Biomedical subjects
G Davies
Publications and source records attributed to G Davies.
Relapse and mortality among HIV-infected and uninfected patients with tuberculosis successfully treated with twice weekly directly observed therapy in rural South Africa.
OBJECTIVE: To determine post-treatment relapse and mortality rates among HIV-infected and uninfected patients with tuberculosis treated with a twice-weekly drug regimen under direct observation (DOT). SETTING: Hlabisa, South Africa. PATIENTS: A group of 403 patients with tuberculosis (53% HIV infected) cured following treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice weekly to 2 months and HR twice weekly to 6 months in the community under DOT. METHODS: Relapses were identified through hospital readmission and 6-monthly home visits. Relapse (culture for Mycobacterium tuberculosis) and mortality given as rates per 100 person-years observation (PYO) stratified by HIV status and history of previous tuberculosis treatment. RESULTS: Mean (SD) post-treatment follow-up was 1.2 (0.4) years (total PYO = 499); 78 patients (19%) left the area, 58 (14%) died, 248 (62%) remained well and 19 (5%) relapsed. Relapse rates in HIV-infected and uninfected patients were 3.9 [95% confidence interval (CI) 1.5-6.3] and 3.6 (95% CI 1.1-6.1) per 100 PYO (P = 0.7). Probability of relapse at 18 months was estimated as 5% in each group. Mortality was four-fold higher among HIV-infected patients (17.8 and 4.4 deaths per 100 PYO for HIV-infected and uninfected patients, respectively; P<0.0001). Probability of survival at 24 months was estimated as 59% and 81%, respectively. We observed no increase in relapse or mortality among previously treated patients compared with new patients. A positive smear at 2 months did not predict relapse or mortality. CONCLUSION: Relapse rates are acceptably low following successful DOT with a twice weekly rifampicin-containing regimen, irrespective of HIV status and previous treatment history. Mortality is substantially increased among HIV-infected patients even following successful DOT and this requires further attention.
Vitamin C increases nitric oxide availability in coronary atherosclerosis.
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Cancer in children of nuclear industry employees: report on children aged under 25 years from nuclear industry family study.
OBJECTIVE: To determine whether children of men and women occupationally exposed to ionising radiation are at increased risk of developing leukaemia or other cancers before their 25th birthday. DESIGN: Cohort study of children of nuclear industry employees. SETTING: Nuclear establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels. SUBJECTS: 39 557 children of male employees and 8883 children of female employees. MAIN OUTCOME MEASURES: Cancer incidence in offspring reported by parents. Employment and radiation monitoring data (including annual external dose) supplied by the nuclear authorities. RESULTS: 111 cancers were reported, of which 28 were leukaemia. The estimated standardised incidence ratios for children of male and female employees who were born in 1965 or later were 98 (95% confidence interval 73 to 129) and 96 (50 to 168) for all malignancies and 109 (61 to 180) and 95 (20 to 277) for leukaemia. The leukaemia rate in children whose fathers had accumulated a preconceptual dose of >/=100 mSv was 5.8 times that in children conceived before their fathers' employment in the nuclear industry (95% confidence interval 1.3 to 24.8) but this was based on only three exposed cases. Two of these cases were included in the west Cumbrian ("Gardner") case-control study. No significant trends were found between increasing dose and leukaemia. CONCLUSIONS: Cancer in young people is rare, and our results are based on small numbers of events. Overall, the findings suggest that the incidence of cancer and leukaemia among children of nuclear industry employees is similar to that in the general population. The possibility that exposure of fathers to relatively high doses of ionising radiation before their child's conception might be related to an increased risk of leukaemia in their offspring could not be disproved, but this result was based on only three cases, two of which have been previously reported. High conceptual doses are rare, and even if the occupational association were causal, the number of leukaemias involved would be small; in this study of over 46 000 children, fewer than three leukaemias could potentially be attributed to such an exposure.
The nuclear industry family study: linkage of occupational exposures to reproduction and child health.
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Effects of acute L-arginine administration in coronary atherosclerosis.
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Relation between exercise and dobutamine stress-induced wall motion abnormalities and severity and location of stenosis in single-vessel coronary artery disease.
