The feasibility and short-term benefits of Blue Prescription: a novel intervention to enable physical activity for people with multiple sclerosis.

PURPOSE: Participation in physical activity for people with Multiple sclerosis (MS) is important but can be difficult to sustain long-term. Facilitators for long-term adherence include choice over activity and control over level of engagement, coupled with support, advice and encouragement from a physiotherapist. This is the basis of Blue Prescription, a novel physiotherapy approach aimed at optimising long-term adherence with physical activity. We evaluated the feasibility and short-term benefits of Blue Prescription in people with MS. METHODS: Twenty-seven people with MS (mean age: 51 ± 11 years, with a range of MS type and disability) were assessed at baseline and immediately post-intervention with the MS Impact Scale, MS Self-efficacy Scale, and European Quality of Life Questionnaire. Change in outcomes were analysed with Wilcoxon signed ranks tests. RESULTS: All participants, irrespective of level of disability, were able to choose a physical activity and to engage in it. The physical component MS Impact Scale score significantly improved by a median change of 6.5 (95% CI = -10.5 to -2.0; p = 0.007; effect size = 0.38). There were no other significant changes in outcomes. CONCLUSION: Blue Prescription appears feasible and potentially beneficial, particularly in reducing the negative impacts of MS upon individuals, and thus warrants further evaluation.

Promoting physical activity for individuals with neurological disability: indications for practice.

PURPOSE: This study explored processes that influenced involvement in recreational exercise for individuals with neurological disability, to identify strategies to promote physical activity for health and well-being in this population. METHOD: Nineteen participants (11 males and eight females), aged 20-71 years, with a range of neurological conditions and functional limitations, were recruited in one large metropolitan area in New Zealand. Individual semi-structured interviews explored participants' views, perceptions, and experiences of undertaking recreational exercise. Data were analysed for themes. RESULTS: For some individuals, recreational exercise is undertaken for its physical, psychological, or social benefits, despite the physical activity itself feeling relatively unsatisfactory. In contrast, individuals who are able to undertake their preferred choice of recreational exercise experience intense satisfaction. This motivates self-maintenance of physical activity, even for those individuals who require carer support or assistance to do so. CONCLUSIONS: This study has identified that there can be two forms of involvement in recreational exercise that allows individuals with neurological disability to become more physically active. The information could be further developed and tested in intervention studies to provide strategies for health professionals to facilitate engagement in physical activity for people with neurological disability.

Dysfluency and involuntary movements: a new look at developmental stuttering.

Studies using modern imaging techniques suggest that, in developmental stuttering, there is dysfunction within the cortical and subcortical areas of the motor control system wider than that pertaining to speech motor control alone. If this is the case, one might expect motor deficits extending beyond and unrelated to the production of speech in people who stutter. This study explored this proposal by investigating the presence and characteristics of involuntary movements accompanying stuttering. Sixteen adults with developmental stuttering and 16 controls matched for age and sex were audio-videotaped during 5 minutes of conversational speech and reading a passage of 350 words. Audio-data were examined for dysfluencies. Movements of the face, head and upper body considered involuntary and not part of normal facial expression or gesture and not part of the mechanics of speech were identified and described from muted video-data. Subjects who stuttered had a higher proportion of classic (within-word) dysfluencies accompanied by involuntary movements (IMs) than controls during speech (24.4% vs. 4.5%, p = .054) and reading (28.6% vs. 4.9%, p = .033). There was no difference in proportion of classic dysfluencies accompanied by IMs between speech and reading for either group. IMs were also seen in both groups during fluent speech, with a similar incidence during free speech (3.9% vs. 3.0%, NS) but a greater incidence in the subjects who stuttered during reading (2.4% vs. 0.8%, p = .03). In contrast, there was no difference between the two groups for IMs accompanying normal (between-word) dysfluencies. This suggests that classic and normal dysfluency and their accompanying IMs have different etiologies. The notion that stuttering and IMs are due to altered function in a motor control system wider than that of speech motor control alone is supported by a higher incidence of IMs in people who stutter during both classic dysfluencies and fluent speech.

Weight loss in a murine cachexia model is not associated with the cytokines tumour necrosis factor-alpha or interleukin-6.

Daily administration of an escalating dose of tumour necrosis factor-alpha (TNF-alpha) to female NMRI mice caused a progressive loss of body weight representing 12% of the original weight over a 6-day period. Weight loss was associated with a decreased food intake and pair-fed controls exhibited a weight loss of similar magnitude to that caused by TNF-alpha. However, weight loss in animals bearing a murine adenocarcinoma (MAC16) occurred without a change in energy intake and thus differed from that produced by TNF-alpha. Anti-TNF-alpha monoclonal antibodies at levels capable of protecting mice against lethal endotoxaemia were ineffective in reversing weight loss in animals bearing the MAC16 tumour and had no effect on the increase in tumour volume. Circulating levels of interleukin-6 were not elevated in animals bearing the MAC16 tumour and with a weight loss between 1.8 and 5.4 g. These results suggest that these cytokines are not involved in the cachexia produced by this murine tumour.

Lipid metabolism in cancer cachexia.

