Tackling the adverse health effects of excess body fat in breast cancer: where does physical activity fit in?

Weight gain is commonly observed during and after breast cancer treatment due to chemotherapy and endocrine therapies, induced menopause, changes in metabolism and food intake and decreased physical activity. Systematic reviews show that women who are overweight or obese at diagnosis, and those who gain weight, have poorer breast cancer survival outcomes than women of a healthy weight, irrespective of menopausal status. Excess body weight after breast cancer also increases the risk of type 2 diabetes mellitus and CVD. The adverse impact of excess body weight on survival outcomes is clearly shown for women with oestrogen receptor-positive (ER+) breast cancer, which accounts for 70 % of all breast cancer cases. Higher body fat is thought to increase the risk of ER+ recurrence because of increased aromatase activity. However, this could be compounded by other risk factors, including abnormal insulin and adipokine metabolism, impaired anti-tumour immunity and chronic low-grade systemic inflammation. Observational evidence linking poorer survival outcomes with excess body fat and low physical activity in women recovering from early-stage curative-intent breast cancer treatment is reviewed, before reflecting on the proposed biological mechanisms. The issues and sensitivities surrounding exercise participation amongst overweight breast cancer patients is also discussed, before providing an overview of the co-design process involved in development of an intervention (support programme) with appropriate content, structure and delivery model to address the weight management challenges faced by overweight ER+ breast cancer patients.

Co-designed weight management intervention for women recovering from oestrogen-receptor positive breast cancer.

BACKGROUND: Weight gain is commonly observed during and after breast cancer treatment and is associated with poorer survival outcomes, particularly in women with oestrogen receptor-positive (ER +) disease. The aim of this study was to co-design (with patients) a programme of tailored, personalised support (intervention), including high-quality support materials, to help female breast cancer patients (BCPs) with ER + disease to develop the skills and confidence needed for sustainable weight loss.  METHODS: ER + BCPs were recruited from two UK National Health Service (NHS) Trusts. The selection criteria included (i) recent experience of breast cancer treatment (within 36 months of completing primary treatment); (ii) participation in a recent focus group study investigating weight management perceptions and experiences; (iii) willingness to share experiences and contribute to discussions on the support structures needed for sustainable dietary and physical activity behaviour change. Co-design workshops included presentations and interactive activities and were facilitated by an experienced co-design researcher (HH), assisted by other members of the research team (KP, SW and JS). RESULTS: Two groups of BCPs from the North of England (N = 4) and South Yorkshire (N = 5) participated in a two-stage co-design process. The stage 1 and stage 2 co-design workshops were held two weeks apart and took place between Jan-March 2019, with each workshop being approximately 2 h in duration. Guided by the Behaviour Change Wheel, a theoretically-informed weight management intervention was developed on the basis of co-designed strategies to overcome physical and emotional barriers to dietary and physical activity behaviour change. BCPs were instrumental in designing all key features of the intervention, in terms of Capability (e.g., evidence-based information, peer-support and shared experiences), Opportunity (e.g., flexible approach to weight management based on core principles) and Motivation (e.g., appropriate use of goal-setting and high-quality resources, including motivational factsheets) for behaviour change. CONCLUSION: This co-design approach enabled the development of a theoretically-informed intervention with a content, structure and delivery model that has the potential to address the weight management challenges faced by BCPs diagnosed with ER + disease. Future research is required to evaluate the effectiveness of the intervention for eliciting clinically-important and sustainable weight loss in this population.

Pragmatic intervention for increasing self-directed exercise behaviour and improving important health outcomes in people with multiple sclerosis: a randomised controlled trial.

