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Biomedical subjects

M Daly

Publications and source records attributed to M Daly.

At least 91 records · Page 5Linked to original sources
PubMed1996

Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: a genetic study of 15 185delAG-mutation kindreds.

We screened 163 women from breast-ovarian cancer-prone families, as well as 178 individuals affected with breast and/or ovarian cancer but unselected for family history, for germ-line mutations in exon 2 of BRCA1, by SSCP analysis and direct sequencing. A total of 25 mutations were detected. Thirteen of 64 Jewish Ashkenazi women and 2 non-Jewish individuals were found to possess the 185delAG mutation. Haplotype data for all 15 individuals, with markers intragenic to BRCA1, suggest that the Jewish Ashkenazi individuals share a common ancestry that is distinct from the lineage shared by the other two women. These data provide the first evidence of two distinct lines of transmission for the 185delAG mutation, only one of which has its origins in the Jewish Ashkenazi population. Our screening also uncovered 10 affected individuals with an 11-bp deletion at nucleotide 188 of BRCA1 (188del11), 4 of whom are Ashkenazi Jews. This is only the third reported mutation detected within the Jewish Ashkenazi population and may represent the second most common alteration in BRCA1 found in Ashkenazi Jews in the United States. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually contribute to the development of inexpensive and routine tests for BRCA1 mutations, as well as to the elucidation of other contributory factors (e.g., diet, environment, and chemical exposures) that may play a key role in cancer initiation and development. The implications of the mutational data, as well as the role that founder effect, demographic history, and penetrance play in the resulting observed phenomena, are discussed.

Adult↗
PubMed1996

Type I antithrombin deficiency: five novel mutations associated with thrombosis.

The genetic basis of Type I antithrombin deficiency has been investigated in six unrelated kindred with positive histories of thrombosis using a PCR amplification/direct sequencing approach. Four frameshift mutations, all introducing premature translation termination codons were identified. Thus, deletions, of a C at nucleotide position 2599 or 2600, a G at position 2601-2602 and a CT dinucleotide at position 7428-7429 were detected in three kindred and confirmed by restriction enzyme analysis. The identical insertion, of a T at nucleotide 2770, was observed in two apparently unrelated families. This finding may have been due to a founder effect since antithrombin gene polymorphism analysis showed all affected individuals to share a common haplotype. An in frame deletion of 6 bp at nucleotide position 2690-2696 causing the removal of codons 76 and 77 encoding Ile 76 and Phe 77 was also detected indicating that these amino acids are essential for stability of the mature antithrombin.

Adult↗
PubMed1996

Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk.

Despite the fact that breast cancer is the most common non-cutaneous cancer and a leading cause of cancer deaths in women, accepted markers of breast cancer risk miss up to 40% of these tumors. Moreover, screening methods involving the analysis of tissue or cells are limited by the need for a surgical biopsy. Nipple aspiration is a quick, efficient, noninvasive method to obtain breast epithelial cells, the cells at risk for transformation to carcinoma. Prostate-specific antigen (PSA), a protein thought to be specific to the prostate but recently found in a subset of breast tumors, has been correlated with improved survival. The purpose of this study was to measure PSA in a group of women with increasing breast cancer risk (no risk or family history of breast cancer, precancerous mastopathy, and invasive cancer) and determine if PSA correlates with risk. Nipple aspirate fluid was obtained from the intact breast and from surgical specimens using a modified breast pump. PSA was then measured in the fluid using a highly sensitive and specific immunofluorometric procedure. PSA was found at levels ranging from 0-13,423 ng/g of total protein, and there was a significant relationship between PSA level and breast cancer risk (P = 0.001). That is, all women with no risk factors and 90% of those with a family history had high PSA levels, whereas 68% of subjects with precancerous mastopathy or invasive cancer had low PSA levels. PSA was higher in premenopausal subjects (P = 0.002). After adjusting for the effect of menopausal status, there remained a significant association between PSA and breast cancer risk. These findings suggest that PSA in nipple aspirate fluid may be a useful marker of breast cancer risk.

Adult↗
PubMed1996

Deliberate self-poisoning, unemployment and public health.

