The effects of a 12-week leisure centre-based, group exercise intervention for people moderately affected with multiple sclerosis: a randomized controlled pilot study

<b>Objective:</b> To establish the effects of a 12-week, community-based group exercise intervention for people moderately affected with multiple sclerosis. <b>Design:</b> Randomised controlled pilot trial. <b>Setting:</b> Two community leisure centres. <b>Participants:</b> Thirty-two participants with multiple sclerosis randomised into intervention or control groups. <b>Intervention:</b> The intervention group received 12 weeks of twice weekly, 60-minute group exercise sessions, including mobility, balance and resistance exercises. The control group received usual care. <b>Main outcome measures:</b> An assessor blinded to group allocation assessed participants at baseline, after eight weeks and after 12 weeks. The primary outcome measure was 25-foot (7.6 m) walk time, secondary outcomes assessed walking endurance, balance, physical function, leg strength, body mass index, activity levels, fatigue, anxiety and depression, quality of life and goal attainment. <b>Results:</b> The intervention made no statistically significant difference to the results of participants’ 25-foot walk time. However the intervention led to many improvements. In the intervention group levels of physical activity improved statistically between baseline and week 8 (P < 0.001) and baseline and week 12 (P = 0.005). Balance confidence results showed a significant difference between baseline and week 12 (P = 0.013). Good effect sizes were found for dynamic balance (d = 0.80), leg strength (d = 1.33), activity levels (d = 1.05) and perceived balance (d = 0.94). <b>Conclusion:</b> The results of the study suggest that community-based group exercise classes are a feasible option for people moderately affected with multiple sclerosis, and offer benefits such as improved physical activity levels, balance and leg strength

The effect of cycling using active-passive trainers on spasticity, cardiovascular fitness, function and quality of life in people with moderate to severe Multiple Sclerosis (MS): a feasibility study

Background: Exercise options for those with moderate to high levels of disability are limited. The aim of the study was to evaluate the feasibility of a progressive, four week lower limb cycling programme using active-passive trainers (APT's) on spasticity, cardiovascular fitness, function and quality of life in people with moderate to severe MS. Methods: Participants were in-patients in the Physical Disability Rehabilitation Unit, Queen Elizabeth University Hospital, Glasgow, UK and randomised to APT + usual care or usual care only. The APT group received 30 min of APT (2 min passive warm up, 26 min active cycling, 2 min passive cool down),five days per week for 4 weeks. Outcome measures; Oxygen Uptake Efficiency Slope, Modified Ashworth Scale, Multiple Sclerosis Spasticity Scale, Functional Independence Measure, Timed 25 foot walk test and the MSQOL-54, were taken before and after the intervention period. Symmetry, distance cycled and active participation were also recorded for each cycling session .Results:24 participants were recruited, 15 to the intervention and 9 to the control group. There was a 100% adherence to the intervention and a significant increase in average speed, power output and distance cycled (p< 0.001 for each) over the four weeks. There were no adverse events and both groups improved in average scores for all outcome measures. Conclusions: APT cycling was well tolerated, while the cycling parameters improved it was difficult to separate the effects of the therapy programme and APT cycling. A longer duration, fully powered trial in a community setting is merited

Dual protection against sexually transmitted infections and pregnancy in South Africa

Promotion of simultaneous protection against sexually transmitted infections (STIs) and unintended pregnancy, referred to as dual protection, represents an important public health intervention. We investigated its prevalence and correlates in South Africa. A cross-sectional survey of 929 sexually active women, aged 15-49 years, was conducted in 89 public primary health care clinics, with dual method use and use of condom alone at last sexual intercourse as outcomes. At last intercourse, 12% of women were protected from both STIs and pregnancy. In multivariate analysis, higher education, being unmarried, and multiple sex partnership in the past year were predictors of dual method use, while younger age, higher education and awareness of the dual function of condoms were predictors of condom use alone. Dual protection is low in this population. The predominance of hormonal contraceptive use in South Africa means that increasing barrier method use among hormonal contraceptive users is an important strategy for increasing dual protectio

Cytochrome P450 CYP3A in human renal cell cancer

Renal cell cancer is the main malignant tumour of the kidney and has an increasing incidence. This type of tumour has a poor prognosis and shows intrinsic resistance to several anti-cancer drugs. The CYP3A P450 family, which consists of three closely related forms, is involved in the oxidative activation and deactivation of a variety of carcinogens and several anti-cancer drugs. In this study the presence and cellular localization of CYP3A has been investigated using a combination of immunohistochemistry, immunoblotting and reverse transcriptase polymerase chain reaction (RT-PCR) in renal cell cancer and corresponding normal kidney. CYP3A was consistently expressed in both renal call cancer and in normal kidney. In renal cell cancer, CYP3A was localized to tumour cells and in normal kidney the predominant cellular localization of CYP3A was to proximal tubular epithelial cells. RT-PCR showed that both CYP3A5 mRNA and CYP3A7 mRNA were consistently present in both tumour and normal samples, while CYP3A4 mRNA was present in 65% of tumours and 90% of normal samples. This study indicates that individual members of the CYP3A family are expressed in renal cell cancer. The presence of CYP3A in renal cell cancer might be important in the metabolic potentiation as well as the detoxification of chemotherapeutic agents used to renal cancer. © 1999 Cancer Research Campaig

The effectiveness and satisfaction of web-based physiotherapy in people with spinal cord injury: a pilot randomised controlled trial

