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S M Schwartz

Publications and source records attributed to S M Schwartz.

At least 19 recordsLinked to original sources
PubMed2006

Coagulation factor VII gene haplotypes, obesity-related traits, and cardiovascular risk in young women.

BACKGROUND: Associations between common F7 haplotypes, plasma factor VII (FVII) levels, and cardiovascular risk have recently been reported in population studies involving predominantly European men. METHODS: We assessed associations between F7 haplotypes and cardiovascular risk in two US population-based studies: a case-control study of these alleles related to a decreased risk of arterial thrombotic outcomes such as myocardial infarction (MI) in young-to-middle-aged women (n = 671), and a cohort study of cardiovascular disease risk factors in young women (n = 1040). RESULTS: The high-expression F7 haplotype B (containing the promoter variant allele -402A) was associated with an increased FVII level among controls, but not with MI risk. Women carrying a> or =1 copy of the low FVII expression level haplotype C (containing the -401T/-323del/-122C and Gln353 alleles) had decreased FVII levels and decreased risk of MI (odds ratio 0.54, 95% CI 0.31-0.93) compared with women homozygous for the most common haplotype A. Haplotype C was also associated with a decreased body mass index (BMI) and an increased high-density lipoprotein (HDL) cholesterol level, but not with MI risk after adjustment for these metabolic risk factors. In a cohort study composed of young US women, individuals homozygous for haplotype C had a lower BMI and lower systolic blood pressure, but the association between the F7 haplotype and HDL cholesterol was not confirmed. CONCLUSION: Common FVII haplotypes may contribute to the risk of MI in women, but the mechanisms appear complex. The association between F7 haplotypes and MI susceptibility may be mediated in part through an influence on atherogenic risk factors such as BMI.

Adolescent↗
PubMed2004

Familial correlations, segregation analysis, and nongenetic correlates of soy isoflavone-metabolizing phenotypes.

Particular intestinal bacteria metabolize the soy isoflavone daidzein to equol and O-desmethylangolensin (O-DMA), metabolites that can be identified in urine. Individuals that harbor bacteria capable of producing equol or O-DMA are known as equol producers (approximately 30%-50% of the population) and O-DMA producers (approximately 80%-90% of the population), respectively. The equol-producer phenotype has been associated with sex hormone-related outcomes in several studies. However, the bacteria responsible for these phenotypes have not yet been identified and factors that influence the manifestation of these phenotypes are not well understood. To evaluate familial clustering of and nongenetic factors associated with these phenotypes, 410 individuals from 112 families participated in phenotyping (3-day soy challenge and Day 4 spot urine collection). In segregation analyses of the equol-producer phenotype, the Mendelian dominant model provided the most parsimonious fit to the data, suggesting that the pattern of inheritance of the equol-producer phenotype is consistent with an autosomal dominant trait. This phenotype was positively associated with education (p trend = 0.01), but not with sex, smoking, or several dietary factors. Results of the segregation analyses of the O-DMA-producer phenotype were inconclusive; no other models provided a more parsimonious fit to the data than the general model. This phenotype was inversely associated with age in a nonlinear model (p = 0.01), positively associated with age- and sex-adjusted height (odds ratio [OR] 10-cm increase = 0.38, 95% confidence interval [CI] = 0.15, 0.95) and body mass index (kg/m(2)) (OR = 0.91, 95% CI = 0.85, 0.96), but not with sex, education, smoking, or several dietary factors. These results suggest the equol-producer phenotype may be under some degree of genetic control and that there are likely other environmental factors not evaluated in the present analysis that contribute to both of these phenotypes. These results provide a foundation for further work to refine our understanding of heritable and environmental determinants of daidzein-metabolizing phenotypes.

Female↗
PubMed2001

Serologic evidence of herpes simplex virus 1 infection and oropharyngeal cancer risk.

