Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Prevalence of latex sensitization and allergy in Portuguese children

The prevalence of latex allergy has been increasing not only in risk groups but also in the general population, where it is accepted to average 1%. In children, latex sensitization prevalence studies are scarce and involve different population sampling and allergy testing methods, which makes it difficult to compare across studies. Nevertheless, existing studies point towards a low prevalence of latex allergy in children, which still needs to be confirmed in the Portuguese population. Aiming at studying the prevalence of latex sensitization and allergy in a sample of Portuguese children, we studied 182 children from two different hospital outpatient clinics. A standardized questionnaire focusing on atopic background, previous history and allergic signs or symptoms on exposure to latex or fruits was given to all children and parents. Skin prick testing was performed with a battery of common aeroallergens as well as latex. Serum total IgE, Phadiatop, F x 5E and latex-specific IgE were determined in all children. Specific IgE to latex-crossreacting fruits was determined in latex-sensitized children. Based upon the questionnaire, the prevalence of latex allergy would be 0.5%. The prevalence of latex sensitization would be 3.8%, when based solely upon skin prick testing, and 12.1% (>/=0.35 IU/ml) or 6.6% (>/=0.70 IU/ml) when based singly upon determination of latex-specific IgE. When positive results for either test were considered, the prevalence of latex sensitization was 14.3%. All latex-sensitized children were atopic. Sensitivity to latex-crossreacting foodstuffs was demonstrated in 61.5% of latex-sensitized children (16/26). This study shows that the prevalence of latex allergy and sensitization in Portuguese atopic and non-atopic children, as analysed using various diagnostic methods, is similar to that observed in other countries. In addition, the assessment of latex allergy and sensitization should always include skin prick testing and determination of serum IgE.     

Causes of Death and Risk Factors for Mortality in Patients With Severe Chronic Obstructive Pulmonary Disease

ObjectiveThe objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD).Patients and methodsWe studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV₁] <50%), who were attended in our respiratory department day hospital (2001-2006). Clinical variables were recorded on inclusion, and clinical course and causes of death were retrospectively reviewed.ResultsThe mean (SD) age of patients was 69 (8) years and the mean FEV₁ was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality.ConclusionsMortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.     

Effects of propafenone on calcium current in guinea-pig ventricular myocytes.

1. The modulation of L-type voltage-sensitive calcium channels in guinea-pig isolated ventricular myocytes by propafenone was examined by the whole cell voltage-clamp technique. 2. Propafenone, 10(-7) -5 x 10(-5) M, produced a concentration-dependent inhibition of Ca current (ICa) without any significant change in the current-voltage relation. Half-blocking concentration (IC50) of propafenone for the peak ICa at +10 mV was 5 x 10(-6) M. 3. The voltage-dependence of ICa inactivation was shifted in the hyperpolarizing direction in the presence of 5 x 10(-6) M propafenone. 4. A frequency-dependent relative block by propafenone was observed after repetitive depolarizing test pulses at a frequency of 0.5 and 1 Hz. The recovery of ICa from inactivation was prolonged by propafenone and the reactivation exhibited an additional exponential component attributed to the slow release from drug block of Ca channels. 5. These results suggest that propafenone, at therapeutic concentrations exhibits Ca channel blocking properties that may be involved in its antiarrhythmic mechanism.     

18F-FDG assessment of glucose disposal and production rates during fasting and insulin stimulation: a validation study.

The glucose analog (18)F-FDG is commonly used to quantify regional glucose uptake in vivo. The aim of this study was to test whether the analysis of plasma (18)F-FDG kinetics could be used to estimate endogenous glucose production (EGP) and the total rate of appearance (Ra), total rate of disappearance (Rd), and the metabolic clearance rate (MCR) of glucose. METHODS: Fourteen pigs were coinjected with (18)F-FDG and 6,6-(2)H-glucose ((2)H-G) during fasting (n = 6) and during physiologic (1.0 mU.kg(-1).min(-1), n = 4) and supraphysiologic (5.0 mU.kg(-1).min(-1), n = 4) euglycemic hyperinsulinemia. Arterial plasma was sampled for 180 min to quantify the parameters for the 2 tracers. RESULTS: Fasting Rd((2))(H-G) and Rd(FDG) were 12.3 +/- 2.1 and 13.3 +/- 1.3 micromol.kg(-1).min(-1) (difference not statistically significant [NS]). M values were more than doubled between the 2 clamp studies (P < 0.0001). Rd((2))(H-G) and Rd(FDG) were dose-dependently higher during the hyperinsulinemic state (19.8 +/- 3.7 vs. 18.9 +/- 1.1 and 31.4 +/- 4.1 vs. 31.9 +/- 2.3 in 1.0 and 5.0 mU.kg(-1).min(-1) studies, respectively; difference between tracers NS) than during the fasting state, with a parallel suppression of EGP((2))(H-G) and EGP(FDG). Parameters estimated by (18)F-FDG and (2)H-G were equivalent in all groups; their agreement was confirmed by Bland-Altman examination. Total Rd(FDG) correlated with Rd((2))(H-G) (r = 0.74; P = 0.003), M (r = 0.92; P = 0.001), MCR((2))(H-G) (r = 0.52; P = 0.037), and EGP((2))(H-G) (r = -0.71; P = 0.004). EGP(FDG) correlated with EGP((2))(H-G) (r = 0.62; P = 0.018), Rd((2))(H-G) (r = -0.78; P = 0.001), and MCR((2))(H-G) (r = -0.67; P = 0.008). The (18)F-FDG mean transit time correlated inversely with the M and Rd values and positively with EGP. CONCLUSION: The glucose analog (18)F-FDG can be used in the simultaneous estimation of whole-body glucose turnover and production and regional (18)F-FDG PET measurements under both fasting and insulin-stimulated conditions.     

