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Biomedical subjects

D Grady

Publications and source records attributed to D Grady.

At least 73 records · Page 4Linked to original sources
PubMed1998

Hormone and nonhormone therapy for the maintenance of postmenopausal health: the need for randomized controlled trials of estrogen and raloxifene.

Multiple health benefits have been postulated for the long-term use of hormone therapy in postmenopausal women, most notably for prevention of osteoporotic fractures and coronary heart disease, as well as several risks, including cancer of the breast and uterus and venous thromboembolism. Cardiovascular disease is the most common cause of death among postmenopausal women. If real, the reduction in risk of coronary heart disease by hormone use suggested by observational studies would likely outweigh the risks. The decision to initiate and maintain hormone therapy is complicated by uncertainties about estrogen's true benefits and risks. Raloxifene, a selective estrogen receptor modulator (SERM), appears to have many of the benefits of estrogen without the cancer risks. It is not known if SERMs can provide significant cardiovascular protection. This article reviews the relation of use of postmenopausal hormones and raloxifene to women's health and addresses the need for large randomized trials to quantify the effect of both postmenopausal estrogen and raloxifene on cardiovascular health.

Cardiovascular Diseases↗
PubMed1998

Serum estrogen levels, cognitive performance, and risk of cognitive decline in older community women.

OBJECTIVE: To determine the association between serum estrogen levels, cognitive performance, and risk of cognitive decline in older women. DESIGN: Prospective cohort study with an average follow-up of 5 years. SETTING: Clinical centers in Baltimore, MD, Minneapolis, MN, Portland, OR, and the Monongahela Valley in Pennsylvania. PARTICIPANTS: 532 women aged 65 years or older who were the controls from two nested case-control studies in the ongoing Study of Osteoporotic Fractures. OUTCOME MEASURES: Three cognitive tests--a modified Mini-Mental Status Exam, Digit Symbol, and Trails B--were administered at study initiation and were then repeated approximately 5 years later. Estrone and estradiol levels were determined by radioimmunoassay at two laboratories from baseline stored serum. RESULTS: The characteristics of the women in the four serum estrogen quartiles did not differ except that body weight and change in weight since age 50 increased directly with higher quartile of serum estrogen (P < .001, for both estrone and estradiol). Initial cognitive performance on all three tests did not differ consistently by quartile of estradiol or by the estradiol to estrone ratio. Women in the higher estrone quartiles had 15% lower (worse) scores on Digit Symbol compared with the lower quartiles (P=.004) but there was no difference by quartile on the modified MMSE or on Trails B. Cognitive function test scores declined over the 5 years of follow-up. There was no difference in amount of change by quartile of estradiol, but women in the higher estrone quartiles had greater reduction of scores on Trails B compared with those in the lower quartiles (P=.012), even after adjusting for age, education, depression, stroke history, weight, and change in weight since age 50. The age-adjusted odds of cognitive decline (defined as tenth percentile of women with the largest decline in cognitive performance) did not vary across quartile of estrone or estradiol. CONCLUSIONS: Endogenous estrogens are not associated consistently with cognitive performance or risk of cognitive decline on a selected battery of cognitive tests in older community-dwelling women. Worse performance on two cognitive tests among women with higher estrone levels was surprising and warrants further investigation.

Aged↗
PubMed1998

Hormone replacement therapy, heart disease, and other considerations.

Multiple observational studies suggest a marked reduction in risk of coronary heart disease (CHD) associated with postmenopausal estrogen use. A new meta-analysis presented here extends these results to estrogen plus progestin regimens. Although the findings from observational studies are strong and consistent, and there are several plausible mechanisms by which estrogen might reduce risk for CHD, most of the known biases would tend to exaggerate estrogen's benefit. Further, estrogen therapy clearly increases risk for endometrial hyperplasia and cancer, venous thromboembolic events and gallbladder disease, and long-term use probably also increases the risk of breast cancer. Therefore, until findings from randomized trials confirm and quantitate the benefit of estrogen therapy for prevention of CHD, we believe it should not be recommended to all postmenopausal women.

Bias↗
PubMed1997

Comparison of risk factors for ductal carcinoma in situ and invasive breast cancer.

