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M Daly

Publications and source records attributed to M Daly.

At least 73 records · Page 4Linked to original sources
PubMed1997

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations in the BRCA1 or BRCA2 genes. PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to breast and ovarian cancer were identified using MEDLINE (National Library of Medicine) and from bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "breast cancer," "ovarian cancer," and "screening," or "surveillance" in combination with "cancer family" and "BRCA1" and "BRCA2." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations. No recommendation is made for or against prophylactic surgery (eg, mastectomy, oophorectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking, and case reports have documented the occurrence of cancer following prophylactic surgery. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Antineoplastic Agents, Hormonal↗
PubMed1997

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations associated with hereditary nonpolyposis colon cancer (HNPCC). PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by the National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to colon cancer were identified using MEDLINE and bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "colon cancer," and "screening" in combination with "cancer family" and "HNPCC." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on observational studies, colonoscopy every 1 to 3 years starting at age 25 years is recommended for individuals known to have HNPCC-associated mutations. Endometrial cancer screening is also recommended, based on expert opinion concerning presumptive benefit. No recommendation is made for or against prophylactic surgery (ie, colectomy, hysterectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Do multiple data sets provide support for a bipolar illness susceptibility locus on chromosome 18?

We carried out nonparametric linkage (NPL) analysis of the five chromosome 18 data sets for bipolar illness, as well as of the combined data set. Prior to analysis, we constructed a common genetic map and computed separate marker allele frequencies for each data set. We also attempted to create two consistent diagnostic categories, Narrow (bipolar I, BPI, only) and Broad. The results of the analysis of the combined data set provided stronger evidence of linkage under the Broad category, but at a level of significance that would be expected to occur by chance 4-5 times in a whole-genome scan. When the data sets were analyzed individually, the NIMH data set showed suggestive evidence of linkage (p = 0.0007). The other four data sets, considered together or separately, failed to support this finding, showing only slightly elevated allele sharing among affecteds at a level that would not be unexpected in an unlinked chromosomal region.

Bipolar Disorder↗
PubMed1997

Relationship-specific social psychological adaptations.

Mainstream social psychology has sought parsimonious explanations of broad general applicability, and has in practice focused on stranger interactions. An evolutionary perspective; however, justifies predicting a rich diversity of relationship-specific social psychological adaptations. The demands of motherhood, fatherhood, mateship, sibship and other relationships are qualitatively distinct, and so, it appears, are the psychophysiological mechanisms that have evolved to deal with them. One window on what distinguishes social relationships is provided by the substance and epidemiology of interpersonal conflicts. Homicides exhibit victim-killer relationship-specific patterns in context, motive and demography, which we discovered only because we adopted an evolutionary psychological perspective. We offer a number of specific hypotheses about possible human psychological adaptations that have yet to be assessed, but are readily derived from consideration of the particular qualities of specific relationship types.

Adaptation, Psychological↗
PubMed1997

Nipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer risk.

To evaluate the feasibility of nipple aspiration and to identify intermediate markers of breast cancer risk, nipple aspirate fluid (NAF) was collected from 177 subjects using a modified breast pump. The first 33 subjects demonstrated that we could obtain NAF quickly, reliably and repeatedly. Specimens from the remaining 144 subjects were collected to evaluate promising cellular biomarkers. NAF was obtained in 167 out of 177 (94%) subjects overall and in 99% of the 144 most recent subjects. Sufficient NAF was obtained to evaluate cytology in 160 out of 167 (96%) cases and specimens were sufficiently cellular to analyse DNA markers in 53% of cases. Among the last 144 subjects, menopausal status did not influence the ability to obtain NAF. NAF cytology correlated with increased breast cancer risk (P = 0.002). Using computerized image analysis of NAF epithelial cells, DNA index (P = 0.0002), percentage of cells in G2M (P = 0.05) and percentage of cells with hypertetraploidy (P = 0.002) increased as cytology became more abnormal. Our data indicate that NAF can be obtained in essentially all eligible subjects; that breast epithelial cells are evaluable in > 95% of NAF samples for cytology and in over half of NAF samples for DNA index (ploidy) and cell cycle analysis; and that abnormal NAF cytology correlates with increased breast cancer risk. This suggests that biomarkers identified in nipple aspirate fluid may prove useful either as an adjunct to currently accepted breast cancer screening methods, or to evaluate response to a chemopreventive agent.

Adult↗
PubMed1997

Evolutionary theory and the human family.

