Decellularized biologic muscle-fascia abdominal wall scaffold graft.

BACKGROUND: Complex abdominal wall reconstruction using biologic mesh can lead to increased recurrence rates, nonincorporation, and high perioperative costs. We developed a novel decellularization method and applied it to porcine muscle fascia to mirror target-tissue architecture. The aims of this study were to analyze mechanical strength and tissue-graft incorporation. METHODS: After serial decellularization, muscle-fascia mesh was created and tested for mechanical strength and DNA content. The muscle-fascia mesh was implanted subcutaneously in rats (n = 4/group) and the cohorts killed 1 to 4 weeks later. Explants were examined histologically or immunohistochemically. RESULTS: Mechanical testing demonstrated equivalent strength compared with a commercially available biological mesh (AlloDerm), with mechanical strength attributable to the fascia component. Grafts were successfully implanted with no observable adverse events. Gross necroscopy revealed excellent subdermal scaffold engraftment. Microscopic evaluation identified progressive collagen deposition within the graft, neoangiogenesis, and presence of CD34 positive cells, in the absence of discernable graft rejection. CONCLUSION: This study confirms a decellularization process can successfully create a DNA-free composite abdominal wall (muscle-fascia) scaffold that can be implanted intraspecies without rejection. Expanding this approach may allow exploitation of the angiogenic capacities of decellularized muscle, concomitant with the inherent strength of decellularized fascia, to perform preclinical analyses of graft strength in animal models in vivo.

Ethnic differences in cytokine gene polymorphisms: potential implications for cancer development.

Differences in incidence and outcome of cancer among ethnic groups may be explained by biological and/or socio-economic factors. Genetic variations that affect chronic inflammation, a potentially important risk factor for carcinogenesis, may differ across ethnic groups. Such differences may help explain cancer disparities among these groups. Single nucleotide polymorphisms (SNPs) within cytokine genes can affect cytokine levels and the degree of inflammation. Associations between cancer and some cytokine SNPs have been suggested. However, these have not been consistently replicated among populations, suggesting that SNP function may differ according to ethnicity, or that SNPs alone do not completely account for regulation of inflammation. We examined seven polymorphisms in African-American (n = 294) and Caucasian (n = 299) newborns in Louisiana: IL1B-511C > T, IL1B-31T > C, IL1B + 3954C > T, IL1RN*2, IL10-1082G > A, IL10-592C > A, and TNF-308G > A. African-American newborns had significantly higher frequencies of IL1B-511T, IL1B-31C, IL10-1082A and IL10-592A alleles and complete linkage equilibrium between IL1B + 3954 and IL1B-31. In contrast, IL1B + 3954T, IL1RN*2, and TNF-308A were more frequent in Caucasian newborns and exhibited strong linkage disequilibrium between IL1B + 3954 and IL1B-31. All allelic frequencies were significantly different between groups. We hypothesize that these dissimilarities may contribute to differences in the inflammatory response and cancer incidence and mortality between African-Americans and Caucasians in Louisiana.

Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and White children with Crohn's disease.

BACKGROUND: Despite a large body of literature on the subject of Crohn's disease (CD), very little information is available on racial/ethnic differences related to disease presentation, clinical course, and genetics. The first identified CD susceptibility gene, CARD15, seems to be present in up to 40% of white children with CD. However, the frequency of this gene among patients with CD of other racial/ethnic groups in the United States is not known. METHODS: We conducted a multicenter study on African American and Hispanic children with CD to describe the phenotypic and genotypic (CARD15) features in comparison with white children with CD. We also analyzed the frequency of CARD15 mutations in large control samples from white, African American, and Hispanic children. RESULTS: The disease location and behavior were similar among all 3 groups, with inflammatory behavior and the ileocolonic location being the most frequent phenotype. However, significantly lower frequencies of CARD15 mutations were seen in African American (P < 0.0001) and Hispanic (P < 0.0001) children with CD compared with white children with CD. This lower CARD15 frequency among African American patients with CD was also mirrored in the general population. CONCLUSIONS: Phenotypic features of CD are similar among African American and Hispanic children compared with white children. CARD15 mutations are not increased among African American and Hispanic children with CD. CARD15 mutational frequencies among African American and Hispanic children within the general population are lower compared with white children within the general population. Future genetics studies will be required to determine the relationships between genotype and CD phenotype in various ethnic and racial groups.

High protein diet mimics hypertyrosinemia in newborn infants.

Tyrosinemia resulting from administration of protein-dense infant diets was detected by newborn screening in two infants. Change of formula resulted in rapid resolution of the hypertyrosinemia. These cases identify nonstandard infant diets as a benign and reversible cause of tyrosinemia and a potential cause of positive newborn phenylketonuria screening.