Meta-analysis of studies analyzing the role of human papillomavirus in the development of bladder carcinoma

PURPOSE We aimed to ascertain the degree of association between bladder cancer and human papillomavirus (HPV) infection. MATERIALS AND METHODS We performed a meta-analysis of observational studies with cases and controls with publication dates up to January 2011. The PubMed electronic database was searched by using the key words "bladder cancer and virus." Twenty-one articles were selected that met the required methodological criteria. We implemented an internal quality control system to verify the selected search method. We analyzed the pooled effect of all the studies and also analyzed the techniques used as follows: 1) studies with DNA-based techniques, among which we found studies with polymerase chain reaction (PCR)-based techniques and 2) studies with non-PCR-based techniques, and studies with non-DNA-based techniques. RESULTS Taking into account the 21 studies that were included in the meta-analysis, we obtained a heterogeneity chi-squared value of Q(exp)=26.45 (p=0.383). The pooled odds ratio (OR) was 2.13 (95% confidence interval [CI], 1.54 to 2.95), which points to a significant effect between HPV and bladder cancer. Twenty studies assessed the presence of DNA. The overall effect showed a significant relationship between virus presence and bladder cancer, with a pooled OR of 2.19 (95% CI, 1.40 to 3.43). Of the other six studies, four examined the virus's capsid antigen and two detected antibodies in serum by Western blot. The estimated pooled OR in this group was 2.11 (95% CI, 1.27 to 3.51), which confirmed the relationship between the presence of virus and cancer. CONCLUSIONS The pooled OR value showed a moderate relationship between viral infection and bladder tumors.

Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study.

Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study. Design Combination of prospective cohort study with representative population based data on alcohol exposure. Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Participants 109 118 men and 254 870 women, mainly aged 37-70. Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer. Results If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women. Conclusions In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.

An antibody-based ELISA for quantification of Ani s 1, a major allergen from Anisakis simplex.

Anisakis simplex is a nematode parasite that can infect humans who have eaten raw or undercooked seafood. Larvae invading the gastrointestinal mucosa excrete/secrete proteins that are implicated in the pathogenesis of anisakiasis and can induce IgE-mediated symptoms. Since Ani s 1 is a potent secreted allergen with important clinical relevance, its measurement could assess the quality of allergenic products used in diagnosis/immunotherapy of Anisakis allergy and track the presence of A. simplex parasites in fish foodstuffs. An antibody-based ELISA for quantification of Ani s 1 has been developed based on monoclonal antibody 4F2 as capture antibody and biotin-labelled polyclonal antibodies against Ani s 1 as detection reagent. The dose-response standard curves, obtained with natural and recombinant antigens, ranged from 4 to 2000 ng/ml and were identical and parallel to that of the A. simplex extract. The linear portion of the dose-response curve with nAni s 1 was between 15 and 250 ng/ml with inter-assay and intra-assays coefficients of variation less than 20% and 10%, respectively. The assay was specific since there was no cross-reaction with other extracts (except Ascaris extracts) and was highly sensitive (detection limit of 1·8 ng/ml), being able to detect Ani s 1 in fish extracts from codfish and monkfish.

Extranodal NK/T-Cell Lymphoma without Nasal Cavity Involvement Associated with Epstein-Barr Virus:AMultimodality-Based Diagnosis of Two Cases

We report two cases of extranodal NK/T-cell lymphoma, nasal type, in immunocompetent patients without nasal cavity involvement. In the two cases, the initial presumptive diagnosis was tuberculosis and there was a rapid dissemination of the tumor with short survival after the hospital admittance. An autopsy was performed showing infiltration in several organs including lymph nodes and mesenteric and retroperitoneal fat. Histological sections showed an angiocentric and angiodestructive growth pattern and the immunophenotype was CD45+, CD3+ (cytoplasmic), as well as Granzyme B+ and EBV+. However, CD56 expression was only positive in a case in which the molecular study showed T-cell gene rearrangement with monoclonal appearance and associated with hemophagocytic syndrome. These cases represent rare examples of NK/T-cell lymphoma disseminated outside the nasal cavity highly aggressive that lead to the rapid death of the patients.

DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists

INTRODUCTION No definitive data are available regarding the value of switching to an alternative TNF antagonist in rheumatoid arthritis patients who fail to respond to the first one. The aim of this study was to evaluate treatment response in a clinical setting based on HAQ improvement and EULAR response criteria in RA patients who were switched to a second or a third TNF antagonist due to failure with the first one. METHODS This was an observational, prospective study of a cohort of 417 RA patients treated with TNF antagonists in three university hospitals in Spain between January 1999 and December 2005. A database was created at the participating centres, with well-defined operational instructions. The main outcome variables were analyzed using parametric or non-parametric tests depending on the level of measurement and distribution of each variable. RESULTS Mean (+/- SD) DAS-28 on starting the first, second and third TNF antagonist was 5.9 (+/- 2.0), 5.1 (+/- 1.5) and 6.1 (+/- 1.1). At the end of follow-up, it decreased to 3.3 (+/- 1.6; Delta = -2.6; p > 0.0001), 4.2 (+/- 1.5; Delta = -1.1; p = 0.0001) and 5.4 (+/- 1.7; Delta = -0.7; p = 0.06). For the first TNF antagonist, DAS-28-based EULAR response level was good in 42% and moderate in 33% of patients. The second TNF antagonist yielded a good response in 20% and no response in 53% of patients, while the third one yielded a good response in 28% and no response in 72%. Mean baseline HAQ on starting the first, second and third TNF antagonist was 1.61, 1.52 and 1.87, respectively. At the end of follow-up, it decreased to 1.12 (Delta = -0.49; p < 0.0001), 1.31 (Delta = -0.21, p = 0.004) and 1.75 (Delta = -0.12; p = 0.1), respectively. Sixty four percent of patients had a clinically important improvement in HAQ (defined as > or = -0.22) with the first TNF antagonist and 46% with the second. CONCLUSION A clinically significant effect size was seen in less than half of RA patients cycling to a second TNF antagonist.

Assessment of Severe Apnoea through Voice Analysis, Automatic Speech, and Speaker Recognition Techniques

This study is part of an ongoing collaborative effort between the medical and the signal processing communities to promote research on applying standard Automatic Speech Recognition (ASR) techniques for the automatic diagnosis of patients with severe obstructive sleep apnoea (OSA). Early detection of severe apnoea cases is important so that patients can receive early treatment. Effective ASR-based detection could dramatically cut medical testing time. Working with a carefully designed speech database of healthy and apnoea subjects, we describe an acoustic search for distinctive apnoea voice characteristics. We also study abnormal nasalization in OSA patients by modelling vowels in nasal and nonnasal phonetic contexts using Gaussian Mixture Model (GMM) pattern recognition on speech spectra. Finally, we present experimental findings regarding the discriminative power of GMMs applied to severe apnoea detection. We have achieved an 81% correct classification rate, which is very promising and underpins the interest in this line of inquiry.

Drugs Associated with Hepatotoxicity and their Reporting Frequency of Liver Adverse Events in VigiBase (TM) Unified List Based on International Collaborative Work