Study Design: Pilot randomised controlled trial. Objectives: The aims of this study were to evaluate the effectiveness and participant satisfaction of web-based physiotherapy for people with Spinal Cord Injury (SCI). Setting: Community patients of a national spinal injury unit in a university teaching hospital, Scotland, UK. Methods: Twenty-four participants were recruited and randomised to receive eight weeks of web-based physiotherapy (intervention), twice per week, or usual care (control). Individual exercise programmes were prescribed based upon participant’s abilities. The intervention was delivered via a website (www.webbasedphysio.com) and monitored and progressed remotely by the physiotherapist. Results: Participants logged on to the website an average of 1.4±0.8 times per week. Between-group differences, although not significant were more pronounced for the 6 minute walk test. Participants were positive about using web-based physiotherapy and stated they would be happy to use it again and would recommend it to others. Overall it was rated as either good or excellent. Conclusions: Web-based physiotherapy was feasible and acceptable for people with SCI. Participants achieved good compliance with the intervention, rated the programme highly and beneficial for health and well-being at various states post injury. The results of this study warrant further work with a more homogenous sample

Cytochrome P450 CYP1B1 activity in renal cell carcinoma

Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has a poor prognosis due to its late presentation and resistance to current anticancer drugs. One mechanism of drug resistance, which is potentially amenable to therapeutic intervention, is based on studies in our laboratory. CYP1B1 is a cytochrome P450 enzyme overexpressed in a variety of malignant tumours. Our studies are now elucidating a functional role for CYP1B1 in drug resistance. Cytochrome P450 reductase (P450R) is required for optimal metabolic activity of CYP1B1. Both CYP1B1 and P450R can catalyse the biotransformation of anticancer drugs at the site of the tumour. In this investigation, we determined the expression of CYP1B1 and P450R in samples of normal kidney and RCC (11 paired normal and tumour and a further 15 tumour samples). The O-deethylation of ethoxyresorufin to resorufin was used to measure CYP1B1 activity in RCC. Cytochrome P450 reductase activity was determined by following the reduction of cytochrome c at 550 nm. The key finding of this study was the presence of active CYP1B1 in 70% of RCC. Coincubation with the CYP1B1 inhibitor alpha-naphthoflavone (10nM) inhibited this activity. No corresponding CYP1B1 activity was detected in any of the normal tissue examined (n = 11). Measurable levels of active P450R were determined in all normal (n = 11) and tumour samples (n = 26). The presence of detectable CYP1B1, which is capable of metabolising anticancer drugs in tumour cells, highlights a novel target for therapeutic intervention

Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer

Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P= 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary. © 2001 Cancer Research Campaign http://www.bjcancer.co

Apolipoprotein E4 Polymorphism and Outcomes from Traumatic Brain Injury : A Living Systematic Review and Meta-Analysis

The mortality of traumatic brain injury (TBI) has been largely static despite advances in monitoring and imaging techniques. Substantial variance exists in outcome, not fully accounted for by baseline characteristics or injury severity, and genetic factors likely play a role in this variance. The aims of this systematic review were to examine the evidence for a link between the apolipoprotein E4 (APOE4) polymorphism and TBI outcomes and where possible, to quantify the effect size via meta-analysis. We searched EMBASE, MEDLINE, CINAHL, and gray literature in December 2017. We included studies of APOE genotype in relation to functional adult TBI outcomes. Methodological quality was assessed using the Quality in Prognostic Studies Risk of Bias Assessment Instrument and the prognostic studies adaptation of the Grading of Recommendations Assessment, Development and Evaluation tool. In addition, we contacted investigators and included an additional 160 patients whose data had not been made available for previous analyses, giving a total sample size of 2593 patients. Meta-analysis demonstrated higher odds of a favorable outcome following TBI in those not possessing an ApoE e4 allele compared with e4 carriers and homozygotes (odds ratio 1.39, 95% confidence interval 1.05 to 1.84; p = 0.02). The influence of APOE4 on neuropsychological functioning following TBI remained uncertain, with multiple conflicting studies. We conclude that the ApoE e4 allele confers a small risk of poor outcome following TBI, with analysis by TBI severity not possible based on the currently available published data. Further research into the long-term neuropsychological impact and risk of dementia is warranted.Peer reviewe

Genetic Influences on Patient-Oriented Outcomes in Traumatic Brain Injury : A Living Systematic Review of Non-Apolipoprotein E Single-Nucleotide Polymorphisms

There is a growing literature on the impact of genetic variation on outcome in traumatic brain injury (TBI). Whereas a substantial proportion of these publications have focused on the apolipoprotein E (APOE) gene, several have explored the influence of other polymorphisms. We undertook a systematic review of the impact of single-nucleotide polymorphisms (SNPs) in non-apolipoprotein E (non-APOE) genes associated with patient outcomes in adult TBI). We searched EMBASE, MEDLINE, CINAHL, and gray literature from inception to the beginning of August 2017 for studies of genetic variance in relation to patient outcomes in adult TBI. Sixty-eight articles were deemed eligible for inclusion into the systematic review. The SNPs described were in the following categories: neurotransmitter (NT) in 23, cytokine in nine, brain-derived neurotrophic factor (BDNF) in 12, mitochondrial genes in three, and miscellaneous SNPs in 21. All studies were based on small patient cohorts and suffered from potential bias. A range of SNPs associated with genes coding for monoamine NTs, BDNF, cytokines, and mitochondrial proteins have been reported to be associated with variation in global, neuropsychiatric, and behavioral outcomes. An analysis of the tissue, cellular, and subcellular location of the genes that harbored the SNPs studied showed that they could be clustered into blood-brain barrier associated, neuroprotective/regulatory, and neuropsychiatric/degenerative groups. Several small studies report that various NT, cytokine, and BDNF-related SNPs are associated with variations in global outcome at 6-12 months post-TBI. The association of these SNPs with neuropsychiatric and behavioral outcomes is less clear. A definitive assessment of role and effect size of genetic variation in these genes on outcome remains uncertain, but could be clarified by an adequately powered genome-wide association study with appropriate recording of outcomes.Peer reviewe