Shared Care to Destination Therapy Left Ventricular Assist Device Site: a Novel Strategy to Start a Successful Mechanical Circulatory Support Program.

PURPOSE OF REVIEW: Heart failure is an important healthcare issue because of its high prevalence, mortality, and morbidity. Advanced heart failure therapies have improved significantly over the years with improved outcomes. Heart transplantation remains an elusive treatment option for most patients; hence, the need for alternative therapy has given rise to the use of mechanical circulatory support (MCS) devices, initially as bridge to transplantation, but with more recent use as destination therapy. This review focuses on the intricacies of establishing a successful left ventricular assist device (LVAD) program for destination therapy in the setting of a growing anticipated need for wider availability of such treatment options. RECENT FINDINGS: Guidelines have established the role of MCS in patients with advanced HF refractory to optimal guideline-directed medical therapy (GDMT) and cardiac device interventions. Multiple studies have shown generational improvement in the overall safety profile of MCS devices with the use of newer devices for destination therapy showing improved outcomes. Heart failure is a growing cardiovascular problem with an anticipated growing need for advanced HF therapies including MCS devices. A model of shared care LVAD to destination therapy implanting site should be considered as a strategy to start a successful LVAD program.

Combination of molecular alterations and smoking intensity predicts bladder cancer outcome: a report from the Los Angeles Cancer Surveillance Program.

BACKGROUND: Traditional single-marker and multimarker molecular profiling approaches in bladder cancer do not account for major risk factors and their influence on clinical outcome. This study examined the prognostic value of molecular alterations across all disease stages after accounting for clinicopathological factors and smoking, the most common risk factor for bladder cancer in the developed world, in a population-based cohort. METHODS: Primary bladder tumors from 212 cancer registry patients (median follow-up, 13.2 years) were immunohistochemically profiled for Bax, caspase-3, apoptotic protease-activating factor 1 (Apaf-1), Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. "Smoking intensity" quantified the impact of duration and daily frequency of smoking. RESULTS: Age, pathological stage, surgical modality, and adjuvant therapy administration were significantly associated with survival. Increasing smoking intensity was independently associated with worse outcome (P < .001). Apaf-1, E-cadherin, and p53 were prognostic for outcome (P = .005, .014, and .032, respectively); E-cadherin remained prognostic following multivariable analysis (P = .040). Combined alterations in all 9 biomarkers were prognostic by univariable (P < .001) and multivariable (P = .006) analysis. A multivariable model that included all 9 biomarkers and smoking intensity had greater accuracy in predicting prognosis than models composed of standard clinicopathological covariates without or with smoking intensity (P < .001 and P = .018, respectively). CONCLUSIONS: Apaf-1, E-cadherin, and p53 alterations individually predicted survival in bladder cancer patients. Increasing number of biomarker alterations was significantly associated with worsening survival, although markers comprising the panel were not necessarily prognostic individually. Predictive value of the 9-biomarker panel with smoking intensity was significantly higher than that of routine clinicopathological parameters alone.

The incidence of trocar-site hernia in minimally invasive bariatric surgery: a comparison of multi versus single-port laparoscopy.

INTRODUCTION: Single-port laparoscopy (SPL) employs a 1.5- to 2.5-cm incision at the umbilicus for the placement of a single working port. We hypothesized that the longer incision created by SPL compared with multiport laparoscopy may increase the incidence of trocar-site hernias. We examined our experience with SPL in bariatric operations. METHODS: There were 734 laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding procedures performed at our institution between 2001 and 2011. Fifty-eight patients were lost to follow-up or had a short duration of follow-up (<1 month). Of the remaining 676 cases, 163 were performed via SPL. All laparoscopic wounds created by trocar size greater than 12 mm were closed with absorbable suture. RESULTS: Patient demographics of the SPL group and the multiport group were similar in terms of age, gender, and comorbidities. The average body mass index (BMI) of the SPL group was lower than the multiport group (43.5 ± 5.3 vs. 45.8 ± 7.7, p < 0.01). The mean follow-up for the SPL group was 11 months versus 24 months for the multiport group. There were three trocar-site hernias out of 513 cases in the multiport compared to one hernia out of 163 cases in the SPL group (0.6 vs. 0.6 %, p = 0.967). All trocar-site hernias occurred at the 15-mm port site. The median time to hernia occurrence for the multiport group was 13 months (range, 1-18). In the SPL group, the hernia occurred at 8 months. On multivariate analysis, age, BMI, SPL, procedure type, and the postoperative weight loss were not associated with the development of trocar-site hernias. CONCLUSIONS: SPL did not increase the rate of trocar-site hernia in this series. A low rate of trocar-site hernia can be achieved with the use of SPL in bariatric surgery.

