To determine the mechanism by which AMP 579, an adenosine A1/A2 agonist, administered at reperfusion protects ischemic myocardium, buffer-perfused rabbit hearts were subjected to 30 min of global ischemia and 2 h of reperfusion. AMP 579 (500 nM) was included in the reperfusate for the first 70 min. Average left ventricular diastolic pressure during reperfusion in hearts receiving AMP 579 was lower than that in control hearts (17.9 ± 2.4 vs. 39.0 ± 6.5 mm Hg, p < 0.05), indicating attenuation of contracture. Left ventricular developed pressure and coronary flow during reperfusion were also significantly improved with AMP 579 treatment. AMP 579's anti-contracture effect was blocked by the adenosine A2-receptor antagonist 8-(3-chlorostyryl)caffeine (CSC), but not by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). CSC, but not DPCPX, also blocked AMP 579's ability to preserve developed pressure and coronary flow in these hearts. AMP 579 significantly reduced infarction in isolated hearts subjected to regional ischemia. The anti-infarct effect again was abolished by CSC but not by DPCPX. Finally, we tested whether 5′-(N-ethylcarboxamido)adenosine (NECA), another A1/A2 agonist, also administered for the initial 70 min of reperfusion, could duplicate the anti-infarct effect of AMP 579. One-hundred-nanomolar NECA duplicated the protection, but neither 50 nM CGS21680, a selective A2 agonist, nor 100 μM adenosine was protective. Therefore, AMP 579 given at reperfusion reduces contracture and infarction. Anti-contracture and anti-infarct effects require the adenosine A2, but not the A1, receptor suggesting that prevention of contracture and tissue salvage are mechanistically related. Not all A2 agonists were able to duplicate the anti-infarct effect, suggesting something unique about AMP579.

Introdução: O alongamento dos músculos isquiotibiais (ISQ) tem sido utilizado com frequência para a correção da contratura em flexão dos joelhos na paralisia cerebral (PC), porém o aumento da anteversão da pelve (AP) e a recidiva da deformidade podem ocorrer a longo prazo. Objetivos: O objetivo deste trabalho foi avaliar se a transferência do semitendíneo para o tubérculo dos adutores (TXST) está relacionada a uma menor taxa de recidiva e a um menor aumento da AP no período pós-operatório, quando comparada ao alongamento deste músculo. Métodos: Foi realizado um estudo tipo coorte retrospectivo. Pacientes com PC diparesia espástica, Gross Motor Function Classification System (GMFCS) I-III, sem cirurgias prévias nos joelhos, submetidos ao alongamento dos ISQ mediais ou à TXST, e com completa documentação no laboratório de marcha foram incluídos no estudo. Foram excluídos aqueles que receberam de forma concomitante a osteotomia extensora do fêmur distal e o encurtamento patelar. Trinta e nove pacientes preencheram os critérios de inclusão e foram divididos em dois grupos de acordo com os procedimentos cirúrgicos realizados: Grupo A (22 pacientes / 44 joelhos), composto por aqueles que receberam o alongamento dos ISQ mediais; Grupo B (17 pacientes / 34 joelhos), formado por aqueles que receberam a TXST ao invés do alongamento do semitendíneo (AST), em conjunto com o alongamento dos demais ISQ mediais. Parâmetros clínicos e de cinemática foram avaliados nos dois grupos antes e após as cirurgias. Resultados: Os grupos não exibiram diferença quanto à distribuição por gênero, idade na cirurgia e tempo de seguimento. A deformidade irredutível em flexão estava presente em 9,1% dos joelhos no Grupo A e em 50% no Grupo B (p < 0,001) antes do tratamento, e em 25% dos joelhos do Grupo A e 20,6% no Grupo B (p=0,647) após os procedimentos cirúrgicos. O número de joelhos com deformidade irredutível em flexão aumentou no Grupo A (p=0,047) e reduziu no Grupo B (p=0,011) após a intervenção. Houve redução significativa da deformidade média em flexão dos joelhos ao exame físico (de 7,3° para 4,4°, p= 0,04) e da flexão dos joelhos durante a fase de apoio da marcha (de 34,2° para 20,2°, p < 0,001) apenas no Grupo B. A AP aumentou nos Grupos A e B após a correção cirúrgica da deformidade em flexão dos joelhos. Conclusão: O aumento da AP foi observado nos dois grupos após o tratamento efetuado. A redução da deformidade em flexão dos joelhos ao exame físico e o aumento da extensão dos joelhos na fase de apoio foram observados apenas nos pacientes submetidos à TXST / Introduction: Hamstrings surgical lengthening has been frequently used for the correction of knee flexion contracture in cerebral palsy (CP), however the increase of anterior pelvic tilt and the recurrence of the deformity can occur in a long-term follow-up. The aim of this study was to evaluate if semitendinosus transfer to distal femur (STTX) is related to less increase of anterior pelvic tilt and less recurrence of knee flexion deformity after treatment than semitendinosus surgical lengthening (STL). Methods: A retrospective cohort study was conducted. Patients with diplegic spastic CP, GMFCS levels I to III, without previous surgical procedures at knee, undergone to bilateral medial hamstrings surgical lengthening or STTX, and with complete documentation at gait laboratory were included in this study. Patients with concomitant distal femur extension osteotomy and patellar tendon shortening were excluded. Thirty-nine patients matched the inclusion criteria and they were divided in two groups according surgical procedures at knees: Group A (22 patients / 44 knees), including patients who received medial hamstrings surgical lengthening as part of multilevel approach; Group B (17 patients / 34 knees), represented by patients who underwent orthopedic surgery including a STTX instead of STL. Clinical and kinematic parameters were evaluated at baseline and at follow-up for all groups. Results: The two groups matched at gender distribution, age at surgery and follow-up time. Fixed knee flexion deformity (FKFD) before surgery was observed at 9.1% of knees in Group A and at 50% in Group B (p < 0.001). At final follow-up, 25% of knees in Group A and 20.6% in Group B shown FKFD (p=0.647). FKFD increased in Group A (p=0.047) and decreased in Group B (p=0.011) after treatment. The reduction of mean FKFD (from 7.3° to 4.4°, p= 0.04) and of knee flexion during gait stance phase (from 34.2° to 20.2°, p< 0.001) were observed only in Group B after surgical procedures. The anterior pelvic tilt increased at both groups after treatment. Conclusion: The increase of anterior pelvic tilt occurred at both groups after correction of knee flexion deformity. Patients who received STTX exhibited less fixed knee flexion deformity and better knee extension during stance phase after surgical treatment than those whom undergone to STL

