Women's views about breast cancer prevention at mammography screening units and well women's clinics.

Background: Women attending mammography screening units (msus) and well women's clinics (wwcs) represent a motivated cohort likely to engage in interventions aimed at primary breast cancer (bca) prevention. Methods: We used a feasibility questionnaire distributed to women (40-49 or 50-74 years of age) attending msus and wwcs in Halifax, Nova Scotia, to examine■ women's views about bca primary prevention and sources of health care information,■ prevalence of lifestyle-related bca risk factors, and■ predictors of prior mammography encounters within provincial screening guidelines.Variables examined included personal profiling, comorbidities, prior mammography uptake, lifestyle behaviours, socioeconomic status, health information sources, and willingness to discuss or implement lifestyle modifications, or endocrine therapy, or both. A logistic regression analysis examined associations with prior mammography encounters. Results: Of the 244 responses obtained during 1.5 months from women aged 40-49 years (n = 75) and 50-74 years (n = 169), 56% and 75% respectively sought or would prefer to receive health information from within, as opposed to outside, health care. Lifestyle-related bca risk factors were prevalent, and most women were willing to discuss or implement lifestyle modifications (93%) or endocrine therapy (67%). Of the two age groups, 49% and 93% respectively had previously undergone mammography within guidelines. Increasing age and marital status (single, separated, or divorced vs. married or partnered) were independent predictors of prior mammography encounters within guidelines for women 40-49 years of age; no independent predictors were observed in the older age group. Conclusions: Women attending msus and wwcs seem to largely adhere to mammography guidelines and appear motivated to engage in bca primary prevention strategies, including lifestyle modifications and endocrine therapy. Women's views as observed in this study provide a rationale for the potential incorporation of bca risk assessment within the "mammogram point of care" to engage motivated women in bca primary prevention strategies.

Prenatal antimicrobial use and early-childhood body mass index.

BACKGROUND/OBJECTIVES: Growing evidence suggests that antibiotic use is associated with childhood body mass index (BMI), potentially via mechanisms mediated by gut microbiome alterations. Less is known on the potential role of prenatal antimicrobial use in offspring obesity risk. We examined whether prenatal antibiotic or antifungal use was associated with BMI at the age of 2 years in 527 birth cohort participants. METHODS/SUBJECTS: Antimicrobial use was obtained from the prenatal medical record. Height and weight were measured at the age of 2 years. Overweight/obesity was defined as a BMI ⩾85th percentile. RESULTS: A total of 303 (57.5%) women used antibiotics and 101 (19.2%) used antifungals during pregnancy. Prenatal antifungal use was not associated with child BMI at the age of 2 years. In the fully adjusted model, prenatal antibiotic use was associated with a 0.20±0.10 (P=0.046) higher mean BMI Z-score at the age of 2 years. Associations between prenatal antibiotic use and childhood BMI varied by trimester of exposure, with first or second-trimester exposure more strongly associated with larger BMI at the age of 2 years for both BMI Z-score (interaction P=0.032) and overweight/obesity (interaction P=0.098) after covariate adjustment. CONCLUSIONS: Prenatal antibiotic, but not antifungal, use is associated with larger BMI at the age of 2 years; associations were stronger for antibiotic exposures in earlier trimesters. Future studies examining whether these associations are due to alterations in the maternal and/or infant microbiome are necessary. Children who are overweight at the age of 2 years are at higher risk for being overweight as they age; prenatal antibiotic use is a potentially modifiable exposure that could reduce childhood obesity.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

BACKGROUND: Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. METHODS: Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). RESULTS: Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). CONCLUSIONS: In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing-suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity.

BACKGROUND/OBJECTIVES: Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring. SUBJECTS/METHODS: Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother-child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode. RESULTS: Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33-154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8-98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS. CONCLUSIONS: In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations.

Ethnic enclaves and gestational diabetes among immigrant women in New York City.

