Case-finding for COPD clinic acceptability to patients in GPs across Hampshire: a qualitative study.

Despite high mortality and morbidity, COPD remains under-diagnosed. Case-finding strategies are possible, but patients' perspectives are unexplored. Using qualitative methods, we explored the patient perspective of a case-finding intervention among at-risk patients in primary care. Semi-structured telephone interviews were transcribed and thematic analysis utilised. Seven patients without (mean age 64.5 years (58-74), n = 4) and 8 with obstructed spirometry (mean age 63.5 (53-75), n = 4) were interviewed. Themes identified were motives, challenges and concerns regarding attending the clinic. These included wanting to be well; to help with research; concern over negative impact to life from COPD diagnosis; perceived utility of the clinic; quality of information given; staff manner, approachability and knowledge; and perceived effects of the clinic on lifestyle, self-management and symptoms. The intervention was generally deemed useful and reassuring, although shared information was too detailed or irrelevant for some. Several reported positive lifestyle changes, improved symptoms and improved self-management.

Optimizing laparoscopic task efficiency: the role of camera and monitor positions.

BACKGROUND: Alterations of video monitor and laparoscopic camera position may create perceptual distortion of the operative field, possibly leading to decreased laparoscopic efficiency. We aimed to determine the influence of monitor/camera position on the laparoscopic performance of surgeons of varying skill levels. METHODS: Twelve experienced and 12 novice participants performed a one-handed task with their dominant hand in a modified laparoscopic trainer. Initially, the camera was fixed directly in front of the participant (0 degrees) and the monitor location was varied between three positions, to the left of midline (120 degrees), directly across from the participant (180 degrees), and to the right of the midline (240 degrees). In the second experiment monitor position was constant straight across from the participant (180 degrees) while the camera position was adjusted between the center position (0 degrees), to the left of midline (60 degrees), and to the right of midline (300 degrees). Participants completed five trials in each monitor/camera setting. The significance of the effects of skill level and combinations of camera and monitor angle were evaluated by analysis of variance (ANOVA) for repeated measures using restricted maximum likelihood estimation. RESULTS: Experienced surgeons completed the task significantly faster at all monitor/camera positions. The best performance in both groups was observed when the monitor and camera were located at 180 degrees and 0 degrees, respectively. Monitor positioning to the right of midline (240 degrees) resulted in significantly worse performance compared to 180 degrees for both experienced and novice surgeons. Compared to 0 degrees (center), camera position to the left or the right resulted in significantly prolonged task times for both groups. Novice subjects also demonstrated a significantly lower ability to adjust to suboptimal camera/monitor positions. CONCLUSION: Experienced subjects demonstrated superior performance under all study conditions. Optimally, the camera should be directly in front and the monitor should be directly across from a surgeon. Alternatively, the monitor/camera could be placed opposite to the surgeon's non-dominant hand. The suboptimal camera/monitor conditions are especially difficult to overcome for inexperienced subjects. Monitor and camera positioning must be emphasized to ensure optimal laparoscopic performance.

Characterization of multidrug resistance-associated protein 2 in the hepatocellular disposition of 4-hydroxynonenal.

4-hydroxynonenal (4HNE) is a major product of peroxidative membrane lipid destruction and exerts a variety of deleterious actions through formation of covalent adducts with cellular nucleophiles. Consequently, a number of cellular enzyme systems exist that are capable of detoxifying this reactive aldehyde by oxidation, reduction, or conjugation with glutathione. In this investigation we characterize the multidrug resistance-associated protein 2 (MRP2) as the primary transmembrane transport protein in hepatocytes responsible for extracellular export of 4HNE-glutathione conjugate (HNE-SG) from the intracellular site of its formation. Suspensions of freshly isolated hepatocytes (10(6) cells/ml) prepared from either wild-type (WT) Wistar rats or TR(-) rats possessing a mutated Mrp2 gene were incubated with 4HNE (50 nmol/10(6) cells). The formation of 4HNE metabolites, 4-hydroxynonenoic acid (HNA) and HNE-SG, was quantified in the intracellular and extracellular fractions. These studies demonstrated that freshly isolated hepatocytes from both WT and TR(-) rats formed and exported the oxidized metabolite (HNA) to similar extents. Likewise, both populations of hepatocytes displayed nearly identical rates of glutathione conjugation with 4HNE. However, the rate of HNE-SG export from TR(-) hepatocytes was approximately fourfold less than that of WT hepatocytes. In TR(-) hepatocytes, HNE-SG accumulated and remained predominantly intracellular throughout the time course, suggesting an absence of compensatory export by other hepatocellular transporters. In conclusion, these data demonstrate that although WT and TR(-) hepatocytes are similar in their conjugative and oxidative metabolism of 4HNE, export of 4HNE-SG is mediated by the MRP2 transporter, a transport system distinct from that involved in HNA efflux.

4-hydroxynonenal decreases interleukin-6 expression and protein production in primary rat Kupffer cells by inhibiting nuclear factor-kappaB activation.

Kupffer cells have been documented to play an important role in the early events of liver injury and regeneration by releasing biologically active mediators such as interleukin-6 (IL-6). 4-Hydroxy-trans-2-nonenal (4-HNE), a major end product of lipid peroxidation, has multiple cytotoxic effects and is implicated in chemical-induced liver injury. Consequently, the purpose of this study was to evaluate the ability of 4-HNE to modulate IL-6 production in isolated primary rat Kupffer cells. 4-HNE (0.1-10 microM) reduced both lipopolysaccharide (LPS)-induced IL-6 protein production and mRNA levels. The role of nuclear factor-kappaB (NF-kappaB) in IL-6 induction was elucidated using Kupffer cells transduced in vitro with a recombinant adenovirus containing a IkappaBalpha super-repressor resistant to phosphorylation and degradation (Ad5IkappaB). Using this system, LPS-induced IL-6 protein production was inhibited by 65% in Ad5IkappaB-infected cells. The treatment of Kupffer cells for 1 h with 4-HNE followed by stimulation for 1 h with LPS (500 ng/ml) resulted in a concentration-dependent decrease in NF-kappaB activation. Similarly, decreased NF-kappaB activity in these cells paralleled a reduction in IkappaBalpha mRNA levels. Furthermore, upon LPS stimulation, 4-HNE stabilized IkappaBalpha, which corresponded to a decrease in phosphorylated IkappaBalpha. At lower 4-HNE concentrations (0-5 microM), interactions between p65 and IkappaBalpha proteins were maintained as detected by immunoprecipitation-immunoblot analyses. In conclusion, these data suggest that 4-HNE inhibits IL-6 production in rat Kupffer cells by preventing activation of the NF-kappaB pathway and suppressing IkappaBalpha phosphorylation. These results have functional implications in that 4-HNE may interfere with the ability of Kupffer cells to produce cytokines proposed to play an important role in liver regeneration.