The purpose of the present investigation was to explore further the known relationship between deliberate self-poisoning and social deprivation. Each individual who attended one of Cork city's three casualty departments following an act of deliberate self-poisoning in 1988 was examined. The place of residence (ward) of each city resident patient was established. The social status of the city's 34 wards was estimated using a number of indices obtained from the 1981 and 1986 census reports and social service records. A comparison was made between the 1988 self-poisoning rate for each ward and the rate found in a 1982 study of the city. Correlations between self-poisoning rate and seven social deprivation indices were found to be significant. Multiple regression, factor, and partial correlation analyses were carried out to examine more closely the interrelationships between the social deprivation indices. With respect to explaining the variation in the self-poisoning rate, unemployment alone performed almost as well as all of the indices together and as well as the factors derived using factor analysis. The correlation between unemployment and self-poisoning rate remained highly significant when the other related variables were controlled for. However, at fixed levels of unemployment, these variables were found to be independent of the self-poisoning rate. It is suggested that whereas clinical intervention may benefit the individual, deliberate self-poisoning as an issue requires a public health approach for its resolution.

Adolescent↗
PubMed1995

Effects of individualized breast cancer risk counseling: a randomized trial.

BACKGROUND: Studies have shown that a majority of women with a family history of breast cancer have exaggerated perceptions of their own risk of this disease and experience excessive anxiety. In response to the need to communicate more accurate risk information to these women, specialized programs for breast cancer risk counseling have been initiated in medical centers across the United States. PURPOSE: Our purpose was 1) to evaluate the impact of a standardized protocol for individualized breast cancer risk counseling on comprehension of personal risk among first-degree relatives of index breast cancer patients and 2) to identify women most and least likely to benefit from such counseling. METHODS: This study is a prospective randomized trial comparing individualized breast cancer risk counseling to general health counseling (control). We studied 200 women aged 35 years and older who had a family history of breast cancer in a first-degree relative. Women with a personal history of cancer were excluded. Risk comprehension was assessed as the concordance between perceived "subjective" lifetime breast cancer risk and estimated "objective" lifetime risk. RESULTS: The results of logistic regression analysis showed that women who received risk counseling were significantly more likely to improve their risk comprehension, compared with women in the control condition (odds ratio [OR] = 3.5; 95% confidence interval [CI] = 1.3-9.5; P = .01). However, in both groups, about two thirds of women continued to overestimate their lifetime risks substantially following counseling. Examination of subjects by treatment interaction effects indicated that risk counseling did not produce improved comprehension among the large proportion of women who had high levels of anxious preoccupation with breast cancer at base line (P = .02). In addition, white women were less likely to benefit than African-American women (OR = 0.34; 95% CI = 0.11-0.99; P = .05). CONCLUSION: Efforts to counsel women about their breast cancer risks are not likely to be effective unless their breast cancer anxieties are also addressed. IMPLICATIONS: Attention to the psychological aspects of breast cancer risk will be critical in the development of risk-counseling programs that incorporate testing for the recently cloned breast cancer susceptibility gene, BRCA1 (and BRCA2 when that gene has also been cloned).

Adult↗
PubMed1995

Coping disposition, perceived risk, and psychological distress among women at increased risk for ovarian cancer.

The authors examined predictors of psychological distress among women who were at increased risk for ovarian cancer. Participants were 103 women who had at least 1 first degree relative with ovarian cancer. Specifically, the authors tested the relationship between the dispositional attentional style of monitoring (the tendency to scan for threat-relevant information), perceptions of risk for ovarian cancer, intrusive thoughts regarding ovarian cancer, and psychological distress. Overall, this sample exhibited moderately high levels of psychological distress. High scores on monitoring were associated with high perceived risk for ovarian cancer and elevated levels of intrusive thoughts and psychological distress. Finally, the authors proposed and tested a path model describing the interrelationships between these variables. The results of this study are discussed in terms of their implications for treating the psychological distress associated with being at increased risk for ovarian cancer.

Adaptation, Psychological↗
PubMed1995

Integration of physical, breakpoint and genetic maps of chromosome 22. Localization of 587 yeast artificial chromosomes with 238 mapped markers.

