The 118 A > G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease.

BACKGROUND: Dispositions for genes encoding opioid receptors may explain some variability in morphine efficacy. Experimental studies show that morphine and morphine-6-glucuronide are less effective in individuals carrying variant alleles caused by the 118 A > G polymorphism in the mu-opioid receptor gene (OPRM1). The purpose of the study was to investigate whether this and other genetic polymorphisms in OPRM1 influence the efficacy of morphine in cancer pain patients. METHODS: We screened 207 cancer pain patients on oral morphine treatment for four frequent OPRM1 gene polymorphisms. The polymorphisms were the -172 G > T polymorphism in the 5'untranslated region of exon 1, the 118 A > G polymorphism in exon 1, and the IVS2 + 31 G > A and IVS2 + 691 G > C polymorphisms, both in intron 2. Ninety-nine patients with adequately controlled pain were included in an analysis comparing morphine doses and serum concentrations of morphine and morphine metabolites in the different genotypes for the OPRM1 polymorphisms. RESULTS: No differences related to the -172 G > T, the IVS2 + 31 G > A and the IVS2 + 691 G > C polymorphisms were observed. Patients homozygous for the variant G allele of the 118 A > G polymorphism (n = 4) needed more morphine to achieve pain control, compared to heterozygous (n = 17) and homozygous wild-type (n = 78) individuals. This difference was not explained by other factors such as duration of morphine treatment, performance status, time since diagnosis, time until death, or adverse symptoms. CONCLUSION: Patients homozygous for the 118 G allele of the mu-opioid receptor need higher morphine doses to achieve pain control. Thus, genetic variation at the gene encoding the mu-opioid receptor contributes to variability in patients' responses to morphine.

Loss of stress-induced expression of catalase3 during leaf senescence in Arabidopsis thaliana is restricted to oxidative stress.

Different stress conditions can induce changes in the activity of the antioxidant enzymes superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11) and catalase (CAT, EC 1.11.1.6). The enzyme activities of all SOD and APX isoforms detected in young Arabidopsis leaves remained unaffected or slightly decreased after moderate paraquat treatment. While CAT2 activity also remained unaffected under these conditions, CAT3 enzyme activity was enhanced. In contrast to the enzyme activities, mRNA levels of both cat2 and cat3 were enhanced under oxidative stress induced by either paraquat or the fungal toxin cercosporin. This indicates that, with respect to enzyme activity level, CAT3 is the enzyme which is most sensitive to oxidative stress in this developmental stage and that the enzyme activity of CAT2 is possibly regulated at the post-transcriptional level. Interestingly, cat3 mRNA level and CAT3 activity are not elevated by paraquat treatment in senescing leaves. In contrast, the response to other stress conditions, such as water stress induced by flooding of detached leaves and heat stress, is maintained in senescing leaves. Since changes in stress response are not a general phenomenon in leaf senescence but appear to be restricted to oxidative stress, this might be a specific mechanism to promote senescence in Arabidopsis thaliana.

Baggage handling postures and the design of conveyors.

The main purpose of this study was to determine the height, angle and velocity of conveyors for baggage handling at Schiphol Airport. These variables have a great influence on the postures and workload of baggage handlers. One hundred and seven healthy male baggage handlers participated in a test, during which a regular baggage handling task was simulated with a mock-up. Eighteen combinations of heights, angles and velocities were tested. Data on postures were collected with the aid of task recording and analysis on computer (TRAC). The minimal volume of open space under the conveyor was determined with light cells that scored the positions of legs and feet of the subjects. In addition, opinions from the baggage handlers were gathered with a questionnaire, immediately after the test. Finally the number of selection errors made and the number of bags that fell off the conveyor were noted, to make sure that ergonomics improvements did not reduce the quality of baggage handling. On the basis of these three information sources, alternative conveyor dimensions were recommended, which are expected to improve the working conditions of the baggage handlers, without any reduction in the quality of work.

Coordination of the leg muscles in backlift and leglift.

Net joint moments are often used to quantify the loading of structures (e.g. the intervertebral disc at L5S1) during lifting. This quantification method is also used to evaluate the loading of the knee, for instance, to determine the effect of backlifting as opposed to leglifting. However, the true loading of the joint as derived from net joint moments can be obscured by a possible co-contraction of antagonists. To unravel the mechanisms that determine the net joint moments in the knee, the leglift was compared to the backlift. Although a completely different net knee moment curve was found when comparing the two lifting techniques, it appeared to be closely related to the ground reaction force vector and its orientation with respect to the joint centre of rotation (R > 0.995). This close relation was established by co-contraction of both flexors and extensors of the knee. Furthermore, a close relation appeared to exist between the joint moment difference between hip and knee and the activity difference between rectus femoris muscle and hamstring (R = 0.72 and 0.83 in leglift and backlift, respectively). The knee-ankle joint moment difference and the activity of the gastrocnemius showed a close relation as well (R = -0.89 and 0.96 in leglift and backlift, respectively). These relations can be interpreted as a mechanism to distribute net moments across joints. It is concluded that during lifting tasks the intermuscular coordination is aimed at coupling of joint moments, such that the ground reaction force points in a direction that provides balance during the movement. The use of net joint moments as direct indicators for joint loading (e.g. knee) seems, therefore, questionable.