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  1. Clinical virology in real time.

    PubMed

    Niesters, Hubert G M

    2002-12-01

    The ability to detect nucleic acids has had and still has a major impact on diagnostics in clinical virology. Both quantitative and qualitative techniques, whether signal or target amplification based systems, are currently used routinely in most if not all virology laboratories. Technological improvements, from automated sample isolation to real time amplification technology, have given the ability to develop and introduce systems for most viruses of clinical interest, and to obtain clinical relevant information needed for optimal antiviral treatment options. Both polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA) can currently be used together with real time detection to generate results in a short turn-around time and to determine whether variants relevant for antiviral resistance are present. These new technologies enable the introduction of an individual patient disease management concept. Within our clinical setting, we have introduced this e.g. for quantitative detection of Epstein-Barr Virus (EBV) in T-dell depleted allogeneic stem cell transplant patients. This enabled us to develop models for pre-emptive anti B-cell immunotherapy for EBV reactivation, thereby effectively reducing not the incidence of EBV-lymphoproliferative disease but the virus related mortality. Furthermore, additional clinically relevant viruses can now easily be detected simultaneously. It also becomes more feasible to introduce molecular testing for those viruses that can easily be detected using classical virological methods, like culture techniques or antigen detection. Prospective studies are needed to evaluate the clinical importance of the additional positive samples detected. It should however be made clear that a complete exchange of technologies is unlikely to occur, and that some complementary technologies should stay operational enabling the discovery of new viruses. The implementation of these molecular diagnostic technologies furthermore

  2. European Society for Clinical Virology - winter meeting.

    PubMed

    Westh, Henrik

    2004-02-01

    The European Society for Clinical Virology annual winter meeting mainly appeals to clinical virologists interested in human disease. Basic and clinical data were presented, highlighting a number of interesting findings. This report briefly describes options in HIV antiviral treatment, and focuses on fusion inhibitors, a new anti-HIV class of drugs. Recent improvements in experimental DNA vaccines are also presented.

  3. Applying proteomic technology to clinical virology.

    PubMed

    Mancone, C; Ciccosanti, F; Montaldo, C; Perdomo, A B; Piacentini, M; Alonzi, T; Fimia, G M; Tripodi, M

    2013-01-01

    Developing antiviral drugs, vaccines and diagnostic markers is still the most ambitious challenge in clinical virology. In the past few decades, data from high-throughput technologies have allowed for the rapid development of new antiviral therapeutic strategies, thus making a profound impact on translational research. Most of the current preclinical studies in virology are aimed at evaluating the dynamic composition and localization of the protein platforms involved in various host-virus interactions. Among the different possible approaches, mass spectrometry-based proteomics is increasingly being used to define the protein composition in subcellular compartments, quantify differential protein expression among samples, characterize protein complexes, and analyse protein post-translational modifications. Here, we review the current knowledge of the most useful proteomic approaches in the study of viral persistence and pathogenicity, with a particular focus on recent advances in hepatitis C research.

  4. Total quality management in clinical virology laboratories.

    PubMed

    Tibbets, M W; Gomez, R; Kannangai, R; Sridharan, G

    2006-10-01

    The diagnostic laboratories in India are progressively promoting higher standards and are moving towards accreditation and international acceptance. Hence, the concept of "Quality" will need to be understood and implemented. Total quality management (TQM) in a laboratory is an integrated program involving all laboratory staff and management. TQM is a framework to operate and it is aiming for integration, consistency, increase in efficiency and a continuous drive for improvement. A well structured clinical virology service will include serology setup, cell culture facility and capacity for molecular diagnosis. The quality of results from the laboratory is significantly influenced by many pre-analytical and post-analytical factors which needed attention. The end goal of the TQM should be to provide the best care possible for the patient.

  5. Myocarditis in puppies: clinical, pathological and virological findings.

    PubMed

    Gagnon, A N; Crowe, S P; Allen, D G; Downey, R S

    1980-07-01

    The clinical, pathological and virological findings in puppies affected with myocarditis are reported. A parvo-like virus was isolated from pooled heart specimens, which is similar to the virus isolated from gastroenteritis cases.

  6. Verification and validation of diagnostic laboratory tests in clinical virology.

    PubMed

    Rabenau, Holger F; Kessler, Harald H; Kortenbusch, Marhild; Steinhorst, Andreas; Raggam, Reinhard B; Berger, Annemarie

    2007-10-01

    This review summarizes major issues of verification and validation procedures and describes minimum requirements for verification and validation of diagnostic assays in clinical virology including instructions for CE/IVD-labeled as well as for self-developed ("home-brewed") tests or test systems. It covers techniques useful for detection of virus specific antibodies, for detection of viral antigens, for detection of viral nucleic acids, and for isolation of viruses on cell cultures in the routine virology laboratory.

  7. Deep sequencing: becoming a critical tool in clinical virology.

    PubMed

    Quiñones-Mateu, Miguel E; Avila, Santiago; Reyes-Teran, Gustavo; Martinez, Miguel A

    2014-09-01

    Population (Sanger) sequencing has been the standard method in basic and clinical DNA sequencing for almost 40 years; however, next-generation (deep) sequencing methodologies are now revolutionizing the field of genomics, and clinical virology is no exception. Deep sequencing is highly efficient, producing an enormous amount of information at low cost in a relatively short period of time. High-throughput sequencing techniques have enabled significant contributions to multiples areas in virology, including virus discovery and metagenomics (viromes), molecular epidemiology, pathogenesis, and studies of how viruses to escape the host immune system and antiviral pressures. In addition, new and more affordable deep sequencing-based assays are now being implemented in clinical laboratories. Here, we review the use of the current deep sequencing platforms in virology, focusing on three of the most studied viruses: human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus.

  8. Deep Sequencing: Becoming a Critical Tool in Clinical Virology

    PubMed Central

    QUIÑONES-MATEU, Miguel E.; AVILA, Santiago; REYES-TERAN, Gustavo; MARTINEZ, Miguel A.

