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Biomedical subjects

L Daly

Publications and source records attributed to L Daly.

At least 19 recordsLinked to original sources

Normal bone density in Irish women: is American normative data suitable for use in Ireland?

The objective of the study was to determine whether or not U.S. normal data for female Vertebral Bone Mineral Density is suitable for use in an Irish population. One hundred and fifty-six healthy Caucasian women of permanent Irish domicile had bone densitometry performed using single energy quantitative computed tomography of L2, L3 and L4 vertebrae. We found that comparison of our results to normal American data shows a slight and progressive increase in bone mineral content of postmenopausal American women with age relative to the Irish population. This difference is small and not sufficient to justify development of separate normal values for Irish women. We conclude that this discrepancy may be due to a combination of environmental and racial factors or to the more rigorous exclusion criteria applied in our study.

Adult

Doxazosin in the management of hypertensive diabetes--a cautionary note (?).

Twenty-two patients with diabetes and hypertension were treated with Doxazosin. An acceptable fall in blood pressure was found with 1 mg. in 50% of patients and 2-8 mgs. in 50%. An increase in HDL cholesterol and a fall in LDL cholesterol levels which reached statistical significance was observed. A small but significant increase in HBA1 levels occurred in the 50% of patients on the higher Doxazosin dose.

Antihypertensive Agents

Simple SAS macros for the calculation of exact binomial and Poisson confidence limits.

Statistical analysis using confidence intervals is now a preferred approach in the medical literature, and confidence limits for binomial proportions and Poisson counts are commonly required. Normal approximations of varying accuracy are often used in such situations and it is not generally realised that non-iterative exact solutions are available. This paper shows that the exact binomial and Poisson confidence limits can be expressed very simply in terms of the inverse beta and inverse gamma distributions, and describes two macros in the SAS programming language to perform the computations. The exact solutions are compared with some approximations and further applications of the techniques are described.

Binomial Distribution

Ha-ras polymorphisms in epithelial ovarian cancer.

Unusual restriction fragment length polymorphisms (RFLPs) of the Ha-ras locus have been found in DNA from leukocytes and tumor tissue of cancer patients. To determine whether rare alleles would be observed frequently in patients with ovarian cancer, Ha-ras RFLPs were studied in DNA from 42 different ovarian epithelial tumors and from the peripheral blood leukocytes of 76 normal individuals. Four common, seven intermediate, and seven rare alleles were detected overall. Similar fractions of rare alleles were found in DNA from ovarian cancers and from the peripheral blood of normal individuals. Thus, the frequency of unusual Ha-ras RFLPs did not distinguish patients with ovarian cancers from apparently healthy individuals.

Alleles

Dynorphin-processing endopeptidase in the rat anterior pituitary lactotrophic cell line, GH4C1.

Several peptide hormones and neurotransmitters are produced by cleavage at the monobasic processing sites. An endoprotease capable of cleaving a dynorphin peptide at the monobasic processing site is secreted from the rat anterior pituitary lactotrophic cell line, GH4C1. When characterized by fast protein liquid chromatography using an ion exchange column, the majority of the endoprotease activity elutes as a single symmetrical peak around 0.3 M NaCl. The protease inhibitor profile suggests that the activity is due to putative thiol protease. These enzymatic properties are similar to a monobasic processing enzyme previously found in bovine pituitary and in the rat brain. The secretory pathway which contains the enzyme activity in GH4C1 cells was characterized by stimulation of secretion by thyrotropin releasing hormone, forskolin, phorbol ester, or potassium chloride. The secretion of the enzyme activity was substantially increased by these compounds suggesting that the GH4C1 cells secrete the activity via the regulated pathway. A hormonal treatment of the GH4C1 cells which has been previously shown to produce a substantial increase in the number of secretory granules and ir-prolactin has been found in this study to elevate this enzyme activity 2-fold. This increase is similar to that seen in the carboxypeptidase E activity, another putative peptide hormone processing enzyme activity. These data suggest that the peptide processing activity is regulated to a small but significant extent and is coordinately regulated with carboxypeptidase E activity.

Amino Acid Sequence

Comparison of a novel assay for breast cancer mucin to CA15-3 and carcinoembryonic antigen.

PURPOSE: To compare the sensitivity and specificity of an automated microparticle enzyme immunoassay (MEIA) for breast cancer mucin (IMx BCM; Abbott Laboratories, North Chicago, IL) to that of CA15-3 and carcinoembryonic antigen (CEA) for detecting and monitoring breast cancer. MATERIALS AND METHODS: IMxBCM was compared to assays of CA15-3 and CEA in 630 serum specimens from healthy women, and from women with breast cancer, other malignancies, benign breast conditions, or other benign diseases. RESULTS: Analysis of the log-transforms for the three markers in all specimens showed a high correlation of IMxBCM with CA15-3 (r = .78), but not with CEA (r = .25). Based on a receiver-operating-characteristics (ROC)-curve analysis for any given specificity, IMxBCM was found to be a more sensitive marker than either CA15-3 or CEA for distinguishing 105 women with advanced or metastatic breast cancer from 89 healthy women (P = .003 and P = .04, respectively), from 98 women with benign breast conditions (P = .02 and P = .002), or from 191 women with benign diseases (P = .03 and P less than .0001). At 95% specificity, the sensitivities of IMxBCM, CA15-3, and CEA for detecting advanced or metastatic breast cancer were 69%, 51%, and 30%, respectively. Serial serum samples (n = 177) were analyzed in 20 additional metastatic breast cancer patients with measurable disease. Serial IMxBCM levels corresponded with the clinical course of disease in 80%, CA15-3 in 65%, and CEA in 60% of the 20 patients. CONCLUSIONS: Increased sensitivity of IMxBCM, despite a high correlation with CA15-3, suggests that IMxBCM and CA15-3 may recognize distinct epitopes on the same molecule. Although further research is indicated, IMxBCM may provide a promising marker in the clinical management of breast cancer patients.

Adult

Childhood leukaemia in Ireland.

In response to professional and public concern about health consequences, in particular cancer risk, from previous and current levels of ionising radiation in the Irish Sea, a study of incidence and mortality from acute lymphoid leukaemia (ALL) and other lymphoid malignancies in children was undertaken. Overall rates were similar to those found in other western populations and distribution of high rates was quite random over the country as a whole. There was a small but significant excess in incidence of ALL for the years 1974-76 in a narrow three mile wide strip along the east coast. It is not possible in the context of this study to postulate aetiological factors which might explain this finding.

Acute Disease

Coordinate elevation of serum markers in ovarian cancer but not in benign disease.

Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost-effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (greater than 35 U/ml) were observed in 91%, CA 15-3 (greater than 30 U/ml) in 57%, TAG 72 (greater than 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15-3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15-3 was elevated in 77%. In the false-positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15-3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost-effective screening strategy for ovarian cancer.

Alkaline Phosphatase

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