BACKGROUND: Quantitative coronary angiography has been shown to allow accurate assessment of coronary stenosis. Exercise and dobutamine stress echocardiography both are established methods for assessing the functional importance of coronary stenosis. The relation, however, between exercise and dobutamine stress-induced wall motion abnormalities and the severity and location of stenosis remains controversial. METHODS AND RESULTS: Thirty patients with single-vessel coronary artery disease with >/=50% minimal luminal reduction and stable angina participated in the study. Severity of coronary artery stenosis was assessed by means of computed angiography. During peak exercise echocardiography 23 patients had wall motion abnormalities and 7 did not. A positive test result was associated with severity of stenosis >/=80% for 65% of stenoses (P <.05 versus severity of stenosis <80%) and with a proximal location of 94% of stenoses (P <.01 versus middle and distal stenoses). A significant correlation was found between area of stenosis and difference in wall motion score between rest and peak exercise (r = 0.53, P <.01). The proportion of positive exercise stress was greater among stenoses with severity <80% (62% versus 46% dobutamine stress, P <.05). During dobutamine stress echocardiography 18 patients had wall motion abnormalities and 12 patients did not. A positive test result was associated with severity of stenosis >/=80% in 72% of stenoses (P <.05 versus severity of stenosis <80%) and with a proximal location in 81% of stenoses (P <.01 versus middle and distal stenoses). A weak correlation was found between area of stenosis and difference in wall motion score between rest and peak dobutamine stress (r = 0.37, P <.05). CONCLUSIONS: Among patients with single-vessel coronary artery disease, positive stress echocardiographic test results usually are associated with proximal >/=80% stenosis. Patients with <80% stenoses are more likely to have a positive exercise stress test result than a positive dobutamine stress test result.
Inhibition of nitric oxide synthesis in human epicardial coronary arteries and stenoses in relation to serum lipid level.
Administration of N(G)-monomethyl-L-arginine (LNMMA), an inhibitor of nitric oxide synthase, causes a reduction in epicardial coronary artery and stenosis diameter in patients with coronary artery disease, indicating that these diseased vessels produce nitric oxide. Elevations of low density lipoprotein cholesterol impair human endothelium-dependent relaxation. The relationship between serum lipid level and nitric oxide production by normal and atheromatous human epicardial coronary arteries in vivo is unknown. The effects of an intracoronary infusion of LNMMA (8 and 16 micromol/min) followed by intracoronary administration of 250 mcg nitroglycerin on non-stenotic proximal and distal coronary segments and coronary stenoses were studied in 11 patients with coronary artery disease and in 19 patients with 'normal arteriograms'. Coronary luminal diameter was measured by computerized quantitative angiography. In patients with cholesterol level> or = 220 mg/dl, no significant response to LNMMA was observed in the proximal segments in either those with 'normal angiograms' or those with coronary disease. In patients with cholesterol <220 mg/dl significant constriction (P<0.01) was observed in the proximal segments of patients with 'normal coronary angiograms' at both 8 and 16 micromol doses, but occurred only at the 16 micromol/min dose (P<0.01) in those with coronary disease. In conclusion the difference in vasomotor response to LNMMA in relation to cholesterol level is localised to the proximal coronary segments, and the response does not correlate with cholesterol or triglyceride level. This is therefore more likely to be an indirect effect of elevated cholesterol, e.g. undetected atheroma, than a direct effect on nitric oxide synthesis.
Simultaneous assessment of myocardial viability and function for the detection of hibernating myocardium using ECG-gated 99Tcm-tetrofosmin emission tomography: a comparison with 201Tl emission tomography combined with cine magnetic resonance imaging.
The aims of this study were to evaluate the simultaneous assessment of myocardial viability and function for the detection of hibernating myocardium using ECG-gated 99Tcm-tetrofosmin single photon emission tomography (SPET), and to compare the technique with 201Tl SPET in combination with cine magnetic resonance imaging (MRI). Fifteen patients aged 41-70 years with impaired left ventricular function (mean LVEF 23.4 +/- 8.1%) and three-vessel coronary artery disease were studied before and after coronary artery bypass grafting (CABG). The following investigations were performed within the 3 months before surgery: stress/redistribution and separate-day rest 201Tl SPET with early and late imaging, stress and ECG-gated rest 99Tcm-tetrofosmin SPET, and resting cine MRI. Between 3 and 6 months post-surgery, stress/redistribution 201Tl SPET and cine MRI were repeated. Tracer uptake in nine segments of the left ventricle was graded visually and by quantitative analysis. Myocardial motion and thickening were graded visually from cine MRI and from gated 99Tcm-tetrofosmin SPET images. Segments were defined as hibernating pre-operatively if tracer uptake was moderately reduced or better but myocardial motion was severely hypokinetic or worse. The accuracy of pre-operative assessment was assessed by comparison with post-operative function assessed by MRI. The sensitivity and specificity for the prediction of functional improvement were 69% and 60% for late rest 201Tl uptake combined with MRI; 58% and 62% for rest 99Tcm-tetrofosmin uptake combined with MRI; and 62% and 45% when gated 99Tcm-tetrofosmin SPET was used to assess both tracer uptake and wall motion. In 21 of 135 segments, contractile function could not be assessed by gated 99Tcm-tetrofosmin SPET because of inadequate tracer uptake; function was improved in 5 (25%) of these segments after CABG. In conclusion, the combined assessment of viability and function using ECG-gated 99Tcm-tetrofosmin SPET is feasible and it allows the assessment of hibernating myocardium with similar accuracy to the combination of ungated 99Tcm-tetrofosmin SPET with MRI. Where tracer uptake is too poor for assessment of function, there is a low incidence of myocardial hibernation. However, ECG-gated 99Tcm-tetrofosmin SPET is not superior to 201Tl SPET combined with cine MRI in the identification of hibernation.
