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Purpose: This study investigated the relationship between severity of symptoms and success of non-operative and operative treatment in patients with carpal tunnel syndrome (CTS).Methods: An observational cohort study regarding the management of CTS was conducted. Thirty patients referred to a tertiary hand centre with a diagnosis of CTS were prospectively followed. Twenty-five of the patients (47 affected hands) were available for long-term follow up to determine management outcomes. Self-report symptoms and physical impairments were assessed and documented at baseline, 6 weeks, and 12 .weeks using the CTS Severity Score (SSS), the Disability-Shoulder, Arm and Hand Score (DASH), and the Levine Functional Score. Longer-term follow-up was conducted to identify status on outcome measures and whether patients proceeded to surgery.Results: Those who proceeded to surgery (n=27/47 hands) had higher initial CTS SSS and DASH scores and also maintained higher scores compared to those who improved with conservative management (p<0.05). Improvements occurred in the SSS (P<0.0001), Functional Score (P<0.001), and DASH score (P<0.05) following surgery in the patients resistant to conservative management. Recovery of grip and dexterity was less satisfactory.Discussion: This study suggests that the SSS is useful in the triage of patients on surgical wait-lists as patients with high initial scores or failure to change in short-term follow-up are likely to proceed to surgical release. Despite prolonged symptoms and previous treatment, patients with lower SSS scores had moderate success with a second trial of conservative management. [ABSTRACT FROM AUTHOR]

Background: Dupuytren's Disease (DD) is a debilitating contractile fibrosis of the palmar fascia characterised by excess collagen deposition, contractile myofibroblast development, increased transforming growth factor-beta levels and beta-catenin accumulation. The aim of this study was to determine if a collagen-enriched environment, similar to in vivo conditions, altered beta-catenin accumulation by primary DD cells in the presence or absence of transforming growth factor-beta.Methods: Primary DD and patient matched, phenotypically normal palmar fascia (PF) cells were cultured in the presence or absence of type-1 collagen and transforming growth factor-beta1. beta-catenin and alpha-smooth muscle actin levels were assessed by western immunoblotting and immunofluorescence microscopy.Results: DD cells display a rapid depletion of cellular beta-catenin not evident in patient-matched PF cells. This effect was not evident in either cell type when cultured in the absence of type-1 collagen. Exogenous addition of transforming growth factor-beta1 to DD cells in collagen culture negates the loss of beta-catenin accumulation. Transforming growth factor-beta1-induced alpha-smooth muscle actin, a marker of myofibroblast differentiation, is attenuated by the inclusion of type-1 collagen in cultures of DD and PF cells.Conclusion: Our findings implicate type-1 collagen as a previously unrecognized regulator of beta-catenin accumulation and a modifier of TGF-beta1 signaling specifically in primary DD cells. These data have implications for current treatment modalities as well as the design of in vitro models for research into the molecular mechanisms of DD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Probiotics--live microorganisms that confer a health benefit when taken in adequate amounts, usually as food supplements--are receiving renewed attention in the medical community. Some have been found to play a role in disease remediation. However, mainstream medicine and science remain divided about the validity of health claims made about them. METHODS: To clarify the potential value of probiotics, we reviewed the scientific data on their role in preventing and treating surgical infections as well as some of our own studies of the effects of certain strains of lactobacilli on surgical implant infections. PRINCIPAL FINDINGS: There is little rigorous evidence that probiotics may be beneficial in the prevention and treatment of wound infections. However, data from 3 clinical trials and from our laboratory indicate that certain strains of probiotic lactobacilli and their byproducts may help reduce infection rates in surgical patients and may ameliorate staphylococcus-related infections of surgical implants. CONCLUSION: Although there is good clinical evidence that certain probiotics may be beneficial in conditions such as diarrheal and inflammatory bowel diseases, more studies are required to apply these concepts to the prevention and treatment of wound and other surgical infections. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Disclosure:This work was supported by grants from the American Association for Hand Surgery and the Arthur Chesley Foundation in Saint John, New Brunswick, Canada. Dr. MacDermid was supported by a Canada Research Chair and the Dr. James Roth Chair (both in musculoskeletal measurement and knowledge translation). The authors have no commercial associations, financial relationships, or conflicts of interest that might pose or create a conflict of interest with information presented in this article., (Copyright © 2022 by the American Society of Plastic Surgeons.)

