ERG overexpression and PTEN status predict capsular penetration in prostate carcinoma.

BACKGROUND: This study examines the combined effect of two common genetic alterations, ERG and PTEN, in prostate carcinoma progression. METHODS: Prostate tissue from 90 patients having unilateral capsular penetrating lesions, and a contra-lateral organ confined second lesion, were examined by immunohistochemistry for the expression of the TMPRSS2:ERG transformation product ERG and the loss of expression of PTEN, a powerful phosphatase inhibiting the PI3 kinase pathway. Multivariate logistic regression was carried out to analyze the data. RESULTS: After adjusting for Gleason score, the odds of having capsular penetration were 5.19 times higher (P = 0.015) for ERG+/PTEN- group as compared to the wild type (ERG-/PTEN+). CONCLUSIONS: This study presents the first evidence that ERG over expression and PTEN deletion is associated with greater risk of capsular penetration. Although further studies are needed, these results have the potential to change clinical assessment for prostate cancer.

Treatment of an individual with piriformis syndrome focusing on hip muscle strengthening and movement reeducation: a case report.

STUDY DESIGN: Case report. OBJECTIVE: To describe an alternative treatment approach for piriformis syndrome using a hip muscle strengthening program with movement reeducation. BACKGROUND: Interventions for piriformis syndrome typically consist of stretching and/or soft tissue massage to the piriformis muscle. The premise underlying this approach is that a shortening or "spasm" of the piriformis is responsible for the compression placed upon the sciatic nerve. CASE DESCRIPTION: The patient was a 30-year-old male with right buttock and posterior thigh pain for 2 years. Clinical findings upon examination included reproduction of symptoms with palpation and stretching of the piriformis. Movement analysis during a single-limb step-down revealed excessive hip adduction and internal rotation, which reproduced his symptoms. Strength assessment revealed weakness of the right hip abductor and external rotator muscles. The patient's treatment was limited to hip-strengthening exercises and movement reeducation to correct the excessive hip adduction and internal rotation during functional tasks. OUTCOMES: Following the intervention, the patient reported 0/10 pain with all activities. The initial Lower Extremity Functional Scale questionnaire score of 65/80 improved to 80/80. Lower extremity kinematics for peak hip adduction and internal rotation improved from 15.9 degrees and 12.8 degrees to 5.8 degrees and 5.9 degrees, respectively, during a step-down task. DISCUSSION: This case highlights an alternative view of the pathomechanics of piriformis syndrome (overstretching as opposed to overshortening) and illustrates the need for functional movement analysis as part of the examination of these patients. LEVEL OF EVIDENCE: Therapy, level 4.

Neuroradiological Endovascular Intervention for Diplopia in a Case of Aneurysmal Aberrant Regeneration of the Third Nerve.

Aberrant regeneration of the third nerve occurs as a result of synkinetic 'miswiring' of the third nerve following its injury, such as in third cranial nerve palsy due to tumor, trauma, or aneurysm. The case presented is an elderly woman with new vertical diplopia, which led to a diagnosis of a third cranial nerve palsy, thought to be caused by a 5 mm blister aneurysm of the posterior communicating artery. However, neuro-ophthalmological evaluation diagnosed aberrant regeneration of the third nerve, with the cause of her new vertical diplopia being an ipsilateral fourth nerve palsy. The patient underwent endovascular treatment of her aneurysm using stent-assisted coiling. This procedure was complicated by an episode of air embolism, from which the patient made a good recovery. This patient's presentation demonstrates that the cause of any diplopia must be established, and presents a novel, semi-schematic illustration of aberrant regeneration of the third nerve that should aid clinicians in its recognition.

Target selection of soluble protein complexes for structural proteomics studies.

BACKGROUND: Protein expression in E. coli is the most commonly used system to produce protein for structural studies, because it is fast and inexpensive and can produce large quantity of proteins. However, when proteins from other species such as mammalian are produced in this system, problems of protein expression and solubility arise 1. Structural genomics project are currently investigating proteomics pipelines that would produce sufficient quantities of recombinant proteins for structural studies of protein complexes. To investigate how the E. coli protein expression system could be used for this purpose, we purified apoptotic binary protein complexes formed between members of the Caspase Associated Recruitment Domain (CARD) family. RESULTS: A combinatorial approach to the generation of protein complexes was performed between members of the CARD domain protein family that have the ability to form hetero-dimers between each other. In our method, each gene coding for a specific protein partner is cloned in pET-28b (Novagen) and PGEX2T (Amersham) expression vectors. All combinations of protein complexes are then obtained by reconstituting complexes from purified components in native conditions, after denaturation-renaturation or co-expression. Our study applied to 14 soluble CARD domain proteins revealed that co-expression studies perform better than native and denaturation-renaturation methods. In this study, we confirm existing interactions obtained in vivoin mammalian cells and also predict new interactions. CONCLUSION: The simplicity of this screening method could be easily scaled up to identify soluble protein complexes for structural genomic projects. This study reports informative statistics on the solubility of human protein complexes expressed in E.coli belonging to the human CARD protein family.

