardial infarction.

BACKGROUND: Several epidemiological studies have suggested a positive association of coronary heart disease with both Helicobacter pylori and Chlamydia pneumoniae infection. The issue has been difficult to resolve because of the potential impact of several confounding factors, in particular, socioeconomic status for H. pylori and smoking for C. pneumoniae. METHODS: A case-control study was carried out of 341 patients with a recent myocardial infarction (MI) and 831 community controls who had serology tests for H. pylori and C. pneumoniae (selected from a total study number of 1745 subjects). Individuals of Pacific Island or Maori ethnicity were excluded because they were infrequent. RESULTS: H. pylori seropositivity was associated with increasing age (P < 0.001) and lower household income (P = 0.0003) but not with gender, smoking status or alcohol intake. H. pylori was associated with lower high-density lipoprotein cholesterol (P = 0.007) and a higher body mass index (P = 0.007). The overall seropositivity for H. pylori was 41.6% for patients with MI and 34.5% for age and sex-matched population controls. The odds ratio was 1.34 (95% confidence interval (CI): 1.00-1.80; P = 0.038) after adjusting for age and sex. C. pneumoniae seropositivity was significantly associated with male sex, younger age (P = 0.03) and smoking status (P = 0.004) but not associated with household income or any other measured risk factor for coronary heart disease. The overall seropositivity for C. pneumoniae was 51.2% for patients with recent MI and 43.5% for controls. After adjusting for age and sex, the odds ratio was 1.24 (95%CI: 0.95-1.62; P = 0.11). Subgroup analysis showed no clear pattern within different age groups. In particular, the odds ratio for H. pylori seropositivity in younger subjects (aged 35-49 years) was similar to the overall group (1.38; 95%CI: 0.83-2.29). CONCLUSION: The association between H. pylori or C. pneumoniae seropositivity and coronary heart disease was significant but may not indicate a causal association.

Adult↗
PubMed2003

Feasibility and reproducibility of off-line tissue Doppler measurement of regional myocardial function during dobutamine stress echocardiography.

AIMS: Off-line post-processing of colour tissue Doppler from digital loops may allow objective quantification of dobutamine stress echocardiography. We assessed the reproducibility of off-line measurements of regional myocardial velocities. METHODS AND RESULTS: Nine observers analysed 10 studies, each making 2400 observations. Coefficients of variation in basal segments from apical windows, at rest and maximal stress, were 9-14% and 11-18% for peak systolic velocity, 16-18% and 17-19% for time-to-peak systolic velocity, 9-17% and 18-24% for systolic velocity time integral, and 18-23% and 21-27% for systolic acceleration. Coefficients of variation for diastolic velocities in basal segments at rest were 11-40%. Coefficients of variation for peak systolic velocity were 10-24% at rest and 14-28% at peak in mid segments, and 19-53% and 29-69% in apical segments. From parasternal windows coefficients of variation for peak systolic velocity were 14-16% in basal posterior, and 19-29% in mid-anterior segments. High variability makes measurement unreliable in apical and basal anterior septal segments. The feasibility of obtaining traces was tested in 92 subjects, and >90% in all basal and mid segments apart from the anterior septum. CONCLUSION: Quantification of myocardial functional reserve by off-line analysis of colour tissue Doppler acquired during dobutamine stress is feasible and reproducible in 11 segments of the left ventricle. The most reliable measurements are systolic velocities of longitudinal motion in basal segments.

Blood Flow Velocity↗
PubMed2003

Prevalence and clinical significance of incidental paraprosthetic valvar regurgitation: a prospective study using transoesophageal echocardiography.

