Search PubMed⌕ Search

Biomedical subjects

L Daly

Publications and source records attributed to L Daly.

At least 73 records · Page 4Linked to original sources

Hyperhomocysteinemia: an independent risk factor for vascular disease.

BACKGROUND: Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine beta-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine beta-synthase deficiency. METHODS: We first established a diagnostic criterion for hyperhomocysteinemia by comparing peak serum levels of homocysteine after a standard methionine-loading test in 25 obligate heterozygotes with respect to cystathionine beta-synthase deficiency (whose children were known to be homozygous for homocystinuria due to this enzyme defect) with the levels in 27 unrelated age- and sex-matched normal subjects. A level of 24.0 mumol per liter or more was 92 percent sensitive and 100 percent specific in distinguishing the two groups. The peak serum homocysteine levels in these normal subjects were then compared with those in 123 patients whose vascular disease had been diagnosed before they were 55 years of age. RESULTS: Hyperhomocysteinemia was detected in 16 of 38 patients with cerebrovascular disease (42 percent), 7 of 25 with peripheral vascular disease (28 percent), and 18 of 60 with coronary vascular disease (30 percent), but in none of the 27 normal subjects. After adjustment for the effects of conventional risk factors, the lower 95 percent confidence limit for the odds ratio for vascular disease among the patients with hyperhomocysteinemia, as compared with the normal subjects, was 3.2. The geometric-mean peak serum homocysteine level was 1.33 times higher in the patients with vascular disease than in the normal subjects (P = 0.002). The presence of cystathionine beta-synthase deficiency was confirmed in 18 of 23 patients with vascular disease who had hyperhomocysteinemia. CONCLUSIONS: Hyperhomocysteinemia is an independent risk factor for vascular disease, including coronary disease, and in most instances is probably due to cystathionine beta-synthase deficiency.

Cerebrovascular Disorders↗

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↗

Risk factors for coronary heart disease: a population survey in County Kilkenny, Ireland, in 1985.

As part of the evaluation of the Kilkenny Health Project, a survey of factors associated with increased risk of coronary heart disease (CHD) was carried out in Kilkenny, Ireland, in 1985. A random sample of 784 men and women aged 35 to 64 years was surveyed. Mean serum total cholesterol was mmol/l in men and women; 7.0% had levels greater than 7.8 mmol/l. Serum total cholesterol was significantly associated with age. 23.4% of males and 23.6% of females were hypertensive. 60.9% of males and 56.4% of females who were hypertensive were not on treatment. The prevalence of regular cigarette smoking was similar in males (27.7%) and females (27.1%). A further 6.3% of males and 1.6% of females smoked cigarettes occasionally or smoked a pipe or cigars regularly. 4.5% had a positive Rose questionnaire for previous myocardial infarction and 3.4% had a positive angina questionnaire. The high median total cholesterol and the low proportion of hypertensives on medication are consistent with findings in other population surveys in the British Isles and with the high mortality rates from CHD in Ireland. The prevalence of hypercholesterolaemia and of untreated hypertension was higher than in population surveys in the United States and Australia where CHD mortality rates are lower and declining at a faster rate than in Ireland.

Adult↗

Obesity: a public health problem in Ireland?

We examined the prevalence of different categories of body weight in a random sample of men and women aged 35 to 64 years studied in 1985 in County Kilkenny, Ireland. The largest group was those classified as overweight-51.1% of men and 44.7% of women. There were 13.7% of men and 19.2% of women in the obese category. The obese were older but the distribution by social class did not differ significantly from the non-obese. Obese women had significantly more children born alive and a higher prevalence of positive angina questionnaire than those who were not obese. Serum total cholesterol was higher in obese men and HDL cholesterol was lower in obese men and obese women. Systolic and diastolic blood pressures were significantly higher in obese men and women but smoking status was similar. In a multiple logistic regression analysis, systolic blood pressure in men and diastolic in women remained significantly associated with obesity; there was an inverse association between obesity and HDL cholesterol in women and between obesity and HDL-cholesterol as a proportion of total cholesterol in men. A cardiovascular disease prevention programme should seek to prevent the increase in the prevalence of obesity with age which occurs in this population. It would also be important to assess other risk factors for coronary heart disease among those who are obese, with a view to reducing their overall level of risk.

