The relationship between myocardial cell contracture and injury during total metabolic inhibition (amylobarbital and iodacetic acid) and ischemia was examined, using 5-50 mm butanedione monoxime (BDM) as an inhibitor of contracture. BDM had no apparent effect on control myocytes during 180 min incubations, but inhibited contracture following anoxia or ischemia in a dose-dependent fashion, as directly quantitated by length/width ratios. Cellular ATP levels decreased at a similar rate in the absence or presence of BDM, following metabolic inhibition. BDM-mediated inhibition of contracture was associated with accelerated cell injury, as defined by: the uptake of an extracellular marker (trypan blue) by the cardiomyocytes, by direct analysis of myoglobin released into the supernatant and by ultrastructural demonstration of defects in sarcolemmal membrane integrity. Calcium was not required for BDM's enhancement of injury, in that cells incubated in calcium free-EGTA buffer showed a similar BDM-mediated acceleration of injury. In the presence or absence of calcium, enhancement of injury was more marked in cells osmotically stressed with a brief incubation in hypotonic buffer, than in cells resuspended in isotonic media. It is concluded that BDM enhances development of osmotic fragility of inhibited or ischemic cardiomyocytes and that contracture is not a necessary contributing factor to myocardial cell death.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Bakgrund: År 2020 efterlyste Statens beredning för medicinsk och social utvärdering, (SBU), en uppdaterad litteraturöversikt gällande effekten av kontrakturprofylax. Kroniska neurologiska tillstånd som föranlett nedsättning av aktiv rörlighet utgör populationen där kontrakturprofylax är en del av den fysioterapeutiska interventionen och då oftast i form av passivt rörelseuttag.  Syftet: Denna systematiska översikt syftar till att undersöka effekten av kontrakturprofylax som förebyggande och behandlande åtgärd för vuxna individer med kroniska neurologiska tillstånd som föranlett nedsättning av aktiv rörlighet. Syftet utöver det var att sammanställa resultatets vetenskapliga kvalitet och tillförlitlighet. Metod: En systematisk översikt över RCT-studier producerade mellan 2013 och 2023, där interventionen syftar till att förebygga eller behandla kontrakturer. Artiklarnas kvalitet granskades med PEDro skalan och det sammanvägda resultatets tillförlitlighet granskades med den studentanpassade versionen av GRADE. Kvaliteten var genomgående hög medan det sammanvägda resultatet har en låg sammanvägd tillförlitlighet. Resultat: Sju artiklar med ett totalt deltagarantal på 367 granskades. Kvaliteten varierade bedömt utifrån PEDro mellan 7 och 10 poäng, samtliga studier inkluderades i den sammanvägda bedömningen av tillförlitlighet. Sammanvägt hade studierna låg tillförlitlighet, detta på grund av bristande samstämmighet och överförbarhet, precisionen ansågs acceptabel.  Slutsatser: Det går inte att dra slutsatser gällande enskild effekt av kontrakturprofylax i form av passiv rörelseträning. Samtidigt framkommer inte något underlag för att kontrakturprofylax skulle negativt påverka andra interventioner. Det behövs mer forskning inom området och mätning av ledrörlighet och definition av kontrakturprofylax bör även standardiseras för ett mer överförbart och samstämmigt resultat. Denna studie kan således inte konkludera om en fysioterapeut bör använda kontrakturprofylax, vare sig som förebyggande eller behandlande åtgärd. / Background: In 2020, the State's preparation for medical and social evaluation, (SBU), called for an updated literature review regarding the effect of contracture prophylaxis. Chronic neurological conditions that have caused a reduction in active mobility make up the population where contracture prophylaxis is part of the physiotherapeutic intervention and then usually in the form of passive range of motion. Aim: The aim of this systematic review was to investigate the effect of contracture prophylaxis as a preventive and treatment measure for adults with chronic neurological conditions that have caused impairment of active mobility. The purpose, in addition to that, was to compile the scientific quality and reliability of the results. Method: A systematic review of RCT-studies produced between 2013 and 2023, where the intervention aims to prevent or treat contractures. The quality of the articles was reviewed with the PEDro scale, and the reliability of the combined results was reviewed with the student-adapted version of GRADE. The quality was considered high, while the summarized result had a low reliability. Results: Seven articles with a total number of participants of 367 were reviewed. The quality varied as assessed based on PEDro between 7 and 10 points, all studies were included in the combined assessment of reliability. Summarized, the studies had low reliability, this due to a lack of consistency and transferability, the precision was considered acceptable. Conclusions: It is not possible to draw conclusions regarding the individual effect of contracture prophylaxis in the form of passive movement training. At the same time, there is no evidence that contracture prophylaxis would negatively affect other interventions. More research is needed in the field and measurement of joint mobility and definition of contracture prophylaxis should also be standardized for a more transferable and consistent result. This study cannot therefore conclude whether a physiotherapist should use contracture prophylaxis, either as preventive care or as treatment.

