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Biomedical subjects

S Cummings

Publications and source records attributed to S Cummings.

At least 19 recordsLinked to original sources
PubMed2005

The determinants of bone mineral density in Chinese men--results from Mr. Os (Hong Kong), the first cohort study on osteoporosis in Asian men.

Mr. Os (Hong Kong) is the first study to address the risk factors for osteoporosis in Asian men. A standardized, structured interview and dual X-ray densitometry (DEXA) were performed on 2,000 Chinese men aged 65-92. By multiple regression, the following factors were found to be positively associated with BMD at both the total hip and the spine: body weight, grip strength and a history of diabetes mellitus. The following factors were found to be negatively associated with BMD at both the total hip and spine: cigarette smoking, a history of gastrectomy or bowel resection, current use of inhaled steroid and a history of fracture after 50 years. Moreover, a history of chronic obstructive pulmonary disease (COPD) was negatively associated with BMD at the total hip, and age, the use of an alpha-blocker, thiazide diuretic and nitrate were associated with a higher BMD at the spine. A total of 21.8% of the variance in total hip and 31.5% of the variance in total spine BMD was accounted for in the multivariate analysis.

Absorptiometry, Photon↗
PubMed2001

A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial.

Vitamin D deficiency leads to secondary hyperparathyroidism, increased bone turnover, and bone loss and, when severe, to osteomalacia. Vitamin D deficiency is common in elderly people, especially the institutionalized. The definition of vitamin D deficiency is hampered by the fact that large interlaboratory differences exist in assays for serum 25-hydroxyvitamin D (25OHD), the main circulating metabolite. The international Multiple Outcomes of Raloxifene Evaluation study, a large prospective intervention trial in postmenopausal women with osteoporosis, offered the opportunity to compare vitamin D status and parathyroid function throughout many countries over the world. For this study, baseline data were available from 7564 postmenopausal women from 25 countries on 5 continents. All women had osteoporosis, i.e. bone mineral density (BMD) at femoral neck or lumbar spine was lower than t-score -2.5, or they had 2 vertebral fractures. Serum 25OHD was measured by RIA, and serum PTH was measured by immunoradiometric assay. BMD was measured by dual x-ray absorptiometry. The mean (+/-SD) serum 25OHD was 70.8 +/- 30.9 nmol/L. A low serum 25OHD (<25 nmol/L) was observed in 4.1% of all women in the Multiple Outcomes of Raloxifene Evaluation study, ranging from 0% in south east Asia (very few patients) to 8.3% in southern Europe. Serum 25OHD was between 25-50 nmol/L in 24.3% of the women. Serum 25OHD showed a significant seasonal relationship, with lower values in all regions in winter. Serum PTH correlated negatively with serum 25OHD (r = -0.25; P < 0.001). This significant negative correlation was observed in all regions. When serum 25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, mean serum PTH levels were 4.8, 4.1, and 3.5 pmol/L, respectively (by ANOVA, P < 0.001). Similarly, mean alkaline phosphatase levels were 83.7, 79.1, and 75.7 U/L (P < 0.001), respectively, with increasing serum 25OHD. The effect of serum 25OHD on BMD was only significant for the BMD of the trochanter where a serum 25OHD level less than 25 nmol/L was associated with a 4% lower BMD. After 6 months of treatment with vitamin D(3) (400-600 IU/day) and calcium (500 mg/day), serum 25OHD increased from 70.8 +/- 29.8 to 92.3 +/- 28.6 nmol/L. Serum PTH decreased significantly after 6 months of treatment, and this decrease depended on baseline serum 25OHD. When baseline serum 25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, serum PTH decreased by 0.8, 0.5, or 0.2 pmol/L, respectively (P < 0.001). In conclusion, serum 25OHD was less than 25 nmol/L in 4% of the women, and this was associated with a 30% higher serum PTH. In 24% of the women serum 25OHD was between 25-50 nmol/L, associated with a 15% higher level of serum PTH compared with women with a serum 25OHD greater than 50 nmol/L. A low serum 25OHD level was also associated with higher serum alkaline phosphatase and lower BMD of the trochanter. Treatment with vitamin D(3) and calcium increased serum 25OHD and decreased serum PTH significantly; the effect was greater for lower baseline serum 25OHD.

Absorptiometry, Photon↗
PubMed2000

Prevalence of BRCA1 and BRCA2 mutations among clinic-based African American families with breast cancer.