Previous research has shown that immigrants living in their own ethnic enclave are at decreased risk of poor health outcomes, but this question has not been studied in relation to gestational diabetes, an important early marker of lifecourse cardiovascular health. We ascertained gestational diabetes, census tract of residence, and individual-level covariates for Sub-Saharan African, Chinese, South Central Asian, Non-Hispanic Caribbean, Dominican, Puerto Rican, Mexican, and Central and South American migrant women using linked birth-hospital discharge data for 89,703 singleton live births in New York City for the years 2001-2002. Using 2000 census data, for each immigrant group we defined a given census tract as part of an ethnic enclave based on the population distribution for the corresponding ethnic group. We estimated odds ratios for associations between living in an ethnic enclave and risk of gestational diabetes adjusted for neighborhood deprivation, percent commercial space, education, age, parity, and insurance status, using multilevel logistic regression. Overall, we found no effect of ethnic enclave residence on gestational diabetes in most immigrant groups. Among South Central Asian and Mexican women, living in a residential ethnic enclave was associated with an increased odds of gestational diabetes. Several explanations are proposed for these findings. Mechanisms explaining an increased risk of gestational diabetes in South Central Asian and Mexican ethnic enclaves should be examined.

Children living in areas with more street trees have lower prevalence of asthma.

BACKGROUND: The prevalence of childhood asthma in the USA increased by 50% from 1980 to 2000, with especially high prevalence in poor urban communities. METHODS: Data on the prevalence of asthma among children aged 4-5 years and on hospitalisations for asthma among children less than 15 years old were available for 42 health service catchment areas within New York City. Street tree counts were provided by the New York City Department of Parks and Recreation. The proximity to pollution sources, sociodemographic characteristics and population density for each area were also measured. RESULTS: Controlling for potential confounders, an increase in tree density of 1 standard deviation (SD, 343 trees/km(2)) was associated with a lower prevalence of asthma (RR, 0.71 per SD of tree density; 95% CI, 0.64 to 0.79), but not with hospitalisations for asthma (RR, 0.89 per SD of tree density; 95% CI, 0.75 to 1.06). CONCLUSIONS: Street trees were associated with a lower prevalence of early childhood asthma. This study does not permit inference that trees are causally related to asthma at the individual level. The PlaNYC sustainability initiative, which includes a commitment to plant one million trees by the year 2017, offers an opportunity for a large prospective evaluation.

Asthma, body mass, gender, and Hispanic national origin among 517 preschool children in New York City.

BACKGROUND: Striking differences in asthma prevalence have been reported among Hispanic adults and children living in different cities of the USA. Prevalence is highest among those of Puerto Rican and lowest among those of Mexican origin. We hypothesized that body size would mediate this association. METHODS: Parents of children in New York City Head Start programs completed a questionnaire including demographic factors, health history, a detailed history of respiratory conditions, lifestyle, and home environment. Children's height and weight were measured in home visits. Logistic regression was used to model the association of asthma with body mass index percentile (<85th percentile, gender/age specific vs>or=85th percentile, gender/age specific), national origin, and other factors. RESULTS: Of 517 children at mean age of 4.0 +/- 0.6 years, 34% met the study criteria for asthma, and 43% were above the 85th percentile. Asthma was strongly associated with non-Mexican national origin, male gender, allergy symptoms, and maternal asthma, and marginally with body size. The odds of asthma among boys of non-Mexican origin was 5.9 times that among boys of Mexican origin [95% confidence interval (CI): 2.9-12.2]; the comparable odds ratio (OR) among girls was 1.8 (95% CI: 0.9-3.6). Body mass was associated with asthma among girls [OR = 2.0 (95% CI: 1.1-3.7)], but not boys [OR = 1.4 (95% CI: 0.8-2.6)]. CONCLUSIONS: The association of asthma with both body mass and national origin was gender-specific among the children in our study. Ours is one of the first studies to report on pediatric asthma in different Hispanic populations in the same city, by gender.

The association between benzo[a]pyrene-DNA adducts and body mass index, calorie intake and physical activity.

Prior work suggests that body size and fat content may influence carcinogen-DNA adduct levels measured in white blood cells. Here we consider energy balance more broadly by assessing the impact of body mass index (BMI), physical activity and calorie intake on the presence of benzo[a]pyrene-DNA (BP-DNA) adducts in white blood cell DNA. Our cross-sectional study employed subjects from a separately conducted intervention trial. Physical activity and food intake data were collected at 12 and 15 months of follow-up, respectively. BP-DNA adducts were measured by high-performance liquid chromatography (HPLC) in white blood cell samples collected at 12 months of follow-up. Complete data on all variables were available from 143 subjects. Logistic regression showed that BMI was inversely associated with the presence of detectable adducts (OR = 0.90, p = 0.02), and that hours of moderate-intensity physical activity were positively associated with the presence of detectable adducts (OR = 1.04, p = 0.04). These results provide further evidence that body fat content influences carcinogen-DNA adduct levels, probably by altering the distribution of the lipophilic parent compound.

