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.      

Radiologically placed temporary hepatic artery catheter for treatment of liver cancer

Hepatic artery infusion (HAI) chemotherapy is associated with higher response rates compared to systemic chemotherapy in those patients with unresectable liver malignancies. Operative hepatic artery catheter (HAC) insertion has significant morbidity and mortality, especially in patients with high‐volume disease, some of whom may not respond to HAI chemotherapy. We report our experience in 45 patients with high‐volume liver disease who were initially treated with HAI chemotherapy via a radiologically placed temporary HAC to try to select the responders who then went on to have an operative HAC. In these 45 patients who had 62 radiologically placed HAC, we found very few major complications, and certainly no complications such as cholecystitis, vascular or malperfusion problems.     

Assembly and Maturation of a T = 4 Quasi-Equivalent Virus Is Guided by Electrostatic and Mechanical Forces

Nudaurelia capensis ω virus (NωV) is a eukaryotic RNA virus that is well suited for the study of virus maturation. The virus initially assembles at pH 7.6 into a marginally stable 480-Å procapsid formed by 240 copies of a single type of protein subunit. During maturation, which occurs during apoptosis at pH 5.0, electrostatic forces guide subunit trajectories into a robust 410-Å virion that is buttressed by subunit associated molecular switches. We discuss the competing factors in the virus capsid of requiring near-reversible interactions during initial assembly to avoid kinetic traps, while requiring robust stability to survive in the extra-cellular environment. In addition, viruses have a variety of mechanisms to deliver the genome, which must remain off while still inside the infected cell, yet turn on under the proper conditions of infection. We conclude that maturation is the process that provides a solution to these conflicting requirements through a program that is encoded in the procapsid and that leads to stability and infectivity.     

Sleep and Sleep-Wake Disturbances in Care Recipient-Caregiver Dyads in the Context of a Chronic Illness: A Critical Review of the Literature

ContextAlterations in sleep-wake patterns of care recipients and their informal caregivers are common in the context of a chronic illness. Given the current notion that sleep may be regulated within and affected by close human relationships, concurrent and interrelated sleep problems may be present in care recipient-caregiver dyads.ObjectivesTo critically analyze evidence regarding concurrent sleep patterns or changes in care recipient-caregiver dyads in the context of a chronic illness and address methodological and research gaps.MethodsUsing a wide range of key terms and synonyms, three electronic databases (Medline, CINAHL, and Embase) were systematically searched for the period between January 1990 and July 2011.ResultsTen studies met prespecified selection criteria and were included for analysis. Study quality was fair to good on average. Seven studies were conducted in the context of dementia or Parkinson's disease, two in the context of cancer, and one study included a group of community elders with mixed related comorbidities and their informal caregivers. Bidirectional associations in the sleep of care recipient-caregiver dyads seem to exist. Concurrent and comparable nocturnal sleep disruptions also may be evident. Yet, inconsistencies in the methods implemented, and the samples included, as well as uncertainty regarding factors coaffecting sleep, still preclude safe conclusions to be drawn on.ConclusionThe dyadic investigation of sleep is a promising approach to the development of truly effective interventions to improve sleep quality of care recipients and their caregivers. Nevertheless, more systematic, longitudinal dyadic research is warranted to augment our understanding of co-occurrence and over time changes of sleep problems in care recipient-caregiver dyads, as well as to clarify covariates/factors that appear to contribute to these problems within the dyad and across time and context of illness.