Comparative study of the diagnostic and prognostic value of antibodies against chimeric citrullinated synthetic peptides and CCP3/CCP3.1 assays.

BACKGROUND: The objective of the study was to compare the diagnostic yield of home-made ELISA tests based on synthetic chimeric fibrin/filaggrin citrullinated peptides (CFFCPs) with CCP3 and CCP3.1 commercial tests to detect anti-citrullinated protein/peptide antibodies (ACPAs) in rheumatoid arthritis (RA) patients. The prognostic value is also studied in a cohort of patients with early RA. Moreover, we transfer immunological assays from microtiter plates to microarray formats to allow the simultaneous analysis of several peptide sequences and reduce the volume of serum from patients. METHODS: The diagnostic study includes: 100 RA patients who fulfilled the 1987 ACR criteria; 100 healthy blood donors; 35 patients with SLE according ACR criteria; 35 patients with PsA fulfilling the Wright and Moll criteria and 30 patients with HCV infection. The prognostic value study includes 50 patients with early RA with follow-up data available. All samples are from outpatients attending the Rheumatology Department of the Hospital Clinic of Barcelona. RESULTS: Similar sensitivity, specificity and predictive values for the diagnosis of RA of CCFCPs compared to CCP3/CCP3.1 were obtained. Although a high concordance is observed between anti-CFFCPs and anti-CCP3/CCP3.1 in the early patients that rendered Larsen radiographic progression, CFFCPs could be a better marker of radiographic outcome. Strong correlations between the microarray and ELISA results were found for individual CFFCPs peptides. CONCLUSIONS: The development of multiplexing techniques combining a different spectrum of markers in a single analysis, including CFFCP peptides, could allow a more detailed analysis of the autoantibodies reactivity found in the sera of patients suffering of this heterogeneous disease.

Effect of synthetic peptides belonging to E2 envelope protein of GB virus C on human immunodeficiency virus type 1 infection.

The use of synthetic peptides as HIV-1 inhibitors has been subject to research over recent years. Although the initial therapeutic attempts focused on HIV-coded enzymes, structural HIV proteins and, more specifically, the mechanisms that the virus uses to infect and replicate are now also considered therapeutic targets. The interest for viral fusion and entry inhibitors is growing significantly, given that they are applicable in combined therapies or when resistance to other antiretroviral drugs is seen and that they act before the virus enters the cell. The 124 synthetic sequences of the GBV-C E2 envelope protein have been obtained by SPPS. The interaction of certain GBV-C peptide sequences with the HIV-1 fusion peptide has been proven through the use of biophysical techniques. We also show how GBV-C E2 domains notably decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner, highlighting their potential utility in future anti-HIV-1 therapies.

Short-term effects of extreme hot summer temperatures on total daily mortality in Barcelona, Spain.

The summer of 2003 was exceptionally hot, leading to an excess of mortality in Europe. Here, we assess the short-term effects of extreme hot summer temperatures on total daily mortality in Barcelona (Spain). Daily mortality from burial records, maximum temperature, relative humidity and photochemical pollutants, were collected for the period 1999-2003. Data was analysed using Poisson regression with generalised additive models. Mortality shows a considerable increase when maximum temperatures are over a threshold temperature of 30.5 degrees C. The risk of death associated with an increase of 1 degrees C above the threshold was 6%, 7% and 5% after 1, 2 and 3 days, respectively. Exposure to extreme hot temperatures leads to an significant increase in mortality.

HIV Type 1 molecular epidemiology in cuba: high genetic diversity, frequent mosaicism, and recent expansion of BG intersubtype recombinant forms.

