Many physiotherapists lack preparedness to prescribe physical activity and exercise to people with musculoskeletal pain: A multi-national survey.

OBJECTIVES: Determine physiotherapists' (i) awareness of physical activity, and exercise prescription guidelines; (ii) perceived role, knowledge, confidence, skills and training in prescribing and progressing aerobic exercise and resistance training to people with musculoskeletal pain; (iii) professional development preferences; and (iv) perceived influences of external factors on exercise prescription for people with musculoskeletal pain. DESIGN: Multi-national cross-sectional survey. METHODS: An open online survey was developed specifically for this study. RESULTS: 1,352 physiotherapists from 56 countries participated. The majority of respondents correctly stated physical activity guidelines for adults (60%) and children (53%), but only 37% correctly stated guidelines for older adults. Eleven percent and 16% could name an accepted guideline for aerobic exercise and resistance training, respectively. Most agreed their role included prescribing aerobic exercise (75%) and resistance training (89%). Fewer reported they had the confidence, training or skills to prescribe aerobic exercise (38-50%) and resistance training (49-70%). Workshops were the most preferred (44%) professional development option. Most respondents believed appointment scheduling and access to equipment and professional development (62-79%) affected their ability to prescribe effective exercise. CONCLUSION: Many physiotherapists lack knowledge and training to provide physical activity advice, and to prescribe aerobic exercise and resistance training to people with musculoskeletal pain.

Microphysical explanation of the RH-dependent water affinity of biogenic organic aerosol and its importance for climate.

A large fraction of atmospheric organic aerosol (OA) originates from natural emissions that are oxidized in the atmosphere to form secondary organic aerosol (SOA). Isoprene (IP) and monoterpenes (MT) are the most important precursors of SOA originating from forests. The climate impacts from OA are currently estimated through parameterizations of water uptake that drastically simplify the complexity of OA. We combine laboratory experiments, thermodynamic modeling, field observations, and climate modeling to (1) explain the molecular mechanisms behind RH-dependent SOA water-uptake with solubility and phase separation; (2) show that laboratory data on IP- and MT-SOA hygroscopicity are representative of ambient data with corresponding OA source profiles; and (3) demonstrate the sensitivity of the modeled aerosol climate effect to assumed OA water affinity. We conclude that the commonly used single-parameter hygroscopicity framework can introduce significant error when quantifying the climate effects of organic aerosol. The results highlight the need for better constraints on the overall global OA mass loadings and its molecular composition, including currently underexplored anthropogenic and marine OA sources.

A walking program for people with severe knee osteoarthritis did not reduce pain but may have benefits for cardiovascular health: a phase II randomised controlled trial.

OBJECTIVE: The primary aim was to evaluate the effect of a dosed walking program on knee pain for patients with severe knee osteoarthritis (OA). Secondary aims evaluated the effects on cardiovascular health, function and quality of life. DESIGN: Participants with severe knee OA and increased cardiovascular risk were randomly assigned to a 12-week walking program of 70 min/week of at least moderate intensity, or to usual care. The primary outcome was knee pain (0-10). Secondary outcomes were of cardiovascular risk including physical activity, blood pressure, blood lipid and glucose levels, body mass index and waist circumference; WOMAC Index scores; physical function; and quality of life. RESULTS: Forty-six participants (23 each group) were recruited. Sixteen participants (70%) adhered to the walking program. Intention to treat analysis showed no between-group difference in knee pain. The walking group had increased odds of achieving a healthy systolic blood pressure (OR = 5.7, 95% CI 1.2-26.9), and a faster walking speed (Mean Difference (MD) = 0.12 m/s, 95% CI 0.02-0.23). Per protocol analysis based on participant adherence showed the walking group had more daily steps (MD = 1345 steps, 95% CI 365-2325); more time walking (MD = 18 min/day, 95% CI 5-31); reduced waist circumference (MD = -5.3 cm, 95% CI -10.5 to -0.03); and increased knee stiffness (MD = 0.9 units, 95% CI 0.07-1.8). CONCLUSIONS: Patients with severe knee OA prescribed a 12-week walking program of 70 min/week may have had cardiovascular benefits without decreasing knee pain. Australian New Zealand Clinical Trials Registry ACTRN12615000015549.

The maximum tolerated dose of walking for people with severe osteoarthritis of the knee: a phase I trial.

OBJECTIVE: To determine how much physical activity, in the form of walking, can be safely and feasibly tolerated for people with severe knee osteoarthritis (OA). DESIGN: Phase I dose response trial with escalating walking doses of 10, 20, 35, 50, 70, and 95 min over 1 week, were prescribed non-randomly to people with severe knee OA. The primary stopping rule was a substantial increase in knee pain. The primary outcomes were an estimation of the maximum tolerated dose of walking; and the proportion of people who did not complete the dose for feasibility reasons. The secondary outcomes were pain, stiffness and activity limitation Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Twenty-four participants (13 women) aged 53-83 years, and average body mass index (BMI) of 34 kg/m(2) (SD 9) were recruited. Three participants were assigned to each dose between 10 and 70 min, and nine participants assigned to the 95-min dose. The trial was stopped at 95 min due to the maximum number of adverse events occurring at this dose. Therefore, the maximum tolerated dose was 70 min. No participant stopped due to reasons related to feasibility. There was a moderate association between dose and increased activity (linear R(2) = 0.31, cubic R(2) = 0.69) and reduced stiffness (linear R(2) = 0.20, cubic R(2) = 0.52), with increased benefits at moderate to higher doses. CONCLUSIONS: There is preliminary evidence that 70 min per week of moderate intensity supervised walking was safe and feasible for people with severe OA of the knee; for higher doses there was a risk of exacerbating knee pain levels.

What proportion of people with hip and knee osteoarthritis meet physical activity guidelines? A systematic review and meta-analysis.

OBJECTIVE: To determine the proportion of people with hip and knee osteoarthritis that meet physical activity guidelines recommended for adults and older adults. METHOD: Systematic review with meta-analysis of studies measuring physical activity of participants with hip and knee osteoarthritis using an activity monitor. Physical activity levels were calculated using the mean average [95% confidence interval (CI)] weighted according to sample size. Meta-analyses determined the proportion of people meeting physical activity guidelines and recommendations of (1) ≥150 min per week of moderate to vigorous physical activity (MVPA) in bouts of ≥10 min; (2) ≥150 min per week of MVPA in absence of bouts; (3) ≥10,000 steps per day and ≥7000 steps per day. The Grades of Research, Assessment, Development and Evaluation (GRADE) approach was used to determine the quality of the evidence. RESULTS: For knee osteoarthritis, 21 studies involving 3266 participants averaged 50 min per week (95% CI = 46, 55) of MVPA when measured in bouts of ≥10 min, 131 min per week (95% CI = 125, 137) of MVPA, and 7753 daily steps (95% CI = 7582, 7924). Proportion meta-analyses provided high quality evidence that 13% (95% CI = 7, 20) completed ≥150 min per week of MVPA in bouts of ≥10 min, low quality evidence that 41% (95% CI = 23, 61) completed ≥150 min per week of MVPA in absence of bouts, moderate quality evidence that 19% (95% CI = 8, 33) completed ≥10,000 steps per day, and low quality evidence that 48% (95% CI = 31, 65) completed ≥7000 steps per day. For hip osteoarthritis, 11 studies involving 325 participants averaged 160 min per week (95% CI = 114, 216) of MVPA when measured in bouts of ≥10 min, 189 min per week (95% CI = 166, 212) of MVPA, and 8174 daily steps (95% CI = 7670, 8678). Proportion meta-analyses provided low quality evidence that 58% (95% CI = 18, 92) completed ≥150 min per week of MVPA in absence of bouts, low quality evidence that 30% (95% CI = 13, 50) completed ≥10,000 steps per day, and low quality evidence that 60% (95% CI = 47, 73) completed ≥7000 steps per day. CONCLUSION: A small to moderate proportion of people with knee and hip osteoarthritis met physical activity guidelines and recommended daily steps. Future research should establish the effects of increasing physical activity in this population to meet the current physical activity guidelines.

The stabilizing role of the rotator cuff at the shoulder--responses to external perturbations.

BACKGROUND: The rotator cuff has been hypothesized as a dynamic stabilizer at the shoulder joint yet evidence supporting this role remains inconclusive. We aimed to investigate the activity levels and recruitment patterns between the rotator cuff and superficial shoulder muscles in response to external perturbations to provide insight into the stabilizing role of the rotator cuff. METHODS: Surface and intramuscular electromyography (EMG) were used to measure timing of onset and level of activation (EMG amplitude as a percentage of maximum voluntary isometric contraction, % MVIC) of rotator cuff (supraspinatus, infraspinatus and subscapularis) and superficial muscles (anterior and posterior deltoid) on 19 healthy participants. Participants received expected and unexpected externally applied perturbations in directions of internal and external rotation at the glenohumeral joint. FINDINGS: All three rotator cuff muscles demonstrated pre-activation in anticipation of the perturbation prior to their representative global synergists, anterior and posterior deltoid (P<0.05). Subscapularis and infraspinatus were activated prior to all other muscles during external rotation and internal rotation perturbation trials respectively (P<0.01). Direction specific activation levels were observed; subscapularis was moderately strongly active (37% MVIC) in response to an external rotation perturbation and infraspinatus was moderately active (28% MVIC) in response to an internal rotation perturbation. No muscle was activated >10% MVIC when not acting as the main muscle opposing the movement. INTERPRETATION: The rotator cuff may function in part as a dynamic stabilizing unit of the shoulder demonstrating a feedforward muscle activation pattern. These results may assist in improving assessment and treatment of shoulder dysfunction.

Measurement of subacromial impingement of the rotator cuff.

OBJECTIVE: Recent evidence suggests that shoulder impingement syndrome arises from primary rotator cuff pathology and may be related to the inability of the rotator cuff to prevent superior humeral head migration in shoulder elevation. Impingement involves compression of subacromial structures, including the rotator cuff. Previously, clinical tests have been shown to be inaccurate in diagnosing rotator cuff impingement. A lack of anatomical validity might explain the inaccuracy of these tests. This study aimed to clarify the anatomical basis of subacromial compression of the rotator cuff by analysing the compression forces generated and observing the structures impinged in a variety of shoulder positions. DESIGN: This observational case series involved the dissection of nine embalmed cadaveric shoulders. METHOD: Pressure transducers were placed deep to the coracoid process, coracoacromial ligament, the anterior acromion and the posterior acromion. Shoulders were moved into internal and external rotation from the positions of flexion, abduction and extension. At each position, pressure readings were recorded and structures being compressed observed visually. RESULTS: Highest pressures were recorded in flexion/internal rotation at the coracoacromial ligament, in abduction/internal rotation at the coracoid process (both involving the rotator interval) and in abduction/internal rotation at the coracoacromial ligament (involving supraspinatus). Supraspinatus was also observed to be compressed in extension/external rotation (against the anterior acromion). Infraspinatus was compressed in extension/external rotation (against the posterior acromion), while subscapularis was compressed in flexion/internal rotation and flexion/external rotation (both against the coracoid process). CONCLUSION: This study identifies shoulder positions likely to impinge particular rotator cuff tendons.

Effects of mitotane treatment on human steroid metabolism: implications for patient management.

Mitotane (o,p'-DDD), an oral adrenolytic agent for treatment of advanced adrenocortical carcinoma (ACC), is reported to inhibit cortisol biosynthesis in vitro and enhance production from exogenous cortisol of urinary 6ß-hydroxycortisol and unidentified polar unconjugated metabolites. We examined urinary steroid profiles by gas chromatography-mass spectrometry of patients with histologically confirmed ACC following surgery, receiving a) hydrocortisone alone (three males and three females) and b) mitotane and hydrocortisone (six males and 11 females). Samples were collected after plasma mitotane had reached the therapeutic range of 14-20 mg/l. Increased excretion of polar unconjugated steroids during mitotane treatment was confirmed, with 6ß-hydroxycortisol and 6ß-hydroxy-20-dihydrocortisols predominating. The proportion of additionally hydroxylated metabolites was <2% in untreated controls and 52, 35-52% (mean, range) in the mitotane plus hydrocortisone group. Ratios of 5α-/5ß- and 20ß-/20α-metabolites of administered cortisol were decreased 50-, 15-fold, and 14-, 8-fold respectively (males, females - mean values) but with no change in metabolite ratios that reflect oxidoreduction at C11 or C20. Patterns of decrease in 5α- relative to 5ß-reduced metabolites were similar to those of patients with 5α-reductase 2 deficiency or on treatment with the 5α-reductase 2 inhibitor finasteride but different from those of patients on dutasteride, indicating specific inhibition of 5α-reductase 2. We conclude that mitotane causes consistent changes in cortisol catabolism, most of which have not been previously recognised. These need not interfere with early detection of ACC recurrence. Induction of 6ß-hydroxylation offers an explanation for a reported decrease in cortisol bioavailability. Mitotane also has potential as a unique steroid metabolic probe for 20ß-reduction.

Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial.

BACKGROUND: Few high-quality trials have examined the effects of progressive resistance training (PRT) on people with multiple sclerosis (MS). OBJECTIVE: To determine the effectiveness of PRT for people with MS, focusing on improving the gait deficits common in this population. METHODS: Using a single blind randomized controlled trial, people with relapsing-remitting MS were randomly allocated to either a PRT program targeting the lower limb muscles twice a week for 10 weeks (n = 36), or usual care plus an attention and social program conducted once a week for 10 weeks (n = 35). Outcomes were recorded at baseline, week 10 and week 22. RESULTS: Participants attended 92% of training sessions, with no serious adverse events. At 10 weeks, no differences were detected in walking performance. However, compared with the comparison group PRT demonstrated increased leg press strength (16.8%, SD 4.5), increased reverse leg press strength (29.8%, SD 12.7), and increased muscle endurance of the reverse leg press (38.7%, SD 32.8). Improvements in favor of PRT were also found for physical fatigue (Mean difference -3.9 units, 95%CI -6.6 to -1.3), and the physical health domain of quality of life (Mean difference 1.5 units, 95%CI 0.1 to 2.9). At week 22 almost no between-group differences remained. CONCLUSION: PRT is a relatively safe intervention that can have short-term effects on reducing physical fatigue, increasing muscle endurance and can lead to small improvements in muscle strength and quality of life in people with relapsing-remitting MS. However, no improvements in walking performance were observed and benefits do not appear to persist if training is completely stopped.

Association between isometric muscle strength and gait joint kinetics in adolescents and young adults with cerebral palsy.

The purpose of this study was to determine the association between isometric muscle strength of the lower limbs and gait joint kinetics in adolescents and young adults with cerebral palsy (CP). Twenty-five participants (11 males) with bilateral spastic CP, aged 14-22 years (mean: 18.9, sd: 2.0 yr) and Gross Motor Function Classification System (GMFCS) level II (n=19) and III (n=6) were tested. Hand held dynamometry was used to measure isometric strength (expressed in Nm/kg) of the hip, knee, and ankle muscles using standardized testing positions and procedures. 3D gait analysis was performed with a VICON system to calculate joint kinetics in the hip, knee and ankle during gait. Ankle peak moments exceeded by far the levels of isometric strength of the plantar flexors, while the knee and hip peak moments were just at or below maximal isometric strength of knee and hip muscles. Isometric muscle strength showed weak to moderate correlations with peak ankle and hip extension moment and power during walking. Despite considerable muscle weakness, joint moment curves were similar to norm values. Results suggest that passive stretch of the muscle-tendon complex of the triceps surae contributes to the ankle moment during walking and that muscle strength assessment may provide additional information to gait kinetics.

Identifying facilitators and barriers to physical activity for adults with Down syndrome.

