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1.
Plast Reconstr Surg ; 149(3): 651-660, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35041636

RESUMO

BACKGROUND: North American surgeons continue to routinely order narcotic medication for postoperative pain relief after carpal tunnel surgery. For some patients, this instigates persistent use. This double-blind, multicenter trial investigated whether over-the-counter medications were inferior to opioid pain control after carpal tunnel release. METHODS: Patients undergoing carpal tunnel release in five centers in Canada and the United States (n = 347) were randomly assigned to postoperative pain control with (opioid) hydrocodone/acetaminophen 5/325 mg versus over-the-counter ibuprofen/acetaminophen 600/325 mg. The two primary outcome measures were the Numeric Pain Rating Scale (0 to 10) and the six-item Patient-Reported Outcome Measurement Information System Pain Interference T-score. Secondary outcome measures were total medication used and overall satisfaction with pain medication management. RESULTS: The authors found no significant differences between opioid and over-the-counter patients in the Numeric Pain Rating Scale scores, Pain Interference T-scores, number of doses of medication, or patient satisfaction. The highest Numeric Pain Rating Scale group difference was the night of surgery, when opiate patients had 0.9/10 more pain than over-the-counter patients. The highest group difference in Pain Interference T-scores (2.1) was on the day of surgery, when the opiate patients had more pain interference than the over-the-counter group. Patient nationality or sex did not generate significant pain score differences. CONCLUSIONS: Pain management is not inferior for patients managed with over-the-counter acetaminophen/ibuprofen versus opioids. This study provides high-quality evidence that U.S. and Canadian surgeons should stop the routine prescription of narcotics after carpal tunnel surgery for patients who are not taking pain medicines daily before surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Síndrome do Túnel Carpal/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática Médica , Acetaminofen/uso terapêutico , Adulto , Idoso , Canadá , Método Duplo-Cego , Feminino , Humanos , Hidrocodona/uso terapêutico , Ibuprofeno/uso terapêutico , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Estados Unidos , Adulto Jovem
2.
J Enzyme Inhib Med Chem ; 34(1): 1489-1497, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31416364

RESUMO

MAO-B leads to an increase in the levels of hydrogen peroxide and oxidative free radicals, which contribute to the aetiology of the AD. Thus, both iron ion chelators and MAO-B inhibitors can be used to treat AD. Taking the coumarin derivatives and hydroxypyridinones as the lead compounds, a series of dual-target hybrids were designed and synthesised by Click Chemistry. The compounds were biologically evaluated for their iron ion chelating and MAO-B inhibitory activity. Most of the compounds displayed excellent iron ion chelating activity and moderate to good anti-MAO-B activity. Compounds 27b and 27j exhibited the most potent MAO-B inhibitory activity, with IC50 values of 0.68 and 0.86 µM, respectively. In summary, these dual-target compounds have the potential anti-AD activity.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Cumarínicos/farmacologia , Quelantes de Ferro/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Piridonas/farmacologia , Doença de Alzheimer/metabolismo , Cumarínicos/síntese química , Cumarínicos/química , Relação Dose-Resposta a Droga , Humanos , Quelantes de Ferro/síntese química , Quelantes de Ferro/química , Estrutura Molecular , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/química , Piridonas/síntese química , Piridonas/química , Relação Estrutura-Atividade
3.
Clin Invest Med ; 41: 29-31, 2018 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-30394278

RESUMO

Bing graduated from the Medical Faculty at Erasmus University in Rotterdam, The Netherlands in 1988. He then completed a PhD in Medical Sciences (University of Calgary), internship (University of Regina) and surgical residency (University of Western Ontario) and post-residency clinical fellowships (University of Toronto and Harvard University) followed by a research post-doctoral fellowship (Department of Cell Biology, University of Toronto). Bing has been with the Roth | McFarlane Hand and Upper Limb Centre at St. Joseph's Health Centre since 1998. He is a Professor of Surgery and Medical Biophysics at Western University. His clinical practice focuses on hand and wrist surgery, microsurgical reconstruction and complex wound reconstruction, with a particular clinical and research interest in patients with Dupuytren's contracture. He is also interested in other fibrosing conditions, such as hypertrophic scarring. Bing was a Canadian Society for Clinical Investigation (CSCI) Member of Council 2004-2011and CSCI President 2009-2011.


