Search PubMed⌕ Search

Biomedical subjects

B Gaffney

Publications and source records attributed to B Gaffney.

17 recordsLinked to original sources
PubMed1997

Prioritising the cardiac surgery waiting list: the angina patient's perspective.

OBJECTIVE: To determine patients' views on how clinical and demographic factors should affect priorities for cardiac revascularisation. DESIGN: A descriptive survey of patients' views conducted immediately after angiography and treatment counselling. SUBJECTS: 136 patients who were awaiting coronary angioplasty in either of the two regional cardiology centres in Northern Ireland. RESULTS: About half the subjects (52%) felt that certain social factors such as having dependent relatives should be taken into account when deciding priority for surgery. A sizeable minority felt that younger subjects and non-smokers (40% and 44%, respectively) should be accorded higher priority, with older subjects and smokers being more likely to hold such views. CONCLUSIONS: While there is little evidence that demographic and lifestyle factors affect the relative efficacy of surgery, the challenge remains to devise a prioritisation guideline that can properly reflect societal values and the evidence base.

Age Factors↗
PubMed1997

Risks and benefits of coronary angioplasty: the patients perspective: a preliminary study.

OBJECTIVES: To describe what cardiac patients in Northern Ireland understand to be the benefits of coronary angioplasty and assess the extent to which they have been able to make informed choices about their treatment. DESIGN: An interview based questionnaire survey completed after the patients had undergone coronary angiography, within hours of treatment counselling. SUBJECTS: 150 patients consecutively recruited from two regional cardiology centres in Belfast, Northern Ireland. MAIN OUTCOME MEASURES: The perceived complication rate and the perceived gain in life expectancy from coronary angioplasty. RESULTS: Although most subjects had asked the consultant questions, 70% (n = 104) thought that they contributed negligibly or not at all to the treatment decision. Although 75% (n = 112) recalled discussing the complication rate from the procedure, only 27% accurately estimated this rate (as between 0.5 and 1.5%). Eighty eight per cent (n = 131) thought that their mortality risks would be substantially or greatly reduced by having the procedure. The patients anticipated a gain in life expectancy of some 10 years (median) and this was significantly in excess of the potential gain in life expectancy which dietary prudence to lower blood cholesterol, not smoking, and taking more exercise might produce (median 5 years respectively; P < 0.0001, Wilcoxon matched pairs signed rank test). CONCLUSIONS: Patients vastly overrate the capacity of angioplasty to control their disease: angioplasty is seen as more effective than risk factor modification.

Adult↗
PubMed1995

Structure of a new crystal form of a DNA dodecamer containing T.(O6Me)G base pairs.

The structure of the synthetic dodecamer (d[CGTGAATTC(O6Me)GCG])2 has been determined to a resolution of 2.25 A and refined to a final R factor of 16.7%. The volume of the unit cell is significantly smaller by 16% than the original Drew and Dickerson parent dodecamer [Drew, H. R., Wing, R. M., Takano, T., Broka, C., Tanaka, S., Itakura, K., & Dickerson, R. E. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 7318-7322]. The double helix is in a different position in the unit cell, rotated by -85.9 degrees, and translated by 9.9 A around the helical axis with respect to the parent structure. The intermolecular arrangement of helices, characterized by double hydrogen bonded guanine-guanine minor groove interactions, remains conserved. The molecular geometry exhibits several significant changes that are related to the changed position of the helix and the presence of two mismatched base pairs with O6-methylguanine. Both mispairs are found in a symmetrical T(anti).(O6Me)G(anti) conformation, and the methyl groups are in proximal orientation. The hydration pattern of the structure is different and can be related to changes in the minor groove geometry. An incorrect model that was isomorphous to the parent dodecamer could be refined to a low R factor. Characteristics of the refinement and of the geometry that are indicative of incorrect structures have been analyzed.

Base Composition↗
PubMed1995

Crystal and molecular structure of a new Z-DNA crystal form: d[CGT(2-NH2-A)CG] and its platinated derivative.

The three-dimensional structure of d[CGTA'CG], where A' = [2-NH2-A], was determined to atomic (1.35 A) resolution by single isomorphous replacement. The d[CGTA'CG] hexamer crystallizes in space group P3221, and is not isomorphous with other DNA hexanucleotides. Despite completely different crystal packing, the essential characteristics of the Z-DNA conformation are maintained. The structure was determined by single isomorphous replacement using a triammine platinum fragment. Thus, this study also demonstrates, for the first time, the feasibility of the use of this reagent for the direct phasing of DNA crystal structures.