BACKGROUND: Ductal carcinoma in situ (DCIS) accounts for approximately 12% of newly diagnosed breast cancers. Knowledge of the factors that predict who will be diagnosed with DCIS is very limited. PURPOSE: The goal of this study was to determine risk factors associated with DCIS and whether these risk factors are similar to those associated with invasive breast cancer. METHODS: We conducted a cross-sectional study of 39,542 women aged 30 years and older who underwent a screening mammographic examination at the University of California San Francisco Mobile Mammography Screening Program from April 1985 through September 1995. A breast cancer risk profile and clinical history were obtained for each woman. Follow-up after abnormal mammography was performed to determine the presence of DCIS or invasive breast cancer by contacting the women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results cancer registry. Multivariate analysis was performed by the use of polytomous logistic regression. Two-sided statistical tests were used to determine P values. RESULTS: Among women aged 30-49 years, a family history of breast cancer (i.e., at least one affected first degree relative) was associated with an increased risk of DCIS (Odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.1-4.9) and body mass index greater than or equal to 25 kg/m2 was associated with a decreased risk of DCIS (OR = 0.4, 95% CI = 0.2 to 0.9). For each of these factors, there was a trend in the same direction bordering on statistical significance for invasive cancer (ORs = 1.7 [95% CI = 0.9-3.4] and 0.6 [95% CI = 0.3-1.1], respectively). Report of a palpable mass was associated with an increased risk of invasive cancer among women aged 30-49 years (OR = 12.0; 95% CI = 7.1-20.0); there was a trend in the same direction for DCIS (OR = 2.0; 95% CI = 0.8-5.1), but the association was much stronger for invasive disease than for DCIS (OR = 6.0; 95% CI = 2.1-18.0; P = .001). Among women aged 50 years and older, family history of breast cancer and nulliparity or age at birth of first child of 30 years or older increased the risk of both DCIS (ORs = 2.2 [95% CI = 1.0-4.2] and 2.3 [95% CI = 1.3-3.8], respectively) and invasive breast cancer (ORs = 1.5 [95% CI = 1.0-2.2] and 1.6 [95% CI = 1.2-2.1], respectively). Report of a palpable mass was not associated with an increased risk of DCIS among women 50 years and older, but it was strongly associated with an increased risk of invasive cancer (OR = 9.3; 95% CI = 6.0-14.0). Increasing age was associated with an increased risk of both DCIS and invasive cancer among women aged 30-49 years, but the association was stronger for invasive disease; a trend in the same direction bordering on statistical significance was observed for women aged 50 years and older. CONCLUSION: Risk factors for DCIS are similar to those for invasive breast cancer. IMPLICATIONS: More research is needed to better understand the malignant potential of DCIS lesions and factors that predict which lesions will become invasive breast cancer if left untreated.

Adult↗
PubMed1997

Development of diagnostic tools for the analysis of 5p deletions using interphase FISH.

Cri-du-chat syndrome is associated with a deletion of the short arm of chromosome 5. Through the phenotypic and molecular analyses of individuals with a subset of the features associated with the syndrome, the genes involved in the syndrome have been mapped to two distinct critical regions. Deletion of a critical region in 5p15.2 results in the distinct facial features associated with the syndrome as well as the severe mental and developmental delay, while a deletion of 5p15.3 is associated only with the characteristic cat-like cry, the key diagnostic feature of the syndrome. Therefore, subtle differences in the extent of the 5p deletion can have a profound affect on the prognosis of the patient. In order to more easily differentiate between deletions that lead to the cri-du-chat syndrome phenotype and deletions that lead only to the isolated cat-like cry, we have constructed YAC contigs that span both critical regions. The YAC clones have been used to isolate cosmids mapping to each critical region and cosmids that lie just within the two critical region boundaries have been identified. We report here on the use of these cosmids as probes for fluorescent in situ hybridization experiments on interphase nuclei as a means of more accurately differentiating between small 5p deletions that coincide with a complete cri-du-chat syndrome phenotype and the severe mental and developmental delay that is associated with it and deletions that only delete the distal critical region that coincide with the isolated cat-like cry and a much improved prognosis.

Animals↗
PubMed1997

A spit tobacco cessation intervention for college athletes: three-month results.

Sixteen colleges were matched on the baseline prevalence of spit tobacco (ST) use, and college pairs were randomized, one to the intervention and the other to the control group. Baseball and football athletes at each intervention college received: an oral examination by a dental professional who pointed out ST-related problems in the athlete's mouth and advised him to quit ST use; counseling by a dental hygienist on strategies to cope with cravings and triggers for use; and two follow-up telephone calls. At the three-month follow-up, quit rates were 24% and 16% for the intervention (n = 171) and control (n = 189) groups, respectively (p < 0.05). As the reported amount of ST used weekly increased, the percent of individuals who quit at 3 mos decreased (p < 0.05). Dental professionals appear to be effective in promoting spit tobacco cessation at 3 mos post-intervention in male college athletes, especially among those using lesser amounts of ST.

Alcohol Drinking↗
PubMed1997

Molecular characterization of patients with 18q23 deletions.