BACKGROUND: Exercise programmes that can demonstrate evidence of long-lasting clinical effectiveness are needed for people with multiple sclerosis (PwMS). OBJECTIVE: The objective of this study was to assess the effects of a practically implemented exercise programme on self-directed exercise behaviour and important health outcomes in PwMS to nine months of follow-up. METHODS: We conducted a parallel-arm, randomised controlled trial: 120 PwMS (Expanded Disability Status Scale (EDSS) 1.0-6.5) randomised to a three-month exercise intervention plus usual care, or usual care only. Two supervised plus one home-exercise session (weeks 1-6) were followed by one supervised and two home-exercise sessions (weeks 7-12). Cognitive-behavioural techniques promoted long-term exercise behaviour change. Outcomes were blindly assessed at baseline and at three and nine months after randomisation. The primary outcome was self-reported exercise behaviour (Godin Leisure Time Exercise Questionnaire (GLTEQ)). Secondary outcomes included fatigue and health-related quality of life (HRQoL). RESULTS: The intervention increased self-reported exercise (9.6 points; 95% CI: 2.0 to 17.3 points; p = 0.01) and improved fatigue (p < 0.0001) and many HRQoL domains (p ≤ 0.03) at three months. The improvements in emotional well-being (p = 0.01), social function (p = 0.004) and overall quality of life (p = 0.001) were sustained for nine months. CONCLUSION: This pragmatic approach to implementing exercise increases self-reported exercise behaviour, improves fatigue and leads to a sustained enhancement of HRQoL domains in PwMS.

Cost effectiveness of a pragmatic exercise intervention (EXIMS) for people with multiple sclerosis: economic evaluation of a randomised controlled trial.

BACKGROUND: Exercise is a safe, non-pharmacological adjunctive treatment for people with multiple sclerosis but cost-effective approaches to implementing exercise within health care settings are needed. OBJECTIVE: The objective of this paper is to assess the cost effectiveness of a pragmatic exercise intervention in conjunction with usual care compared to usual care only in people with mild to moderate multiple sclerosis. METHODS: A cost-utility analysis of a pragmatic randomised controlled trial over nine months of follow-up was conducted. A total of 120 people with multiple sclerosis were randomised (1:1) to the intervention or usual care. Exercising participants received 18 supervised and 18 home exercise sessions over 12 weeks. The primary outcome for the cost utility analysis was the incremental cost per quality-adjusted life year (QALY) gained, calculated using utilities measured by the EQ-5D questionnaire. RESULTS: The incremental cost per QALY of the intervention was £10,137 per QALY gained compared to usual care. The probability of being cost effective at a £20,000 per QALY threshold was 0.75, rising to 0.78 at a £30,000 per QALY threshold. CONCLUSION: The pragmatic exercise intervention is highly likely to be cost effective at current established thresholds, and there is scope for it to be tailored to particular sub-groups of patients or services to reduce its cost impact.

Interventions to improve exercise behaviour in sedentary people living with and beyond cancer: a systematic review.

BACKGROUND: To systematically review the effects of interventions to improve exercise behaviour in sedentary people living with and beyond cancer. METHODS: Only randomised controlled trials (RCTs) that compared an exercise intervention to a usual care comparison in sedentary people with a homogeneous primary cancer diagnosis, over the age of 18 years were eligible. The following electronic databases were searched: Cochrane Central Register of Controlled Trials MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; SportDiscus; PEDro from inception to August 2012. RESULTS: Fourteen trials were included in this review, involving a total of 648 participants. Just six trials incorporated prescriptions that would meet current recommendations for aerobic exercise. However, none of the trials included in this review reported intervention adherence of 75% or more for a set prescription that would meet current aerobic exercise guidelines. Despite uncertainty around adherence in many of the included trials, the interventions caused improvements in aerobic exercise tolerance at 8-12 weeks (SMD=0.73, 95% CI=0.51-0.95) in intervention participants compared with controls. At 6 months, aerobic exercise tolerance is also improved (SMD=0.70, 95% CI=0.45-0.94), although four of the five trials had a high risk of bias; hence, caution is warranted in its interpretation. CONCLUSION: Expecting the majority of sedentary survivors to achieve the current exercise guidelines is likely to be unrealistic. As with all well-designed exercise programmes, prescriptions should be designed around individual capabilities and frequency, duration and intensity or sets, repetitions, intensity of resistance training should be generated on this basis.

Pragmatic exercise intervention for people with multiple sclerosis (ExIMS trial): study protocol for a randomised controlled trial.

Exercise is an effective intervention for improving function, mobility and health-related quality of life in people with multiple sclerosis (PwMS). Questions remain however, regarding the effectiveness of pragmatic exercise interventions for evoking tangible and sustained increases in physical activity and long-term impact on important health outcomes in PwMS. Furthermore, dose-response relationships between exercise and health outcomes have not previously been reported in PwMS. These issues, and improved knowledge of cost effectiveness, are likely to influence key decisions of health policy makers regarding the implementation of exercise therapy as part of the patient care pathway for PwMS. Hence, the primary aim of this study is to investigate whether a 12-week tapered programme of supervised exercise, incorporating cognitive-behavioural techniques to facilitate sustained behaviour change, is effective for evoking improvements in physical activity and key health outcomes in PwMS over 9 months of follow-up. A total of 120 PwMS will be randomised (1:1) to either a 12-week pragmatic exercise therapy intervention or usual care control group. Participants will be included on the basis of a clinical diagnosis of MS, with an expanded disability status score (EDSS) between 1 and 6.5. Outcome measures, to be assessed before and after the intervention and 6 months later, will include physical activity, clinical and functional measures and health-related quality of life. In addition, the cost effectiveness of the intervention will be evaluated and dose-response relationships between physical activity and the primary/secondary outcomes in those with mild and more severe disease will be explored.

Effects of an exercise and hypocaloric healthy eating program on biomarkers associated with long-term prognosis after early-stage breast cancer: a randomized controlled trial.

Excess body weight at diagnosis and weight gain after breast cancer are associated with poorer long-term prognosis. This study investigated the effects of a lifestyle intervention on body weight and other health outcomes influencing long-term prognosis in overweight women (BMI > 25.0 kg/m(2)) recovering from early-stage (stage I-III) breast cancer. A total of 90 women treated 3-18 months previously were randomly allocated to a 6-month exercise and hypocaloric healthy eating program (n = 47, aged 55.6 ± 10.2 year) or control group (n = 43, aged 55.9 ± 8.9 year). Women in the intervention group received three supervised exercise sessions per week and individualized dietary advice, supplemented by weekly nutrition seminars. Body weight, waist circumference, waist/hip ratio [WHR], cardiorespiratory fitness, blood biomarkers associated with breast cancer recurrence and cardiovascular disease risk, and quality of life (FACT-B) were assessed at baseline and 6 months. Three-day diet diaries were used to assess macronutrient and energy intakes. A moderate reduction in body weight in the intervention group (median difference from baseline of -1.09 kg; IQR -0.15 to -2.90 kg; p = 0.07) was accompanied by significant reductions in waist circumference (p < 0.001), WHR (p = 0.005), total (p = 0.021) and saturated fat (p = 0.006) intakes, leptin (p = 0.005), total cholesterol (p = 0.046), and resting diastolic blood pressure (p = 0.03). Cardiopulmonary fitness (p < 0.001) and FACT-B quality of life (p = 0.004) also showed significant improvements in the intervention group. These findings suggest that an individualized exercise and a hypocaloric healthy eating program can positively impact upon health outcomes influencing long-term prognosis in overweight women recovering from early-stage breast cancer.

Exercise training and the control of skin blood flow in older adults.

The ability to control skin blood flow decreases with primary aging, making older adults less able to adequately thermoregulate and repair cutaneous wounds. Lifestyle factors such as physical activity, diet, and smoking might interact with the aging process to modulate "normal" age-associated changes in the cutaneous microcirculation. The main focus of this brief review is the effects of exercise training on the control of skin blood flow in older adults.

Physiological predictors of maximum treadmill walking performance in patients with intermittent claudication.

The purpose of this investigation was to identify physiological predictors of maximum treadmill walking performance (MWD) in patients with intermittent claudication. Forty-five claudicants performed a graded treadmill test to determine MWD, peak oxygen uptake, and gas exchange threshold. Calf muscle oxygenation (StO (2)) at 1 min and time to minimum StO (2) were also measured using near-infrared spectroscopy. On other occasions, peak calf blood flow, resting ankle-brachial index, and pulmonary oxygen uptake kinetics during steady-state walking were assessed. A forward stepwise multiple regression analysis was performed to determine predictors of MWD. A regression model comprising time to minimum StO (2), peak oxygen uptake, and StO (2) at 1 min explained 64% of the variation in MWD. The results suggest that cardiopulmonary fitness and the ability to match oxygen delivery to metabolic demand are important determinants of walking performance in claudicants, and that certain near-infrared spectroscopy variables might be useful in studies that evaluate the mechanisms of clinical improvement with different treatment interventions.

Nordic poles immediately improve walking distance in patients with intermittent claudication.

OBJECTIVES: To investigate the immediate effects of Nordic pole walking (NPW) on walking distance and cardiopulmonary workload in patients with intermittent claudication. METHODS: Using a standardised treadmill test (3.2 km h(-1) at 4% gradient), walking distance, cardiopulmonary responses, leg pain and perceived exertion during NPW were compared to responses evoked by normal walking in 20 patients with intermittent claudication. The distance to onset of claudication pain (claudication distance: CD) and to maximum walking distance (MWD), heart rate (HR), expired gas parameters, leg pain (Borg's CR-10 Scale) and perceived exertion (Borg's Rating of Perceived Exertion: RPE Scale) were compared. RESULTS: CD increased significantly from a median (range) distance of 77 m (28-503) to 130 m (41-1080) and MWD increased significantly from 206 m (81-1078) to 285 m (107-1080) when patients used the Nordic poles (P=0.000). The level of leg pain at MWD was also significantly reduced during NPW (P=0.002). Perceived exertion at MWD did not increase despite an increase in cardiopulmonary work, as indicated by an increase in oxygen consumption (16.5%; P=0.000). CONCLUSION: These results show that NPW immediately enables patients with intermittent claudication to walk further with less pain, despite a higher workload. NPW might also be a useful exercise strategy for improving the cardiovascular fitness of patients with intermittent claudication.

Effect of upper- and lower-limb exercise training on circulating soluble adhesion molecules, hs-CRP and stress proteins in patients with intermittent claudication.

OBJECTIVES: To investigate the effects of exercise training on levels of circulating biomarkers associated with the progression of atherosclerosis and risk of cardiovascular events in patients with intermittent claudication. METHODS: Circulating levels of soluble adhesion molecules (sVCAM-1, sICAM-1, sE-selectin), high sensitivity C-reactive protein (hs-CRP) and stress proteins (Hsp60 and Hsp70) in patients randomised to a 24-week programme of arm- or leg-cranking exercise were compared with those in usual care controls. RESULTS: Arm and leg exercise similarly improved lower-limb aerobic exercise capacity (20% vs 19%, respectively; P<0.001) and maximum walking distance (30% vs 35%, respectively; P<0.001). Improvements in training limb-specific peak oxygen consumption were attenuated for patients in the highest vs lowest quartile for circulating sVCAM-1 levels at baseline (3% vs 25% respectively, P<0.001). Although circulating hs-CRP levels tended to be lower in the arm-cranking group (-1.55 [95% CI: -1.06 to -2.26]mgl(-1)), exercise training had no effect on circulating levels of soluble adhesion molecules or stress proteins. CONCLUSIONS: These findings suggest that high levels of circulating sVCAM-1 are associated with an attenuated exercise training response and that arm-cranking exercise may provide an effective stimulus for evoking systemic anti-inflammatory adaptations in patients with intermittent claudication.

Rehabilitation of two-part fractures of the neck of the humerus (two-year follow-up).

The 2-year results of a randomized, prospective, controlled trial of minimally displaced proximal humeral fractures treated either by immediate physiotherapy (group A) or after 3 weeks of immobilization (group B) are reported. At 1 year shoulder disability, as measured with the Croft shoulder disability questionnaire, was found in 42.8% of patients in group A and 72.5% in group B (P < .01). By 2 years, shoulder disability in group A remained unchanged (43.2%) but had reduced in group B (59.5%). This difference was not statistically significant. Immediate physiotherapy after a minimally displaced proximal humeral fracture results in faster recovery, with maximal functional benefit being achieved at 1 year. Delayed rehabilitation by 3 weeks of shoulder immobilization produces a slower recovery, which continues for at least 2 years after the time of injury.