Emlen's (1995) paper "An evolutionary theory of the family" reviewed existing ideas about the nature of family systems and the reasons why they have evolved in certain animal species. His theorizing led him to propose 15 predictions about how family systems function, based on favorable evidence from various species, mostly birds. While he suggested that these predictions can be applied to the human case, he himself did not attempt to do so. We consider the applicability of Emlen's 15 predictions to the study of human family systems, and find that several aspects of the life history and ecology of Homo sapiens require that they be modified. These considerations include: (1) the importance of intragroup solidarity in the context of intergroup competition: unlike in many other species where dispersal constraints arise from food or breeding site shortages, the primary pressure driving human sociality seems to be competition from other human groups; (2) the complex nature of exchange and reciprocity in human society: reciprocal altruism in particular is integral to human social interaction and leads to a particularly high degree of non-nepotistic helping behavior; and (3) the implications of menopause and the existence of potentially dominant, postreproductive helpers: helpers of this sort have little incentive to disperse or to encourage offspring to disperse, thus greatly increasing family stability.

Animals↗
PubMed1997

Assessment of postoperative pain management: patient satisfaction and perceived helpfulness.

OBJECTIVE: Increasing attention has been given to the assessment of patient satisfaction as a way to monitor quality of care in hospital settings. Postoperative patient satisfaction has been thought to be related to level of pain intensity, expectations of outcome, perceived concern by the staff, and helpfulness of treatments. The aim of this study is to develop a simple, reliable measure to assess pain and satisfaction in postsurgical patients and to examine factors related to patient satisfaction. DESIGN: A satisfaction questionnaire was developed for this study and administered to 119 patients who had undergone a major orthopedic surgical procedure. The majority of the patients were diagnosed with osteoarthritis and reported moderate to severe preoperative pain. The 13-item measure was found to be reliable (test-retest r = .86; interexaminer r = .98), valid (exploratory factor analyses; intercorrelations), and easy to administer. RESULTS: Results showed that the majority of the patients were satisfied with their care (91%), postoperative pain intensity (94%), and the way they were treated by the physicians and nurses (98%). Patients with low postoperative pain ratings who perceived that the physicians and nurses showed concern with how much pain they were feeling reported greatest satisfaction with their care (p < .001). In general, lower postoperative pain ratings were the best predictors of satisfaction and helpfulness of treatment. Preoperative pain status, expected level of postoperative pain, and time waiting for pain medication after a request was made were not significantly correlated with ratings of postoperative pain or satisfaction. CONCLUSIONS: These results highlight the important influence of adequate treatment of postoperative pain and perceived concern by the hospital staff on patient satisfaction.

Arthroplasty, Replacement, Hip↗
PubMed1997

Factor V Leiden in Greek thrombophilic patients: relationship with activated protein C resistance test and levels of thrombin-antithrombin complex and prothrombin fragment 1 + 2.

We studied 172 Greek patients (72 men aged 44.0 +/- 16.7 years and 100 women aged 46.5 +/- 14.1 years) with an unexplained thrombophilic tendency. One hundred and four apparently healthy persons (63 men aged 34.2 +/- 10.0 years and 41 women aged 37.1 +/- 13.3 years) were included as a control group. We performed the activated protein C resistance (APC-r) test using a clotting test (Chromogenix kit), detection of factor V Leiden using polymerase chain reaction (PCR)-restriction fragment length polymorphisms and measurement of thrombin-antithrombin complexes (TAT) and prothrombin fragment 1 + 2 (F1 + 2) levels with an immunoenzymatic assay. The normal range for the APC-r test (> 2.12) was determined from the controls. The factor V Leiden mutation was found in 31.9% of all the patients tested, in 28.1% of the unrelated patients with documented thrombophilic tendency of unknown origin and in 4.8% of the healthy controls. The APC-r test had a sensitivity of 0.42 and a specificity of 0.91 for the detection of factor V Leiden. Furthermore, we found no significant difference in levels of TAT and F1 + 2 between patients with and without the mutation and there was no correlation between aPC-r values and levels of TAT and F1 + 2.

Adult↗
PubMed1997

[Microbial behavior and hurdles in Venezuelan intermediate moisture food].

Sixteen Venezuelan IMF, dairy products, dry-salted fish products, meat products and vegetable products (specially fruit products) were characterized; water activity, pH, moisture, acidity and humectants were determined, allowing us to identify the main hurdles. Parallelly the microbial profile and her evolution for each IMF were established in function of time and storage conditions. This information permits us to explain the different stability compartments for our IMF; simple modifications that will increase their stability are suggested. Water activity is not enough as a hurdle if it is not accompanied by an appropriate packaging, specially in tropical countries, that would limit water migrations.

Candy↗
PubMed1996

Behavior of late potentials on the body surface during programmed ventricular stimulation.