The 18q- syndrome is a deletion syndrome that is characterized by mental retardation, hearing loss, midfacial hypoplasia, growth deficiency, and limb anomalies. Most patients with this syndrome have deletions from 18q21-qter. We report on three patients with deletions of 18q23. A mother and daughter with identical deletions of 18q23 have many of the typical features of the 18q- syndrome, including midfacial hypoplasia and hearing loss. In contrast, the third patient has few of the symptoms of the 18q- syndrome. A contig of the 18q23 region was generated to aid in the mapping of the breakpoints. FISH was used to map both breakpoints to the same YAC clone. Furthermore, somatic-cell hybrids from the daughter and the third patient were isolated. The mapping results of sequence-tagged sites relative to the two breakpoints were identical, suggesting that the two deletion breakpoints map very close to one another. The analyses of these patients demonstrate that the critical region for the 18q- syndrome maps to 18q23 but that a deletion of 18q23 does not always lead to the clinical features associated with the syndrome. These patients demonstrate the wide phenotypic variability associated with deletions of 18q.

Abnormalities, Multiple↗
PubMed1996

Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis.

OBJECTIVE: To estimate the risk of myocardial infarction (MI) and death in patients with unstable angina who are treated with aspirin plus heparin compared with patients treated with aspirin alone. DATA SOURCES: Studies were retrieved using MEDLINE, bibliographies, and consultation with experts. STUDY SELECTION: Only published trials that enrolled patients with unstable angina, randomized participants to aspirin plus heparin vs aspirin alone, and reported incidence of myocardial infarction or death were included in the meta-analysis. DATA EXTRACTION: Patient outcomes including MI or death, recurrent ischemic pain, and major bleeding during randomized treatment; revascularization procedures after randomization; and MI or death during the 2 to 12 weeks following randomization were extracted by 2 authors, 1 of whom was blinded to the journal, institution, and author of each study. DATA SYNTHESIS: Six randomized trials were included. The overall summary relative risk (RR) of MI or death during randomized treatment was 0.67 (95% confidence interval [CI], 0.44-1.02) in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The summary RRs for secondary endpoints in patients treated with aspirin plus heparin compared with those treated with aspirin alone were 0.68 (95% CI, 0.40-1.17) for recurrent ischemic pain; 0.82 (95% CI, 0.56-1.20) for MI or death 2 to 12 weeks following randomization; 1.03 (95% CI, 0.74-1.43) for revascularization; and 1.99 (95% CI, 0.52-7.65) for major bleeding. We found no statistically significant heterogeneity among individual study findings. CONCLUSIONS: Our findings are consistent with a 33% reduction in risk of MI or death in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The bulk of evidence suggests that most patients with unstable angina should be treated with both heparin and aspirin.

Angina, Unstable↗
PubMed1996

Likelihood ratios for modern screening mammography. Risk of breast cancer based on age and mammographic interpretation.

OBJECTIVE: To determine the sensitivity, specificity, and likelihood ratios (LRs) for modern screening mammography by decade of age and mammographic interpretation. DESIGN: Cross-sectional. SETTING: Nine counties in northern California. PARTICIPANTS: A total of 26,057 women aged 30 years and older who underwent a total of 41,747 first and subsequent screening mammographic examinations at the Mobile Mammography Screening Program of the University of California, San Francisco, from April 1985 to September 1991. MEASUREMENTS: Breast cancer risk profile, 2 standard mammographic views per breast, and follow-up of abnormal and normal mammograms of contacting women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results tumor registry. False-negative examinations were normal examinations that occurred within 13 months of a diagnosis of invasive breast cancer or ductal carcinoma in situ. RESULTS: The sensitivity of first screening mammography increased with age: 77.3% for ages 30 to 39 years, 86.7% for ages 40 to 49 years, 93.6% for ages 50 to 59 years, 94.1% for ages 60 to 69 years, and 91.2% for ages 70 years and older (P = .04). Specificity was similar for all ages, ranging from 92.6% to 95.2%. Of all abnormal first screening examinations, 92.9% were reported as "additional evaluation needed." The LRs for that category ranged from 5.2 to 8.8 and did not vary with age. Based on the risk of breast cancer before mammography, which increases with age, the risk of breast cancer after mammography associated with these LRs were 0.01 for ages 30 to 39 years, 0.02 for ages 40 to 49 years, 0.05 for ages 50 to 59 years, 0.07 for ages 60 to 69 years, and 0.07 for ages 70 years and older. The LRs for mammography reported as "suspicious for malignancy" ranged from 88 to 144 and did not vary across age groups. These LRs were associated with a risk of breast cancer about 10 times greater than when mammography was reported as "additional evaluation needed." CONCLUSION: Most abnormal first screening mammography are interpreted as "additional evaluation needed" and are associated with LRs of about 7. Given this low LR, the risk of breast cancer after mammography is primarily influenced by a woman's age-specific risk of breast cancer before mammography. The LRs for screening mammography interpreted as "suspicious for malignancy" are high (about 124) and are associated with a substantial increase in the risk of breast cancer irrespective of age, but these interpretations comprise only a small proportion of abnormal mammography.