OBJECTIVE: To assess the prevalence, mechanisms, and significance of paraprosthetic regurgitation detected incidentally by transoesophageal echocardiography (TOE) in patients after heart valve replacement. DESIGN: Prospective observational study. SETTING: Tertiary referral centre. PATIENTS: 360 consecutive patients (mean (SD) age 65.8(9.5) years, 193 women) undergoing elective first ever valve replacement. METHODS: Postoperative and follow up TOE, and tests for haemolysis and anaemia. RESULTS: There were 243 aortic, 90 mitral, and 27 double valve replacements, using 316 mechanical and 44 tissue valves, giving 270 aortic and 117 mitral valves. One patient with severe paraprosthetic mitral regurgitation underwent immediate reoperation and was excluded from subsequent analyses. Paraprosthetic jets were detected around 16 (6%) of the aortic and 38 (32%) of the mitral valves (p < 0.05) at the postoperative study. Follow up TOE was available for 151 aortic and 67 mitral valves, 0.9 (0.5) years after operation. Paraprosthetic jets were present in 15 (10%) of the aortic and 10 (15%) of the mitral valves (NS). Two thirds of the aortic and a fifth of the mitral jets were new. Paraprosthetic jets were more common in aortic valves in a supra-annular (12 of 88, 14%) than in an intra-annular position (4 or 182, 2%; p < 0.005) and in mitral valves inserted with continuous (36 of 88, 41%) rather than interrupted sutures (2 of 28, 7%; p < 0.001). Lactate dehydrogenase concentration was higher in patients with paraprosthetic jets than in those without (752 (236) v 654 (208) IU/l, p < 0.001). Haemoglobin and haptoglobin concentrations were not different. CONCLUSIONS: Small paraprosthetic leaks are common, are related to surgical factors, are not associated with increased subclinical haemolysis, and are benign during the first year after heart valve replacement.

Aged↗
PubMed2003

Incidence of embolism and paravalvar leak after St Jude Silzone valve implantation: experience from the Cardiff Embolic Risk Factor Study.

BACKGROUND: Silver coating of the sewing ring (Silzone) was introduced as a modification of the St Jude Medical standard valve to provide antibacterial protection, but the valve has recently been withdrawn. OBJECTIVE: To study patients with these prostheses to assess possible adverse effects, and to guide their follow up. DESIGN: Prospective observational study of risk factors for stroke after valve replacement. SETTING: Cardiology and cardiac surgery departments in a tertiary centre. PATIENTS: There were 51 patients with Silzone and 116 with St Jude Medical standard valves. Patients undergoing aortic valve replacement were well matched for stroke risk factors. Silzone patients with mitral valve replacement were younger (mean (SD) age 61 (10) v 66 (7) years), more likely to be female (95% v 65%), and had more pulmonary arterial hypertension (100% v 78%), but fewer coronary artery bypass grafts (5% v 33%) than patients with standard mitral valve replacements (all p < 0.05). RESULTS: Follow up was 100% in the Silzone group (mean duration 3.0 (0.9) years) and 97.4% in the standard group (4.7 (1.4) years). Survival, morbidity, and anticoagulant control were documented over 682 follow up years (153 for Silzone and 529 for standard). There were six embolic strokes and one peripheral embolism in the Silzone group, all within three months after operation, and five embolic strokes and one peripheral embolism in the standard group. Freedom from major thromboembolism at three months was 65% in the Silzone mitral valve replacement group and 100% in the standard mitral valve replacement group (difference 35%, 95% confidence interval 8% to 62%). There was one reoperation for paravalvar leak in the standard group, but none in the Silzone group (NS). Anticoagulant control in the two groups was similar. CONCLUSIONS: Patients with Silzone mitral valves had a high rate of early postoperative embolism but no excess paravalvar leak.

Adult↗
PubMed2002

The efficacy of methotrexate for maintaining remission in inflammatory bowel disease.

BACKGROUND: The management of patients with inflammatory bowel disease who are resistant to or intolerant of azathioprine remains a challenge. Low-dose methotrexate has been shown to be effective in inducing remission in Crohn's disease. AIM: This review was conducted because there are limited long-term follow-up data during and after stopping treatment. There are also limited data on the use of methotrexate in ulcerative colitis. METHODS: The study was a retrospective review of clinical notes. Remission was defined as minimal bowel symptoms without the need for oral steroids for 3 months. Relapse was defined as bowel symptoms that required steroid treatment or surgery. RESULTS: Seventy patients were reviewed; 48 had Crohn's disease and 22 had ulcerative colitis. The mean duration of treatment was 17.1 months; the mean maintenance dose was 20 mg weekly. Remission was achieved in 34 of 55 patients who completed more than 3 months of treatment (62%). Life-table analysis showed that the chances of remaining in remission at 12, 24 and 36 months (if treatment was continued) were 90%, 73% and 51%, respectively. The chances of remaining in remission after stopping treatment at 6, 12 and 18 months were 42%, 21% and 16%, respectively. The dose of methotrexate (mg/kg) was associated with the induction of remission (P=0.02). Treatment was equally effective for Crohn's disease and ulcerative colitis. CONCLUSIONS: Maintenance methotrexate treatment gives acceptable remission rates for treatment periods up to 3 years. After stopping treatment, relapse is frequent and occurs early (usually within 1 year).

Diarrhea↗
PubMed2002

Long-term risk of malignancy after treatment of inflammatory bowel disease with azathioprine.

