Body mass index and the risk of venous thrombosis among postmenopausal women.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
N L Smith
Publications and source records attributed to N L Smith.
The differential association of conjugated equine estrogen and esterified estrogen with activated protein C resistance in postmenopausal women.
OBJECTIVES: Clinical trials have demonstrated that oral conjugated equine estrogen (CEE) therapy with or without medroxyprogesterone (MPA) increases venous thrombotic risk but this safety issue has not been investigated for other oral estrogens. Based on observational study findings that esterified estrogen (EE) was not associated with venous thrombotic risk whereas CEE was, we hypothesized that CEE users would be more resistant to activated protein C (APC), a prothrombotic phenotype, than EE users. METHODS: We conducted an observational, cross-sectional study of postmenopausal women 30-89 years old who were controls in a case-control study of venous thrombosis. Use of CEE, EE, and MPA at the time of phlebotomy was determined using computerized pharmacy records. APC resistance was measured in plasma by the endogenous thrombin potential normalized APC sensitivity ratio. Adjusted mean APC resistance values were compared across estrogen type and CEE:EE ratios are presented. RESULTS: There were 119 CEE and 92 EE users at the time of phlebotomy. Compared with EE users, CEE users had APC resistance measures that were 52% higher (1.52; 95% confidence intervals: 1.07-2.17) in adjusted analyses. Restricting to modal dose users (0.625 mg) and stratifying by MPA use did not materially change associations. CONCLUSIONS: CEE use was associated with higher levels of APC resistance when compared with EE use in postmenopausal women. These findings might provide an explanation for the higher risk of venous thromboembolism previously observed with CEE compared with EE use and, if replicated, may have safety implications for women when choosing an estrogen for symptom relief.
Activated Protein C Resistance↗
Statins and cognitive function in the elderly: the Cardiovascular Health Study.
OBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults. METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy. RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups. CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.
Aged↗
Intracardiac extension of a large cell undifferentiated carcinoma of lung.
Explore the source record for details and available documents.
Carcinoma, Large Cell↗
Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups.
OBJECTIVE: To perform a health maintenance organization-based case-control study to evaluate the association of total and high density lipoprotein (HDL) cholesterol with the risk of stroke subtypes and in patient subgroups. METHODS: Cases had a confirmed incident ischemic stroke (n = 1,242) or hemorrhagic stroke (n = 313). Controls (n = 6,455) were identified in a companion myocardial infarction study. Risk of stroke was modeled using logistic regression. RESULTS: The highest total cholesterol quintile was associated with an increased risk of ischemic stroke compared to the lowest quintile (OR = 1.6, 95% CI 1.3 to 2.0) with the strongest subtype associations for atherosclerotic stroke (OR = 3.2) and lacunar stroke (OR = 2.4). The highest HDL cholesterol quintile was associated with a decreased risk of ischemic stroke compared to the lowest quintile (OR = 0.8, CI 0.6 to 1.0). Subgroup analyses suggested that the total cholesterol association was more important for patients < 66 years of age and those with HDL < 50 mg/dL; the HDL association was more important for patients without diabetes or atrial fibrillation. The second through fourth total cholesterol quintiles were associated with a decreased risk of hemorrhagic stroke compared to the lowest quintile (OR = 0.7, CI 0.5 to 1.0). CONCLUSIONS: Higher total and lower HDL cholesterol levels were associated with increased risk of ischemic stroke, especially certain stroke subtypes and patient subgroups. The lowest levels of total cholesterol were associated with an increased risk of all hemorrhagic strokes.
Adult↗
Experimental observation of the tilting mode of an array of vortices in a dilute Bose-Einstein condensate.
We have measured the precession frequency of a vortex lattice in a Bose-Einstein condensate of Rb87 atoms. The observed mode corresponds to a collective motion in which all the vortices in the array are tilted by a small angle with respect to the z axis (the symmetry axis of the trapping potential) and synchronously rotate about this axis. This motion corresponds to excitation of a Kelvin wave along the core of each vortex and we have verified that it has the handedness expected for such helical waves, i.e., precession in the opposite sense to the rotational flow around the vortices.