    2014-01-01

    Population (Sanger) sequencing has been the standard method in basic and clinical DNA sequencing for almost 40 years; however, next-generation (deep) sequencing methodologies are now revolutionizing the field of genomics, and clinical virology is no exception. Deep sequencing is highly efficient, producing an enormous amount of information at low cost in a relatively short period of time. High-throughput sequencing techniques have enabled significant contributions to multiples areas in virology, including virus discovery and metagenomics (viromes), molecular epidemiology, pathogenesis, and studies of how viruses to escape the host immune system and antiviral pressures. In addition, new and more affordable deep sequencing-based assays are now being implemented in clinical laboratories. Here we review the use of the current deep sequencing platforms in virology, focusing on three of the most studied viruses: human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus. PMID:24998424

  9. The potential advantages of digital PCR for clinical virology diagnostics.

    PubMed

    Hall Sedlak, Ruth; Jerome, Keith R

    2014-05-01

    Digital PCR (dPCR), a new nucleic acid amplification technology, offers several potential advantages over real-time or quantitative PCR (qPCR), the current workhorse of clinical molecular virology diagnostics. Several studies have demonstrated dPCR assays for human cytomegalovirus or HIV, which give more precise and reproducible results than qPCR assays without sacrificing sensitivity. Here we review the literature comparing dPCR and qPCR performance in viral molecular diagnostic assays and offer perspective on the future of dPCR in clinical virology diagnostics.

  10. Molecular virology in the clinical laboratory.

    PubMed

    Josko, Deborah

    2010-01-01

    As one can see by the tests listed at www.amp.org, molecular diagnostic techniques have enabled the laboratory professionals to play an integral role in the identification and quantitation of viral infectious agents. Viral loads can be determined for HIV, HBV, and HCV using a variety of molecular methods such as real-time PCR, TMA, NASBA, and bDNA. Determining the amount of viral particles in a sample can not only monitor the status and progression of the disease, but can also guide recommendations for antiviral therapy. Other assays listed include cytomegalovirus, enterovirus, and human metapneumovirus detection, HPV testing, influenza and respiratory virus panels, and West Nile virus detection in blood donations using a variety of molecular methodologies. The use of molecular methodologies in the detection of viral pathogens has grown at an astounding rate, especially in the past two decades. It is now widely accepted that PCR is the "gold standard" for nucleic acid detection in the clinical laboratory as well as in research facilities. This article only touched on some of the common, widely used assays and platforms used in the identification process. With more and more assays being developed, the cost behind molecular testing has decreased since there are more competitors on the market. At one point, laboratorians may have thought of routine molecular testing as the wave of the future. It is obvious the future is upon us. Molecular diagnostics has become part of the daily, routine workload in most clinical laboratories. The advent of fully automated systems with faster turn around times has given laboratory professionals the tools necessary to report out accurate and sensitive results to clinicians who can ultimately improve patient care and outcomes by rendering a correct and rapid diagnosis.

  11. A role for arrays in clinical virology: fact or fiction?

    PubMed

    Clewley, Jonathan P

    2004-01-01

    Microarrays of DNA probes have at least three roles in clinical virology. These are: firstly, in diagnosis, to recognise the causative agent of an illness; secondly, for molecular typing for (i) patient management, (ii) epidemiological reasons (e.g. investigating routes of transmission), (iii) purposes related to vaccine use; and thirdly, in research, to investigate the interactions between the virus and the host cell. Microarrays intended for syndromic diagnostic purposes require genome specific probes to capture the unknown target viral sequences and thereby reveal the presence of that virus in a test sample. Microarrays intended for typing and patient management, e.g. monitoring antiviral drug resistant mutations require a set of probes representing the important sequence variants of one or more viral genes. Microarrays intended for research into virus-host interactions require probes representative of each individual gene or mRNA of either the virus or the host genome. Diagnostic microarrays are dependent for their utility and versatility on generic, multiplex or random polymerase chain reactions that will amplify any of several (unknown) viral target sequences from a patient sample. In this review, the existing and potential applications of microarrays in virology, and the problems that need to be overcome for future success, are discussed.

  12. Quantification of HBsAg: basic virology for clinical practice.

    PubMed

    Lee, Jung Min; Ahn, Sang Hoon

    2011-01-21

    Hepatitis B surface antigen (HBsAg) is produced and secreted through a complex mechanism that is still not fully understood. In clinical fields, HBsAg has long served as a qualitative diagnostic marker for hepatitis B virus infection. Notably, advances have been made in the development of quantitative HBsAg assays, which have allowed viral replication monitoring, and there is an opportunity to make maximal use of quantitative HBsAg to elucidate its role in clinical fields. Yet, it needs to be underscored that a further understanding of HBsAg, not only from clinical point of view but also from a virologic point of view, would enable us to deepen our insights, so that we could more widely expand and apply its utility. It is also important to be familiar with HBsAg variants and their clinical consequences in terms of immune escape mutants, issues resulting from overlap with corresponding mutation in the P gene, and detection problems for the HBsAg variants. In this article, we review current concepts and issues on the quantification of HBsAg titers with respect to their biologic nature, method principles, and clinically relevant topics.

  13. Development of working reference materials for clinical virology.

    PubMed

    Fryer, Jacqueline F; Baylis, Sally A; Gottlieb, Anna L; Ferguson, Morag; Vincini, Giuseppe A; Bevan, Valerie M; Carman, William F; Minor, Philip D

    2008-12-01

    Nucleic acid amplification technique (NAT)-based assays are replacing traditional diagnostic methods in clinical laboratories. However, many of these assays are developed in-house and the lack of standardised reference materials has hindered assay implementation and control. Consequently, in the UK, the Clinical Virology Network (CVN), the National Institute for Biological Standards and Control (NIBSC), and the Health Protection Agency (HPA), are working in collaboration to develop working standards or 'run controls' for diagnostic NAT-based assays, particularly real-time PCR. These run controls are intended for use in microbiology laboratories and are designed to be extracted and amplified in the same way as clinical samples and included in each assay run. The aim is to enable clinical laboratories to continuously monitor the performance of their diagnostic NAT assays on a run-by-run basis allowing inter-laboratory comparisons, and ultimately improving the consistency of results. At present, eight candidate run controls representing clinically relevant viral targets have been prepared for evaluation by CVN laboratories. Data have been returned on the performance of each run control in routine diagnostic assays. Preliminary results presented here indicate a high level of variability in intra- and inter-assay detection of these targets, highlighting the need for standardisation of assays within molecular diagnostics.

