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Biomedical subjects

L Bernstein

Publications and source records attributed to L Bernstein.

At least 19 recordsLinked to original sources
PubMed2005

Reproductive factors and subtypes of breast cancer defined by hormone receptor and histology.

Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Women's Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case-control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER - PR - tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin.

Adult↗
PubMed2005

Myocardial infarction risk and tamoxifen therapy for breast cancer.

Tamoxifen prevents recurrence after breast cancer and breast cancer among high-risk women, and may prevent myocardial infarction (MI). To assess the impact of tamoxifen on MI risk, we conducted a case-control study of first MI after breast cancer nested among women diagnosed with breast cancer, while enrolled in a health maintenance organisation from 1980 to 2000. We obtained information on breast cancer treatment and MI risk factors through medical record reviews and interviews. Data were analysed using conditional logistic regression. Of 11,045 women with breast cancer, 134 met MI criteria and were matched to two MI-free control subjects on year of birth and breast cancer diagnosis. After adjusting for smoking, hypertension and diabetes, tamoxifen was unassociated with MI (odds ratio (OR)=1.2, 95% confidence interval (CI)=0.7-1.9). Duration, cumulative dose and recency of use were not associated with MI. Radiation therapy was associated with MI (OR=2.0, 95% CI=1.1-3.5), an association that varied slightly but not statistically significantly by tamoxifen use (radiation with tamoxifen, OR=2.0, 95% CI=0.9-4.4; radiation without tamoxifen, OR=2.9, 95% CI=1.2-7.5). Tamoxifen treatment for breast cancer does not appear to increase or decrease MI risk, although radiation therapy appears to increase MI risk.

Aged↗
PubMed2005

Potential surfaces and dynamics of the O(3P)+H2O(X1A1)-->OH(X2pi)+OH(X2pi) reaction.

We present global potential energy surfaces for the three lowest triplet states in O(3P)+H2O(X1A1) collisions and present results of classical dynamics calculations on the O(3P)+H2O(X1A1)-->OH(X2pi)+OH(X2pi) reaction using these surfaces. The surfaces are spline-based fits of approximately 20,000 fixed geometry ab initio calculations at the complete-active-space self-consistent field+second-order perturbation theory (CASSCF+MP2) level with a O(4s3p2d1f)/H(3s2p) one electron basis set. Computed rate constants compare well to measurements in the 1000-2500 K range using these surfaces. We also compute the total, rovibrationally resolved, and differential angular cross sections at fixed collision velocities from near threshold at approximately 4 km s(-1) (16.9 kcal mol(-1) collision energy) to 11 km s(-1) (122.5 kcal mol(-1) collision energy), and we compare these computed cross sections to available space-based and laboratory data. A major finding of the present work is that above approximately 40 kcal mol(-1) collision energy rovibrationally excited OH(X2pi) products are a significant and perhaps dominant contributor to the observed 1-5 micro spectral emission from O(3P)+H2O(X1A1) collisions. Another important result is that OH(X2pi) products are formed in two distinct rovibrational distributions. The "active" OH products are formed with the reagent O atom, and their rovibrational distributions are extremely hot. The remaining "spectator" OH is relatively rovibrationally cold. For the active OH, rotational energy is dominant at all collision velocities, but the opposite holds for the spectator OH. Summed over both OH products, below approximately 50 kcal mol(-1) collision energy, vibration dominates the OH internal energy, and above approximately 50 kcal mol(-1) rotation is greater than vibrational energy. As the collision energy increases, energy is diverted from vibration to mostly translational energy. We note that the present fitted surfaces can also be used to investigate direct collisional excitation of H2O(X1A1) by O(3P) and also OH(X2pi)+OH(X2pi) collisions.

Journal Article↗
PubMed2004

Association of body composition and weight history with breast cancer prognostic markers: divergent pattern for Hispanic and non-Hispanic White women.

Body composition and weight gain are breast cancer risk factors that may influence prognosis. The Health, Eating, Activity, and Lifestyle Study was designed to evaluate the relations of body composition, weight history, hormones, and lifestyle factors to prognosis for women with breast cancer. In the cross-sectional analysis of this cohort study specific to 150 Hispanic and 466 non-Hispanic White women in New Mexico diagnosed between 1996 and 1999, the authors hypothesized that obesity measures are associated with baseline prognostic markers and that these associations are modified by ethnicity. Ethnic-stratified multiple logistic regression analyses showed divergent results for a tumor size of 1.0 cm or more and, to a lesser extent, positive lymph node status. Among Hispanics, the highest quartile for body mass index (29.5 vs. <22.5 kg/m2: odds ratio (OR) = 0.16, 95% confidence interval (CI): 0.03, 0.84) and for waist circumference (> or =95.0 vs. <78.5 cm: OR = 0.09, 95% CI: 0.01, 0.78) was significantly associated with a reduced tumor size. In contrast, for overweight and obese non-Hispanic White women, there was an increased association with obesity-related measures, particularly striking for the highest quartile of waist circumference (OR = 2.76, 95% CI: 1.45, 5.26). These findings suggest that Hispanics may have a different breast cancer phenotype than non-Hispanic Whites, which associates differently with body composition and weight history.