Improving the quality of public health guidance: A business rules approach.

Context: In this article, the authors discuss potential advantages that business rules methodology offers for improvement of public health operational guidance and documents. Program: Immunization Information Systems (IIS) program at the Centers for Disease Control and Prevention (CDC). Implementation: Systematic methods of business analysis and business rules were successfully employed in two multi-year efforts to develop guidance for various aspects of IIS operations. Evaluation: Independent evaluation findings indicate that application of these best practice recommendations in the IIS domain of state and local health departments resulted in improved data quality, reduced staff time, and increased efficiencies across immunization programs, as well as in uniformity and reduced ambiguity for clinical decision support. Also, to illustrate the approach, a special case study presents a systematic analysis of highly regarded work by the prominent scientist and renowned writer Isaac Asimov, identifying inconsistencies, typical challenges, and areas for improvement. Discussion: The two successful case studies in the IIS domain of public health point to the potential of applying business rules methods in rigorously documenting operational guidance, substantially reducing ambiguity, and ultimately, improving the uniformity, completeness, and practicality of information within critical documents of public health programs. Experience gained with these projects can be leveraged and built upon going forward. Also, a special study of writings by Dr. Asimov provides a strong word of caution about the unintended consequences and potential shortcomings of formulating guidance without leveraging a systematic approach, such as offered by business rules techniques. This is an opportune time for public health to embrace this proven methodology, expanding its arsenal of practicable tools to analyze and improve public health guidance.

No association between the SRD5A2 gene A49T missense variant and prostate cancer risk: lessons learned.

The steroid 5-alpha reductase type II gene (SRD5A2) encodes the enzyme which converts testosterone (T) to the more active androgen dihydrotestosterone. A non-synonymous single-nucleotide polymorphism, A49T (rs9282858), in SRD5A2 has been implicated in prostate cancer risk; however, results have been inconsistent. In 1999, we reported a strong association between the A49T variant and prostate cancer risk among African-Americans and Latinos in the Hawaii-Los Angeles Multiethnic Cohort (MEC). We report here an updated analysis of MEC data including the five major ethnic groups of the MEC, an increased sample size, improved genotyping technology and a comprehensive meta-analysis of the published literature. We found a non-statistically significant positive association between prostate cancer risk and carrying either the AT or TT genotype [odds ratio (OR) = 1.16, 95% confidence interval (CI) 0.79-1.69] in the MEC. This finding is in contrast to our previous results of ORs of 3.28 and 2.50 for the association between prostate cancer risk and the variant in African-American and Latino men, respectively; this can be accounted for by genotyping error in our earlier study. Meta-analysis of the published literature, including the current MEC data, shows a summary OR of 1.13 (95% CI 0.95-1.34) for the A49T variant with prostate cancer risk among sporadic, unselected cases. After evaluating more than 6000 cases and 6000 controls, there is little evidence of a role for the SRD5A2 A49T variant in prostate cancer risk. Overall, this report highlights the importance of rigorous genotyping quality control measures and replication efforts in genetic association studies.

Resource utilization in the management of young patients with syncope in a combat theater of operations.

UNLABELLED: Clinical features of young patients presenting with syncope have been underreported. METHODS: Retrospective review using U.S. Military Health System's Theater Medical Data Store and Joint Medical Workstation identified patients evaluated for syncope from January 2005 to October 2007 while deployed to a combat zone. RESULTS: We identified 848 patients with syncope. The majority (80.8%) were under the age of 40. The diagnostic yield of the ECG was 2.0%. In those <40 years, there were no head CTs or transthoracic echocardiograms that identified a cause of syncope. There was no difference in evacuation out of theater between those <40 years and those >40 years (10.8% vs. 8.6%, p = 0.08). Patients with a prior episode of syncope were more likely to undergo medical evacuation outside of the combat zone (16.0% vs. 7.7%, p < 0.01). DISCUSSION: Evacuation of those <40 years to facilities with advanced imaging did not add diagnostic information.

Prophylactic Retrograde Distal Common Femoral Access as a Bail-out Strategy in Patients with Increased Risk for Femoral Access Complication During Transfemoral Aortic Valve Replacement.