  14. Virological efficacy of PI monotherapy for HIV-1 in clinical practice

    PubMed Central

    El Bouzidi, Kate; Collier, Dami; Nastouli, Eleni; Copas, Andrew J.; Miller, Robert F.; Gupta, Ravindra K.

    2016-01-01

    Background Clinical trials of PI monotherapy indicate that most participants maintain viral suppression and emergent protease resistance is rare. However, outcomes among patients receiving PI monotherapy for clinical reasons, such as toxicity or adherence issues, are less well studied. Methods An observational study of patients attending an HIV treatment centre in London, UK, who had received PI monotherapy between 2004 and 2013, was conducted using prospectively collected clinical data and genotypic resistance reports. Survival analysis techniques were used to examine the times to virological failure and treatment discontinuation. Results Ninety-five patients had PI monotherapy treatment for a median duration of 126 weeks. Virological failure occurred during 64% of episodes and 8% of patients developed emergent protease mutations. We estimate failure occurs in half of episodes within 2 years following initiation. Where PI monotherapy was continued following virological failure, 68% of patients achieved viral re-suppression. Despite a high incidence of virological failure, many patients continued PI monotherapy and 79% of episodes were ongoing at the end of the study. The type of PI used, the presence of baseline protease mutations and the plasma HIV RNA at initiation did not have a significant impact on treatment outcomes. Conclusions There was a higher incidence of virological failure and emerging resistance in our UK clinical setting than described in PI monotherapy clinical trials and other European observational studies. Despite this, many patients continued PI monotherapy and regained viral suppression, indicating this strategy remains a viable option in certain individuals following careful clinical evaluation. PMID:27402006

  15. Application of MALDI-TOF Mass Spectrometry in Clinical Virology: A Review

    PubMed Central

    Cobo, Fernando

    2013-01-01

    MALDI-TOF mass spectrometry is a diagnostic tool of microbial identification and characterization based on the detection of the mass of molecules. In the majority of clinical laboratories, this technology is currently being used mainly for bacterial diagnosis, but several approaches in the field of virology have been investigated. The introduction of this technology in clinical virology will improve the diagnosis of infections produced by viruses but also the discovery of mutations and variants of these microorganisms as well as the detection of antiviral resistance. This review is focused on the main current applications of MALDI-TOF MS techniques in clinical virology showing the state of the art with respect to this exciting new technology. PMID:24222805

  16. Application of maldi-tof mass spectrometry in clinical virology: a review.

    PubMed

    Cobo, Fernando

    2013-01-01

    MALDI-TOF mass spectrometry is a diagnostic tool of microbial identification and characterization based on the detection of the mass of molecules. In the majority of clinical laboratories, this technology is currently being used mainly for bacterial diagnosis, but several approaches in the field of virology have been investigated. The introduction of this technology in clinical virology will improve the diagnosis of infections produced by viruses but also the discovery of mutations and variants of these microorganisms as well as the detection of antiviral resistance. This review is focused on the main current applications of MALDI-TOF MS techniques in clinical virology showing the state of the art with respect to this exciting new technology.

  17. Hepatitis B virus in Buenos Aires, Argentina: genotypes, virological characteristics and clinical outcomes.

    PubMed

    Pezzano, S C; Torres, C; Fainboim, H A; Bouzas, M B; Schroder, T; Giuliano, S F; Paz, S; Alvarez, E; Campos, R H; Mbayed, V A

    2011-02-01

    Hepatitis B virus (HBV) is classified into eight major genotypes, A-H, which are geographically distributed worldwide. The aim of this work was to describe the clinical characteristics associated with the HBV genotypes circulating in Buenos Aires city. The study included 139 patients infected with HBV, whose clinical courses were classified as acute symptomatic self-limiting hepatitis, inactive carrier state and chronic active hepatitis (HBV e-antigen (HBeAg)-positive and HBeAg-negative). The HBV genotypes were determined in 128 patients by PCR-restriction fragment length polymorphism and phylogenetic analysis. Biochemical, virological, clinical and histological features were analysed. A differential distribution of genotypes between acute symptomatic and chronic infections was found. Among the acute cases, genotype F was predominant (65.2%, 30/46) and genotype D was rare (4.3%, 2/46), whereas among the chronic infections, a homogeneous distribution of genotypes A (26.8%, 22/82), D (31.7%, 26/82) and F (36.6%, 30/82), with an unusual presence of genotypes B (1.2%, 1/82) and C (3.7%, 3/82), was observed. Regarding the liver histology of chronically infected patients, genotype F tended to display higher histological activity indexes. Mutations related to HBV surface antigen immunoreactivity, antiviral resistance and HBeAg-negative status were studied. This work constitutes, to our knowledge, the first description of the clinical characteristics related to HBV genotypes in Argentina, where the distribution of genotypes in patients with acute infection has not been reported previously. Finally, it was established that genotype F is the prevalent genotype among the acute symptomatic infections in Buenos Aires city, and that it shows a tendency to cause an adverse disease outcome among the chronic cases.

  18. HIV-1 Amino Acid Changes Among Participants With Virologic Failure: Associations With First-line Efavirenz or Atazanavir Plus Ritonavir and Disease Status

    PubMed Central

    Mollan, Katie; Daar, Eric S.; Sax, Paul E.; Balamane, Maya; Collier, Ann C.; Fischl, Margaret A.; Lalama, Christina M.; Bosch, Ronald J.; Tierney, Camlin; Katzenstein, David

    2012-01-01

    Background. Although specific human immunodeficiency virus type 1 (HIV-1) drug resistance mutations are well studied, little is known about cumulative amino acid changes, or how regimen and participant characteristics influence these changes. Methods. In the AIDS Clinical Trials Group randomized study A5202 of treatment-naive HIV-infected participants, cumulative HIV-1 amino acid changes from pretreatment to virologic failure were evaluated in protease and reverse transcriptase (RT) gene sequences. Results. Among 265 participants with virologic failure, those assigned atazanavir plus ritonavir (ATV/r) did not have significantly more protease changes compared with those assigned efavirenz (EFV) (P ≥ .13). In contrast, participants with virologic failure assigned EFV had more RT changes, including and excluding known resistance codons (P < .001). At pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures (all P < .001), hepatitis C antibody negativity (P = .05), and black race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes. Conclusions. Virologic failure following EFV-containing treatment was associated with more HIV-1 amino acid changes compared to failure of ATV/r-containing treatment. Furthermore, we show that non–drug resistance mutations occurred more frequently among those failing EFV, the clinical relevance of which warrants further investigation. Pretreatment immunologic status may play a role in viral evolution during treatment, as evidenced by increased amino acid changes among those with lower pretreatment CD4 count. Clinical Trials Registration. NCT00118898. PMID:23148287

  19. The laboratory of clinical virology in monitoring patients undergoing monoclonal antibody therapy.

    PubMed

    Cavallo, R

    2011-12-01

    The relevant efficacy of monoclonal antibodies (mAbs) has resulted in the successful treatment of several diseases, although susceptibility to infections remains a major problem. This review summarizes aspects of the literature regarding viral infections and mAbs, specifically addressing the risk of infection/reactivation, the measures that can reduce this risk, and the role played by the laboratory of clinical virology in monitoring patients undergoing mAb therapy.

