Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.     

MRI evaluation of fatty liver in day to day practice: Quantitative and qualitative methods

Intracellular fat accumulation is a common feature of liver disease. Steatosis is the histological hallmark of non-alcoholic fatty liver disease (NAFLD) but also may occur with alcohol abuse, viral hepatitis, HIV and genetic lipodystrophies, and chemotherapy. This condition is common in the Western population and is typically associated with obesity and the metabolic syndrome. Early diagnosis and early treatment of NAFLD are important to prevent the development of end-stage liver disease and cancer. In addition, liver fat is a risk factor for postoperative complications after liver resection and transplantation. MRI has become a primary modality to assess hepatic steatosis, both qualitatively and quantitatively. In this article we discuss various MRI methods for evaluation of hepatic steatosis.     

Tyrosine-derived novel antimicrobial hydantoin polymers: synthesis and evaluation of anti-bacterial activities

A new approach for the design and synthesis of cyclic N-halamine polymers having anti-bacterial activity based on a vinyl derivative of tyrosine-derived hydantoin is reported. The synthesis of N-halamine polymers generally involves the chemical modification of 5,5′-disubstituted hydantoin to introduce polymerizable vinyl moieties thereby restricting the halogen capture only on the amide nitrogen. Here we show the possibility of synthesizing vinyl monomers of N-halamine from α-amino acids wherein both the amide and imide nitrogens are available for halogen capture. Thus, a hydantoin monomer was synthesized from L-tyrosine and copolymerized with methyl methacrylate and 2-(hydroxyethyl)methacrylate, to obtain random co-polymers. The monomer and its co-polymers were characterized using NMR, IR, HRMS, GPC, DSC, EDAX and TGA analysis. Films of the co-polymers cast from 10% acetone solutions were exposed to sodium hypochlorite solution to activate the hydantoin moieties. The oxidative chlorine content of the films ranged from 0.6 to 0.9%. The activated films were exposed to both Gram positive (S. aureus) and Gram negative (E. coli) bacteria using standard protocols. Polymers having chlorine content as little as 0.6% exhibited 6 log reduction in the bacterial growth within 30 min of exposure. The method allows the halogenation of both amide and imide nitrogens and could be applied to the preparation of a number of vinyl hydantoins from many amino acids.     

Differential Modulation of Intracellular Survival of Cytosolic and Vacuolar Pathogens by Curcumin

Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Leishmania infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter- and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria.     

The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions

The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of ‘race'' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3–5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry.     

Effect on gallbladder function subsequent to truncal vagotomy and gastrojejunostomy for chronic duodenal ulcer.

The effect of truncal vagotomy on gallbladder function and on the incidence of lithogenesis has remained controversial. A prospective and retrospective investigational study was undertaken to evaluate the effect of truncal vagotomy and gastrojejunostomy on gallbladder function. The study included a total of 76 patients and 77 controls. In Group I (Prospective group), 32 consecutive patients with chronic duodenal ulcer and gastric outlet obstruction undergoing truncal vagotomy and gastrojejunostomy were included. Group II included 25 age and gender matched controls (prospective group). Group III included 44 patients who had undergone truncal vagotomy and gastrojejunostomy 3 years or more prior to presentation (Retrospective group) and Group IV included 52 age and gender matched controls for the retrospective group. The patients in the prospective groups were followed up for a period of 1 year. An alkaline tide test was done in the prospective and retrospective group to assess for the completeness of vagotomy. Gallbladder contractile response to fatty meal and the presence of stones and sludge were noted in all the four groups by ultrasonography. There were 30 patients in the prospective group and 40 in the retrospective group after excluding patients with incomplete vagotomy. On ultrasound examination, there was no significant difference in the gallbladder volume and contractility of the study group when compared with the controls. Gallbladder sludge was found in 16 to 25% of patients in the prospective group (group I) during follow up, where as similar finding was documented in 8% of the matched control (group II (P>0.1). However, in the retrospective (group III) 10% (4 out of 40) had calculi and 20% of patients demonstrated sludge which was significantly higher when compared with the controls (p = 0.001). Truncal vagotomy and gastrojejunostomy did not affect gallbladder contractility, but it might predispose to the formation of sludge and subsequent calculi in a proportion of patients in long term.