Depleting anti-CD4 monoclonal antibody cures new-onset diabetes, prevents recurrent autoimmune diabetes, and delays allograft rejection in nonobese diabetic mice

BACKGROUND: The prevention of recurrent autoimmunity is a prerequisite for successful islet transplantation in patients with type I diabetes. Therapies effective in preserving pancreatic beta-cell mass in patients with newly diagnosed diabetes are good candidates for achieving this goal. Anti-CD3 monoclonal antibody (mAb) and antilymphocyte antisera are the only therapies to date that have cured early diabetic disease in the nonobese diabetic (NOD) mouse. We investigated whether other immunosuppressive therapies, including short-term depleting anti-CD4 mAb or costimulation blockade, would affect the disease progression in recently diabetic NOD mice. We also evaluated the effect of the anti-CD4 mAb on syngeneic and allogeneic graft survival in diabetic NOD recipients. METHODS AND RESULTS: We demonstrate that a short course of anti-CD4 mAb early after hyperglycemia onset cured diabetes. Normal islets and islets with CD4+ and CD8+ T-cell peri-insulitic infiltrate were found in the pancreata of cured NOD mice. A similar regimen prevented the recurrence of autoimmune diabetes in NOD/severe combined immunodeficient disease (SCID) islet isografts and delayed the rejection of allogeneic C57BL/6 islet allografts in diabetic female NOD mice. The co-transfer of diabetogenic splenocytes with splenocytes from anti-CD4 mAb-treated and cured NOD mice into 7-week-old, irradiated, NOD male mice was not able to protect from diabetes occurrence. This indicates that an anti-CD4-mediated cure of diabetes is independent of the induction of immunoregulatory T cells. Anti-CD154 mAb and cytotoxic T-lymphocyte antigen 4 immunoglobulin were ineffective in early-onset diabetes. CONCLUSION: Our results provide the first evidence that newly established autoimmune islet destruction in NOD mice responds to a short course of anti-CD4 mAb. In contrast, costimulation blockade is ineffective in this clinically relevant model.     

The stiff knee: Causes and cures

Gender, race, age, BMI, and pre-operative motion have been correlated with post-operative motion after TKA. Surgical techniques to achieve full motion include appropriate sizing and positioning of the implants, proper gap balancing and soft tissue release, removal of posterior condylar osteophytes, and adequate tibial slope. Patient education, pain management, and participation in post-operative rehabilitation are also important. If adequate motion is not achieved, then manipulation can be helpful particularly up to 3 months after surgery. Once scar tissue is more mature, 6 months to a year after surgery, arthroscopy to resect arthrofibrotic scar is an appropriate option. For stiffness beyond 1 year after surgery revision, TKA can be expected to result in modest improvement in motion, but pain relief may be quite variable.     

The stiff knee: Causes and cures

Stiffness after total knee arthroplasty one of the most common postoperative challenges. Stiffness is currently defined as mild, moderate or severe and is based on loss of flexion or terminal extension. The causes of postoperative stiffness are multifactorial and include poor preoperative range of motion, overly tight flexion or extension gaps, component malrotation, infection, or arthrofibrosis. Treatment can be separated into early or chronic stiffness and is treated with appropriate physical therapy, followed by manipulation under anesthesia which is best performed within 3 months of surgery. For chronic stiffness, arthroscopic lysis of adhesions and MUA is an option, particularly for flexion deficits, or open lysis of adhesions with polyethylene downsizing. Component revision is usually performed after one year from surgery for the severely stiff knee and those with malrotated/malaligned components. For MUA, around 85% of patients will return to normal function and ROM. For the remaining 15%, further surgical intervention can improve ROM by around 15 to 30 degrees. For component revision in the correct patient, ROM can improve significantly but complication, reoperation rates are higher than for aseptic revision surgery. This article reviews the causes and potential cures for stiffness after total knee arthroplasty.     

My Hours My Life

Me&Movie《忠烈杨家将》主演:郑伊健、林峰、郑少秋上映日期:2013年4月4日聚集郑伊健、于波、周渝民、李晨、林峰、吴尊、付辛博七大型男分别饰演杨家七郎,以及郑少秋、徐帆分饰杨令公及佘太君,因此这部杨家将除了传统的忠义、战争等元素,热血、青春、帅气也是一大看点     

Biofeedback successfully cures detrusor-sphincter dyssynergia in pediatric patients