  20. Vitamin D Status and Virologic Response to HCV Therapy in the HALT-C and VIRAHEP-C Trials

    PubMed Central

    Loftfield, Erikka; O’Brien, Thomas R.; Pfeiffer, Ruth M.; Howell, Charles D.; Horst, Ron; Prokunina-Olsson, Ludmila; Weinstein, Stephanie J.; Albanes, Demetrius; Morgan, Timothy R.; Freedman, Neal D.

    2016-01-01

    More than 150 million people worldwide are chronically infected with hepatitis C virus (HCV) and face higher risk of cirrhosis and hepatocellular carcinoma. Highly effective HCV treatments have recently been developed; however, they are costly and therefore poorly suited for application in resource-limited settings where HCV burden is high. Pegylated-interferon alpha (PEG-IFNα) and ribavirin (RBV) therapy is far less costly, but also less effective. Vitamin D supplementation has been proposed as an inexpensive adjuvant to treatment, however, prior epidemiological evidence on its effectiveness is inconsistent, with little data available among African Americans who naturally have lower vitamin D concentrations. We thus evaluated associations between baseline vitamin D status, measured by circulating 25-hydroxyvitamin D (25(OH)D), which is considered to be the best marker of vitamin D status in humans, and subsequent response to PEG-IFNα/RBV therapy in two large clinical trials that together included 1292 patients infected with HCV genotype 1. We used race-stratified logistic regression models to evaluate multivariable-adjusted associations of 25(OH)D with early virologic response (EVR; 2-log10 HCV RNA decline at week 12) and sustained virologic response (SVR). Among African Americans, we saw no associations. Among European Americans, we saw no association with low vitamin D (≤20 ng/mL) versus sufficient concentrations (20-<30 ng/mL). However, patients with 25(OH)D ≥30 ng/mL were actually less likely to attain EVR (OR = 0.64, 95% CI = 0.43–0.94) than those with sufficient concentrations, with a similar but non-significant association observed for SVR (OR = 0.49, 95% CI = 0.20–1.17). Conclusion Higher vitamin D status was not beneficially associated with responses to therapy; if anything, patients with higher vitamin D concentrations were less likely to attain SVR. Our data do not support a role for vitamin D supplementation as an adjuvant therapy for HCV

  1. Virology, Immunology, and Clinical Course of HIV Infection.

    ERIC Educational Resources Information Center

    McCutchan, J. Allen

    1990-01-01

    Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

  2. Oncolytic parvoviruses: from basic virology to clinical applications.

    PubMed

    Marchini, Antonio; Bonifati, Serena; Scott, Eleanor M; Angelova, Assia L; Rommelaere, Jean

    2015-01-29

    Accumulated evidence gathered over recent decades demonstrated that some members of the Parvoviridae family, in particular the rodent protoparvoviruses H-1PV, the minute virus of mice and LuIII have natural anticancer activity while being nonpathogenic to humans. These studies have laid the foundations for the launch of a first phase I/IIa clinical trial, in which the rat H-1 parvovirus is presently undergoing evaluation for its safety and first signs of efficacy in patients with glioblastoma multiforme. After a brief overview of the biology of parvoviruses, this review focuses on the studies which unraveled the antineoplastic properties of these agents and supported their clinical use as anticancer therapeutics. Furthermore, the development of novel parvovirus-based anticancer strategies with enhanced specificity and efficacy is discussed, in particular the development of second and third generation vectors and the combination of parvoviruses with other anticancer agents. Lastly, we address the key challenges that remain towards a more rational and efficient use of oncolytic parvoviruses in clinical settings, and discuss how a better understanding of the virus life-cycle and of the cellular factors involved in virus infection, replication and cytotoxicity may promote the further development of parvovirus-based anticancer therapies, open new prospects for treatment and hopefully improve clinical outcome.

  3. Next-generation sequencing technology in clinical virology.

    PubMed

    Capobianchi, M R; Giombini, E; Rozera, G

    2013-01-01

    Recent advances in nucleic acid sequencing technologies, referred to as 'next-generation' sequencing (NGS), have produced a true revolution and opened new perspectives for research and diagnostic applications, owing to the high speed and throughput of data generation. So far, NGS has been applied to metagenomics-based strategies for the discovery of novel viruses and the characterization of viral communities. Additional applications include whole viral genome sequencing, detection of viral genome variability, and the study of viral dynamics. These applications are particularly suitable for viruses such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus, whose error-prone replication machinery, combined with the high replication rate, results, in each infected individual, in the formation of many genetically related viral variants referred to as quasi-species. The viral quasi-species, in turn, represents the substrate for the selective pressure exerted by the immune system or by antiviral drugs. With traditional approaches, it is difficult to detect and quantify minority genomes present in viral quasi-species that, in fact, may have biological and clinical relevance. NGS provides, for each patient, a dataset of clonal sequences that is some order of magnitude higher than those obtained with conventional approaches. Hence, NGS is an extremely powerful tool with which to investigate previously inaccessible aspects of viral dynamics, such as the contribution of different viral reservoirs to replicating virus in the course of the natural history of the infection, co-receptor usage in minority viral populations harboured by different cell lineages, the dynamics of development of drug resistance, and the re-emergence of hidden genomes after treatment interruptions. The diagnostic application of NGS is just around the corner.

  4. Pandemic and Avian Influenza A Viruses in Humans: Epidemiology, Virology, Clinical Characteristics, and Treatment Strategy.