Highly diverse HIV-1 genetic forms are circulating in Cuba, including subtypes B and G and two recombinant forms of African origin (CRF18_cpx and CRF19_cpx). Here we phylogenetically analyze pol sequences from a large collection of recent samples from Cuba, corresponding to 425 individuals from all Cuban provinces, which represents approximately 12% of prevalent infections in the country. RNA from plasma was used to amplify a pol segment by reverse transcription-polymerase chain reaction; phylogenetic analyses were performed with neighbour-joining trees and bootscanning. The distribution of genetic forms was subtype B, 41.2%; CRF19_cpx, 18.4%; BG recombinants, 11.6%; CRF18_cpx, 7.1%; subtype C, 6.1%; subtype G, 3.8%; B/CRF18 recombinants, 2.6%; subtype H, 2.1%; B/CRF19 recombinants, 1.7%; and others, 5.4%. Seventy-five (17.6%) viruses were recombinant between genetic forms circulating in Cuba. In logistic regression analyses, adjusting by gender and region, subtype B was more prevalent (OR 5.0, 95% CI 2.0-12.3) and subtype G less prevalent (OR 0.1, 95% CI 0.0-0.5) among men who have sex with men (MSM) than among heterosexuals. Within the main genetic forms of Cuba there were phylogenetic subclusters, several of which correlated with risk exposure or region. BG recombinants formed three phylogenetically related subclusters, corresponding to three different mosaic structures; most of these recombinants were from MSM from Havana City, among whom they have expanded recently, reaching 31% HIV-1 infections diagnosed in 2003. This study confirms the high HIV-1 diversity and frequent recombination in Cuba and reveals the recent expansion of diverse related BG recombinant forms in this country.

Antimicrobial resistance in non-typhoidal Salmonella from human sources, Spain, 2001-2003.

OBJECTIVES: To determine the current state of antimicrobial resistance among non-typhoidal Salmonella strains isolated from humans in Spain. METHODS: All strains of Salmonella from human sources received in the reference laboratory from 2001 to 2003 were serotyped and phage types were determined in the most common serovars. A systematic sampling procedure was carried out in order to obtain a random sample for susceptibility testing. The selected strains were tested for susceptibility to 12 different antimicrobial agents by a disc diffusion method using Mueller-Hinton agar. Results were scored as susceptible, moderately susceptible or resistant, according to CLSI criteria. RESULTS: From 2001 to 2003, 5777 strains of Salmonella were tested for susceptibility. Fifty per cent of strains of Salmonella Enteritidis were resistant to nalidixic acid. This was the most frequent resistance pattern of this serovar and it was characteristic of PT1, the most frequent phage type of Salmonella Enteritidis in Spain. Seventy-four per cent of Salmonella Typhimurium strains were resistant to four antibiotics or more. Resistance to ampicillin, chloramphenicol, streptomycin, sulphonamide and tetracycline was the most frequent resistance pattern of Salmonella Typhimurium and it was characteristic of DT104, the most frequent phage type in Spain. Sixty-nine per cent of Salmonella Hadar strains were resistant to at least four antibiotics. CONCLUSIONS: The results of our study showed both a worrying percentage of strains of Salmonella Enteritidis resistant to nalidixic acid and of strains of Salmonella Typhimurium with a pattern of resistance to four antibiotics or more. Surveillance of antimicrobial resistance should carry on and improve in order to be able to evaluate the control measures carried out for decreasing resistance in Salmonella, specifically that addressed to the prudent use of antimicrobial agents by farmers and veterinarians.

Delirium in Parkinson's disease patients. a five-year follow-up study.

OBJECTIVE: To assess the significance of delirium in parkinsonian patients in a 5-year follow-up case-control study with three groups of patients: Parkinsonian and Delirium (PDG), Parkinsonian (PG) and Control (CG). METHODS: Comparisons of Short Test of Mental Status (STMS) and Unified Parkinson's Disease Rating Scale-motor section (UPDRS(m)) between groups were performed using analysis of variance with repeated measurements. Comparisons of survival functions and Cox regression models were used to analyse the time until death. RESULTS: STMS and UPDRS(m) mean scores were statistically different between PDG group and the other two groups (p < 0.001) and between PDG and PG groups (p < 0.001), respectively. Including all groups, PG's patients (HR = 0.29; 95% C.I. = 0.09-0.93) and CG's patients (HR = 0.13; 95% C.I. = 0.03-0.60) had less hazard to die than PDG's patients; patients with a STMS basal score >33 (HR = 0.37; 95% C.I. = 0.13-0.99) had less hazard to die than patients with a score < or =33. Finally, including PDG and PG groups, patients with basal UPDRS(m) score >17 (HR = 4.88; 95% C.I. = 1.11-21.48) had higher hazard to die than patients with a score < or =17. CONCLUSION: For patients with Parkinson's, delirium is an increased risk factor for developing dementia, to have a more severe motor impairment and to death.