OBJECTIVE: Several patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) have complex peripheral arterial disease (PAD) that increases risk of vascular complications and failure of vascular closure device (VCD). Endovascular bailout of failed VCD is performed through contralateral femoral access. Further due to multiple different anatomic reasons the contralateral femoral access and "up and over" approach is unavailable for endovascular bailout of the VCD failure. We evaluated a novel bailout technique of obtaining an additional access in ipsilateral common femoral artery (CFA) or superficial femoral artery (SFA) distal to the main CFA access used for TAVR device. METHODS: We prospectively identified patients who were at high risk for VCD failure and had unavailable contralateral CFA approach from the pre-TAVR evaluation with multislice CT angiography. The data was collected prospectively for the TVT registry and retrospectively reviewed. All patients had an additional distal access obtained in the CFA or proximal SFA under direct fluoroscopy guidance after achieving main CFA access for TAVR. Using an inner 0.021″ micro-dilator from the 4-Fr micropuncture mini stick max access kit (AngioDynamics, Marlborough, MA) and a 200 cm long 0.018″ wire, the distal access was secured in place through the TAVR procedure. After completing the TAVR if the VCD gained successful hemostasis, the 0.021″ dilator was removed with manual pressure. If the VCD failed to achieve hemostasis, the distal access was upsized to a 7 Fr sheath for carrying out endovascular repair of the TAVR access. If the distal access was upsized to 7 Fr, that access was treated with VCD. The patients were monitored for acute in-hospital complication and followed for 6 months. RESULTS: During 2017 & 2018, 97.4% of 186 TAVRs were performed via femoral approach at our center. Six patients met the criteria for high-risk access and non-availability of the contralateral "up and over" approach. Of the 6 patients enrolled in this prospective study, 3 required endovascular management of TAVR access because of failed VCDs and were treated with covered stents using the distal ipsilateral access. The remaining 3 patients had successful use of VCDs for the TAVR access and the prophylactic access with 0.021″ dilator was managed with manual pressure. None of the six patients suffered any further vascular complication or bleeding. At the 6-month follow up no vascular complications or clinically driven events were identified from the TAVR access or additional distal ipsilateral access. CONCLUSION: This novel technique of prophylactic ipsilateral distal femoral access can provide an alternative bailout strategy for patients at high risk of closure device failure and unavailable contralateral femoral approach during transfemoral TAVR.

Methyl 2-[2-((Z)-{1-trans-[2-(4-fluoro-3-methyl-phen-yl)-2-methyl-cyclo-prop-yl]ethyl-idene}amino-oxymeth-yl)phen-yl]-2-[(E)-methoxy-imino]-acetate.

The title compound, C(24)H(27)FN(2)O(4), is an important inter-mediate in the synthesis of fungicidal strobilurin-type compounds. In the crystal structure, the oxime bond attached to the cyclo-propane ring adopts a Z configuration, while the oxime bond attached to the benzene ring adopts an E configuration. The fluoro-methyl-phenyl group adopts a trans configuration with respect to the remainder of the mol-ecule, and its mean plane forms a dihedral angle of 56.1 (1)° with the plane of the cyclo-propane ring.

Long-term recreational physical activity and risk of invasive and in situ breast cancer: the California teachers study.

BACKGROUND: Long-term physical activity may affect breast cancer risk. Few prospective studies have evaluated in situ or invasive breast cancer risk, or breast cancer receptor subtypes, in relation to long-term activity. METHODS: We examined the association between recreational physical activity and risk of invasive and in situ breast cancer in the California Teachers Study, a cohort of women established in 1995-1996. Of 110 599 women aged 20 to 79 years with no history of breast cancer followed up through December 31, 2002, 2649 were diagnosed as having incident invasive breast cancer and 593 were diagnosed as having in situ breast cancer. Information was collected at cohort entry on participation in strenuous and moderate recreational activities during successive periods from high school through the current age or age 54 years (if older at enrollment) and in the past 3 years. A summary measure of long-term activity up to the current age, or age 54 years if older, was constructed for each woman. RESULTS: Invasive breast cancer risk was inversely associated with long-term strenuous activity (>5 vs 5 vs

Physical activity and colon cancer risk among women in the California Teachers Study.