    PubMed

    Li, Hui; Cao, Bin

    2017-03-01

    The intermittent outbreak of pandemic influenza and emergence of novel avian influenza A virus is worldwide threat. Although most patients present with mild symptoms, some deteriorate to severe pneumonia and even death. Great progress in the understanding of the mechanism of disease pathogenesis and a series of vaccines has been promoted worldwide; however, incidence, morbidity, and mortality remains high. To step up vigilance and improve pandemic preparedness, this article elucidates the virology, epidemiology, pathogenesis, clinical characteristics, and treatment of human infections by influenza A viruses, with an emphasis on the influenza A(H1N1)pdm09, H5N1, and H7N9 subtypes.

  5. Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D.

    PubMed

    Fouad, Rabab; Abdo, Mahmoud; Eldeen, Hadeel Gamal; Sabry, Dina; Atef, Mira; Ahmed, Rasha; Zayed, Naglaa

    2016-05-01

    Hepatitis delta virus (HDV) usually have an unfavorable clinical outcome in chronic hepatitis B virus (HBV) patients. In Egypt, data about epidemiology, the spectrum of disease, and impact of HDV on HBV infection are rare. To assess the prevalence, clinical and virological characteristics of HDV infection among Egyptian patients with chronic HBV. Adult patients with Hepatitis B surface antigen (HBsAg)-positive were evaluated for the presence of HDV using anti HDV-IgG and HDV RNA by RT-PCR. Routine laboratory investigations, genotypes and subtypes for both HBV and HDV, abdominal sonography, and transient elastography (TE) were done. Liver biopsy was performed only in whenever indicated. One hundred and twenty-one treatment-naïve chronic HBV patients were included. Wild HBV genotype-D2 was found in 98.2% and 81.9% were HBeAg negative. Prevalence of HDV was 8.3% by anti-HDV IgG and 9.9% by RT-PCR. Wild HDV genotype-IIb was reported in 83.3%. HDV infection was more common in males, 90.9% of delta patients were HBeAg negative. Compared to the mono-infected HBV, concomitant HBV/HDV infection was not associated with more derangment in ALT nor advanced stage of fibrosis. 66.7% of HDV patients had significantly lower HBV-DNA level compared to the non-delta patients (P < 0.001). HDV is not uncommon in Egypt. HBV genotype-D was associated with HDV genotype-IIb. Delta infection was associated with negative HBeAg status, reduction of HBV replication, but neither influenced the clinical course nor increased significant liver damage risk.

  6. Efavirenz versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes

    PubMed Central

    Cain, Lauren E.; Caniglia, Ellen C.; Phillips, Andrew; Olson, Ashley; Muga, Roberto; Pérez-Hoyos, Santiago; Abgrall, Sophie; Costagliola, Dominique; Rubio, Rafael; Jarrín, Inma; Bucher, Heiner; Fehr, Jan; van Sighem, Ard; Reiss, Peter; Dabis, François; Vandenhende, Marie-Anne; Logan, Roger; Robins, James; Sterne, Jonathan A. C.; Justice, Amy; Tate, Janet; Touloumi, Giota; Paparizos, Vasilis; Esteve, Anna; Casabona, Jordi; Seng, Rémonie; Meyer, Laurence; Jose, Sophie; Sabin, Caroline; Hernán, Miguel A.

    2016-01-01

    Abstract Objective: To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. Design: Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. Methods: HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the “intention-to-treat” effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. Results: A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: −0.7%, 0.8%) and the AIDS-free survival difference was −0.3% (−1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm3 lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens. Conclusion: Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival. PMID:27741139

  7. Quantitative nucleic acid amplification methods and their implications in clinical virology

    PubMed Central

    Singh, Mini P; Galhotra, Shipra; Saigal, Karnika; Kumar, Archit; Ratho, Radha Kanta

    2017-01-01

    Recently, a number of techniques have been approved for quantification of viral nucleic acids in clinical samples. Viral load (VL) tests have considerable importance in the management of patients and are widely used in routine diagnosis. In clinical virology, VL testing are important to monitor the antiviral treatment, to initiate preemptive therapy, to understand pathogenesis, and to evaluate the infectivity. These tests have now become a part of many diagnostic and treatment guidelines. Considering the various challenges for in-house viral testing related to the standardization, validation, and precision; they are gradually being replaced by the United States Food and Drug Administration (US FDA) cleared tests. This review summarizes the various viral quantification methods and also discusses the clinical applicability of these in human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus, Cytomegalovirus, and Epstein Barr virus infected patients. Further the challenges and future perspectives of VL testing have also been discussed. PMID:28251100

  8. Quantitative nucleic acid amplification methods and their implications in clinical virology.

    PubMed

    Singh, Mini P; Galhotra, Shipra; Saigal, Karnika; Kumar, Archit; Ratho, Radha Kanta

    2017-01-01

    Recently, a number of techniques have been approved for quantification of viral nucleic acids in clinical samples. Viral load (VL) tests have considerable importance in the management of patients and are widely used in routine diagnosis. In clinical virology, VL testing are important to monitor the antiviral treatment, to initiate preemptive therapy, to understand pathogenesis, and to evaluate the infectivity. These tests have now become a part of many diagnostic and treatment guidelines. Considering the various challenges for in-house viral testing related to the standardization, validation, and precision; they are gradually being replaced by the United States Food and Drug Administration (US FDA) cleared tests. This review summarizes the various viral quantification methods and also discusses the clinical applicability of these in human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus, Cytomegalovirus, and Epstein Barr virus infected patients. Further the challenges and future perspectives of VL testing have also been discussed.

  9. Keeping kids in care: virological failure in a paediatric antiretroviral clinic and suggestions for improving treatment outcomes.