Assuntos
Pesquisa Biomédica , Canadá , Humanos , Ontário , Pesquisadores
4.
J Dermatol Sci ; 83(2): 131-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27245865

RESUMO

BACKGROUND: Dupuytren's Disease is a common disorder of the connective tissue characterized by progressive and irreversible fibroblastic proliferation affecting the palmar fascia. Progressive flexion deformity appears over several months or years and although usually painless, it can result in a serious handicap causing loss of manual dexterity. There is no cure for the disease and the etiology is largely unknown. A genome-wide association study of Dupuytren's Disease identified nine susceptibility loci with the strongest genetic signal located in an intron of EPDR1, the gene encoding the Ependymin Related 1 protein. OBJECTIVE: Here, we investigate the role of EPDR1 in Dupuytren's Disease. METHODS: We research the role of EPDR1 by assessing gene expression in patient tissue and by gene silencing in fibroblast-populated collagen lattice (FPCL) assay, which is used as an in vitro model of Dupuytren's contractures. RESULTS: The three alternative transcripts produced by the EPDR1 gene are all detected in affected Dupuytren's tissue and control unaffected palmar fascia tissue. Dupuytren's tissue also contracts more in the FPCL paradigm. Dicer-substrate RNA-mediated knockdown of EPDR1 results in moderate late stage attenuation of contraction rate in FPCL, implying a role in matrix contraction. CONCLUSION: Our results suggest functional involvement of EPDR1 in the etiology of Dupuytren's Disease.


Assuntos
Contratura de Dupuytren/genética , Contratura de Dupuytren/metabolismo , Contração Muscular/genética , Miofibroblastos/fisiologia , Proteínas de Neoplasias/metabolismo , Células Cultivadas , Colágeno/metabolismo , Fáscia/metabolismo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Miofibroblastos/metabolismo , Proteínas de Neoplasias/genética , Proteínas do Tecido Nervoso , Polimorfismo de Nucleotídeo Único , Cultura Primária de Células , Interferência de RNA
5.
J Cell Commun Signal ; 9(4): 347-52, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26123754

RESUMO

Dupuytren's disease (DD) is a fibroproliferative and contractile fibrosis of the palmar fascia that, like all other heritable fibroses, is currently incurable. While DD is invariably benign, it exhibits some molecular similarities to malignant tumours, including increased levels of ß-catenin, onco-fetal fibronectin, periostin and insulin-like growth factor (IGF)-II. To gain additional insights into the pathogenesis of DD, we have assessed the expression of WT1, encoding Wilm's tumour 1, an established tumour biomarker that is syntenic with IGF2, the gene encoding IGF-II in humans. We found that WT1 expression is robustly and consistently up regulated in primary fibroblasts derived from the fibrotic palmar fascia of patients with DD (DD cells), whereas syngeneic fibroblasts derived from the macroscopically unaffected palmar fascia in these patients and allogeneic fibroblasts derived from normal palmar fascia exhibited very low or undetectable WT1 transcript levels. WT1 immunoreactivity was evident in a subset of cells in the fibrotic palmar fascia of patients with DD, but not in macroscopically unaffected palmar fascia. These findings identify WT1 expression as a novel biomarker of fibrotic palmar fascia and are consistent with the hypothesis that the pathogeneses of DD and malignant tumours have molecular similarities.

6.
Clin Invest Med ; 37(4): E262-7, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25090267

RESUMO

PURPOSE: Frozen Shoulder Syndrome is a fibrosis of the shoulder joint capsule that is clinically associated with Dupuytren's disease, a fibrosis of the palmar fascia. Little is known about any commonalities in the pathophysiology of these connective tissue fibroses. ß-catenin, a protein that transactivates gene expression, and levels of IGF2 mRNA, encoding insulin-like growth factor-II, are elevated in Dupuytren's disease. The aim of this study was to determine if correlating changes in ß-catenin levels and IGF2 expression are evident in Frozen Shoulder Syndrome. METHODS: Tissue from patients with Frozen Shoulder Syndrome and rotator cuff tear were obtained during shoulder arthroscopies. Total protein extracts were prepared from tissue aliquots and ß-catenin immunoreactivity was assessed by Western immunoblotting. In parallel, primary fibroblasts were derived from these tissues and assessed for IGF2 expression by quantitative PCR. RESULTS: ß-catenin levels were significantly increased in Frozen Shoulder Syndrome relative to rotator cuff tear when assessed by Western immunoblotting analyses. IGF2 mRNA levels were significantly increased in primary fibroblasts derived from frozen shoulder syndrome tissues relative to fibroblasts derived from rotator cuff tissues. CONCLUSIONS: As in Dupuytren's disease, ß-catenin levels and IGF2 expression are elevated in Frozen Shoulder Syndrome. These findings support the hypothesis that these connective tissue fibroses share a common pathophysiology.