OBJECTIVES: This study sought to evaluate the behavior of late potentials on the body surface by signal averaging during programmed stimulation and to correlate the findings with the cycle length of induced ventricular tachycardia. BACKGROUND: Clinically relevant late potentials may be concealed within the QRS complex and may be missed by the conventional signal-averaged electrocardiogram (SAECG). In contrast, some late potentials may arise from dead-end pathways or pathways not capable of supporting sustained ventricular tachycardia (VT). It has been shown that durations of late potentials in sinus rhythm correlate poorly with VT cycle length. METHODS: Signal-averaged electrocardiography during sinus rhythm, right ventricular pacing (S1) and introduction of a right ventricular extrastimulus (S2) was performed in 95 patients: 11 patients with a structurally normal heart and no inducible VT (Group I); 44 with a previous myocardial infarction (MI) and no inducible monomorphic VT (Group II); and 40 with a previous MI and inducible monomorphic VT (Group III). RESULTS: The best subset of SAECG variables and the best cut points for each variable to differentiate between patients with and without VT were first established for each rhythm studied. Total duration of the filtered QRS complex (QRSD) was found to be the only independent predictor of inducibility of VT. When late potentials were defined for these criteria (QRSD > OR = 113, > or = 178 and > or = 168 ms for the SAECG during sinus rhythm, S1 and S2, respectively), there was no difference in the incidence of false positive (16% vs. 18%) or false negative (30% vs. 26%) late potentials between sinus rhythm and S1. During S2, there were significantly fewer false positive late potentials (11% vs. 16%) and fewer false negative late potentials (17% vs. 30%) than with sinus rhythm. Compared with sinus rhythm, 31% of the false positive late potentials detected during sinus rhythm were lost, whereas 43% of the false negative late potentials became detectable after S2, resulting in improved sensitivity (83% vs. 70%), specificity (89% vs. 84%) and predictive accuracy (86% vs. 77%, p < 0.05). Among the patients with VT, QRSD during S2 achieved the best correlation with VT cycle length (r = 0.74) and was the only independent predictor of VT cycle length when all SAECG variables were considered. CONCLUSIONS: Late potentials revealed by ventricular extrastimuli but concealed during sinus rhythm may be clinically relevant and may explain some of the false negative late potentials and reduced sensitivity of the conventional SAECG in predicting VT. In contrast, those late potentials that are detected during sinus rhythm but lost after ventricular extrastimuli are often clinically irrelevant and may account for the false positive late potentials and reduced specificity of the conventional SAECG.

Aged↗
PubMed1996

A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Ashkenazi and non-Jewish individuals.

Recent studies have identified mutations in the breast and (ovarian cancer susceptibility gene 2 (BRCA2), one which has been found in the germline of several males and one female affected with breast cancer. To establish the carrier frequency of this mutation in a large population of individuals affected with cancer, we evaluated constitutional DNA isolated from 83 individuals diagnosed with breast cancer and 93 diagnosed with ovarian cancer at any age, 42 of whom reported a family history of cancer. Using a simple allele-specific PCR-based nonradioactive method, we detected a total of eight individuals (4.5%) carrying a 1-bp deletion at nucleotide 6174 of the BRCA2 gene (6174delT). The age of disease onset in the mutant allele carriers was highly variable and typically late onset (41-72 years for breast cancer and 48-73 years for ovarian cancer). Evaluation of family histories for the eight mutant allele carriers revealed that several individuals had significant cancer histories that included, in addition to breast and/or ovarian cancer, an increased incidence of colon, esophageal, pancreatic, stomach, and hematopoietic cancers. Interestingly, seven of the eight individuals were of Ashkenazi Jewish descent. Haplotype data for the mutant allele carriers using markers spanning the region of the BRCA2 gene on chromosome 13ql2-ql3 suggest that only two of the confirmed Jewish Ashkenazi individuals share a single common ancestry, indicating several independent origins for this mutation. These data provide evidence for the presence of a specific BRCA2 mutation which has its origins in both Jewish Ashkenazi and non-Jewish populations. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually help contribute to the development of inexpensive and routine tests such as the one described in our study.

Adult↗
PubMed1996

Evolutionary adaptationism: another biological approach to criminal and antisocial behaviour.

Although in a sense "genetic', the conceptual framework of evolutionary psychology, behavioural ecology and sociobiology is distinct from that of behaviour genetics. Considerable confusion has resulted from failures to recognize the distinctions. These disciplines are primarily concerned with the characterization of evolved adaptations, which are usually species-typical and environmentally contingent, so theory and research in these fields mainly concerns environmental rather than genetic sources of behavioural variation. Heritable behavioural variation is in general neither predicted by nor supportive of adaptationist theories. One might even say that substantial heritability of an apparently consequential attribute is a datum that challenges the tenets of adaptationism. Behaviour genetics and evolutionary adaptationism have had only limited mutual influence, but increasing knowledge of the processes by which genotypes affect behavioural phenotypes should facilitate development of a more synthetic approach.