    PubMed

    Purchase, Susan; Cunningham, Jayne; Esser, Monika; Skinner, Donald

    2016-09-01

    The burden of paediatric HIV in South Africa is extremely high. Antiretrovirals (ARVs) are now widely accessible in the country and the clinical emphasis has shifted from initiation of treatment to retention in care. This study describes the cumulative virological failure rate amongst children on ARVs in a peri-urban clinic, and suggests ways in which clinics and partners could improve treatment outcomes. The study was conducted by the non-profit organisation HOPE Cape Town Association. A retrospective file audit determined the cumulative virological failure rate, that is, the sum of all children with a viral load >1000 copies/ml, children on monotherapy, children who had stopped treatment, children lost to follow-up (LTFU) and children who had died. Interviews were conducted with a purposive sample of 12 staff members and a random sample of 21 caregivers and 4 children attending care. Cumulative virological failure rate was 42%, with most of those children having been LTFU. Both staff and caregivers consistently identified pharmacy queues, ongoing stigma and unpalatable ARVs as barriers to adherence. Staff suggestions included use of adherence aids, and better education and support groups for caregivers. Caregivers also requested support groups, as well as "same day" appointments for caregivers and children, but rejected the idea of home visits. Simple, acceptable and cost-effective strategies exist whereby clinics and their partners could significantly reduce the cumulative virological failure rate in paediatric ARV clinics. These include actively tracing defaulters, improving education, providing support groups, and campaigning for palatable ARV formulations.

  10. Clinical and virologic efficacy of herpes simplex virus type 2 suppression by acyclovir in a multi-continent clinical trial

    PubMed Central

    Fuchs, Jonathan; Celum, Connie; Wang, Jing; Hughes, James; Sanchez, Jorge; Cowan, Frances; Reid, Stewart; Delany-Moretlwe, Sinead; Corey, Lawrence; Wald, Anna

    2010-01-01

    Acyclovir suppressive therapy (400 mg twice daily) reduces herpes simplex virus type 2 (HSV-2) associated genital ulcer disease (GUD) and lesional HSV shedding. In an international trial of acyclovir for HSV-2 suppression to prevent HIV acquisition (HPTN 039), acyclovir had a smaller effect on the frequency of GUD as well as the frequency and quantity of lesional HSV DNA in African women and Peruvian men compared with men in the United States. The observed regional variation in the clinical and virologic efficacy of acyclovir for HSV suppression warrants further evaluation of determinants of responses to acyclovir. PMID:20214474

  11. The vulnerability of men to virologic failure during antiretroviral therapy in a public routine clinic in Burkina Faso

    PubMed Central

    Penot, Pauline; Héma, Arsène; Bado, Guillaume; Kaboré, Firmin; Soré, Ibrahim; Sombié, Diamasso; Traoré, Jean-Richard; Guiard-Schmid, Jean-Baptiste; Fontanet, Arnaud; Slama, Laurence; Sawadogo, Adrien Bruno; Laurent, Christian

    2014-01-01

    Introduction Gender differences in antiretroviral therapy (ART) outcomes are critical in sub-Saharan Africa. We assessed the association between gender and virologic failure among adult patients treated in a public routine clinic (one of the largest in West Africa) in Burkina Faso. Methods We performed a case-control study between July and October 2012 among patients who had received ART at the Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six months. Cases were all patients with two consecutive HIV loads >1000 copies/mL (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL associated with immunologic or clinical failure criteria. Controls were all patients who only had HIV loads <300 copies/mL. The association between gender and virologic failure was assessed using a multivariate logistic regression, adjusted on age, level of education, baseline CD4+ T cell count, first and current antiretroviral regimens and time on ART. Results Of 2303 patients (74.2% women; median age: 40 years; median time on ART: 34 months), 172 had virologic failure and 2131 had virologic success. Among the former, 130 (75.6%) had confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four (2.3%) had viro-clinical failure. The proportion of men was significantly higher among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to controls, cases were also younger, more immunodeficient at ART initiation, less likely to receive a protease inhibitor-based antiretroviral regimen and had spent a longer period of time on ART. After adjustment, male gender remained strongly associated with virologic failure (odds ratio 2.52, 95% CI: 1.77–3.60; p<0.001). Conclusions Men on ART appeared more vulnerable to virologic failure than women. Additional studies are needed to confirm the poorer prognosis of men in this setting and to

  12. Clinical and virologic efficacy of herpes simplex virus type 2 suppression by acyclovir in a multicontinent clinical trial.

    PubMed

    Fuchs, Jonathan; Celum, Connie; Wang, Jing; Hughes, James; Sanchez, Jorge; Cowan, Frances; Reid, Stewart; Delany-Moretlwe, Sinead; Corey, Lawrence; Wald, Anna

    2010-04-15

    Acyclovir suppressive therapy (400 mg twice daily) reduces herpes simplex virus (HSV) type 2-associated genital ulcer disease and lesional HSV shedding. In an international trial of acyclovir for suppression of HSV type 2 to prevent human immunodeficiency virus (HIV) acquisition (HIV Prevention Trials Network 039), acyclovir had a smaller effect on the frequency of genital ulcer disease as well as a smaller effect on the frequency and quantity of lesional HSV DNA in African women and Peruvian men, compared with its effects in men in the United States. The observed regional variation in the clinical and virologic efficacy of acyclovir for HSV suppression warrants further evaluation of determinants of responses to acyclovir. (ClinicalTrials.gov identifier: NCT00076232.).

  13. Comparison of Adherence Monitoring Tools and Correlation to Virologic Failure in a Pediatric HIV Clinical Trial

    PubMed Central

    Intasan, Jintana; Vonthanak, Saphonn; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Apornpong, Tanakorn; Kerr, Stephen; Ananworanich, Jintanat; Puthanakit, Thanyawee

    2014-01-01

    Abstract There is no consensus on a gold standard for monitoring adherence to antiretroviral therapy (ART). We compared different adherence monitoring tools in predicting virologic failure as part of a clinical trial. HIV-infected Thai and Cambodian children aged 1–12 years (N=207) were randomized to immediate-ART or deferred-ART until CD4% <15%. Virologic failure (VF) was defined as HIV-RNA >1000 copies/mL after ≥6 months of ART. Adherence monitoring tools were: (1) announced pill count, (2) PACTG adherence questionnaire (form completed by caregivers), and (3) child self-report (self-reporting from children or caregivers to direct questioning by investigators during the clinic visit) of any missed doses in the last 3 days and in the period since the last visit. The Kappa statistic was used to describe agreement between each tool. The median age at ART initiation was 7 years with median CD4% 17% and HIV-RNA 5.0 log10copies/mL and 92% received zidovudine/lamivudine/nevirapine. Over 144 weeks, 13% had VF. Mean adherence by announced pill count before VF in VF children was 92% compared to 98% in children without VF (p=0.03). Kappa statistics indicated slight to fair agreement between tools. In multivariate analysis adjusting for gender, treatment arm ethnicity and caregiver education, significant predictors of VF were poor adherence by announced pill count (OR 4.56; 95%CI 1.78–11.69), reporting any barrier to adherence in the PACTG adherence questionnaire (OR 7.08; 95%CI 2.42–20.73), and reporting a missed dose in the 24 weeks since the last HIV-RNA assessment (OR 8.64; 95%CI 1.96–38.04). In conclusion, we recommend the child self-report of any missed doses since last visit for use in HIV research and in routine care settings, because it is easy and quick to administer and a strong association with development of VF. PMID:24901463