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.

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., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

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.

Hypertrophic scarring is characterized by the excessive development and persistence of myofibroblasts. These cells contract the surrounding extracellular matrix resulting in the increased tissue density characteristic of scar tissue. Periostin is a matricellular protein that is abnormally abundant in fibrotic dermis, however, its roles in hypertrophic scarring are largely unknown. In this report, we assessed the ability of matrix-associated periostin to promote the proliferation and myofibroblast differentiation of dermal fibroblasts isolated from the dermis of hypertrophic scars or healthy skin. Supplementation of a thin type-I collagen cell culture substrate with recombinant periostin induced a significant increase in the proliferation of hypertrophic scar fibroblasts but not normal dermal fibroblasts. Periostin induced significant increases in supermature focal adhesion formation, α smooth muscle actin levels and collagen contraction in fibroblasts cultured from hypertrophic scars under conditions of increased matrix tension in three-dimensional type-I collagen lattices. Inhibition of Rho-associated protein kinase activity significantly attenuated the effects of matrix-associated periostin on hypertrophic scar fibroblasts and myofibroblasts. Depletion of endogenous periostin expression in hypertrophic scar myofibroblasts resulted in a sustained decrease in α smooth muscle actin levels under conditions of reducing matrix tension, while matrix-associated periostin levels caused the cells to retain high levels of a smooth muscle actin under these conditions. These findings indicate that periostin promotes Rho-associated protein kinase-dependent proliferation and myofibroblast persistence of hypertrophic scar fibroblasts and implicate periostin as a potential therapeutic target to enhance the resolution of scars., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2014 Wiley Periodicals, Inc.)

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. β-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 β-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 β-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: β-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, β-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.

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.

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.

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., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

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.

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.

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).

Background: Nutritional supplementation is a potential adjunct in the conservative management of carpal tunnel syndrome (CTS). This study investigated whether astaxanthin (a beta-carotenoid) increased the effectiveness of splinting in managing CTS., Methods: This is a triple-blinded randomized controlled trial where 63 patients with electrodiagnostically confirmed CTS were randomly allocated into either the experimental group (n = 32) (astaxanthin-4-mg capsules + splinting) or the control group (n = 31) (placebo + splinting). Medications were taken for 9 weeks followed by a 3-week washout. The primary outcome measure was the Symptom Severity Scale (SSS). Secondary outcome measures in the study included physical impairments, disability, and health status measures. Electrodiagnostic testing was performed before entry into the study and again at 12 weeks. All other outcomes were measured at baseline, 6, and 12 weeks., Results: There was a reduction in symptoms as measured by the SSS over the course of treatment in both groups (p = 0.002), but no differences between the groups (p = 0.18). The Disability of Arm, Shoulder and Hand questionnaire and the Short Form 36-item Health Survey showed no effects over time or between treatment groups. The baseline difference between the groups in the level of total cholesterol and low-density lipoproteins remained constant over the course of the study. Impairment measures demonstrated no significant changes in grip, dexterity, or sensation., Conclusion: At present, the role for astaxanthin as an adjunct in conservative management of CTS has not been established.

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.

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.

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., Competing Interests: statement None declared., (Crown Copyright (c) 2009. Published by Elsevier Ltd. All rights reserved.)

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.

Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, alpha smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

Background: Restoring sensory innervation may be a useful adjunct in free flap head and neck reconstruction but, as yet, has not been shown to improve outcomes of breast reconstruction. The authors' previous study demonstrated objectively improved sensation in a group of innervated transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction patients relative to noninnervated flaps. This study compared patient-rated outcomes of free TRAM breast reconstruction in innervated versus noninnervated flaps., Methods: Twenty-seven women were randomized prospectively to undergo either innervated or noninnervated free TRAM flap breast reconstruction. For innervated flaps, the T10 intercostal nerve was harvested with the TRAM flap and neurotized to the T4 sensory nerve at the recipient site. Three validated outcome tools were administered after surgery: the Medical Outcomes Study 36-Item Short Form Health Survey, the Body Image after Breast Cancer Questionnaire, and the Functional Assessment of Cancer Therapy-Breast. Results were correlated with previously reported objective sensibility outcomes., Results: Eighteen of 27 women returned their questionnaires a mean 48 months after free TRAM flap reconstruction. Demographic analysis revealed no significant differences in patient age, height, smoking, radiation therapy, and nipple-areola complex reconstruction between randomized patient groups. There was a statistically significant improvement in all three measures in patients who were randomized to receive innervated free TRAM flaps compared with those receiving noninnervated flaps., Conclusion: This study demonstrates that innervation of free TRAM flaps used for breast reconstruction not only improves sensibility but also has a positive effect on patient-rated quality of life.

Purpose: The measurement of protein kinase activity is central to understanding the signaling pathways that regulate cellular proliferation and apoptosis in virtually all disease processes. These measurements typically involve either indirect, time consuming assessment methods that require large amounts of sample, such as western immunoblotting, or the use of high maintenance, specialized equipment not typically available to a small clinical research facility. The purpose of this project was to determine if a benchtop Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) unit could be used to detect and directly assess kinase activity of the serine/threonine kinase Akt., Method: Biotinylated substrate peptides, predicted to be recognized and phosphorylated by Akt to varying extents, were incubated in crude lysates of primary cells derived directly from clinical isolates. Streptavidin-coated chips were then used to isolate the substrate peptides from the lysates after incubation. Finally SELDI-TOF-MS was used to detect the peptide substrates and identify any changes in mass resulting from phosphorylation., Results: The biotinylated peptide substrates were readily detected and a simple, rapid procedure that allows direct measurement of Akt activity in less than 1 microg of cell lysate in a 2microL volume was developed. Further, a linear correlation between native to phospho-peptide ratios and SELDI-TOF-MS output demonstrated that this approach is semi-quantitative., Conclusion: This assay avoids many of the pitfalls associated with the currently available kinase protocols as well as labour-intensive mass-spectrometry analysis by specialist laboratories. We propose that this approach may be a viable alternative for clinical research laboratories aiming to measure the activity of kinases in clinical isolates.

Background: Atherosclerosis, a response to injury, may be thought of as scarring in the artery wall. TGF-beta and associated signaling molecules have been implicated in the pathophysiology of keloid scarring, Dupuytren's Contracture and atherosclerotic plaques in independent studies., Purpose: To test the hypothesis that excess cutaneous scarring and Dupuytren's contractures predispose independently to carotid atherosclerosis ., Methods: Among 1,747 patients with plaque measurements and complete data for multivariable regression analysis, 57 Caucasian patients had Dupuytren's contractures and 12 had keloid scars. Carotid total plaque area (TPA) was measured by 2-Dimensional ultrasound., Results: In linear multivariable regression analysis with coronary risk factors, keloid scars were associated with TPA (P= 0.018), but Dupuytren's contractures were not. Patients with keloid scarring were younger (P < 0.0001), and more likely to be diabetic (P < 0.0001), Conclusions: Keloid scarring is a clinical clue to excess atherosclerosis not explained by traditional risk factors. Such patients may benefit from therapy directed at targets related to signalling molecules common to both the process of keloid scarring and atherosclerosis. These findings suggest previously unexplored possibilities for the prevention and treatment of atherosclerosis. The differences between Dupuytren's and keloid scars that may identify such targets are discussed.

Dupuytren's contracture (DC) is the most common inherited connective tissue disease of humans and is hypothesized to be associated with aberrant wound healing of the palmar fascia. Fibroblasts and myofibroblasts are believed to play an important role in the genesis of DC and the fibroproliferation and contraction that are hallmarks of this disease. This study compares the gene expression profiles of fibroblasts isolated from DC patients and controls in an attempt to identify key genes whose regulation might be significantly altered in fibroblasts found within the palmar fascia of Dupuytren's patients. Total RNA isolated from diseased palmar fascia (DC) and normal palmar fascia (obtained during carpal tunnel release; 6 samples per group) was subjected to quantitative analyses using two different microarray platforms (GE Code Linktrade mark and Illuminatrade mark) to identify and validate differentially expressed genes. The data obtained was analyzed using The Significance Analysis of Microarrays (SAM) software through which we identified 69 and 40 differentially regulated gene transcripts using the CodeLinktrade mark and Illuminatrade mark platforms, respectively. The CodeLinktrade mark platform identified 18 upregulated and 51 downregulated genes. Using the Illuminatrade mark platform, 40 genes were identified as downregulated, eleven of which were identified by both platforms. Quantitative RT-PCR confirmed the downregulation of three high-interest candidate genes which are all components of the extracellular matrix: proteoglycan 4 (PRG4), fibulin-1 (FBLN-1) transcript variant D, and type XV collagen alpha 1 chain. Overall, our study has identified a variety of candidate genes that may be involved in the pathophysiology of Dupuytren's contracture and may ultimately serve as attractive molecular targets for alternative therapies.

Background: Botulinum toxin type A is approved by the U.S. Food and Drug Administration for the treatment of facial rhytides. However, the complete spectrum of action of botulinum toxin A has not yet been completely defined. Little is known about the metabolism of muscle after botulinum toxin A injection. This information may give insight into the additional effects botulinum toxin A may have on muscle. The authors assessed the influence of botulinum toxin A on the metabolism of muscle using dynamic investigative techniques., Methods: Twenty New Zealand White rabbits were divided into control, paralysis, and sham groups. Masseter muscle paralysis was achieved with botulinum toxin A. Dynamic computed tomographic and positron emission tomographic scans were obtained. Masseter muscle blood flow, blood volume, permeability surface, and mean transit time and glucose uptake were measured., Results: Eighteen animals completed the study. Masseter blood perfusion showed consistent results across all parameters. Blood flow, blood volume, and permeability surface were significantly increased at weeks 4 and 8 on the paralyzed side. Mean transit time at week 4 was decreased on the paralyzed side. Positron emission tomographic scans showed that injected muscles in the botulinum toxin A group tended to have increased glucose uptake compared with untreated muscles., Conclusions: Botulinum toxin A injection increases muscle blood perfusion parameters and glucose uptake for a transient period. This increase is similar in duration to the known interval of botulinum toxin A-induced paralysis. These changes have been identified in a dynamic fashion and may represent changes in calcitonin gene-related peptide release.

Introduction: Peyronie's disease (PD) continues to be a major source of sexual dysfunction among the 3-9% of affected men. The challenge in treating PD is determining the natural history and clinical course for the individual patient. Currently, there exists no reliable means to predict whether a penile plaque of PD will progress, regress, or remain stable. This represents a significant deficiency in contemporary management, one that may be addressed with newer technologies such as proteomic profiling., Aim: This review assesses the potential use of protein alterations measured by various novel technologies, to predict progression, regression, or stabilization of PD in an affected individual., Methods: A comprehensive literature review of the past decade in the field of gene profiling and protein expression of PD was performed., Main Outcome Measures: A critical analysis of the existing worldwide literature evaluating surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS or SELDI) and other proteonomic techniques., Results: SELDI and other technologies can provide the clinician with innovative data indicating the presence of unique individual factors that act to suppress or promote the fibrotic process in PD. Determining the clinical implications of altered protein expression in an individual is not yet defined., Conclusions: The area of proteomics has begun to revolutionize the study of medicine in the postgenomic era, by allowing researchers to study the role that proteins play in health and disease. Applying this knowledge clinically has already led to innovative discoveries in early cancer detection in a number of malignancies, including prostate, ovarian, and bladder. Prior to the widespread use and acceptance of proteomic technology in PD, a critical assessment of its therapeutic and diagnostic value will be required.