Relative tolerance to upper- and lower-limb aerobic exercise in patients with peripheral arterial disease.

OBJECTIVES: To investigate the effects of peripheral arterial disease (PAD) on relative tolerance to upper- and lower-limb aerobic exercise. METHODS: Peak cardiorespiratory responses evoked by an incremental arm-cranking test (ACT) and an incremental leg-cranking test (LCT) were compared in patients with PAD (N=101; median age 69 year, range 50-85 years). Claudication distance (CD) and total distance before intolerable claudication pain (maximum walking distance: MWD) were also assessed during walking. RESULTS: Peak oxygen consumption (V O(2)) for the ACT was 94% of that measured for the LCT (1.01+/-0.03 versus 1.10+/-0.03lmin(-1), respectively; P<0.001), but in a significant proportion of patients (35%; P<0.001), exceeded that recorded for the LCT. The ratio of upper- to lower-limb peak V O(2) was higher (0.98+/-0.04 compared to 0.98+/-0.05lmin(-1) and 1.00+/-0.06 compared to 1.21+/-0.06lmin(-1); P<0.01), whereas walking performance (CD: 94+/-14 versus 187+/-25 m, P<0.01; MWD: 227+/-20 versus 394+/-33 m, P<0.01) was lower for patients in the lowest ankle to brachial pressure index quartile compared to patients in the highest quartile, respectively. CONCLUSION: Upper-limb aerobic conditioning could be a useful exercise stimulus for maintaining or improving cardiorespiratory function in patients with severe PAD as they have a greater relative upper-limb aerobic power.

The inflammatory response to upper and lower limb exercise and the effects of exercise training in patients with claudication.

PURPOSE: We have previously shown that a program of upper limb exercise training can induce significant improvements in walking distance in patients with claudication. This study assessed whether upper limb exercise avoids the systemic inflammatory responses associated with lower limb exercise and also whether the inflammatory response to acute lower limb exertion is modified by a program of supervised exercise training. METHODS: Fifty-two patients with stable intermittent claudication were randomized into two groups who underwent 6 weeks of supervised upper (n = 26) or lower (n = 26) limb cardiorespiratory exercise training. A parallel control group (n = 15) was provided with lifestyle advice only. Neutrophil activation markers (CD11b and CD66b) and plasma levels of von Willebrand factor (marker of endothelial damage) in response to an acute bout of sustained upper and lower limb exercise were assessed before and after the period of training. Plasma levels of soluble E-selectin (marker of endothelial activation) were also determined before and after the training period. RESULTS: An acute bout of sustained lower limb exercise significantly increased the intensity of CD11b and CD66b expression by peripheral blood neutrophils in all groups, whereas upper limb exercise had no effect. Resting neutrophil expression of CD11b and CD66b and circulating von Willebrand factor levels were unaffected by the training program, as were the inflammatory responses to an acute bout of sustained upper and lower limb muscular work, despite the fact that both training programs significantly increased walking distances. CONCLUSIONS: These findings indicate that upper limb exercise training programs may offer certain advantages over currently prescribed lower limb programs. Our results show that exercising nonischemic muscles in a way that promotes improved cardiorespiratory function and walking capacity can avoid the potentially deleterious systemic inflammatory responses associated with lower limb exertion in patients with stable intermittent claudication.

Activated parathyroid hormone/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone.