In vitro and animal models suggest that the herpes simplex virus 1 (HSV1) may contribute to the development of oropharyngeal squamous cell carcinoma (OSCC). To determine whether the risk of OSCC is related to infection with HSV1 in humans, we recruited 260 patients from 18 to 65 years old who were newly diagnosed with OSCC between 1990-1995 while residing in three western Washington State counties. For comparison, we recruited at random 445 controls frequency matched to cases on age and sex. Participants completed in-person interviews and provided serum samples that were tested for antibody response to HSV1. After adjusting for sex, cigarette smoking, alcohol consumption, age, and income, HSV1 antibody positivity was associated with a slightly increased risk of OSCC [adjusted odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9-2.0]. The adjusted association between HSV1 antibody positivity and OSCC risk among those who were current cigarette smokers (OR, 4.2; CI, 2.4-7.1) was stronger than would be predicted based on the additive combination of smoking alone (OR, 2.3; CI, 1.2-4.2) and HSV1 seropositivity alone (OR, 1.0; CI, 0.6-1.7). There was suggestive evidence that the association between HSV1 infection and OSCC was similarly modified by evidence of HPV infection but no evidence of effect modification with alcohol consumption. This population-based study suggests that HSV1 may enhance the development of OSCC in individuals who are already at increased risk of the disease because of cigarette smoking or HPV infection.

Adolescent↗
PubMed2001

Unrecognized pulmonary venous desaturation early after Norwood palliation confounds Gp:Gs assessment and compromises oxygen delivery.

BACKGROUND: Hemodynamic stability after Norwood palliation often requires manipulation of pulmonary vascular resistance to alter the pulmonary-to-systemic blood flow ratio (Qp:Qs). Qp:Qs is often estimated from arterial saturation (SaO2), a practice based on 2 untested assumptions: constant systemic arteriovenous O2 difference and normal pulmonary venous saturation. METHODS AND RESULTS: In 12 patients early (</=3 days) after Norwood palliation, simultaneous arterial, superior vena caval (SsvcO2), and pulmonary venous (SpvO2) oximetry was used to test whether SaO2 accurately predicts Qp:Qs. Stepwise multiple regression assessed the contributions of SaO2, SsvcO2, and SpvO2 to Qp:Qs determination. SaO2 correlated weakly with Qp:Qs (R2=0.08, P<0.05). Inclusion of SsvcO2 and SpvO2 improved Qp:Qs prediction accuracy. Pulmonary venous desaturation (SpvO2 <95%) was observed frequently (30%), especially at FiO2 </=0.21, but normalized with higher FiO2 or PEEP in all patients. In 6 patients, FiO2 was increased incrementally from 0.17 to 0.50 to determine whether this was an effective means to manipulate Qp:Qs. Qp:Qs failed to change predictably with increased FiO2. In 5 of 6 patients, however, higher SpvO2 and SaO2 enhanced systemic oxygen delivery, as demonstrated by improvement in oxygen extraction. CONCLUSIONS: SaO2 correlated poorly with Qp:Qs because of variability in SsvcO2 and SpvO2. A novel observation was that pulmonary venous desaturation occurred frequently early after Norwood palliation but normalized with higher FiO2 or PEEP. Because unrecognized pulmonary venous desaturation confounds p:s assessment and compromises SaO2 and oxygen delivery, judicious use of inspired oxygen and PEEP may be beneficial in selected patients early after Norwood palliation.

Heart Defects, Congenital↗
PubMed2001

Low density lipoprotein particle size and risk of early-onset myocardial infarction in women.