PURPOSE: We assessed the efficacy of voiding and bladder biofeedback for achieving perineal synergy and curing symptoms in children with detrusor-sphincter dyssynergia MATERIALS AND METHODS: A total of 16 boys and 27 girls 4 to 14 years old with detrusor-sphincter dyssynergia diagnosed by uroflowmetry and electromyography underwent biweekly voiding biofeedback therapy consisting of perineal floor electromyography during uroflowmetry. The 6 patients with enuresis and an unstable bladder also underwent bladder biofeedback training during cystometry. Biofeedback continued until detrusor-sphincter dyssynergia resolved. Followup consisted of electromyography and uroflowmetry 1 month after completing biofeedback training, and telephone interviews after 2 and 4 years. RESULTS: Biofeedback resolved detrusor-sphincter dyssynergia in all children, although the condition disappeared significantly sooner in girls (p <0.02). Secondary enuresis disappeared significantly earlier than primary enuresis (p <0.0001). The 2-year success rate of 87.18% for enuresis decreased to 80% at the 4-year followup. CONCLUSIONS: Voiding and bladder biofeedback achieves perineal synergy and cures symptoms in children with detrusor-sphincter dyssynergia     

The stiff total knee arthroplasty: causes and cures

Stiffness following TKA can be related to patient factors, intraoperative technical errors, or postoperative surgical complications. The best management is prevention by providing thorough preoperative patient education, aggressive postoperative physiotherapy, and avoidance of technical errors.     

我的看法

对肝门胆管癌术前可切除性的评估我没有做过深入研究,凭临床经验得出的印象是能否切除最终要看手术探查的结果,术前难以定论。因为门静脉主干、左干、右干管腔无狭窄时,难以在术前判断门静脉壁是否受癌肿侵犯,而受侵犯与未受侵犯的预后是不一样的。我个人认为:(1)本文为回顾性资料     

Résultats des cures opératoires de l'hallux valgus

Summary The overall results have shown that the treatment of hallux valgus was always beneficial, but that the results depended on the severity of the initial hallux valgus and on the operative techniques. Allowing for these factors, the following operative indications are suggested: early but painful hallux valgus, where the metatarsophalangeal deformity is less than 30°, is dealt with by the MacBride or Petersen operation, taking care to avoid the risks of overcorrection of these procedures; habitual hallux valgus of 30 to 45° is most benefited by techniques of metatarseal osteotomy, either of the base, combinent with recentering of the sesamoid sling and exostectomy, or of the extra-articular metatarsal neck (Hohmann) to secure the best support strength from the pulp of the great toe; very severe hallux valgus, exceeding 50°, is best stabilised by metatarsophalangeal arthrodesis despite the fact that Swanson's arthroplasty is concurrent. But this is rivalled by biologic criticisms of intolerance to silastic, though this was not noted in the present series; we can no longer recommend the Keller-Brandes operation, even for the elderly, who will most benefit from metatarsophalangeal arthrodesis, nor can we recommend retensioning of the sesamoid sling by itself as advised by Lelièvre, although one of us, Max Perrin, is satisfied with this provided it is combined with dorsal release of the toes to correct the metatarsal fixity.

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Résultats des cures opératoires de l'hallux valgus

Résumé Les résultats globaux ont montré que la cure de l'hallux valgus était toujours bénéfique, mais que les résultats dépendaient de l'importance de l'hallux valgus initial et des techniques opératoires. Compte tenu de ces éléments, les indications opératoires suivantes peuvent être proposées : l'hallux valgus débutant, mais douloureux, dont la déformation métatarso-phalangienne est inférieure à 30°, est du domaine de l'opération de Mac Bride ou de Petersen, tout en se méfiant des risques d'hypercorrection de ces interventions; l'hallux valgus habituel de 30 à 45° bénéficiera au mieux des techniques d'ostéotomie métatarsienne, soit de la base associée à un recentrage de la sangle sésamoïdienne et d'une exostosectomie, soit du col métatarsien extra-articulaire selon Hohmann, permettant d'obtenir la meilleure force d'appui de la pulpe du gros orteil; l'hallux valgus, très important, supérieur à 50°, sera au mieux stabilisé par une arthrodèse métatarso-phalangienne, bien que l'arthroplastie de Swanson soit concurentielle. Mais celle-ci est entachée de critiques biologiques d'intolérance au sylastic, qui toutefois n'a pas été constatée dans la série présente; nous ne pouvons plus conseiller l'opération de Keller-Brandes, même chez la personne âgée, qui bénéficiera au mieux de l'arthrodèse métatarso-phalangienne, ni la remise en tension isolée de la sangle sésamoïdienne, selon Lelièvre, bien que l'un de nous, Max Perrin, en soit satisfait, à condition d'y associer la libération dorsale des orteils corrigeant l'enclavement métatarsien.

     

围手术期综合救治对颈前路手术并发症的影响

颈椎伤病致颈髓损伤是极具破坏性损伤，常常危及生命。颈前路减压植骨内固定是治疗颈椎伤病重要而有效的手术方法。围手术期综合救治对颈前路手术良好实施、促进颈髓神经功能恢复、有效防止各种并发症发生具有重要作用。现将自2004年3月-2006年1月开展的16例颈前路手术围手术期综合救治情况作如下分析。