Serum interleukin 8 levels correlate with synovial fluid levels in patients with aseptic loosening of hip prosthesis

Levels of inflammatory cytokines (tumor necrosis factor alpha, interleukin [IL] 6, and IL-8) in serum from patients with osteolysis on radiographs after hip arthroplasty [osteolysis(+), n = 28], patients without osteolysis after hip arthroplasty [osteolysis(-), n = 24], and nonoperated healthy subjects [controls, n = 20] were determined. In addition, cytokine levels in synovial fluid from patients undergoing revision total hip arthroplasty (n = 14) for loosening were measured and compared with each other and with the area of osteolysis on radiographs. Serum IL-6 and IL-8 levels were significantly higher in the osteolysis(+) group than in the osteolysis(-) or the control groups. Furthermore, a significant correlation was found between the serum and synovial fluid IL-8 levels and between synovial fluid IL-8 levels and the area of osteolysis in patients undergoing revision total hip arthroplasty. Therefore, serum IL-8 levels could be a useful periprosthetic osteolysis marker.     

Cost-effectiveness of long-acting bronchodilators for chronic obstructive pulmonary disease

OBJECTIVE: To evaluate and compare the cost-effectiveness of long-acting bronchodilators by estimating incremental costs per quality-adjusted life-year (QALY) gained in patients with moderate to severe chronic obstructive pulmonary disease. METHODS: This cost-effective analysis was conducted from a third-party payer's perspective. The study was a retrospective pooled analysis, and the effectiveness evidence was derived from a systematic review of literature published from January 1, 1980, to April 14, 2006. Incremental QALYs were estimated by converting the St George's Respiratory Questionnaire scores into EuroQoL-5D scores and using these combined scores as the summary benefit measure. RESULTS: The incremental cost per additional QALY was $26,094 (range, $11,780-$77,214) for tiotropium and $41,000 (range, $23,650-$98,750) for salmeterol compared with placebo. The cost per QALY gained was lower with tiotropium compared with salmeterol or ipratropium based on either the pooled data of available trials or a head-to-head trial. Treatment with tiotropium could save $391 per year while gaining 13 quality-adjusted days compared with ipratropium. CONCLUSION: Tiotropium appears to be more cost-effective than the alternatives and may be the preferred agent for maintenance therapy in patients with moderate to severe chronic obstructive pulmonary disease. Compared with ipratropium, tiotropium could be cost saving. Because of the wide ranges of cost-effectiveness ratios for tiotropium and salmeterol and the significant overlap between them, a large prospective head-to-head trial would help address the uncertainty and confirm the results of this analysis.     

NMDA Receptor Binding in Adult Rat Brain after Several Chronic Ethanol Treatment Protocols

The amino acid L-glutamate is a major excitatory neurotransmitter that is involved in many CNS functions, including learning, memory, long-term potentiation, and synaptic plasticity. Acute exposures to ethanol (50 to 200 mM) have been shown to inhibit NMDA receptor responses, whereas chronic exposure to ethanol leads to adaptive supersensitivity thought to be involved in ethanol dependence and tolerance. To investigate the effects of chronic ethanol exposure on glutamate receptor density, we examined the binding of both NMDA and non-NMDA ligands in rat brain after several chronic ethanol treatment protocols using a number of different rat strains. No increases in the binding of [³H]MK-801, [³H]CGP 39653, or the polyamine specific competitive antagonist, [³H]ifenprodil, were seen after two well-used chronic ethanol treatments. These included the 2-week liquid diet developed by Frye et al. (J. Pharmacol. Exp. Ther. 216:306-314, 1981) and the 4-day binge treatment developed by Ma-jchrowicz (Psychopharmacologia 43:245-254, 1975). However, small increases in the binding of both the NMDA noncompetitive antagonist [³H]MK-801, as well as the competitive NMDA antagonist [³H]CGP 39653, were seen in select frontal brain regions after 3 weeks of the Walker-Freund chronic ethanol liquid diet When this chronic liquid diet treatment was extended to a period of 6 weeks, these increases in receptor binding were diminished to nonsignificant levels. The binding of the non-NMDA ligands [³H]AMPA and [³H]kainate were not significantly affected by either length of Walker-Freund liquid diet exposure. When rats were treated chronically with ethanol for 30 days using the paradigm developed by Tsukamoto et al. (Hepatology 5:224-232, 1985), small, but significant, increases in the binding of [³H]MK-801 were seen in the CA1 and dentate gyrus regions of the hippocampus. These studies indicate that robust increases in NMDA receptor binding do not occur with several chronic ethanol treatment protocols, and suggests that NMDA receptor supersensitivity during the development of tolerance and dependence to ethanol may not simply be due to changes in the density of NMDA receptors, but may involve other mechanisms.     