Preliminary studies on the effect of moderate physical activity on blood levels of glutathione.

Molecular epidemiological approaches are being used to study how physical activity may protect against cancer. Prior epidemiological data suggest that physical activity protects against lung cancer; however, interpretation of these data is complicated by potential confounding by smoking. Glutathione (GSH) detoxifies cigarette smoke carcinogens and the paper tests whether physical activity levels are associated with blood GSH levels. Study subjects were enrolled in a chemoprevention trial testing whether antioxidant micronutrient supplementation reduces genetic damage from cigarette smoking. Physical activity data were collected by questionnaire from 178 subjects at 12 months of follow-up in the trial. Total GSH (tGSH), which is the sum of free and protein-bound GSH and glutathione disulfide levels, was measured using the 5,5'-dithiobis-(2-nitrobenzenoic acid) colormetric assay with red blood cell samples collected at the 12-month time point. In multivariate linear regression analyses that controlled for gender and cigarettes smoked per day, tGSH was positively associated with hours per week of moderate intensity activity (beta=0.005, p=0.02). Hours per week of vigorous intensity activity were unassociated with tGSH and the effect of moderate activity remained after control for vigorous activity. The results are consistent with prior research showing differential effects of moderate and vigorous activity and suggest a mechanism through which physical activity may influence lung cancer risk.

Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study.

BACKGROUND: Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the beta2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent. METHODS AND RESULTS: The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial Infarction Study (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >/=120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (P=0.33). CONCLUSIONS: RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points.

Death or nonfatal stroke in patients with acute myocardial infarction treated with tissue plasminogen activator. Participants in the National Registry of Myocardial Infarction 2.

In a retrospective cohort of patients treated in community hospitals, tissue plasminogen activator (t-PA) was associated with decreased odds of in-hospital death or nonfatal stroke. However, the relative benefit was less evident in older patients and women, and some older subgroups did not benefit from treatment.

Intracranial hemorrhage rates and effect of immediate beta-blocker use in patients with acute myocardial infarction treated with tissue plasminogen activator. Participants in the National Registry of Myocardial Infarction-2.

In acute myocardial infarction (AMI), immediate beta-blocker therapy reduces the incidence of reinfarction and recurrent chest pain in patients receiving tissue plasminogen activator (t-PA). Data from the Thrombolysis in Myocardial Infarction (TIMI)-2 trial also raises the possibility that such therapy may reduce the rate of intracranial hemorrhage (ICH). We reviewed data obtained from 60,329 patients treated with t-PA who were enrolled in the National Registry of Myocardial Infarction 2. Of the 60,329 in the study cohort, 23,749 patients (39.4%) were treated with immediate beta-blocker therapy and 542 patients (0.9%) developed an ICH. In a multivariate model that included all covariates known to be associated with the development of ICH, immediate beta-blocker therapy was associated with a 31% reduction in the ICH rate (odds ratio 0.69, 95% confidence intervals 0.57 to 0.84). Thus, in the present study, the use of immediate beta-blocker therapy in patients with AMI treated with t-PA was associated with a significant reduction in ICH. This finding supports the observations made in the TIMI 2 trial and serves to reinforce the recommendations made by the American College of Cardiology/American Heart Association task force that immediate beta-blocker therapy should be administered to all patients with AMI who do not have contraindications to this therapy.

The association between glutathione S-transferase M1 genotype and polycyclic aromatic hydrocarbon-DNA adducts in breast tissue.