Background: Understanding the effects of muscle function on facial bone growth may help us treat children with facial anomalies. Facial bone growth is known to be a result of both genetic and epigenetic influences. One of the main epigenetic factors controlling growth is thought to be muscle action. The purpose of this study was to establish a model of single facial muscle paralysis and to identify the effects masseter muscle paralysis has on mandible and zygoma growth., Methods: Twenty New Zealand white rabbits were divided into control, paralysis, and sham groups. Masseter muscle paralysis was achieved with botulinum toxin A (BTX). Computed tomographic and single-photon emission computed tomography (SPECT) scans and cephalometric measurements were performed. Masseter weights and mandible and zygoma volumes, shapes, and metabolism were measured., Results: Eighteen animals completed the study. Significant decreases in zygoma and mandible volumes with minimal changes in shape were seen on the paralyzed sides. SPECT showed a decrease in bone production in both zygomas and mandibles on the paralyzed sides., Conclusions: An animal model has been created in which the effects of single muscle paralysis on bone growth can be studied. Masseter muscle function may be responsible in maintaining mandible and zygoma volume by controlling bone production. Masseter function alone has less influence on mandible and zygoma shape.

Background: Beta-catenin has been historically recognized as both an intermediate in the "canonical Wnt signaling pathway" and as a component of functional adherens junctions., Materials and Methods: Cellular accumulation of beta-catenin levels can result in transactivation of gene transcription and cellular proliferation during normal cellular and disease development. Recent evidence has identified beta-catenin in an additional role as a component of cutaneous wound healing., Results: This finding is in keeping with previous observations that post-translational modifications of beta-catenin that are associated with its cytoplasmic accumulation are frequently observed in fibroproliferative diseases with characteristics of dysregulated wound healing. These diseases include hypertrophic scar formation, aggressive fibromatoses, Lederhose disease, and Dupuytren's contracture (DC)., Conclusions: While its precise roles in disease initiation and progression remain to be explored, this review highlights our current knowledge of beta-catenin regulation and describes some potential upstream mediators of beta-catenin accumulation and signaling in fibroproliferative disease.

As the scope of plastic surgical practice expands to include disorders of the carpus and wrist, it has become increasingly important for plastic surgeons to understand pathoanatomy that has not traditionally been considered an integral component of training. The Essex-Lopresti injury consists of a radial head fracture with associated injury to the forearm interosseus membrane and longitudinal instability of the distal radioulnar joint. Early recognition of this disorder usually results in a predictable and satisfactory outcome. However, when this disorder is unrecognized, late reconstruction is challenging and unpredictable, and treatment may be misdirected to the wrist alone if the forearm and elbow are not considered as a component of this injury. The present report describes the importance of examining the elbow in all cases of wrist pain. As well, the literature is reviewed regarding the differences in treatment of acute and chronic Essex-Lopresti injuries. As plastic surgeons become more involved in the treatment of wrist injuries, the conscientious practitioner should be aware of more complicated pathology that may present as a seemingly straightforward wrist problem.

Background: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in finger flexion contractures. Increased cellular beta-catenin levels have been identified as characteristic of this disease. As Wnts are the most widely recognized upstream regulators of cellular beta-catenin accumulation, we have examined Wnt gene expression in surgical specimens and in DD-derived primary cell cultures grown in two-dimensional monolayer culture or in three-dimensional FPCL collagen lattice cultures., Results: The Wnt expression profile of patient-matched DD and unaffected control palmar fascia tissue was determined by a variety of complimentary methods; Affymetrix Microarray analysis, specific Wnt and degenerative primer-based Reverse Transcriptase (RT)-PCR, and Real Time PCR. Microarray analysis identified 13 Wnts associated with DD and control tissues. Degenerate Wnt RT-PCR analysis identified Wnts 10b and 11, and to a lesser extent 5a and 9a, as the major Wnt family members expressed in our patient samples. Competitive RT-PCR analysis identified significant differences between the levels of expression of Wnts 9a, 10b and 11 in tissue samples and in primary cell cultures grown as monolayer or in FPCL, where the mRNA levels in tissue > FPCL cultures > monolayer cultures. Real Time PCR data confirmed the down-regulation of Wnt 11 mRNA in DD while Wnt 10b, the most frequently isolated Wnt in DD and control palmar fascia, displayed widely variable expression between the methods of analysis., Conclusion: These data indicate that changes in Wnt expression per se are unlikely to be the cause of the observed dysregulation of beta-catenin expression in DD.