Superiority of minipool nucleic acid amplification technology for hepatitis B virus over chemiluminescence immunoassay for hepatitis B surface antigen screening

BACKGROUND AND OBJECTIVES: The Japanese Red Cross (JRC) have developed a fully automated multiplex (MPX) nucleic acid amplification technology (NAT) system for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1). This is used to test serologically negative blood units from volunteer, non-remunerated donors. The system utilizes a 50-sample pool for NAT screening with an input volume of each pool. This results in a significantly higher sensitivity for hepatitis B than that seen with highly sensitive hepatitis B surface antigen (HBsAg) testing. MATERIALS AND METHODS: From 1 February 2000 to 15 October 2001, over 11 million donations, which were serologically negative, were tested using the MPX NAT system. Donations found to be HBV DNA positive were further tested by using the chemiluminescence immunoassay (CLIA). RESULTS: Out of 181 HBV DNA-positive donations, 96 (53%) and 76 (42%) were negative by individual enzyme immunoassay (EIA) and CLIA testing, respectively. CONCLUSIONS: The sensitivity of the 50-sample pool MPX NAT system was higher than that of individual HBsAg screening by CLIA. By adopting this NAT-screening system, the JRC has improved the safety of the blood supply and maintained supply across Japan.     

Production and characterization of serovar-specific monoclonal antibodies to serovars 4, 8, and 9 of Mycobacterium intracellulare.

Serovar-specific monoclonal antibodies against Mycobacterium avium-Mycobacterium intracellulare-Mycobacterium scrofulaceum complex serovars 4, 8, and 9 were prepared. Nine, four, and one monoclonal antibodies, respectively, to the serovars were prepared by the usual cell fusion technique. All nine monoclonal antibodies to serovar 4 were monospecific for their homologous serovar and reacted with several native glycopeptidolipids (GPLs) and one major deacylated GPL from the homologous serovar. One of the four monoclonal antibodies to serovar 8 seemed to be monospecific for its homologous serovar, but the other cross-reacted with serovar 6 because serovar 6 organisms contain the same components as does the major deacylated GPL from serovar 8. One monoclonal antibody to serovar 9 was monospecific for its homologous serovar and reacted with one of the two major deacylated GPLs from this serovar. These antibody preparations proved useful for serovar identification.     

A retrospective study on the efficacy of cervical lymph node dissection in well-differentiated carcinoma of the thyroid

The management of cervical lymph node metastases in well-differentiated carcinoma of the thyroid is controversial. In our department, from 1963 to 1972, node plucking was performed only in patients with cervical lymphadenopathy whereas, from 1973 to 1983, modified radical neck dissection was therapeutically or electively performed. In order to determine whether the more extensive dissection is adequate, a retrospective analysis was performed using two groups of patients who were managed differently with regard to the treatment of cervical lymph node metastases. From this series of 206 patients with more than five years follow-up, it was found that the rates of survival and lymph node recurrence did not differ between the two groups. However, since the well-differentiated carcinoma of the thyroid has relatively indolent biological behaviour, further long-term follow-up seems to be necessary for demonstrating the efficacy of neck dissection.     