The knee joint is a diarthrodial joint that rotates in the flexion-extension axis to provide individuals mobility. A limitation in the passive range of motion (ROM) is detrimental for function and this limitation is termed a joint contracture. A commonly shared characteristic between conditions that lead to contracture formation is prolonged periods of immobilization. However, the etiology of immobility-induced joint contractures is not well described and requires quantitative data on anatomical structures limiting knee mobility to design new interventions aimed at restoring function. In turn, our research group has developed an experimental animal model to study the temporal pathophysiology of knee immobilization and reversibility through unassisted remobilization. With durations of immobilization ranging from 1 to 32 weeks and remobilization up to 48 weeks, our experimental design provides a comprehensive temporal overview on the various stages of contracture formation: initiation, progression, and severity. A combination of muscles and articular structures are involved in the pathophysiology of knee flexion contractures, but the posterior joint capsule is of particular interest. Through histomorphological analysis, we provided quantitative data on the contribution of the reduced posterior capsule length in the limitation of knee extension and increased joint stiffness. Moreover, elucidation of synoviocyte profiles within the synovium of the capsule provided insights to potential mechanisms of capsule shortening. Our novel measurable outcome of mechanical joint stiffness revealed distinct temporal differences with ROM measurements after joint immobilization and remobilization, suggesting that alterations in the biomechanical properties of articular tissue structures are also contributing to the limitation in function. Malleability of the dynamic reciprocal relationship between trabecular bone loss and accumulation of marrow adipose tissue (predominately through adipocyte hyperplasia) after knee immobilization underscores the sensitivity of the bone marrow microenvironment in response to mechanical stimuli and lack thereof. Remobilization of the knee joint is limited in its capacity to reverse detriments induced by extended periods of joint immobilization. Findings from this work point to the temporal changes detected in different musculoskeletal tissues during knee immobilization and emphasizes the contribution of the joint capsule in limiting joint mobility.

As the survival rate increases, the importance of quality of life post-cancer is increasing. This, in conjunction with genetic screening, has increase the number of breast reconstructions 36%. The most common complication causing revision of reconstructive surgery is the formation of a dense scar capsule around the silicone implant called capsular contracture. Nearly all patients will experience this complication, though with different degrees of response, ranging from moderate scarring to major disfigurement and pain at the implant site. Presently, there is no way to predict the degree of contraction capsule formation that individual patients will suffer prospectively, nor is there clinical approach to preventing this complication. Patient information and tissue was collected in a uniform manner to address these lingering problems. Clinical data was used to construct a predictive model which can accurately predict capsular contracture severity in breast reconstruction patients. Histological analysis demonstrated differences in structure and cell composition between different capsule severities. Of particular note, a new region was described which could serve as the communication interface between innate immune cells and fibroblasts. RNA-seq analysis identified 1029 significantly dysregulated genes in severe capsules. Pathway enrichment was then performed which highlights IL4/13 signaling, extracellular matrix organization, antigen presentation, and interferon signaling as importantly dysregulated pathways. These RNA results were also compared to various clinical and histological measurements to evaluate novel correlations. PVT-1, a long non-coding RNA associated with cancer, was strongly correlated to capsules formed after cancer removal. This suggests cancerous transformations of cell types that remain after the tumor is removed. Furthermore, transgelin and caspase 7 correlated to myofibroblasts density, suggesting an abnormal fibroblasts that are resistant to cell death and may have enhanced contractile abilities. Capsule formation is a complex process however, with well controlled clinical models quantitative differences can be found. These results serve as stepping stone for the field to move beyond retrospective clinical trials and pursue treatments and preventative measures. / Ph. D.