Does Chronic Hypotony following Trabeculectomy Represent Treatment Failure?

PURPOSE: To measure the rate of complications from chronic hypotony following trabeculectomy and clarify the definition of postoperative hypotony. MATERIALS AND METHODS: In this retrospective case-control study, the rate of complications was compared between 34 eyes with chronic hypotony and 34 eyes without hypotony. Chronic hypotony was defined as those eyes with an intraocular pressure (IOP) of less than 6 mm Hg on two consecutive clinic visits at least 3 months after trabeculectomy. Cases were identified from a database of two glaucoma surgeons between 2010 and 2013. Outcomes measured included visual acuity, presence of choroidal effusion, hypotensive maculopathy and cataract development/progression. Factors associated with the development of hypotony were considered using analysis of variance (ANOVA) multivariate regression. RESULTS: Maculopathy was seen in 23.5% of hypotony eyes but not in controls (p < 0.01). No significant difference in the rate of choroidal effusion or cataract was documented between groups. Control eyes were more likely to remain complication free (58.8 vs 32.4%, p < 0.03). Spontaneous recovery from hypotony occurred in 32.4% of hypotony eyes. CONCLUSION: Sight threatening complications occur more frequently in eyes with chronic hypotony following glaucoma surgery. However, not all eyes with chronic hypotony develop sight threatening complications. A definition of hypotony that combines IOP criteria with the presence of structural and/or functional changes is recommended. How to cite this article: Yun S, Chua B, I Clement C. Does Chronic Hypotony following Trabeculectomy Represent Treatment Failure? J Curr Glaucoma Pract 2015;9(1):12-15.

Utilisation of a Novel Test to Measure Severity and Treatment Efficacy of Posterior Blepharitis.

Background. This study evaluated the effectiveness of managing posterior blepharitis (PB) using a novel Posterior Blepharitis Management Protocol (PBMP). Design. Prospective, consecutive case series with 100% followup to one month. Participants. 27 patients (54 eyes) with PB from an Ophthalmology practice in Sydney, Australia. Methods. Each patient's PB was assessed by grading the nature and expressibility of the central lower lid tarsal gland secretions on Compression Of The Eyelid (COTE). Patients were then instructed in detail to undertake daily PB management sessions at home using our modified PBMP. Main Outcome Measures. On a subjective scale, patients compared their symptoms at one month with baseline. COTE scores were reevaluated to assess the objective effectiveness of each individual's PBMP. COTE scoring was described as grades 1 (clear oil), 2 (pus, liquid), 3 (toothpaste-like secretions), and 4 (complete tarsal gland obstruction). Results. Patients reported a mean 77.8% ± 13.5% subjective improvement in symptoms. There was a trend towards improvement in COTE grading at one month compared with baseline: grades 1 (0 to 7.4%), 2a (22.2 to 16.6%), 2b (7.4 to 3.7%), 3 (18.5 to 27.7%), and 4 (51.8 to 44%). Conclusions. PBMP provided a rapid, inexpensive, simple, effective, and safe method of treating PB.

Role of CD44+ stem cells in mural cell formation in the human choroid: evidence of vascular instability due to limited pericyte ensheathment.

PURPOSE: To examine mural cell differentiation and pericyte ensheathment during human choroidal vascular formation and into adulthood. METHODS: Triple- and double-labeled immunohistochemistry (alpha-smooth muscle actin [αSMA], desmin, NG2, calponin, caldesmon, CD44, CD34, and CD39) were applied to human fetal (8-32 weeks' gestation) and adult choroidal and retinal wholemounts and histologic cross-sections. Transmission electron microscopy (TEM) was also undertaken. RESULTS: Early in development CD44+ stem cells also stained with αSMA and CD39, suggesting a common precursor. At 12 weeks' gestation, αSMA+ mural precursor cells, confirmed by TEM, were found scattered and isolated over the primordial vascular tree. During development, αSMA+ cells formed a continuous sheath around large arterioles; in veins there were gaps in αSMA expression. The choriocapillaris had an extensive vascular bed but limited coverage by αSMA+ and NG2+ mural cells. Calponin was expressed only on large vessels, and no caldesmon was detected. Pericyte ensheathment of adult capillaries was 11% for choroid versus 94% for retina. Remarkably, choroidal pericytes had no visible intermediate filaments (IFs) on TEM, though IFs were present in retinal pericytes. Neither retinal nor choroidal pericytes stained with desmin. CONCLUSIONS: CD44+ stem cells are involved in the formation of mural cells in the human choroidal vasculature. A marked reduction in pericyte ensheathment of human choroidal vessels suggests a permanently open "plasticity window" and a predisposition to vascular instability and poor autoregulatory ability.