Intrahepatic activation of naive CD4+ T cells by liver-resident phagocytic cells.

Naive T cell activation is normally restricted to the lymphoid organs, in part because of their limited ability to migrate into the parenchyma of peripheral tissues. The liver vasculature is unique, however, and circulating leukocytes within the hepatic sinusoids have direct access to liver-resident cells, which include an abundant population of Kupffer cells. It is well accepted that recognition of cognate Ag within the liver leads to naive CD8(+) T cell activation in situ, but it is unclear whether the liver also supports naive CD4(+) T cell activation. In this study, we show that naive CD4(+) T cells can be activated to proliferate in the liver when cognate Ag expression is induced in hepatocytes by recombinant adeno-associated viral vectors. Ag-specific retention and activation of naive CD4(+) T cells within the liver are independent of lymphoid tissues but dependent on a clodronate liposome-sensitive population of liver-resident phagocytic cells. To our knowledge, this study provides the first unequivocal evidence that naive CD4(+) T cells can be activated in a nonlymphoid organ. It also gives critical insight into how CD4(+) T cells specific for Ag expressed in the liver are recruited to participate in protective or pathological responses during hepatotropic infections and autoimmune liver disease.

Induction intravenous cyclophosphamide followed by maintenance oral immunosuppression in refractory myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) can be refractory to conventional immunotherapy. We report on the efficacy and durability of intravenous (IV) remission-induction cyclophosphamide (CYC) followed by oral immunosuppression in refractory MG. METHODS: We identified 8 patients from our medical records with moderate or severe refractory MG who were treated with 6 cycles of IV CYC (0.75 g/m(2) ) every 4 weeks followed by oral immunosuppression. RESULTS: Six patients improved within 3 months of treatment. Four patients remained in clinical remission (mean follow-up 31 months). Two patients responded partially, and 1 patient relapsed after 11 months. Two patients were non-responders. CYC was well tolerated. Acetylcholine receptor antibody levels remained below pretreatment levels in patients in clinical remission. The leukocyte nadir was lower in CYC responders. CONCLUSIONS: Remission-induction IV CYC followed by oral immunosuppression is a rapid, effective, and durable treatment for refractory MG. Adding a post-CYC immunosuppressant may account for low relapse rates compared with other published series.

Retinoids for preventing the progression of cervical intra-epithelial neoplasia.

BACKGROUND: Invasive cervical carcinoma is preceded by a precancerous phase, cervical intra-epithelial neoplasia (CIN), which can be detected on cervical smears and confirmed by colposcopy and biopsy. Moderate and severe cases of intra-epithelial neoplasia (CIN2 and CIN3) are treated mainly with surgery to prevent progression to invasive carcinoma. Medical methods of preventing the progression or inducing the regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation that may have potential for the treatment of CIN. OBJECTIVES: To ascertain whether retinoids can cause regression or prevent progression of CIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Review Group's Specialised Register and Non-Trials Database, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2010), and MEDLINE and EMBASE (July 2010).For the 2013 update, the searches were re-run as follows: CENTRAL, Issue 3, 2013; MEDLINE, April, Week 2, 2013; and EMBASE, Week 16, 2013. SELECTION CRITERIA: Randomized controlled trials (RCTs) and non-RCTs of retinoids for treating CIN in women. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data from the trials. Adverse effects information was also collected from the trials. MAIN RESULTS: Five RCTs comparing the efficacy of four different retinoids were identified. Two studies examined the effects on CIN2 and CIN3 of the retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) and 9-cis-retinoic acid (aliretinoin) given orally. Two examined the effect of all-trans-retinoic acid administered topically to the cervix. The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally to human immunodeficiency virus (HIV)-positive participants with CIN1 and condyloma.Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, and the fifth did not report data on progression. In all studies retinoids had no significant effect on regression of CIN3. Two studies reported that retinoids were associated with regression of CIN2. One reported a greater complete regression of CIN2 over that seen with placebo, which was of borderline statistical significance (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.25 to 1.02). The other study reported a nonsignificant dose-related trend toward increased rates of complete and partial regression compared with placebo. One study reported significantly worse outcomes in women receiving retinoid (OR for regression 6.00, 95% CI 1.00 to 35.91). In general, the retinoid medications were well tolerated.In the 2010 review and in this update, no new studies were identified for inclusion. AUTHORS' CONCLUSIONS: The retinoids studied are not effective in causing regression of CIN3 but may have some effect on CIN2. The data on CIN1 are inadequate. Retinoids are not effective in preventing progression of CIN of any grade. At the doses given for the duration of treatment studied, the retinoids were reasonably well tolerated.

The glenoid center point: a magnetic resonance imaging study of normal scapular anatomy.

Using 10 normal cadaveric glenoids, Matsen and colleagues described the anatomic concept and clinical use of the glenoid centering point during shoulder arthroplasty. In the study reported here, we used magnetic resonance imaging scans of 50 patients with nonarthritic conditions of the glenohumeral joint to evaluate the relationship between the glenoid center line and the scapular neck. Results from this larger group of patients confirmed that a reproducible anatomic relationship of the glenoid centering line and the centering point on the anterior glenoid neck exists and can be used to restore normal anatomy in cases of posterior glenoid wear. An understanding of this anatomic relationship vis-à-vis shoulder arthroplasty may aid in recreating a normal glenoid version.

Retrieval of an intact, intraarticular bullet by hip arthroscopy using the lateral approach.