Adult↗
PubMed2004

Exercise activity, body size and premenopausal breast cancer survival.

We evaluated prediagnosis predictors of breast cancer survival among 717 premenopausal breast cancer patients enrolled in a population-based case-control study and followed for 10.4 years. Using Cox's proportional hazards models, lifetime exercise, weight, and height were not associated with survival. Higher body mass index (trend P=0.21) and recent exercise activity (trend P=0.31) were weakly associated with longer survival.

Adult↗
PubMed2004

Growth hormone deficiency associated with methylmalonic acidemia.

Poor growth is a common finding in patients with organic acidemias. Growth hormone (GH) therapy has been considered in the management of these disorders as a mode to enhance anabolism and lower the high levels of methylmalonic acid. We report two patients with methylmalonic acidemia (mut(o)) and GH deficiency. Both patients had persistently elevated serum concentrations of methylmalonic acid, which failed to respond to conventional therapy. In anticipation of using GH therapy to reduce high methylmalonic acid concentrations, the first patient underwent GH testing utilizing a provocative glucagon stimulation test and was found to be deficient. He was subsequently treated with GH and demonstrated improved growth, but his methylmalonic acid concentrations remain elevated. The second patient was also found to be GH deficient. These findings suggest that GH deficiency may be an etiologic factor in the poor growth seen in patients with organic acidemia.

Acidosis↗
PubMed2003

ATM variants 7271T>G and IVS10-6T>G among women with unilateral and bilateral breast cancer.

Recent reports suggest that two ATM gene mutations, 7271T>G and IVS10-6T>G, are associated with a high risk of breast cancer among multiple-case families. To assess the importance of these two mutations in another 'high-risk' group, young women (under age 51) with multiple primaries, we screened a large population-based series of young women with bilateral breast cancer and compared the frequency of these mutations among similar women diagnosed with unilateral breast cancer. The 1149 women included were enrolled in an ongoing population-based case-control study of the genetic factors that contribute to bilateral breast cancer; they were not selected on the basis of family history of cancer. Screening for 7271T>G and IVS10-6T>G ATM gene mutations was conducted using DHPLC followed by direct sequencing. The 7271T>G mutation was detected in one out of 638 (0.2%) women with unilateral breast cancer and in none of the bilateral cases, and the IVS10-6T>G mutation in one out of 511 (0.2%) bilateral and in eight out of 638 (1.3%) unilateral breast cancer cases. Carriers of either mutation were not limited to women with a family history. Given the likelihood that young women with bilateral breast cancer have a genetic predisposition, the observed mutation distribution is contrary to that expected if these two mutations were to play an important role in breast carcinogenesis among individuals at high risk.

Adult↗
PubMed2002

Reduced risk of synovial sarcoma in females: X-chromosome inactivation?

Synovial sarcoma shows a characteristic t(X;18) translocation but not the expected female predominance in incidence. We speculate that, among females, one X-chromosome is inactivated and that only the translocation to an active X-chromosome leads to development of synovial sarcoma. Population-based cancer registry data from the SEER program support this hypothesis.

Adolescent↗
PubMed2002

Ethnic differences in ovulatory function in nulliparous women.

African-American women have a long-standing approximately 20% higher breast cancer incidence rate than USA White women under age 40 while rates among Latinas are lower than those of Whites. The reasons for this are not clear, however they may be due to ethnic differences in circulating oestradiol and progesterone levels. In a cross-sectional study, we investigated whether anovulation frequency and circulating serum oestradiol and/or progesterone levels vary among normally cycling nulliparous African-American (n=60), Latina (n=112) and non-Latina White (n=69) women. Blood and urine specimens were collected over two menstrual cycles among healthy 17- to 34-year-old women. Frequency of anovulation was greater among White women (nine out of 63, 14.3%) than African-American women (four out of 56, 7.1%) or Latina women (seven out of 102, 6.9%), although these differences were not statistically significant. African-American women had 9.9% (P=0.26) higher follicular phase oestradiol concentrations than Latina women and 17.4% (P=0.13) higher levels than White women. African-American women also had considerably higher levels of luteal phase oestradiol (vs Latinas, +9.4%, P=0.14; vs Whites, +25.3%, P=0.003) and progesterone (vs Latinas, +15.4%, P=0.07; vs Whites, +36.4%, P=0.002). Latina women were also observed to have higher follicular oestradiol, and luteal oestradiol and progesterone levels than White women (follicular oestradiol: +6.8%, P=0.48; luteal oestradiol: +14.6%, P=0.04; luteal progesterone: +18.2%, P=0.06). These results suggest that exposure to endogenous steroid hormones may be greater for young African-American and Latina women than for Whites.