Detailed physical maps of the human genome are important resources for the identification and isolation of disease genes and for studying the structure and function of the genome. We used data from STS content mapping of YACs and natural and induced chromosomal breakpoints to anchor contigs of overlapping yeast artificial chromosome (YAC) clones spanning extensive regions of human chromosome 22. The STSs were assigned to specific regions (bins) on the chromosome using cell lines from a somatic hybrid mapping panel defining a maximum of 25 intervals. YAC libraries were screened by PCR amplification of hierarchical pools of yeast DNA with 238 markers, and a total of 587 YAC clones were identified. These YACs were assembled into contigs based upon their shared STS content using a simulated annealing algorithm. Fifteen contigs, containing between 2 and 74 STSs were assembled, and ordered along the chromosome based upon the cytogenetic breakpoint, meiotic and PFG maps. Additional singleton YACs were assigned to unique chromosomal bins. These ordered YAC contigs will be useful for identifying disease genes and chromosomal breakpoints by positional cloning and will provide the foundation for higher resolution physical maps for large scale sequencing of the chromosome.

Chromosome Mapping↗
PubMed1995

Requirement for nursing care services and associated costs in acute spinal cord injury.

The purpose of this study was to analyze the requirement for professional nursing care and the nursing care costs for patients with acute spinal cord injury. This descriptive study used a convenience sample of 50 consecutively admitted spinal cord-injured (SCI) patients who agreed to participate. Trained data collectors interviewed patients daily, reviewed the chart and spoke with the patient's nurses, after which nursing diagnoses were determined and acuity calculated. The sample consisted of 26 quadriplegic (Q), 5 ventilator-dependent quadriplegic (V) and 19 paraplegic (P) SCI subjects. The median length of stay (LOS) was 16 days with an intensive care unit (ICU) LOS of 4 days. LOS in the intermediate unit was 11 days. Median hours of nursing care was 143 (translating to $2458) for the entire acute care hospitalization. Specific hours of care and consequent costs were determined for all three groups through both phases of care. Significant differences were found in the hours of nursing care required among the three groups (X2 7.18, df = 2, p < .03), even though no difference was found in the LOS. A nursing consumption ratio (hours of nursing care/hours of LOS) demonstrated that ventilator-dependent SCI patients required the greatest number of nursing care hours.

Acute Disease↗
PubMed1995

Donor families' experience of organ donation.

This retrospective study surveyed families who consented to organ donation in the State of Queensland, Australia, from January 1991 to December 1992 inclusive, and evaluated their experience of the organ donation process. The survey questioned families in relation to the preparation they received, their understanding of brain death, the request process, influencing factors, and post donation follow-up. One hundred and eight families consented to organ donation over this 24-month period. Twelve families of paediatric donors under the age of twelve years were excluded, and twelve families were not able to be contacted. Of the remaining 84 families, 42 participated in this study. Overall the study results indicated a positive attitude towards the organ donation process. The majority of families did not find the process stressful and indicated that they were provided with sufficient information and preparation, and that the request was made in a sensitive manner. A few important issues and areas for improvement were highlighted: in particular, the need for families to have an opportunity to view the body after procurement, and the importance of counselling throughout and after the donation process.

Attitude to Death↗
PubMed1995

Nurse practitioners.

The department of health is keen to explore the potential of the nurse practitioner to substitute some areas of health care for the more expensive medical practitioner. The RCN has developed a specialist course for nurse practitioners. But as yet there is no clear definition of the role or educational status of the nurse practitioner. This professional briefing examines the issues, and suggests that attempts to define a specific nurse practitioner discipline and role limits its potential, and the potential for the development of current community nursing practitioners.

Humans↗
PubMed1994

The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.

Diastrophic dysplasia (DTD) is a well-characterized autosomal recessive osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities. The disease occurs in most populations, but is particularly prevalent in Finland owing to an apparent founder effect. DTD maps to distal chromosome 5q and, based on linkage disequilibrium studies in the Finnish population, we had previously predicted that the DTD gene should lie about 64 kb away from the CSF1R locus. Here, we report the positional cloning of the DTD gene by fine-structure linkage disequilibrium mapping. The gene lies in the predicted location, approximately 70 kb proximal to CSF1R, and encodes a novel sulfate transporter. Impaired function of its product is likely to lead to undersulfation of proteoglycans in cartilage matrix and thereby to cause the clinical phenotype of the disease. These results demonstrate the power of linkage disequilibrium mapping in isolated populations for positional cloning.

Amino Acid Sequence↗
PubMed1994

Evolution of treatment strategies for adenocarcinoma of the esophagus and gastroesophageal junction.