Journal Article↗
HMG CoA reductase inhibitors and the risk of venous thrombosis among postmenopausal women.
Explore the source record for details and available documents.
Adult↗
Experimental observation of a superfluid gyroscope in a dilute Bose-Einstein condensate.
We have observed a three-dimensional gyroscopic effect associated with a vortex in a dilute Bose-Einstein condensed gas. A condensate with a vortex possesses a single quantum of circulation, and this causes the plane of oscillation of the scissors mode to precess around the vortex line. We have measured the precession rate of the scissors oscillation. From this we deduced the angular momentum associated with the vortex line and found a value close to Planck's over 2pi per particle, as predicted for a superfluid.
Journal Article↗
The location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence is not conserved.
Polysaccharide-degrading enzymes are generally modular proteins that contain non-catalytic carbohydrate-binding modules (CBMs), which potentiate the activity of the catalytic module. CBMs have been grouped into sequence-based families, and three-dimensional structural data are available for half of these families. Clostridium thermocellum xylanase 11A is a modular enzyme that contains a CBM from family 6 (CBM6), for which no structural data are available. We have determined the crystal structure of this module to a resolution of 2.1 A. The protein is a beta-sandwich that contains two potential ligand-binding clefts designated cleft A and B. The CBM interacts primarily with xylan, and NMR spectroscopy coupled with site-directed mutagenesis identified cleft A, containing Trp-92, Tyr-34, and Asn-120, as the ligand-binding site. The overall fold of CBM6 is similar to proteins in CBM families 4 and 22, although surprisingly the ligand-binding site in CBM4 and CBM22 is equivalent to cleft B in CBM6. These structural data define a superfamily of CBMs, comprising CBM4, CBM6, and CBM22, and demonstrate that, although CBMs have evolved from a relatively small number of ancestors, the structural elements involved in ligand recognition have been assembled at different locations on the ancestral scaffold.
Amino Acid Sequence↗
Body mass index and the risk of recurrent coronary events following acute myocardial infarction.
Although excess adiposity appears to increase the risk of coronary heart disease in the general population, its importance in patients with established coronary disease is less defined. We evaluated a population-based inception cohort of survivors to hospital discharge following first acute myocardial infarction (AMI) (n = 2,541) to assess the association between body mass index (BMI) and the risk of recurrent coronary events and to explore the mechanisms for this relation. Using Cox proportional-hazards regression, we assessed the risk of recurrent coronary events associated with levels of adiposity as defined by BMI and then investigated potential mechanisms through which adiposity conferred risk by examining how adjustment for diabetes mellitus, systemic hypertension, and dyslipidemia affected the association. Forty-one percent of the cohort were overweight (BMI 25 to 29.9), and 27.8% were obese (BMI > or =30). After adjustment for other risk factors, the risk of recurrent coronary events (n = 418) increased as BMI increased, especially among those who were obese. Using a BMI of 16 to 24.9 as the reference group, for mildly overweight patients (BMI 25 to 27.4), the relative risk (RR) was 0.93 (95% confidence interval [CI] 0.70 to 1.24); it was 1.16 for more severe overweight patients (BMI 27.5 to 29.9; 95% CI 0.87 to 1.55). For patients with class I obesity (BMI 30 to 34.9), the RR was 1.49 (95% CI 1.12 to 1.98), and for class II to III obesity (BMI > or =35), the RR was 1.80 (95% CI 1.30 to 2.48). We estimated that clinical measurements of diabetes, hypertension, and dyslipidemia explained approximately 43% of this risk. Thus, excess adiposity as measured by BMI was associated with an increased risk of recurrent coronary events following AMI, particularly among those who were obese.
Adult↗
Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women.