Assuntos
Bursite/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , beta Catenina/metabolismo , Bursite/genética , Contratura de Dupuytren/genética , Contratura de Dupuytren/metabolismo , Humanos , Técnicas In Vitro , Fator de Crescimento Insulin-Like II/genética , beta Catenina/genética
7.
J Wrist Surg ; 3(2): 85-90, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25032074

RESUMO

Background Ulnar impaction syndrome is a condition in which the ulna impacts on the ulnar carpus. This most commonly occurs when the ulna is longer than the radius, but it can also occur in wrists with ulnar neutral and ulnar negative variance. Materials and Methods In this paper we outline our surgical technique for ulnar shortening osteotomy. A previously published retrospective case series of 28 patients treated at our center is presented. Fifty consecutive patients who underwent ulnar shortening osteotomy (USO) for ulnar impaction syndrome were approached for study, and 28 consented to review. Mean preoperative ulnar variance was +2.3 mm, and mean postoperative ulnar variance was -0.8 mm. Mean follow-up time was 21.2 months (8 to 41 months) and ten of 28 were receiving workers' compensation. Mean preoperative pain score (visual analog scale; VAS) was 7.9. Univariate analysis was performed to assess clinical and demographic data. In addition, subgroup analysis of workers' compensation patients and smokers was performed. Description of Technique A longitudinal incision over the subcutaneous border of the ulna is used to expose the ulna between the distal and middle third of the ulna from the ulna styloid. Preoperative posteroanterior (PA) X-rays are reviewed to determine the amount of shortening required, with a goal of creating -2 mm variance postoperatively. A 6-hole dynamic compression plate is predrilled distally prior to performing two oblique osteotomies separated by the desired shortening length. The fragments are reduced, controlling for rotation, and plated using compression. In some cases, a lag screw is employed across the oblique osteotomy site. Results Mean pain scores were significantly reduced postoperatively (VAS 7.9 versus 3.1, P < 0.0001). The mean Disabilities of the Arm, Shoulder, and Hand (DASH) score was 37.2 postoperatively. Flexion, extension, and supination were reduced compared with the contralateral unaffected extremity (84.6%, 85.3%, and 86.9% of normal). Patients receiving workers' compensation and smokers had significantly more pain postoperatively (VAS 5.2 vs. 2.0, P = 0.0002 and VAS 4.4 vs 2.4, P < 0.05, respectively). Eleven of 28 patients required hardware removal for plate irritation, and five of 28 patients had a nonunion. Conclusion We present our surgical technique for ulnar shortening osteotomy. Pain was significantly improved in our population; however, patients receiving workers' compensation and smokers had less improvement in pain and higher disability scores.

8.
J Cell Physiol ; 229(9): 1121-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24676899

RESUMO

There is a critical need for techniques that directly monitor protein synthesis within cells isolated from normal and diseased tissue. Fibrotic disease, for which there is no drug treatment, is characterized by the overexpression of collagens. Here, we use a bioinformatics approach to identify a pair of glycine and proline isoacceptor tRNAs as being specific for the decoding of collagen mRNAs, leading to development of a FRET-based approach, dicodon monitoring of protein synthesis (DiCoMPS), that directly monitors the synthesis of collagen. DiCoMPS aimed at detecting collagen synthesis will be helpful in identifying novel anti-fibrotic compounds in cells derived from patients with fibrosis of any etiology, and, suitably adapted, should be widely applicable in monitoring the synthesis of other proteins in cells.


Assuntos
Colágeno/biossíntese , Fibroblastos/metabolismo , Transferência Ressonante de Energia de Fluorescência , Microscopia Confocal , RNA de Transferência de Glicina/metabolismo , RNA de Transferência de Prolina/metabolismo , Animais , Carbocianinas/metabolismo , Células Cultivadas , Fibroblastos/patologia , Fibrose , Corantes Fluorescentes/metabolismo , Humanos , Cinética , Camundongos , Camundongos Knockout , PTEN Fosfo-Hidrolase/deficiência , PTEN Fosfo-Hidrolase/genética , RNA de Transferência de Glicina/genética , RNA de Transferência de Prolina/genética , Transfecção
9.
Biochim Biophys Acta ; 1832(10): 1511-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23623986

