Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence.

Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5- and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral-induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy.     

Empty Sella and Headache

SYNOPSIS
Empty sella is an anatomical condition caused by herniation of the subarachnoid space into the pituitary fossa through an incompetent seller diaphragm. Headache seems to be one of the most frequently reported symptoms. We studied 13 headache patients (12 females, 1 male) presenting with primary empty sella (PES) on CT scan. The characteristics of the headache were analyzed and plasma levels of pituitary hormones or cortisol assessed. We confirmed the nonspecific nature of the headache in PES even though the majority of our patients complained of daily headache, mostly localized anteriorly. Hormone plasma levels were within normal range in all the patients assessed. However, four patients reported earlier endocrine disorders and more than half of the patients presented with obesity.
In our opinion, PES should be suspected in middle-aged overweight women with daily headache even in the absence of endocrine symptomatology.     

Susceptibility to multiple sclerosis mediated by HLA-DRB1 is influenced by a second gene telomeric of the TNF cluster

Susceptibility to multiple sclerosis (MS) is clearly associated with human leukocyte antigen (HLA)-DRB1*1501, but some studies show associations with HLA-B7 and -B18. These are often co-expressed with DRB1*1501 in the ancestral haplotypes (AH) denoted 7.1 (HLA-A3, B7, tumor necrosis factor [TNF]a11b4, DRB1*1501) and 18.1 (HLA-A25, B18, TNFa10b4, DRB1*1501). Here we present a systematic study of 218 patients and 274 controls typed at all standard class II and TNF microsatellite loci, and a novel non-synonymous polymorphism in the central major histocompatibility complex gene, inhibitor of κ B-like protein (IKBL). The C allele at IKBL+738 is only found on the 7.1 haplotype. HLA-DRB1*1501 was associated with disease, as expected. When subjects expressing DRB1*1501 were analyzed separately, TNFa11b4 and IKBL+738C were less common in the patients and, hence, mark an allele that mediates resistance which lies telomeric of IKBL.

TNFa10b4 and TNFa1b5 were more common in DRB1*1501 patients than in controls. These alleles have been associated with the 18.1 and 18.2 AH, respectively. Since no component of these haplotypes was an independent risk factor in this study, it appears likely that a gene linked to TNFa10b4 and TNFa1b5 modifies the effect of the susceptibility locus marked by HLA-DRB1*1501. Potential candidate genes telomeric of the TNF cluster are discussed.     

Comparison of latex agglutination with enzyme immunoassay for detection of rotavirus in fecal specimens

Human rotaviruses are the most important etiologic agents of acquired diarrhea in infants and young children worldwide. Early diagnosis is essentialfor effective patient treatment. The latex agglutination (LA) assays for rotavirus diagnosis are rapid, inexpensive, and the most widely used to screen specimens. The performance of the LA Rotagen (Biokit S.A., Barcelona, Spain) was evaluated for rotavirus detection infecal samples of outpatients with acute gastroenteritis. This assay was compared with the enzyme immunoassay (EIA) EIARA (Bio-Manguinhos, Rio de Janeiro, Brazil). From January to October 2000, 285 fecal specimens were analyzed. Forty-four samples (15.4%) were reactive, 214 (75.4%) were nonreactive, and 27 (9.5%) were indeterminate by LA. All LA-positive samples were positive by EIA, and 2 LA-negative samples were positive by EIA. Of specimens indeterminate by LA, 67% were positive by EIA. The sensitivity, specificity, and accuracy of LA were 69%, 100%, and 93%, respectively. These results indicate that assay is as sensitive and specific as the EIA, and it could be applied on a large scale for screening stool specimens in suspected rotavirus diarrhea. However, the indeterminate results must be confirmed by other methods, such as EIA.     

Peripheral cytokine release in Alzheimer patients: correlation with disease severity

Various studies suggested that inflammation is involved in the pathogenesis of Alzheimer's disease (AD). We investigated cytokine release from LPS-stimulated blood cells of 32 AD patients, with different disease severity, compared to 16 age-related controls. A significant decrease of IL-1beta and IL-6 secretion was observed in severely demented patients; TNF-alpha release was also decreased, but not significantly. By contrast, mild and moderate patients showed a cytokine release similar to controls. IL-1beta, IL-6 and TNF-alpha secretion was negatively correlated with the severity of dementia, quantified by the MMSE. Our data suggest that alterations of the immune profile are associated with AD progression.     

Human monoclonal antibodies against amyloid-beta from healthy adults

Two anti-amyloid-beta human antibody-producing cell lines were established from amyloid-beta (Abeta)-selected lymphocytes from peripheral blood of healthy adults. ELISA and Western blot analysis showed that the monoclonal antibodies bound with high affinity to the 43 amino acid-long amyloid-beta peptide. The antigen epitope of these antibodies encountered within amino acids 1-16 of the amyloid-beta peptide. The antibodies did not bind to several immunoglobulin light chain amyloids (AL) and amylin. One of the monoclonals was tested by immunohistochemistry for the binding to frozen sections of brains derived from patients with Alzheimer's disease. It specifically and intensively stained diffuse and core amyloid-beta plaques; whereas, sections from normal brains were not stained. Concomitant staining with a commercial mouse anti-amyloid-beta monoclonal antibody co-localized with that of the human antibody. Simultaneous staining with the human antibody and Congo red implied that the antibody binds primarily to an early immature form of beta-amyloid. Human monoclonal antibodies, which resemble physiologically normal non-pathogenic and possibly protective antibodies in healthy adults, might be attractive candidates for immune therapy of Alzheimer's disease.