Dupuytren's contracture (DC) is a fibromatous disease of the palmar fascia of unknown etiology. The present study was undertaken in order to assess pathophysiological mechanisms and consequences. In a cohort study of 2,375 patients operated for DC at the Department of Hand Surgery, Uppsala there was a male: female ratio of 5.9:1. Women had a higher mean age at first operation than men. One-third of the men and one-quarter of the women required repeated surgery. Early age at first operation was associated with recurrent disease. The risk of cancer was determined in 15,212 patients operated on for DC in Sweden. The overall relative risk was increased by 24%. There was a significantly increased risk for buccal, oesophageal, gastric, lung and pancreatic cancers, which indicates that smoking and alcohol abuse are probable risk factors for DC. Furthermore, there was an increased frequency of fibrosarcoma and malignant fibrous histiocytoma, the cause of which is unexplained The causes of death were evaluated in a national cohort of 16,517 patients operated for DC. There was an overall increased mortality (SMR=1.06), inversely related to age and significant for both sexes, in patients under 70 years. The risk estimate was highest for endocrine-, gastrointestinal-, and respiratory diseases, and accidents. There was also an increased SMR for cardiovascular diseases in younger patients more than 10 years after surgery. The most probable mechanism is related to smoking and other lifestyle factors. Outcome after surgery was not related to the immunohistochemical expression of connective tissue activation markers, such as collagen type IV, integrin α5, laminin, smooth muscle α-actin, procollagen type I, and desmin, in surgical specimens in a prospectively investigated group of patients. Furthermore, there were no associations between gender, age at onset of DC, number of operations, heredity, diabetes mellitus, or medication for cardiovascular disease, and the expression of the different markers. The individual characteristics that place a person at high risk are, thus, not obviously related to ongoing connective tissue production at time of surgery or to connective tissue activity in its conventionally used sense.

No description available.

Elbow contractures in burn survivors lead to difficulties in their ability to perform meaningful occupations. Interventions focus on improving movement at the elbow while considering social and psychological factors in the individual's environmental context. The purpose of the review was to determine the methodological quality of research evaluating splinting and serial casting to improve elbow contractures and resulting functional limitations. A comprehensive search strategy uncovered 10 research studies. Standardized critical appraisal tools and protocols were used to analyze the research. Although some methodological issues were identified, the findings were positive. Strengths and weaknesses of the research were delineated to support and guide the use of serial casting and splinting. A body of research was found to warrant consideration of social and psychological factors. Conclusion. There is preliminary quality of evidence to support the use of splinting and serial casting and important considerations for future research. / Rehabilitation Science - Occupational Therapy