BACKGROUND: Adults with Down syndrome are typically sedentary, and many do not participate in the recommended levels of physical activity per week. The aim of this study was to identify the facilitators and barriers to physical activity for this group. METHOD: Semi-structured interviews were conducted to elicit the views of adults with Down syndrome and their support people about what factors facilitate physical activity and what factors are barriers to activity. A sample of 18 participants (3 men, 15 women) was recruited through two agencies providing services for adults with disabilities; six participants were adults with Down syndrome and 12 participants were support people (four were parents of adults with Down syndrome and eight participants were employed by day programmes attended by the adults with Down syndrome). The interviews were recorded, transcribed verbatim and independently coded by two researchers. RESULTS: Three themes around facilitators to physical activity were identified: (1) support from others; (2) that the physical activity was fun or had an interesting purpose; and (3) routine and familiarity. Three themes around barriers were also identified: (1) lack of support; (2) not wanting to engage in physical activity; and (3) medical and physiological factors. CONCLUSIONS: The results suggest that support people play a key role, both as facilitators and barriers, in the participation by adults with Down syndrome in physical activity. Many of the barriers and facilitators of activity for adults with Down syndrome indentified are similar to those reported for adults without impairment. Our findings are also consistent with established theories in the field of health behaviour change.

Psychosocial predictors of failure to return to work in non-chronic non-specific low back pain: a systematic review.

OBJECTIVES: To identify psychosocial predictors of failure to return to work in non-chronic (lasting less than 3 months) non-specific low back pain (NSLBP). METHODS: A systematic review of prognostic studies was carried out. Medline, Embase, PsychINFO, CINAHL and PEDro electronic bibliographic databases up to April 2006 were searched. Included studies took baseline measures in the non-chronic phase of NSLBP (ie, within 3 months of onset), included at least one psychosocial variable and studied a sample in which at least 75% of participants had NSLBP. Baseline measures had to be used to predict at least one work-specific outcome. RESULTS: The search identified 24 studies meeting the inclusion criteria. From these studies there is strong evidence that recovery expectation is predictive of work outcome and that depression, job satisfaction and stress/psychological strain are not predictive of work outcome. There is moderate evidence that fear avoidance beliefs are predictive of work outcome and that anxiety is not predictive of work outcome. There is insufficient evidence to determine whether compensation or locus of control are predictive of work outcome. CONCLUSIONS: To predict work outcome in non-chronic NSLBP, psychosocial assessment should focus on recovery expectation and fear avoidance. More research is needed to determine the best method of measuring these constructs and to determine how to intervene when a worker has low recovery expectations.

A reliability study of the new Back Strain Monitor based on clinical trials.

A new Back Strain Monitor (BSM) device has been developed in order to measure, record and analyze movements of the lower back. The purpose of this study was to examine the inter-tester and the intra-tester reliability of the movement measurements given by the BSM accelerometers, and compare it with the reliability of two other conventional measurement methods: the Double Inclinometer method (DI) and the Modified-Modified Schober (MMS) method. The clinical studies included 23 participants (16 males, 7 females) with no recent history of lower back pain, who wore the device during a combination of different anatomical movements (flexion, extension, left lateral flexion and right lateral flexion of the lumber spine). The tests were conducted by three therapists (testers). The reliability results for the BSM accelerometers clearly outperform the results obtained for the DI and the MMS methods. The inter-tester reliability gives the Intra-Class Correlation (ICC) value of 0.95 for the BSM flexion, 0.89 for the DI flexion and 0.74 for the MMS. The intra-tester reliability gives the ICC value of 0.99 for BSM flexion, 0.94 for DI flexion and 0.77 for the MMS. The BSM accelerometers were highly reliable in assessing back movements, measuring these movements with less error than the DI and MMS methods.

Qualitative outcomes of progressive resistance exercise for people with COPD.

