A non-transferrin-bound serum iron in idiopathic hemochromatosis

The nature of iron in the serum of patients with idiopathic hemochromatosis has been studied utilizing an isotope labeling method and results have been compared with those from normal individuals and patients with other forms of liver disease. Between 2 and 4% of a tracer dose of⁵⁹Fe added to normal serum was retained by DEAE Sephadex and has been designated non-transferrin-bound. Alcoholic liver disease, chronic active hepatitis, and iron deficiency have no effect on this fraction. In idiopathic hemochromatosis 34.6±3.9% of the added iron was not bound to transferrin at diagnosis, representing approximately 700 μg Fe/liter serum. Treatment lowers this fraction before serum iron concentration falls to normal. The majority of the non-transferrin-bound iron is of low molecular weight and is not bound to albumin. The presence of this fraction may contribute significantly to the development of tissue siderosis.     

Pegylated interferon-alpha2beta in combination with ribavirin does not aggravate thyroid dysfunction in comparison to regular interferon-alpha2beta in a hepatitis C population: meta-analysis

BACKGROUND: Interferon (IFN) has been well documented to cause thyroid dysfunction, especially in high risk patients and when combined with ribavirin (RBV). There is very sparse data to assess if pegylated IFN will further aggravate the thyroid disease risk in comparison to regular IFN. The purpose of this study was to assess the risk of developing thyroid disease with pegylated IFN (pIFN) versus regular IFN (rIFN) therapy (in combination with RBV). We also pooled our results with previous studies in a meta-analysis. METHODS: An observational study was made retrospectively of 24 patients who underwent a combination of rIFN and RBV therapy for hepatitis C virus (HCV) infection. As these patients failed to obtain an initial satisfactory response, they were retreated using pIFN and RBV. Monthly thyrotropin (TSH) levels were assessed while undergoing both treatment regimens. A meta-analysis was performed using available published data in PubMed. RESULTS: No difference in TSH levels was observed when comparing rIFN/RBV with pIFN/RBV. None of the patients developed hypo- or hyperthyroidism. TSH levels fluctuated during the treatment but did not extend outside the reference range. No further investigation was carried out in the absence of clinical and biochemical thyroid disease. The result of the meta-analysis failed to find any excess risk of thyroid dysfunction using pIFN above that of rIFN. CONCLUSIONS: The pegylation of IFN, in combination with RBV, did not aggravate thyroid diseases in the hepatitis C population. This finding is reassuring and dictates that no deviation from current practice regarding thyroid surveillance is required whilst undergoing HCV treatment.     

Serological surveillance reveals patterns of exposure to H5 and H7 influenza A viruses in European poultry

Influenza A viruses of H5 and H7 subtype in poultry can circulate subclinically and subsequently mutate from low to high pathogenicity with potentially devastating economic and welfare consequences. European Union Member States undertake surveillance of commercial and backyard poultry for early detection and control of subclinical H5 and H7 influenza A infection. This surveillance has moved towards a risk‐based sampling approach in recent years; however, quantitative measures of relative risk associated with risk factors utilized in this approach are necessary for optimization. This study describes serosurveillance for H5 and H7 influenza A in domestic and commercial poultry undertaken in the European Union from 2004 to 2010, where a random sampling and thus representative approach to serosurveillance was undertaken. Using these representative data, this study measured relative risk of seropositivity across poultry categories and spatially across the EU. Data were analysed using multivariable logistic regression. Domestic waterfowl, game birds, fattening turkeys, ratites, backyard poultry and the ‘other’ poultry category holdings had relatively increased probability of H5 and/or H7 influenza A seropositivity, compared to laying‐hen holdings. Amongst laying‐hen holdings, free‐range rearing was associated with increased probability of H7 seropositivity. Spatial analyses detected ‘hotspots’ for H5 influenza A seropositivity in western France and England, and H7 influenza A seropositivity in Italy and Belgium, which may be explained by the demographics and distribution of poultry categories. Findings suggest certain poultry category holdings are at increased risk of subclinical H5 and/or H7 influenza A circulation, and free‐range rearing increases the likelihood of exposure to H7 influenza A. These findings may be used in further refining risk‐based surveillance strategies and prioritizing management strategies in influenza A outbreaks.     

Ethanol-Altered Liver-Associated T Cells Mediate Liver Injury in Rats Administered Concanavalin A (Con A) or Lipopolysaccharide (LPS)

BACKGROUND: Recent work from our laboratory implicates T cells in the pathogenesis of alcoholic liver disease. We have studied the role of liver-associated T cells in acute hepatitis produced in control rats administered Concanavalin A (Con A) after adoptive transfer of T cells from alcohol-consuming animals. METHODS: Liver-associated T cells from ethanol-consuming rats were transferred via tail vein to nonethanol-consuming rats. They then received Con A (20 mg/kg body weight) intravenously. This produced a severe hepatitis. Serum was collected for the assay of alanine aminotransferase (ALT) and cytokines. RESULTS: Hepatic necrosis was accompanied by an increase in plasma levels of ALT, interleukin-6, and tumor necrosis factor-alpha. These increases correlated with increased production of interleukin-6 and tumor necrosis factor-alpha in culture of liver-associated T cells stimulated or unstimulated with Con A. Immunohistology staining showed increased infiltration of inflammatory cells comprised of neutrophils and mononuclear cells, which included greater numbers of CD4+ T cells in the portal tract areas and around the central vein. Focal and lobular necrosis was seen with inflammatory cells in the necrotic area. Hepatocytes isolated from the liver showed increased apoptosis compared with rats that received liver-associated T cells from nonethanol-consuming rats. Injection of endotoxin LPS, in the same model, was associated with less hepatocyte injury indicating a distinct role for T cells as opposed to Kupffer cells in this model of liver disease. CONCLUSIONS: Chronic ethanol consumption induces a lesion in a pool of liver-associated T cells which can mediate liver injury after polyclonal mitogen activation.     

