Randomised controlled trial of exercise for low back pain : clinical outcomes, costs and preferences

Objective: To evaluate effectiveness of an exercise programme in a community setting for patients with low back pain to encourage a return to normal activities. Design: Randomised controlled trial of progressive exercise programme compared with usual primary care management. Patients' preferences for type of management were elicited independently of randomisation. Participants: 187 patients aged 18-60 years with mechanical low back pain of 4 weeks to 6 months' duration. Interventions: Exercise classes led by a physiotherapist that included strengthening exercises for all main muscle groups, stretching exercises, relaxation session, and brief education on back care. A cognitive-behavioural approach was used. Main outcome measures: Assessments of debilitating effects of back pain before and after intervention and at 6 months and 1 year later. Measures included Roland disability questionnaire, Aberdeen back pain scale, pain diaries, and use of healthcare services. Results: At 6 weeks after randomisation, the intervention group improved marginally more than the control group on the disability questionnaire and reported less distressing pain. At 6 months and 1 year, the intervention group showed significantly greater improvement in the disability questionnaire score (mean difference in changes 1.35, 95% confidence interval 0.13 to 2.57). At 1 year, the intervention group also showed significantly greater improvement in the Aberdeen back pain scale (4.44, 1.01 to 7.87) and reported only 378 days off work compared with 607 in the control group. The intervention group used fewer healthcare resources. Outcome was not influenced by patients' preferences. Conclusions: The exercise class was more clinically effective than traditional general practitioner management, regardless of patient preference, and was cost effective

Synthesis and Biological Evaluation of Analogues of AKT (Protein Kinase B) Inhibitor-IV

Inhibitors of the PI3-kinase/AKT (protein kinase B) pathway are under investigation as anticancer and antiviral agents. The benzimidazole derivative AKT inhibitor-IV (ChemBridge 5233705) affects this pathway and exhibits potent anticancer and antiviral activity. To probe its biological activity, we synthesized AKT inhibitor-IV and 21 analogues using a novel six-step route based on ZrCl4-catalyzed cyclization of 1,2-arylenediamines with α,β-unsaturated aldehydes. We examined effects on viability of HeLa carcinoma cells, viability of normal human cells (NHBE), replication of recombinant parainfluenza virus 5 (PIV5) in HeLa cells, and replication of the intracellular bacterium Mycobacterium fortuitum in HeLa cells. Replacement of the benzimidazole N-ethyl substitutent of AKT inhibitor-IV with N-hexyl and N-dodecyl groups enhanced antiviral activity and cytotoxicity against the cancer cell line, but these compounds showed substantially lower toxicity (from 6-fold to >20-fold) against NHBE cells, and no effect on M. fortuitum, suggesting inhibition of one or more host protein(s) required for proliferation of cancer cells and PIV5. The key structural elements identified here may facilitate identification of targets of this highly biologically active scaffold

An analysis of the refuge area concept as an adequate life safety system in high-rise buildings

M.S.John Arche

Acute fatigue in chronic fatigue syndrome

Background:- Chronic fatigue syndrome (CFS) patients often complain that they are more susceptible to acute mental fatigue. It is important to determine whether this is observed using objective tests of sustained attention and responding. Methods:- Sixty-seven patients who fulfilled the criteria for CFS proposed by Sharpe et al. (1991) were compared with 126 matched healthy controls. Acute fatigue was assessed by comparing performance at the start and end of a lengthy test session and by examining changes over the course of individual tasks. Results:- CFS patients showed impaired performance compared to the controls and these differences increased as the volunteers developed acute fatigue. In addition, differences between the two groups were larger at the end of the test session. Conclusions:- The present results show that CFS patients are more susceptible to acute fatigue than healthy controls. This could reflect motor fatigue or an inability to compensate for fatigue with increased effort. This profile is consistent with previous research on fatigue and suggests that interpretation of certain aspects of CFS may be helped by considering it as the end point of a continuum of fatigue rather than a distinct disease