A major goal in molecular epidemiology is to identify preventable environmental risk factors and susceptible subpopulations. In a hospital-based molecular epidemiological case-control study of breast cancer, we investigated the relationship between DNA damage from exposure to polycyclic aromatic hydrocarbons (PAHs) and susceptibility attributable to inherited deletion of the xenobiotic detoxifying gene, glutathione S-transferase M1 (GSTM1). Prior to breast surgery, women (n = 227) were enrolled and interviewed and donated a blood sample. PAH-DNA adduct levels were measured by immunohistochemistry in breast tissue samples retrieved from pathology blocks, and GSTM1 genotype was determined by PCR using WBC DNA. The GSTM1 analysis included 95 cases and 87 benign breast disease controls. GSTM1 genotype was not associated with breast cancer case-control status (odds ratio = 0.73; 95% confidence interval, 0.37-1.44). However, the GSTM1 null genotype predicted PAH-DNA adduct levels in malignant (beta = 0.407; P = 0.003) and nonmalignant (beta = 0.243; P = 0.05) breast tissue from cases. This relationship was not seen in tissue from controls (beta = 0.095; P = 0.341). When tissue from controls was compared with tumor tissue from cases, there was a significant case-control difference in PAH-DNA adduct levels among women who were GSTM1 null. There was no such case-control difference among women who were homozygous or heterozygous for GSTM1. There was an interaction between GSTM1 and case-control status on adduct levels in breast tissue (P = 0.002). The results suggest that genetic susceptibility to the formation of PAH-DNA adducts in breast tissue may play a role in breast cancer development.

The relationship between genetic damage from polycyclic aromatic hydrocarbons in breast tissue and breast cancer.

A number of polycyclic aromatic hydrocarbons (PAH) are widespread environmental contaminants that cause mammary cancer experimentally. We investigated whether exposure and susceptibility to PAH, as measured by PAH-DNA adducts in breast tissue, are associated with human breast cancer. We carried out a hospital-based case-control study using immunohistochemical methods to analyze PAH-DNA adducts in tumor and nontumor breast tissue from cases and benign breast tissue from controls. The subjects were white, African-American and Latina women without prior cancer or treatment, including 119 women with breast cancer and 108 with benign breast disease without atypia. PAH-DNA adducts measured in breast tumor tissue of 100 cases and in normal tissue from 105 controls were significantly associated with breast cancer (OR=4.43, 96% CI 1.09-18.01) after controlling for known breast cancer risk factors and current active and passive smoking, and dietary PAH. There was substantial interindividual (17-fold) variability in adducts overall, with 27% of cases and 13% of controls having elevated adducts. The odds ratio for elevated adducts in tumor tissue compared with control tissue was 2.56 (1. 05-6.24), after controlling for potential confounders. Adduct levels in tumor tissue did not vary by stage or tumor size. Among 86 cases with paired tumor and nontumor tissue, adducts levels in these two tissues were highly correlated (r=0.56, P<0.001). However, the corresponding associations between case-control status and adducts measured in nontumor tissue from 90 cases and in normal tissue from 105 controls were positive but not statistically significant. Overall, neither active nor passive smoking, or dietary PAH were significantly associated with PAH-DNA adducts or breast cancer case-control status. These results suggest that genetic damage reflecting individual exposure and susceptibility to PAH may play a role in breast cancer; but more research is needed to determine whether the findings are relevant to causation or progression of breast cancer.

Body mass index (BMI) in Turner Syndrome before and during growth hormone (GH) therapy.

OBJECTIVE: To study whether body mass index (BMI) is different in girls with Turner syndrome (TS) compared to normal girls, and whether BMI in TS is affected by growth hormone (GH) treatment. DESIGN: A retrospective cross-sectional study. SUBJECTS: 2468 girls with TS enrolled in the National Cooperative Group Study (NCGS), a collaborative surveillance study for assessing GH-treated children. MEASUREMENTS: BMI and BMI standard deviation score (BMI SDS) at baseline and during GH treatment were computed from height and weight data. RESULTS: BMI in TS patients increases with age as expected. However, BMI SDS increased starting at about age 9 y. A similar pattern of increase in BMI SDS was observed after each year of GH treatment for up to 4 y, but GH treatment did not change the magnitude of increase. BMI and BMI SDS curves before and during GH treatment were essentially superimposable. CONCLUSION: These findings suggest that mechanisms specific for TS are responsible for the age-related increase in BMI SDS. This increase was unaffected by GH treatment.

Reperfusion therapy for acute myocardial infarction: observations from the National Registry of Myocardial Infarction 2.