CONTEXT: Estrogens are known to be prothrombotic, and findings from the Heart and Estrogen/progestin Replacement Study suggest that in women with clinically recognized heart disease, hormone replacement therapy (HRT) may be associated with early harm and late benefit in terms of coronary events. OBJECTIVE: To assess whether, as hypothesized, prothrombotic mutations modify the association between HRT use and incidence of first myocardial infarction (MI). DESIGN AND SETTING: Population-based, case-control study conducted in a Seattle-based health maintenance organization. PARTICIPANTS: Cases were 232 postmenopausal women aged 30 to 79 years who had their first nonfatal MI between 1995 and 1998. Controls were a stratified random sample of 723 postmenopausal women without MI who were frequency-matched to cases by age, calendar year, and hypertension status. MAIN OUTCOME MEASURE: Risk of first nonfatal MI based on current use of HRT and the presence or absence of coagulation factor V Leiden and prothrombin 20210 G-->A variants among cases and controls, stratified by hypertension. RESULTS: One hundred eight MI cases and 387 controls had hypertension and 124 MI cases and 336 controls did not. Among hypertensive women, the prothrombin variant was a risk factor for MI (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.52-12.1) and, in this stratum, there was also a significant interaction between use of HRT and presence of the prothrombin variant on risk of MI. Compared with nonusers of HRT with wild-type genotype, women who were current users and who had the prothrombin variant (n = 8) had a nearly 11-fold increase in risk of a nonfatal MI (OR, 10.9; 95% CI, 2.15-55.2). The interaction with the prothrombin variant was more pronounced in analyses assuming 100% compliance than in those assuming 80% compliance with HRT. The interaction was absent among nonhypertensive women and was less pronounced if hypertensive and nonhypertensive women were combined into 1 group. No interaction was found for factor V Leiden in either hypertensive or nonhypertensive women. Among hypertensive women, the estimates were affected only in trivial ways by adjustment, and the interaction with the prothrombin variant was specific to HRT. CONCLUSIONS: Our results suggest that among postmenopausal hypertensive women, the association between HRT use and MI risk differed between those with and without the prothrombin 20210 G-->A variant. If these findings are confirmed in other studies, screening for the prothrombin variant may permit a better assessment of the risks and benefits associated with HRT in postmenopausal women.
Adult↗
Antihypertensive drug therapies and the risk of ischemic stroke.
BACKGROUND: The relative effectiveness of various antihypertensive drugs with regard to the reduction of stroke incidence remains uncertain. OBJECTIVE: To assess the association between first ischemic stroke and use of antihypertensive drugs. METHODS: A population-based case-control study was performed among enrollees of the Group Health Cooperative of Puget Sound. Case patients included pharmacologically treated hypertensive patients who sustained a first ischemic stroke (fatal or nonfatal; n = 380) between July 1, 1989, and December 31, 1996. Control subjects were a random sample of treated hypertensive enrollees without a history of a stroke (n = 2790). Medical record review and a telephone interview of consenting survivors were used to collect information on risk factors for stroke. Computerized pharmacy records were used to assess antihypertensive drug use. RESULTS: Among 1237 single-drug users with no history of cardiovascular disease, the adjusted risk of ischemic stroke was higher among users of a beta-blocker (risk ratio [RR], 2.03; 95% confidence interval [CI], 1.05-3.94), calcium channel blocker (RR, 2.30; 95% CI, 1.16-4.56), or angiotensin-converting enzyme inhibitor (RR, 2.79; 95% CI, 1.47-5. 27) than among users of a thiazide diuretic alone. Among 673 single-drug users with a history of cardiovascular disease, the RRs were 1.22 (95% CI, 0.63-2.35), 1.18 (95% CI, 0.59-2.33), and 1.45 (95% CI, 0.70-3.02) among users of a beta-blocker, calcium channel blocker, and angiotensin-converting enzyme inhibitor, respectively, compared with users of a thiazide diuretic alone. CONCLUSIONS: In this study of pharmacologically treated hypertensive patients, antihypertensive drug regimens that did not include a thiazide diuretic were associated with an increased risk of ischemic stroke compared with regimens that did include a thiazide. These results support the use of thiazide diuretics as first-line antihypertensive agents.
