Biomedical subjects
M Daly
Publications and source records attributed to M Daly.
A common region of deletion on chromosome 17q in both sporadic and familial epithelial ovarian tumors distal to BRCA1.
Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans approximately 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.
Communication between patients with breast cancer and health care providers. Determinants and implications.
BACKGROUND: This study evaluated the perceptions of patients with breast cancer of their medical interactions with providers. The determinants and psychological consequences of communication problems also were examined. METHODS: Ninety-seven patients with Stage I or II breast cancer completed a set of validated questionnaires before initiating postoperative therapy. Data on psychological distress were collected at baseline and 3-month follow-up, and multivariate models were fit to explain the relationship between pretreatment communication problems and subsequent psychological distress. Data on clinical variables were abstracted from medical records. RESULTS: A substantial proportion of patients (84%) reported difficulties communicating with the medical team. Communication problems were more common among patients who were less optimistic about their disease and had less assertive coping styles. Patient-reported communication problems were associated with increased anxiety, depression anger, and confusion at the 3-month follow-up. The association between communication problems and mood disturbance remained significant, although small, after adjusting for baseline mood disturbance, demographic, clinical, and coping style variables. CONCLUSION: Interventions that enhance communication between patients with breast cancer and their providers may improve patients' psychological adjustment to treatment. Conversely, interventions that lower distress and modify coping style may enhance communication.
Paracetamol and acute biliary pain with cholestasis.
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Mammography adherence and psychological distress among women at risk for breast cancer.
BACKGROUND: Previous studies estimate that first-degree relatives of women with breast cancer have a twofold to 10-fold increased risk of developing breast cancer. Recently, attention has focused on the mammography screening practices of women who are at high risk for breast cancer. PURPOSE: Our purpose was to characterize mammography screening practices in a sample of first-degree relatives of breast cancer patients and to identify variables that may serve as barriers to or facilitators of adherence to mammography. METHODS: Cross-sectional (rather than prospective) data were collected by telephone interviews with 140 women aged 35-79 years who had a family history of breast cancer in at least one first-degree relative (mother, sister, or daughter). Data were recorded on mammography screening patterns, depression, stress impact, and breast cancer worries. RESULTS: Women whose mammography history adhered to age-specific recommendations varied by age: 76% of first-degree relatives aged 35-39 years, 86% aged 40-49 years, and 63% aged 50 years or more. In bivariate analyses, level of education (P = .001), employment (P = .046), and time since diagnosis of the index patient (P = .044) were significantly and positively associated with mammography adherence. Variables associated negatively with adherence included age (P = .019), intrusive thoughts about breast cancer (P = .042), and breast cancer worries that interfered with daily functioning (P = .004). Multivariate analysis by logistic regression indicated that only breast cancer worries (odds ratio [OR] = 2.5; 95% confidence interval [CI] = 1.09-5.9) and education (OR = 4.8; CI = 1.6-14.3) were significant independent predictors of mammography adherence. CONCLUSIONS: This study suggests that most women at high risk for breast cancer adhere to the recommended mammography screening guidelines of the National Cancer Institute. However, rates of adherence among high-risk women aged 50 years and older are suboptimal; only 63% of these women received annual screening mammograms, and 13% had never been screened. Breast cancer worries may pose a barrier to mammography adherence among high-risk women, particularly those with less formal education. IMPLICATIONS: Prospective longitudinal studies are needed to validate the present findings and to evaluate the impact of psychoeducational interventions for women with affected first-degree relatives.
Treatment of postmenopausal osteoporosis with daily parathyroid hormone plus calcitriol.
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A de novo mutation in exon 28 of the von Willebrand factor gene in a patient with type IIA von Willebrand's disease coincides with an MboI polymorphism in the von Willebrand factor pseudogene.
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A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin "add-back" regimens for women with leiomyomata uteri.
Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. In this 2-yr study, women with myomas were treated with GnRH-a plus one of two steroid "add-back" regimens to minimize adverse sequelae of chronic hypoestrogenism. Fifty-one premenopausal women with large, symptomatic uterine myomas all received the GnRH-a, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or progestin-only add-back regimen for an additional 92 weeks. Efficacy parameters assessed included serial uterine volumes, hemoglobin concentrations, and hematocrits; safety parameters evaluated included serial bone mineral density measurements, lipid profiles, and medication-related symptoms. This report analyzes the first 52 weeks of study data. Mean uterine volume decreased to 64% of pretreatment size at 12 weeks of LAD treatment in both groups. The estrogen-progestin add-back group had no significant regrowth of uterine volume, which was 75% of pretreatment size at treatment week 52; in contrast, the progestin add-back group had a mean uterine volume of 92% of pretreatment size by treatment week 52. Both groups demonstrated significant improvements in mean hemoglobin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol concentration, which was not seen in the estrogen-progestin add-back group. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regimen groups. GnRH-a/steroid add-back regimens provide a useful long-term treatment strategy in women with large, symptomatic uterine myomas and may obviate the need for surgical intervention in selected cases. The estrogen-progestin add-back regimen was superior or equal to the progestin add-back regimen in all efficacy and safety parameters assessed.
An evolutionary psychological perspective on male sexual proprietariness and violence against wives.
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Spousal homicide risk and estrangement.
