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Hereditary hemochromatosis (HH) is a genetic disease associated with progressive iron overload, eventually leading in some cases to damage of parenchymal organs, such as the liver, pancreas, and heart. Although the gene had been identified (HFE), HH pathogenesis remains to be fully elucidated. We report here, for the first time, a case of inadvertent transplantation of a liver from a donor with C282Y/H63D compound heterozygosity into a nonhemochromatotic 19-year-old Caucasian male recipient with primary sclerosing cholangitis. Progressive iron overload occurred over 1.5 years, as observed in liver biopsies and iron studies, after ruling out secondary causes of iron overload. This case strengthens the hypothesis that the liver, rather than the small intestine, plays a primary role in the maintenance of iron homeostasis. [ABSTRACT FROM AUTHOR]

Up to 30% of patients with hepatitis C virus (HCV) infection and normal serum alanine aminotransferase (NALT) have significant liver disease. Currently, many of these patients undergo a liver biopsy to guide therapeutic decisions. The BreathID® continuous online 13C-methacetin breath test (MBT) reflects hepatic microsomal function and correlates with hepatic fibrosis. To assess its role in identifying intrahepatic inflammation and fibrosis in NALT patients, we tested 100 patients with untreated chronic HCV infection, and 100 age- and sex-matched healthy volunteers using 13C MBT following ingestion of 75 mg methacetin. All HCV patients had undergone a liver biopsy within 12 months of performing the MBT. Patients with a necroinflammatory grade ≤4 or >4, based on Ishak (modified HAI) score, HAIa + HAIb + HAIc + HAId, were defined as having low or high inflammation, respectively. Patients with a histological activity fibrosis stage ≤2 or >2, were defined as having nonsignificant or significant fibrosis, respectively. A proprietary algorithm to differentiate intrahepatic inflammation within chronic HCV patients with NALT achieved an area under the curve (AUC) of 0.90. Setting a threshold on the point of best agreement (at 83%) results in 82% sensitivity and 84% specificity. With application of another proprietary algorithm to differentiate patients with nonsignificant or significant fibrosis, 67% of liver biopsies performed in the patient group could have been avoided. This algorithm achieved an AUC of 0.92, with a sensitivity of 91% and a specificity of 88%. There was no correlation between body mass index (BMI) and MBT scores for patients with the same histological score. The continuous BreathID®13C MBT is an accurate tool for measuring the degree of inflammation and fibrosis in patients with chronic HCV infection and NALT. As such, it may prove to be a powerful, noninvasive alternative to liver biopsy in the management of this patient population. [ABSTRACT FROM AUTHOR]

Background: Mast cells have been implicated in chronic inflammatory conditions resulting in fibrosis, such as Crohn disease. However, a link between inflammation, fibrosis and mast cells has not been demonstrated in human or animal intestinal diseases. This work was undertaken to analyze whether mast cells play a role in inflammation and fibrosis in the TNBS-induced rat colitis. Methods: Rats were rectally instilled 2,4,6,-trinitrobenzene sulfonic acid in ethanol, and immediately or 4 days later injected daily i.p. with nedocromil sodium, a mast cell stabilizer, compound 48/80, a mast cell activator, or saline. Rats were sacrificed 5 days post-TNBS, or on day 21. Intestinal inflammation and fibrosis were assessed by gross and histopathological evaluation. Colonic mast cell numbers (toluidine blue) and collagen (type I mRNA expression) were evaluated. Mast cell sonicate was added to rat colon fibroblasts. Fibroblast proliferation ([sup 3] H-thymidine), collagen synthesis ([sup 3] H-proline) and contractile activity (tridimensional collagen lattice contraction) were then assessed. Results: Nedocromil reduced inflammation and fibrosis possibly by decreasing mast cell numbers and activation and consequent collagen production. Compound 48/80 slightly enhanced the severity of the disease by activating mast cells. Mast cells increased fibroblast proliferation, collagen production and contractile activity. Conclusions: Mast cells are involved in the gastrointestinal tract inflammation and fibrosis of the TNBS-colitis rats. [ABSTRACT FROM AUTHOR]

Focuses on a study which determined the effect of chronic secretion of interleukin-6 on lipid metabolism and body composition. Information on interleukin-6; Methodology; Results of the study.

Objective. To determine whether thalidomide is an effective prophylactic agent against acute graft-versus-host disease (GVHD) and whether it exerts an effect on graft-versus-leukemia (GVL) reactivity, the drug was administered to leukemic mice that were exposed to allogeneic bone marrow transplantation. Methods. Mice (BALB/c × C57BL/6) F[sub 1] were inoculated with 10[sup 7] B cell leukemia cells (BCL1) and conditioned with total body irradiation followed by reconstitution with bone marrow plus splenic cells harvested from C57BL/6 mice. After transplant, mice were treated with oral thalidomide (20 mg/kg/day) for a period of 10 days. Results. Stable chimerism was documented in all recipients with ≥73% (mean) donor-type C57 cells. In this semi-allogeneic murine model, thalidomide failed to prevent or alleviate the acute GVHD symptoms; however, the drug did not impair GVL reactivity. The antileukemia allogeneic effect was similar in the thalidomide and non-thalidomide-treated animals. Comparison of the GVL reactivity occurring in the allogeneically transplanted groups with that in the syngeneic recipients revealed a significant difference (P = 0.001). Conclusions. Although thalidomide did not exert any effect against acute GVHD, the fact that the GVL reactivity was spared holds promise for its use as a treatment modality in chronic GVHD. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 44-year-old patient of Ethiopian descent, previously diagnosed with HIV which manifested again with severe epigastric pain preventing him from consuming solid food, thereby leading to a weight loss of 20 kg. It notes Baermann funnel and Koga agar culture methods are more sensitive but are laborious.