TGFbeta promotes Wnt expression during cataract development.

TGFbeta induces lens epithelial cells to undergo epithelial mesenchymal transition (EMT) and many changes with characteristics of fibrosis including posterior capsular opacification (PCO). Consequently much effort is directed at trying to block the damaging effects of TGFbeta in the lens. To do this effectively it is important to know the key signaling pathways regulated by TGFbeta that lead to EMT and PCO. Given that Wnt signaling is involved in TGFbeta-induced EMT in other systems, this study set out to determine if Wnt signaling has a role in regulating this process in the lens. Using RT-PCR, in situ hybridization and immunolocalization this study clearly shows that Wnts 5a, 5b, 7b, 8a, 8b and their Frizzled receptors are upregulated in association with TGFbeta-induced EMT and cataract development. Both rat in vitro and mouse in vivo cataract models show similar profiles for the Wnt and Frizzled mRNAs and proteins that were assessed. Currently it is not clear if the canonical beta-catenin/TCF signaling pathway, or a non-canonical pathway, is activated in this context. Overall, the results from the current study indicate that Wnt signaling is involved in TGFbeta-induced EMT and development of fibrotic plaques in the lens.

Defecation proctography and translabial ultrasound in the investigation of defecatory disorders.

OBJECTIVES: Defecation proctography is the standard method used in the investigation of obstructed defecation. Translabial ultrasound has recently been shown to demonstrate rectocele, enterocele and rectal intussusception. We performed a comparative clinical study to determine agreement between the two methods. METHODS: Thirty-seven women scheduled to undergo defecation proctography for obstructed defecation were recruited. Using both proctography and translabial ultrasound, we determined the anorectal angle, presence of a rectocele and rectocele depth, rectal intussusception and prolapse. Measurements were obtained by operators blinded to all other data. All patients rated discomfort on a scale of 0-10. RESULTS: Six women did not attend defecation proctography, leaving 31 cases for comparison. The mean age was 53 years. Patients rated discomfort at a median of 1 (range 0-10) for ultrasound and 7 (range 0-10) for defecation proctography (P < 0.001). Defecation proctography suggested rectocele and rectal intussusception/prolapse more frequently than did ultrasound. While the positive predictive value of ultrasound (considering defecation proctography to be the definitive test) was 0.82 for rectocele and 0.88 for intussusception/prolapse, negative predictive values were only 0.43 and 0.27, respectively. Cohen's kappa values were 0.26 and 0.09, respectively. There was poor agreement between ultrasound and defecation proctography measurements of anorectal angle and rectocele depth. CONCLUSIONS: Translabial ultrasound can be used in the initial investigation of defecatory disorders. It is better tolerated than defecation proctography and also yields information on the lower urinary tract, pelvic organ prolapse and levator ani. Agreement between ultrasound and defecation proctography in the measurement of quantitative parameters was poor, but when intussusception or rectocele was diagnosed on ultrasound these results were highly predictive of findings on defecation proctography.

Intravitreal steroids for macular edema in diabetes.

BACKGROUND: Macular edema is secondary to leakage from diseased retinal capillaries and is an important cause of poor central visual acuity in patients with diabetic retinopathy. OBJECTIVES: This review evaluated the effectiveness and safety of intraocular steroids in treating diabetic macular edema (DME). SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE in June 2007, reference lists, Science Citation Index and conference proceedings. SELECTION CRITERIA: We included randomized clinical trials (RCTs) evaluating any form of intravitreal steroids for treating DME. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility, methodological quality and extracted data. We performed meta-analyses when appropriate. MAIN RESULTS: Seven studies, involving 632 DME eyes were included. Four examined the effectiveness of intravitreal triamcinolone acetate injection (IVTA), three examined intravitreal steroids implantation (fluocinolone acetonide implant (FAI) or dexamethasone drug delivery system (DDS)). Two trials were at low risk of bias, one was at median risk of bias, two were at high risk of bias and the remaining two were at unclear risk of bias. The preponderance of data suggest a beneficial effect from IVTA. Comparing IVTA with controls, the mean difference in visual acuity was -0.15 LogMAR (95% CI -0.21 to -0.09) at 3 months (based on three trials), -0.23 LogMAR (95% CI -0.33 to -0.13) at 6 months (two trials), -0.29 LogMAR (95% CI -0.47 to -0.11) at 9 months (one trial), and -0.11 LogMAR (95% CI -0.20 to -0.03) at 24 months (one trial), all in favor of IVTA. The relative risk (RR) for one or more lines improvement in visual acuity was 2.85 (95% CI 1.59 to 5.10) at 3 months (two trials), 1.25 (95% CI 0.66 to 2.38) at 6 months (one trial), and 2.17 (95% CI 1.15 to 4.11) at 24 months (one trial), all in favor of IVTA. We did not find evidence for three or more lines improvement in visual acuity. The mean difference in retinal thickness was -131.97 um (95% CI -169.08 to -94.86) at 3 months (two trials), -135.00 um (95% CI -194.50 to -75.50) at 6 months (one trial), -133.00 um (95% CI -199.86 to -66.14) at 9 months (one trial), and -59.00 um (95% CI -103.50 to -14.50) at 24 months (one trial), all in favor of IVTA. The RR for at least one grade macular edema resolution was 5.15 (95% CI 2.23 to 11.88) at 3 months in favor of IVTA (one trial). Two trials reported improved clinical outcome when FAI was compared to standard of care. Beneficial effect was also observed in one dexamethasone DDS trial. Increased intraocular pressure and cataract formation were side effects requiring monitoring and management. AUTHORS' CONCLUSIONS: RCTs included in this review suggest that steroids placed inside the eye by either intravitreal injection or surgical implantation may improve visual outcomes in eyes with persistent or refractory DME. Since the studies in our report focused on chronic or refractory DME, the question arises whether intravitreal steroids therapy could be of value in other stages of DME, especially the earlier stages either as standalone therapy or in combination with other therapies, such as laser photocoagulation.

Radiotherapy in the management of recurrent synovial chondromatosis.

Synovial chondromatosis is a rare, benign condition characterized by the formation of multiple cartilaginous nodules that are generally intra-articular and can lead to chronic pain and limit the function of involved joints. We report on the novel use of radiotherapy that was used to treat a 42-year-old man with rapid recurrences of extensive synovial chondromatosis in the knee refractory to multiple operations. Based on follow-up MRI scans and clinical findings, the disease process was halted with no progression seen over 5 years.