Breast implant capsular contracture (CC) formation is a significant clinical complication post augmentation/reconstruction, which often necessitates re-operation. CC, which occurs in over half of patients post augmentation, is the formation of a fibrous internal capsule which constricts around the prosthesis leading to firmness, deformity and pain. The pathoetiology of CC is poorly understood with minimal understanding of the triggers, signalling pathways or dysregulated genes implicated in its formation. Therefore, the first aim of the present thesis was to investigate biomarkers implicated in CC formation, through whole genome microarray, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) on capsule samples ranging from normal capsules (Baker Grade 1) to severely contracted capsules (Baker Grade 4). After targeted enrichment analysis, microarray identified 6 genes which were significantly dysregulated in contracted capsules. After further genomic and proteomic validation, two potential diagnostic, prognostic or therapeutic biomarkers for CC, interleukin 8 (IL8) and tissue inhibitor of metalloproteinase 4 (TIMP 4), were identified as being significantly dysregulated in CC. However, the role of each of the multiple cell types which populate a contracted capsule has yet to be determined. Therefore, the role of capsular fibroblasts was investigated using immunocytochemistry, qRT-PCR, cytokine arrays and a fibroblast populated 3D collagen matrix. IL8 and TIMP were investigated, in addition to other pro-fibrotic and pro-inflammation related candidates, to identify the role of breast capsule fibroblasts in CC formation. Normal breast fibroblast populated collagen matrices were significantly more contracted after supplementation with contracted-capsule fibroblast conditioned media, in comparison to normal growth media. It was discovered that breast-derived fibroblasts were potentially instigating and/or perpetuating CC through the transformation of normal breast fibroblasts into contracted capsule fibroblast like cells, via a paracrine signalling mechanism. The results of this work on capsular fibroblasts, and the previous work on capsular tissue, increased our understanding of the cell types and signalling molecules which are dysregulated leading to CC formation. Therefore, a novel silicone implant surface potentially capable of averting CC formation could be fabricated. Acellular dermal matrix (ADM) has been used as an adjunct in breast implant augmentation/reconstruction resulting in reduced rates of CC formation. Therefore, the micro and nanoscale topography of ADM was reproduced in a silicone surface, through a novel fabrication technique utilising comprehensive characterisation of ADM with atomic force microscopy (AFM), maskless grayscale photolithography, modified deep reactive ion etching (DRIE) and replica moulding. The features of ADM were successfully re-created in silicone to within 5 nm (Sa) and 655 nm (Sz), at a length scale of 90x90 µm2. Biological evaluation revealed that ADM PDMS surfaces promoted cell adhesion, proliferation and survival when compared to commercially available implant surfaces while cell adhesion regulating genes were upregulated and pro-inflammatory/pro-fibrotic related genes were downregulated. A reduced inflammatory cytokine response was also observed. This study demonstrates that biomimetic prosthetic implant surfaces might significantly attenuate the acute in vitro foreign body reaction to silicone. In conclusion, the results of the present thesis have enhanced our knowledge and understanding of the pathological cellular and molecular mechanisms leading to CC, in addition to the design and development of a novel, biomimetic implant surface that is potentially capable of averting the identified pathological processes in vivo.