Base Sequence↗
PubMed1995

Treatment of angina pectoris in the community: is medical therapy given a chance?

OBJECTIVE: To describe the routine management of patients with chronic stable angina by GPs in Northern Ireland and the factors which they perceived affected the success of medical therapy. DESIGN: A questionnaire survey of all general practitioners in Northern Ireland (n = 962). SETTING: A survey conducted collaboratively by the Departments of Public Health Medicine in each of the four Health Boards in the province. Total population served, 1.5 million. MAIN OUTCOME MEASURES: The relationship between the perceived reasons for medical treatment failure and the stated referral and prescribing practice of the GPs. RESULTS: A total of 541 GPs replied; the response rate was 56%. The two most important reasons given for the perceived failure of medical therapy were (i) underlying disease progression and (ii) an adverse patient lifestyle such as smoking or obesity (cited as of primary importance by (i) 264 and (ii) 225 doctors respectively). The ranking differed significantly according to the doctor's propensity to prescribe triple therapy, with those doctors in the highest tertile of this distribution being less likely to cite the patient's lifestyle as a primary reason for treatment failure (chi-squared = 6.7, d.f. = 2, P = 0.035) and more likely to cite underlying disease progression as a primary reason (chi-square = 7.0, d.f. = 2, p = 0.031). The overall ranking of the primary reasons for referral differed significantly according to the proportion of patients given a trial of triple therapy and to the doctor's propensity to refer. Doctors who had given a greater proportion of their patients at least a trial of triple therapy (in the highest tertile of the distribution) were more likely to cite the need for revascularisation assessment as the primary reason (chi-square = 12.5, d.f. = 2, P = 0.0019). On the other hand, the need for further advice on medical therapy was generally ranked higher by those doctors who had given fewer of their patients at least a trial of triple therapy (chi-square = 7.3, d.f. = 2, P = 0.027). GPs who had referred fewer of their new patients to hospital were more likely to be those doctors with fewer patients given at least a trial of triple therapy. Doctors with a greater percentage of their patients managed primarily by a hospital specialist tended to have more who had had a trial of triple therapy for their symptoms. CONCLUSIONS: The results suggest the need for clearer definition for GPs of the place of revascularisation and of medical therapy for patients with stable angina.

Angina Pectoris↗
PubMed1995

Expanding access to coronary artery bypass surgery: who stands to gain?

OBJECTIVE: To determine the perceptions of general practitioners (GPs) about the benefits of coronary artery bypass surgery, in terms of gains in life expectancy, for different groups of patients. DESIGN: A questionnaire survey of all GPs in Northern Ireland. SETTING: A survey conducted collaboratively by the departments of public health medicine in each of the four health boards in the province, serving a total population of 1.5 million. MAIN OUTCOME MEASURES: The median and mean gain in life expectancy perceived by groups of doctors for smoking and non-smoking male and female 55 year old patients. The percentage of 50 year old and 70 year old non-smoking patients considered likely to have their lives extended with bypass surgery. Differences were assessed using the Mann-Whitney U test for unpaired samples and the Wilcoxon signed rank tests for paired. RESULTS: 541 GPs replied (response rate 56%). The median (and mean) perceived gain in life expectancy after cardiac surgery for non-smoking 55 year old subjects was 120 (104) months for men and 120 (112) months for women (z = 6.42; P < 0.0001; Wilcoxon signed rank test). For male and female smokers of the same age, the perceived gains were 48 (47) and 60 (52) months respectively (z = 6.72; P < 0.0001; Wilcoxon signed ranks test), both figures being significantly different than for non-smokers. The median (and mean) percentage of patients that the doctors considered would have their lives extended by bypass surgery was 70 (64) of every 100 "young" patients and 40 (42) of every 100 "old" patients, (z = 16.2; P < 0.0001). CONCLUSIONS: These results point to a significant overestimation of the benefits of coronary artery bypass surgery by GPs in Northern Ireland and to a need to develop guidelines for referral.

Age Factors↗
PubMed1995

Are the economically active more deserving?