BACKGROUND Challenges exist in the clinical diagnosis of drug-induced liver injury (DILI) and in obtaining information on hepatotoxicity in humans. OBJECTIVE (i) To develop a unified list that combines drugs incriminated in well vetted or adjudicated DILI cases from many recognized sources and drugs that have been subjected to serious regulatory actions due to hepatotoxicity; and (ii) to supplement the drug list with data on reporting frequencies of liver events in the WHO individual case safety report database (VigiBase). DATA SOURCES AND EXTRACTION (i) Drugs identified as causes of DILI at three major DILI registries; (ii) drugs identified as causes of drug-induced acute liver failure (ALF) in six different data sources, including major ALF registries and previously published ALF studies; and (iii) drugs identified as being subjected to serious governmental regulatory actions due to their hepatotoxicity in Europe or the US were collected. The reporting frequency of adverse events was determined using VigiBase, computed as Empirical Bayes Geometric Mean (EBGM) with 90% confidence interval for two customized terms, 'overall liver injury' and 'ALF'. EBGM of >or=2 was considered a disproportional increase in reporting frequency. The identified drugs were then characterized in terms of regional divergence, published case reports, serious regulatory actions, and reporting frequency of 'overall liver injury' and 'ALF' calculated from VigiBase. DATA SYNTHESIS After excluding herbs, supplements and alternative medicines, a total of 385 individual drugs were identified; 319 drugs were identified in the three DILI registries, 107 from the six ALF registries (or studies) and 47 drugs that were subjected to suspension or withdrawal in the US or Europe due to their hepatotoxicity. The identified drugs varied significantly between Spain, the US and Sweden. Of the 319 drugs identified in the DILI registries of adjudicated cases, 93.4% were found in published case reports, 1.9% were suspended or withdrawn due to hepatotoxicity and 25.7% were also identified in the ALF registries/studies. In VigiBase, 30.4% of the 319 drugs were associated with disproportionally higher reporting frequency of 'overall liver injury' and 83.1% were associated with at least one reported case of ALF. CONCLUSIONS This newly developed list of drugs associated with hepatotoxicity and the multifaceted analysis on hepatotoxicity will aid in causality assessment and clinical diagnosis of DILI and will provide a basis for further characterization of hepatotoxicity.

Graph based study of allergen cross-reactivity of plant lipid transfer proteins (LTPs) using microarray in a multicenter study.

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens.

Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound.

Aquaporins (AQPs) are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III) complexes screened on human red blood cells (hRBC) and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC(50) = 0.8±0.08 µM in hRBC). Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III) to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III) complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range) together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development.

Application of Molecular Diagnostic Techniques for Viral Testing.

Nucleic acid amplification techniques are commonly used currently to diagnose viral diseases and manage patients with this kind of illnesses. These techniques have had a rapid but unconventional route of development during the last 30 years, with the discovery and introduction of several assays in clinical diagnosis. The increase in the number of commercially available methods has facilitated the use of this technology in the majority of laboratories worldwide. This technology has reduced the use of some other techniques such as viral culture based methods and serological assays in the clinical virology laboratory. Moreover, nucleic acid amplification techniques are now the methods of reference and also the most useful assays for the diagnosis in several diseases. The introduction of these techniques and their automation provides new opportunities for the clinical laboratory to affect patient care. The main objectives in performing nucleic acid tests in this field are to provide timely results useful for high-quality patient care at a reasonable cost, because rapid results are associated with improvements in patients care. The use of amplification techniques such as polymerase chain reaction, real-time polymerase chain reaction or nucleic acid sequence-based amplification for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range. This review is an up-to-date of the main nucleic acid techniques and their clinical applications, and special challenges and opportunities that these techniques currently provide for the clinical virology laboratory.

Effective diagnosis of Alzheimer's disease by means of large margin-based methodology.

BACKGROUND Functional brain images such as Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been widely used to guide the clinicians in the Alzheimer's Disease (AD) diagnosis. However, the subjectivity involved in their evaluation has favoured the development of Computer Aided Diagnosis (CAD) Systems. METHODS It is proposed a novel combination of feature extraction techniques to improve the diagnosis of AD. Firstly, Regions of Interest (ROIs) are selected by means of a t-test carried out on 3D Normalised Mean Square Error (NMSE) features restricted to be located within a predefined brain activation mask. In order to address the small sample-size problem, the dimension of the feature space was further reduced by: Large Margin Nearest Neighbours using a rectangular matrix (LMNN-RECT), Principal Component Analysis (PCA) or Partial Least Squares (PLS) (the two latter also analysed with a LMNN transformation). Regarding the classifiers, kernel Support Vector Machines (SVMs) and LMNN using Euclidean, Mahalanobis and Energy-based metrics were compared. RESULTS Several experiments were conducted in order to evaluate the proposed LMNN-based feature extraction algorithms and its benefits as: i) linear transformation of the PLS or PCA reduced data, ii) feature reduction technique, and iii) classifier (with Euclidean, Mahalanobis or Energy-based methodology). The system was evaluated by means of k-fold cross-validation yielding accuracy, sensitivity and specificity values of 92.78%, 91.07% and 95.12% (for SPECT) and 90.67%, 88% and 93.33% (for PET), respectively, when a NMSE-PLS-LMNN feature extraction method was used in combination with a SVM classifier, thus outperforming recently reported baseline methods. CONCLUSIONS All the proposed methods turned out to be a valid solution for the presented problem. One of the advances is the robustness of the LMNN algorithm that not only provides higher separation rate between the classes but it also makes (in combination with NMSE and PLS) this rate variation more stable. In addition, their generalization ability is another advance since several experiments were performed on two image modalities (SPECT and PET).