Adult↗
PubMed2002

Correlates of vitamin supplement use in the United States: data from the California Teachers Study cohort.

OBJECTIVE: To describe factors associated with vitamin supplement use in a large cohort of adult women. METHODS: California teachers and administrators (n = 133,479) completed a questionnaire on lifestyle factors and medical history. Specific supplement users regularly used at least one specific vitamin supplement in the past year; multivitamin users regularly used a multivitamin; and multivitamin and specific supplement users took a multivitamin and one or more specific supplements. Associations between supplement use and other variables were quantified using means, cross-tabulations, and age-adjusted prevalence odds ratios. RESULTS: Multivitamin and specific supplement users tended to be older and Caucasian. Compared to non-users, they were also leaner (odds ratio [OR] for BMI > or = 30 kg/m2 = 0.6 for specific supplement users with or without multivitamins, and OR = 0.7 for multivitamin only users), and were less likely to be current smokers (OR for current smoking = 0.8 for multivitamin plus specific supplement users, OR = 0.9 for specific supplement only users, and OR = 0.7 for multivitamin only users). Specific supplement users (with or without multivitamins) were more likely to use cancer screening tests, eat fruits and vegetables, and exercise than were multivitamin only users or non-users. CONCLUSIONS: A variety of demographic, dietary, and health-related factors were associated with different categories of supplement use.

Body Weight↗
PubMed2001

Impact of troponin T determinations on hospital resource utilization and costs in the evaluation of patients with suspected myocardial ischemia.

The evaluation and triage of patients with suspected myocardial ischemia in the emergency department remains challenging and costly. Previous studies of cardiac troponins have focused predominantly on patients with chest pain and have not randomized patients to different diagnostic strategies. Eight hundred fifty-six patients with suspected myocardial ischemia were prospectively randomized to receive a standard evaluation, including serial electrocardiographic and creatine phosphokinase-MB determinations (controls) or a standard evaluation with the addition of serial troponin T determinations (troponin group). The primary end points were length of stay and hospital charges. Significant reductions in length of hospital stay were seen in troponin T patients both with (3.6 vs 4.7 days; p = 0.01) and without (1.2 vs 1.6 days; p = 0.03) acute coronary syndromes compared with controls. Total hospital charges were reduced in a similar fashion in troponin patients with and without acute coronary syndromes ($15,004 vs $19,202; p = 0.01, and $4,487 vs $6,187; p = 0.17, respectively) compared with controls. Troponin patients without acute coronary syndromes had fewer hospital admissions (25% vs 31%; p = 0.04), whereas troponin patients with acute coronary syndromes had shorter telemetry and coronary care unit lengths of stay (3.5 vs 4.5 days; p = 0.03) compared with controls. Thus, utilization of troponin T in a broad spectrum of emergency department patients with suspected myocardial ischemia improves hospital resource utilization and reduces costs.

Adult↗
PubMed2001

Changing relationship between socioeconomic status and prostate cancer incidence.

BACKGROUND: Understanding the relationship between socioeconomic status (SES) and prostate cancer incidence could identify populations that should be targeted for intervention and prevention programs. We examined this relationship within the major racial/ethnic groups during the period 1972 through 1997, which spans the introduction of prostate-specific antigen (PSA) testing. METHODS: We used data from the population-based Los Angeles Cancer Surveillance Program to examine age-adjusted prostate cancer incidence rates in five SES groups over three specific calendar periods by racial/ethnic subpopulation (white, black, Asian, and Hispanic) and by stage of disease at diagnosis. Linear regression analysis was used to test for trends in the age-adjusted incidence rates that were associated with increasing levels of SES. All P values were two-sided. RESULTS: For men diagnosed with prostate cancer before 1987, when the test for PSA was not widely available, we found no association between SES and the incidence of prostate cancer in any of four racial/ethnic subpopulations or between SES and the stage of disease at diagnosis. In contrast, among men who were diagnosed with prostate cancer after 1987, SES was statistically significantly and positively associated with prostate cancer incidence in men from all racial/ethnic subpopulations except Asians (P =.01 for white men, P =.001 for black men, P =.02 for Hispanic men, P =.06 for Asian men, and P =.01 for all men combined). Higher SES was statistically significantly associated with cancers of earlier stage (P =.01 for localized cancer and P =.00 for regional cancer) for men who were diagnosed with prostate cancer after 1987. CONCLUSIONS: The association between SES and prostate cancer incidence after 1987 may reflect more prevalent PSA screening in populations with higher SES due to their greater access to health care. SES should, therefore, be considered an important factor in interpreting variations and time trends in prostate cancer incidence.

California↗
PubMed2001

Epigenetic patterns in the progression of esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) arises after normal squamous mucosa undergoes metaplasia to specialized columnar epithelium (intestinal metaplasia or Barrett's esophagus), which can then ultimately progress to dysplasia and subsequent malignancy. Epigenetic studies of this model have thus far been limited to the DNA methylation analysis of a few genes. In this study, we analyzed a panel of 20 genes using a quantitative, high-throughput methylation assay, METHYLIGHT: We used this broader approach to gain insight into concordant methylation behavior between genes and to generate epigenomic fingerprints for the different histological stages of EAC. Our study included a total of 104 tissue specimens from 51 patients with different stages of Barrett's esophagus and/or associated adenocarcinoma. We screened 84 of these samples with the full panel of 20 genes and found distinct classes of methylation patterns in the different types of tissue. The most informative genes were those with an intermediate frequency of significant hypermethylation [ranging from 15% (CDKN2A) to 60% (MGMT) of the samples]. This group could be further subdivided into three classes, according to the absence (CDKN2A, ESR1, and MYOD1) or presence (CALCA, MGMT, and TIMP3) of methylation in normal esophageal mucosa and stomach, or the infrequent methylation of normal esophageal mucosa accompanied by methylation in all normal stomach samples (APC). The other genes were less informative, because the frequency of hypermethylation was below 5% (ARF, CDH1, CDKN2B, GSTP1, MLH1, PTGS2, and THBS1), completely absent (CTNNB1, RB1, TGFBR2, and TYMS1), or ubiquitous (HIC1 and MTHFR), regardless of tissue type. Each class undergoes unique epigenetic changes at different steps of disease progression of EAC, suggesting a step-wise loss of multiple protective barriers against CpG island hypermethylation. The aberrant hypermethylation occurs at many different loci in the same tissues, suggestive of an overall deregulation of methylation control in EAC tumorigenesis. However, we did not find evidence for a distinct group of tumors with a CpG island methylator phenotype. Finally, we found that normal and metaplastic tissues from patients with evidence of associated dysplasia or cancer had a significantly higher incidence of hypermethylation than similar tissues from patients with no further progression of their disease. The fact that the samples from these two groups of patients were histologically indistinguishable, yet molecularly distinct, suggests that the occurrence of such hypermethylation may provide a clinical tool to identify patients with premalignant Barrett's who are at risk for further progression.

Adenocarcinoma↗
PubMed2001

Reproductive factors and risk of intermediate- or high-grade B-Cell non-Hodgkin's lymphoma in women.

PURPOSE: The incidence rates of non-Hodgkin's lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS: We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood. RESULTS: Women who had used oral contraceptives had significantly lower risk of intermediate- or high-grade NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to 0.86) than women who had never used these compounds. Among parous women, those who had used lactation suppressants (which contain high levels of estrogen) had significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85) than unexposed women. Postmenopausal women had a somewhat greater risk of NHL than premenopausal women, whereas those postmenopausal women who had used hormone replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those who had not used HRT. CONCLUSION: Exogenous estrogens seem to have a protective effect on the risk of high- and intermediate-grade B-cell NHL. Although the mechanisms for such protection are not known, alterations in immune reactivity, cytokine expression, or B-cell modulation may play a role.

Adult↗
PubMed2001

A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinomas of the stomach and esophagus (United States).