Background: To study the protein expression profiles associated with Dupuytren's contracture (DC) to identify potential disease protein biomarkers (PBM) using a proteomic technology--Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS)., Methods: Normal and disease palmar fascia from DC patients were analyzed using Ciphergen's SELDI-TOF-MS Protein Biological System II (PBSII) ProteinChip reader. Analysis of the resulting SELDI-TOF spectra was carried out using the peak cluster analysis program (BioMarker Wizard, Ciphergen). Common peak clusters were then filtered using a bootstrap algorithm called SAM (Significant Analysis of Microarrays) for increased fidelity in our analysis., Results: Several differentially expressed low molecular weight (<20 kDa) tissue proteins were identified. Spectra generated using both ZipTipC18 aided Au array and WCX2 array based SELDI-TOF-MS were reproducible, with an average peak cluster mass standard deviation for both methods of <1.74 x10(-4). Initial peak cluster analysis of the SELDI spectra identified both up-(14) and down-(3)regulated proteins associated with DC. Further analysis of the peak cluster data using the bootstrap algorithm SAM identified three disease-associated protein features (4600.8 Da, 10254.5 Da, and 11405.1 Da) that were elevated (5.45, 11.7, and 4.28 fold, respectively, with a 0% median false discovery rate)., Conclusion: SELDI-TOF-MS identified three potential low molecular weight tissue protein markers (p4.6DC, p1ODC, p11.7DC) for DC. The ability of SELDI-TOF-MS to resolve low molecular weight proteins suggests that the method may provide a means of deciphering the biomarker-rich low molecular weight region of the human proteome. Application of such novel technology may help clinicians to focus on specific molecular abnormalities in diseases with no known molecular pathogenesis, and uncover therapeutic and/or diagnostic targets.

Background: The free transverse rectus abdominis musculocutaneous (TRAM) flap has proven to be a reliable means of recreating the aesthetic breast form after mastectomy. The purpose of this study was to determine whether neurotization of the free TRAM flap improved sensation of the reconstructed breast., Methods: Twenty-seven patients undergoing 37 free TRAM flap reconstructions were randomized to receive either an innervated (12 patients, 18 breasts) or a noninnervated flap (15 patients, 19 breasts). A nerve repair between the T10 intercostal of the TRAM flap and the anterior sensory branch of the fourth intercostal nerve was performed for innervation. Sensory testing (Semmes-Weinstein monofilaments, hot-cold discrimination, two-point discrimination) was performed by one blinded examiner in a standardized pattern., Results: Mean follow-up was 16 months. Demographic analysis revealed no significant differences in patient age, height, smoking, radiation therapy, and nipple-areola reconstruction between patient groups (p > 0.3). Patients in the noninnervated group, however, were heavier (p = 0.03). Preoperative sensation was not significantly different in the noninnervated and innervated groups. Postoperative pressure threshold and temperature discrimination were significantly improved in the innervated flaps (p < 0.05). Noninnervated flaps displayed a pattern of increasing sensibility from the center toward the periphery while innervated flaps regained sensation throughout., Conclusions: Innervation of the free TRAM flap provides improved sensation to the reconstructed breast and is a simple adjunct to breast reconstruction.

Background: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells., Methods and Findings: We characterized in vivo interactions between group A streptococci (GAS) and cells involved in innate immune responses, using human biopsies (n = 70) collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria., Conclusions: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections highlights a need for alternative therapeutic strategies.

