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...

Purpose: To establish a new scoring system for limbal dermoid, in order to unify the diagnostic criteria and assess the prognosis. Methods: A retrospective study was conducted on 261 patients with limbal dermoid. The basic information, clinical features, and pathology of dermoids were recorded, and the prognosis at 1 year after keratoplasty was assessed at follow-up. A new visual scoring system was created for the area of corneal involvement, the area of conjunctival involvement, and the surface shape. Results: There were 154 females and 107 males with mean age of 4 6 3 years at surgery. After scoring, 59% (136) of patients were classified as grade I, 26% (60) as grade II, and 14% (33) as grade III. The pathological results were 124 dermoid cases, 76 lipodermoid, 5 complex choristoma, and 10 epibulbar osseous choristoma. Moreover , patients with lower clinical scores presented a better prognosis; the mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity in grade I patients was 0.38 6 0.05, which was better than the grade II value of 0.61 6 0.09 (P , 0.05) and the grade III value of 0.94 6 0.11 (P , 0.001). Conclusions: New grading systems for limbal dermoid were useful for clinical diagnosis and may have prognostic value in predicting visual acuity. A lower-grade dermoid exhibited better vision postoperatively.

We report on a paper device capable of carrying out target-induced rolling circle amplification (RCA) to produce massive DNA amplicons that can be easily visualized. Interestingly, we observed that RCA was more proficient on paper than in solution, which we attribute to a significantly higher localized concentration of immobilized DNA. Furthermore, we have successfully engineered a fully functional paper device for sensitive DNA or microRNA detection via printing of all RCA-enabling molecules within a polymeric sugar film formed from pullulan, which was integrated with the paper device. This encapsulation not only stabilizes the entrapped reagents at room temperature but also enables colorimetric bioassays with minimal steps.

Summary Background:  Peptic ulcer disease is mainly caused by Helicobacter pylori infection and the use of non‐steroidal anti‐inflammatory drugs. Aim:  To investigate the trends in the prevalence of peptic ulcer disease, H. pylori infection and non‐steroidal anti‐inflammatory drug use in uninvestigated dyspeptic patients over recent years in Hong Kong. Methods:  Data from consecutive patients with uninvestigated dyspeptic symptoms referred by family physicians for open access upper endoscopy during 1997 and 2003 were analysed in relation to peptic ulcer disease, H. pylori infection and non‐steroidal anti‐inflammatory drug use. Results:  Among 2700 patients included, 405 (15%) had peptic ulcer disease and 14 (0.5%) had gastric cancer. There was a reduced trend from 1997 to 2003 in the prevalence of peptic ulcer disease (17, 20, 14, 16, 13, 14 and 14%, respectively, χ2 = 5.80, P = 0.016) (mainly because of decrease in duodenal ulcers), H. pylori infection (44, 50, 49, 44, 40, 40, 36 and 43%, respectively, χ2 = 13.55, P < 0.001) and non‐steroidal anti‐inflammatory drug use (13, 5, 5, 6, 3, 4, 4 and 5% respectively, χ2 = 13.61, P < 0.001). The prevalence of peptic ulcer disease, H. pylori infection and non‐steroidal anti‐inflammatory drug use between 2001 and 2003 were significantly lower than that between 1997 and 2000 (17% vs. 13%, OR = 0.78, 95% CI: 0.63–0.96, P = 0.020 for peptic ulcer disease; 47% vs. 39%, OR =0.72, 95% CI: 0.60–0.86, P < 0.001 for H. pylori infection; and 6% vs. 4%, OR = 0.56, 95% CI: 0.39–0.82, P = 0.002 for non‐steroidal anti‐inflammatory drug use). H. pylori infection was associated with both duodenal ulcer (OR = 15.87, 95% CI: 10.60–23.76, P < 0.001) and gastric ulcer (OR = 3.12, 95% CI: 2.15–4.53, P < 0.001) whereas non‐steroidal anti‐inflammatory drug use was only associated with gastric ulcer (OR = 2.97, 95% CI: 1.70–5.20, P < 0.001). Conclusions:  The prevalence of peptic ulcer disease, mainly duodenal ulcers, was reduced in association with a decreasing trend in the prevalence of H. pylori infection and non‐steroidal anti‐inflammatory drug use from 1997 to 2003.