Previous studies of middle-aged men have shown a univariate association between low density lipoprotein (LDL) particle diameter (size) and coronary heart disease, but this association has yet to be examined in younger women. Using a subsample from a population-based case-control study of women living in western Washington State, the authors examined the association between LDL particle size and risk of early-onset myocardial infarction (MI) in 1992-1995. Gradient gel electrophoresis was used to characterize LDL subclasses in nonfasting blood samples from 72 MI cases and 159 controls aged 20-44 years. Mean LDL particle size in cases was significantly smaller compared with controls (26.4 vs. 26.9 nm, p < 0.001), with an odds ratio of 2.3 (p < 0.0001) for a 1-nm smaller LDL particle size. These results were independent of age, menopausal status, smoking, diabetes, hypertension, and LDL cholesterol (odds ratios = 1.9-2.3 for a 1-nm smaller LDL particle size, all p < 0.02) but were not independent of body mass index, high density lipoprotein cholesterol, or triglyceride (odds ratios = 1.4, 1.4, and 1.1, respectively; all p > 0.05). Therefore, in age-adjusted analyses, smaller LDL particle size was associated with MI in young women, but the risk was attenuated after adjustments for metabolic factors related to both LDL particle size and MI.

Adult↗
PubMed2001

Human papillomavirus and prognosis of invasive cervical cancer: a population-based study.

PURPOSE: To determine the association between human papillomavirus (HPV) type and prognosis of patients with invasive cervical carcinoma. PATIENTS AND METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer between 1986 and 1997 while residents of three Washington State counties were included (n = 399). HPV typing was performed on paraffin-embedded tumor tissue using polymerase chain reaction methods. Patients were observed for a median of 50.8 months. Total mortality (TM) and cervical cancer-specific mortality (CCSM) were determined. Hazards ratios (HR) adjusted for age, stage, and histologic type were estimated using multivariable models. RESULTS: Eighty-six patients had HPV 18-related tumors and 210 patients had HPV 16-related tumors. Cumulative TM among patients with HPV 18-related tumors and among patients with HPV 16-related tumors were 33.7% and 27.6%, respectively; cumulative CCSM in these two groups were 26.7% and 18.1%, respectively. Compared with patients with HPV 16-related cancers, patients with HPV 18-related cancers were at increased risk for TM (HR(TM), 2.2; 95% confidence interval [CI], 1.3 to 3.6) and CCSM (HR(CCSM), 2.5; 95% CI, 1.4 to 4.4). The HPV18 associations were strongest for patients with FIGO stage IB or IIA disease (HR(TM), 3.1; 95% CI, 2.3 to 4.2; and HR(CCSM), 5.8; 95% CI, 3.9 to 8.7), whereas no associations were observed among patients with FIGO stage IIB to IV disease. Virtually identical associations were found in the subset of patients with squamous cell carcinoma (n = 219). CONCLUSION: HPV 18-related cervical carcinomas, particularly those diagnosed at an early stage, are associated with a poor prognosis. Elucidating the mechanism or mechanisms underlying this association could lead to new treatment approaches for patients with invasive cervical carcinoma.

Adenocarcinoma↗
PubMed2001

Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites.

Human papillomavirus (HPV) DNA has been detected in the great majority of cancers of the uterine cervix and anus, whereas the association of HPV DNA with cancer at other anogenital sites has produced less consistent results. This study was designed to compare HPV exposure among anogenital cancer cases and matched controls. Cases (1782) of anogenital cancer diagnosed in the Seattle area from 1978 to 1998 were identified and interviewed. Their responses were compared with those of 2383 age- and sex-matched controls. Blood was drawn at interview from both cases and controls and tested for antibodies to HPV-16 and HPV-18. Tissue blocks were tested for HPV DNA for 649 cases. Serum antibodies to HPV-16 were associated with in situ and invasive cancer at all sites among men and women with the exception of in situ penile cancer. Anti-HPV-18 antibodies were associated with cancers at all sites among women. The increased risk of cancer associated with HPV-16 seropositivity ranged from odds ratio = 1.8 (95% confidence interval, 1.4-2.5) for adenocarcinoma of the cervix to odds ratio = 5.9 (95% confidence interval, 3.4-10.3) for anal cancer in men. Associations between seroprevalence and cancers were stronger when analyses were restricted to HPV-16- or HPV-18 DNA-positive cases. HPV DNA was detected in >80% of cancers from all sites tested. HPV-16 DNA was the type most frequently detected at all sites (range, 40.9-82.2%). HPV-18 DNA was detected in 44.7% of adenocarcinomas of the cervix but detected much less often (2.6-18.1%) at other sites. These findings support an important role for HPV infection in anogenital cancer at all sites. Differences in the proportion of seropositives among HPV-16 DNA-positive cases by site suggest either that the immune response varies by site or that cancer development may lead to changes in antibody responses in a site-specific fashion.