The outcomes of quantitative investigations examining the effectiveness of exercise interventions for people with COPD are limited by the small number of measurement tools that can be included. In contrast, qualitative inquiry allows broader exploration of the perceived outcomes of an intervention. The purpose of this investigation is to explore the qualitative outcomes of a progressive resistance exercise (PRE) program for people with COPD. People with COPD, enrolled in a randomized controlled trial of PRE, were invited to participate in two semi-structured interviews conducted at the end (12 weeks) and 12 weeks after the training intervention (24 weeks). Interviews were audiotaped, transcribed and then coded independently by two researchers. Themes relating to training outcomes were then developed and described. Twenty-two participants were interviewed at 12 weeks, and 19 participants at 24 weeks. After PRE, participants reported a range of physical gains, particularly with regard to improved strength and reduced breathlessness during daily activities. Improved control and confidence during activities of daily living were important psychological benefits perceived by people with COPD, as was the social support experienced during group training sessions. At 24 weeks, confidence persisted despite a perceived plateau or dissipation of physical gains. People with COPD reported physical, psychological and social benefits after PRE, which had a positive effect on activity performance. Although the perceived physical benefits of training were not prominent at 24 weeks, feelings of increased confidence and control persisted.

Progressive resistance exercise for people with multiple sclerosis.

PURPOSE: This study aimed to determine if participation in a progressive resistance exercise (PRE) programme can: (1) increase the ability to generate maximal muscle force, (2) increase muscle endurance, (3) increase functional activity, and (4) improve overall psychological function of people with multiple sclerosis (MS). METHODS: A pre-post single group research design with a 4-week baseline familiarisation phase was used. Nine people (mean age 45.6 years, SD 10.7) with MS attended a gymnasium three times over 4 weeks for familiarization. Participants then completed a twice-weekly 10-week PRE programme, with two sets of 10 - 12 repetitions of each exercise. Outcome measures of muscle strength (1RM for arms and legs), muscle endurance (repetitions at half 1RM), walking speed, the 2-min walk test (2MWT), a timed stairs test, and the impact of MS on physical and psychological function were taken at weeks 2, 4, and 14. RESULTS: Participants attended 94.3% (SD 8.2%) of the training sessions, with no adverse events. After accounting for baseline stability, significant improvements (P < 0.05) were found in arm strength (14.4%), leg endurance (170.9%), fast walking speed (6.1%), and there was a trend for increased distance in the 2MWT (P = 0.06). The perceived impact of MS on physical function was reduced (P = 0.02). CONCLUSIONS: Adults with MS benefited from a PRE programme by improving muscle performance and physical activities, without adverse events. These findings suggest that PRE may be a feasible and useful fitness alternative for people with mild to moderate disability due to MS.

A qualitative analysis of a progressive resistance exercise programme for people with multiple sclerosis.

PURPOSE: This qualitative study explored the perceptions of adults with multiple sclerosis about the positive and negative effects of a progressive resistance strengthening programme; and identified factors that might facilitate or create barriers to participation. METHODS: Seven women and two men (mean age 45.6 years, SD 10.7) with multiple sclerosis participated in a 10-week gymnasium based progressive resistance strengthening programme held twice a week. Participants were interviewed at the end of the programme. The recorded interviews were transcribed and then independently coded by three researchers. From these codes, the main themes emerged. RESULTS: Reports about the programme were very positive with physical, psychological and social benefits noted. Most participants said that they had less fatigue as a result of the programme. Few negative outcomes were reported and these were minor such as aches and pains. Key extrinsic factors for programme completion were the leaders' encouragement and knowledge of exercise; and the group aspect of the programme. Key intrinsic factors were enjoyment, determination, seeing the signs of progress, and a previously held positive attitude about the benefits of exercise. CONCLUSIONS: The results of this study suggest that progressive resistance strength training is a feasible fitness option for some people with multiple sclerosis. Factors perceived to be important for programme completion suggest that choosing encouraging leaders with knowledge of exercise, and exercising in a group may contribute to programme success.

Investigation into possible causes of interference in serum testosterone measurement in women.