Between 1980 and 1988, 91 patients with adenocarcinoma of the esophagus were treated by surgical resection and selective postoperative therapy. Operative mortality was 2%. Pathologic stage was I in 4, II in 26, and III in 61. Actuarial 2- and 5-year survival was 24% and 8%. From 1987 to 1989, 16 patients with adenocarcinoma of the esophagus were treated with two cycles of 5-fluorouracil and cisplatin followed by surgical resection. There was 1 complete response (6%), 5 partial responses (31%), and 10 with no response (63%). Twelve patients had resection. Pathologic stage was I in 1, II in 4, and III in 8. There was one chemotherapy-related death and one surgical death. Actuarial 4-year survival is 42%. From 1990 to 1993, 22 patients with adenocarcinoma of the esophagus were treated with two cycles of etoposide, doxorubicin, and cisplatin followed by surgical resection. There was 1 complete response (5%), 11 partial responses (50%), and 10 with no response (45%). Eighteen patients had resection. Pathologic stage was 0 in 1, II in 8, and III in 9. There were no treatment-related deaths. The actuarial 2-year survival is 58%. Conclusions are necessarily limited because the patients were not treated in a randomized fashion. These preliminary results with preoperative chemotherapy appear improved (p = 0.04 and p = 0.004, respectively) as compared with results from 1980 to 1988 without preoperative chemotherapy.

Adenocarcinoma↗
PubMed1994

Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen-progestin or progestin 'add-back' for 2 years.

Treatment of women with leiomyomata with gonadotrophin-releasing hormone agonists (GnRHa) for > 6 months is not recommended because of concerns regarding adverse sequelae of prolonged hypoestrogenism. It has been postulated that addition of low-dose sex steroids to GnRHa treatment, i.e. 'add-back' therapy, may avert some of these adverse effects (accelerated bone resorption, vasomotor flushes) without altering the efficacy of GnRHa therapy. To evaluate the effects of long-term GnRHa therapy on uterine size, bleeding patterns, bone mass and lipids, 51 pre-menopausal women with leiomyomata were treated with the GnRHa leuprolide acetate depot, 3.75 mg every 4 weeks for 2 years. After 3 months of leuprolide therapy, the women were randomized to receive either low-dose continuous oestropipate, 0.75 mg daily, plus cyclic norethindrone, 0.7 mg on days 1-14 each month (the oestrogen-progestin add-back group) or higher-dose norethindrone, 10 mg daily (the progestin add-back group), for the remaining 21 months. Mean uterine volume decreased by 40% in both treatment groups during the first 3 months on leuprolide treatment. There was no significant change in uterine size following oestrogen-progestin add-back. However, mean uterine volume in the progestin add-back group increased to 87% of pre-treatment size by treatment month 12 and 95% of pre-treatment size by treatment month 24. Mean bone density of the lumbar spine as measured by dual X-ray absorptiometry decreased significantly by 2.6% during the first 3 months in all patients, but did not change significantly following steroid add-back in both treatment groups during the final 21 treatment months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Methotrexate mishap.

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Arthritis, Rheumatoid↗
PubMed1994

Attitudes about genetic testing for breast-ovarian cancer susceptibility.

PURPOSE: In anticipation of the availability of genetic testing for a breast-ovarian cancer susceptibility gene (BRCA1), this study examined interest in and expectations about the impact of a potential genetic test. PATIENTS AND METHODS: The subjects were 121 first-degree relatives (FDRs) of ovarian cancer patients. The design was cross-sectional. Subjects completed a structured telephone interview of attitudes about cancer and genetic testing, and self-report psychologic questionnaires to assess coping style and mood disturbance. RESULTS: Overall, 75% of FDRs said that they would definitely want to be tested for BRCA1 and 20% said they probably would. In bivariate analyses, interest was associated positively with education, perceived likelihood of being a gene carrier, perceived risk of ovarian cancer, ovarian cancer worries, and mood disturbance. In logistic regression analysis, perceived likelihood of being a gene carrier was associated strongly with interest (odds ratio, 3.7; P = .006). Results of stepwise linear regression modeling indicated that an anticipated negative impact of genetic testing was associated with being younger (beta = -.66, P = .009), having more mood disturbance (beta = .015, P = .01), and having an information-seeking coping style (beta = .19, P = .002). CONCLUSION: These results suggest that the demand for genetic testing for BRCA1 among FDRs of cancer patients may be great. Moreover, those who elect to participate may represent a more psychologically vulnerable subgroup of high-risk women.

Adolescent↗