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Biomedical subjects

R Conroy

Publications and source records attributed to R Conroy.

At least 37 records · Page 2Linked to original sources

Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F.

E2F is a mammalian transcription factor that appears to play an important role in cell cycle regulation. While at least two proteins (E2F-1 and DP-1) with E2F-like activity have been cloned, studies from several laboratories suggest that additional homologs may exist. A novel protein with E2F-like properties, designated E2F-2, was cloned by screening a HeLa cDNA library with a DNA probe derived from the DNA binding domain of E2F-1 (K. Helin, J. A. Lees, M. Vidal, N. Dyson, E. Harlow, and A. Fattaey, Cell 70:337-350, 1992). E2F-2 exhibits overall 46% amino acid identity to E2F-1. Both the sequence and the function of the DNA and retinoblastoma gene product binding domains of E2F-1 are conserved in E2F-2. The DNA binding activity of E2F-2 is dramatically enhanced by complementation with particular sodium dodecyl sulfate-polyacrylamide gel electrophoresis-purified components of HeLa cell E2F, and anti-E2F-2 antibodies cross-react with components of purified HeLa cell E2F. These observations are consistent with a model in which E2F binds DNA as a heterodimer of two distinct proteins, and E2F-2 is functionally and immunologically related to one of these proteins.

Amino Acid Sequence↗

A case control study of malignant melanoma.

A case-control study of 100 cases of malignant melanoma (MM) and 100 matched controls has been completed. The male:female ratio of patients with MM was 1:2.4, which is similar to that found in other European studies and the mean age was 49.1 years (range 19-82 years). Significant differences were seen between cases and controls for area of residence and social class, more cases than controls came from rural areas (P = 0.007) and cases were of higher social class than controls (P = 0.003) and had attained a higher level of education (P = 0.005). Phenotypic differences between cases and controls were also observed, namely cases were more likely to have light coloured (blue/grey/green) eyes (P = 0.003) and to have had fair/red hair at age 20 (P = 0.004). Cases were also more likely than controls to dislike exposure to hot sun (P = 0.008) to report sunburning easily (P = 0.001) and to have experienced episodes of sunburn with blistering more frequently than controls (P = 0.01). History of longterm exposure to ultraviolet radiation (UV) through working outdoors, leisure activities, living abroad in sunny climates, or sun holidays was similar between cases and controls. This study supports evidence from elsewhere that episodes of acute sunburn in susceptible individuals increase risk of MM and that longterm regular exposure to UV which is important in non-melanoma skin cancer does not play a major role in the development of MM.

Adult↗

Management of epiphrenic esophageal diverticula. A fifteen-year experience.

Epiphrenic esophageal diverticula represent an unusual cause of dysphagia, pain, and weight loss. Although commonly associated with motility disorders, distal esophageal diverticula also have been associated with reflux strictures or other lesions. To determine the most appropriate diagnostic evaluation and operative approach, we reviewed the recent 15-year experience with epiphrenic esophageal diverticula at our institution. Over the study period, 18 patients were diagnosed with pulsion epiphrenic diverticula. Nine patients (50%) with symptomatic diverticula were referred for surgical management. All referred patients were evaluated with preoperative manometry, endoscopy, and contrast esophagography. Diverticulectomy was performed via posterolateral thoracotomy in all patients, combined with myotomy in the 6 patients (67%) with abnormal manometric results and in 2 patients with normal manometric results. The third patient with normal manometric results underwent simple diverticulectomy. There was no operative mortality. One complication, a small esophageal leak, was managed successfully by early reoperation. All patients were free of dysphagia at discharge. Follow-up was obtained for 17 patients (94%) ranging from 3 months to 12 years. Good to excellent results (measured by relief of symptoms, weight gain, and absence of clinical recurrence) were seen in all 9 surgical patients; 6 of 9 nonsurgical patients remained or became symptomatic. This experience demonstrates the efficacy of surgical management of symptomatic epiphrenic esophageal diverticula. Diverticulectomy combined with selective myotomy permits excellent operative results and resolution of associated symptoms.

Deglutition Disorders↗

Laser-assisted versus mechanical recanalization of femoral arterial occlusions.