Flavin levels in the rat retina.

Exposure of riboflavin and its coenzymes adenine dinucleotide (FAD) and riboflavin-5'-phosphate (FMN) to UV and visible light results in the generation of radicals and photodegradative products that can damage surrounding macromolecules. Vertebrates and invertebrates have lost the ability to synthesize riboflavin and must obtain it or its coenzymes from food. The present study evaluated the relationship between FAD, FMN, and riboflavin concentrations in retina and blood of male Sprague-Dawley rats. Rations were provided in the form of purified diets containing 0, 3, 6, 30, and 300 mg riboflavin kg-1 diet. Analysis of flavins by HPLC showed that saturation levels of FAD, FMN and riboflavin in the retina and blood were achieved with diets containing 3 mg riboflavin kg-1. Retinal flavins were not significantly elevated by further increases in dietary riboflavin concentration, but an unidentified flavin appeared in the blood of rats given rations containing concentrations above 3 mg kg-1. The concentration of this unknown flavin varied in proportion to the level of dietary riboflavin.     

Can the response to interferon treatment be predicted in patients with chronic active hepatitis C?

Twenty-one of 40 patients with chronic non-A, non-B hepatitis (37 anti-HCV positive) were randomised to receive interferon α2b (3 million units subcutaneously thrice weekly for 24 weeks) and then to be observed for six months. Among the other 19 patients (controls) randomised to be observed without treatment for 12 months, eight have subsequently been treated with interferon for six months. One treated patient and three controls were lost to follow-up. A return to normal serum alanine aminotransferase levels which lasted until the end of the treatment period occurred in 18 (64%) of the 28 patients given interferon (and in 13 of 21 (62%) randomised to treatment), but only in one of the 16 untreated controls (p < 0.001). Multivariant analysis indicated that, compared with the ten nonresponders, the 18 patients who responded to interferon were more likely to have acquired infection by intravenous drug abuse than by blood transfusion (p < 0.05), and were more likely to have histologically less severe chronic liver disease (p < 0.01). Thus, all 13 patients with less severe liver disease histologically responded to interferon, but only five of 15 patients with cirrhosis or bridging fibrosis responded. Among 17 responders followed for more than four months, five (28%) are still in remission a median of 13 months (range four months to 24 months) after stopping interferon. The characteristics which favoured a response during treatment also appeared to distinguish those who experienced sustained post-treatment remission. Thus, five of 12 patients with less severe chronic hepatitis C histologically appear to have a sustained remission of disease activity after treatment for six months with interferon, whereas none of five patients with cirrhosis or bridging fibrosis has had a sustained remission after interferon treatment. It is proposed that continued treatment with interferon may be required for long-term suppression of chronic active hepatitis C among patients with bridging fibrosis or cirrhosis, but one course of interferon may provide a lasting response in 40% of patients with less severe disease.     

Outpatient detoxification in heroin users — A comparison of a hemineurin and a clonidine regime

Heroin using clients often demand help to detoxify from their drug habit but for a variety of reasons, resist inpatient care. This paper reports methods and results employed at Westmead Drug and Alcohol Units in outpatient detoxification. It is demonstrated that heroin detoxification can be successfully achieved in an outpatient setting for carefully selected patients, with a low dropout rate and few complications with daily attendance, using either of two different drug regimes.     

Mini-laparoscopy-assisted placement of Tenckhoff catheters: an improved technique to facilitate peritoneal dialysis

BACKGROUND AND PURPOSE: Despite its overall efficacy and patient satisfaction with it, peritoneal dialysis has a history of significant complications, which has contributed to the evolution in the technique from open laparotomy to minimally invasive placement of the catheters. Our goal was twofold: (1) to review our early experience with a technique of mini-laparoscopy-assisted (MLA) placement of dialysis catheters compared with open placement and (2) to demonstrate that urologists are able to provide a satisfactory procedure while concurrently developing and maintaining laparoscopic skills within a residency training program. PATIENTS AND METHODS: The charts of the first 14 consecutive patients who underwent MLA placement of Tenckhoff dialysis catheters by a single surgeon (LCM) from January 1, 2000, through March 31, 2001, were reviewed. Postoperative narcotic analgesia, length of hospital stay, operative times, days until cycling, and rates of leakage, infection, and malfunction necessitating removal of catheters were compared with the corresponding data from 12 consecutive patients who underwent traditional open placement during the same time period. A telephone survey was performed to corroborate and supplement the findings from the chart review. RESULTS: Differences in complications necessitating catheter removal were not significant. The difference in the mean operative times of 41.7 minutes in the MLA group and 55.7 minutes for open placement was statistically significant. Postoperatively, the MLA group used less narcotic analgesia, had shorter hospital stays, and returned earlier to usual activities. The incidence of leakage after catheter placement was greater in the open group, although this difference was not statistically significant. CONCLUSIONS: The MLA technique of dialysis catheter placement appears to have similar or greater efficacy than the open technique. It is a viable teaching procedure, and with reusable 3-mm ports and shorter operative times, it is cost efficient as well.