BACKGROUND: Direct (non-extracted) testosterone immunoassays may give spuriously high results in women. The presumed interferents may be removed if testosterone is extracted into an organic phase before being measured. We aimed to clarify possible causes and effects of interference in testosterone measurement in women. METHODS: Women who had a blood sample referred to Hope Hospital Clinical Biochemistry laboratory for measurement of serum testosterone concentration over a six-month period were studied. Clinical and treatment data were recorded. A difference (direct-minus-extracted testosterone) of less than 1.0 nmol/L was used to define a group with low interference. A difference of 2.5 nmol/L or more was used to define a group with significant interference. RESULTS: The distribution of interference in 1271 serum samples from female patients was unimodal. There were no group differences in clinical presentation or treatment. The median degree of interference was 1.4 nmol/L. In 42 female patients with varying degrees of interference, identified on routine assay, regression analysis showed strong association between dehydroepiandrosterone sulphate (DHEA-S) and interference (direct-minus-extracted testosterone) (r = 0.77, P < 0.001). CONCLUSIONS: Given that DHEA-S is present in very variable amounts in blood, it is possible that even with a low cross reactivity, DHEA-S or one of its metabolites significantly interferes in the testosterone assay when at higher concentrations.

A novel point mutation in P450c17 (CYP17) causing combined 17alpha-hydroxylase/17,20-lyase deficiency.

CONTEXT: Combined 17alpha-hydroxylase/17,20-lyase deficiency is a rare cause of congenital adrenal hyperplasia and hypogonadism. Novel single amino acid changes in P450c17 provide potentially important insights into key structural domains for enzyme function. OBJECTIVE, DESIGN, AND SETTING: We report a novel missense mutation in P450c17 in a 17-yr-old female presenting with a malignant mixed germ cell tumor with yolk sac elements who demonstrated clinical and biochemical features of combined 17alpha-hydroxylase/17,20-lyase deficiency. METHODS: Quantitative urinary steroid analysis was performed by high resolution gas chromatography. All eight coding exons of CYP17 were PCR amplified and sequenced. The position of arginine at codon 96 was modeled using the CYP17 structure 2c17 (www.rcsb.org). The CYP17 genes were subcloned into pcDNA3, expressed in HEK-293 cells, and chromatographed. PATIENT AND RESULTS: 17alpha-Hydroxylase deficiency was confirmed by marked reductions in urinary and serum cortisol, androgens, and estradiol. Mutational analysis revealed a novel homozygous R96Q missense mutation in P450c17, affecting an amino acid in a key substrate-binding region of the enzyme, leading to complete inactivity. CONCLUSION: The description of a second missense mutation at codon 96 (R96W and R96Q) in the substrate-binding region of P450c17 provides strong evidence for the key role of this amino acid in 17alpha-hydroxylase/17,20-lyase function. An association between a malignant germ cell tumor and 17alpha-hydroxylase deficiency has not been reported previously, although the presence of gonadoblastoma in the ovary of a patient with this condition has recently been described.

A randomised clinical trial of activity-focussed physiotherapy on patients with distal radius fractures.

INTRODUCTION: Physiotherapy is considered by some authorities to be an important aspect of management in patients following distal radius fractures. There is evidence of improvement in impairment with physiotherapy; however, there is no evidence to support early return of functional activity. Traditional physiotherapy management has focussed on improving impairment; however, there are no trials with emphasis on skill acquisition via motor re-learning principles. MATERIALS AND METHODS: Forty-one participants with conservatively managed distal radius fractures were studied in a randomised, single-blinded, prospective trial. Two treatment options were compared: exercise and advice versus activity-focussed physiotherapy with measurement periods of 6 weeks after removal of cast and follow-up at 24 weeks. RESULTS: Participants allocated to the exercise and advice group consulted a physiotherapist an average of 0.9 (SD 0.4) times, while the participants allocated to the more intensive activity-focussed group consulted with physiotherapy a mean of 4.4 (SD 2.3) times. At both 6 and 24 weeks there were no significant differences between the groups for change in impairment (as measured by grip strength, range of motion of wrist flexion and extension and pain intensity), activity limitation and participation restriction, as measured by the Patient-Rated Wrist Evaluation (PRWE). Exercise and advice given by a physiotherapist were equally as effective as activity-focussed physiotherapy in recovery both at 6 and 24 weeks. CONCLUSION: The results suggest that after removal of cast from fracture of distal radius, patients may routinely require no more than a single session of advice and exercise provided by a physiotherapist.