The National Registry of Myocardial Infarction 2 (NRMI-2) provides a unique opportunity to evaluate the practice patterns among participating cardiology and emergency medicine departments involved in the care of patients with acute myocardial infarction. The data from NRMI-2 suggest that almost 1/3 of all non-transfer-in and non-transfer-out patients are eligible for reperfusion therapy. Furthermore, of those patients who are clearly eligible for reperfusion therapy, 24% are not given this proven therapy. Specifically, women, the elderly, patients without chest pain on presentation, and those patients at highest risk for in-hospital mortality were least likely to be treated with reperfusion therapy. The reason for underuse of reperfusion therapy may in part reflect a concern for adverse bleeding events associated with the use of thrombolytic therapy. The data from NRMI-2 also suggest that patients with contraindications to thrombolysis may be very appropriate for primary angioplasty. Realizing the full potential benefits of reperfusion therapy in terms of reduced cardiovascular morbidity and mortality will require that clinical practice patterns be aligned more closely with the recommended national guidelines, which are based on extensive clinical trial data that show the benefit of reperfusion therapy in a wide range of patients with acute myocardial infarction. By using observational databases, such as the NRMI-2, which describe how clinical care is administered in nonclinical trial settings, we can continually monitor our progress and initiate changes to ensure that patients are given access to the many therapies that have been shown to improve their quality of life and survival.

Bundle-branch block and in-hospital mortality in acute myocardial infarction. National Registry of Myocardial Infarction 2 Investigators.

BACKGROUND: Left bundle-branch block (BBB) is considered an important predictor of poor outcome in patients with acute myocardial infarction, but the consequences of right BBB are not well understood. OBJECTIVES: To 1) estimate the prevalence of left and right BBB in patients with myocardial infarction; 2) compare the clinical characteristics of and treatments received by patients with left, right, or no BBB; and 3) determine the independent association of left BBB and right BBB with in-hospital death. DESIGN: Retrospective cohort study. SETTING: Multicenter registry of 1571 U.S. hospitals. PATIENTS: 297,832 patients with acute myocardial infarction who had left, right, or no BBB on initial electrocardiography. MEASUREMENTS: Presence and type of BBB, clinical characteristics of patients, therapies given, and in-hospital death. RESULTS: Patients with left BBB (n = 19,967; 6.7%) or right BBB (n = 18,354; 6.2%) were older and had more comorbid illness and congestive heart failure than patients with no BBB. Among patients for whom thrombolytic therapy was clearly indicated, fewer patients with left or right BBB (16.6% and 32.0%, respectively) than patients with no BBB (66.5%) received this therapy (P < 0.001). Fewer patients with left or right BBB (60.6% and 67.3%, respectively) than patients with no BBB (75.6%) received aspirin within the first 24 hours (P < 0.001), and fewer patients with left or right BBB (23.9% and 31.8%, respectively) than patients with no BBB (40.4%) received beta-blockers within the first 24 hours (P < 0.001). Unadjusted in-hospital mortality rates were almost twice as high for patients with left or right BBB (22.6% and 23.0%, respectively) as for patients with no BBB (13.1%) (P < 0.001). Compared with no BBB and no ST-segment elevation, left BBB was associated with a 34% increase (odds ratio, 1.34 [95% CI, 1.28 to 1.39]) and right BBB was associated with a 64% increase (odds ratio, 1.64 [CI, 1.57 to 1.71]) in the risk for in-hospital death, after adjustment for potential confounders. CONCLUSIONS: In patients with acute myocardial infarction, prevalences of right and left BBB are similar. Patients with BBB have more comorbid conditions, are less likely to receive therapy, and have an increased risk for in-hospital death compared with patients with no BBB. Compared with left BBB, right BBB seems to be a stronger independent predictor of in-hospital death.

Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers.

