Genetic polymorphism and cancer risk

Inter-individual variability in carcinogen metabolism has been attributed in part to the polymorphic expression of several phase I and II detoxification enzymes. The role of these genetic polymorphisms in cancer susceptibility has been most extensively evaluated for isozymes of cytochrome P450 (CYP1A1, CYP2D6, and CYP2E1), N-acetyltransferase (NAT1 and NAT2), glutathione S-transferase (GSTM1, GSTT1, and GSTP1), microsomal epoxide hydrolase, and NAD(P)H:quinone oxidoreductase. Our understanding of the genetic basis of cancer risk has been enhanced most recently by establishment of genotype-phenotype correlations in humans and identification of numerous diverse factors, both genetic and environmental, that can modify risk.     

Outcomes in CCG-2961, a children's oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children's oncology group

CCG-2961 incorporated 3 new agents, idarubicin, fludarabine and interleukin-2, into a phase 3 AML trial using intensive-timing remission induction/consolidation and related donor marrow transplantation or high-dose cytarabine intensification. Among 901 patients under age 21 years, 5-year survival was 52%, and event-free survival was 42%. Survival improved from 44% between 1996 and 1998 to 58% between 2000 and 2002 (P = .005), and treatment-related mortality declined from 19% to 12% (P = .025). Partial replacement of daunomycin with idarubicin in the 5-drug induction combination achieved a remission rate of 88%, similar to historical controls. Postremission survival was 56% in patients randomized to either 5-drug reinduction or fludarabine/cytarabine/idarubicin. For patients with or without a related donor, respective 5-year disease-free survival was 61% and 50% (P = .021); respective survival was 68% and 62% (P = .425). Donor availability conferred no benefit on those with inv(16) or t(8;21) cytogenetics. After cytarabine intensification, patients randomized to interleukin-2 or none experienced similar outcomes. Factors predictive of inferior survival were age more than 16 years, non-white ethnicity, absence of related donor, obesity, white blood cell count more than 100 000 x 10(9)/L, -7/7q-, -5/5q-, and/or complex karyotype. No new agent improved outcomes; experience may have contributed to better results time.     

Group A streptococcal infections

? GAS is a common cause of upper respiratory tract and skin infections.? Based on strong research evidence, (1) throat culture is the gold standard for diagnosing GAS pharyngitis.? Based on strong research evidence, (1) oral penicillin V K is the antibiotic treatment of choice for GAS pharyngitis because of its efficacy, safety, and narrow spectrum.? Based on strong research evidence, (2) primary prevention of complications of GAS such as ARF involves prompt diagnosis and antibiotic treatment of GAS pharyngitis.? GAS nonsuppurative and suppurative complications may occur and are mediated by interactions between GAS antigens or exotoxins and the patient’s immunesystem.     

Smoking in Boston bars before and after a 100% smoke-free regulation: an assessment of early compliance.

The objective of this study was to assess compliance with Boston's 100% smoke-free bar regulation within the first 3 months of implementation. An observational survey was conducted of a random sample of 102 bars in Boston before and after the smoking ban went into effect. Forty bars were observed both pre- and postban, serving as a true comparison group; 62 additional bars were observed postban only. From preban to postban, highly significant decreases were found in the mean proportion of patrons smoking inside (22.5% to 0.19%, p < 0.0001), in the proportion of bars with smoking patrons (100% to 2.5%, p < 0.0001), and in the average number of ashtrays present in each bar (24 to 0, p < 0.0001). A highly significant increase was found in the average number of "no smoking" signs posted in each bar (0 to 3.3, p < 0.0001). Within the 3 months immediately following the 100% smoke-free bar regulation in Boston, bars were highly compliant with the ban, including not allowing patrons and employees to smoke, removing ashtrays, and posting signs indicating that smoking is prohibited. Therefore, with proper time and preparation, public health practitioners can change social norms before a ban goes into effect and can implement smoke-free policies smoothly and with immediate compliance.     