Introdução: O alongamento dos músculos isquiotibiais (ISQ) tem sido utilizado com frequência para a correção da contratura em flexão dos joelhos na paralisia cerebral (PC), porém o aumento da anteversão da pelve (AP) e a recidiva da deformidade podem ocorrer a longo prazo. Objetivos: O objetivo deste trabalho foi avaliar se a transferência do semitendíneo para o tubérculo dos adutores (TXST) está relacionada a uma menor taxa de recidiva e a um menor aumento da AP no período pós-operatório, quando comparada ao alongamento deste músculo. Métodos: Foi realizado um estudo tipo coorte retrospectivo. Pacientes com PC diparesia espástica, Gross Motor Function Classification System (GMFCS) I-III, sem cirurgias prévias nos joelhos, submetidos ao alongamento dos ISQ mediais ou à TXST, e com completa documentação no laboratório de marcha foram incluídos no estudo. Foram excluídos aqueles que receberam de forma concomitante a osteotomia extensora do fêmur distal e o encurtamento patelar. Trinta e nove pacientes preencheram os critérios de inclusão e foram divididos em dois grupos de acordo com os procedimentos cirúrgicos realizados: Grupo A (22 pacientes / 44 joelhos), composto por aqueles que receberam o alongamento dos ISQ mediais; Grupo B (17 pacientes / 34 joelhos), formado por aqueles que receberam a TXST ao invés do alongamento do semitendíneo (AST), em conjunto com o alongamento dos demais ISQ mediais. Parâmetros clínicos e de cinemática foram avaliados nos dois grupos antes e após as cirurgias. Resultados: Os grupos não exibiram diferença quanto à distribuição por gênero, idade na cirurgia e tempo de seguimento. A deformidade irredutível em flexão estava presente em 9,1% dos joelhos no Grupo A e em 50% no Grupo B (p < 0,001) antes do tratamento, e em 25% dos joelhos do Grupo A e 20,6% no Grupo B (p=0,647) após os procedimentos cirúrgicos. O número de joelhos com deformidade irredutível em flexão aumentou no Grupo A (p=0,047) e reduziu no Grupo B (p=0,011) após a intervenção. Houve redução significativa da deformidade média em flexão dos joelhos ao exame físico (de 7,3° para 4,4°, p= 0,04) e da flexão dos joelhos durante a fase de apoio da marcha (de 34,2° para 20,2°, p < 0,001) apenas no Grupo B. A AP aumentou nos Grupos A e B após a correção cirúrgica da deformidade em flexão dos joelhos. Conclusão: O aumento da AP foi observado nos dois grupos após o tratamento efetuado. A redução da deformidade em flexão dos joelhos ao exame físico e o aumento da extensão dos joelhos na fase de apoio foram observados apenas nos pacientes submetidos à TXST / Introduction: Hamstrings surgical lengthening has been frequently used for the correction of knee flexion contracture in cerebral palsy (CP), however the increase of anterior pelvic tilt and the recurrence of the deformity can occur in a long-term follow-up. The aim of this study was to evaluate if semitendinosus transfer to distal femur (STTX) is related to less increase of anterior pelvic tilt and less recurrence of knee flexion deformity after treatment than semitendinosus surgical lengthening (STL). Methods: A retrospective cohort study was conducted. Patients with diplegic spastic CP, GMFCS levels I to III, without previous surgical procedures at knee, undergone to bilateral medial hamstrings surgical lengthening or STTX, and with complete documentation at gait laboratory were included in this study. Patients with concomitant distal femur extension osteotomy and patellar tendon shortening were excluded. Thirty-nine patients matched the inclusion criteria and they were divided in two groups according surgical procedures at knees: Group A (22 patients / 44 knees), including patients who received medial hamstrings surgical lengthening as part of multilevel approach; Group B (17 patients / 34 knees), represented by patients who underwent orthopedic surgery including a STTX instead of STL. Clinical and kinematic parameters were evaluated at baseline and at follow-up for all groups. Results: The two groups matched at gender distribution, age at surgery and follow-up time. Fixed knee flexion deformity (FKFD) before surgery was observed at 9.1% of knees in Group A and at 50% in Group B (p < 0.001). At final follow-up, 25% of knees in Group A and 20.6% in Group B shown FKFD (p=0.647). FKFD increased in Group A (p=0.047) and decreased in Group B (p=0.011) after treatment. The reduction of mean FKFD (from 7.3° to 4.4°, p= 0.04) and of knee flexion during gait stance phase (from 34.2° to 20.2°, p< 0.001) were observed only in Group B after surgical procedures. The anterior pelvic tilt increased at both groups after treatment. Conclusion: The increase of anterior pelvic tilt occurred at both groups after correction of knee flexion deformity. Patients who received STTX exhibited less fixed knee flexion deformity and better knee extension during stance phase after surgical treatment than those whom undergone to STL