A randomized clinical trial was performed to test the hypothesis that a laser-heated probe is superior to standard techniques to reopen occluded femoral arteries. Twenty patients were treated with a standard guidewire and balloon dilation method. In a second group of 20 patients, the laser probe was initially used as a nonheated mechanical device. If the probe was unsuccessful in mechanically reopening the artery, an Argon laser was activated to heat the probe. The mean length of occlusion was 15.9 +/- 10.3 cm. The success rate for the laser probe was 15 of 20 (75%), which was not significantly different from the standard method, 19 of 20 (95%). Most of the success in the laser-probe group was due to the probe's mechanical properties. The laser probe was successful as a cold, mechanical device in 13 of 15 (87%) arteries. It was necessary to heat the probe in 5 patients. When heated, the laser probe assisted recanalization in 2 but perforated the artery in 3 cases. The results of this randomized trial do not support the hypotheses behind the use of the thermal laser probe. The laser probe functions primarily as a mechanical device. The thermal activation does not significantly improve the success rate without increasing the risk of perforation. This small additional benefit does not justify the large cost of current thermal laser devices. This controlled study also demonstrates a higher success rate in long occlusions than previous reports of mechanical balloon recanalization. This is due to a combination approach of retrograde and anterograde probing of the occluded segment.

Adult↗

The Kilkenny Health Project: a community research and demonstration cardiovascular health programme.

Ireland has one of the highest death rates in the world from coronary heart disease (CHD) and has not shared in the rapid decline in mortality which has occurred in other countries. The Kilkenny Health Project was established as a community-based research and demonstration programme for cardiovascular disease prevention in County Kilkenny and as a pilot project for future national initiatives. The first phase of the health promotion programme in Kilkenny is being carried out between 1985 and 1990. Changes in behaviour and in factors associated with CHD will be estimated by the difference in changes over time between Kilkenny and the reference area, as measured by independent random sample surveys of men and women aged 35 to 64 years. CHD and stroke events, fatal and non-fatal, will be registered in both areas from 1987-1992. The Project has studied attitudes to CHD and its prevention. Health behaviours have been studied in adults and in post-primary school pupils. Risk factors for CHD have been measured in adults in accordance with the methods of the international MONICA Project. It has been demonstrated that health and education professionals can incorporate preventive activities and health education into everyday practice.

Adult↗

Registration of myocardial infarction and stroke in the Kilkenny Health Project: methodology.

A myocardial infarction and stroke register was established in January 1987 as part of the evaluation of the Kilkenny Health Project. This is a community programme which aims to reduce risk factors for coronary heart disease. The register records acute myocardial infarction and stroke in residents of County Kilkenny and of the reference county. This will provide accurate estimates of the incidence of these diseases and of trends over time. Methods used comply with the protocol in use by the WHO MONICA Project. This will allow comparison of the incidence of coronary heart disease and stroke in this register with that in other MONICA locations, including that in Belfast, Northern Ireland. Information is obtained from sources in hospitals and the community about relevant history, symptoms and investigations. Information about deaths is also obtained from these sources, and from coroners, death registers and the Central Statistics Office. Appropriate steps are taken to ensure confidentiality of the information. Each event satisfying the MONICA diagnostic criteria for myocardial infarction and stroke is coded in accordance with the MONICA protocol, categorised and registered.

Adult↗

A heart health assessment programme in general practice in County Kilkenny, Ireland.

The Kilkenny Faculty of the Irish College of General Practitioners and the Kilkenny Health Project have established a Health Assessment Programme (HAP) to standardise the examination and recording of coronary heart disease (CHD) risk factors in general practice. Criteria were agreed for classification and coding of demographic data, relevant medical history and risk behaviours. Height, weight and blood pressure are measured and venous blood sample is taken for total cholesterol estimation. The assessment is followed by appropriate counselling. The HAP was first targetted at men and women aged 40 to 49 years. During the first 16 months of the programme, 2102 assessments were carried out by 41 general practitioners, which represents 29% of the target group. Those taking part had a lower social class distribution when compared with participants in the KHP baseline survey in 1985. There were no significant differences between the two groups in smoking prevalence or in the distribution of body mass index. Median cholesterol was 5% lower in the HAP group than at the baseline survey. 16% of the HAP clients had diastolic blood pressures of 90 mm Hg or more. The HAP has demonstrated that it is feasible to measure CHD risk factors in a variety of general practice settings. The format facilitates a preventive orientation and has proved acceptable to patients.

Adult↗

Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.