The effects of maternal betamethasone administration on the intrauterine growth-restricted fetus

Intrauterine growth restriction (IUGR) is associated with altered fetal cardiovascular function to ensure adequate perfusion of essential organs. IUGR fetuses are at risk of preterm delivery and so are likely to receive antenatal glucocorticoids to promote lung maturation. Because glucocorticoids alter vascular tone, we questioned whether such treatment may induce fetal cardiovascular alterations. Using pregnant sheep carrying twins, we induced IUGR at approximately 0.7 gestation by single umbilical artery ligation in one twin, using the other twin as a control. In each fetus, we monitored carotid blood flow and arterial blood gases. We administered 11.4 mg betamethasone (n = 5) or vehicle (n = 4) to the ewe on d 5 (BM1) and 6 (BM2) postsurgery. On d 7, fetal brains were collected for immunohistochemistry. In control fetuses, carotid blood flow decreased 3.5 h post-BM1 by 24% (P < 0.001), returning to baseline at 5.5 h. In IUGR fetuses, carotid flow decreased 2.5 h post-BM1 by 27% and then increased by 25% over baseline, peaking at 11 h (P < 0.001). Compared to control + saline, we observed a significant increase in oxidative damage (4-hydroxynonenal-positive cells) in the fetal hippocampus and subcallosal area of all treatment groups (IUGR + BM > IUGR + saline = control + BM). There was a significant correlation between carotid blood flow reperfusion after betamethasone and the number of 4-hydroxynonenal-positive cells in the cortex and hippocampus. These data suggest that antenatal betamethasone may induce brain injury in the IUGR fetus but not in the normally grown fetus.     

The maternal-effect, selfish genetic element Medea is associated with a composite Tc1 transposon

Maternal-Effect Dominant Embryonic Arrest ("Medea") factors are selfish nuclear elements that combine maternal-lethal and zygotic-rescue activities to gain a postzygotic survival advantage. We show that Medea(1) activity in Tribolium castaneum is associated with a composite Tc1 transposon inserted just downstream of the neurotransmitter reuptake symporter bloated tubules (blot), whose Drosophila ortholog has both maternal and zygotic functions. The 21.5-kb insertion contains defective copies of elongation initiation factor-3, ATP synthase subunit C, and an RNaseD-related gene, as well as a potentially intact copy of a prokaryotic DUF1703 gene. Sequence comparisons suggest that the current distribution of Medea(1) reflects global emanation after a single transpositional event in recent evolutionary time. The Medea system in Tribolium represents an unusual type of intragenomic conflict and could provide a useful vehicle for driving desirable genes into populations.     

Perceptions of Aging in Two Cultures: Korean and American Views on Old Age

The current study investigated whether beliefs about aging vary by culture, age, and gender. The Lasher and Faulkender (Int. J. Aging Hum. Dev., 37:247–259, 1993) Anxiety about Aging scale was administered to 153 American and 167 South Korean men and women divided into three age groups: young (18–39), middle-aged (40–59), and older (60–91) adults. Significant cultural differences were found for the total anxiety scale and three of the four subscales. Compared to Americans, Koreans portrayed higher overall levels of anxiety about aging, and greater fear of old people, psychological concerns, and concerns over physical appearance. For Koreans, younger adults had greater fear of old people, whereas among Americans, older adults had greater fear of old people. In both cultures, the older adults had greater psychological concerns and fear of losses than did the younger groups, and American women showed more anxiety about aging and concerns over physical appearance than their male counterparts. Results are discussed in relation to aging in different cultural contexts.     

Differential HIV Risk Behavior among Men who have Sex with Men Seeking Health-Related Mobile Van Services at Diverse Gay-Specific Venues

Distinguishing between gay venues may provide important information to better understand patterns of environmental influence and HIV/STI behavioral risk among MSM. Massachusetts MSM accessing State Health Department mobile van services (n = 214) at Gay Pride events, bars/clubs, and private safer sex parties completed a one-time, cross-sectional survey via ACASI. In the past 12 months, private safer sex party attendees reported a higher mean number of anonymous partners, were more likely to report meeting sex partners via the Internet, and were more likely to report sex while drunk; in logistic regression analyses, they were less likely to report both unprotected insertive and receptive anal sex in the past year relative to men from other venues. Private safer sex parties may represent a strategy used by some MSM to reduce HIV/STI risk. Differentiating risk behavior by venue type provides valuable information with which to effectively target interventions to reach MSM at greatest risk.