nuclear fragmentation and ultrastructural changes in skeletal muscle after immobilisation

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Physiotherapy January 2000/vol 86/no 1 32 Physiotherapy January 2000/vol 86/no 1 Nuclear Fragmentation and Ultrastructural Changes in Skeletal Muscle after Immobilisation Linda Maxwell, H Smith University of Auckland, New Zealand Nuclear DNA fragmentation and ultrastructural changes, indicative of myonuclear apoptosis, were examined in adult skeletal muscle in response to short-term immobilisation. Adult rabbits were allocated to two (n = 5) or six (n = 5), days of unilateral casting of the ankle in full plantarflexion, or were used as untreated controls (n = 2). Atrophy of the soleus muscle was apparent by significant reductions in wet mass of 15% and 26% after two and six days of casting (p 0.05) respectively. Mean fibre cross-sectional area and myonuclear number per section were also lower (17% and 9.1% respectively) after six days of casting, in comparison to contralateral control muscles (p 0.05). Electron microscopic examination showed condensed chromatin and irregularly shaped myonuclei and capillary endothelial cell nuclei in muscles immobilised for either two or six days. Myofibrillar disruption, and abnormalities of the subsarcolemmal mitochondria were also apparent in casted muscles in the absence of inflammation or plasma membrane alterations. Longitudinal and transverse sections showed abundant in-situ end-labelling of DNA strand breaks (TUNEL) after two days, with less after six days, of immobilisation. Positive labelling corresponded to myonuclear locations within fibres, yet additional TUNEL-positive nuclei indicated DNA fragmentation in capillary endothelial cells and fibroblasts. The data indicate that the immobilisation of slow--twitch skeletal muscle in a shortened position rapidly induces morphological alterations consistent with mitochondrial dysfunction and apoptotic myonuclear elimination. Physiotherapy and Parkinson’s Disease: Evaluating best practice Ann Ashburn, Diana Jones, Brenda Lovgreen, Rowena Plant Parkinson’s Disease: Physiotherapy Evaluation Project UK Research Team Purpose: The aims of this evaluation of physiotherapy and Parkinson’s disease were to develop a consensus on best practice and propose a baseline model of physiotherapy practice. Methods: Stage 1 was a Delphi survey of specialist physiotherapists (senior I or above; at least two years working with the client group; a current caseload) in which 32 statements relating to context, reasons, actions and effects of practice generated from the literature were rated. In stage 2, case studies of best practice trusts identified from Delphi participants were undertaken. In three trusts, interviews were conducted with clinicians, managers, and team members. Ten patients and carers were interviewed at each site and a documentary analysis undertaken of their physiotherapy notes. In six sites telephone interviews were undertaken with clinicians and managers. Case study data sources were analysed separately, triangulated and related to Delphi results. Results: Responses from Delphi participants (49 specialists, mean of 20 years post-qualification and mean of 10 years treating the client group) highlighted marked variation in the actual context of practice. High levels of consensus about what was desirable allowed a service framework to be proposed, and the reason for physiotherapy – to maximise functional ability and minimise secondary complications through movement rehabilitation – to be articulated. An eclectic treatment approach was deemed best, and there was agreement on measuring effects at a functional level and related to specified aims of physiotherapy. Case study data focused on service structure, clinical activity and patient views. A theoretical framework for physiotherapy intervention has been proposed, together with a framework to link core areas of practice to service structure and treatment. Conclusion: This exploratory project has developed a multifaceted methodological process for therapy evaluation. It has provided frameworks on which focused research, guidelines and educational initiatives will be mounted. This study has been conducted under the auspices of the Parkinson’s Disease Society with funding from Glaxo Wellcome.

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Page 1: Nuclear Fragmentation and Ultrastructural Changes in Skeletal Muscle after Immobilisation

Physiotherapy January 2000/vol 86/no 1

32

Physiotherapy January 2000/vol 86/no 1

Nuclear Fragmentation andUltrastructural Changes in SkeletalMuscle after Immobilisation

Linda Maxwell, H SmithUniversity of Auckland, New ZealandNuclear DNA fragmentation and ultrastructural changes,indicative of myonuclear apoptosis, were examined in adultskeletal muscle in response to short-term immobilisation. Adultrabbits were allocated to two (n = 5) or six (n = 5), days ofunilateral casting of the ankle in full plantarflexion, or wereused as untreated controls (n = 2). Atrophy of the soleus musclewas apparent by significant reductions in wet mass of 15% and26% after two and six days of casting (p ≤ 0.05) respectively.

Mean fibre cross-sectional area and myonuclear number persection were also lower (17% and 9.1% respectively) after six days of casting, in comparison to contralateral controlmuscles (p ≤ 0.05).

Electron microscopic examination showed condensedchromatin and irregularly shaped myonuclei and capillaryendothelial cell nuclei in muscles immobilised for either two orsix days. Myofibrillar disruption, and abnormalities of thesubsarcolemmal mitochondria were also apparent in castedmuscles in the absence of inflammation or plasma membranealterations.

Longitudinal and transverse sections showed abundant in-situend-labelling of DNA strand breaks (TUNEL) after two days,with less after six days, of immobilisation. Positive labellingcorresponded to myonuclear locations within fibres, yetadditional TUNEL-positive nuclei indicated DNA fragmentationin capillary endothelial cells and fibroblasts.

The data indicate that the immobilisation of slow--twitchskeletal muscle in a shortened position rapidly inducesmorphological alterations consistent with mitochondrialdysfunction and apoptotic myonuclear elimination.

Physiotherapy and Parkinson’sDisease: Evaluating best practice

Ann Ashburn, Diana Jones, Brenda Lovgreen, Rowena Plant Parkinson’s Disease: Physiotherapy Evaluation Project UKResearch TeamPurpose: The aims of this evaluation of physiotherapy andParkinson’s disease were to develop a consensus on best practiceand propose a baseline model of physiotherapy practice.

Methods: Stage 1 was a Delphi survey of specialistphysiotherapists (senior I or above; at least two years workingwith the client group; a current caseload) in which 32statements relating to context, reasons, actions and effects ofpractice generated from the literature were rated.

In stage 2, case studies of best practice trusts identified fromDelphi participants were undertaken. In three trusts, interviewswere conducted with clinicians, managers, and team members.Ten patients and carers were interviewed at each site and adocumentary analysis undertaken of their physiotherapy notes.In six sites telephone interviews were undertaken with cliniciansand managers. Case study data sources were analysed separately,triangulated and related to Delphi results.

Results: Responses from Delphi participants (49 specialists, meanof 20 years post-qualification and mean of 10 years treating theclient group) highlighted marked variation in the actual contextof practice. High levels of consensus about what was desirableallowed a service framework to be proposed, and the reason forphysiotherapy – to maximise functional ability and minimisesecondary complications through movement rehabilitation – tobe articulated. An eclectic treatment approach was deemedbest, and there was agreement on measuring effects at afunctional level and related to specified aims of physiotherapy.Case study data focused on service structure, clinical activity andpatient views. A theoretical framework for physiotherapyintervention has been proposed, together with a framework tolink core areas of practice to service structure and treatment.

Conclusion: This exploratory project has developed amultifaceted methodological process for therapy evaluation. Ithas provided frameworks on which focused research, guidelinesand educational initiatives will be mounted.

This study has been conducted under the auspices of the Parkinson’s

Disease Society with funding from Glaxo Wellcome.