Lung, liver and bone cancer mortality in Mayak workers

Workers at the Mayak nuclear facility in the Russian Federation offer the only adequate human data for evaluating cancer risks from exposure to plutonium. Risks of mortality from cancers of the lung, liver and bone, the organs receiving the largest doses from plutonium, were evaluated in a cohort of 17,740 workers initially hired 1948-1972 using, for the first time, recently improved individual organ dose estimates. Excess relative risk (ERR) models were used to evaluate risks as functions of internal (plutonium) dose, external (primarily gamma) dose, gender, attained age and smoking. By December 31, 2003, 681 lung cancer deaths, 75 liver cancer deaths and 30 bone cancer deaths had occurred. Of these 786 deaths, 239 (30%) were attributed to plutonium exposure. Significant plutonium dose-response relationships (p < 0.001) were observed for all 3 endpoints, with lung and liver cancer risks reasonably described by linear functions. At attained age 60, the ERRs per Gy for lung cancer were 7.1 for males and 15 for females; the averaged-attained age ERRs for liver cancer were 2.6 and 29 for males and females, respectively; those for bone cancer were 0.76 and 3.4. This study is the first to present and compare dose-response analyses for cancers of all 3 organs. The unique Mayak cohort with its high exposures and well characterized doses has allowed quantification of the plutonium dose-response for lung, liver and bone cancer risks based on direct human data. These results will play an important role in plutonium risk assessment.     

Parabrachial neuron discharge in the cat is altered during the carbachol-induced REM sleep-like state (DCarb)

Pontine parabrachial neurons have been suggested to play a regulatory role in both respiratory and sleep cycle control. Encouraged by the finding that microinjections of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) of the cat produced respiratory changes paralleling those observed during rapid eye movement (REM) sleep (Neurosci. Lett., 102 (1989) 211–216), this study tested the hypothesis that cholinergic mechanisms in the mPRF can also cause state-dependent changes in the discharge of parabrachial neurons. This paper describes extracellular recordings of parabrachial neurons during REM sleep and during the carbachol-induced REM sleep-like state (DCarb). Cells which were activated (REM-on) or inactivated (REM-off) during REM maintained these same state-dependent firing patterns during the DCarb state. These results support the hypothesis that cholinergic mechanisms in the mPRF can cause state-dependent changes in the discharge of parabrachial neurons.     

Performance characteristics of updated INNO-LiPA assays for molecular typing of human leukocyte antigen A (HLA-A), HLA-B, and HLA-DQB1 alleles

We carried out a multicenter performance evaluation of three new DNA-based human leukocyte antigen (HLA) typing assays: INNO-LiPA HLA-A Update, INNO-LiPA HLA-B Update, and INNO-LiPA HLA-DQB1 Update. After optimization, the accuracy rates were all 100%, and the final observed resolutions were 99.4, 92.4, and 85.6%, respectively. These rapid and easy-to-perform assays yielded results fully concordant with other DNA-based tissue typing tests.     

Use of a multiplex PCR-based reverse line blot (mPCR/RLB) hybridisation assay for the rapid identification of bacterial pathogens.

The aim of this study was to develop a sensitive and reliable method for the molecular identification of pathogenic bacteria. A multiplex PCR-based reverse line blot (mPCR/RLB) hybridisation assay was developed and evaluated for the rapid identification of 24 systemic and respiratory bacterial pathogens in routine diagnosis. All species-specific probes designed for the RLB hybridised with amplified DNA only from the corresponding species. Sensitivity limits of the mPCR/RLB assay varied among the 24 target organisms from 0.05 pg to 0.5 ng of genomic DNA. The sensitivity of the assay was 2 x 10(2) CFU/mL for Streptococcus pneumoniae and 6 x 10(2) CFU/mL for Escherichia coli. The specificity of each probe was tested against 24 species. There were no cross-reactions among any of the 43 probes. The mPCR/RLB assay appeared to be a useful alternative tool for the molecular identification of common pathogens.     

Distribution of genotypes and antibiotic resistance genes among invasive Streptococcus agalactiae (group B streptococcus) isolates from Australasian patients belonging to different age groups.

Serotype distribution and antibiotic resistance (AR) among group B streptococci (GBS) affect GBS disease prevention strategies, but vary among patient groups. A multiplex PCR-based reverse line blot (mPCR/RLB) hybridisation assay was used to compare the distributions of GBS serotypes, serotype III subtypes and AR-associated genes among 666 invasive isolates from 663 patients, divided into five age groups: infants, early-onset (EO; 0-6 days) and late-onset (LO; 7-90 days); children (aged 3 months to 14 years); women of childbearing age (WCBA; aged 15-45 years); and other adults (males aged >15 years; females aged >45 years). Serotypes Ia and V and serosubtype III-1 accounted for 60% of infections. Serosubtype III-2, which corresponds to a virulent clone belonging to sequence type (ST)17, was relatively uncommon overall (7%), but was associated strongly with LO infant infections, in which it was significantly more common than in adult infections (25/104 (24%) vs. 9/392 (2%), p <0.0001) or in EO infections (25/104 (24%) vs. 14/155 (9%), p <0.005). Erythromycin resistance genes were found in 8% of all isolates (ermB 3%, ermA 2.5% and mefA/E 2%), in 11-15% of isolates of serotypes II and V and subtype III-1, but in none of the isolates of serosubtype III-2 (III-2, 0/49 vs. all others, 54/618 (9%), p <0.04). In summary, the virulent serosubtype III-2 was associated strongly with LO infant GBS infection, but was less likely than other serotypes or serosubtype III-1 to carry AR genes.     

A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group

BACKGROUND AND METHODS. In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase. RESULTS. Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry. Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53). Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage. There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1). Survival and toxicity were similar in the two maintenance-treatment groups. CONCLUSIONS. In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis. Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection.     

Triblock copolymers via thermal “macroiniferters”: Block copolymers of ethyl acrylate with methyl methacrylate or styrene

The concept of macro iniferter (MI) was applied to realize the synthesis of triblock copolymers of ethyl acrylate (EA) with styrene (St) or methyl methacrylate (MMA), with EA forming the end blocks. The syntheses involved 3 steps. Secondary amine terminated poly(ethyl acrylate) was synthesisted by polymerization of EA in presence of butyl-(2-mercaptoethyl)ammonium chloride as a functional chain-transfer agent. The macroamine so obtained was converted to the macrothiuram disulfide by reaction with CS₂ and I₂. Thermal polymerization of MMA or St in presence of this macroiniferter led to the respective triblock copolymers. The kinetics of polymerization of MMA and styrene using MI and two different chain lengths was done in limited concentration ranges. The kinetic parameters indicated that the iniferter action was not affected by the incorporation of the thiuram disulfide groups in the polymer backbone. Triblock copolymers of differing block lengths of hard and soft segments could be prepared by varying the chain length of the macroamine and the concentration of the iniferter in the reaction system. The copolymers were characterized by GPC analysis and spectral or elemental analyses. In the case of St, analysis showed formation of perfect triblocks, whereas for MMA, tendencies to form diblocks were observed on increasing the chain length of the iniferter-forming block. DSC analyses showed demixing of the soft EA block and the hard central blocks.