Linkage mapping of a nonspecific form of X‐linked mental retardation (MRX53) in a large Pakistani family

Nonspecific X‐linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X‐linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2–26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081. © 2001 Wiley‐Liss, Inc.     

Factors influencing outcome of lamivudine in anti-HBe-positive chronic hepatitis B

BACKGROUND/AIMS: Lamivudine has been shown to benefit patients with anti-HBe/HBV-DNA-positive chronic hepatitis B. The aim of the study was to evaluate factors influencing outcome of lamivudine therapy during two years of post-treatment follow-up in a prospective clinical trial. METHODOLOGY: Thirty-one consecutive patients, submitted to liver biopsy, were treated with lamivudine at 100mg/daily for twelve months and followed-up for twenty-four months. The patients were never treated before with interferon or stopped at least six months before starting lamivudine. ALT was measured monthly and HBV-DNA every three months. RESULTS: At the end of therapy 25 (81%) patients had both biochemical and virological response; 2 (6%) patients showed persistent viremia and 4 (13%) patients developed viral resistance during treatment. Twenty-three (92%) out of 25 responders relapsed during the follow-up; over 50% of all cases relapsed within 6 months. The relapse is related to higher HBV-DNA baseline levels. At relapse, 4/23 (17%) patients had symptomatic acute hepatitis. CONCLUSIONS: Lamivudine is associated with the risk of developing viral mutants and, after therapy discontinuation, to high rate of relapse. In relapsing patients severe acute recurrence of hepatitis B may occur. Decisions about lamivudine monotherapy should take into account the limited long-term efficacy, effects of relapse, costs and predictive factors for response.     

Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.     

Congenital infection with human herpesvirus 6 variant B associated with neonatal seizures and poor neurological outcome

Human herpesvirus 6 (HHV 6) has neurotropic and neuroinvasive properties. The virus has been found in the cerebrospinal fluid of many children with aseptic meningoencephalitis. Intrauterine transmission has been documented by HHV 6 DNA detection in cord blood specimens of apparently healthy newborns and in fetuses following spontaneous abortions. A patient is described with early neonatal afebrile seizures resulting from a congenital HHV 6 variant B infection disclosed by repeated detection of viral genome by polymerase chain reaction (PCR) in cerebrospinal fluid in the first days of life. At follow-up, magnetic resonance imaging (MRI) studies disclosed hyperintensities in the periventricular white matter and basal ganglia, associated with cerebral atrophy. Further follow-up at 18 months revealed poor neurological outcome with mild neurodevelopmental retardation, strabismus and hypertonia of legs. This report provides evidence of neurological involvement after HHV 6 vertical transmission, and the association with neurological sequelae.     

Predicted 30‐year protection after vaccination with an aluminum‐free virosomal hepatitis A vaccine

Few studies have examined the duration of protection following vaccination against hepatitis A virus (HAV) with currently licensed HAV vaccines. This study explored the long‐term immunogenicity in individuals vaccinated with the virosomal hepatitis A virus, Epaxal®. Adult volunteers (N = 130) previously enrolled into four different studies between 1992 and 1994 and who had completed a 0/12‐month immunization regimen (primary and booster dose) were asked to participate in this follow‐up study. Yearly anti‐HAV titers up to 6 years following booster vaccination, and then once 9–11 years after booster were measured using two assays, Enzygnost® and AxSYM® HAVAB 2.0. Based on the Enzygnost® assay, the seroprotection rate 9–11 years after booster was 100%, with a geometric mean concentration (GMC) of anti‐HAV antibodies of 526 mIU/ml. Females had markedly higher GMCs than males (741 mIU/ml vs. 332 mIU/ml). Using an anti‐HAV cut‐off titer of ≥10 mIU/ml, a linear mixed mathematical model predicted a median duration of protection of 52.1 years. A duration of protection ≥35.7 years was predicted for 95% of subjects. A more stringent cut‐off of ≥20 mIU/ml shortened the median predicted duration of protection to 45.0 years. In conclusion, a two‐dose Epaxal® vaccination regimen confers in healthy adults a real‐time protection of at least 9–11 years; this protection is predicted to last at least 30 years in over 95% of individuals. Further studies are necessary to assess the real duration of seroprotection and whether an additional booster is necessary later. J. Med. Virol. 82:1629–1634, 2010. 2010 Wiley‐Liss, Inc.