The association between large congenital melanocytic naevi and cutaneous melanoma: preliminary findings from an Internet-based registry of 379 patients

There is ample evidence in the literature to support the fact that there is an increased risk of the development of melanoma in individuals with a large congenital melanocytic naevus (LCMN). The published melanoma risk estimates, by and large, do not distinguish between cutaneous and extracutaneous melanomas. It is currently not known to what extent each contributes to the overall cited melanoma risk estimates. In order to obtain a better understanding of the association between LCMN and cutaneous melanoma arising within an LCMN, we report the preliminary findings of a cross-sectional study of 379 patients, with a median age of 3 years, from the first self-referred, Internet-based registry of patients with LCMN. To date, no cutaneous melanoma has been reported; possible reasons for this finding are discussed. Further research is required to clarify the risk of the development of cutaneous melanoma separate from non-cutaneous melanoma and to identify subgroups of patients with LCMN at highest risk for the development of melanoma. This information will help to formulate appropriate decisions concerning the management of patients with LCMN.     

Evolution of an in vivo bioreactor.

The ideal bone graft substitute requires osteoconductive, osteoinductive, and osteogenic components. This study introduces an "in vivo bioreactor," a model in which pluripotent cells are recruited from circulating blood to a vascularized coralline scaffold supplemented with bone morphogenetic protein-2 (BMP-2). The bioreactor generates new, ectopic host bone with the capability of vascularized tissue transfer. More importantly, bone is reproducibly formed in a closed and malleable environment. In a rat model, the superficial inferior epigastric vessels were isolated, ligated, and then threaded through a prefabricated coral cylinder (hydroxyapatite, ProOsteon 500). Experimental groups were characterized by the following variables: (1) with/without incorporation of vascular pedicle; (2) with/without addition of BMP-2 (0.02 mg/cm3). Scaffolds were harvested 6 weeks after implantation, embedded and sectioned. Tissue samples were decalcified, fixed, and stained with H&E, trichrome green, and CD31/PECAM-1 (a marker of endothelial cells). Vascularized coral scaffolds supplemented with BMP-2 presumably recruited circulating mesenchymal stem cells to generate bone. Bone formation was quantified through histological analysis, and reported as a percentage, area bone/area cross section scaffold x 100. Mean bone formation was 11.30%+/-1.19. All scaffolds supplied by the vascular pedicle, regardless of BMP-2 supplementation, demonstrated neo-vascular ingrowth. Scaffolds lacking a pedicle showed no evidence of vascular ingrowth or bone formation. This paper introduces a model of a novel "in vivo bioreactor" that has future clinical and research applications. The tissue engineering applications of the "bioreactor" include treatment of skeletal defects (nonunion, tumor post-resection reconstruction). The bioreactor also may serve as a unique model in which to study primary and metastatic cancers of bone.     

Lipid Peroxidation in Bariatric Candidates with Nonalcoholic Fatty Liver Disease (NAFLD) – Preliminary Findings

Background: Pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains incompletely known, and oxidative stress is one of the mechanisms incriminated. The aim of this study was to evaluate the role of liver oxidative stress in NAFLD affecting morbidly obese patients. Methods: 39 consecutive patients with BMI >40 kg/m² submitted to Roux-en-Y gastric bypass were enrolled, and wedge liver biopsy was obtained during operation. Oxidative stress was measured by concentration of hydroperoxides (CEOOH) in liver tissue. Results: Female gender was dominant (89.7%) and median age was 43.6 ± 11.1 years. Histology showed fatty liver in 92.3%, including 43.6% with nonalcoholic steatohepatitis (NASH), 48.7% with isolated steatosis and just 7.7% with normal liver. Liver cirrhosis was present in 11.7% of those with nonalcoholic steatohepatitis. Concentration of CEOOH was increased in the liver of patients with NASH when compared to isolated steatosis and normal liver (0.26± 0.17, 0.20± 0.01 and 0.14± 0.00 nmol/mg protein, respectively) (P <0.01). Liver biochemical variables were normal in 92.3% of all cases, and no difference between NASH and isolated steatosis could be demonstrated. Conclusions: 1) Nonalcoholic steatosis, steatohepatitis and cirrhosis were identified in substantial numbers of morbidly obese patients; 2) Concentration of hydroperoxides was increased in steatohepatitis, consistent with a pathogenetic role for oxidative stress in this condition.     

M+C plan county exit decisions 1999-2001: implications for payment policy

The primary legislative response to diminishing private plan participation in the Medicare+Choice (M+C) program since 1999 has been substantial payment increases. Analysis of M+C decisions to continue serving or drop counties from 1999-2000 and 2000-2001 reveals that payment amounts, although important, did not have a consistent impact on these decisions. Plan decisions varied depending on the year and the intention to continue participating in M+C at all. Simulations show that M+C plans were better off, on average, with the payment methodology imposed by the Balanced Budget Act (BBA) of 1997 than under the previous payment system and that large payment increases would increase plan retention.