Linkage studies and mutation analysis of the PDEB gene in 23 families with Leber congenital amaurosis.

The phenotype in the rd mouse is similar to the clinical presentation of Leber congenital amaurosis (LCA) in humans. Recently a nonsense mutation in the beta subunit of the cGMP phosphodiesterase (Pdeb) gene has been defined as the cause for the rd phenotype in the mouse and has raised the question as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using highly polymorphic (CA)n microsatellites has excluded the PDEB gene as a cause for LCA in 6 families. In the remaining 17 families, we have searched for mutations in the 22 exons of the PDEB gene using single-strand gel electrophoresis (SSGE). Multiple exonic polymorphisms have been determined. However, no DNA changes in the PDEB gene have been identified in our study population which could be causative for the LCA phenotype.     

In vitro selection of human rhinovirus relatively resistant to soluble intercellular adhesion molecule-1.

Variants of human rhinovirus serotype 39 (HRV-39) relatively resistant to inhibition by soluble intercellular adhesion molecule-1 (sICAM-1) were selected by serial passages in HeLa or WI-38 cells in the presence of sICAM-1. Moderate resistance (four- to fivefold increases in 50% effective inhibitory concentrations [EC50s]) was observed after the second passage in HeLa cells and remained constant during six further passages in the presence of 10 micrograms of sICAM-1 per ml. A 7- to 17-fold increase in EC50s was observed in WI-38 cells during passage with 10 micrograms/ml, and reversion to a nonresistant phenotype was not observed after four passages in the absence of sICAM-1. Resistance of a higher degree was obtained by passing HRV-39 in the presence of 100 micrograms of sICAM-1 per ml in HeLa cells (30-fold EC50 increase). The sICAM-1-resistant phenotype was estimated to constitute 1 in 10(4) to 1 in 10(5) PFU of a nonexposed HRV-39 population. Low to moderate levels of resistance to sICAM-1 inhibition emerge readily during in vitro passage in the presence of sICAM-1 and appear to be phenotypically stable.     

Colorectal Cancer Screening Pilot Program for Underserved Women in Cumberland County,Maine

Over 800 Maine residents will be diagnosed with colorectal cancer (CRC) this year, and nearly 300 will die from the disease. While CRC screening can reduce these rates, it is only among insured populations that screening rates exceed 50%. This project aimed to reduce barriers to, and increase rates of CRC screening among underinsured and uninsured women, ages 50 years and over, residing in Cumberland County, Maine. The existing network of the Maine Breast and Cervical Health Program (MBCHP) was used to reach the target population. A packet containing (1) an offer for no-cost fecal occult blood test (FOBT) screening and CRC-related educational materials, and (2) a stamped, addressed postcard specifying the woman’s interest in these resources, was mailed to 300 MBCHP enrollees residing in Cumberland County. Women requesting screening were contacted by phone to further determine eligibility. Ninety-three women (31%) requested FOBT kits and 29 of these women requested educational materials. Ten women were ineligible for screening because of previous colonoscopy. Fifty-two completed FOBT kits (63%) were returned; all were negative. An additional 42 (14%) women requested educational materials only. To reduce the burden of CRC in Maine and nationally, disparate populations must be reached with efficient and effective screening services. Established networks are proven means for reaching uninsured and underinsured individuals with education, screening services, and necessary follow-up care. This project serves as a model for the future development of similar programs statewide and nationally.     

Anastomotic leak after oesophagectomy and stent implantation: a systematic review

Anastomotic leaks following oesophageal cancer resection have a high mortality. Stents have an established position in the palliation of dysphagia due to malignancy and in treating malignant perforation or fistula. They are increasingly used for benign conditions such as spontaneous oesophageal perforation with encouraging results. In this systematic review we examine the available evidence and attempt to define the role of stents in the management of oesophageal anastomotic leaks after resection for cancer. It is evident from the review that plastic- and metal-covered stents are an effective strategy for the treatment of anastomotic leaks. Vigilance is required as complications such as stent migration and incomplete sealing are not uncommon. Further clinical studies with greater methodological rigor in terms of sample size and study design may confirm that stents have an important contribution to make in the management of oesophageal anastomotic leak.     

In vitro activity of zinc salts against human rhinoviruses.

The antiviral activity of zinc salts against rhinovirus types 1A and 39 was assayed by yield reduction and inhibition of cytopathic effect in cell culture. The findings indicate that the zinc salts tested have low in vitro therapeutic indices and suggest that the possible beneficial effects of zinc lozenges in reducing cold symptoms may not be related to selective antirhinovirus activity.     

Sonography of acute appendicitis in childhood: perforation versus nonperforation.

We evaluated the sonographic findings in 133 consecutive children referred for suspected appendicitis. Fifty-eight of these patients (44%) ultimately underwent surgery, with 54 of these proved to have acute appendicitis. Thirty-one (58%) of the 54 had nonperforated appendicitis, and 23 (43%) had evidence of perforation. Previously described sonographic findings that have been employed in the diagnosis of appendicitis were evaluated, with the presence or absence of these findings being compared in patients with non-perforated and perforated appendicitis. In those patients who did not undergo surgery, the following findings were documented and compared to the findings in patients with proved appendicitis: (1) an identifiable appendix and its sonographic characteristics, (2) fluid localized to the right peritoneal reflection or periappendiceal region, or both, (3) free pelvic fluid, and (4) right lower quadrant adenopathy. Our results suggest that high-resolution, real-time sonography, using graded compression, is very sensitive in the identification of acute nonperforated appendicitis. Perforated appendicitis, however, can be a more difficult diagnosis because the appendix frequently decompresses with perforation and yet may not "wall off" or form a well-defined abscess. As a result, the appendix can be very difficult to identify.     

CTLA-4 is required for the induction of high dose oral tolerance

Mucosal and systemic administrations of high dose antigens induce long- lasting peripheral T cell tolerance. We and others have shown that high dose peripheral T cell tolerance is mediated by anergy or deletion and is preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune regulation. In the present study, we examined the roles of the B7 co-stimulation pathway in the generation of high dose peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction completely abrogated peripheral T cell tolerance induced by either oral or i.p. antigens. These results suggest that CTLA-4-mediated feedback regulation plays a crucial role in the induction of high dose peripheral T cell tolerance.