OBJECTIVE: To investigate the possibility of an association between the duration of medical treatment before coronary angiography and demographic and non-clinical factors. DESIGN: A systematic review of a random sample of 500 patients undergoing their first angiographic assessment. SUBJECTS: 500 cases were selected randomly from patients investigated in 1991 at the two catheterisation centres in Northern Ireland. MAIN OUTCOME MEASURES: The duration of medical management before angiography. RESULTS: 346 had elective and 154 urgent catheterisation. The duration of medical management was adjusted for both case mix (age at onset, body mass index, angina grade, history of myocardial infarction, history of hypertension, diabetes or hyperlipidaemia, treatment intensity) and other demographic variables (sex, smoking status, an indicator of "deprivation", and distance of the patient's area of residence from the hospital). After this adjustment the mean duration of medical management before angiography was twice as long for economically inactive patients as for those who were economically active. In a multiple regression, the relevant beta coefficient was 0.44 (95% confidence interval 0.33 to 0.58, P < 0.0001). CONCLUSIONS: These results suggest that, in making discretionary decisions about when to refer patients with angina for revascularisation assessment, doctors may be influenced by non-clinical factors unrelated to disease severity.

Age Factors↗
PubMed1995

Predictors for waiting time for coronary angioplasty in a high risk population.

Objective--To describe the clinical and non-clinical factors which influence the waiting time from initial angiography to angioplasty. Design--Follow up of a random sample of 106 patients undergoing their first coronary angiography for whom a decision to revascularise by percutaneous transluminal angioplasty was made in 1991. The period between the date of angiography and the date of angioplasty and various clinical characteristics of patients were retrieved from medical notes in mid 1993. Patients were sampled from those investigated in the two Northern Ireland catheterisation laboratories in Belfast, which provide services for the whole of the province (population 1.5 million). Main measures--The dependent variable was the period between initial angiography and angioplasty, and the independent variables included age, sex, distance from cardiac catheterisation centre, referral source, characteristics of the clinical history, severity of angina, and anatomical extent of disease. Cox's proportional hazards analysis was used to derive a relative hazard, expressing the relative chances of revascularisation occurring at any time during follow up. Results--Of the 106 patients studied, 93 had had percutaneous transluminal angioplasty at follow up. The most important predictors of waiting time were the presence of severe angina (relative hazards 3.1(95 % confidence interval (95% CI) 1.4-6.8) and 2.7(1.2-6.2) for Canadian Cardiovascular grades III and IV v angina grade I angina), a recent history of myocardial infarction (relative hazard, 2.5(1.3-4.8), and whether or not the patient was economically active (relative hazard 0.6(0.4-1.0) for economically inactive v active patients). Although there was also an association with the relative deprivation of the area of residence of the patient it had no clear linear trend. Conclusions--Although waiting time for percutaneous transluminal angioplasty was predictably related to the patient's clinical presentation, demographic factors may also be important in determining access to intervention. These factors clearly merit further study; ultimately, the evaluation of equity in a waiting time distribution may more properly be a societal rather than a clinical judgment.

Angioplasty, Balloon, Coronary↗
PubMed1995

Priority for coronary artery surgery: who gets by-passed when demand outstrips capacity?

We investigated the clinical and non-clinical factors which influence the waiting time from initial angiography to bypass surgery, by follow-up of a random sample of 141 patients undergoing their first coronary angiography, for whom a decision to revascularize was made in 1991. The period between the date of angiography and the date of surgery, and a variety of clinical patient characteristics, were retrieved from medical notes in mid-1993. Patients were sampled from those investigated in the two Northern Ireland catheterization laboratories in Belfast, both of which were served by one local surgical centre. Of the 141 patients studied, 86 had had surgery at follow-up. The most important predictors of waiting time were: the presence of severe stenosis of the left main-stem coronary artery [relative hazards, 3.4 (1.6-7.3)], the presence of unstable angina at the time of angiography, [relative hazards, 2.2 (0.97-5.0)], age at angiography, [relative hazards, 2.2 (1.1-4.2) for > 65 years vs. < 50 years], having a positive family history of premature coronary artery disease in a first-degree relative, [relative hazards, 1.8 (1.1-2.9)] and smoking habit at angiography, [relative hazards 0.6 (0.3-1.1), for current vs. never/ex-smokers]. More weight appears to be given to maximizing life extension rather than its quality enhancement in determining who gets priority for surgery. The exception to this may be in regard to smokers, and purchasers might find it useful to set targets for secondary prevention activities with respect to such patients.