Parathyroid hormone (PTH), an important regulator of calcium homeostasis, targets most of its complex actions in bone to cells of the osteoblast lineage. Furthermore, PTH is known to stimulate osteoclastogenesis indirectly through activation of osteoblastic cells. To assess the role of the PTH/PTH-related protein receptor (PPR) in mediating the diverse actions of PTH on bone in vivo, we generated mice that express, in cells of the osteoblastic lineage, one of the constitutively active receptors described in Jansen's metaphyseal chondrodysplasia. In these transgenic mice, osteoblastic function was increased in the trabecular and endosteal compartments, whereas it was decreased in the periosteum. In trabecular bone of the transgenic mice, there was an increase in osteoblast precursors, as well as in mature osteoblasts. Osteoblastic expression of the constitutively active PPR induced a dramatic increase in osteoclast number in both trabecular and compact bone in transgenic animals. The net effect of these actions was a substantial increase in trabecular bone volume and a decrease in cortical bone thickness of the long bones. These findings, for the first time to our knowledge, identify the PPR as a crucial mediator of both bone-forming and bone-resorbing actions of PTH, and they underline the complexity and heterogeneity of the osteoblast population and/or their regulatory microenvironment.

A review of current literature on physiological tests and soft tissue biomarkers applicable to work-related upper limb disorders.

Work-related upper limb disorders (WRULD) are among the most commonly reported occupational illnesses. Epidemiological evidence of work-relatedness has been reported for a number of conditions, including carpal tunnel syndrome, hand/wrist tendinitis, shoulder tendinitis and hand-arm vibration syndrome. A range of electrodiagnostic techniques and psychophysical tests has been used to assess neurological dysfunction associated with WRULD, whereas only very few studies have examined biochemical markers of soft tissue injury. This report reviews key literature on physiological tests and biochemical markers of musculoskeletal stress/injury, which are applicable to studies of WRULD. The paper concludes by proposing new ways that testing might be implemented during occupational health surveillance to enable early warning of impending problems and to provide more insight into the underlying nature of soft tissue disorders.

Influence of upper- and lower-limb exercise training on cardiovascular function and walking distances in patients with intermittent claudication.

PURPOSE: The effects of upper-limb (arm cranking) and lower-limb (leg cranking) exercise training on walking distances in patients with intermittent claudication was assessed. METHODS: Sixty-seven patients (33 to 82 years old) with moderate to severe intermittent claudication were recruited, and the maximum power generated during incremental upper- and lower-limb ergometry tests was determined, as were pain-free and maximum walking distances (by using a shuttle walk test). Patients were randomly assigned to an upper-limb training group (n = 26) or a lower-limb training group (n = 26). An additional untrained group (n = 15) was recruited on an ad hoc basis in parallel with the main trial by using identical inclusion criteria. This group was subsequently shown to possess a similar demographic distribution to the two exercise groups. Supervised training sessions were held twice weekly for 6 weeks. RESULTS: Both training programs significantly improved the maximum power generated during the incremental upper- and lower-limb ergometry tests (P <. 001), which may reflect an increase in central cardiovascular function that was independent of the training mode. More importantly, pain-free and maximum walking distances also improved in both training groups (P <.001). The improvements in the training groups were similar; there were no changes in the untrained control group. These findings suggest that the symptomatic improvement after upper-limb exercise training may result, in part, from systemic cardiovascular effects rather than localized metabolic or hemodynamic changes. CONCLUSION: Carefully prescribed upper-limb exercise training can evoke a rapid symptomatic improvement in patients with claudication, while avoiding the physical discomfort experienced when performing lower-limb weight-bearing exercise.

Manipulation of knee extensor force using percutaneous electrical myostimulation during eccentric actions: effects on indices of muscle damage in humans.

Percutaneous electrical myostimulation (PES) was used to manipulate the force produced by the knee extensor muscles during eccentric exercise, thereby providing a model to investigate the role of force in muscle damage. Two eccentric exercise bouts of equal work were performed by nine subjects, using fixed voltage PES at 20 Hz (to produce moderate muscle forces) and 100 Hz (to produce high muscle forces). Muscle contractility, serum creatine kinase activity (CK) and muscle soreness (MS) were evaluated before, and up to 14 days after exercise. Data are presented as means+/-SEM, and were analysed using repeated measures analysis of variance (ANOVA), t-tests and Wilcoxon tests. Peak forces were higher during the 100 Hz bout than the 20 Hz bout for repetitions 1 (472+/-60 vs 237+/-23 Newtons), 10 (381+/-26 vs 233+/-26 Newtons), 20 (310+/-24 vs 218+/-24 Newtons), all p < 0.01, t-test and 30 (297+/-27 vs 204+/-21 Newtons), p < 0.05, t-test. Following the 100 Hz bout, maximum voluntary contractile force (MVC) was lower (p<0.01, ANOVA), and CK was higher (p<0.0001, ANOVA) than after the 20 Hz bout. Subjects also reported greater MS on days 2 to 6 (p<0.05, Wilcoxon test) following the 100 Hz bout. Despite a decline in the stimulated 20:100 Hz tetanic force ratio after each bout (p<0.01, ANOVA) there was no difference between bouts (p>0.05, ANOVA). The higher rise in CK and MS after the 100 Hz bout, together with the greater deficit in MVC, suggest that in humans, muscle force is a contributing factor to muscle injury during eccentric actions.