The intravenous administration of heparin to patients before open heart surgery reduced ristocetin cofactor activity by 58% (P less than 0.01, t test), and this impairment of von Willebrand factor-dependent platelet function was closely related to plasma heparin levels (r2 = 0.9), but not to plasma von Willebrand factor (vWF) levels. We hypothesized that heparin may inhibit vWF-dependent platelet hemostatic functions by directly binding vWF in solution and interfering with vWF-GpIb binding. Using the in vitro techniques of ristocetin-induced platelet agglutination, fluorescent flow cytometric measurement of vWF-platelet binding, and conventional radioligand binding assays we observed that heparin inhibited both vWF-dependent platelet function and vWF-platelet binding in a parallel and dose-dependent manner. Heparin also inhibited platelet agglutination induced by bovine vWF and inhibited the binding of human asialo-vWF to platelets in ristocetin-free systems. The inhibitory potency of heparin was not dependent upon its affinity for antithrombin III, but was molecular weight dependent: homogeneous preparations of lower molecular weight were less inhibitory. Heparin impairment of vWF function may explain why some hemorrhagic complications of heparin therapy are not predictable based on techniques for monitoring the conventional anticoagulant effects of heparin.

Agglutination↗

Sex steroids, adiposity and smoking in the pathogenesis of idiopathic hirsutism and polycystic ovary syndrome.

Hyperestronemia may be central to the development of polycystic ovary syndrome. The present study was designed to examine whether increased availability of androstenedione or increased aromatase closely associated with adiposity, plays the dominant role in the development of hyperestronemia. We measured plasma androstenedione, estrone and the estrone/androstenedione ratio (an indirect index of peripheral aromatase activity), in 141 patients with idiopathic hirsutism and in 88 patients with polycystic ovary syndrome. Estrone levels were higher in polycystic ovary syndrome, 250.4 +/- 129 (mean +/- standard deviation) than in idiopathic hirsutism, 210.6 +/- 119 pmol/l, p less than 0.05. Plasma androstenedione levels were higher in polycystic ovary syndrome, 8.24 +/- 3.5, than in idiopathic hirsutism, 7.1 +/- 1.7 nmol/l, p less than 0.0025. However, the estrone/androstenedione ratio was similar in the two groups. In all patients who smoked, androstenedione was higher, 8.14 +/- 3.22 than in nonsmokers, 6.99 +/- 2.96 nmol/l, p less than 0.005. Smokers had a lower body mass index, 23.9 +/- 2.3, than non-smokers 25.6 +/- 4.8 kg/m2, p less than 0.025. However, estrone levels were similar in smokers and in non-smokers. These data indicate that elevated estrone is more closely related to increased availability of androstenedione than to increased aromatase activity. While cigarette smoking appears to increase androstenedione levels, it may inhibit aromatase activity either directly or indirectly because of an associated reduction in adiposity. However, since the relative frequency of polycystic ovary syndrome and idiopathic hirsutism was similar in smokers and non-smokers, smoking did not appear to reduce estrone bioactivity as had been claimed.

Adrenal Glands↗

Does intensive medical therapy influence the outcome in unstable angina?

Three hundred and forty-six patients of all ages and both sexes were admitted to coronary care with documented unstable angina. Management was conservative, without the routine use of beta-blockers or calcium antagonists. Mortality was 3.2%, and the nonfatal myocardial infarction rate was 10.1% during the first 28 days. After one year, coronary mortality was 10.5% with a nonfatal infarction rate of 13.1%. Twenty-six patients were subjected to coronary artery bypass surgery, eleven during the first 28 days and fifteen subsequently. No patient underwent coronary angioplasty. The factors influencing immediate and long-term prognosis in these patients were studied. Persistence of pain in hospital, previous chronic angina, and age had an adverse effect on outcome. A total of 143 patients complained of persistent pain lasting for 24 hours or more. The use of beta blockers or calcium antagonists in patients with persistent pain exceeding five days did not appear to influence outcome. The current widespread adherence to "intensive medical treatment," including the routine use of beta blockers and calcium antagonists, is questioned.

Adrenergic beta-Antagonists↗

The health and risk factor status of industrial employees.

2,183 employees from 13 Irish industries volunteered to take part in a risk factor identification and health counselling programme. Data are presented about the risk factor profile of the group. Alcohol abuse, overweight and hyperlipidaemia were prevalent, particularly among men. Hypertension, although relatively infrequent, was commoner among men and, like hyperlipidaemia and obesity, increased significantly with age. The subjects who smoked cigarettes accounted for 33% of the population studied, while 21% were ex-smokers, with substantially more ex-smokers among men than women. Only 22% of subjects took adequate exercise. Work stress was unusual but personal stress common. Only 75% of subjects used their seat belts regularly and the majority received no regular dental care. The role of industrial health programmes in disease prevention and health education, and in providing benefit to industry, is examined. Recommendations are made about effective means of encouraging healthy living in an industrial environment.