Chronic Alcohol Ingestion Enhances Tumor Necrosis Factor-α Expression and Salivary Gland Apoptosis

We investigated the extent of induction in sublingual salivary gland cells apoptosis and tumor necrosis factor-α (TNF-α) expression with chronic ethanol ingestion. The experiments were conducted on rats pair-fed for 8 weeks with alcohol-containing and control liquid diet. The animals were killed, their sublingual glands dissected, and the glandular tissue used for quantitization of TNF-α expression and the assays of acinar cells apoptosis employing sandwich enzyme immunoassay for histone-associated DNA fragments. The mean value for TNF-α in sublingual gland of the control group was 22.3 pg/mg of protein and showed a 1.6-fold increase in the chronic ethanol diet group to 36.5 pg/mg of protein. In comparison with the controls, the sublingual gland of the chronic ethanol diet group also exhibited a 3.4-fold enhancement in acinar cell apoptosis. These findings suggest that chronic ethanol ingestion causes the enhancement in TNF-α expression and leads to the induction in salivary gland acinar cells apoptosis. Thus, the diminished secretion of saliva in alcoholics may be a direct result of increased salivary gland apoptosis.     

Molecular epidemiologic studies of polycyclic aromatic hydrocarbon-DNA adducts and breast cancer

We review our studies on the role of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in breast cancer. Additionally we report on analyses of the reliability of the scoring procedures used with immunohistochemical assay for PAH-DNA adducts and of potential bias arising from the use of benign breast disease (BBD) controls. We conducted a case-control study utilizing two control groups: BBD controls who donated tissue and blood samples, and healthy controls who donated blood samples. In comparisons of tumor tissue from cases and benign tissue from BBD controls, increasing adduct levels were significantly associated with case-control status [odds ratio (OR) = 2.40, 95% confidence interval (CI) 1.18-4.92], whereas in comparisons of nontumor tissue from cases and benign tissue from BBD controls the association was nonsignificant (OR = 1.97, 95% CI 0.94-4.17). We also show among cases, but not among BBD controls, that the GSTM1 null genotype is associated with increased adduct levels in breast tissue. Our reliability study found the scoring procedures used with the immunohistochemical assay to have high reliability, 0.93 in nontumor, 0.82 in tumor, and 0.74 in benign tissues. However, we found that the technician significantly contributed to the total variability of a series of data. Finally, we did not find a consistent bias to the null associated with the use of BBD controls; however, BBD controls may overestimate the prevalence of family history of breast cancer compared to that of healthy controls (18% vs.14%). We hypothesize that the higher prevalence results from a referral bias and discuss how this may influence our results.     

Risk factors for pneumonia in urban-dwelling HIV-infected women: a case-control study in Nairobi,Kenya

In sub-Saharan Africa, respiratory tract infections (RTI) are the leading cause of serious morbidity and mortality in HIV-infected persons. This study sought to investigate demographic, socioeconomic, and environmental risk factors for pneumonia in a cohort of HIV-infected women. The authors performed a nested case-control study in a cohort of HIV-1-infected adults followed in Nairobi, Kenya. Thirty-nine women who developed pneumonia during the follow-up period were selected as cases, and 66 women who did not develop pneumonia were randomly chosen to serve as control subjects. A questionnaire was administered in subjects' homes that assessed demographics, home environment, and socioeconomic status. Women were followed in the cohort for a median of 36.8 months (range, 27.3-39.3). Adjusting for length of follow-up period, factors associated with lower socioeconomic status (lower monthly spending [OR = 3.2; 95% CI, 1.2-8.4 per 10,000 Kenyan shilling decrease], having no savings [OR = 4.1; 95% CI, 1.4-11.9], less sturdy home construction material such as mud or cement walls [OR = 2.6; 95% CI, 1.1-5.9] or dirt floors [OR = 2.8; 95% CI, 1.0-7.6], and lack of a window in the home [OR = 5.5; 95% CI, 0.9-32.2]) and being widowed (OR = 4.3; 95% CI, 1.2-15.1) or single (OR = 3.3; 95% CI, 1.0-11.2) were associated with an increased risk of pneumonia. In multivariate analysis, widowed (AOR = 5.9; 95% CI, 1.3-26.3), single (AOR = 7.7; 95% CI, 1.6-36.4), and divorced (AOR = 4.5; 95% CI, 1.0-20.1) women, those without savings (AOR = 3.7; 95% CI, 1.2-11.7), and those living in more crowded and contagious conditions (AOR = 1.5; 95% CI, 1.1-2.1) remained at increased risk of pneumonia. If confirmed by prospective investigation, these findings could help identify persons and subpopulations of HIV-infected women with the greatest risk of pneumonia.