Objectives: The most commonly used primary treatment for trigger fingers is corticosteroid injection in the flexor tendon sheath, followed by surgical release if unsuccessful. This study examines the surgical and nonsurgical treatment of patients with trigger fingers presenting to a large Canadian tertiary referral center. The treatment success and side-effect profile of steroid injection therapy and surgical release were examined in the context of comorbid illness, specifically, diabetes mellitus., Design: Retrospective review of all patients with trigger finger who were seen by the senior authors between January 1999 and June 2004., Results: In the study period, 118 trigger digits were treated. This study included 92 nondiabetic, 21 type 2 diabetic, and five type 1 diabetic trigger fingers. Of the 89 digits that received at least one steroid injection, 46 (52%) resolved completely and 42 (47%) were improved. Nondiabetic digits were treated successfully in 40 out of 70 digits (57%) with steroid injection therapy. Diabetic patients had a success rate of 6 of 19 (32%) with steroid injections, which is significantly lower than nondiabetics (P = 0.04). All type 1 diabetics (n = 5) required surgical treatment. Surgical treatment was successful in 71 of 72 (99%) digits. No side effects of steroid injection were noted, and short-term postoperative side effects were noted in 26 of 72 surgical patients (36%). No statistically significant differences were found in surgical complication rates in diabetics vs. nondiabetics or type 1 diabetics vs. type 2 diabetics., Conclusions: Steroid injection therapy should be the first-line treatment of trigger fingers in nondiabetic patients. In diabetics, the success rate of steroid injection is significantly lower. Injection therapy for type 1 diabetics was ineffective in this study. Surgical release of the first annular (A1) pulley is most effective overall in diabetics and nondiabetics alike, with no higher rates of surgical complications in diabetics.

Background: As a component of the progression from genomic to proteomic analysis, there is a need for accurate assessment of protein post-translational modifications such as phosphorylation. Traditional kinase assays rely heavily on the incorporation of gamma-P32 radiolabeled isotopes, monoclonal anti-phospho-protein antibodies, or gel shift analysis of substrate proteins. In addition to the expensive and time consuming nature of these methods, the use of radio-ligands imposes restrictions based on the half-life of the radionucleotides and pose potential health risks to researchers. With the shortcomings of traditional assays in mind, the aim of this study was to develop a high throughput, non-radioactive kinase assay for screening Glycogen Synthase Kinase-3beta (GSK-3beta) activity., Results: Synthetic peptide substrates designed with a GSK-3beta phosphorylation site were assayed with both recombinant enzyme and GSK-3beta immunoprecipitated from NIH 3T3 fibroblasts. A molecular weight shift equal to that of a single phosphate group (80 Da.) was detected by surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) in a GSK-3beta target peptide (2B-Sp). Not only was there a dose-dependent response in molecular weight shift to the amount of recombinant GSK-3beta used in this assay, this shift was also inhibited by lithium chloride (LiCl), in a dose-dependent manner., Conclusion: We present here a novel method to sensitively measure peptide phosphorylation by GSK-3beta that, due to the incorporation of substrate controls, is applicable to either purified enzyme or cell extracts. Future studies using this method have the potential to elucidate the activity of GSK-3beta in vivo, and to screen enzyme activity in relation to a variety of GSK-3beta related disorders.

In Canada, hydroxyethyl starch 264/0.45 (HES 264/0.45; molar weight 264 kDa, molar substitution 0.45) has largely replaced albumin as the colloidal fluid of choice for perioperative intravascular volume expansion. The maximum recommended dose of HES 264/0.45 is 28 mL/kg; however, there are no clinical data supporting this limit. In this study we compared the hemostatic effects of HES 264/0.45 versus 5% albumin in doses up to 45 mL/kg over 24 h during major reconstructive head and neck surgery. Fifty patients were randomized to receive HES 264/0.45 or 5% human albumin from the induction of anesthesia until 24 h thereafter. Both albumin and HES 264/0.45 effectively maintained physiologic variables in the perioperative and postoperative periods. The partial thromboplastin time and international normalized ratio were significantly increased in the HES 264/0.45 group compared with the albumin group after infusion of 30 mL/kg and 45 mL/kg (P < 0.05). Factor VIII activity and von Willebrand factor level were significantly reduced in the HES 264/0.45 group compared with the albumin group after infusion of 15 mL/kg, 30 mL/kg, and 45 mL/kg (P < 0.05). Significantly more subjects in the HES 264/0.45 group received allogeneic red blood cell transfusions (P < 0.02). We conclude that HES 264/0.45 infusions >30 mL/kg over 24 h impair coagulation to a greater extent than albumin, possibly leading to more allogeneic transfusions.