  14. Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults

    PubMed Central

    Chen, Wei-Ju; Arnold, John C.; Fairchok, Mary P.; Danaher, Patrick J.; McDonough, Erin A.; Blair, Patrick J.; Garcia, Josefina; Halsey, Eric S.; Schofield, Christina; Ottolini, Martin; Mor, Deepika; Ridoré, Michelande; Burgess, Timothy H.; Millar, Eugene V.

    2015-01-01

    Background Human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. Objectives To characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. Study design Observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. Results Eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18y. Fifty-four were HRV-A, 11 HRV-B, and 19 HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (Ptrend=0.01). Conclusions Among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding. PMID:25728083

  15. Systematic review of severe fever with thrombocytopenia syndrome: virology, epidemiology, and clinical characteristics.

    PubMed

    Liu, Shelan; Chai, Chengliang; Wang, Chengmin; Amer, Said; Lv, Huakun; He, Hongxuan; Sun, Jimin; Lin, Junfen

    2014-03-01

    Severe fever with thrombocytopenia syndrome (SFTS) was firstly discovered in China in 2010, followed by several reports from many other countries worldwide. SFTS virus (SFTSV) has been identified as the causative agent of the disease and has been recognized as a public health threat. This novel Bunyavirus belongs to the Phlebovirus genus in the family Bunyaviridae. This review also describes the different aspects of virology, pathogenesis, epidemiology, and clinical symptoms on the basis of the published article surveillance data and phylogenetic analyses of viral sequences of large, medium, and small segments retrieved from database using mega 5.05, simplot 3.5.1, network 4.611, and epi information system 3.5.3 software. SFTS presents with fever, thrombocytopenia, leukocytopenia, and considerable changes in several serum biomarkers. The disease has 10~15% mortality rate, commonly because of multiorgan dysfunction. SFTSV is mainly reported in the rural areas of Central and North-Eastern China, with seasonal occurrence from May to September, mainly targeting those of ≥50 years of age. A wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs, and chickens have been proven seropositive for SFTSV. Ticks, especially Haemaphysalis longicornis, are suspected to be the potential vector, which have a broad animal host range in the world. More studies are needed to elucidate the vector-animal-human ecological cycle, the pathogenic mechanisms in high level animal models and vaccine development.

  16. Hepatitis C virus genotype 6: Virology, epidemiology, genetic variation and clinical implication

    PubMed Central

    Thong, Vo Duy; Akkarathamrongsin, Srunthron; Poovorawan, Kittiyod; Tangkijvanich, Pisit; Poovorawan, Yong

    2014-01-01

    Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6. PMID:24659883

  17. Hepatitis C virus genotype 6: virology, epidemiology, genetic variation and clinical implication.

    PubMed

    Thong, Vo Duy; Akkarathamrongsin, Srunthron; Poovorawan, Kittiyod; Tangkijvanich, Pisit; Poovorawan, Yong

    2014-03-21

    Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.

  18. Updates and achievements in virology.

    PubMed

    Buonaguro, Franco M; Campadelli-Fiume, Gabriella; De Giuli Morghen, Carlo; Palù, Giorgio

    2010-07-01

    The 4th European Congress of Virology, hosted by the Italian Society for Virology, attracted approximately 1300 scientists from 46 countries worldwide. It also represented the first conference of the European Society for Virology, which was established in Campidoglio, Rome, Italy in 2009. The main goal of the meeting was to share research activities and results achieved in European virology units/institutes and to strengthen collaboration with colleagues from both western and developing countries. The worldwide representation of participants is a testament to the strength and attraction of European virology. The 5-day conference brought together the best of current virology; topics covered all three living domains (bacteria, archaea and eucarya), with special sessions on plant and veterinary virology as well as human virology, including two oral presentations on mimiviruses. The conference included five plenary sessions, 31 workshops, one hepatitis C virus roundtable, ten special workshops and three poster sessions, as well as 45 keynote lectures, 191 oral presentations and 845 abstracts. Furthermore, the Gesellschaft fur Virologie Loeffler-Frosch medal award was given to Peter Vogt for his long-standing career and achievements; the Gardner Lecture of the European Society for Clinical Virology was presented by Yoshihiro Kawaoka, and the Pioneer in Virology Lecture of the Italian Society for Virology was presented by Ulrich Koszinowski.

  19. Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

    PubMed Central

    Vernet, Marie-Astrid; Reynard, Stéphanie; Fizet, Alexandra; Schaeffer, Justine; Pannetier, Delphine; Rives, Max; Georges, Nadia; Garcia-Bonnet, Nathalie; Sylla, Aboubacar I.; Grovogui, Péma; Kerherve, Jean-Yves; Savio, Christophe; Savio-Coste, Sylvie; de Séverac, Marie-Laure; Linares, Sandrine; Harouna, Souley; Abdoul, Bing M’Lebing; Petitjean, Frederic; Samake, Nenefing; Kinda, Moumouni; Koundouno, Fara Roger; Mateo, Mathieu; Lecine, Patrick; Page, Audrey; Tchamdja, Tang Maleki; Schoenhals, Matthieu; Barbe, Solenne; Simon, Bernard; Tran-Minh, Tuan; L’Hériteau, François

    2017-01-01

    BACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P. falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of

  20. The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study

    PubMed Central

    2013-01-01

    Objective To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Design Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Methods Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the ‘intention-to-treat’ effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. Results A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Conclusions Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine. PMID:22546987