Effect of ex vivo storage on human peripheral blood neutrophil expression of CD11b and the stabilizing effects of Cyto-Chex.

CD11b is the alpha sub-unit of the CD11b/CD18 heterodimeric complex that has a key role in neutrophil-endothelial cell interactions and early events in inflammatory responses. Accurate assessment of CD11b expression by neutrophils can be problematic since the procedures that isolate cells from whole blood can increase antigen expression. This study used whole blood flow cytometry to monitor neutrophil CD11b expression following 0, 1, 2, 3 and 4 h of ex vivo incubation at room temperature and examined the effects of storage at 4 degrees C and the cell stabilization solution, Cyto-Chex, on antigen expression. Cyto-Chex-treated samples were also re-analyzed after 7 days storage at 4 degrees C. Neutrophil CD11b expression was high (> 90%) in five of the seven samples studied and incubation at room temperature induced a progressive upregulation which was significant after 2, 3, and 4 h (p < 0.05). Storage at 4 degrees C tempered this effect, although an increased expression (from baseline) was still observed after 4 h (p < 0.05). Cyto-Chex had no effect on the light scatter characteristics of treated cells and prevented CD11b upregulation in samples stored at room temperature. Furthermore, expression in Cyto-Chex-treated samples after 7 days was not significantly different from that observed in baseline (time 0) samples. In two samples demonstrating low neutrophil CD11b expression, a temperature-independent increase in the proportion of CD11b+ cells was observed over time. However, this increase was attenuated by treatment with Cyto-Chex. These findings indicate that sample storage significantly affects CD11b expression and caution should be exercised when interpreting data. Given that Cyto-Chex had no effect on the light scatter properties of cells and prevents antigen upregulation, this reagent may be useful for studies involving analysis of neutrophil activation antigen expression.

Comparison of eccentric knee extensor muscle actions at two muscle lengths on indices of damage and angle-specific force production in humans.

In this study, we investigated the effects of knee extensor length during eccentric exercise on indices of muscle damage and adaptation. Subjects (n = 7) performed two bouts of 75 maximal voluntary eccentric muscle actions at a knee joint angular velocity of 1.57 rad s(-1). One bout was performed at a short muscle length (bout S) with a knee joint range of motion of 2.79 to 1.40 radians (160 degrees to 80 degrees), and a second with the contralateral knee extensors at a long muscle length (bout L) with a range of motion of 2.01 to 0.7 radians (120 degrees to 40 degrees). The maximum voluntary contractile force (MVC) was measured before and 5 min after exercise, and again on days 3, 5, 7, 10 and 12, at knee angles of 160 degrees, 120 degrees and 80 degrees. Muscle soreness was measured before exercise and on each day after exercise. Serum creatine kinase activity was measured before exercise and on days 3, 5, 7, 10 and 12 post-exercise. The MVC declined after each bout (P < 0.01), with a greater decline after bout L (P < 0.05). Muscle soreness was higher relative to bout S on days 1, 2, 3, 5 and 6 (P < 0.05). Although serum creatine kinase activity was elevated after both exercise bouts (P < 0.01), there was no difference between bouts. Functional muscle damage markers and muscle soreness suggest greater damage after bout L. Post-exercise angle-specific force decrements suggest a transient increase in muscle length after bout L but not bout S.