Whole muscle length-tension properties vary with recruitment and rate modulation in areflexive cat soleus

The length-tension relationship is a fundamental property of muscle. In its classic form, which is used in muscle models incorporated into studies of motor control, the length-tension relationship is measured during maximal activation via tetanic electrical stimulation in whole muscles or during high intracellular calcium levels in single muscle fibers. In this study, we measured the length-tension relationship of the cat soleus muscle during different levels of natural activation consisting of recruitment and rate modulation of motor units generated by the crossed extension reflex. The ipsilateral dorsal roots were cut to eliminate sensory feedback from the soleus. Length-tension was measured by large shortening steps that transiently allowed force to drop to zero. Force then recovered to a new steady value as the shorter length was maintained for several seconds. The effects of various levels of crossed extension activation on length-tension were compared with direct electrical stimulation of the muscle at 5, 10, 20, and 100 Hz. At all levels of crossed extension, the slope of the length-tension function was much steeper than the slope for tetanic stimulation at 100 Hz. Most slopes for crossed extension fell between the slopes seen with electrical stimulation at 10 and 20 Hz. There was a modest overall tendency for slope to decrease with the level of crossed extension activation. Because much of the normal movement repertoire requires submaximal activation, muscle models based on the tetanic length tension relationship will greatly underestimate the contribution of this relationship to force modulation at different muscle lengths.     

The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies.

PURPOSE: Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. METHODS: Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. RESULTS: The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. CONCLUSIONS: To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.     

Magnetic resonance perfusion diffusion mismatch and thrombolysis in acute ischaemic stroke: a systematic review of the evidence to date

Background

The mismatch between perfusion and diffusion lesions on magnetic resonance perfusion‐weighted imaging (PWI)/diffusion‐weighted imaging (DWI) may help identify patients for thrombolysis. Evidence underlying this hypothesis was assessed.

Methods

All papers describing magnetic resonance PWI/DWI findings in patients with acute ischaemic stroke, and their functional and/or radiological outcome at 1 month, with or without thrombolysis were systematically reviewed.

Results

11 papers fulfilled the inclusion criteria. Among these, there were 5 different mismatch definitions and at least 7 different PWI methods. Only 3 papers including 61 patients with and 18 without mismatch provided data on mismatch, outcome and influence of thrombolysis. Mismatch (v no mismatch) without thrombolysis was associated with a non‐significant twofold increase in the odds of infarct expansion (odds ratio (OR) 2.2, 95% confidence interval (CI) 0.34 to 14.1), which did not change with thrombolysis (OR 2.0, 95% CI 0.37 to 10.9). Half of the patients without mismatch also had infarct growth (with or without thrombolysis). No data were available on functional outcome.

Conclusions

Standardised definitions of mismatch and perfusion are needed. Infarct growth may occur even in the absence of mismatch. Currently, data available on mismatch are too limited to guide thrombolysis in routine practice. More data are needed from studies including patients with and without mismatch, and randomised treatment allocation, to determine the role of mismatch.Ischaemic stroke is a global problem, for which few acute treatments are available. Thrombolysis has to be given rapidly and, when guided by plain computed tomography scan of the brain, carries a risk of intracranial haemorrhage. Imaging the mismatch between diffusion‐weighted imaging (DWI) and perfusion‐weighted imaging (PWI) on magnetic resonance imaging (MRI) (or presumed reversible ischaemia on computed tomography perfusion¹) might help identify patients with tissue at risk of infarction (even beyond the current 3 h time window), thereby avoiding thrombolysis in those with little chance of benefit.^2,3 These techniques are used increasingly where technology is available, and in acute‐stroke trials (http://www.strokecenter.org/trials).⁴The increasing use of this approach in trials and routine practice suggests that there are clear definitions of what constitutes mismatch and substantial evidence to justify its use. However, it is now known that the DWI lesion is not irreversible (initial DWI lesions may disappear spontaneously or after thrombolysis⁵), and that the appearance of PWI lesion depends on which of the many methods were used to calculate it. Different perfusion parameters (eg, mean transit time (MTT), regional cerebral blood flow⁶ and arterial input function⁷) give different perfusion lesion volumes in the same patient. Thus, it is unclear whether the presence (v absence) of mismatch affects prognosis. If mismatch is to be used to select patients for treatment, then the key point is to determine whether thrombolysis has a greater effect in the presence than in the absence of mismatch. This requires a randomised controlled trial in which patients with and without mismatch are randomly selected to receive thrombolysis or control treatment, an expensive and difficult undertaking given the large sample size needed.⁸As there is already a considerable body of literature available on the magnetic resonance mismatch concept, we undertook this systematic review to assess all current evidence on the effect of magnetic resonance PWI/DWI mismatch in patients with acute ischaemic stroke on outcome (clinical and radiological) and whether this is modified by thrombolysis. We set rigorous prespecified inclusion and exclusion criteria based on scientific principles for observational studies and randomised trials to minimise bias.     

Handgrip strength in English schoolchildren

Aims: The aims of this study were to evaluate patterns of handgrip (HG) strength in relation to gender and age in English schoolchildren and to compare this with existing data and produce reference data for this population. Methods: The HG of 7147 English schoolchildren (3773 boys and 3374 girls) aged 10–15.9 years was measured using a portable Takei handgrip dynamometer (Takei Scientific Instruments Co. Ltd, Tokyo, Japan). Centile data were produced using the Generalized Additive Models for Location, Scale and Shape. Z‐scores were generated using existing data for European children. Age and gender interactions were analysed using analysis of covariance. Results: In boys and girls, significant increases in HG were found between every age‐group (p < 0.001). Boys were significantly stronger than girls at every age (p < 0.001) and the boys’ age‐related increase was significantly greater than the girls’ (p < 0.001). Conclusion: This study provides reference data for handgrip strength in English schoolchildren. Handgrip strength in English children is broadly similar to existing European data, after adjusting for mass and stature. These data could be used for clinical or athletic screening of low and high strength in this population.     

A randomised control trial of physical activity in a perceived environment on self-esteem and mood in UK adolescents

This study assessed whether exercising whilst viewing natural or built scenes affected self-esteem (SE) and mood in adolescents. Twenty-five adolescents participated in three exercise tests on consecutive days. A graded exercise test established the work rate equivalent to 50% heart rate reserve for use in subsequent constant load tests (CLTs). Participants undertook two 15-min CLTs in random order viewing scenes of either natural or built environments. Participants completed Rosenberg’s SE scale and the adolescent profile of mood states questionnaire pre- and post-exercise. There was a significant main effect for SE (F(1) = 6.10; P < 0.05) and mood (F(6) = 5.29; P < 0.001) due to exercise, but no effect of viewing different environmental scenes (P > 0.05). Short bouts of moderate physical activity can have a positive impact on SE and mood in adolescents. Future research should incorporate field studies to examine the psychological effects of contact with real environments.     

Resting autonomic modulations and the heart rate response to exercise

Objectives  

Identify the underlying role of resting heart rate variability (HRV) in the hearts response to graded exercise testing (GXT).