RESUMO

Dupuytren's disease (DD) is a common and heritable fibrosis of the palmar fascia that typically manifests as permanent finger contractures. The molecular interactions that induce the development of hyper-contractile fibroblasts, or myofibroblasts, in DD are poorly understood. We have identified IGF2 and IGFBP6, encoding insulin-like growth factor (IGF)-II and IGF binding protein (IGFBP)-6 respectively, as reciprocally dysregulated genes and proteins in primary cells derived from contracture tissues (DD cells). Recombinant IGFBP-6 inhibited the proliferation of DD cells, patient-matched control (PF) cells and normal palmar fascia (CT) cells. Co-treatments with IGF-II, a high affinity IGFBP-6 ligand, were unable to rescue these effects. A non-IGF-II binding analog of IGFBP-6 also inhibited cellular proliferation, implicating IGF-II-independent roles for IGFBP-6 in this process. IGF-II enhanced the proliferation of CT cells, but not DD or PF cells, and significantly enhanced DD and PF cell contractility in stressed collagen lattices. While IGFBP-6 treatment did not affect cellular contractility, it abrogated the IGF-II-induced contractility of DD and PF cells in stressed collagen lattices. IGF-II also significantly increased the contraction of DD cells in relaxed lattices, however this effect was not evident in relaxed collagen lattices containing PF cells. The disparate effects of IGF-II on DD and PF cells in relaxed and stressed contraction models suggest that IGF-II can enhance lattice contractility through more than one mechanism. This is the first report to implicate IGFBP-6 as a suppressor of cellular proliferation and IGF-II as an inducer of cellular contractility in this connective tissue disease.


Assuntos
Proliferação de Células , Contratura de Dupuytren/fisiopatologia , Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Fator de Crescimento Insulin-Like II/fisiologia , Células Cultivadas , Contratura de Dupuytren/patologia , Humanos , Ligantes , Reação em Cadeia da Polimerase em Tempo Real
10.
Cell Stress Chaperones ; 18(4): 397-404, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23292503

RESUMO

Dupuytren's contracture (DC) is a fibroproliferative disorder of unknown etiology characterized by a scar-like contracture that develops in the palm and/or digits. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is increased in fibrotic wound healing, and is essential for the accumulation of α-smooth muscle actin (α-SMA) in fibroblasts. The purpose of this study was to determine if CCT-eta is similarly implicated in the aberrant fibrosis seen in DC and to investigate the role of CCT-eta in the behavior of myo/fibroblasts in DC. Fibroblasts were obtained from DC-affected palmar fascia, from adjacent phenotypically normal palmar fascia in the same DC patients (PF), and from non-DC palmar fascial tissues in patients undergoing carpal tunnel (CT) release. Inherent contractility in these three populations was examined using fibroblast-populated collagen lattices (FPCLs) and by cell traction force microscopy. Expression of CCT-eta and α-SMA protein was determined by Western blot. The effect of CCT-eta inhibition on the contractility of DC cells was determined by deploying an siRNA versus CCT-eta. DC cells were significantly more contractile than both matching palmar fascial (PF) cells and CT cells in both assays, with PF cells demonstrating an intermediate contractility in the FPCL assay. Whereas α-SMA protein was significantly increased only in DC cells compared to PF and CT cells, CCT-eta protein was significantly increased in both PF and DC cells compared to CT cells. siRNA-mediated depletion of CCT-eta inhibited the accumulation of both CCT-eta and α-SMA protein in DC cells, and also significantly decreased the contractility of treated DC cells. These observations suggest that increased expression of CCT-eta appears to be a marker for latent and active disease in these patients and to be essential for the increased contractility exhibited by these fibroblasts.


Assuntos
Chaperonina com TCP-1/metabolismo , Fibroblastos/fisiologia , Actinas/metabolismo , Biomarcadores/metabolismo , Células Cultivadas , Chaperonina com TCP-1/antagonistas & inibidores , Chaperonina com TCP-1/genética , Contratura de Dupuytren/metabolismo , Contratura de Dupuytren/patologia , Fáscia/citologia , Fibroblastos/citologia , Humanos , Contração Muscular/fisiologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo
11.
Can J Plast Surg ; 21(1): 11-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24431929

RESUMO

There appears to be increased use of computed tomography angiography (CTA) in the preoperative planning of autologous perforator flap breast reconstruction. Despite the advantages of providing superior anatomical detail, concerns regarding cost and radiation exposure of this technique remain. In the current study, a paper-based survey was distributed to 44 plastic surgeons with a special interest in breast reconstruction at 19 different centres across Canada to collect their perspectives and practice characteristics with respect to the use of CTA as a preoperative imaging modality in breast reconstruction. The response rate of the survey was 75%. The majority of respondents commonly use perforator flap breast reconstruction and CTA in their breast reconstruction practice. Surgeons identified particular benefits of CTA in patients who had previously undergone abdominal surgery. However, more than one-half of the overall cohort was concerned about radiation exposure associated with CTA. A review of the literature suggests that it may be worthwhile to reduce the unnecessary risks of additional radiation exposure to the breast cancer population. A prospective study may help to better define the group of patients in whom CTA will provide optimal benefits in terms of reducing perioperative microvascular morbidity.


On semble utiliser davantage l'angiographie par tomodensitométrie (ATD) lors de la planification préopératoire d'une reconstruction mammaire au moyen d'un lambeau perforant autologue. Malgré les avantages associés à une meilleure précision anatomique, on s'inquiète du coût de cette technique et de l'exposition aux radiations qu'elle entraîne. Dans la présente étude, 44 chirurgiens plasticiens ayant un intérêt pour la reconstruction mammaire provenant de 19 centres du Canada ont reçu un sondage papier afin de colliger leurs points de vue et les caractéristiques de leur pratique à l'égard de l'utilisation de l'ATD comme modalité d'imagerie en prévision d'une reconstruction mammaire. Le sondage a obtenu un taux de réponse de 75 %. La majorité des répondants utilisent souvent la reconstruction mammaire par lambeau perforant et l'ATD dans le cadre de leur pratique de reconstruction mammaire. Les chirurgiens ont souligné les avantages particuliers de l'ATD chez les patients qui avaient déjà subi une opération abdominale. Cependant, plus de la moitié de l'ensemble de la cohorte s'inquiétait de l'exposition aux radiations associée à l'ATD. D'après l'analyse bibliographique, il pourrait être avantageux de réduire les risques inutiles liés à une exposition supplémentaire aux radiations de la population atteinte d'un cancer du sein. Une étude prospective pourrait contribuer à mieux définir le groupe de patients chez qui l'ATD réduit de manière optimale la morbidité microvasculaire périopératoire.

12.
Can J Plast Surg ; 21(4): 229-33, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24497764

RESUMO

PURPOSE: To examine treatment trends and costs associated with Dupuytren's disease (DD) in Canada. METHODS: Data regarding fasciectomies, fasciotomies and digit amputations performed for DD from 2005 to 2010 were extracted from the Canadian Institute for Health Information database. The data were analyzed according to year, sex and five-year age groups. The estimated annual physician reimbursement costs for DD in Ontario were calculated using Ontario Health Insurance Plan billing information and the 2010 Physician Schedule of Benefits. RESULTS: The number and rate of fasciectomies remained stable from 2005 to 2009 (mean of 4067 and 1.24 per 10,000, respectively), but increased in the 2009/2010 fiscal year (to 4458 and 1.32 per 10,000). The number of fasciotomies increased from 133 in 2005/2006 to 201 in 2008/2009, but dropped to 183 in 2009/2010. The mean number of amputations remained stable (12 procedures).The ratio of males to females undergoing fasciectomies remained stable (4:1). The highest rate of fasciectomies was performed for the age groups 65 to 69 years and 70 to 74 years. Estimated mean physician remuneration for DD in Ontario remained stable ($3.2 million per annum). DISCUSSION: The results regarding patient demographics are comparable with results from previous literature. There was a trend toward an increasing number of fasciectomies and fasciotomies annually, with fasciotomies increasing faster than fasciectomies, which is reflective of the aging population and the recent attention to fasciotomies in the literature. The present study was the first to investigate treatment trends and physician reimbursement costs for the management of DD in Canada.


OBJECTIF: Examiner les tendances thérapeutiques et les coûts associés à la maladie de Dupuytren (MD) au Canada. MÉTHODOLOGIE: Les chercheurs ont extrait des bases de données de l'Institut canadien d'information sur la santé les données relatives aux fasciectomies, aux fasciotomies et aux amputations de doigts effectuées en raison de la MD entre 2005 et 2010. Ils ont analysé les données selon l'âge, le sexe et les groupes d'âge par tranches de cinq ans. Ils ont calculé les coûts estimatifs annuels du remboursement des médecins attribuables à la MD en Ontario, au moyen de l'information de facturation tirée du Régime d'assurance-maladie de l'Ontario et du barème des prestations des médecins pour 2010. RÉSULTATS: Le nombre et le taux de fasciectomies sont demeurés stables de 2005 à 2009 (moyenne de 4 067 et de 1,24 sur 10 000, respectivement), mais ont augmenté pendant l'exercice 2009­2010 (à 4 458 et 1,32 sur 10 000). Le nombre de fasciotomies est passé de 133 à 2005­2006 à 201 en 2008­2009, mais a reculé à 183 en 2009­2010. Le nombre moyen d'amputations est demeuré stable (12 interventions). Le ratio d'hommes qui ont subi une fasciectomie par rapport aux femmes est également demeuré stable (4:1). Le plus fort taux de fasciectomies s'observait dans les groupes de 65 à 69 ans et de 70 à 74 ans. Enfin, la rémunération estimative moyenne des médecins pour soigner la MD en Ontario est demeurée stable (3,2 millions de dollars par année). EXPOSÉ: Les résultats relatifs à la démographie des patients sont comparables à ceux des publications antérieures. On a constaté une tendance vers une augmentation annuelle du nombre de fasciectomies et de fasciotomies. L'augmentation des fasciotomies était plus marquée que celle des fasciectomies, ce qui reflète le vieillissement de la population et l'intérêt récent pour les fasciotomies dans les publications. La présente étude était la première à examiner les tendances en matière de traitement et les coûts du remboursement des médecins pour la prise en charge de la MD au Canada.

13.
BMC Med Genomics ; 5: 15, 2012 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-22559715

RESUMO

BACKGROUND: Dupuytren's contracture (DC) is a fibroproliferative disorder characterized by the progressive development of a scar-like collagen-rich cord that affects the palmar fascia of the hand and leads to digital flexion contractures. DC is most commonly treated by surgical resection of the diseased tissue, but has a high reported recurrence rate ranging from 27% to 80%. We sought to determine if the transcriptomic profiles of fibroblasts derived from DC-affected palmar fascia, adjacent phenotypically normal palmar fascia, and non-DC palmar fascial tissues might provide mechanistic clues to understanding the puzzle of disease predisposition and recurrence in DC. METHODS: To achieve this, total RNA was obtained from fibroblasts derived from primary DC-affected palmar fascia, patient-matched unaffected palmar fascia, and palmar fascia from non-DC patients undergoing carpal tunnel release (6 patients in each group). These cells were grown on a type-1 collagen substrate (to better mimic their in vivo environments). Microarray analyses were subsequently performed using Illumina BeadChip arrays to compare the transcriptomic profiles of these three cell populations. Data were analyzed using Significance Analysis of Microarrays (SAM v3.02), hierarchical clustering, concordance mapping and Venn diagram. RESULTS: We found that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected fascia of DC patients exhibited a much greater overlap than fibroblasts derived from the palmar fascia of patients undergoing carpal tunnel release. Quantitative real time RT-PCR confirmed the differential expression of select genes validating the microarray data analyses. These data are consistent with the hypothesis that predisposition and recurrence in DC may stem, at least in part, from intrinsic similarities in the basal gene expression of diseased and phenotypically unaffected palmar fascia fibroblasts. These data also demonstrate that a collagen-rich environment differentially alters gene expression in these cells. In addition, Ingenuity pathway analysis of the specific biological pathways that differentiate DC-derived cells from carpal tunnel-derived cells has identified the potential involvement of microRNAs in this fibroproliferative disorder. CONCLUSIONS: These data show that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected palmar fascia in DC patients are highly similar, and differ significantly from the transcriptomic profiles of fibroblasts from the palmar fascia of patients undergoing carpal tunnel release.


Assuntos
Contratura de Dupuytren/metabolismo , Fáscia/citologia , Fibroblastos/metabolismo , Células Cultivadas , Análise por Conglomerados , Colágeno Tipo I/metabolismo , Contratura de Dupuytren/patologia , Perfilação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , RNA/isolamento & purificação , RNA/metabolismo
15.
Can J Plast Surg ; 20(1): e1-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23598767

RESUMO

BACKGROUND: Ulnar-sided wrist pain is a common problem in the upper extremity. It affects a broad patient population and can be difficult to treat. Ulnar impaction syndrome (UIS) is major cause of ulnar-sided wrist pain and a number of different operations have been used to correct it, including ulnar shortening osteotomy (USO). OBJECTIVE: To retrospectively review functional outcomes and complication rates of USO for UIS at the Hand and Upper Limb Centre (London, Ontario) over a two-year period. METHODS: Twenty-eight patients who underwent USO between 2007 and 2009 participated in the present study. Ulnar variance pre- and post-surgery was assessed using standard radiographic examination. Patient-rated outcomes were measured using a visual analogue scale (VAS) for pain and the Disabilities of the Arm, Shoulder and Hand (DASH) survey for functional outcomes. Objective grip strength and range of motion were compared with the contralateral extremity. RESULTS: On average, USO achieved a 3.11 mm reduction in ulnar variance. Nonunion occurred in five patients and required a secondary bone grafting procedure. All USO eventually healed. Overall, pain improved by 47.2% and the mean DASH score after surgery was 37.21. Flexion, extension and supination range of motion decreased by 10° compared with the unaffected side. Eleven patients (39%) elected to undergo a second surgery for hardware removal. Patients receiving compensation from the Workplace Safety and Insurance Board experienced significantly higher residual pain (VSA 5.24 versus 1.97) and disability levels (DASH 60.23 versus 25.70). Smokers also experienced worse outcomes in terms of pain (VSA 4.43 versus 2.36) and disability (DASH 51.06 versus 29.67). In this cohort, smoking was not associated with a higher rate of nonunion. CONCLUSION: USO is effective in reducing pain in UIS and improves disability, at the price of a small decrease in range of motion. Smokers and people receiving compensation from the Workplace Safety and Insurance Board, however, have significantly worse subjective outcomes (VAS and DASH), but similar objective outcomes (range of motion).