Adenocarcinoma↗
PubMed2001

The Kozak sequence polymorphism of platelet glycoprotein Ibalpha and risk of nonfatal myocardial infarction and nonfatal stroke in young women.

Several platelet membrane glycoprotein polymorphisms have been identified as potential risk factors for cardiovascular disease. Recently a nucleotide -5T/C dimorphism in the translation initiation site (Kozak sequence) of the platelet glycoprotein Ibalpha (GPIbalpha) gene was associated with increased platelet surface levels of the GPIb-IX-V receptor complex. The role of this GPIbalpha Kozak sequence polymorphism in the occurrence of arterial thrombotic disease is unknown. We performed genotype analysis of the Kozak sequence polymorphism of GPIbalpha in a population-based study of 18- to 44-year-old women with nonfatal myocardial infarction (MI) (n = 78), nonfatal stroke (n = 106), and 384 demographically similar female control subjects. Analysis of -5T/C genotypes revealed that at least one copy of the C allele was present in 14.1% of MI cases, 23.6% of stroke cases, and 23.7% of controls. The age-adjusted odds ratio for MI in women carrying at least one copy of the C allele was 0.53 (95% confidence interval [CI] 0.27-1.05). The age-adjusted odds ratio for stroke in women carrying at least one copy of the C allele was 0.99 (95% CI 0.59-1.65). Analyses stratified by stroke type (ischemic, hemorrhagic) yielded similar results. In conclusion, young women carrying the C allele of the Kozak sequence polymorphism of GPIbalpha are not at increased risk of MI or stroke. Paradoxically, the C allele may even be associated with a reduced risk of MI in this population. This finding requires further study.

Adolescent↗
PubMed2001

Invited commentary: Studying the epidemiology of uterine leiomyomata--past, present, and future.

Uterine leiomyomata have a substantial impact on women's reproductive health, but epidemiologists have focused relatively little energy on identifying risk factors for this condition. Only a handful of studies, most of which were not designed to address methodological challenges posed by these tumors, have been conducted. These studies focused almost exclusively on reproductive and hormonal characteristics as possible risk factors, but consistent relations have not emerged. Three new reports (from two studies) in this issue of the Journal target the paucity of information on uterine leiomyomata risk factors by testing novel hypotheses, by employing designs that incorporate subclinical tumors or account for variable management of clinically recognized disease, or by using a combination of these approaches. The success of these strategies and the contributions of the new findings are discussed. Recommendations are made for a program of research that eventually could improve our knowledge of uterine leiomyomata etiology and yield clues to the prevention of associated morbidity.

Epidemiologic Studies↗
PubMed2001

Use of alternative medicine by children with cancer in Washington state.