Age Factors↗
PubMed1994

Crystal structure of a mispaired dodecamer, d(CGAGAATTC(O6Me)GCG)2, containing a carcinogenic O6-methylguanine.

The crystal structure of the synthetic deoxydodecamer d(CGAGAATTC(O6Me)GCG)2 has been determined and refined to an R-factor of 16.9% with data up to 2.9-A resolution. This sequence contains two mismatched base pairs between O6-methylguanine and adenine with the arrangement A(syn).(O6-Me)G(anti) which differs from the geometry observed in solution by NMR. The intermolecular arrangement is equivalent to the other isomorphous deoxydodecamers. However, the weakening of some significant crystal packing contacts was observed and related to the effect of stacking between the mispaired adenine and the adjacent guanine in the sequence. The structure is highly hydrated, with a total of 49 solvent molecules located. The methyl group and the mismatched base-pair geometry locally disrupt the B-DNA-type solvent network with two solvent molecules found close to the N1 and N6 of the mispaired adenine.

Adenine↗
PubMed1994

Is choice of general practitioner important for patients having coronary artery investigations?

OBJECTIVE: To determine whether particular sociodemographic characteristics of patients with stable angina affected their general practitioners' (GPs') decisions to refer them for revascularisation assessment. DESIGN: Postal questionnaire survey. SETTING: Collaborative survey by the departments of public health medicine in each of the four health boards in Northern Ireland, serving a total population of 1.5 million. SUBJECTS: All (962) GPs. MAIN MEASURES: The relation between GPs' referral decisions and patients' age, sex, employment status, home circumstances, smoking habits, and obesity. RESULTS: 541 GPs replied (response rate 56%). Most were "neutral" towards a patient's sex (428, 79%), weight (331, 61%), smoking habit (302, 56%), employment status (431, 80%), and home circumstances (408, 75%) in making decisions about referral. In assigning priority for surgery most were neutral towards the patient's sex (459, 85%), employment status (378, 70%), and home circumstances (295, 55%). However, most GPs (518, 95%) said that younger patients were more likely to be referred, and a significant minority were less likely to refer patients who smoked (202, 37%) and obese patients (175, 32%) and more likely to refer employed patients (97, 18%) and those with dependents (117, 22%) (compared with patients with otherwise comparable clinical characteristics); these views paralleled the priority which GPs assigned these groups. The stated likelihood of referral of young patients was independent of the GPs' belief in ability to benefit from revascularisation, but propensity to refer and perception of benefit were significantly associated for all other patient characteristics. CONCLUSION: GPs' weighting of certain characteristics in reaching decisions about referral for angiography is not uniform and may contribute to unequal access to revascularisation services for certain patient groups.

Age Factors↗
PubMed1993

Access to coronary catheterisation: fair shares for all?

OBJECTIVE: To determine the effects of patient's sex and area's material deprivation on utilisation rates of coronary catheterisation and angiography in the investigation of ischaemic heart disease. DESIGN: Retrospective analysis of routinely collected hospital statistics. SETTING: Acute hospitals throughout Northern Ireland. SUBJECTS: 24,179 episodes of patients discharged from hospital with a primary diagnosis of ischaemic heart disease and 1270 episodes relating to patients with an underlying diagnosis of ischaemic heart disease who had either coronary catheterisation or angiography. MAIN OUTCOME MEASURES: Age standardised admission rates for heart disease and age standardised utilisation rates for catheterisation or angiography, or both, for 566 electoral wards ranked by Townsend "deprivation" scores. RESULTS: Catheterisation-angiography rates in men were over fivefold those of women, ranging from 85.5/100,000 v 16/100,000 in patients from "well off" areas to 123/100,000 v 22/100,000 for patients from deprived areas. After admission rates for heart disease were controlled for, the overall rate ratio for women was 0.48 (95% confidence interval 0.38 to 0.60). After differential admission rates for heart disease and other potential clinical confounders were controlled for, the investigation rates of patients from the least and most "deprived" areas were not significantly different (rate ratio 1.04 (0.87 to 1.25)). CONCLUSION: Although investigation rates were significantly lower in women than in men, further clinical data would be required before labelling this underutilisation as evidence of bias. There was no significant difference in invasive investigation rates for heart disease in areas of varying deprivation or affluence.