Validation of an asthma symptom diary for interventional studies.
OBJECTIVE: The Pediatric Asthma Diary was developed and validated to assess efficacy of interventions in children with asthma. DESIGN, PATIENTS, AND SETTING: Diary validation was performed in a three week, prospective study of 106 children aged 6-14 years with asthma. Children were classified at baseline as either stable (requiring no additional asthma treatment) or new onset/worse (requiring either addition of or increase in anti-inflammatory treatment). RESULTS: A daytime symptom scale and "day without asthma" were defined from diary questions. Both measures demonstrated significant validity and responsiveness to anti-inflammatory treatment. The stable group experienced a higher percentage of days without asthma during week 1 compared with the new onset/worse group (39.6% v 11.6%, respectively). The new onset/worse patients experienced significant improvement in days without asthma (24.5%) compared with stable patients (6.4%). CONCLUSIONS: The Pediatric Asthma Diary daytime symptom scale and day without asthma are acceptable measures for use in asthma intervention studies of children aged 6-14 years.
Evidence of partially preserved endothelial dilator function in diseased coronary arteries.
OBJECTIVE: To examine the effects of substance P (endothelium dependent vasodilator) and glyceryl trinitrate (endothelium independent vasodilator) on epicardial coronary arteries in patients with normal coronary angiograms and patients with coronary artery disease. DESIGN: Intracoronary infusions of normal saline, the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min each for five minutes), and glyceryl trinitrate (250 microg bolus) were given in 24 patients with coronary artery disease and stable angina, and in nine patients with normal angiograms. The diameter of proximal and distal coronary segments was measured by computerised quantitative angiography RESULTS: Proximal segments of patients with coronary artery disease dilated less than those of patients with normal angiograms in response to 27.8 pmol/min substance P (mean (SEM): 7.9 (1.3)% v 15 (2.3)% respectively, p < 0. 01). The proximal segments of diseased arteries also dilated less than those of "normal" arteries in response to glyceryl trinitrate (10.2 (1.6)% v 18.4 (2.9)%, respectively, p < 0.01). The responses of distal segments to substance P and glyceryl trinitrate were similar in the two patient groups. There were correlations (all p < 0.001) between the coronary diameter after substance P and after glyceryl trinitrate in normal proximal segments (r = 0.94) and normal distal segments (r = 0.64), in diseased proximal segments (r = 0.95) and diseased distal segments (r = 0.89), and for coronary stenoses (r = 0.93). CONCLUSIONS: Proximal segments of patients with coronary disease dilated less than the proximal segments of "normal" patients in response to substance P and glyceryl trinitrate. The response to substance P is substantial and closely correlated with the response to glyceryl trinitrate in both "normal" patients and those with coronary disease. This suggests that although the proximal segments of diseased coronary arteries have a reduced capacity to dilate in response to direct stimulation of smooth muscle cell relaxation, they retain much of their endothelium dependent vasodilator function.
Nuclear industry family study:methods and description of a United Kingdom study linking occupational information held by employers to reproduction and child health.
OBJECTIVE: To describe the methods used in the nuclear industry family study for which a comprehensive database has been assembled that links employment in the nuclear industry and dosimetry records to information on employees' reproductive health and the health of their children. To discuss the response rates and characteristics of the study population. METHODS: Occupational cohort design leading to a retrospective cohort study of reproductive outcomes reported by 46 396 current and former employees of both sexes in the nuclear industry. Employees of nuclear establishments in the United Kingdom operated by the Atomic Energy Authority, the Atomic Weapons Establishment, and British Nuclear Fuels were surveyed with postal questionnaires ot collect information on pregnancies, children,and periods of infertility. Information on employment and monitoring for ionising radiation was supplied by the employing nuclear authority and was linked to pregnancies and periods of infertility with unique personal identification numbers. RESULTS: The design and completion of this study resulted in high quality data on a representative population of the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels workforces. The response to the survey was extremely good (82% for male workers and 88% for female workers, excluding undelivered questionnaires), and a unique relational database has been created which will enable infertility, pregnancy, and child health outcomes to be examined with respect to the employment and radiation monitoring characteristics of parents. CONCLUSION: This is the first United Kingdom study to link detailed reproductive history data to occupational information held by employers. The methods developed for the study were found to be feasible and successful. The design can be adapted for other investigations of reproductive hazards to men and women in the workplace and is currently in use to survey over 100 000 armed forces personnel in an investigation of reproductive outcome among veterans of the Gulf war.