The effect of cancer cachexia on the oxidative metabolism of lipids has been studied in mice transplanted either with the MAC16 adenocarcinoma, which induces profound loss of body weight and depletion of lipid stores, or the MAC13 adenocarcinoma, which is the same histological type, but which grows without an effect on host body weight or lipid stores. While oxidation of D-[U-14C]glucose did not differ between animals bearing tumours of either type and non-tumour bearing controls, oxidation of [1-14C]triolein administered by intragastric intubation was significantly (P less than 0.05) higher in animals bearing the MAC16 tumour than in either non tumour-bearing controls or in animals bearing the MAC13 tumour. Intestinal absorption of [14C]lipid was significantly (P less than 0.05) reduced in animals bearing the MAC13 tumour when compared with either non tumour-bearing animals or MAC16 tumour-bearing animals, but was not significantly different in the latter two groups. The level of labelled lipids in heart and adipose tissue after an oral [14C]lipid load was significantly lower in animals bearing the MAC16 tumour compared with the other two groups. The level of tumour lipids was also higher in the MAC16 than in the MAC13 tumour after both an oral [14C]lipid load or by direct injection of [U-14C]palmitate complexed to albumin into epididymal fat pads. Oxidation of [U-14C]palmitate was also significantly enhanced in liver and heart homogenates from animals bearing the MAC16 tumour. These results suggest that in cachectic tumour-bearing animals mobilisation of body lipids is accompanied by an increased utilisation.

Effect of the lipid-lowering agent bezafibrate on tumour growth rate in vivo.

The growth rate of the MAC16 tumour in cachectic animals was significantly enhanced by the hypolipidemic agent bezafibrate, while the growth rate of a histologically similar tumour, the MAC13, which grows without an effect on host body compartments was unaffected. Growth of the MAC16 in vitro was unaffected by bezafibrate, suggesting that it was an in vivo phenomenon only. The stimulatory effect of bezafibrate correlated with the maximum plasma levels of free fatty acids (FFA) arising from the catabolism of adipose tissue. Accumulation of 14C-lipid from 1-14C-triolein administered by intragastric intubation was enhanced in heart, gastrocnemius muscle and tumour of bezafibrate treated animals, while the total lipid absorption did not differ from solvent treated controls. The increased lipid accumulation in the heart, but not the tumour correlated with an increased tissue lipoprotein lipase level. The increased tumour level may arise from an increased uptake of FFA arising from a weakening of the bonds between FFA and albumin. These results suggest that growth of certain tumours is dependent on maintaining sufficient lipid levels and that the lipid mobilising effect of the tumour may be necessary to sustain tumour growth.

Metabolic substrate utilization by tumour and host tissues in cancer cachexia.

Utilization of metabolic substrates in tumour and host tissues was determined in the presence or absence of two colonic tumours, the MAC16, which is capable of inducing cachexia in recipient animals, and the MAC13, which is of the same histological type, but without the effect on host body composition. Glucose utilization by different tissues was determined in vivo by the 2-deoxyglucose tracer technique. Glucose utilization by the MAC13 tumour was significantly higher than by the MAC16 tumour, and in animals bearing tumours of either type the tumour was the second major consumer of glucose after the brain. This extra demand for glucose was accompanied by a marked decrease in glucose utilization by the epididymal fat-pads, testes, colon, spleen, kidney and, in particular, the brain, in tumour-bearing animals irrespective of cachexia. The decrease in glucose consumption by the brain was at least as high as the metabolic demand by the tumour. This suggests that the tissues of tumour-bearing animals adapt to use substrates other than glucose and that alterations in glucose utilization are not responsible for the cachexia. Studies in vitro showed that brain metabolism in the tumour-bearing state was maintained by an increased use of lactate and 3-hydroxybutyrate, accompanied by a 50% increase in 3-oxoacid CoA-transferase. This was supported by studies in vivo which showed an increased metabolism of 3-hydroxybutyrate in tumour-bearing animals. Thus ketone bodies may be utilized as a metabolic fuel during the cancer-bearing state, even though the nutritional conditions mimic the fed state.

Lipogenesis in tumour and host tissues in mice bearing colonic adenocarcinomas.

Although animals bearing the MAC16 colon adenocarcinoma showed progressive weight loss, the average food consumption (15.1 +/- 0.6 Kcal day-1) did not differ from non tumour-bearing controls (15.3 +/- 0.3 Kcal day-1), while animals bearing a related colon adenocarcinoma, MAC13, which had no effect on body weight had a significantly (P less than 0.01) elevated food intake (16.4 +/- 0.3 Kcal day-1) above controls. Weight loss in animals bearing the MAC16 tumour was associated with a significant reduction in the percentage contribution of the kidneys, colon and epididymal fat pads to the total body weight. Although loss of body fat occurred only in the MAC16 model, both tumours were capable of synthesising lipids from glucose both in vitro and in vivo at the same rate. In addition both tumours increased the rate of lipogenesis from glucose in kidney, liver and epididymal fat pads of the host. Lipogenesis from glucose would be expected to result in a loss of utilisable carbohydrate energy and thus would be expected to increase the overall energy requirements in the tumour-bearing state leading to catabolism of host body tissues if the energy intake is not increased.

Lipolytic factors associated with murine and human cancer cachexia.

We have identified a lipolytic factor in extracts of a cachexia-inducing murine carcinoma (MAC16) that shows characteristics of an acidic peptide and appears to be composed of three fractions of apparent molecular weights corresponding to 3 kd, 1.5 kd, and 0.7 kd, as determined by exclusion chromatography. Material with identical chromatographic and molecular weight characteristics was also present in the serum of patients with clinical cancer cachexia but absent from normal serum, even under conditions of starvation. The MAC16 lipid factor, when injected into animals bearing the non-cachexia-inducing tumor MAC13, was capable of inducing weight loss without a significant reduction in food intake. Similar lipolytic material, although in lower concentration, was also found in the MAC13 tumor extracts. These findings suggest that cachexia may arise from the enhanced expression of a lipolytic factor associated with tumor cells.