Minimum infectious dose of hepatitis B virus in chimpanzees and difference in the dynamics of viremia between genotype A and genotype C

BACKGROUND: In planning optimal hepatitis B virus (HBV) blood screening strategies, the minimum infectious dose and early dynamics of HBV need to be determined for defining the window period for HBV DNA as well as for hepatitis B surface antigen (HBsAg). STUDY DESIGN AND METHODS: Pairs of chimpanzees were inoculated with preacute-phase inocula containing HBV of genotype A or genotype C to determine the minimum infectious dose, and two pairs of chimps infected with the lowest infectious dose of genotypes A and C were followed for HBV markers. RESULTS: The minimum 50 percent chimpanzee infectious dose (CID50) was estimated to be approximately 10 copies for genotype A and for genotype C. In the two chimps inoculated with the lowest infectious dose, the HBV DNA window was 55 to 76 days for genotype A and 35 to 50 days for genotype C, respectively. The HBsAg window was 69 to 97 days for genotype A and 50 to 64 days for genotype C, respectively. The doubling times of HBV DNA were 3.4 days (95% confidence interval [CI], 2.6-4.9 days) for genotype A and 1.9 days (95% CI, 1.6-2.3 days) for genotype C. When comparing the replication velocity of HBV DNA between the two genotypes, the doubling time of genotype C was significantly shorter than that of HBV genotype A (p < 0.01). CONCLUSION: Although the CID50 of approximately 10 copies was similar for the two HBV genotypes, the doubling time and pre-HBV nucleic acid amplification technology (<100 copies/mL) window period in chimps infected with the lowest infectious dose seemed to be shorter for genotype C than for genotype A.     

Age- and gender-specific distributions of hepatitis B virus (HBV) genotypes in Japanese HBV-positive blood donors

BACKGROUND: There are an increasing number of reports on the hepatitis B virus (HBV) genotype distribution in acute or chronic HBV-infected patients in Japan; however, reports on the HBV genotype of blood donors are few. To compare the HBV genotypes of hepatitis B surface antigen (HBsAg)-positive blood donors with infected patients, all the HBsAg-positive donors' genotypes were determined.
STUDY DESIGN AND METHODS: Data on Japanese blood donors from October 2006 to September 2007 were obtained from the Japanese Red Cross database. The number of available samples was 1979, and the HBV genotypes were determined in 1887 samples. The six major genotypes of HBV (A-F) were determined by enzyme-linked immunosorbent assay. The presence of the immunoglobulin M (IgM) antibody against the HBV core antigen was determined by enzyme immunoassay among all HBsAg-positive donors.
RESULTS: A significant difference in the HBV genotype distribution between donors and patients was in the C/B genotype ratio. The ratios were low in blood donors (2.0-3.9) and high in patients (5.3-18.2). The genotype B ratio increases from 13.8% in teenage donors to 42.4% in those in their 50s; however; the genotype C ratio decreases from 83.1% in teenage donors to 55.1% in those in their 50s. In both IgM antibody against hepatitis B core antigen and nucleic acid test–positive donors, genotypes A and B were restricted to male donors.
CONCLUSIONS: The age-specific distribution of HBV genotypes in Japanese blood donors was observed in the B/C genotype ratio. The gender-specific distribution of HBV genotype A, which originated from the US or Western countries, was observed in male Japanese donors.     

Early dynamics of hepatitis C virus in the circulation of chimpanzees with experimental infection

Two chimpanzees were inoculated with hepatitis C virus (HCV) and followed on a daily basis for 12 days. HCV RNA became detectable in their sera on day 5 by polymerase chain reaction with the detection limit of 10(2) copies/ml. Based on an exponential growth observed until 8 or 9 days after inoculation in their sera, the doubling time of HCV in the circulation was estimated at 6.3-8.6 h and log time (time required to grow 10-fold) at 31.3- 42.9 h. The exact doubling time of HCV determined in them would help plan an efficient strategy for screening out blood donors in the window period of infection between the exposure and the development of antibody to HCV in serum.     

Application of proteomic technologies to tumor analysis

The sequencing of the human genome has had an enormous impact on the proteomic analysis of cancer by providing a sequence-based framework for understanding the human proteome of tumor cells, tissues, and biological fluids. There is intense interest in applying proteomic technologies to uncover, at the protein level, processes involved in neoplastic transformation and new biomarkers that correlate with early diagnosis, as well as to accelerate the development of new therapeutic targets. To that effect, new technologies are being developed in order to meet the needs for the high throughput and high sensitivity that is required for cancer-related applications of proteomics. These innovative technologies have greatly enhanced our ability to separate and characterize complex protein mixtures, and have aided our ability to identify proteins with greater sensitivity, thereby providing the groundwork for future scientific breakthroughs and possibly providing impetus for the development of personalized cancer therapy.