Chronic hepatitis B: current testing strategies.

The worldwide burden of hepatitis B mandates accurate and timely diagnosis of patients infected with the hepatitis B virus (HBV) and the use of treatment strategies derived from evidence-based guidelines. HBV is a DNA virus that produces a series of viral protein products circulating HBV DNA. Serologic and nucleic acid testing are critical to disease prevention and treatment objectives. Information from such testing helps determine patients' infectivity and immune status, appropriate monitoring strategies, and the efficacy of treatment, as well as providing data that contributes to a better understanding of the natural history and epidemiology of the disease. This article reviews the clinical use of state-of-the-art serologic and nucleic acid tests, including the relevance of hepatitis B e antigen and antibody and HBV DNA measurements as markers of disease activity. Viral load can be used to distinguish between active and inactive disease, define response to therapy, and detect the development of antiviral resistance. Some recent reports have suggested that high viral load is associated with poorer patient outcomes (eg, more rapid progression to cirrhosis and a higher incidence of hepatocellular carcinoma). Durable suppression of HBV DNA is evolving to become the primary goal of therapy, although all currently licensed medications have used histology as the primary end point of therapy. Suggested frequencies for HBV DNA monitoring are presented.     

Improving clinical trial design for hepatocellular carcinoma treatments

Despite its place as the third leading cause of cancer deaths worldwide, there are currently no approved chemotherapeutic agents, devices or techniques to treat hepatocellular carcinoma. Importantly, there have been no phase III studies demonstrating survival benefit, nor any randomized studies of treatment except for transarterial chemoembolization and most recently sorafenib. The importance of well-designed clinical trials of agents to treat HCC has never been greater. However, general clinical study design issues, combined with HCC-specific issues pose significant challenges in structuring such studies. HCC-related challenges include the heterogeneity of this cancer and the fact that it is frequently accompanied by significant comorbidities at diagnosis, such as active hepatitis B or C virus replication, substantial past or on-going alcohol use, and cirrhosis, itself often a fatal disease. The recently published comparison of a newer treatment, nolatrexed to doxorubicin, and comments about this study’s initial HCC diagnostic criteria, staging system, comparator therapy and choice of endpoints have provided a platform to discuss the challenges unique to the design of HCC clinical trials. The difficulty in accurately framing study results obtained from the constantly changing HCC clinical landscape and approaches to meet these challenges will be reviewed.     

De Novo Non-Alcoholic Fatty Liver Disease Following Orthotopic Liver Transplantation

Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized clinico-pathologic entity typically associated with obesity, type II diabetes and hyperlipidemia. It has been noted to recur after orthotopic liver transplantation (OLT). We report four patients who developed de novo NAFLD within 3 months of OLT without the typical predisposing factors of diabetes mellitus or obesity. Three of the four patients underwent OLT for hepatitis C-related cirrhosis, and the other for alcoholic cirrhosis. Examination of the liver explants revealed no evidence of steatosis. No surreptitious alcohol use or a drug-induced process could be identified in these patients. Treatment of recurrent hepatitis C infection in one patient with interferon and ribavirin led to sustained suppression of the viral RNA to undetectable levels, but no improvement in histology or liver enzymes. All four patients had histologic evidence of preservation injury on the initial post-OLT biopsies, but the significance of this finding in relationship to the development of NAFLD is unknown. NAFLD can develop without any of the known predisposing conditions after transplantation, and this raises further questions about the pathogenesis of this condition .     

导数光谱系数倍率法测定多组分体系感冒清胶囊中盐酸吗啉胍的含量

This paper provides a basic principle and experimental technique of derivative signal multiplier spectrophotometry in multicomponent mixture. A microcomputer was used to process the spectral data measured on a manual spectrophotometer (UV-7520) for the determination of moroxydine hydrochloride in Gan Mao Qing capsules. Quantitative analysis of multicomponent mixture can be done without sample separation. The selection of optimal wavelength pairs is performed through the program with a computer. The method needs no special spectrophotometer and is simple, rapid and easy to operate. The mean recovery was 99.98 +/- 0.53% (n = 12).     

Application of reflectance spectroscopy to the estimation of uric acid, urea and glucose: an evaluation of the Ames Seralyzer

An original approach to the measurement of analytes in clinical chemistry has now become available, in which dry reagent strip technology is linked to measurement by reflectance spectroscopy. The present studies have evaluated the performance of the first of these test systems—for uric acid, urea and glucose, in serum—by comparison with conventional liquid chemistry methods. Satisfactory performance in terms of both precision and accuracy was obtained for all three test systems, the current “state-of-the-art” performance criteria being met; the Seralyzer system proved reliable and easy to use in the hands of trained operators. It should find a place as a “Stat” analyser in the laboratory, in specified wards and in Health Centres.     

Permeation of human ovarian tissue with cryoprotective agents in preparation for cryopreservation

The recent improvements in the treatment of cancer by chemo- and radiotherapy have led to a significant increase in the survival rates of patients with malignant disease, but at the expense of distressing side effects. One major problem, especially for younger patients, is that aggressive therapy destroys a significant proportion of the follicular population, which can result in either temporary or permanent infertility. Freeze-banking pieces of ovarian cortex prior to treatment is one strategy for preserving fecundity. When the patient is in remission, fertility could, theoretically, be restored by autografting the thawed tissue at the orthotopic site or by growing isolated follicles to maturity in vitro. Recent studies have found good follicular survival in frozen-thawed human ovarian tissue but to optimize the process an effective cryopreservation method needs to be developed. An essential part of such a technique is to permeate the tissue with a cryoprotectant to minimize ice formation and the extent of this equilibration is an important determinant of post-thaw cellular survival. In the current study, we have investigated the diffusion of four cryoprotective agents into human tissue at both 4 degrees C and 37 degrees C. We have also studied the effect of adding different concentrations of the non penetrating cryoprotective agent, sucrose, to the freezing media using the release of lactate dehydrogenase as a measure of its protective effect. At 4 degrees C propylene glycol and glycerol penetrated the tissue significantly slower than either ethylene glycol or dimethyl sulphoxide. At the higher temperature of 37 degrees C all four cryoprotectants penetrated at a faster rate, however concern about enhanced toxicity prevents the use of these conditions in practice. Thus, the results suggest that the best method of preparing tissue for freezing is exposure for 30 min to 1.5 M solutions of ethylene glycol or dimethyl sulphoxide at 4 degrees C; this achieved a mean tissue concentration that was almost 80% that of the bathing solution. We also report that the addition of low concentrations of sucrose to the freezing medium does not have a significant protective effect against freezing injury.