Adaptation, Psychological↗
PubMed1996

Methotrexate removal during haemodialysis in a patient with advanced laryngeal carcinoma.

A 62-year-old patient on long-term haemodialysis who developed an inoperable T2N3Mo squamous-cell carcinoma of the larynx was treated with weekly low-dose methotrexate (MTX) after failing to respond to radiotherapy. The patient was initially given one dose of 10 mg MTX (6 mg/m2) as a 1-h infusion, then he received three further i.v. doses of 20 mg (12 mg/m2). Haemodialysis was performed 15-18 h after each dose and the patient received folinic acid (30 mg i.v.q 6 h) until the MTX concentration was < 0.1 mumol/l. The MTX concentration was measured regularly until it reached < 0.1 mumol/l, and additional samples were withdrawn pre- and post-dialysis. The MTX elimination rate constant and half-life were estimated with the patient on and off dialysis. The patient failed to respond to treatment but did not experience MTX-related toxicity. The elimination half-life ranged from 22 to 42 h when he was off dialysis but fell to a median of 5.5 h during dialysis. Low-dose MTX was given to a patient on regular haemodialysis without evidence of toxicity. The rate of MTX elimination was increased during haemodialysis, although high MTX concentrations persisted for several days and prolonged rescue with folinic acid was required.

Antimetabolites, Antineoplastic↗
PubMed1996

A randomized trial of breast cancer risk counseling: interacting effects of counseling, educational level, and coping style.

The authors evaluated the impact of individualized breast cancer risk counseling (BCRC) on breast-cancer-specific distress and general distress in 239 women with a family history of breast cancer. Following a baseline assessment of demographics, risk factors, coping styles, and distress, participants were assigned randomly to receive either BCRC or general health education (GHE; i.e., control group). After controlling for education level, women who received BCRC had significantly less breast-cancer-specific distress at 3-month follow-up compared with women who received GHE. A significant Education Level x Treatment Group interaction indicated that the psychological benefits of BCRC were greater for women with less formal education. In both the BCRC and GHE groups, participants who had monitoring coping styles exhibited increases in general distress from baseline to follow-up.

Adaptation, Psychological↗
PubMed1996

BRCA2 germline mutations in male breast cancer cases and breast cancer families.

The breast cancer susceptibility gene, BRCA2 on chromosome 13q12-13, was recently isolated. Mutations in BRCA2 are thought to account for as much as 35% of all inherited breast cancer as wall as a proportion of inherited ovarian cancer. Many BRCA2-linked families also contain cases of male breast cancer. We have analysed germline DNA from 50 males with breast cancer (unselected for family history) and 26 individuals from site-specific female breast and breast-ovarian cancer families for mutations in BRCA2. All 17 breast-ovarian cancer families have been screened for BRCA1 coding region mutations and none were detected. Conformation-sensitive gel electrophoresis (CSGE) analysis of PCR-amplified DNA followed by direct sequencing was used to detect sequence variants. Three of eleven individuals carry the same mutation, all are of Ashkenazi Jewish descent, supporting the observation by Neuhausen et al. in this issue that there is a common mutation in this population. Eleven truncating mutations and nine polymorphisms were identified -- all were coding region variants. No loss-of-transcript mutations were identified in the sixteen samples for which this analysis was possible. Seven of the nine disease-associated mutations were detected in the 50 men with breast cancers; for thus in our series, BRCA2 mutations account for 14% of male breast cancer, all but one of which had a family history of male and/or female breast cancer.

BRCA2 Protein↗
PubMed1996

Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families.

Non-insulin dependent diabetes mellitus (NIDDM) affects more than 100 million people worldwide and is associated with severe metabolic defects, including peripheral insulin resistance, elevated hepatic glucose production, and inappropriate insulin secretion. Family studies point to a major genetic component, but specific susceptibility genes have not yet been identified-except for rare early-onset forms with monogenic or mitochondrial inheritance. We have screened over 4,000 individuals from a population isolate in western Finland, identified 26 families (comprising 217 individuals) enriched for NIDDM and performed a genome-wide scan using non-parametric linkage analysis. We found no significant evidence for linkage when the families were analysed together, but strong evidence for linkage when families were classified according to mean insulin levels in affecteds (in oral glucose tolerance tests). Specifically, families with the lowest insulin levels showed linkage (P = 2 x 10(-6)) to chromosome 12 near D12S1349. Interestingly, this region contains the gene causing the rare, dominant, early-onset form of diabetes MODY3. Unlike MODY3 families, the Finnish families with low insulin have an age-of-onset typical for NIDDM (mean = 58 years). We infer the existence of a gene NIDDM2 causing NIDDM associated with low insulin secretion, and suggest that NIDDM2 and MODY3 may represent different alleles of the same gene.

Adult↗