This molecular epidemiologic case-control study of lung cancer incorporated three complementary biomarkers: the glutathione S-transferase M1 (GSTM1) null genotype, a potential marker of susceptibility, and polycyclic aromatic hydrocarbon-DNA adducts (PAH-DNA) and sister chromatid exchanges (SCE), both indicators of environmentally induced genetic damage. Associations between biomarkers and lung cancer were investigated, as were possible gene-environment interactions between the GSTM1 null genotype and tobacco smoke exposure. Subjects included 136 primary non-small cell lung cancer surgical patients and 115 controls at the Columbia Presbyterian Medical Center. Questionnaire and Tumor Registry data, pre-treatment blood samples and biomarker measurements on blood were obtained. Overall, GSTM1 null genotype was significantly associated with lung cancer [odds ratio (OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 and lung cancer were significant in females (2.50, 1.09-5.72) and smokers (2.25, 1.11-4.54) and not significant in males (1.4, 0.58-3.38) and non-smokers (0.88, 0.18-4.33). However, ORs for males versus females and smokers versus non-smokers did not differ significantly. The OR for GSTM1 and lung cancer in female smokers was 3.03 (1.09-8.40), compared with 1.42 (0.53-4.06) in male smokers. In contrast to PAH-DNA adducts in leukocytes, SCE did not differ between cases and controls. Neither biomarker differed significantly between the two GSTM1 genotypes. The combined effect of elevated PAH-DNA adducts and GSTM1 genotype on case-control status (16.19, 1.2-115) appeared multiplicative. Results suggest that the effect of the GSTM1 null genotype is greatest in female smokers, which is consistent with other evidence that indicates that women are at higher risk of lung cancer than males, given equal smoking. Persons with both the GSTM1 deletion and elevated PAH-DNA adducts may represent a sensitive subpopulation with respect to carcinogens in tobacco smoke and other environmental media.

Weight relative to height before and during growth hormone therapy in prepubertal children.

We used the Genentech National Cooperative Growth Study database to examine differences in weight relative to height (weight for height standard deviation score or WTHTZ) in 3460 patients at enrollment and after one year of therapy with recombinant human growth hormone (rhGH), and in a subset of 450 patients treated for three years with rhGH. The major diagnostic categories were idiopathic growth hormone deficiency (IGHD), organic GH deficiency (OGHD), and idiopathic short stature (ISS). Children with IGHD and ISS were underweight for height at baseline but had a progressive increase in WTHTZ during three years of rhGH therapy. The same pattern applied to children with IGHD associated with septo-optic dysplasia and CNS trauma or infection. However, children with OGHD associated with craniopharyngiomas, other CNS tumors, leukemia, or CNS irradiation were overweight when starting rhGH and showed a decrease in WTHTZ during the first year of rhGH therapy. The increase in WTHTZ during rhGH treatment in children with ISS and OGHD suggests that the GH-induced increase in muscle mass exceeded loss of fat mass. Because children with neoplasm-related OGHD were overweight at baseline, the decline in WTHTZ during the first year of rhGH therapy suggests that loss of fat mass is the predominant effect in this subgroup.

Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Participants in the National Registry of Myocardial Infarction 2.

BACKGROUND: The efficacy of thrombolytic therapy in reducing mortality from acute myocardial infarction has been unequivocally shown. However, thrombolysis is related to bleeding complications, including intracranial hemorrhage. OBJECTIVE: To determine the frequency of and risk factors for intracranial hemorrhage after recombinant tissue-type plasminogen activator (tPA) given for acute myocardial infarction in patients receiving usual care. DESIGN: Large national registry of patients who have had acute myocardial infarction. SETTING: 1484 U.S. hospitals. PATIENTS: 71073 patients who had had acute myocardial infarction from 1 June 1994 to 30 September 1996, received tPA as the initial reperfusion strategy, and did not receive a second dose of any thrombolytic agent. MEASUREMENT: Intracranial hemorrhage confirmed by computed tomography or magnetic resonance imaging. RESULTS: 673 patients (0.95%) were reported to have had intracranial hemorrhage during hospitalization for acute myocardial infarction; 625 patients (0.88%) had the event confirmed by computed tomography or magnetic resonance imaging. Of the 625 patients with confirmed intracranial hemorrhage, 331 (53%) died during hospitalization. An additional 158 patients (25.3%) who survived to hospital discharge had residual neurologic deficit. In multivariable models for the main effects of candidate risk factors, older age, female sex, black ethnicity, systolic blood pressure of 140 mm Hg or more, diastolic blood pressure of 100 mm Hg or more, history of stroke, tPA dose more than 1.5 mg/kg, and lower body weight were significantly associated with intracranial hemorrhage. CONCLUSIONS: Intracranial hemorrhage is a rare but serious complication of tPA in patients with acute myocardial infarction. Appropriate drug dosing may reduce the risk for this complication. Other therapies, such as primary coronary angioplasty, may be preferable in patients with acute myocardial infarction who have a history of stroke.