BACKGROUND: Existing data suggest that physical activity reduces colon cancer risk, but the association is not consistently observed in women. One potential explanation for this inconsistency is that hormone therapy, which is associated with lower colon cancer risk, acts as a modifier of the physical activity/colon cancer relationship. METHODS: Participants in the California Teachers Study (N = 120,147), a prospective cohort of female teachers and administrators residing in California, ages 22 to 84 years at baseline and with no prior history of colon cancer were eligible for study. Between 1996 and 2002, 395 patients were diagnosed with invasive colon cancer. The relative risks (RR) associated with lifetime (high school through age 54 years or current age) and recent (past 3 years) strenuous and moderate recreational physical activity were estimated using Cox proportional hazards regression models. RESULTS: Combined lifetime moderate and strenuous recreational physical activity was only modestly associated with colon cancer risk in the cohort [>or=4 versus or=4 versus

Discovery of the aryl heterocyclic amine insecticides: synthesis, insecticidal activity, field results, mode of action and bioavailability of a leading field candidate.

BACKGROUND: γ-Amino butyric acid (GABA) antagonists are proven targets for control of lepidopteran and other pests. New heterocyclic compounds with high insecticidal activity were discovered using a competitive-intelligence-inspired scaffold-hopping approach to generate analogs of fipronil, a known GABA antagonist. These novel aryl heterocyclic amines (AHAs) displayed broad-spectrum activity on a number of chewing insect pests. RESULTS: Through >370 modifications of the core AHA structure, a 7-pyrazolopyridine lead molecule was found to exhibit much improved activity on a number of insect pests. In field trial studies, its performance was 2-4 times lower than commercial standards and also appeared to be species dependent, with good activity seen for larvae of Spodoptera exigua, but inactivity on larvae of Trichoplusia ni. CONCLUSION: An extensive investigational biology effort demonstrated that these AHA analogs appear to have multiple modes of action, including GABA receptor antagonism and mitopotential or uncoupler activity. The limited capability in larvae of T. ni to convert the lead molecule to its associated open form correlates with the low toxicity of the lead molecule in this species. This work has provided information that could aid investigations of novel GABA antagonists. © 2016 Society of Chemical Industry.

Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a case-control and a case-case comparison.

INTRODUCTION: It has been suggested that hormonal risk factors act predominantly on estrogen receptor and progesterone receptor (ER/PR)-positive breast cancers. However, the data have been inconsistent, especially in younger women. METHODS: We evaluated the impact of age at menarche, pregnancy history, duration of breastfeeding, body mass index, combined oral contraceptive use, and alcohol consumption on breast cancer risk by ER/PR status in 1,725 population-based case patients and 440 control subjects aged 20 to 49 years identified within neighborhoods of case patients. We used multivariable unconditional logistic regression methods to conduct case-control comparisons overall as well as by ER/PR status of the cases, and to compare ER+PR+ with ER-PR- case patients. RESULTS: The number of full-term pregnancies was inversely associated with the risk of ER+PR+ breast cancer (ptrend = 0.005), whereas recent average alcohol consumption was associated with an increased risk of ER+PR+ breast cancer (ptrend = 0.03). Neither of these two factors was associated with the risk of ER- PR- breast cancer. Late age at menarche and a longer duration of breastfeeding were both associated with decreased breast cancer risk, irrespective of receptor status (all ptrend< or = 0.03). CONCLUSION: Our results suggest that the number of full-term pregnancies and recent alcohol consumption affect breast cancer risk in younger women predominantly through estrogen and progesterone mediated by their respective receptors. Late age at menarche and breastfeeding may act through different hormonal mechanisms.

Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China.

BACKGROUND: Insulin-like growth factor I (IGF-I) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor. The major binding protein for IGF-I, insulin-like growth factor-binding protein 3 (IGFBP-3), modulates the effects of IGF-I but also inhibits cell growth and induces apoptosis independent of IGF-I and its receptor. In a prospective study of men in Shanghai, China, we examined the association between serum levels of IGF-I and IGFBP-3 and the subsequent risk of lung cancer. METHODS: From 1986 to 1989, serum was collected from 18,244 men aged 45-64 years living in Shanghai without a history of cancer. We analyzed IGF-I and IGFBP-3 levels in serum from 230 case patients who developed incident lung cancer during follow-up and from 740 control subjects. RESULTS: Among 230 case patients and 659 matched control subjects, increased IGF-I levels were not associated with increased risk of lung cancer. However, for subjects in the highest quartile relative to the lowest quartile of IGFBP-3, the odds ratio (OR) for lung cancer, adjusted for smoking and IGF-I, was 0.50 (95% confidence interval [CI] = 0.25 to 1.02). When the analysis was restricted to ever smokers (184 case patients and 344 matched control subjects), the OR for lung cancer in men in the highest quartile of IGFBP-3 relative to those in the lowest quartile, adjusted for smoking and IGF-I, was 0.41 (95% CI = 0.18 to 0.92). CONCLUSIONS: In this prospective study of Chinese men, higher serum levels of IGF-I did not increase the risk of lung cancer. However, subjects with higher serum levels of IGFBP-3 were at reduced risk of lung cancer. This finding is consistent with experimental data that indicate that IGFBP-3 can inhibit cellular proliferation and induce apoptosis independent of IGF-I and the IGF-I receptor.