Adult↗

Psychological factors in cardiac rehabilitation.

Patients who are recovering from myocardial infarction or coronary surgery may have psychological symptoms but they are not psychiatric patients. Their emotional responses are normal. With appropriate psychological support, they will be able to adapt to and master the changes in their lives.

Activities of Daily Living↗

The spectrum of farming accidents seen in Irish general practice: a one-year survey.

A one-year prospective survey of farming accidents in three Irish counties recruited 37 general practitioners in a wide geographical sample. The response rate to the survey was 84%. There were 319 accident cases seen by the general practitioners in the survey period, and 175 (55%) of these were farmers. Children accounted for 52 (16%) of all accident cases. The majority of cases (256, 80%) were treated by the general practitioner, and the spectrum of injuries treated was very broad. Many injuries required extensive suturing and follow-up of soft-tissue injuries. General practitioner coroners were involved with five fatal farm accident cases. It is concluded that the Irish rural general practitioner is providing a significant trauma service to farm accident victims, and is a valuable source of information on these incidents. The general practitioner would be a local source of expertise in a health education campaign directed at increasing the awareness among the farming community on the extent of farm accident morbidity and mortality. Continuing education for rural general practitioners should be directed towards regular updates on trauma management.

Accidents, Occupational↗

Childhood farm accidents: a continuing cause for concern.

Farms in Ireland remain a dangerous environment for children despite increasing publicity about farming hazards based on international research. A one year prospective study on farm accidents was carried out in four Irish accident and emergency departments. During this time, four deaths and 62 cases of injury aged 15 years and under were seen. Half the cases required admission to hospital; tractor accidents were common and serious. Most injuries occurred to the extremities but 13 (21 per cent) had multiple injuries. Forty-three (69 per cent) of the children required outpatient follow-up and twenty-seven of these (63 per cent) had more than one outpatient re-visit. The Irish farming community is still unappreciative of the risks to their children on the farm, and urgent attention needs to be directed towards educational and legislative measures to improve the safety profile of Irish farms.

Accident Prevention↗

Risk factors for non-melanoma skin cancer.

A case control study of risk factors for non-melanoma skin cancer (NMSC) was carried out on 396 patients and individually age and sex-matched controls. Cases were significantly more likely than controls to have had a rural domicile (P = 0.007), light eye colour (P = 0.004) a tendency to develop sunburn very easily (P less than 0.05) and a family history of NMSC (P less than 0.001). Other indices of exposure or sensitivity to ultraviolet (UV) radiation did not differ significantly between the two groups. It is suggested that while the role of UV radiation in the aetiology of NMSC is not in doubt, other factors not yet identified must also be important, at least among the Irish population.

Female↗

Surgical treatment of skin cancer.

Eight hundred and twenty cases of skin cancer treated surgically at Saint Luke's Hospital over a ten-year period were reviewed retrospectively. Those undergoing excision, ie simple excision and primary closure, had significantly shorter hospitalization than those requiring grafts or amputation. The only prognostic factor in this particular series identified for local recurrence was a past history of skin carcinoma. Surgery was effective both as primary treatment and after failed irradiation. Local recurrence rates for skin carcinoma and melanoma were 8% and 10% respectively.

Basal Cell Carcinoma↗

The long-term work record of post-infarction patients subjected to an informal rehabilitation and secondary prevention programme.

The St Vincent's Cardiac Rehabilitation Programme is based on an out-patient non-institutionalized service with long-term follow-up and home-based exercise programmes. Return to work rates of more than 90% in the 1960s and 1970s were reported but these rates have not been sustained in the past seven years. These secular changes in return to work rates are attributed to recent changes in the social and economic climate in Ireland. Medical, social, demographic, and psychological factors which may influence successful return to work were studied. The previously employed, young patients and those in the higher social groups, patients with less severe attacks and those free from post-infarction angina, reported the best return to work rates. Reasons for failure to return to work could be attributed equally to organic and functional causes. Factors affecting secondary preventive measures, including smoking cessation, desirable dietary and weight changes, and aerobic exercise programmes, were also studied. These changes were best achieved by young patients, white-collar workers, the better educated and urban dwellers. It is concluded that informal out-patient rehabilitation programmes aimed at early return to a normal life, active secondary prevention measures and home-based exercise programmes, are effective and safe in the great majority of patients recovering from myocardial infarction and coronary bypass surgery.

Coronary Artery Bypass↗