To define the prevalence and relative contributions of BRCA1 and BRCA2 mutations among African American families with breast cancer, we analyzed 28 DNA samples from patients identified through two oncology clinics. The entire coding regions of BRCA1 and BRCA2 were screened by protein truncation test, heteroduplex analysis, or single-stranded conformation polymorphism followed by DNA sequencing of variant bands. Deleterious protein-truncating BRCA1 and BRCA2 mutations were identified in five patients or 18% of the entire cohort. Only 8% (1 of 13) of women with a family history of breast cancer, but no ovarian cancer, had mutations. The mutation rates were higher for women from families with a history of breast cancer and at least one ovarian cancer (three of six, 50%). One woman with a family history of undocumented cancers was also found to carry a deleterious mutation in BRCA2. The spectrum of mutations was unique in that one novel BRCA1 mutation (1625del5) and three novel BRCA2 mutations (1536del4, 6696delTC, and 7795delCT) were identified. No recurrent mutations were identified in this cohort, although one BRCA2 (2816insA) mutation had been previously reported. In addition, two BRCA1 and four BRCA2 missense mutations of unknown significance were identified, one of which was novel. Taken together with our previous report on recurrent mutations seen in unrelated families, we conclude that African Americans have a unique mutation spectrum in BRCA1 and BRCA2 genes, but recurrent mutations are likely to be more widely dispersed and therefore not readily identifiable in this population.

Adult↗
PubMed1999

Obstetrics anyone? How family medicine residents' interests changed.

OBJECTIVE: To determine family medicine residents' attitudes and plans about practising obstetrics when they enter and when they graduate from their residency programs. DESIGN: Residents in each of 4 consecutive years, starting July 1991, were surveyed by questionnaire when they entered the program and again when they graduated (ending in June 1996). Only paired questionnaires were used for analysis. SETTING: Family medicine residency programs at the University of Toronto in Ontario. PARTICIPANTS: Of 358 family medicine residents who completed the University of Toronto program, 215 (60%) completed questionnaires at entry and exit. MAIN OUTCOME MEASURES: Changes in attitudes and plans during the residency program as ascertained from responses to entry and exit questionnaires. RESULTS: Analysis was based on 215 paired questionnaires. Women residents had more interest in obstetric practice at entry: 58% of women, but only 31% of men were interested. At graduation, fewer women (49%) and men (22%) were interested in practising obstetrics. The intent to undertake rural practice was strongly associated with the intent to practise obstetrics. By graduation, residents perceived lifestyle factors and compensation as very important negative factors in relation to obstetric practice. Initial interest and the eventual decision to practise obstetrics were strongly associated. CONCLUSIONS: Intent to practise obstetrics after graduation was most closely linked to being a woman, intending to practise in a rural area, and having an interest in obstetrics prior to residency. Building on the interest in obstetrics that residents already have could be a better strategy for producing more physicians willing to practise obstetrics than trying to change the minds of those uninterested in such practice.

Adult↗
PubMed1998

Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study.

BACKGROUND: Though among the most abundant human steroid hormones, the physiologic role of dehydroepiandrosterone and its sulfate (DHEAS) is not known. Our goal was to determine if DHEAS is associated with cognition and mood in older women, and if baseline DHEAS levels are predictive of cognitive decline. METHODS: In a prospective cohort, we studied 394 randomly selected community-dwelling women, aged 65 years or older, currently enrolled in the Study of Osteoporotic Fractures. Subjects were administered a modified Mini-Mental State Exam, Trials B, Digit Symbol, and the Geriatric Depression Scale-Shortened (GDSS), at study onset and 4-6 years later. Serum was obtained at study initiation for DHEAS analysis. RESULTS: DHEAS levels declined with age, as expected. There was no consistent association of DHEAS quartile or log DHEAS with any of the four outcomes, even after multivariate adjustment. Change in cognitive performance overtime was not associated with DHEAS levels. Analysis of the 32 women without any detectable DHEAS compared to those with detectable levels revealed higher measures on the GDSS (mean score 3.4 +/- 3.6 compared with 1.6 +/- 2.3, p = .028) and a higher percentage with depression (21.7% compared with 4.6%, p = .001). CONCLUSIONS: Serum DHEAS is not a sensitive predictor of cognitive performance or decline on a selected neuropsychological battery in elderly community women; however, nondetectable levels may be associated with depression.

Aged↗
PubMed1998

Hormone replacement therapy: determinants of women's decisions.

