What do we need to know about nonA—to-E viral hepatitis?

The list of potential hepatotrophic viruses continues to grow, with the recent discovery of the GB virus-C, the TT virus, and the SEN virus. Prevalence rates of the GB virus-C have ranged from 1.2% to 13% among healthy blood donors from all over the world. Higher prevalence rates have been reported among intravenous drug users. Similarly, the TT virus has a global distribution. However, in spite of numerous reports of the presence of both of these viruses in various kinds of liver diseases, definite evidence linking it to a specific disease or illness is lacking. The SEN virus is thought to be a novel viral agent that may be linked to cryptogenic chronic hepatitis, but data are awaited.     

Likelihood ratios in the diagnosis of renal artery stenosis by magnetic resonance angiography compared with renal angiography

BACKGROUND: Renal angiography (RA) is considered to be the gold standard for the diagnosis of renal artery stenosis (RAS). However, it is invasive and potentially harmful; hence there is a need for an optimal noninvasive test. Magnetic resonance angiography (MRA) is currently accepted as the optimal noninvasive test by many. However, its major drawback is its inability to grade quantitatively the degree of stenosis. In this study, likelihood ratios (LR) were used to compare the diagnostic accuracy of MRA with that of RA. METHODS: To test the hypothesis that semiquantitatively graded MRA would correlate with RA, a retrospective analysis was performed to determine the LR of MRA to diagnose RAS compared with RA. It was believed that LR > or = 10.0 or < or =0.1 might generate conclusive changes from pretest to post-test probabilities. In this study a total of 94 renal arteries from 48 patients were analyzed for RAS by MRA and RA. Stenoses were graded by MRA as mild (<50%), moderate (50% to 75%), or severe (>75%); and by RA as <75% or > or =75% stenosis. RESULTS: The LR was 0.13 (95% CI = 0.09 to 0.19) for mild stenosis, 0.11 (95% CI = 0.08 to 0.15) for moderate stenosis, and 2.2 (95% CI = 1.9 to 3.1) for severe stenosis by MRA. CONCLUSIONS: Nonsevere stenosis can be sufficiently diagnosed by MRA and may not warrant RA. However, it may be insufficiently precise to establish severe RAS based on LR results. Therefore, for severe RAS by MRA, the decision to obtain RA can be made with the help of post-test probability, which is determined using pretest probability and LR.     

Nature and Behavior of Serum Cytokines in Type 1 Autoimmune Hepatitis

To assess the relationship between serum cytokine behavior and treatment outcome in type 1 autoimmune hepatitis, serum levels of interferon-, interleukin-2, interleukin-4, and interleukin-10 were measured by enzyme immunoassay in 43 patients and 20 normal subjects. Serum samples were similarly tested in 38 patients after corticosteroid treatment. Serum levels of interleukin-2 and interleukin-4 were significantly lower in patients than in normal subjects. Interleukin-2 was the least common cytokine detected before (3%), during (0%), or after treatment (0%). Serum levels of interleukin-10 at presentation did not differ from those of normal subjects but they did decrease during therapy, especially in patients who entered remission. Changes in these levels, however, did not always parallel treatment outcome or histological activity. We conclude that serum levels of interleukin-2 and interleukin-4 are lower than normal in type 1 autoimmune hepatitis. Serum concentrations of interleukin-10 diminish during corticosteroid therapy but changes do not closely reflect outcome. The rarity of interleukin-2 in serum may be a distinguishing feature.     

Advances in the Care of Primary Immunodeficiencies (PIDs): from Birth to Adulthood

Primary immunodeficiencies (PIDs) are a widely heterogeneous group of inherited defects of the immune system consisting of many clinical phenotypes with at least 300 underlying genetic deficits currently known. Patients with PIDs can present with, or develop during the course of their life, a susceptibility to recurrent and chronic infection along with autoimmune, allergic, inflammatory, and/or proliferative disorders, all potentially leading to end-organ damage. In recent years, a combination of basic and clinical research has greatly improved understanding of the underlying immunological and genetic defects in PIDs, leading to improved diagnosis, classification, and treatment approaches. In this review, we consider some of the key understandings that should direct diagnostic and treatment approaches in PID and offer insights into current and emerging management approaches and the lifelong care of patients from childhood through to adulthood.     