Adult↗

Physical activity and risk of coronary heart disease in a survey of adults in Kilkenny, Ireland.

A questionnaire survey was carried out to estimate activity levels in a sample of 784 men and women aged 35 to 64 years in County Kilkenny, Ireland. Men were more likely to have sedentary, heavy or very heavy work activity while the majority of women had moderate activity during an average day. Only a small minority of respondents walked or cycled to work. 44% of those surveyed had leisure pursuits which were sedentary. At leisure, a higher proportion of men were involved in active sports or other vigorous activities for at least three hours per week. Men also spent longer each day walking, cycling or jogging. 16.5% of those surveyed engaged in vigorous activities for at least 20 minutes on one to three occasions weekly while 5.1% did so on four or more occasions. Younger people were more likely to take such exercise while older people were more likely to take less vigorous exercise. Path analysis using multiple regression techniques found that an increase in activity levels in this population could lead to substantial reductions in blood pressure, some of which would be mediated through changes in body weight.

Adult↗

Expression and amplification of the HER-2/neu (c-erbB-2) protooncogene in epithelial ovarian tumors and cell lines.

Amplification of the c-erbB-2 protooncogene has been associated with a poor prognosis in human breast and ovarian cancers. Our study was undertaken to examine whether amplification, rearrangement, or overexpression of c-erbB-2 and other protooncogenes was frequently observed in epithelial ovarian cancers. c-erbB-2 was expressed in 87% of 22 ovarian cancers analyzed, but expression was significantly increased in only one of the 22 tumor specimens. In this case elevated c-erbB-2 expression was associated with dramatic amplification of the gene. In another tumor a 3.8 kb EcoRI fragment was found, in addition to the usual 4.4 and 6.0 kb fragments; this is consistent with a possible gene rearrangement or a restriction fragment length polymorphism. To place these results in perspective, expression of several other protooncogenes has been examined in ovarian carcinomas. The c-fos, c-myc, n-myc, c-fms, and c-Ha-ras protooncogenes were expressed in different fractions of tumors, but expression of l-myc, c-erbB, c-myb, c-sis, and c-mos was not detectable. Aside from c-erbB-2, neither amplification nor rearrangement was observed among the other protooncogenes studied. Expression of c-erbB-2, c-fms, c-myc, n-myc, c-fos, and c-Ha-ras deserves further evaluation as a prognostic factor in ovarian cancer.

Female↗

Increased serum levels of macrophage colony-stimulating factor in ovarian cancer.

Macrophage colony-stimulating factor is a cytokine that stimulates proliferation and differentiation of phagocytic cells. Macrophage colony-stimulating factor is produced by ovarian epithelial cancer cell lines and might provide a useful serum marker for the disease. Among sera from 69 patients with clinically apparent epithelial ovarian cancer, 47 (68%) had at least 2.5 ng/ml macrophage colony-stimulating factor, whereas only two of 80 apparently healthy donors (2.5%) had a comparable elevation of macrophage colony-stimulating factor. Circulating levels of macrophage colony-stimulating factor did not correlate with serum levels of CA 125. Moreover, 14 of 25 ovarian cancer patients (56%) with clinically evident disease and normal levels of CA 125 (less than 35 U/ml) had elevated levels of macrophage colony-stimulating factor. Among 29 patients with serum CA 125 levels less than 35 U/ml before positive surgical surveillance procedures, 9 (31%) had at least 2.5 ng/ml macrophage colony-stimulating factor. Elevated levels of macrophage colony-stimulating factor were also found in patients with carcinomas from other primary sites and in 31% of 134 patients with benign diseases. If intercurrent benign disease can be taken into account, macrophage colony-stimulating factor deserves further evaluation in combination with CA 125 in monitoring ovarian cancer.

Antigens, Tumor-Associated, Carbohydrate↗

A multicentre study of coagulation and haemostatic variables during oral contraception: variations with geographical location and ethnicity. Task Force on Oral Contraceptives--WHO Special Programme of Research, Development and Research Training in Human Reproduction.