The sequential modular curriculum for oral health personnel: an evaluation of the Fijian experience after five years.
In 1993 a new sequential modular curriculum was introduced for the training and education of oral health personnel in Pacific Island countries. The five-year model provided a multi-stage course with the opportunity to exist at the level of dental hygienist after two years, dental therapist or dental technologist after three years and dental surgeon after five years. After five years' experience the principles involved in the introduction of such a curriculum have been confirmed as educationally sound. The model may also be useful for introduction in other countries providing its structure and the details of individual modules are tailored to local social, cultural and demographic needs.
Representing staff grade doctors.
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Barriers to optimum management of heart failure by general practitioners.
BACKGROUND: Published research offers clear pointers to the management of heart failure; however, the evidence for implementation into practice is sub-optimal. AIM: To identify the salient barriers to adopting evidence-based management of heart failure in the community. METHOD: Structured interviews were used to elicit the views of a stratified sample of 100 general practitioners (GPs) about the diagnosis and treatment of heart failure. Responses to three heart failure case scenarios provided an indication of the degree to which GPs' knowledge of heart failure and trial results might be applied to diagnosis and treatment intentions. RESULTS: Participants were generally well aware of clinical trials that showed that prognosis could be improved by treatment, but trial results appeared to have little influence on treatment intentions in the three case scenarios. The major barriers to optimum management were the difficulties of differential diagnosis and the perceived properties of angiotensin-converting enzyme inhibitors (ACE-I) relative to diuretics. In the case scenarios, less than 30% reported that they would undertake basic investigations, such as chest X-ray or haemoglobin, or prescribe ACE-I. Over 70% perceived diuretics to be a useful diagnostic tool. The most frequent reasons for not prescribing ACE-I were the perceived inconvenience and risks of adverse effects (41%) and the view that most patients can be managed successfully on diuretics alone (27%). Over two-thirds of the sample were dissatisfied with the quality of information accompanying heart failure patients discharged from hospital. CONCLUSION: Facilitating evidence-based management of heart failure in the community requires further support for GPs in the form of additional training in the diagnosis of heart failure and the optimum use of both ACE-I and diuretics, and by improved communication between GPs and hospital doctors on a case-by-case basis.
A man with heart failure refuses to be admitted.
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Comparison of 201Tl, 99mTc-tetrofosmin, and dobutamine magnetic resonance imaging for identifying hibernating myocardium.
BACKGROUND: Both radionuclide perfusion tracers and contractile response to dobutamine have been used to identify hibernating myocardium. The aim was to compare 201Tl (thallium) single photon emission CT (SPECT), 99mTc-tetrofosmin (tetrofosmin) SPECT, and dobutamine cine MRI for identifying regions of reversible myocardial dysfunction. METHODS AND RESULTS: Thirty patients with 3-vessel coronary artery disease and impaired left ventricular function (mean LVEF, 24.0%; SD, 8.3%) scheduled for coronary bypass grafting were recruited. All underwent rest/dobutamine stress (5 to 10 microg . kg-1 . min-1) cine MRI, stress/rest tetrofosmin SPECT, and stress/redistribution and separate-day rest/redistribution thallium SPECT before surgery. Stress/redistribution thallium SPECT and resting MRI were repeated after surgery. In a 9-segment model, SPECT images were scored visually for tracer uptake, which was also measured from a polar plot of myocardial counts. MRI was scored visually for endocardial motion, myocardial thickening, and thickness. Five patients died before follow-up, and 2 declined postoperative investigation. In the remaining 23 patients, mean LVEF increased from 24.0% (SD, 8.3%) to 29.7% (SD, 11.1%) (P<0.05). Of 207 segments analyzed, 145 had significantly abnormal wall motion before surgery, and 82 of these improved function after revascularization. The criteria for predicting recovery of severely hypokinetic segments on preoperative imaging were tracer uptake graded "moderately reduced" or better, or positive inotropic response on dobutamine MRI. Late-rest thallium images showed the highest sensitivity (76%), compared with stress-redistribution thallium (68%) and rest tetrofosmin (66%) (P<0.05). All 3 tracer techniques were nonspecific (44%, 51%, and 49%, respectively). Redistribution of thallium after the resting injection was insensitive (18%) but highly specific (83%). Inotropic response to dobutamine was also insensitive (50%) but specific (81%). CONCLUSIONS: Radionuclide uptake is a sensitive but nonspecific predictor of myocardial functional recovery, whereas dobutamine MRI is specific but insensitive.
Acetylcholine and endothelial function
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