BACKGROUND: Use of alternative medicine is widespread among adult cancer patients, but considerably less is known about the use of these therapies by pediatric cancer patients. Our objective was to investigate the distribution and patterns of alternative medicine use by children diagnosed with cancer in Washington State. METHODS: Pediatric cancer patients (< or =18 years) with first primary neoplasms were identified from the Cancer Surveillance System of western Washington. Telephone interviews were conducted with parents of 75 patients to obtain data on the prevalence and types of alternative medicine used, satisfaction with conventional and alternative medicine, motivations for use of alternative medicine, adverse effects, and costs. RESULTS: Seventy-three percent of patients used at least one alternative treatment or therapy. Twenty-one percent of patients consulted an alternative provider (e.g., acupuncturist, naturopathic doctor), and insurance companies covered 75% of these costs. Twenty-eight percent used high-dose dietary supplements such as vitamins C or E, and 35% used herbal preparations. Although use of alternative medicine was associated with parental dissatisfaction with their child's physician (P = 0.02), no patient used alternative medicine as a substitute for standard medical care. Most patients used alternative medicine to cope with disease symptoms or the side effects of the medical treatments. CONCLUSIONS: Pediatric oncology patients use alternative treatments as adjuncts to conventional care. Both researchers and health care providers should remain informed about the benefits and adverse effects of alternative therapies in order to discuss treatment options with patients and their families and to monitor treatment efficacy.

Adolescent↗
PubMed2001

Changes in left ventricular mass in children and adolescents during chronic dialysis.

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiac mortality in adults with end-stage renal disease (ESRD). It is prevalent in pediatric patients on chronic dialysis. The objectives of this study were to evaluate left ventricular mass (LVM) in children and adolescents at the initiation of dialysis and to assess its changes during chronic dialysis therapy. In this longitudinal analysis, 29 patients aged 4-18 years had an echocardiographic evaluation within 90 days of starting dialysis therapy and a follow-up study at least 6 months later. LVH was defined as LVM index (g/m2.7) > 95th percentile for normal children and adolescents. On the initial echocardiogram 20 of 29 (69%) patients had LVH and 24 patients (83%) had abnormal LV geometry (38% eccentric LVH, 31% concentric LVH, and 14% concentric remodelling). Patients with LVH were more likely to be on antihypertensive medications (16/20) than patients without LVH (3/9) (P = 0.005). Repeat echocardiogram, performed after 10 +/- 3 months on chronic dialysis, showed no significant difference in the mean LVM index (49.6 +/- 17.5 g/m2.7 and 49.7 +/- 16.1 g/m2.7, respectively) or in the prevalence of LVH or LV geometric pattern. However, 14 of 29 patients had a progressive increase in LVM index and 15 patients had regression. Multiple regression analysis showed that baseline LVM index (P = 0.005) and interval change in indexed systolic blood pressure (P = 0.027) were independent predictors for LVM index changes. In summary, LVH and abnormal LV geometry are already prevalent in children and adolescents with renal failure at the time of initiation of dialysis therapy, indicating that LVH develops during the pre-ESRD course. Early intervention to control blood pressure may be an important factor to improve and prevent progression of LVH in pediatric patients with ESRD.

Adolescent↗
PubMed2001

Family history as a risk factor for early onset myocardial infarction in young women.

BACKGROUND: The relation between a family history of heart attack and the occurrence of early myocardial infarction (MI) has not been studied extensively in women. In addition, whether recognized and newly-identified coronary heart disease (CHD) risk factors account for the familial aggregation of these events remains unknown. We therefore examined these questions in a population-based case-control study among female 18- to 44-year-old residents of western Washington State. METHODS AND RESULTS: The patients consisted of 107 women with first acute MI, and the control subjects comprised 526 women similar in age identified from the community and without a history of recognized clinical coronary heart disease or stroke. Trained interviewers used a structured questionnaire to elicit a detailed history of heart attack in first-degree relatives. Information about other known MI risk factors was collected and biochemical measurements performed, and common polymorphisms in various candidate genes were determined. The rate of MI among first-degree relatives of MI cases was twice as high as among first-degree relatives of controls (relative risk, 1.96; 95% confidence interval (CI), 1.46-2.48); this association was present for each familial relationship. Sibling history of MI but not parental history was associated with MI, after controlling for established CHD risk factors. In a subsample of subjects with blood measurements, further adjustment for lipids, lipoproteins and specific genetic risk factors slightly reduced the association with sibling MI history (from odds ratio (OR), 5.17; 95% CI, 1.93-13.85 to OR, 3.97; 95% CI, 0.92-17.17). CONCLUSION: Family history of MI is positively associated with the risk of early MI in women. While the association with parental history of MI is mediated through the clustering of other common risk factors, the association of sibling history of MI with early-onset MI in young women is only partially explained by the clustering of established and newly-identified risk factors.