Adult↗
PubMed1992

Crystal and molecular structure of a DNA fragment containing a 2-aminoadenine modification: the relationship between conformation, packing, and hydration in Z-DNA hexamers.

The crystal and molecular structure of d(CGUA'CG)2 (where A' is 2-aminoadenine) has been determined and refined to an R factor of 13.8% for data 8.0-1.3 A. The structure is very similar to the original Z-DNA structures with the sequence d(CGCGCG)2 [Gessner, R. V., Frederick, C. A., Quigley, G. J., Rich, A., & Wang, A. H.-J. (1989) J. Biol. Chem. 264, 7921] and shows that the substitution of 2-aminoadenine-uracil base pairs in the two central steps is consistent with Z-DNA formation. In addition, we show how waters mediating intermolecular interactions may help to explain the ZI-ZII conformational pattern found in many Z-DNA structures.

2-Aminopurine↗
PubMed1991

Characterization by 1H NMR of glycosidic conformations in the tetramolecular complex formed by d(GGTTTTTGG).

We have conducted two dimensional NOESY studies on the molecule d(G2T5G2) to characterize the structure of the tetramolecular complex previously identified by calorimetric and spectroscopic studies (1). Analysis of the NOE and exchange cross peaks observed in the NOESY spectra establishes the formation of structured conformations at low temperature (5 degrees C). Significantly, within each strand of these structured conformations, the G1 and G8 residues adopt syn glycosidic torsion angles, while the G2 and G9 residues adopt anti glycosidic torsion angles. Consequently, any structure proposed for the tetramolecular complex of d(G2T5G2) must have alternating G(syn) and G(anti) glycosidic torsion angles within each strand. The implications of this observation for potential structures of the tetramolecular complex of d(G2T5G2) are discussed.

Base Sequence↗
PubMed1988

Estimation of genetic trend in racing performance of thoroughbred horses.

Thoroughbred horses have been bred exclusively for racing in England since Tudor times and thoroughbred horse racing is now practised in over 40 countries and involves more than half-a-million horses worldwide. The genetic origins of the thoroughbred go back largely to horses imported from the Middle East and North Africa to England in the late seventeenth and early eighteenth centuries. Since the establishment of the Stud Book in 1791, the population has been effectively closed to outside sources, and over 80% of the thoroughbred population's gene pool derives from 31 known ancestors from this early period. Despite intense directional selection, especially on the male side, and the generally high heritabilities of various measures of racing performance, winning times of classic races have not improved in recent decades. One possible explanation for this is that additive genetic variance in performance may have been exhausted in the face of strong selection. To test this, we have estimated the genetic trend in performance over the period 1952-77 using TIMEFORM handicap ratings which are based entirely on the horse's own performance, and express its racing merit as a weight in pounds which the compilers believe the horse should carry in an average free-handicap race. These ratings take into account such factors as the firmness of the ground, the distance and the level of the competition. Our results indicate that the failure of winning times to improve is not due to insufficient genetic variance in the thoroughbred population as a whole.

Animals↗
PubMed1986

Repair of oligodeoxynucleotides containing O6-methylguanine by O6-alkylguanine-DNA-alkyltransferase.

O6-Alkylguanine-DNA-alkyltransferase is a DNA repair protein known to carry out the transfer of alkyl groups from the O6-position of guanine in alkylated DNA to a cysteine acceptor site contained within its own protein sequence. We have examined the ability of this protein isolated from either E. coli or mammalian cells to perform this repair reaction in short oligodeoxynucleotides. Dodecadeoxynucleotides of the sequence 5'-dCGNGAATTCm6GCG-3' where N is any one of the normal four bases were all repaired very rapidly by the protein with 50% repair in less than 15 s at 0 degree C. The hexadeoxynucleotide 5'-dCGCm6GCG-3' was repaired slightly more slowly with 50% removal taking 7 min at 0 degree C and 1.5 min at 37 degrees C. The tetradeoxynucleotide 5'-dTm6GCA-3' was also a substrate but was repaired much more slowly requiring 45 min for 50% repair at 37 degrees C. These results indicate that (a) the AGT has a strong but not absolute preference for double-stranded DNA substrates; (b) the repair of O6-methylguanine is independent of the base opposite the lesion; and (c) that oligodeoxynucleotides as short as tetramers are substrates for repair by this protein.

DNA Repair↗