To assess the ability of 5 cerebrospinal fluid (CSF) biomarkers to differentiate between common dementia and parkinsonian disorders.
Factors associated with hepatitis B virus (HBV) DNA breakthrough and the significance of YMDD variants without the presence of wild-type YMDD during prolonged lamivudine treatment are unknown. We studied the amino acid sequence of codon 552 (YMDD motif) and codon 528 by means of a line probe assay in 159 chronic HBV patients (median follow-up 29.6 months). Pretreatment HBV DNA levels and alanine transaminase (ALT) levels correlated inversely with the time to HBV DNA breakthrough with YMDD variants (r ؍ ؊0.46, P ؍ .001; r ؍ ؊0.45, P ؍ .001 respectively). Patients harboring YMDD variants 3 months before HBV DNA breakthroughs had higher HBV DNA breakthrough levels compared with those without YMDD variants 3 months before HBV DNA breakthroughs (18.9 ؋ 10 6 vs. 5.4 ؋ 10 6 copies/mL, P ؍ .007). Patients with HBV DNA breakthroughs had higher percentages of YMDD variants without the presence of wild-type YMDD compared with patients without HBV DNA breakthrough (25.6% vs. 9%, P ؍ .007 for single M552I variant; 20.9% vs. 8.1%, P ؍ .026 for single M552V variant; 30.2% vs. 9.9%, P ؍ .004 for M552I/M552V variants). Patients with HBV DNA levels of more than 10 3 copies/mL after 6 months of lamivudine therapy had a 63.2% chance of subsequently developing YMDD variants. HBeAg seroconversion occurred in 2 patients after the emergence of YMDD variants. Only one patient developed YMDD variant after HBeAg seroconversion. There was no increase in the rate of development of YMDD variants or L528M mutation in patients receiving lamivudine 25 mg daily or famciclovir 500 mg 3 times a day before being given lamivudine 100 mg daily. (HEPATOLOGY 2001;34:785-791.)Hepatitis B virus (HBV) infection is a major international health problem leading to around 1.2 million deaths per year world-wide. 1 Because of its profound suppression of HBV replication resulting in significant histologic improvement, lamivudine is commonly used as a treatment of chronic HBV infection. [2][3][4] However, in 14% to 32% of patients, a 1-year treatment regimen of lamivudine 100 mg daily is associated with mutation of the tyrosine, methionine, aspartate, aspartate (YMDD) motif in the C domain of the HBV DNA polymerase gene, corresponding to the amino acid codon 552 of the HBV. 2,3 The number of patients with YMDD mutation is higher with prolonged use of lamivudine. 5 For the YMDD variants, the methionine is substituted with either isoleucine (I), designated M552I or valine (V), giving rise to M552V. There may be another concomitant mutation occurring at the B domain of the HBV polymerase gene with the leucine (L) at amino acid codon 528 substituted by methionine (L528M). This mutation has been described for patients on famciclovir. 6,7 With lamivudine treatment, L528M is usually associated with M552V though M552I/L528M has also been reported. 8 Both in vitro and in vivo studies show that YMDD variants are less replication-competent compared with the wild-type, are associated with lower HBV DNA levels compared with pretreatment HBV DNA levels, and can...
Although safe and effective vaccines for the prevention of hepatitis B virus (HBV) infection have been available for almost 20 years, the disease remains a major cause of morbidity and mortality worldwide. It is currently estimated that 350 million people are chronic carriers of the virus, often as a result of infection during childhood. Approximately one third to one quarter of these individuals will develop progressive liver disease, including cirrhosis and primary hepatocellular carcinoma (13, 15). Some 1.2 million people die prematurely each year from conditions directly related to HBV infection.Current treatment of chronic hepatitis B aims at interrupting the progression and clinical outcomes of the disease by suppressing viral replication, as evidenced by hepatitis B virus E antigen seroconversion to hepatitis B virus E antibodies (14) or by a decrease in viral load. The first approved therapeutic agent was alpha interferon. Unfortunately, alpha interferon is expensive, is effective in no more than 30% of patients, has to be administered by injection, and is associated with numerous side effects which may necessitate dosage reduction or even treatment discontinuation (13,15).In 1998, the nucleoside analogue lamivudine was approved for use in patients with chronic hepatitis B (7). The convenience of a one-pill-per-day regimen and the low incidence of side effects make it a preferred treatment for many physicians and patients. However, viral breakthrough is detected in approximately 16% to 32% of patients after 1 year of treatment (12). Newer oral nucleoside/nucleotide analogues in clinical trials, such as adefovir dipivoxil (4), entecavir (6), and emtricitabine (19, 18), appear to be at least as potent as lamivudine. In vitro and in vivo studies showed that adefovir and entecavir are also effective in suppressing lamivudine-resistant HBV (8).Mutations in codon 552 [204] (proposed revised nomenclature according to Stuyver et al. [22] is shown in brackets) within the YMDD (tyrosine-methionine-aspartic acid-aspartic acid) motif of the HBV reverse transcriptase/polymerase with substitution of the methionine for valine or isoleucine (M552V/I [M204V/I]) are implicated in the decrease of viral susceptibility to lamivudine (1,5,10,11). In addition, mutations in codons 528 [180] (2, 3, 11) and 555 [207] (9, 17) have also been linked to lamivudine and famciclovir resistance. Sensitive and early detection of emerging resistance may not only help monitor
Because CSF α-synuclein levels were significantly higher in AD as compared with synucleinopathies, α-synuclein might have a value as a biomarker for differential dementia diagnosis.
Although in a pilot study, a late increase in plasma tau protein seems to be associated with a worse outcome after hypothermia treatment after CA, although more studies are needed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.