Adrenergic beta-Antagonists↗
Lipid-rich carcinoid tumor of the thymus gland: diagnosis by fine-needle aspiration biopsy.
In this report we describe the cytologic features of an unusual thymic carcinoid tumor containing prominent cytoplasmic lipid vacuoles that was diagnosed by fine-needle aspiration biopsy. The tumor presented as a presternal subcutaneous mass in an 81-yr-old female, with a contiguous mediastinal mass on computed tomography. The cytomorphologic features included numerous discohesive cells with eccentric, round to oval nuclei, granular chromatin, and scant cytoplasm containing numerous intracytoplasmic, clear vacuoles. The neoplastic cells were reactive for neuroendocrine markers by immunocytochemistry and showed reactivity of the intracytoplasmic vacuoles with an oil red-O stain for neutral lipid. Ultrastructural examination confirmed the presence of intracytoplasmic lipid vacuoles and neurosecretory granules. Subsequent surgical excision confirmed the diagnosis. We believe this to be the first report describing these features in a primary thymic carcinoid tumor. The differential diagnosis of mediastinal tumors with clear-cell features and cytoplasmic vacuolization is also discussed.
Aged↗
Immunohistochemical distribution of tumor-associated antigen CA6 in gynecological neoplasms as detected by monoclonal antibody DS6.
DS6 is a murine monoclonal antibody developed using ovarian papillary serous adenocarcinoma as the immunogen. DS6 immunohistochemically reacts with a tumor-associated antigen, CA6, which has a limited range of expression in normal human tissues and is not expressed by benign mesothelium. We have studied the spectrum of immunohistochemical reactivity of antibody DS6 in 293 formalin-fixed, paraffin-embedded human gynecological neoplasms. The CA6 antigen shows strong expression in serous adenocarcinomas of the ovary (56/58 cases) and endometrium (6/6). CA6 is also expressed by the majority of ovarian endometrioid adenocarcinomas and Brenner tumors and by the majority of endometrioid adenocarcinomas, mucinous adenocarcinomas, and clear cell adenocarcinomas of the endometrium. CA6 is detected in 14% of ovarian clear cell carcinomas and is not detected in ovarian mucinous cystadenomas (0/7), mucinous intestinal-type borderline tumors (0/8), mucinous adenocarcinomas (0/10), or in malignant mesotheliomas (0/8). In neoplasms with papillary or glandular growth patterns, CA6 is detected along luminal cell membranes. CA6 is also seen along peripheral cell membranes and focally in the cytoplasm in some epithelial neoplasms. There is heterogeneity in immunohistochemical staining for DS6 both within an individual neoplasm and between neoplasms. Reactivity is not detected in neoplasms of sex cord-stromal, mesenchymal or germ cell origin.
Adenocarcinoma↗
Monoclonal antibody DS6 detects a tumor-associated sialoglycotope expressed on human serous ovarian carcinomas.
A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope"). SDS-PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non-disulfide-linked glycoprotein containing N-linked oligosaccharides. Two-dimensional non-equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies. The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn.
Antibodies, Monoclonal↗
Past use of erythromycin, tetracycline, or doxycycline is not associated with risk of first myocardial infarction.
A population-based case-control study of patients enrolled at Group Health Cooperative of Puget Sound was conducted to evaluate whether past use of antibiotics active against Chlamydia pneumoniae is associated with a decrease in the risk of first myocardial infarction (MI). Cases with incident fatal and nonfatal MI from mid-1986 through 1995 (n=1796) were compared with randomly sampled controls frequency-matched to cases for age, sex, and year (n=4882). Use of erythromycin, tetracycline, or doxycycline during the previous 5 years was not associated with an alteration in the risk of first MI. In an adjusted logistic regression model, the odds ratios and 95% confidence intervals for categories of cumulative duration of therapy with any of the three agents combined for 0, 1-14, 15-28, and >/=29 days were 1.0 (reference), 0.93 (0.81-1.07), 0.99 (0.81-1.20), and 1.03 (0.84-1.26), respectively. These results suggest little or no association between past use of erythromycin or tetracycline antibiotics and the risk of first MI among this population.