Author: Bc. Antonín Mařík Title: Capture of the abduction contracture of the hip joint as a biomechanical cause of idiopathic scoliosis The theme of the thesis is based on lectures and numerous publications by Professor Tomasz Karski, MD, PhD from Lublin, published in international journals (from the 1990s to the present). The work is based on the biomechanical cause of the "so-called idiopathic" scoliosis, the cause of which is considered primarily the restriction of adduction in the right hip joint - so-called an abduction contracture. This contracture is one of the symptoms of "Syndrome of Contracture" according to Prof. Hans Mau (Tübingen, Germany). The years-long prevailing "standing easy" attitude on the right lower limb is a manifestation of the abduction contracture in the right hip joint and the cause of scoliosis in two groups and three types of classification of "biomechanical" scoliosis according to Karski. The main object of the thesis is an objective assessment of the relationship between the abduction contracture of the right hip joint and the idiopathic scoliosis (IS) of the spine in the examined set of probands. Clinical and anthropological examinations were performed in a group of 20 patients with idiopathic scoliosis and 16 control probands, including specialized tests on the...

Author: Bc. Antonín Mařík Title: Capture of the abduction contracture of the hip joint as a biomechanical cause of idiopathic scoliosis The theme of the thesis is based on lectures and numerous publications by Professor Tomasz Karski, MD, PhD from Lublin, published in international journals (from the 1990s to the present). The work is based on the biomechanical cause of the "so-called idiopathic" scoliosis, the cause of which is considered primarily the restriction of adduction in the right hip joint - an abduction contracture. This contracture is one of the symptoms of "contractures and deformity syndrome" according to Prof. Hans Mau (Tübingen, Germany). The years-long prevailing "standing easy" attitude on the right lower limb is a manifestation of the restriction of abduction - the abduction contracture in the right hip joint and the cause of scoliosis in two groups and three types of classification of "biomechanical" scoliosis according to Karski. The main object of the thesis is an objective assessment of the relationship between the abduction contracture of the right hip joint and the idiopathic scoliosis of the spine in the examined set of probands. The thesis focuses, among other things, on the recent overview of the knowledge about idiopathic scoliosis, especially on diagnostics and...

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The present study aimed to assess the heat generated by a therapeutic ultrasound (TUS) in a metal bone plate and adjacent structures after fixation to the femur of canine cadavers. Ten pairs of hindlimbs were used, and they were equally distributed between groups that were subjected to 1- and 3-MHz frequencies, with each frequency testing 1- and 2-W/cm² intensities. The right hindlimb was defined as the control group (absence of the metal plate), and the left hindlimb was the test group (presence of the metal plate). Therefore, the control groups (CG) were denominated CGI, using TUS with 1-MHz frequency and 1-W/cm² intensity; CGII, using 1-MHz frequency and 2-W/cm² intensity; CGIII, using 3-MHz frequency and 1-W/cm² intensity; and CGIV, using 3-MHz frequency and 2-W/cm² intensity. For each control group, its respective test group (TG) was denominated TGI, TGII, TGIII and TGIV, respectively. The TUS was applied to the lateral aspect of the thigh using the continuous mode and a 3.5-cm² transducer in a 6.25-cm² area for 2 minutes. Sensors were coupled to digital thermometers that measured the temperature in different sites before (t0) and after (t1) of the TUS application. The temperatures in t1 were higher in all tested groups. The intramuscular temperature was significantly higher (P < 0.05) in the groups used to test the 3-MHz frequency in the presence of the metal plate. The therapeutic ultrasound in the continuous mode using frequencies of 1 and 3 MHz and intensities of 1 and 2 W/cm2 for 2 minutes caused heating of the metal plate and adjacent structures after fixation to the femur of canine cadavers. / O objetivo deste estudo foi avaliar o aquecimento gerado pelo ultrassom terapêutico (UST) na placa óssea metálica e estruturas adjacentes após a fixação no fêmur de cadáveres caninos. Foram utilizados dez pares de membros pélvicos, distribuídos igualmente entre os grupos que utilizaram as frequências de 1 e 3 MHz. Cada frequência testou as intensidades de 1 e 2 W/cm², sendo que o membro pélvico direito foi definido grupo controle (ausência da placa óssea metálica) e o membro pélvico esquerdo o grupo teste (presença da placa óssea metálica). Portanto, os grupos controles foram denominados GCI, com UST na frequência de 1 MHz e intensidade de 1 W/cm², GCII com 1 MHz e 2 W/cm², GCIII com frequência de 3 MHz e intensidade de 1 W/cm² e GCIV com 3 MHz e 2 W/cm². Para cada grupo controle, seu respectivo grupo teste foi denominado GTI, GTII, GTIII e GTIV. O UST foi aplicado na face lateral da coxa utilizando o modo contínuo, transdutor de 3,5 cm² em uma área de 6,25 cm², durante dois minutos. Foram utilizados sensores acoplados a termômetros digitais que mediram a temperatura em diferentes locais antes (t0) e após (t1) a aplicação do UST. Pode-se verificar que as temperaturas em t1 foram maiores em todos os grupos testados. Os grupos que testaram a frequência de 3 MHz demonstraram que a temperatura intramuscular foi significativamente maior (P<0,05) na presença da placa óssea metálica. O ultrassom terapêutico no modo contínuo de 1 e 3 MHz e intensidades de 1 e 2 W/cm2 durante dois minutos promove o aquecimento da placa óssea metálica e estruturas adjacentes após a fixação no fêmur de cadáveres caninos.