A Case Study of Environmental Injustice: The Failure in Flint.

The failure by the city of Flint, Michigan to properly treat its municipal water system after a change in the source of water, has resulted in elevated lead levels in the city's water and an increase in city children's blood lead levels. Lead exposure in young children can lead to decrements in intelligence, development, behavior, attention and other neurological functions. This lack of ability to provide safe drinking water represents a failure to protect the public's health at various governmental levels. This article describes how the tragedy happened, how low-income and minority populations are at particularly high risk for lead exposure and environmental injustice, and ways that we can move forward to prevent childhood lead exposure and lead poisoning, as well as prevent future Flint-like exposure events from occurring. Control of the manufacture and use of toxic chemicals to prevent adverse exposure to these substances is also discussed. Environmental injustice occurred throughout the Flint water contamination incident and there are lessons we can all learn from this debacle to move forward in promoting environmental justice.

Prosthetic Aortic Valve Fixation Study: 48 Replacement Valves Analyzed Using Digital Pressure Mapping.

OBJECTIVE: Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). METHODS: Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 × 4-mm, 12 × 4-mm, or 9 × 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand-tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. RESULTS: Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 × 4-mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 × 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 × 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 × 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). CONCLUSIONS: Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security.

Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer?

PURPOSE: We and other investigators have previously shown that postmenopausal combined estrogen and progestin replacement therapy (EPRT) increases the risk of breast cancer and that the risk associated with EPRT is substantially higher than for estrogen replacement therapy (ERT) alone. The present study was conducted to determine whether any particular subgroup of women are at particularly high risk of breast cancer if they use EPRT and whether tumor characteristics in women who develop cancer while on ERT or EPRT are different from those in women not using ERT or EPRT. PATIENTS AND METHODS: We conducted a population-based case-control study in Los Angeles, CA, with patients diagnosed with breast cancer in the late 1980s and early 1990s. Control subjects were matched to patients on age, ethnicity, and neighborhood of residence. We present data on 1,897 postmenopausal patients and 1,637 controls aged 55 to 72 years who had not undergone a simple hysterectomy. RESULTS: Relative risk of breast cancer associated with EPRT use did not vary with body mass index (body mass index at or below v above median [24.6 kg/m(2)]; P =.98), alcohol intake (> or + one v < one drink per week; P =.16), parity (nulliparous v parous; P =.45), history of benign breast disease (yes v no; P =.99), or family history of breast cancer (first degree v none; P =.57). All of these results were compatible with our previously reported estimate of an increased risk of breast cancer of 5% per year of use of EPRT. Hormone users, principally EPRT users, were more likely to have hormone receptor--positive, especially progesterone-positive, tumors. CONCLUSION: We found no evidence that the risk of breast cancer associated with EPRT is limited to subgroups of women with specific cofactors. Tumors in EPRT users are more often hormone receptor--positive, indicating that they may have a better prognosis than breast cancer overall.

Residential mobility in the California Teachers Study: implications for geographic differences in disease rates.

BACKGROUND: Especially for cancers with long latency periods, such as breast cancer, the issue of residential mobility hinders ecologic analyses seeking to examine the role of environmental contaminants in chronic disease etiology. This study describes and evaluates characteristics associated with residential mobility in a sub-sample of the California Teachers Study (CTS) cohort. METHODS: In 2000, lifetime residential histories were collected for a sub-sample of 328 women enrolled in the CTS; women's degree of residential mobility and associated factors were analyzed. RESULTS: While most women moved many times during their lives (average = 8.9), the average number of years at their residence when they enrolled in the study was reasonably long (15.1 years). Age strongly predicted duration at current residence but was not related to the number of lifetime residences. After adjusting for age, California-born women and women living in high socioeconomic status (SES) neighborhoods were significantly more residentially stable. Agreement between self-reported urbanization of recent residences and that based on census data of the geocoded residences was very good (80% concordant). Among women currently living in urban areas, an average of 43.3 years, or 77%, of their lifetimes were spent in urban residences; among women currently living in a rural area, an average of 37.3 years, or 67% of their lifetimes were spent in rural residences. CONCLUSIONS: This suggests that analyses of incidence rates based on current residence, while not capturing a woman's full exposure history, may reasonably reflect some aspect of longer term chronic exposures, especially those related to urbanization, at least in professional women.