Intravenous polyspecific immunoglobulin G (IVIG) has been reported to be efficacious as adjunctive therapy in patients with toxic shock syndrome caused by a group A streptococci (GAS). GAS is also an important cause of necrotizing fasciitis, for which an early and extensive surgical intervention is currently advocated. Here we report on the use of an aggressive medical regimen including high-dose IVIG together with a conservative surgical approach in severe GAS soft tissue infection. We describe 7 patients with severe soft tissue infection caused by GAS, who all were treated with effective antimicrobials and high-dose IVIG. Surgery was either not performed or only limited exploration was carried out. Six of the patients had toxic shock syndrome. All patients survived. Immunostaining of tissue biopsies from 2 of the patients revealed high levels of GAS, superantigen and pro-inflammatory cytokines initially, which were dramatically reduced in a repeat biopsy of the initial operative site collected from 1 of the patients 66 h post-IVIG administration. The study suggests that the use of a medical regimen including IVIG in patients with severe GAS soft tissue infections may allow an initial non-operative or minimally invasive approach, which can limit the need to perform immediate wide debridements and amputations in unstable patients.

The extensor tendons to the index, long, ring and small fingers are motored by the common extensor digitorum communis muscle body. Effective function of this muscle can only occur if the gliding amplitude of each of its four extensor tendons is normal. As a corollary, limitation of the excursion of any of the individual tendons by adhesions at a fracture or tendon repair site, a fixed flexion contracture at the metacarpophalangeal joint, or by rupture, attenuation or laceration of a saggital band or juncturae tendinum, will result in reduction of the excursion of the adjacent extensor tendons. This pathological state has been termed the extensor quadriga because of its similarities to the analogous pathology affecting the flexor digitorum profundus system. Improper management of this clinical entity may lead to an abnormal pathomechanical kinematic chain imbalance. Early identification and treatment is critical to address this entity appropriately.

Background: Dupuytren's disease (DD) is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions (nodules and cords) leading to flexion contractures of the fingers and loss of hand function. Although the molecular mechanism of DD is unknown, it has been suggested that transforming growth factor-beta2 (TGF-beta2) may play an important role in the underlying patho-physiology of the disease. The purpose of this study was to further explore this hypothesis by examining the effects of TGF-beta2 on primary cell cultures derived from patient-matched disease and normal palmar fascia tissue using a three-dimensional collagen contraction assay., Methods: Fibroblast-populated collagen lattice (FPCL) contraction assays using primary cell cultures derived from diseased and control fascia of the same DD patients were studied in response to exogenous TGF-beta2 and neutralizing anti-TGF-beta2 antibodies., Results: Contraction of the FPCLs occurred significantly faster and to a greater extent in disease cells compared to control cells. The addition of TGF-beta2 enhanced the rate and degree of collagen contraction in a dose-dependent fashion for both control and diseased cells. Neutralizing anti-TGF-beta2 antibodies abolished exogenous TGF-beta2 stimulated collagen contraction, but did not inhibit the enhanced basal collagen contraction activity of disease FPCL cultures., Conclusions: Although exogenous TGF-beta2 stimulated both disease and control FPCL contraction, neutralizing anti-TGF-beta2 antibodies did not affect the elevated basal collagen contraction activity of disease FPCLs, suggesting that the differences in the collagen contraction activity of control and disease FPCL cultures are not due to differences in the levels of endogenous TGF-beta2 activity.

Background: Ulceration of the lower extremities is a common disorder that can be very painful. It occurs most frequently in the elderly population as a result of venous hypertension. We report an unusual case of a 32-year-old man with an 11-year history of extensive, painful, bilateral leg ulcers resistant to conventional treatment necessitating above-knee amputation of the left leg. Eventually, the patient was treated with prednisone, which led to almost complete healing of the ulcers of the right leg., Objective: The objective of this report is to discuss a rare cause of chronic bilateral leg ulceration., Methods: Detailed histopathologic examination showed a complex pattern of overlapping features of several specific dermatologic conditions, including necrobiosis lipoidica (NL), necrobiotic xanthogranuloma (NXG), and the destructive form of granuloma annulare (GA)., Conclusion: The characteristics of our patient suggest a variant of a cutaneous necrobiotic disorder that has not been previously reported. When clinicians are confronted with recalcitrant ulcerations in the lower extremity, this group of disorders should be considered in the differential diagnosis.