Estimation of Recent and Ancient Inbreeding in a Small Endogamous Tunisian Community Through Genomic Runs of Homozygosity

Runs of homozygosity (ROHs) are extended genomic regions of homozygous genotypes that record populations’ mating patterns in the past. We performed microarray genotyping on 15 individuals from a small isolated Tunisian community. We estimated the individual and population genome‐wide level of homozygosity from data on ROH above 0.5 Mb in length. We found a high average number of ROH per individual (48.2). The smallest ROH category (0.5–1.49 Mb) represents 0.93% of the whole genome, while medium‐size (1.5‐4.99 Mb) and long‐size ROH (≥5 Mb) cover 1.18% and 0.95%, respectively. We found that genealogical individual inbreeding coefficients (F_ped) based on three‐ to four‐generation pedigrees are not reliable indicators of the current proportion of genome‐wide homozygosity inferred from ROH (F_ROH) either for 0.5 or 1.5 Mb ROH length thresholds, while identity‐by‐descent sharing is a function of shared coancestry. This study emphasizes the effect of reproductive isolation and a prolonged practice of consanguinity that limits the genetic heterogeneity. It also provides evidence of both recent and ancient parental relatedness contribution to the current level of genome‐wide homozygosity in the studied population. These findings may be useful for evaluation of long‐term effects of inbreeding on human health and for future applications of ROHs in identifying recessive susceptibility genes.     

Survival outcomes for men with mediastinal germ-cell tumors: The University of Texas M. D. Anderson Cancer Center experience

ObjectivePrimary mediastinal germ-cell tumors are rare, and the effect of newer drugs and treatment strategies in this disease on overall survival is not known. We retrospectively assessed treatment outcomes at a single institution.Materials and methodsWe identified men seen at our institution from 1998 through 2005 for mediastinal germ-cell tumors. Medical records were reviewed for patient characteristics, histology, tumor markers, treatment, and survival outcome.ResultsThirty-four patients met study criteria, of whom 27 had nonseminomatous germ-cell tumor (NSGCT) and 7 had pure seminoma. Eleven patients (41%) with NSGCT were alive at last contact with a median overall survival time of 33.5 months. Among 13 patients with NSGCT referred to us at initial diagnosis, 7 (54%) were alive and recurrence-free at a median follow-up of 56.5 months. Progression-free survival was associated with absence of risk factors (any histology other than endodermal sinus tumor, β-hCG > 1000 mIU/mL, or disease outside the mediastinum). For the patients whose disease progressed (n = 5) or who had been referred to us for salvage treatment (n = 14), the 3-year overall survival from the date of first progression was 23%. Conversely, patients with seminoma did uniformly well with platinum-based chemotherapy; most did not undergo radiation or surgery.ConclusionChemotherapy given to maximum effect followed by surgical consolidation resulted in long-term progression-free survival for 54% of patients with mediastinal NSGCT. The number of risk factors present at diagnosis may be associated with survival outcome and should be studied in a larger test group.     

Comparison of arthroplasty trial publications after registration in ClinicalTrials.gov

In 2005, the International Committee of Medical Journal Editors established a mandatory trial registration before study enrollment for publication in member journals. Our primary objective was to evaluate the publication rates of arthroplasty trials registered with ClinicalTrials.gov (CTG). We further aimed to examine the consistency of registration summaries with that of final publications. We searched CTG for all trials related to joint arthroplasty and conducted a thorough search for publications resulting from registered closed trials. Of 101 closed and completed trials, we found 23 publications, for an overall publication rate of 22.8%. Registration of arthroplasty trials in CTG does not consistently result in publication or disclosure of results. In addition, changes are frequently made to the final presentation of the data that are not reflected in the trial registry.     

Guillain-Barré syndrome triggered by influenza vaccination in a recipient of liver transplant on FK506.

Guillain-Barré syndrome (GBS) has been rarely reported after liver transplantation and generally has good outcome. We report a liver transplant patient on FK506 (tacrolimus) who developed GBS 6 months after liver transplantation. There was no evidence of liver rejection or active infection. Despite treatment with intravenous immunoglobulin, the patient expired. GBS occurred despite downregulation of T cells by FK506, suggesting that humoral dysfunction might be the predominant mechanism of GBS in this report.