Aged↗
Control of blood pressure and risk of stroke among pharmacologically treated hypertensive patients.
BACKGROUND AND PURPOSE: Despite improved control of blood pressure during the last decades in the United States, a considerable proportion of treated hypertensives have not achieved target blood pressure levels. We estimated the proportion of strokes occurring among treated hypertensive patients that may be attributable to uncontrolled blood pressure. METHODS: A population-based case-control study was conducted among treated hypertensive members of Group Health Cooperative of Puget Sound. Cases were treated hypertensive patients who sustained a first fatal or nonfatal, ischemic (n=460) or hemorrhagic (n=95) stroke during 1989-1996. Controls were a random sample of stroke-free, treated hypertensive Group Health Cooperative enrollees (n=2966), similar in age to the stroke cases. Multiple measurements of blood pressure and other cardiovascular risk factors were collected from medical records. Logistic regression was used to estimate the risk of ischemic stroke and hemorrhagic stroke associated with uncontrolled blood pressure, defined as diastolic blood pressure >90 mm Hg or systolic blood pressure >140 mm Hg. The fraction of strokes attributable to uncontrolled blood pressure among treated hypertensives was calculated. RESULTS: Blood pressure was uncontrolled in 78% of ischemic stroke cases, 85% of hemorrhagic stroke cases, and 65% of controls. After adjustment for potential confounders, uncontrolled blood pressure among treated hypertensive patients was moderately associated with ischemic stroke (risk ratio=1.5 [95% CI, 1.2 to 1. 9]) and strongly related to hemorrhagic stroke (risk ratio=3.0 [95% CI, 1.7 to 5.4]). We estimated that 27% (95% CI, 11% to 39%) of the ischemic strokes and 57% (95% CI, 26% to 75%) of the hemorrhagic strokes among treated hypertensive patients were attributable to uncontrolled blood pressure. Overall, 32% (95% CI, 14% to 45%) of all strokes were attributable to uncontrolled blood pressure. CONCLUSIONS: A considerable proportion of incident strokes among treated hypertensive patients may be prevented by achieving control of blood pressure.
Aged↗
The risk of myocardial infarction associated with inhaled beta-adrenoceptor agonists.
Beta-adrenoceptor agonists (beta-agonists), in widespread clinical use for obstructive lung disease, have been associated with an increased risk of cardiovascular mortality. The objective of this study was to assess the association between incident myocardial infarction and the use of inhaled beta-agonists. We performed a case-control study within the Group Health Cooperative of Puget Sound (GHC). Between 1989 and 1994, we identified 1,444 cases with an incident myocardial infarction and 4,094 control subjects frequency-matched on age, sex, hypertension, and index date. The computerized pharmacy database of the health maintenance organization (HMO) was used to assess the use of beta-agonists by metered dose inhaler (MDI). Cardiovascular risk factor information was obtained from medical record review. In comparison to subjects who did not fill a beta-agonist prescription, subjects who had filled one beta-agonist MDI prescription in the 3 mo prior to their index date had an elevated estimated risk of myocardial infarction (adjusted odds ratio [OR]: 1.67 [95% CI, 1.07 to 2.60]). The elevated risk was limited to those subjects who had a history of cardiovascular disease (adjusted OR: 3.22 [95% CI, 1.63 to 6.35]) and among those with cardiovascular disease, to new users of beta-agonists (adjusted OR: 7.32 [95% CI, 2.34 to 22.8]). There was no dose-response relationship between beta-agonists use and risk of myocardial infarction. In this study, new use of beta-agonists was associated with an increased risk of myocardial infarction, although we cannot determine if the association is causal. Our study suggests that clinicians should exercise caution when giving an initial beta-adrenoceptor agonist prescription to patients with cardiovascular disease.
Administration, Inhalation↗