Hormone replacement therapy: determinants of women's decisions. The purpose of this qualitative study was to explore the decision-making process used by menopausal women initiating or remaining on hormone replacement therapy (HRT), stopping HRT, or never starting HRT. Eight focus groups, composed of women reflecting these categories, were conducted. Four major themes or spheres of influence emerged as important in the women's decision-making process: the woman's internal influence--the interface between her perceptions and feelings including the symptoms of menopause, the benefits realized by HRT usage, and the experiences of negative side effects; interpersonal relationships, including the patient-physician relationship, family, friends and information networks; external influences, such as ageism and sexism; and consequences resulting from whichever treatment decision was chosen. A new concept was elucidated called "weighted influence" to underscore the dynamic interplay among the spheres. As information about HRT continues to grow and change, an understanding and application of these spheres of influence can assist physicians in engaging in a dialogue with their patients that allows individual evaluation and application of this new information.

Adult↗
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

Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.

PURPOSE: Previous studies of mutations in BRCA1 or BRCA2 have used detection methods that may underestimate the actual frequency of mutations and have analyzed women using heterogeneous criteria for risk of hereditary cancer. PATIENTS AND METHODS: A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one first- or second-degree relative with either diagnosis underwent sequence analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was discovered in BRCA1). Results were correlated with personal and family history of malignancy. RESULTS: Deleterious mutations were identified in 94 (39%) women, including 59 of 117 (50%) from families with ovarian cancer and 35 of 121 (29%) from families without ovarian cancer. Mutations were identified in 14 of 70 (20%) women with just one other relative who developed breast cancer before age 50. In women with breast cancer, mutations in BRCA1 and BRCA2 were associated with a 10-fold increased risk of subsequent ovarian carcinoma (P = .005). CONCLUSION: Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.

Adult↗
PubMed1998

Predisposition testing for inherited breast cancer.

Predisposition testing (i.e., genetic testing that provides information about a person's susceptibility to disease) is now available for several inherited forms of cancer. Individuals who are found to have an altered gene (e.g., a germ-line mutation in a cancer susceptibility gene) have a higher risk of developing cancer than those who do not carry an altered gene. Therefore, predisposition testing can be a powerful clinical tool for assessing a person's risk for developing cancer. All health care providers, particularly cancer care providers, should be knowledgeable about cancer predisposition testing options. This article provides an overview of predisposition testing for inherited breast cancer, including general facts about testing, potential risks and benefits, specific genetic counseling issues, and molecular details of known breast cancer susceptibility genes.

Adult↗
PubMed1997

Sex steroid hormones, bone mineral density, and risk of breast cancer.

Increased bone mineral density (BMD), as a marker of higher integrated estrogen exposure over time, could be an important risk factor for postmenopausal breast cancer. In the Study of Osteoporotic Fractures 8065 non-black women age 65 years and older were followed for an average of 3.2 years. There were 121 incident breast cancer cases. The age adjusted incidence rate/1000 person years of breast cancer was substantially higher among women with high BMD at several measured bone sites. There was approximately a 2-fold higher risk of breast cancer for women in the upper as compared to the lower 25th percentile of BMD. Considerable controversy exists about the association of hormone replacement therapy (HRT) and increased risk of breast cancer. In this paper we modeled the effects of selection for HRT, presuming that women with lower BMD would be more likely to be on HRT, then estimated the observed versus potential risk of breast cancer among HRT users as compared to nonusers. The model suggests that the potential risk of breast cancer associated with HRT could be greatly underestimated and that postmenopausal women with high BMD who are placed on HRT could have a substantially increased risk of breast cancer. This model of increased risk of breast cancer associated with BMD and HRT needs to be evaluated within clinical trials and larger observational studies that include measures of BMD.

Aged↗
PubMed1997

The potential role of fecal carbonic anhydrase II in screening for colorectal cancer.

Several studies have demonstrated a relationship between mucosal carbonic anhydrase (CA) isoenzymes, particularly CA II, and cancer of the large intestine. Recent work has suggested the potential usefulness of fecal CA assay for colorectal cancer screening. This clinical study examined the accuracy of fecal CA II as a marker of adenocarcinoma of the colon and rectum. An enzyme-linked immunosorbent assay was used to measure CA II in urine, serum, and stool samples from 31 colorectal cancer patients and 26 control subjects. An immunochemical fecal occult blood test was also performed in all study participants. Urine and serum CA II were similar in the two study groups. However, both the prevalence and the mean level of fecal CA II in the cancer patients were significantly higher than those in the control group. The detection rate for CA II in the stool was 65 per cent for the cancer patients versus 4 per cent for the control population. The fecal CA II test was similar in sensitivity and specificity to the immunochemical fecal occult blood test (65 vs 48%; 96 vs 100%). Measurement of fecal CA II might be useful in screening for colorectal cancer.

Biomarkers, Tumor↗