HISTORIQUE: La douleur au cubitus du poignet est un problème courant des membres supérieurs. Elle touche une grande population de patients et peut être difficile à traiter. Le syndrome d'impaction ulnaire (SIU) est une cause importante de douleur au cubitus du poignet. Diverses opérations ont été utilisées pour la corriger, y compris l'ostéotomie de raccourcissement ulnaire (ORU). OBJECTIF: Procéder à l'analyse rétrospective des issues fonctionnelles et des taux de complication d'ORU du SIU au Hand and Upper Limb Centre de London, en Ontario, sur une période de deux ans. MÉTHODOLOGIE: Vingt-huit patients qui ont subi une ORU entre 2007 et 2009 ont participé à la présente étude. Les chercheurs ont évalué la variance ulnaire avant et après l'opération au moyen d'un examen radiographique classique. Ils ont mesuré les issues classées par les patients au moyen d'une échelle analogique visuelle (ÉAV) de la douleur et du sondage DASH sur les incapacités du bras, de l'épaule et de la main évaluant les issues fonctionnelles. Ils ont comparé la force de préhension et l'amplitude de mouvement objectives à celles du membre controlatéral. RÉSULTATS: En moyenne, l'ORU a permis d'obtenir une réduction de 3,1 mm de la variance ulnaire. Chez cinq patients, une non-fusion a exigé une greffe osseuse secondaire. Toutes les ORU ont fini par guérir. Dans l'ensemble, la douleur a diminué de 47,2 %, et l'indice DASH moyen après l'opération s'élevait à 37,21. L'amplitude de flexion, d'extension et de supination a diminué de 10° par rapport au côté non touché. Onze patients (39 %) ont choisi de subir une deuxième opération afin d'extraire les tiges de métal. Les patients indemnisés par la Commission de la sécurité professionnelle et de l'assurance contre les accidents du travail ressentaient une douleur résiduelle (ÉAV de 5,24 par rapport à 1,97) et des taux d'invalidité (DASH de 60,23 par rapport à 25,70) considérablement plus élevés. Les fumeurs présentaient également une issue moins favorable sur le plan de la douleur (ÉAV de 4,43 par rapport à 2,36) et de l'invalidité (DASH de 51,06 par rapport à 29,67). Au sein de cette cohorte, le tabagisme ne s'associait pas à un taux plus élevé de non-fusion. CONCLUSION: L'ORU est efficace pour réduire la douleur en cas de SIU et amenuise l'incapacité au prix d'une légère diminution de l'amplitude de mouvement. Les fumeurs et les personnes indemnisées par la Commission de la sécurité professionnelle et de l'assurance contre les accidents du travail, cependant, ont une issue subjective bien pire (ÉAV et DASH), mais une issue objective similaire (amplitude de mouvement).

16.
Pain Res Treat ; 2011: 362396, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22110923

RESUMO

Purpose. Little attention has been given to syringe design and local anaesthetic administration methods. A microprocessor-controlled anaesthetic delivery device has become available that may minimize discomfort during injection. The purpose of this study was to document the pain experience associated with the use of this system and to compare it with use of a conventional syringe. Methods. A prospective, randomized clinical trial was designed. 40 patients undergoing carpal tunnel release were block randomized according to sex into a two groups: a traditional syringe group and a microprocessor-controlled device group. The primary outcome measure was surgical pain and local anaesthetic administration pain. Secondary outcomes included volume of anaesthetic used and injection time. Results. Analysis showed that equivalent anaesthesia was achieved in the microprocessor-controlled group despite using a significantly lower volume of local anaesthetic (P = .0002). This same group, however, has significantly longer injection times (P < .0001). Pain during the injection process or during surgery was not different between the two groups. Conclusions. This RCT comparing traditional and microprocessor controlled methods of administering local anaesthetic showed similar levels of discomfort in both groups. While the microprocessor-controlled group used less volume, the total time for the administration was significantly greater.

17.
Ther Clin Risk Manag ; 6: 383-90, 2010 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-20856684

RESUMO

Dupuytren's disease (DD) is a common disease of the hand and is characterized by thickening of the palmar fascia and formation of tight collagenous disease cords. At present, the disease is incurable and the molecular pathophysiology of DD is unknown. Surgery remains the most commonly used treatment for DD, but this requires extensive postoperative therapy and is associated with high rates of recurrence. Over the past decades, more indepth exploration of the molecular basis of DD has raised the hopes of developing new treatment modalities. This paper reviews the clinical presentation and molecular pathophysiology of this disease, as well as current and emerging treatment. It also explores the implications of new findings in the laboratory for future treatment.

