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.      

Engraftment and growth of transplanted pancreatic islets

Transplantation of pancreatic islets may provide a cure for type 1 diabetes. However, this treatment can currently be offered only to very few patients. To improve transplantation success we need to understand better the mechanisms of how the implanted islets survive, grow and/or maintain adequate function. We herein report on our studies to evaluate the factors responsible for the engraftment, i.e. revascularization, reinnervation etc., of transplanted islets and relate these factors to the metabolism and growth of the islets. Graft metabolism can be monitored by microdialysis probes that allow for the measurement of minute amounts of islet metabolites and hormonal products. Growth of the endocrine cells can be stimulated both in vitro before implantation and in vivo post-transplantation. Another problem is rejection of transplanted islets, which may be overcome by the microencapsulation of islets. The knowledge gained by the present studies will enable us to elucidate the optimal treatment of islets to ensure a maximal survival of the transplanted islets, and may be applied also to clinical islet transplantation.     

DNA damage induced by radiation of different linear energy transfer: initial fragmentation

PURPOSE: To investigate DNA fragmentation as a function of linear energy transfer (LET) after exposure to accelerated ions in the LET range 40-225 keV/microm. MATERIALS AND METHODS: Fragmentation patterns of double-stranded DNA in the range 5 kilobasepairs (kbp) to 5.7 megabasepairs (Mbp) were analysed after irradiation of low-passage GM 5758 normal human fibroblast cells with 60Co-photons, helium ions at 40 keV/microm and high-LET nitrogen ions between 80 and 225 keV/microm. Two separate pulsed-field gel electrophoresis protocols were used, optimized for separation of 1-6 Mbp and 5 kbp to 1.5 Mbp fragments. RESULTS: An increased probability of formation of short and medium-sized DNA fragments was revealed following high-LET irradiation. The DNA double-strand break (dsb) induction yields were, respectively, 5.8 and 6.9-8.8 x 10(-9) dsb bp(-1) Gy(-1) for 60Co-photons and ions. The ion yields were some 80-110% higher than those calculated according to a conventional approach, disregarding the fragment distributions. For photons, the yield was 13% higher. The corresponding relative biological effectiveness (RBE) of dsb induction was in the range 1.2-1.5. CONCLUSIONS: A significant non-random contribution to the number of dsb after irradiation with high-LET was confirmed by detailed fragment analysis using pulsed-field gel electrophoresis. The LET had a strong influence on the initial DNA fragment distribution, and hence also on the induction yields measured. However, when the LET was increased to the highest values studied for nitrogen ions, the yield decreased slightly.     

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.     

Tranexamic acid reduces blood loss in total hip replacement surgery

Intraoperatively administered, tranexamic acid (TA) does not reduce bleeding in total hip replacement (THR). Therefore, its prophylactic use was attempted in the present study because this has been shown to be more effective in cardiac surgery. We investigated 40 patients undergoing THR in a prospective, randomized, double-blinded study. Twenty patients received TA given in two bolus doses of 10 mg/kg each, the first just before surgical incision and the second 3 h later. In addition, a continuous infusion of TA, 1.0 mg. kg(-1). h(-1) for 10 h, was given after the first bolus dose. The remaining 20 patients formed a control group. Both groups used preoperative autologous blood donation and intraoperative autotransfusion. Intraoperative bleeding was significantly less (P: = 0.001) in the TA group compared with the control group (630 +/- 220 mL vs 850 +/- 260 mL). Postoperative drainage bleeding was correspondingly less (P: = 0.001) (520 +/- 280 vs 920 +/- 410 mL). Up to 10 h postoperatively, plasma D-dimer concentration was halved in the TA group compared with the control group. One patient in each group had an ultrasound-verified late deep vein thrombosis. In conclusion, we found TA, administrated before surgical incision, to be efficient in reducing bleeding during THR. Implications: In a prospective, double-blinded study of 40 patients undergoing total hip replacement, the preoperative administration of tranexamic acid reduced bleeding by 35%, probably by decreasing induced fibrinolysis. Whether tranexamic acid therapy can replace predonation of autologous blood or intraoperative autotransfusion requires further study.     

Cholecystectomy: costs and health-related quality of life: a comparison of two techniques.

BACKGROUND: Outcomes of previous health economic evaluations comparing minilaparotomy cholecystectomy and laparoscopic cholecystectomy have been inconsistent. OBJECTIVE: To compare costs for minilaparotomy cholecystectomy and laparoscopic cholecystectomy and to study changes in quality of life induced by these operations. DESIGN: Single-blind, randomized controlled trial, run from 1 March 1997 to 30 April 1999. SETTING: One university hospital and four non-university hospitals in Sweden. MAIN MEASURE: : Cost and perceived health estimation according to the global quality of life instrument EuroQol-5D. RESULTS: Of 1719 cholecystectomy patients at five centres, 724 entered the trial and were treated with minilaparotomy cholecystectomy or laparoscopic cholecystectomy, 362 in each group. Total health care costs were less for minilaparotomy cholecystectomy than for laparoscopic cholecystectomy (median values US$2428 for minilaparotomy cholecystectomy versus US$2613 or US$3006 for laparoscopic cholecystectomy with 100 operations per year and reusable trocars or 50 operations per year and disposable trocars, respectively). There was no significant difference in total costs (including costs due to loss of production) between minilaparotomy cholecystectomy and laparoscopic cholecystectomy with 100 operations per year and reusable trocars in laparoscopic cholecystectomy (US$3731 versus US$3649, respectively). However, in calculations assuming 50 operations per year and disposable trocars in laparoscopic cholecystectomy, this technique was more expensive than minilaparotomy cholecystectomy (US$4042 versus US$3731). Health-related quality of life was slightly but significantly lower for the minilaparotomy cholecystectomy group 1 week after surgery. One month and 1 year postoperatively no difference between the randomized groups was found. CONCLUSION: Total costs did not differ between minilaparotomy cholecystectomy and laparoscopic cholecystectomy with high-volume surgery and disposable trocars, whereas laparoscopic cholecystectomy was more expensive with fewer operations and disposable trocars. The gain in health-related quality of life with laparoscopic cholecystectomy compared with minilaparotomy cholecystectomy was small and of limited duration.     

Improvement of urge- and mixed-type incontinence after acupuncture treatment among elderly women - a pilot study

The aim of this study was to investigate if sensory stimulation in the form of manual acupuncture could influence urge- or mixed-type incontinence among elderly women who were not satisfactorily relieved by standard pharmacological and non-pharmacological treatments given at a specialised incontinence unit. The study is an open clinical follow-up study. The study included 15 elderly women who were treated with manual acupuncture 12 times. Both subjective scorings and objective measurements in the form of leakage in grams (48 h Inco-test) were used. Evaluations were performed at discharge and 1 and 3 months thereafter. Almost all outcome measurements were significantly improved even at follow-up 3 months after the last treatment. Global scorings showed that 12 of the 15 women considered themselves improved even at the follow-up 3 month after treatments were completed. The possible mechanisms of action are discussed, as is the way to perform more studies in this field.