Introduction: Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder affecting the palms of the hands of certain patient groups. Whether changes in DD fibroblasts are due to genetic alterations alone or related to metabolic dysregulation has not yet been investigated. Hypotheses: 1. DD is a disease of several networks rather than of a single gene. 2. DD may be investigated more effectively by employing systems biology. 3. Strict definition of cell passage number is important for the revelation of any DD phenotype. 4. Some of the differences between DD and healthy tissues reside in a difference in their respiratory metabolism. 5. Any such differences are akin the Warburg effect noted for tumour cells in the literature. Methods: We induced hypoxia in healthy and disease cells to test whether the difference in disease cell types and healthy is the same as the difference in control fibroblasts cultured in normoxia and hypoxia. We investigated both at the metabolic level (intracellular and extracellular) and at the transcript level. This study also employed Fourier transform infrared spectroscopy to permit profiling of cells: (1) DD cords and nodules against the unaffected transverse palmar fascia (internal control), (2) those (1) with carpal ligamentous fascia (external controls) (3) those in (1) against DD fat surrounding the nodule, and skin overlying the nodule. We then compared metabolic profiles of the above to determine the effect of serial passaging by assessment of reproducibility. Subsequently, a novel protocol was employed in carefully controlled culture conditions for the parallel extraction of the metabolome and transcriptome of DD-derived fibroblasts and control at normoxic and hypoxic conditions to investigate this hypothesis. Gas chromatography-mass spectrometry combined with microarrays was employed to identify metabolites and transcript characteristic for DD tissue phenotypes. The extracellular metabolome was also studied for a selected subset. The metabolic and transcriptional changes were then integrated employing a network approach. Results: Carefully controlled culture conditions combined with multivariate statistical analyses demonstrated metabolic differences in DD and unaffected transverse palmar fascia, in addition to the external control. Differences between profiles of the four DD tissue phenotypes were also demonstrated. In addition early passage (0-3) metabolic differences were observed where a clear separation pattern in clusters was observed. Subsequent passages (4-6) displayed asynchrony, losing distinction between diseased and non-diseased sample phenotypes. A substantial number of dysregulated metabolites involved in amino acid metabolism, carbohydrate metabolism and also metabolism of cofactors and vitamins including downregulated cysteine and aspartic acid have been identified from the integrative analyses. Metabolic and transcriptional differences were revealed between fibroblast cell samples (passage number 3) cultured in 1% and 21% oxygen. The hypothesis that the difference in disease and healthy cells maybe akin to the differences in healthy cells in normoxia and hypoxia was rejected as only a very small number of significant molecules from these studies coincided in perturbed fascia and disease samples. No lactic acid was observed and little difference in the pyruvate concentrations. Yet, upon perturbation several of these transcripts and metabolites involved in the afore-mentioned pathways were significantly dysregulated. Conclusion: Early, but not late, passage numbers of primary cells provide representative metabolic and transcript fingerprinting for investigating DD. A unique parallel analysis of transcript and metabolic profiles of DD fibroblasts and control, enabled a robust characterization of DD and correlation of parameters across the various levels of systemic description. The tools that should facilitate our understanding of these complex systems are immature, but the pleiotropy of the difference between healthy and DD tissue suggest the aetiology of a network-based disease.