OBJECTIVES: Since the 1970s incidence rates for esophageal and gastric cardia adenocarcinomas have risen substantially, particularly among white males in the United States. Reasons for the increase of these tumor types are not well understood. We sought to determine the role of smoking, alcohol use, and body size characteristics in the etiology of esophageal, gastric cardia, and distal gastric adenocarcinomas. MATERIALS AND METHODS: A population-based case-control study that included Whites, African-Americans, Latinos and Asian-Americans diagnosed with incident esophageal (n = 222), gastric cardia (n = 277), and distal gastric adenocarcinomas (n = 443), and 1356 control subjects was conducted in Los Angeles County. Unconditional logistic regression was used to calculate odds ratios (ORs), as an estimate of the relative risk, and corresponding 95% confidence intervals (CIs) for the three tumor types of interest. RESULTS: After adjustment for age, gender, race, birthplace, and education, current cigarette smoking was a significant risk factor for all tumor types; the association was strongest for esophageal adenocarcinomas (OR = 2.80, 95% CI = 1.8-4.3), intermediate for gastric cardia adenocarcinomas (OR = 2.12, 95% CI = 1.5-3.1), and weaker for distal gastric adenocarcinomas (OR= 1.50, 95% CI = 1.1-2.1). For esophageal adenocarcinomas only, cigarette smoking had a long-lasting deleterious effect, even 20 years after smoking cessation. Alcohol use was not associated with an increased risk of these tumor types. Risks of esophageal and gastric cardia adenocarcinomas also increased statistically significantly in a dose-dependent manner with increasing body mass index measured at ages 20 and 40 years and recently. The positive associations with smoking and body mass index were generally consistent when evaluated separately for Whites, non-Whites, males, and females. CONCLUSIONS: Cigarette smoking and high body mass index are significant, independent risk factors for esophageal and gastric cardia adenocarcinomas. Studies designed to understand the mechanisms whereby smoking and high body mass influence these tumor types are needed.

Adenocarcinoma↗
PubMed2001

Ability of young women to recall past body size and age at menarche.

OBJECTIVE: The ability of young women (n = 132, average age 17 years) to recall body size and age at menarche was examined. The use of body silhouettes to assist women in recalling their body size at menarche and to represent their current body size was also evaluated. RESEARCH METHODS AND PROCEDURES: Subjects, who previously participated in a cohort study, were asked to recall height and weight at the time of menarche, to select body silhouettes that best reflected their body shape at the time of menarche and their current body shape, and to recall age at menarche. Two sets of body silhouettes were developed, one representative of an adult body shape and another representative of an adolescent body shape. RESULTS: Pearson correlation coefficients between the adult and adolescent body figures and actual body mass index (BMI; kg/m(2)) at the time of menarche were not significantly different (r = 0.82 for adult figures vs. r = 0.72 for adolescent figures, p > 0.05). The correlation between actual BMI at the time of menarche and body silhouette (r = 0.77, all subjects) was similar to the correlation between actual and recalled BMI at the time of menarche (r = 0.83) as well as the correlation between current BMI and current body silhouette (r = 0.75). Recalled and actual ages at menarche were highly correlated (r = 0.83). DISCUSSION: The recall of body shape was considered to be a less precise measure of body size than asking about height and weight, but use of body silhouettes may offer advantages in certain situations.

Adolescent↗
PubMed2001

Intake and blood levels of fatty acids in treated patients with phenylketonuria.

BACKGROUND: Investigators in Italy and Spain have suggested that therapy for patients with phenylketonuria (PKU) may result in essential fatty acid (EFA) deficiency. Objectives of this study were to determine if the diets of patients with PKU in the United States provided adequate EFA intakes and whether patients could form long-chain polyunsaturated fatty acids. METHODS: Patients (1-13 years of age) with classic PKU undergoing therapy and their non-PKU sibling closest in age were compared. Nutrient intakes were calculated from 3-day diet diaries. Fatty acids in plasma and erythrocytes were identified and quantified. Paired t tests compared results for the patients and their non-PKU siblings. RESULTS: Twenty-eight patients and 26 siblings were studied. Mean fat intake was greatest by siblings (34.8 +/- 1.3% of energy) and lowest by Phenyl-Free-fed patients (19.5 +/- 1.2% of energy; P < 0.05). Fat intake (30.4 +/- 1.8% of energy) by Phenex-fed patients did not differ from that of siblings. Percentage of energy ingested as C18:2n-6 and C18:3n-3 did not differ significantly between patients and siblings. No clinically significant, consistent differences were found in fatty acid levels (wt%) in plasma or erythrocytes between patients with PKU and siblings. CONCLUSIONS: No patient in this study exhibited a Holman index of EFA deficiency. Siblings ingested animal protein containing C20:5n-3 and C22:6n-3 fatty acids, and this may account for their greater wt% of these plasma and erythrocyte fatty acids. Because patients with PKU do not ingest fatty acids >C18 but C20:4n-6, C20:5n-3, and C22:6n-3 were found in their plasma and erythrocytes, in vivo synthesis from C18:2n-6 and C18:3n-3 appears to occur. Lack of EFA deficiency in patients in this study may be the result of the use of canola and soy oils containing C18:2n-6 and C18:3n-3 rather than olive oil in the diets.

Adolescent↗