Frequencies of homicide victimization of wives and husbands, while cohabiting and when separated, are reported for all spousal homicides known to the police in Canada (1974-1990), in New South Wales, Australia (1968-1986), and in Chicago (1965-1990). In all three data sets, the degree to which spousal homicide victimization was female-biased was significantly greater when the couple were estranged than when they were coresiding. Victim counts and population-at-large estimates of coresiding and separated now-married spouses were combined to estimate differential homicide rates incurred by coresiding and estranged married persons. Wives in all three countries incurred substantially elevated risk when separated as compared to when coresiding.
Community healthcare week 1993. Marketing the message.
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Insertions/deletions in the antithrombin gene: 3 mutations associated with non-expression.
We have investigated the molecular basis of antithrombin deficiency in 3 individuals, 2 of whom had a proven family history of thromboembolic disease. An approximate 50% reduction in functional and immunologic levels of antithrombin was detected in plasma from the propositi indicating an allelic deficiency of antithrombin. In each case direct sequencing of amplified DNA revealed a novel mutation involving single bases: two being insertions, of a T in codon 48 and an A in codon 208, and the third being the deletion of an A in codon 370. The three mutations, which were confirmed by cloning and sequencing the normal and variant alleles, all caused frameshifts leading to premature termination of protein translation. In no case could a truncated antithrombin be detected in plasma from the propositus suggesting either that it fails to be secreted, or is rapidly degraded.
Specific expression of the annexin VIII gene in acute promyelocytic leukemia.
Since the translocation breakpoint t(15;17) (q22;q21) in acute promyelocytic leukemia (APL) occurs within the retinoic acid receptor-alpha (RARA) gene, the expression of many genes normally regulated by RARA may be affected by this translocation. To identify genes that may be aberrantly expressed in APL, a subtraction cDNA library of an APL patient with t(15;17) was constructed. A cDNA, pRD1, specifically expressed in APL was identified. DNA sequence analysis of pRD1 showed that this gene is similar to the DNA sequence of annexin VIII, a gene which encodes a vascular anticoagulant. The annexin VIII gene was assigned to chromosome 10, which indicates that specific expression of this gene in APL is not directly involved in the t(15;17) breakpoint region. We have analyzed the expression of annexin VIII gene in nine t(15;17)-positive APL patients and one APL patient with a chromosome 17q-abnormality. We found that all APL samples expressed high levels of the annexin VIII gene. Expression of the annexin VIII gene in all other leukemias, including acute myelogenous leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphoblastic leukemia, was undetectable, except in one patient with acute myelogenous leukemia in which a very low level of expression was detected. Annexin VIII is highly expressed in the APL cell line, NB4. Its expression was significantly reduced after 8 hours of all-trans retinoic acid (ATRA) treatment, whereas the expression of RARA increased several-fold within 4 hours postinduction. Thus, increased expression of RARA preceded the downregulation of annexin VIII after ATRA induction, suggesting an inverse relationship between RARA and annexin VIII expression. Since increased expression of the fusion transcript was seen after ATRA induction and an APL without a t(15;17) translocation expressed high levels of annexin VIII, it appears that increased expression of annexin VIII in APL is not related to the fusion transcript. Therefore, dysregulation of the RARA gene may be related to the overexpression of annexin VIII in APL.
Recurrence of myomas after myomectomy in women pretreated with leuprolide acetate depot or placebo.
The recurrence of myomas and myoma-related symptoms was evaluated in women participating in a randomized, double-blind, P-controlled study of the efficacy of LA depot before myomectomy. After 27 to 38 months of follow-up, the recurrence of myomas was found to be greater when at least four myomas were resected. Myoma recurrence was not associated with pretreatment or preoperative uterine volume, resected myoma mass, or preoperative medical therapy.
Powerlessness in acute spinal cord injury patients: a descriptive study.
The purpose of this study was to describe the frequency and characteristics of the nursing diagnosis, powerlessness, in an acute spinal cord injury (SCI) population. This descriptive study had a sample of 50 SCI patients admitted during the acute phase of injury to a model systems SCI center. Patients with a length of stay of greater than or equal to 15 days experienced a significantly higher (p less than .01) occurrence of powerlessness than did those with hospitalization of less than 15 days. Powerlessness was not found to cluster or occur in any pattern but was random throughout hospitalization. There was a statistically significant relationship (p less than .01) between the occurrence of powerlessness and patient acuity, with the occurrence increasing as acuity increased in severity. Quadriplegics and patients over the age of 60 years had a higher occurrence of powerlessness (p less than .05). This study demonstrated powerlessness was a commonly occurring diagnosis in acute SCI.
The influence of antidepressants in overdose on the increased suicide rate in Ireland between 1971 and 1988.
There has been almost a threefold increase in the incidence of suicide in Ireland during the past 20 years. When each case occurring between 1971 and 1988 was reviewed, the major causes of death were found to be drowning and hanging. Deliberate overdoses with tricyclic antidepressants accounted for less than 4% of all suicides, over the 17 years studied, and during this time, overdose with tricyclics has made a proportionately smaller contribution to the total number of suicides. Greater attention should be paid to identifying and treating the majority of suicidal patients who are at risk by other methods.
Predictors of uterine volume reduction in women with myomas treated with a gonadotropin-releasing hormone agonist.
A retrospective analysis of 104 women with leiomyomata uteri treated with LA for at least 12 weeks demonstrated a negative correlation between the percent reduction in uterine volume and serum E2 concentration at treatment week 12. The patient's age, height, or pretreatment uterine volume were not correlated with the degree of uterine shrinkage.