18.
Med Hypotheses ; 74(3): 510-2, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19896280

RESUMO

Dupuytren's disease is a pathological condition of the palmar fascia characterized by the formation of contractile disease cords that result in permanent finger contracture. This condition is believed to progress from a myofibroblast-rich nodule in the early clinical stages of the disease to a contractile disease cord spanning a portion of the fascia, leading to contracture of one or more digits. The mechanism(s) by which this disease progresses from a nodule to a collagenous disease cord are poorly understood. Here, we discuss two possible models of disease progression. Firstly, disease progression might be mediated by the proliferation and outward migration of disease cells from within the nodule to populate the adjacent palmar fascia, resulting in a disease cord containing contractile cells derived from the nodule itself. Alternatively, nodular cells may secrete disease-associated factors into the surrounding extra-cellular matrix, thereby altering its composition and triggering quiescent, phenotypically normal cells in the adjacent palmar fascia to take on a proliferative and contractile phenotype. Based on the available evidence and the current state of knowledge of myofibroblast biology, we hypothesize that extra-cellular matrix interactions resulting in conversion of adjacent palmar fascia cells to a disease phenotype is more likely than cell migration from the nodule. Understanding the mechanisms of Dupuytren's disease progression will assist in the development of effective therapeutic interventions to address the high clinical recurrence rate of this condition.


Assuntos
Movimento Celular , Contratura de Dupuytren/fisiopatologia , Matriz Extracelular/metabolismo , Fáscia/fisiopatologia , Fibroblastos , Modelos Biológicos , Mioblastos , Animais , Progressão da Doença , Humanos , Recidiva
19.
J Sex Med ; 7(1 Pt 1): 99-106, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19889147

RESUMO

INTRODUCTION: The molecular pathogenesis of Peyronie's Disease (PD) remains unclear more than 250 years after its initial description. Because of this, no test is currently available to accurately predict PD progression among those affected. AIM: To investigate the expression of wound healing and fibrosis-associated proteins in primary cell cultures of PD fibroblasts to determine whether altered protein expression patterns can be used as predictors of clinical course and natural history. METHODS: Primary cell cultures derived from normal Tunica albuginea tissue and PD plaque tissue were examined by immuno-cytochemistry. Protein expression profiles were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) and Western immunoblotting. MAIN OUTCOME MEASURES: Expression of wound healing and fibrosis-associated proteins and protein expression patterns were assessed. RESULTS: Statistically significant increases in smooth muscle alpha-actin, beta-catenin, and Heat shock proteins (Hsp47) were identified in cells derived from PD relative to cells derived from normal Tunica albuginea tissue. Changes in TGFbeta-1 receptor and Fibronectin were also observed. In addition, altered expression of additional as yet unidentified proteins at 4.7, 8.9, 10.8, 16.8, and 76.8 kDa were detected by complementary SELDI-TOF-MS approaches. CONCLUSIONS: Primary cells derived from PD plaques display up-regulated expression of several proteins that are established components of fibrosis and wound healing. In addition, changes in other, as yet unidentified proteins were measured. It will be of interest to conduct further studies to see whether these dysregulated protein peaks represent potential biological markers of disease progression.


Assuntos
Biomarcadores/metabolismo , Fibroblastos/patologia , Induração Peniana/patologia , Análise Serial de Proteínas/métodos , Proteômica/métodos , Actinas/metabolismo , Células Cultivadas , Fibronectinas/metabolismo , Fibrose/patologia , Proteínas de Choque Térmico HSP47/metabolismo , Humanos , Masculino , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima/fisiologia , Cicatrização/fisiologia , beta Catenina/metabolismo
20.
Can J Plast Surg ; 18(1): e5-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21358864

RESUMO

The treatment of digital ischemia remains difficult. Sildenafil (Viagra, Pfizer UK), a selective phosphodiesterase inhibitor, increases blood flow and is currently marketed for the treatment of erectile dysfunction. A case of a 57-year-old man with progressive episodic ischemia and pain of the fingertips resulting in finger tip ulceration is presented. After failure of medical and surgical management, a trial of oral sildenafil resulted in marked symptomatic improvement of his bilateral digital ischemia. Review of the literature shows that, particularly in patients with an underlying disease such as sclero-derma with a vasospastic component, a marked improvement in digital blood flow may be observed with sildenafil use. Overall, based on a number of case reports and preliminary animal studies in the literature, sildenafil appears to have a growing significance in the treatment of hand ischemia. Similarly, there is evidence that phosphodiesterase 5 inhibitors may be used as an adjunct to improving skin flap survival.

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