Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model for Best Disease

PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5′- and 3′-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. All exons and the flanking splice junctions were screened by direct sequencing. RESULTS. The clinical phenotype and pathology of cmr closely resemble lesions of BMD. Canine VMD2 spans 13.7 kb of genomic DNA on CFA18 and shows a high level of conservation among eukaryotes. The transcript is predominantly expressed in RPE/choroid and encodes bestrophin, a 580-amino acid protein of 66 kDa. Immunocytochemistry of normal canine retina demonstrated specific localization of protein to the RPE basolateral plasma membranes. Two disease-specific sequence alterations were identified in the canine VMD2 gene: a C73T stop mutation in cmr1 and a G482A missense mutation in cmr2. CONCLUSIONS. The authors propose these two spontaneous mutations in the canine VMD2 gene, which cause cmr, as the first naturally occurring animal model of BMD. Further development of the cmr models will permit elucidation of the complex molecular mechanism of these retinopathies and the development of potential therapies

Capturing residents' values for urban green space: mapping, analysis and guidance for practice

Planning for green space is guided by standards and guidelines but there is currently little understanding of the variety of values people assign to green spaces or their determinants. Land use planners need to know what values are associated with different landscape characteristics and how value elicitation techniques can inform decisions. We designed a Public Participation GIS (PPGIS) study and surveyed residents of four urbanising suburbs in the Lower Hunter region of NSW, Australia. Participants assigned dots on maps to indicate places they associated with a typology of values (specific attributes or functions considered important) and negative qualities related to green spaces. The marker points were digitised and aggregated according to discrete park polygons for statistical analysis. People assigned a variety of values to green spaces (such as aesthetic value or social interaction value), which were related to landscape characteristics. Some variables (e.g. distance to water) were statistically associated with multiple open space values. Distance from place of residence however did not strongly influence value assignment after landscape configuration was accounted for. Value compatibility analysis revealed that some values co-occurred in park polygons more than others (e.g. nature value and health/therapeutic value). Results highlight the potential for PPGIS techniques to inform green space planning through the spatial representation of complex human-nature relationships. However, a number of potential pitfalls and challenges should be addressed. These include the non-random spatial arrangement of landscape features that can skew interpretation of results and the need to communicate clearly about theory that explains observed patterns

Trends in laparoscopic splenectomy for massive splenomegaly

Hypothesis: During the past 10 years, expertise with minimally invasive techniques has grown, leading to an increase in successful laparoscopic splenectomy (LS) even in the setting of massive and supramassive spleens. Design Retrospective series of patients who underwent splenectomy from November 1, 1995, to August 31, 2005. Setting Academic tertiary care center. Patients Adult patients who underwent elective splenectomy as their primary procedure (n =3D 111). Main Outcome Measures Demographics, spleen size and weight, conversion from LS to open splenectomy, postoperative length of stay, and perioperative complications and mortality. Massive splenomegaly was defined as the spleen having a craniocaudal length greater than 17 cm or weight more than 600 g, and supramassive splenomegaly was defined as the spleen having a craniocaudal length greater than 22 cm or weight more than 1600 g. Results: Eighty-five (77%) of the 111 patients underwent LS. Of these 85 patients, 25 (29%) had massive or supramassive spleens. These accounted for 40% of LSs performed in 2004 and 50% in 2005. Despite this increase in giant spleens, the conversion rate for massive or supramassive spleens has declined from 33% prior to 1999 to 0% in 2004 and 2005. Since January 2004 at our institution, all of the massive or supramassive spleens have been removed with a laparoscopic approach. Patients with massive or supramassive spleens who underwent LS had no reoperations for bleeding or deaths and had a significantly shorter postoperative length of stay (mean postoperative length of stay, 3.8 days for patients who underwent LS vs 9.0 days for patients who underwent open splenectomy; P<.001). Conclusions: Despite conflicting reports regarding the safety of LS for massive splenomegaly, our data indicate that with increasing institutional experience, the laparoscopic approach is safe, shortens the length of stay, and improves mortality

Nodular Lymphocyte Predominant Hodgkin Lymphoma of the Ileum

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma derived from germinal center B lymphocytes that typically presents with localized lymph node involvement and can mimic a variety of both reactive and other neoplastic conditions. Extranodal involvement is uncommon in NLPHL and typically occurs in the context of previously documented or synchronous nodal disease. Involvement of the gastrointestinal tract is exceedingly rare. Here, we present the first case to our knowledge of NLPHL involving the ileum that was discovered incidentally on routine screening colonoscopy in an asymptomatic patient. An awareness of the spectrum of clinical presentations, careful morphologic evaluation, and a comprehensive panel of immunohistochemical stains are essential for correct diagnosis of NLPHL presenting in unusual anatomic sites