Etre capable de marcher sans ressentir de douleur, fatigue ou autres altérations est considéré comme une priorité pour les activités quotidiennes et est étroitement lié à la qualité de vie de chacun. De nombreuses atteintes du système neuro-musculo-squelettique peuvent engendrer des altérations de la marche. Une compréhension précise de ces altérations est nécessaire pour optimiser les stratégies thérapeutiques. Parmi ces atteintes, la rétraction musculaire est l'une des plus fréquentes. Elle correspond à un raccourcissement permanent du complexe musculotendineux limitant ainsi la mobilité des articulations. Elle est impliquée dans de nombreuses pathologies (paralysie cérébrale, hémiplégie, pieds bots, brûlures, etc.) L'objectif global de ce travail de thèse était d'étudier les effets des rétractions sur la marche humaine. Pour cela, un dispositif permettant d'émuler des rétractions a été mis en place et évalué. Ce dispositif est composé d'un exosquelette et de cordes permettant de limiter les amplitudes articulaires, simulant ainsi la rétraction des principaux muscles des membres inférieurs atteints par cette pathologie. Grâce à ce dispositif, l'effet des rétractions des muscles a été analysé. Des rétractions isolées ont été émulées sur 35 participants unilatéralement et bilatéralement et une analyse quantifiée de la marche a été réalisée. Les patterns cinématiques obtenus sur chaque articulation ont été ensuite utilisés pour analyser les liens entre altérations de marche et rétractions musculaires. Il a été montré que la rétraction des gastrocnemius peut provoquer un pattern de marche genoux fléchis, alors qu'une rétraction du soleus montre peu de modifications de la cinématique du genou. De plus, le lien entre la sévérité de la rétraction des gastrocnemius / soleus et la progression de la marche digitigrade (augmentation de la flexion plantaire pendant la marche) n'est pas linéaire. La marche «genoux fléchis» peut être causée par les rétractions des ilio-psoas, ischio-jambiers et gastrocnemius. Des patterns cinématiques particuliers ont été identifiées en lien avec les muscles responsables de la marche «genoux fléchis». Il a été également montré que les rétractions des muscles du membre inférieur ont des effets importants spécifiques sur la position moyenne du tronc et du bassin dans le plan sagittal. Derrière son objectif scientifique, les résultats obtenus dans ce projet ont le potentiel d'améliorer le choix des stratégies de traitement et donc d'avoir un impact sur la qualité de vie des patients / Preserving or restoring the ability to walk without pain, fatigue or any gait alterations is considered a priority for activities of daily living and is closely related to quality of life. Numerous alterations of the neuro-musculo-skeletal system lead to gait deviations. To treat these alterations, a precise understanding of gait deviations is required. For patients with gait disorders, instrumented gait analysis can be performed to measure precisely the gait deviations. Among the varied causes of gait alterations, one of the most frequent is contractures that affect numerous pathologies. It corresponds to a permanent shortening of a musculo-tendinous complex limiting the mobility of the joints. It is involved in many pathologies (cerebral palsy, stroke, clubfoot, burns, etc.) The global objective of this thesis was to study the effects of contractures on human walking. For this purpose, a device for emulating contractures has been built and evaluated. This device consists of an exoskeleton and ropes to limit joint range of motion of the major lower limb muscles affected by contractures. With this device, the effect of contractures of the musculo-tendinous complex was analysed. Isolated contractures were emulated on 36 participants unilaterally and bilaterally and an instrumented gait analysis was performed. The kinematic patterns obtained for each joint were then used to link kinematic gait alterations with muscle contractures. It has been shown that contracture of gastrocnemius can cause a knee flexion pattern, while a contracture of the soleus shows moderate changes in knee kinematics. Moreover, the relationship between the level of contracture of gastrocnemius / soleus and the progression of the equinus gait (increase in plantar flexion during walking) is not linear. «Knee flexion» gait pattern may be caused by the contractures of the iliopsoas, hamstrings and gastrocnemius. Particular kinematic patterns have been identified in relation to the muscles responsible to the «knee flexion» gait pattern. It has also been shown that retractions of the muscles of the lower limb have important specific effects on the mean position of the trunk and pelvis in the sagittal plane. Behind the scientific objective, the results of this project have the potential to improve the choice of treatment strategies and therefore to have an impact on patient’s quality of life

Introduktion: Uppsatsen är en systematisk litteraturstudie där författaren kritiskt granskar adekvata artiklar och annan aktuell litteratur, vilka beskriver Dupuytren´s kontraktur. Dupuytrens kontraktur är en fibroproliferativ sjukdom i palmar fascia och kännetecknas av en överdriven kollageninlagring. Syfte: Syftet med studien var att undersöka situationen för det kliniska arbetet samt forskning, hur man med den samlade kunskapen kan behandla Dupuytren´s kontraktur, vilka behandlings-metoder som har evidens idag samt vilken praxis som tillämpas inom området. Metod: En litteratursökning genomfördes i PubMed med sökord och kombination med Booleska sökoperationer för framtagning av relevanta artiklar, vilka faller inom ramen för uppsatta inklusionskriterier samt matchar syftet för uppsatsen. Resultat: Ingen behandling är överlägsen någon annan behandling och det finns en betydande och delad uppfattning om respektive metoder. Mindre invasiva tekniker, såsom perkutan nålfasciotomi samt injektionsbehandling med enzymet Kollagenas, är många gånger ett alternativ till kirurgi Slutsats: Hanteringen av en handkontraktur hos patienter med Dupuytrens sjukdom innebär fortfarande många utmaningar för handkirurger, trots framsteg inom medicinsk vetenskap och kirurgiska tekniker.

No description available.