A comparative study of the effects of combined oral contraceptives (OC) on coagulation and fibrinolytic variables using standardized laboratory technique and methodology has been performed in Dublin (Ireland), Salvador (Brazil), Santiago (Chile) and Singapore. Of 777 entrants to the study, 622 were randomly allocated to receive one of four different OC formulations. The remainder did not opt for OC. The progestogenic component was levonorgestrel (LNG) in three of the OC formulations and norethisterone acetate (NEA) in the fourth. Results for the three LNG user groups were pooled. The changes in haematological variables observed over 12 months in the LNG and NEA users were examined in relation to the changes seen in the women not on OC. Women in Salvador differed markedly from those in the other three centres, in showing no acceleration of the prothrombin time and no increase in either fibrin plate lysis or plasminogen following the use of OC. After adjusting the findings in OC users for those in non-users, significant differences in response between centres were also detected for activated partial thromboplastin time (accelerated only in Dublin and Santiago), factor VII activity (increased mainly in Salvador and Santiago) and fibrinogen (for which the most marked changes were an increase in Dublin and a decrease in Salvador). This variability between centres in the effects of OC on coagulation and fibrinolysis suggests that OC administration in different populations may not carry equal thrombotic risks.

Adult↗

Hypothermia and mortality and morbidity. An epidemiological analysis.

STUDY OBJECTIVE: The aim was to identify socioeconomic variables associated with deaths and hospital admissions due to hypothermia and to quantify the risk due to ambient outside temperature. DESIGN: The study was a survey of deaths and hospital admissions due to hypothermia (ICD 991.6), for the period 1979-85 inclusive, identified from death certificates and Hospital Inpatient Enquiry (HIPE) data. SETTING: The study included all deaths and hospital admissions due to hypothermia (1979-85) in the 26 counties of the Republic of Ireland, population 3.5 million. SUBJECTS: All deaths coded during the study period as being due to hypothermia and all persons admitted to hospital during the study period for whom hypothermia was recorded as a discharge diagnosis in HIPE data. MEASUREMENTS AND MAIN RESULTS: Demographic data and date of death/diagnosis were obtained from both data sets. Complete national temperature records were obtained from the meteorological service and a temperature was assigned to each case representing ambient outside temperature at which hypothermia developed. Risk of hypothermia at a given temperature was obtained by dividing the number of cases at that temperature by the appropriate person-years of exposure of the entire national population. Incidence of and mortality from hypothermia doubled with each 5 degrees C and 4 degrees C fall in temperature respectively; the majority of deaths and hospital admissions occurred between October and March. Incidence and mortality increased with age and men had 30% higher case fatality than women. Single men had four times the incidence and 6.5 times the mortality, and single women had double the incidence and four times the mortality of married men and women respectively. Low population density was also an important risk marker. CONCLUSIONS: The risk of hypothermia due to ambient outside temperature has been quantified and a high risk group was identified. A combination of statutory support measures and good neighbourliness could prevent illness and deaths from hypothermia.

Age Factors↗

Comparative studies of 30 micrograms ethinyl estradiol combined with gestodene and desogestrel on blood coagulation, fibrinolysis, and platelets.

An association between an increase in the incidence of thromboembolic disease and the use of combined oral contraceptives has been shown by several epidemiologic studies. Evidence of the vascular complications of oral contraceptives suggests that venous thromboembolism correlates with estrogen dosage and arterial complications with both estrogen and progestogen components. In 60 healthy, randomly allocated women, the effects of ethinyl estradiol, 30 micrograms, combined with gestodene, 75 micrograms, and desogestrel, 150 micrograms, on blood coagulation, fibrinolysis, and platelet function were compared. Subjects were studied before oral contraceptive use, at 12, 24, 36, and 48 weeks of treatment, and at 6 and 12 weeks after treatment. Both oral contraceptives affected the hemostatic system, but our results indicate that the ethinyl estradiol/gestodene combination causes changes in the hemostatic system similar to those in the ethinyl estradiol/desogestrel combination. Factors VII and X activity were slightly higher with the ethinyl estradiol/desogestrel combination than with the ethinyl estradiol/gestodene combination, possibly reflecting a greater estrogenic effect.

Adolescent↗

The prognostic significance of CA 125 half-life in patients with ovarian cancer who have received primary chemotherapy after surgical cytoreduction.