Adult↗
PubMed1996

Effect of age, breast density, and family history on the sensitivity of first screening mammography.

OBJECTIVE: To determine factors that influence the sensitivity of modern first screening mammography. DESIGN: Cross-sectional. SETTING: Nine counties in northern California. PARTICIPANTS: A total of 28 271 women aged 30 years and older referred for first screening mammography to the Mobile Mammography Screening Program of the University of California, San Francisco, from April 1985 to March 1992, of whom 238 were subsequently diagnosed as having breast cancer. MEASUREMENTS: Breast cancer risk profile, 2 standard mammographic views per breast, breast density, and follow-up of abnormal and normal mammography by contacting women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results tumor registry to determine the occurrence of any invasive cancer or ductal carcinoma in situ. RESULTS: For women aged 50 years and older, the sensitivity of first screening mammography was relatively high and decreased slightly with increasing length of follow-up after mammography: 98.5% for 7 months of follow-up, 93.2% for 13 months, and 85.7% for 25 months. Sensitivity was higher among women aged 50 years and older when breast density was primarily fatty rather than primarily dense (98.4% vs 83.7%; P < .01). For women younger than 50 years, the sensitivity of first screening mammography also decreased with increasing length of follow-up but was significantly lower than for older women: 87.5% for 7 months of follow-up, 83.6% for 13 months, and 71.4% for 25 months. For women younger than 50 years, breast density did not affect the sensitivity of mammography (81.8% for those with primarily fatty breasts vs 85.4% for those with primarily dense breasts) and was lower among those with a family history of breast cancer (68.8%). CONCLUSIONS: The sensitivity of modern mammography is highest among women aged 50 years and older who have primarily fatty breast density. Sensitivity is lowest among women younger than 50 years and particularly low when the time between screenings is about 2 years or when women have a family history of breast cancer, possibly because of rapid tumor growth.

Adipose Tissue↗
PubMed1996

Growth hormone replacement in healthy older men improves body composition but not functional ability.

OBJECTIVE: To determine whether growth hormone replacement in older men improves functional ability. DESIGN: Randomized, controlled, double-blind trial. SETTING: General community. PATIENTS: 52 healthy men older than 69 years of age with well-preserved functional ability but low baseline insulin-like growth factor 1 levels. INTERVENTION: Growth hormone (0.03 mg/kg of body weight) or placebo given three times a week for 6 months. MEASUREMENTS: Body composition, knee and hand grip muscle strength, systemic endurance, and cognitive function. RESULTS: The participants' mean age was 75.0 years (range, 70 to 85 years). At 6 months, lean mass had increased on average by 4.3% in the growth hormone group and had decreased by 0.1% in the placebo group, a difference of 4.4 percentage points (95% CI, 2.1 to 6.8 percentage points). Fat mass decreased by an average of 13.1% in the growth hormone group and by 0.3% in the placebo group, a difference of 12.8 percentage points (CI, 8.6 to 17.0 percentage points). No statistically or clinically significant differences were seen between the groups in knee or hand grip strength or in systemic endurance. The mean Trails B score in the growth hormone group improved by 8.5 seconds, whereas scores in the placebo group deteriorated by 5.0 seconds, a difference of 13.5 seconds (CI, 3.1 seconds to 23.9 seconds; P = 0.01). However, the growth hormone group's score on the Mini-Mental Status Examination deteriorated by 0.4, whereas the placebo group's score improved by 0.2, a difference of 0.6 (P = 0.11). The two treatment groups had almost identical scores on the Digit Symbol Substitution Test (P > 0.2). Twenty-six men in the growth hormone group had 48 incidents of side effects, and 26 placebo recipients had 14 incidents of side effects (P = 0.002). Dose reduction was required in 26% of the growth hormone recipients and in none of the placebo recipients (P < 0.001). CONCLUSIONS: Physiologic doses of growth hormone given for 6 months to healthy older men with well-preserved functional abilities increased lean tissue mass and decreased fat mass. Although body composition improved with growth hormone use, functional ability did not improve. Side effects occurred frequently.

Affect↗