Adult↗
PubMed2001

Colorectal cancer following tamoxifen therapy for breast cancer (United States).

BACKGROUND: An analysis combining data from several clinical trials has raised concern that tamoxifen therapy may increase the risk of a subsequent colorectal malignancy. We conducted a nested case-control study to test this hypothesis. METHODS: A cohort of women diagnosed with breast cancer in 1978-1992 was identified from the western Washington population-based cancer registry. Cases included women who subsequently developed colorectal cancer prior to 1995. Controls were a random sample of the cohort who did not develop a second primary malignancy, matched to cases on age, stage, and year of initial cancer diagnosis. Tamoxifen use was ascertained by medical record abstraction and physician questionnaires. RESULTS: Thirty-six percent of the 122 cases for whom information could be obtained received tamoxifen versus 38% of 194 controls. Relative to non-users and adjusted for receipt of other therapies, there was no increased risk of colorectal cancer associated with tamoxifen use in general (matched odds ratio [mOR] = 0.9, 95% CI 0.6-1.6), longer durations of use (for > or =37 months, mOR = 0.8, 95% CI 0.4-1.9), higher cumulative doses of therapy (for > or =15 g, mOR = 0.8, 95% CI 0.4-1.6), or use that started at least 5 years prior to the end of study follow-up (mOR = 1.1, 95% CI 0.3-3.7). CONCLUSIONS: We found no overall increased risk for colorectal cancer among tamoxifen users.

Adult↗
PubMed2001

Changes in left ventricular mass index in children and adolescents after renal transplantation.

Recent reports indicate a high prevalence of left ventricular hypertrophy (LVH) in children on dialysis and after renal transplantation (Tx), as identified by cross-sectional analysis. However, the evolution of LVH in pediatric patients with end-stage renal disease after renal Tx is not well established. To assess changes of left ventricular mass (LVM), we prospectively performed echocardiography in 23 children and adolescents between November 1998 and July 2000. Each patient had an echocardiographic evaluation while on dialysis (for at least 6 weeks) and a follow-up evaluation at least 6 months after successful renal Tx (i.e. with a measured glomerular filtration rate [GFR] of at least 40 mL/min/1.73 m2). The LVM index was estimated by indexing LVM to height(2.7). Sixteen patients had a cadaveric transplant and seven had a live donor transplant; the mean duration between the two studies was 1.9 +/- 1.6 yr; and the mean GFR was 55.0 +/- 21.4 mL/min/1.73 m2. There was no significant difference in the mean values of the LVM index while on dialysis and after renal Tx (43.9 +/- 17.8 g/m2.7 and 39.3 +/- 12.0 g/m2.7, respectively, p = 0.19), or in the prevalence of LVH (52% and 56%, respectively). Interval changes in the LVM index in individual subjects between the two studies were significantly associated with interval changes in indexed systolic (r = 0.42, p = 0.04) and diastolic (r = 0.42, p = 0.05) blood pressures. Interval changes in hemoglobin, blood urea nitrogen (BUN), creatinine, and duration after Tx did not correlate with changes in the LVM index. There was no significant difference in LVM index change according to the type of dialysis, donor source, and the cause of renal failure. In multivariate analysis, the baseline LVM index and changes in indexed SBP were independent predictors for LVM index change after renal Tx. We conclude that LVH persists in children and adolescents after renal Tx. Control of blood pressure might be an important factor in regression or prevention of progression of LVH in these patients.

Adolescent↗