Induction of unscheduled DNA synthesis in suspensions of rat hepatocytes by an environmental toxicant, 3,3'4,4'-tetrachloroazobenzene.

Unscheduled DNA synthesis was induced by 3,3'4,4'-tetrachloroazobenzene (TCAB)) in freshly isolated suspensions of rat hepatocytes. A dose-dependent response was demonstrated. Hepatocellular DNA was obtained after the chloroform-isoamyl alchohol-phenol extraction of the isolated nuclei. The induction of unscheduled DNA synthesis was measured by the incorporation of [3H]-thymidine in the presence of hydroxyurea as determined by the scintillation counting assay. DNA repair data obtained in this study on benzo[a]pyrene and methyl methanesulfonate are comparable to a previous report using primary cultures of hepatocytes and cesium chloride gradients. Hence, the present method offers promise as a rapid and sensitive screen for chemical carcinogens.     

Physical activity and diabetes risk in postmenopausal women

BACKGROUND: To evaluate the hypothesis that physical activity independently predicts type 2 diabetes risk in postmenopausal African-American, Hispanic, Asian, and Caucasian women. METHODS: We prospectively evaluated the relationship between incident type 2 diabetes, walking, and total physical activity at baseline in the Women's Health Initiative Observational Study. Baseline data were collected between September 1994 and December 1998; incident diabetes was identified through August 2002. Hazard ratios for self-reported diabetes adjusted for body mass index (BMI) and other variables were evaluated across categories of physical activity in Caucasian, African-American, Hispanic, and Asian/Pacific Islander women. RESULTS: Incident diabetes was reported by 2.2% of Caucasian, 6.2% of African-American, 4.5% of Hispanic, 3% of Asian, and 5.7% of American Indian women (p <0.0001 across ethnic groups) during 458,018 woman-years of follow-up. Among Caucasian women, walking (multivariate-adjusted hazard ratios 1.00, 0.85, 0.87, 0.75, 0.74; p <0.001 for trend across exercise quintiles) and total physical activity score (hazard ratios 1.00, 0.88, 0.74, 0.80, 0.67; p =0.002) demonstrated a strong inverse relationship with diabetes risk. In BMI-adjusted models, African-American women in higher physical activity categories were less likely to develop diabetes than women in the lowest physical activity category. After adjusting for age and multiple risk factors, however, no significant association between physical activity and diabetes risk was apparent for African-American, Hispanic, or Asian women. CONCLUSIONS: These findings suggest a stronger and more independent association of physical inactivity with development of diabetes in Caucasian women than in minority women, but could also be explained by less precise risk estimates in minority women or the role of chance.     

Streptococcal toxic shock syndrome in children without skin and soft tissue infection: report of four cases

Streptococcal toxic shock syndrome is a fulminant, highly fatal disease characterized by evidence of group A beta-haemolytic streptococcus infection and early shock with consecutive organ failure. In adults, affected individuals usually have preceding skin or soft tissue infection. However, in paediatric patients, except for varicella, the background focus is usually respiratory tract infection, and early diagnosis of streptococcal toxic shock syndrome in such patients is difficult. We report four previously healthy children with streptococcal toxic shock syndrome. Pharyngitis was identified in three cases. All of them had constitutional symptoms such as fever, vomiting, diarrhoea, abdominal pain and physical findings of tachycardia and diffuse abdominal tenderness, but no concomitant skin infection. CONCLUSION: Streptococcal toxic shock syndrome should be considered in paediatric patients with fever, vomiting, diarrhoea, abdominal pain and early shock. Early diagnosis, prompt initiation of antibiotics and aggressive fluid therapy are lifesaving for such patients.     

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial

Context  Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. Objective  To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. Intervention  Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. Main Outcome Measures  The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. Results  In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. Conclusions  The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.      

Nivalenol, a main Fusarium toxin in dietary foods from high-risk areas of cancer of esophagus and gastric cardia in China, induced benign and malignant tumors in mice

This is the first report that a Fusarium toxin nivalenol (NIV) naturally existing at high levels in dietary food in high-risk areas of cancer of esophagus and gastric cardia in China induced benign and malignant tumors in mice. The levels of two Fusarium toxins, nivalenol and deoxynivalenol (DON) were quantitated using high performance liquid chromatography (HPLC) in a total of 97 samples of dietary wheat flour, barley and corn collected from families in two areas with high mortality rate of cancer of esophagus and gastric cardia (132/100,000), Linxian, Henan province and Cixiang, Hepei province, China. The mean level of NIV and DON in three dietary foods was 830+/-927 microg/kg (range 584-1,780 microg/kg) and 4,281+/-6,114 microg/kg (range 732-10,980 microg/kg) respectively. The highest mean level of NIV was 1,780+/-1,705 microg/kg found in barley from Linxian, that of DON was 10,980+/-10,139 microg/kg found in corn from Cixiang. NIV was undetectable in 2 samples of rice from USA. The mean levels of NIV in three main dietary foods in those two high-risk areas were estimated at 400 to 800-fold higher than that in the USA, where NIV was undetectable in dietary food, and the mortality rate of esophageal cancer is <5/100,000 in white Caucasians in the USA, (odds ratio was estimated at 17-34, p<0.000005). These data suggest that Linxian and Cixiang peasants who consumed a diet with high NIV had significantly higher risk for developing esophageal cancer than the US residents who consumed food without or with negligible amounts of NIV. Three repeated experiments were performed using Balb/C mice with inter-mittent application of NIV, alternate with 12-Tetradeconoyl-phorbol-13-acetate (TPA) application on skin. Papillomas and carcinomas developed in a total of 23/49 (47%) mice that survived 11-60 weeks of experiments. Among all the tumors, 4 carcinomas in 3 mice were identified. No tumors were found in the 60 control mice applying either TPA or acetone (solvent) only on skin.     

Pearls of wisdom for clinical teaching: expert educators reflect

A group of expert educators, each with more than 20 years of experience in midwifery education, was asked to contribute a "pearl (or pearls) of wisdom" for clinical teaching. Despite minimal instructions regarding what type of wisdom was being solicited, remarkable similarities emerged from the educators' contributions. Themes included the need for self-evaluation to become a competent preceptor, the role-modeling function of the preceptor, the development of critical thinking in students, the need to appreciate students' varying learning styles and individual ways of functioning, and the use of positive reinforcement. Although these may seem like universally accepted concepts in clinical teaching, one contributor related stories she heard from students about "hazing" behaviors that have a negative impact on learning. This points to the need for ongoing education about being an educator, another theme echoed in several of the contributions.