A twenty-seven-year-old man sustained a gunshot wound to the left gluteal region. Both plain films and a computed tomography (CT) scan confirmed that the bullet was in the hip joint. Using the lateral approach, the patient underwent hip arthroscopy, and the bullet was removed without difficulty. After surgery, the patient went on to an uneventful recovery. The use of arthroscopy for bullet removal minimized the surgical dissection, avoided an extensive capsulotomy, and reduced the associated risk of injury to the blood supply of the femoral head and osteonecrosis. This report illustrates the application of hip arthroscopy in the removal of retained bullets with minimal associated morbidity and further expands the indications for this procedure.

Lateral elbow ecchymosis as a clinical sign of lateral humeral condylar fractures.

Given the appropriate clinical history and mechanism of injury, the presence of localized lateral elbow ecchymosis in a young child is usually the sign of lateral condyle fracture of the humerus. Recognition of this clinical sign helps in directing the diagnostic studies and empiric treatment toward a lateral condyle fracture of the humerus not apparent on initial radiographs.

Trapezium excision and suture suspensionplasty (TESS) for the treatment of thumb carpometacarpal arthritis.

Basilar thumb arthritis, or first carpometacarpal arthritis, is a common condition affecting older women and some men. It is estimated that as many as one third of postmenopausal woman are affected. Surgical treatment of this condition includes options ranging from arthrodesis to prosthetic arthroplasty. Intermediate options include complete or partial trapezial excision with or without interposition of a cushioning/stabilizing material (auto source, allo source, synthetic source). A multitude of methods appear to offer similar end results, although some methods definitely involve more surgical work and perhaps greater patient risk. Through retrospective evaluation of a cohort of patients who underwent suture suspensionplasty, we determined the postoperative effect on strength, motion, patient satisfaction, complications, and radiographic maintenance of the scaphoid-metacarpal distance. This review shows the method to be clinically effective and, by comparison with a more traditional ligament reconstruction trapezial interposition arthroplasty, the method does not require use of autograft or allograft tendon and has fewer surgical steps. Forty-four patients were included in this retrospective study. The results showed that 91% of patients were satisfied with the procedure. Pinch and grip strength remained the same preoperatively and postoperatively. A Disabilities of the Arm, Shoulder, and Hand patient-reported outcome instrument (DASH) scores averaged 30 at final follow-up. Three patients developed a late complication requiring further surgical intervention. In summary, this technique appears to be technically reproducible, requires no additional tendon material, and achieves objectively and subjectively similar results to other reported procedures used to manage first CMC Arthritis.

The effect of the forearm support band on forces at the origin of the extensor carpi radialis brevis: a cadaveric study and review of literature.

The forearm support band is hypothesized to reduce force, and thus inflammation, at the extensor carpi radialis brevis (ECRB) origin. Very little published evidence supports an actual effect on the forces at the ECRB origin, however. The authors describe a cadaveric study in which forces at the ECRB origin were measured while various pressures were applied to the forearm support band and the ECRB tendon was loaded distally. The results reveal an increased effect with increased band pressure and a decreased relative effect with increased force applied distally. For clinical correlation, application pressure was also measured in nine patients using a counterforce brace. While further clinical evaluation is necessary to determine the most appropriate clinical indications for use of a forearm support band, these results suggest that the forearm support band may be most effective when applied at a force of 40 to 50 mmHg and used during light-duty activities.

Modeled evidence of force reduction at the extensor carpi radialis brevis origin with the forearm support band.

PURPOSE: Although the forearm support band has been hypothesized to reduce force and thus inflammation and degeneration at the extensor carpi radialis brevis (ECRB) origin, little evidence exists to support an actual effect. We present both a cadaveric and clinical model that show the effect and principles of the forearm support band. METHOD: The cadaver model measured forces at the ECRB origin as various pressures were applied to the forearm support band and while the ECRB tendon was loaded distally. For clinical correlation support band pressure during rest and activity was measured in healthy individuals. RESULTS: Our results revealed an increased forearm support band effect with increased band pressure and a decreased relative effect with increased force applied distally. For clinical correlation the support band pressure during activity was measured in 21 healthy volunteers while controlling for the application pressure in 2 common support band designs. This resulted in activity pressures ranging from 43 to 192 mm Hg dependent on the starting pressure of application. CONCLUSIONS: Although further clinical evaluation is necessary to determine the most appropriate clinical indications and application pressures for the forearm support band these combined results suggest that the forearm support band may be most effective when applied to 30 to 50 mm Hg at rest, resulting in up to 120 mm Hg pressure during activity. According to our model this would result in a force reduction at the ECRB origin of approximately 13% to 15% throughout a range of activity levels.

Superiorly based laminoplasty in children: average 6.8-year follow-up of 21 patients.

This study is a retrospective review of patients with pediatric laminoplasty. The objective was to determine the incidence of postlaminoplasty deformity. Long-term follow-up of patients with pediatric laminoplasty is lacking. Previous studies have shown spine deformity to be as high as 100% following laminectomy procedures. From 1986 until present, 31 superiorly based laminoplasties were performed on pediatric patients, ranging from two to 12 levels. Twenty-one of the 31 were available for complete review. A retrospective review of the radiographic deformity of these patients was conducted. Preoperative and postoperative scoliotic and kyphotic deformities were measured, and the correlating diagnoses were recorded. The average follow-up period was 6.8 years, and average age at follow-up was 11.9 years. Sixteen of 21 showed no increase in spinal deformity. Five of 21 showed nonunion at one or more levels. Five patients showed an increased deformity, of which two required surgical intervention to correct deformity. Although the technique of laminoplasty has very low morbidity (essentially no different from laminectomy), this review has not shown that this procedure eliminates postsurgical deformity. However, we recommend the use of laminoplasty in the pediatric patient because it may reduce the incidence of deformity, allow future segmental instrumentation if necessary, and has a low morbidity.