Improving integrated care in chronic kidney failure patients with a standard-based interoperability framework.

This paper introduces the evaluation report after fostering a Standard-based Interoperability Framework (SIF) between the Virgen del Rocío University Hospital (VRUH) Haemodialysis (HD) Unit and 5 outsourced HD centres in order to improve integrated care by automatically sharing patients' Electronic Health Record (EHR) and lab test reports. A pre-post study was conducted during fourteen months. The number of lab test reports of both emergency and routine nature regarding to 379 outpatients was computed before and after the integration of the SIF. Before fostering SIF, 19.38 lab tests per patient were shared between VRUH and HD centres, 5.52 of them were of emergency nature while 13.85 were routine. After integrating SIF, 17.98 lab tests per patient were shared, 3.82 of them were of emergency nature while 14.16 were routine. The inclusion of a SIF in the HD Integrated Care Process has led to an average reduction of 1.39 (p=0.775) lab test requests per patient, including a reduction of 1.70 (p=0.084) in those of emergency nature, whereas an increase of 0.31 (p=0.062) was observed in routine lab tests. Fostering this strategy has led to the reduction in emergency lab test requests, which implies a potential improvement of the integrated care.

Lactococcus garvieae endocarditis in a native valve identified by MALDI-TOF MS and PCR-based 16s rRNA in Spain: A case report.

Lactococcus garvieae is a Gram-positive, catalase negative coccus arranged in pairs or short chains, well-known as a fish pathogen. We report a case of Infective Endocarditis (IE) by L. garvieae in a native valve from a 68-year-old male with unknown history of contact with raw fish and an extensive history of heart disease. This case highlights the reliability of MALDI-TOF MS compared to conventional methods in the identification of rare microorganisms like this.

Are the health messages in schoolbooks based on scientific evidence? A descriptive study.

BACKGROUND Most textbooks contains messages relating to health. This profuse information requires analysis with regards to the quality of such information. The objective was to identify the scientific evidence on which the health messages in textbooks are based. METHODS The degree of evidence on which such messages are based was identified and the messages were subsequently classified into three categories: Messages with high, medium or low levels of evidence; Messages with an unknown level of evidence; and Messages with no known evidence. RESULTS 844 messages were studied. Of this total, 61% were classified as messages with an unknown level of evidence. Less than 15% fell into the category where the level of evidence was known and less than 6% were classified as possessing high levels of evidence. More than 70% of the messages relating to "Balanced Diets and Malnutrition", "Food Hygiene", "Tobacco", "Sexual behaviour and AIDS" and "Rest and ergonomics" are based on an unknown level of evidence. "Oral health" registered the highest percentage of messages based on a high level of evidence (37.5%), followed by "Pregnancy and newly born infants" (35%). Of the total, 24.6% are not based on any known evidence. Two of the messages appeared to contravene known evidence. CONCLUSION Many of the messages included in school textbooks are not based on scientific evidence. Standards must be established to facilitate the production of texts that include messages that are based on the best available evidence and which can improve children's health more effectively.

Edge vascular response after polymer-free vs. polymer-based paclitaxel-eluting stent implantation.

BACKGROUND It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024). CONCLUSIONS PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms.