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Biomedical subjects

L Daly

Publications and source records attributed to L Daly.

At least 55 records · Page 3Linked to original sources

An investigation of brain tumours and other malignancies in an agricultural research institute.

A historical cohort study was carried out in an agricultural research institute in the Republic of Ireland to investigate a perceived excess of cancer deaths among employees. The objectives of the study were (a) to confirm whether or not total or cause specific death rates among selected employees were higher than expected based on national figures, and to quantify any excess, and (b) to identify centres and employee grades associated with any excess risk. The cohort comprised all administrative, research, and technical staff employed for at least two years between 1960 and 1980, giving a final total for analysis of 1323 employees. Employment history was categorised by place of work and employment grade. Deaths among the cohort were identified and causes of deaths verified. Overall the cohort had a lower than expected mortality compared with national rates (O/E = 0.67). Female deaths were too few for analysis but, among the male employees, there was an excess of all cancers (O/E = 1.24; 95% confidence interval (95% CI) 0.8-1.9), in particular brain cancer (O/E = 4.69; 95% CI 1.2-11.4) and bladder cancer (O/E = 9.31, 95% CI 1.9-27.2). The pattern of brain tumour deaths was consistent with an occupational aetiology but it was not possible to identify specific exposures associated with the excess. All four cases occurred among research workers in the plant and soil science area. The pattern of bladder cancers was difficult to interpret. The authors are at present participating in a multicentre study to further investigate cancer risk in laboratory workers.

Adult↗

Identification of inappropriate radiological referrals with suspected gallstones: a prospective audit.

The objective of this study was to derive and test clinical scoring system in order to predict the presence of gallstones and to identify inappropriate referrals. The design of this scoring system comprised a prospective audit of all referrals with suspected gallstones and a prospective validation of the system on new patients. The subjects used in the study consisted of 300 inpatient, outpatient and general practitioner referrals to a radiology department with suspected gallstones during the period 1984-1986 (1st cohort) and 200 similar referrals from 1987 to 1988 (2nd cohort). The main outcome measures were gallstones as determined by oral cholecystogram and/or ultrasound of the gallbladder. 32.7% and 24.0% of referrals in the first and second cohorts, respectively, had gallstones. A scoring system to predict gallstones was derived on the first cohort based on age, Murphy's sign, duration and type of pain, presence or absence of flatulence, and source of referral. This scoring system discriminated well between those with and without stones in both cohorts. Low risk groups, comprising about 15% of the referrals in each cohort, were identified with a prevalence of gallstones of 4.5% (1st cohort) and 3.0% (2nd cohort). If these patients had not been referred the radiological workload would have dropped by 15%, with a very small reduction in diagnostic yield. We conclude that prior to radiological assessment it is possible, on the basis of source of referral and symptoms, to identify a group of patients with a low prevalence of gallstones. These cases, with a low diagnostic yield, contribute substantially to the workload of a radiological department.

Adult↗

Breast cancer screening. Interpreting new data for clinical practice.

While multiple trials support routine mammography for women aged 50 to 69 demonstrating a reduction in breast cancer deaths by about 30%, experts disagree on breast cancer screening recommendations for women 40 to 49 years old. A review of the data and its interpretation illustrate the areas of controversy: lack of statistical power, prolonged screening intervals, suboptimal mammographic technical quality, and difficulty applying the data to current mammographic screening practice. Clinical decision making for health care providers and women aged 40 to 49 is guided by understanding the risk of breast cancer and weighing the risk and benefits of screening mammography. Further research to resolve whether breast cancer screening is effective in decreasing breast cancer deaths in women aged 40 to 49 is needed.

Adult↗

Elevation of multiple serum markers in patients with stage I ovarian cancer.

BACKGROUND: The high overall mortality from ovarian cancer (> 60%) relates, in part, to delays in diagnosis. When ovarian cancer is detected in stage I (International Federation of Gynecology and Obstetrics staging), up to 90% of patients can be cured. Transvaginal sonography can detect early-stage disease with great sensitivity, but it is expensive and lacks specificity. Although serum marker assays could provide a less expensive and more convenient initial screening test, the sensitivity of assays varies. Measurement of serum CA 125 in conjunction with ultrasound screening as a second-line test confers high specificity but detects only about one half of early stage ovarian carcinomas. PURPOSE: The purpose of this retrospective study was to determine whether assays of multiple serum markers would improve sensitivity by detecting a higher percentage of stage I ovarian cancers than the CA 125 assay alone. METHODS: Using immunoradiometric assays, we measured preoperative serum levels of CA 125 tumor-associated antigen, macrophage colony-stimulating factor (M-CSF), and OVX1 in 46 patients with stage I ovarian cancer of different histologies and 237 patients with benign pelvic masses. We also assayed sera from 204 apparently healthy women who had participated in a screening trial and remained free from cancer at 1 year of followup. All specimens were obtained from cryopreserved aliquots. Marker levels were considered to be elevated when levels of CA 125 were greater than 30 U/mL, M-CSF levels were greater than 3.1 ng/mL, or OVX1 levels were greater than 12.1 U/mL. RESULTS: At least one of the serum markers was elevated in 98% of patients with stage I ovarian cancer; CA 125 levels were elevated in 67%. By the same criteria, 11% of healthy individuals and 51% of patients with benign pelvic masses had at least one elevated marker value. Thus, the sensitivity of the combination of assays for the three serum markers was significantly greater than the sensitivity of the CA 125 assay (P < .0005) and specificity was moderate. CONCLUSION: A panel of these three tumor markers can identify early-stage ovarian cancer with extremely high sensitivity and moderate specificity. IMPLICATIONS: Elevation of one or more serum markers should be evaluated further as an indication for transvaginal sonography in apparently healthy women. Such a strategy might substantially reduce the expense and improve the specificity of screening compared to the use of ultrasound alone. Prospective studies with a large cohort of patients at high risk for ovarian cancer will be required to confirm these findings.

Antigens, Neoplasm↗

A circadian distribution to febrile episodes in neutropenic patients.

Four-hourly temperature charts relating to 63 febrile neutropenic episodes in 32 patients were assessed for a circadian distribution to the onset of fever (> 37.5 degrees C) using the Edward's test. A highly significant distribution was found with the maximum incidence of febrile events between the hours of 5 p.m. and midnight (acrophase 9.30 p.m.). Patients were 5.53 times more likely to develop fever at 9.30 p.m. that 9.30 a.m.

Adolescent↗

An epidemiological study of Wilson's disease in the Republic of Ireland.

In a population based study of the prevalence of Wilson's disease in the Republic of Ireland from 1970-89, 26 definite and probable cases were ascertained. The adjusted birth incidence rate was 17.0 per million live births (95% (confidence interval 9.9 to 27.2)) for the 20 year period 1950-69. The gene frequency was 0.41% (95% (confidence interval 0.31% to 0.52%) indicating that one in 122 of the population was a gene carrier. Allowing for a maximal degree of consanguinity, the gene frequency is reduced to 0.36% and the proportion of heterozygotes to one in 139 of the population. The consistency of the adjusted birth incidence rates over the decades 1950-59 and 1960-69 suggests a high degree of ascertainment of diagnosed cases of Wilson's disease.

Adolescent↗

OVX1 radioimmunoassay complements CA-125 for predicting the presence of residual ovarian carcinoma at second-look surgical surveillance procedures.

PURPOSE: At second-look surgical surveillance procedures, normal CA-125 levels can be associated with persistent disease in 50% to 60% of patients. A novel radioimmunoassay (RIA) has been evaluated for the ability to identify patients with persistent disease who have normal levels of CA-125. MATERIALS AND METHODS: The OVX1 double-determinant assay used a murine monoclonal antibody to detect an epitope on a high-molecular weight mucin-like glycoprotein. RESULTS: Apparently healthy individuals had serum OVX1 levels of 2.23 +/- 2.48 U/mL (mean +/- SD). Elevated serum OVX1 levels (> 7.2 U/mL) were found in 5% of 184 normal individuals and in 70% of 93 epithelial ovarian cancer patients with clinically evident disease. Among sera from these ovarian cancer patients, OVX1 was elevated in 68% of 76 samples with CA-125 levels more than 35 U/mL and in 76% of 17 samples with CA-125 levels less than 35 U/mL. In serum samples obtained at the time of positive second-look laparotomy, 59% of 41 patients with CA-125 levels less than 35 U/mL had elevated OVX1 antigen levels, whereas 41% of 22 patients with CA-125 levels more than 35 U/mL had elevated serum OVX1 levels. In patients with negative second-look laparotomies, false-positive results were eliminated by increasing the threshold of OVX1 to 10.5 U/mL. At this level, 32% of 41 patients with positive second-look operations had an elevated OVX1 level, despite a normal CA-125 level. When used in combination, CA-125 (> 35 U/mL) and OVX1 (> 10.5 U/mL) detected persistent disease in 56% of 63 patients with positive surveillance procedures, compared with 35% when CA-125 was used alone (P < .05). CONCLUSION: An elevated OVX1 level can alert oncologists to the possibility that ovarian cancer has persisted, despite the return of CA-125 to a normal range.

Animals↗

Penetration of the Kilkenny Health Project Education Programme.

The Kilkenny Health Project (KHP) was established in 1985 as a community-based research and demonstration programme for cardiovascular disease in County Kilkenny, Ireland, and as a pilot programme for future national initiatives. This article examines the penetration of the Project into the community, the extent of knowledge of, contact with, or participation in its activities.

Adult↗

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↗