Fifty-four patients with advanced epithelial ovarian cancer were monitored with serial serum CA 125 levels after surgical cytoreduction and during multi-agent chemotherapy with cisplatin-containing regimens. CA 125 half-life of less than 20 days was associated with prolonged overall survival (p less than 0.015). In those patients who eventually were found to be disease-free at surgical surveillance procedures, normalization of serum CA 125 levels to less than 35 U/ml within 65 days of primary operation also suggested an improved survival (p less than 0.059).

Adenocarcinoma, Mucinous↗

Detection of breast carcinoma cells in human bone marrow using fluorescence-activated cell sorting and conventional cytology.

Flow cytometry has been compared with conventional cytology as a method for detecting breast carcinoma cells in human bone marrow. Breast cancer cells from patient effusion fluids or from established cell lines were mixed with normal human bone marrow at dilutions ranging from 1:10 to 1:100,000. Cells were labeled with five directly fluoresceinated murine monoclonal antibodies reactive against epithelial cell surface determinants of 42, 55, 72, 200, and more than 200 kD. Fluorescence of tumor cells within the mixtures was then analyzed with the use of a fluorescence-activated cell sorter. In multiple experiments, one tumor cell in 10,000 nucleated marrow cells could be detected by flow cytometry. In addition, a linear correlation was observed over approximately 3 logs between the number of tumor cells added and the number of tumor cells detected. In a double-blind study comparing flow cytometry and cytology, flow cytometric analysis detected one tumor cell among 10,000 marrow precursors in 14 of 15 instances, whereas standard cytologic methods detected similar tumor contamination in 9 of 15 instances. Neither technique used individually could detect one tumor cell in 100,000 bone marrow cells. Used in combination, however, flow cytometry and cytology could detect one breast cancer cell among 100,000 normal marrow progenitors.

Antibodies, Monoclonal↗

Preoperative serum tumor-associated antigen levels in women with pelvic masses.

Preoperative sera were assayed for tumor-associated antigens CA 125, TAG 72, and CA 15-3 in 100 women with pelvic masses. Serum CA 125 levels were elevated above 65 U/mL in 83% of 42 patients with ovarian malignancies, in 58% of 12 patients with nonovarian malignancies, and in 17% of 46 patients with benign pelvic masses. Elevations of TAG 72 and CA 15-3 levels occurred less frequently in all groups of patients. Serum CA 125 levels distinguished most effectively between patients with malignant pelvic masses and those with benign pelvic masses, having a sensitivity of 78% and a specificity of 83% at a threshold level of 65 U/mL. When comparing 33 patients with epithelial ovarian carcinomas to 46 patients with benign masses, the CA 125 level alone yielded a sensitivity of 88% with a specificity of 83%. Coordinate elevations of CA 125 (above 65 U/mL) and TAG 72 (above 10 U/mL) or CA 15-3 (above 30 U/mL) distinguished ovarian epithelial carcinomas from benign masses with a sensitivity of 73% and a specificity of 98%, which improved to 81 and 100%, respectively, among patients over 50 years of age. Given the marked increase in specificity observed with this panel of three serum tumor-associated antigens, use of multiple markers might facilitate screening for ovarian carcinoma and appropriate referral of patients with pelvic masses for cytoreductive operations.

Antigens, Tumor-Associated, Carbohydrate↗

A comparison of two different T-grain films in rare-earth screens with a standard film-screen combination for intravenous pyelography and bone examinations.

T-grain film is claimed to give significantly improved image quality, allowing the use of faster screens without loss of quality and thus reducing radiation dose. We tested this claim for two systems. In each case comparison was made with our usual screen-film combination, Agfa Curix RP1 film with Kodak Xomatic Regular screens (a nominally 200 speed system). The systems tested were Kodak TMatG in Kodak Lanex Medium screens (300 speed) and Agfa STG in Kodak Lanex Regular screens (400 speed). The Agfa STG-Lanex Regular system performed less well than the standard system for intravenous pyelograms (IVPs), bones and soft-tissue detail. Its speed advantage was not apparent below 70 kV. The Kodak TMatG-Lanex Medium system was better than the standard system for IVPs but not as good for bones. It gave virtually no speed advantage below 90 kV. Kodak T-grain film in a medium-speed, rare-earth screen was found to be better than the standard system for IVPs. Agfa T-grain film in a fast rare-earth screen was unsatisfactory for IVPs. Neither combination was as good as the standard system for bones.

Bone and Bones↗