BACKGROUND AND AIM: Data from renal transplant and rheumatoid arthritis patients suggest that there is an increased risk of malignancy after treatment with azathioprine. Whether this is true for patients with inflammatory bowel disease remains uncertain. METHOD: A retrospective review of clinical notes was performed. RESULTS: Azathioprine was given to 626 of 2204 patients (855 with Crohn's disease and 1349 with ulcerative colitis). The mean total duration of azathioprine use was 27 months. The mean follow-up from diagnosis was 13.7 years and the mean follow-up from the start of azathioprine treatment was 6.9 years. Thirty-one cancers were observed in 30 patients treated with azathioprine (4.5%) and 77 cancers were observed in 70 patients not treated with azathioprine (4.5%; P=N.S.). Logistic regression analysis (including in the model the age, sex, diagnosis and extent of disease) showed that treatment with azathioprine did not significantly affect the risk of the development of cancer. Eight patients had lymphoma; three had been given azathioprine (P=N.S.). For patients with ulcerative colitis, the number of colorectal cancers (including high-grade dysplasia) in patients given azathioprine was eight of 355 (2.2%), compared with 28 of 994 (2.8%) for patients not given azathioprine (P=N.S.). The cumulative risk of colorectal cancer or dysplasia/dysplasia-associated lesion or mass (adjusted to exclude post-colectomy patients) after 10, 20, 30 and 40 years of ulcerative colitis was 0.4%, 1.3%, 9%and 15.5%, respectively. CONCLUSION: No increased risk of cancer diagnosis following azathioprine treatment was observed.

Adolescent↗
PubMed2002

The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review.

BACKGROUND: There are limited data on factors predicting response to azathioprine and uncertainty regarding the optimal duration of treatment. PATIENTS AND METHODS: The notes of patients attending the Oxford IBD clinic from 1968 to 1999 were reviewed. Remission was defined as no need for oral steroids for at least three months and relapse was defined as active disease requiring steroids. RESULTS: A total of 622 of 2205 patients were treated with azathioprine (272 Crohn's disease, 346 ulcerative colitis, and four indeterminate colitis). Mean duration of the initial course of treatment was 634 days. The overall remission rates were 45% for Crohn's disease and 58% for ulcerative colitis. For the 424 patients who received more than six months of treatment, remission rates were 64% and 87%, respectively. Factors favouring remission were ulcerative colitis (p=0.0001), lower white blood cell (WBC) or neutrophil count (p=0.0001), higher mean cell volume (p=0.0001), and older age (p=0.05). For Crohn's disease, colonic disease favoured remission (p=0.03). Factors that were not significant were age, sex, lymphocyte count, and dose (mg/kg). The proportion of patients remaining in remission at one, three, and five years was 0.95, 0.69, and 0.55, respectively. The chance of remaining in remission was higher if WBC was less than 5 x 10(9) (p=0.03) and in male patients (p=0.01; Crohn's disease only). There was no difference in relapse rates between Crohn's disease and ulcerative colitis. After stopping azathioprine, the proportion of patients remaining in remission at one, three, and five years was 0.63, 0.44, and 0.35 (222 patients). Duration of azathioprine treatment did not affect the relapse rate after stopping treatment (p=0.68). CONCLUSIONS: Azathioprine is effective treatment for ulcerative colitis and Crohn's disease. The efficacy of azathioprine is reasonably well sustained over five years.

Adult↗
PubMed2002

Adenosine provokes diastolic dysfunction in microvascular angina.

Adenosine stress echocardiography was performed in nine patients (58 (+/-3) years, eight women) with documented microvascular angina. Global ventricular function was assessed by Tc(99m) blood pool imaging and Doppler, whereas longitudinal ventricular function was assessed by simultaneous tissue Doppler echocardiography of the lateral mitral annulus. Adenosine was infused incrementally to onset of chest pain in all patients. There was no significant change in global or longitudinal systolic function. Adenosine induced global diastolic dysfunction, demonstrated by blood pool imaging and by Doppler of the transmitral flow. All patients had long axis diastolic dysfunction at peak adenosine, revealed by a ratio of early to late diastolic velocity of lateral mitral annulus <1, which was absent at rest. Adenosine, as a stress agent, provokes regional and global diastolic dysfunction in microvascular angina, which may be a consequence of subendocardial ischaemia. Long axis diastolic dysfunction can be easily revealed by tissue Doppler of the lateral annular motion.

Adenosine↗