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.      

Exploring the decision-making preferences of people with colorectal cancer

OBJECTIVES: To explore patient views on participation in treatment, physical care and psychological care decisions and factors that facilitate and hinder patients from making decisions. DESIGN: Qualitative study using semi-structured interviews with patients. SETTING AND PARTICIPANTS: Three NHS Trusts in the north-west of England. Theoretical sampling including 41 patients who had been treated for colorectal cancer. RESULTS: For patients, participation in the decision-making process was about being informed and feeling involved in the consultation process, whether patients actually made decisions or not. The perceived availability of treatment choices (surgery, radiotherapy, chemotherapy) was related to type of treatment. Factors that impacted on whether patients wanted to make decisions included a lack of information, a lack of medical knowledge and trust in medical expertise. Patients perceived that they could have a more participatory role in decisions related to physical and psychological care. CONCLUSION: This study has implications for health professionals aiming to implement policy guidelines that promote patient participation and shared partnerships. Patients in this study wanted to be well informed and involved in the consultation process but did not necessarily want to use the information they received to make decisions. The presentation of choices and preferences for participation may be context specific and it cannot be assumed that patients who do not want to make decisions about one aspect of their care and treatment do not want to make decisions about other aspects of their care and treatment.     

Transdermal nitroglycerine enhances spinal neostigmine postoperative analgesia following gynecological surgery

BACKGROUND: Intrathecal neostigmine causes analgesia by inhibiting the breakdown of acetylcholine. Experimental data suggest that the production of endogenous nitric oxide is necessary for tonic cholinergic inhibition of spinal pain transmission. The purpose of this study was to determine whether association of transdermal nitroglycerine would enhance analgesia from a low dose of intrathecal neostigmine in patients undergoing gynecologic surgery during spinal anesthesia. METHODS: Forty-eight patients were randomized to one of four groups. Patients were premedicated with use of 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 1 ml test drug intrathecally (saline or neostigmine, 5 microgram). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control (Con) group received spinal saline and transdermal placebo. The neostigmine group received spinal neostigmine and transdermal placebo. The nitroglycerin group received spinal saline and a transdermal nitroglycerine patch. Finally, the neostigmine-nitroglycerin group received spinal neostigmine and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale. RESULTS: Patients in the groups were similar regarding age, weight, height, and American Society of Anesthesiologists status. Sensory level to pin prick at 10 min, surgical duration, anesthetic duration, and visual analog scale score for pain at the time of administration of first rescue medication were statistically the same for all groups. The time to administration of first rescue analgesic (min) was longer in the neostigmine-nitroglycerin group (550 min; range, 458-1,440 min; median, 25-75th percentile) compared with the other groups (P < 0.001). The neostigmine-nitroglycerin group required fewer rescue analgesics in 24 h than did the control group (P < 0.0005), whereas the neostigmine group required less analgesics compared with the control group (P < 0.02). The incidence of perioperative adverse effects (nausea, vomiting, headache, back pain) was similar among groups (P > 0.05). CONCLUSION: Although neither intrathecal 5 microgram neostigmine alone nor transdermal nitroglycerine alone (5 mg/day) delayed the time to administration of first rescue analgesics, the combination of both provided an average of 14 h of effective postoperative analgesia after vaginoplasty, suggesting that transdermal nitroglycerin and the central cholinergic agent neostigmine may enhance each other's antinociceptive effects at the dose studied.     

Changes in social emotion recognition following traumatic frontal lobe injury

Changes in social and emotional behaviour have been consistently observed in patients with traumatic brain injury. These changes are associated with emotion recognition deficits which represent one of the major barriers to a successful familiar and social reintegration. In the present study, 32 patients with traumatic brain injury, involving the frontal lobe, and 41 ageand education-matched healthy controls were analyzed. A Go/No-Go task was designed, where each participant had to recognize faces representing three social emotions (arrogance, guilt and jealousy). Results suggested that ability to recognize two social emotions (arrogance and jealousy) was significantly reduced in patients with traumatic brain injury, indicating frontal lesion can reduce emotion recognition ability. In addition, the analysis of the results for hemispheric lesion location (right, left or bilateral) suggested the bilateral lesion sub-group showed a lower accuracy on all social emotions.