Résumé : Dans la sclérodermie systémique (ScS), les contractures aux mains, pour lesquelles il n'existe aucun traitement prouvé, sont courantes et associées à de l'incapacité de la main, globale et au travail. Toutefois, quelques études sur les effets d'interventions comprenant des techniques manuelles ont montré des résultats prometteurs. Ainsi, le but de l'étude était d'explorer les effets d’un traitement ostéopathique sur la fonction de la main, des symptômes globaux de la maladie et le statut fonctionnel de personnes atteintes de ScS. Une série d'études à cas uniques (A[indice inférieur 1]-B-A[indice inférieur 2]) fut réalisée. Six participantes atteintes de ScS ont été recrutées parmi la cohorte du Groupe de recherche canadien sur la sclérodermie à deux sites (Hôpital général juif de Montréal et Centre hospitalier universitaire de Sherbrooke). Les participantes ont reçu neuf séances hebdomadaires d’ostéopathie semi-standardisées, ciblées sur les membres supérieurs, le thorax et la base du crâne. Des mesures répétées pendant les trois phases de l'étude ont été prises à une fréquence bihebdomadaire pour la raideur aux mains (RM) et les symptômes de douleur, dyspnée et fatigue; et hebdomadaire pour l'amplitude de mouvement des doigts (AMD), la fonction de la main (FM) et l'incapacité globale (IG). L'épaisseur/rigidité de la peau main/avant-bras (ÉPMA), l'incapacité au travail (IT) et la qualité de vie reliée à la santé (QVS) ont été mesurées à trois temps (avant et après l'intervention, ainsi qu'au suivi à un mois). Les variables à mesures répétées ont été représentées sur des graphiques linéaires soumis à des analyses visuelles, complétées du test Sheward's two Standard Deviation Band. Les différences ont été calculées pour les variables mesurées à trois temps. Toutes les participantes (n=6) ont montré une amélioration des variables reliées à la fonction manuelle (RM, AMD et FM), sauf pour l'ÉPMA (n=4). La majorité des participantes ont montré une amélioration des symptômes (douleur n=6, fatigue n=4 et dyspnée n=3/4) et des variables reliées au statut fonctionnel (IG n=5/5, IT n=4, score résumé physique n=6 et mental n=4 de la QVS). La plupart des effets se sont maintenus au suivi à un mois. Lorsque la comparaison était possible, presque toutes les améliorations observées ont été supérieures aux différences minimales cliniquement importantes suggérées pour cette population. Ces résultats suggèrent que l'ostéopathie pourrait être efficace pour réduire l'incapacité découlant des contractures aux mains de personnes souffrant de ScS, et devraient être vérifiés dans un essai clinique randomisé. // Abstract : In systemic sclerosis (SSc), hand contractures are common and associated with hand, global and work disability. There are no known effective treatments, although there have been a few promising studies with manual therapies. Our aim was to explore the effects of osteopathy on hand function, disease symptoms and functional status in SSc patients. A series of single case studies (A[subscript 1]-B-A[subscript 2] was undertaken. Six female SSc patients with hand contractures were recruited among subjects enrolled in the Canadian Scleroderma Research Group cohort at 2 sites (Jewish General Hospital, Montreal and Centre hospitalier universitaire de Sherbrooke, Sherbrooke). Participants received 9 weekly semi-standardized sessions of osteopathy targetted on upper limbs, thorax and cranial base. Repeated measures were taken during the three phases of the study, twice a week for hand stiffness and disease symptoms of pain, dyspnea and fatigue; and once a week for range of motion of fingers, hand disability and global disability. Upper limbs skin score, work disability and health-related quality of life were measured at baseline, after treatments and at 1-month follow-up. Data for each variable with repeated measures were represented on simple line graphs and visually interpreted, completed by the Sheward's two Standard Deviation Band test. Differences were calculated for variables measured at 3 time points. All participants (n=6) showed improvement in variables related to hand function (hand stiffness, range of motion of fingers and hand disability), except for upper limbs skin score (n=4). The majority of participants showed improvement in disease symptoms (pain n=6, fatigue n=4, et dyspnea n=3/4) as well as variables related to functional status (global disability n=5/5, work disability n=4, physical n=6 and mental n=4 component summary of health-related quality of life). Most improvements were maintained at 4 week follow up. When the comparison was possible, almost all observed improvements were higher than the minimal clinically important differences suggested for this population. These findings suggest that osteopathy may be effective in reducing disability from hand contractures in SSc. A randomized controlled trial is needed to confirm these results.