Nonsmoking-related arylamine exposure and bladder cancer risk.

Roughly one-half of bladder cancer incidence in the United States can be attributed to known causes, mainly cigarette smoking, and it has been hypothesized that the aromatic amines in tobacco smoke are important etiological agents. Nonsmokers are also exposed, through unknown sources, to many of the same carcinogenic aromatic amines that are present in cigarette smoke. Previous epidemiological studies have not tested whether either of these aromatic amine exposures are associated with cancer risk. We conducted a population-based case-control study in Los Angeles County, California, involving 761 case patients with bladder cancer and 770 individually matched control subjects. In-person interviews provided information on tobacco smoking and other potential risk factors. Quantitative analysis of hemoglobin adducts of 4- and 3-aminobiphenyl (ABP) was used to assess aromatic amine exposure. Adducts of both aminobiphenyls were significantly higher in cases than in controls, independent of cigarette smoking at the time of blood collection and lifetime smoking history. Adjustment for other risk factors as well as for metabolic differences did not materially alter the associations. Our findings strengthen the connection between exposure to aromatic amines in tobacco smoke and cigarette smoking-related bladder cancer and suggest that environmental exposure to arylamines may account for a significant proportion of nonsmoking-related bladder cancer in the general population.

Prediagnostic levels of serum micronutrients in relation to risk of gastric cancer in Shanghai, China.

Data on blood levels of specific carotenoids and vitamins in relation to gastric cancer are scarce. Little is known about the relationship between prediagnostic serum levels of carotenoids other than beta-carotene and risk of gastric cancer especially in non-Western populations. Prediagnostic serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, alpha-tocopherol, gamma-tocopherol, and vitamin C were determined on 191 cases and 570 matched controls within a cohort of 18,244 middle-aged or older men in Shanghai, China, with a follow-up of 12 years. High serum levels of alpha-carotene, beta-carotene, and lycopene were significantly associated with reduced risk of developing gastric cancer (all Ps for trend /=3 drinks of alcohol per day; the odds ratios (95% confidence intervals) for the second, third, and fourth quartile categories were 0.69 (0.28-1.70), 0.36 (0.14-0.94), and 0.39 (0.15-0.98), respectively, compared with the lowest quartile of vitamin C (P for trend = 0.02). There were no statistically significant relationships of serum levels of beta-cryptoxanthin, lutein/zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol with gastric cancer risk. The present study implicates that dietary carotenes, lycopene, and vitamin C are potential chemopreventive agents for gastric cancer in humans.

Patterns of alcohol consumption and breast cancer risk in the California Teachers Study cohort.

Alcohol consumption of approximately two drinks or more per day has been associated with elevated breast cancer risk in the California Teachers Study cohort as well as in many other populations. The objective of this analysis is to examine effects of age at drinking and drinking patterns and to identify effect modifiers. Of the 103,460 at-risk cohort members, age <85, who resided in California and completed the baseline alcohol assessment, 1,742 were diagnosed with invasive breast cancer after joining the cohort and before January 2001. Incident breast cancers were identified through the California Cancer Registry and follow-up for death and confirmation of continued California residence used various sources. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RRs). Elevated breast cancer risk was most evident for recent drinking [RR = 1.28, 95% confidence interval (CI): 1.06-1.54 for >/=20 g/day versus nondrinkers], with no clear pattern for consumption during earlier periods of life. This elevation in risk was 32% among postmenopausal women (95% CI: 1.06-1.63) and 21% among pre/perimenopausal women (95% CI: 0.76-1.92). Highest risks associated with heavy alcohol consumption were observed among postmenopausal women with a history of biopsy-diagnosed benign breast disease (RR = 1.97, 95% CI: 1.39-2.79 compared to nondrinkers without benign breast disease) or who had used combination hormone replacement therapy (HRT) (RR = 2.24, 95% CI: 1.59-3.14 compared to nondrinkers who never used HRT). Recent alcohol consumption equivalent to two or more drinks per day increases the risk of invasive breast cancer, with the greatest RRs observed among heavy drinkers who are also postmenopausal and have a history of benign breast disease or who use HRT.