  1. Clinical, virological, immunological and pathological evaluation of four porcine circovirus type 2 vaccines.

    PubMed

    Seo, Hwi Won; Han, Kiwon; Park, Changhoon; Chae, Chanhee

    2014-04-01

    The objective of this study was to rigorously compare the efficacy of four porcine circovirus type 2 (PCV2) vaccines of varying antigen type and dose under experimental conditions based on well-defined clinical (average daily weight gain [ADWG]), virological (evidence of viraemia), immunological (presence of PCV2-specific neutralising antibodies [NA], interferon-γ-secreting cells [IFN-γ-SCs], and CD3(+) and CD4(+) T cell subsets), and pathological (lymphoid lesion and PCV2 antigen score) criteria. A total of 60, 3-week old piglets were assigned to six groups of 10/group and were vaccinated either with 1/4 commercially available one-dose vaccines or were not vaccinated. At 7 weeks of age, vaccinated and control animals were inoculated intranasally with 2 mL of PCV2b. All pigs were euthanased and subjected to post-mortem examination at 25 weeks of age. From 9 to 16 weeks of age, the ADWG of vaccinated animals was significantly higher than that of non-vaccinates. Significant (P<0.05) differences were observed between vaccinated and positive control groups in the quantity of log-transformed PCV2b DNA in the blood and nasal swabs, log-transformed NA titres, and PCV2-specific IFN-γ-SCs at 0, 7, 14, 21, and 42 days post challenge (dpc). The proportion of CD4(+) cells at 7 and 14 dpc was also significantly different between vaccinated and control pigs (P<0.05). The histopathological lesions and PCV2-antigen scores in the lymph nodes were significantly lower (P<0.05) in vaccinated animals. All four vaccines were found to be highly efficacious in controlling experimental PCV2 challenge based on this range of criteria.

  2. Clinical laboratory, virologic, and pathologic changes in hamsters experimentally infected with Pirital virus (Arenaviridae): a rodent model of Lassa fever.

    PubMed

    Sbrana, Elena; Mateo, Rosa I; Xiao, Shu-Yuan; Popov, Vsevolod L; Newman, Patrick C; Tesh, Robert B

    2006-06-01

    The clinical laboratory, virologic, and pathologic changes occurring in hamsters after infection with Pirital virus (Arenaviridae) are described. Pirital virus infection in the hamsters was characterized by high titered viremia, leukocytosis, coagulopathy, pulmonary hemorrhage and edema, hepatocellular and splenic necrosis, and marked elevation of serum transaminase levels. All of the animals died within 9 days. The clinical and histopathological findings in the Pirital virus-infected hamsters were very similar to those reported in severe human cases of Lassa fever, suggesting that this new animal model could serve as a low-cost and relatively safe alternative for studying the pathogenesis and therapy of Lassa fever.

  3. The trichodysplasia spinulosa-associated polyomavirus: virological background and clinical implications.

    PubMed

    Kazem, Siamaque; van der Meijden, Els; Feltkamp, Mariet C W

    2013-08-01

    Trichodysplasia spinulosa-associated polyomavirus (TSPyV) is a new species of the family Polyomaviridae that was discovered in 2010. TSPyV infects humans and is associated with the development of a rare disease called trichodysplasia spinulosa. Trichodysplasia spinulosa is a skin disease of severely immunocompromised hosts characterized by follicular distention and keratotic spine formation especially on the face. Electron microscopy, immunohistochemistry, and viral load measurements indicate an etiological role of active TSPyV infection in the development of this disease. This review will address virological and pathogenic properties of TSPyV, as well as epidemiologic, diagnostic, and therapeutic aspects of TSPyV infection.

  4. Virological and Immunological Status of the People Living with HIV/AIDS Undergoing ART Treatment in Nepal

    PubMed Central

    Dumre, Shyam Prakash

    2016-01-01

    Antiretroviral therapy (ART) has increased the life span of the people living with HIV (PLHIV), but their virological and immunological outcomes are not well documented in Nepal. The study was conducted at a tertiary care center including 826 HIV-1 seropositive individuals undergoing ART for at least six months. Plasma viral load (HIV-1 RNA) was detected by Real Time PCR and CD4+ T-lymphocyte (CD4+) counts were estimated by flow cytometry. The mean CD4+ count of patients was 501 (95% CI = 325–579) cells/cumm, but about 35% of patients had CD4+ T cell counts below 350 cells/cumm. With increasing age, average CD4+ count was found to be decreasing (p = 0.005). Of the total cases, 82 (9.92%) were found to have virological failure (viral load: >1000 copies/ml). Tenofovir/Lamivudine/Efavirenz (TDF/3TC/EFV), the frequently used ART regimen in Nepal, showed virological failure in 11.34% and immunological failure in 37.17% of patients. Virological failure rate was higher among children < 15 years (14.5%) (p = 0.03); however, no association was observed between ART outcomes and gender or route of transmission. The study suggests there are still some chances of virological and immunological failures despite the success of highly active ART (HAART). PMID:27547761

  5. Pediatric Virology

    PubMed Central

    Portnoy, Bernard

    1965-01-01

    Pediatric virology is not an isolàted discipline. Rather, the syndromes associated with viral infection are modified by the unique characteristics of infancy and childhood. Fortunately for the pediatrician, and certainly for children, viral infections in childhood are rarely fatal, and are almost never serious. Future efforts of the pediatrician and virologist should be directed toward increased fetal salvage as with rubella and the prevention of severe, viral lower respiratory tract disease. PMID:14298871

  6. Early Warning Indicators for First-Line Virologic Failure Independent of Adherence Measures in a South African Urban Clinic

    PubMed Central

    Wu, Baohua; Hampton, Jane; Ordóñez, Claudia E.; Johnson, Brent A.; Singh, Dinesh; John, Sally; Gordon, Michelle; Hare, Anna; Murphy, Richard; Nachega, Jean; Kuritzkes, Daniel R.; del Rio, Carlos; Sunpath, Henry

    2013-01-01

    Abstract We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after≥5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and controls (2:1) if they had VL≤1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF (p<0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures. PMID:24320011

  7. Physical virology

    NASA Astrophysics Data System (ADS)

    Roos, W. H.; Bruinsma, R.; Wuite, G. J. L.

    2010-10-01

    Viruses are nanosized, genome-filled protein containers with remarkable thermodynamic and mechanical properties. They form by spontaneous self-assembly inside the crowded, heterogeneous cytoplasm of infected cells. Self-assembly of viruses seems to obey the principles of thermodynamically reversible self-assembly but assembled shells (`capsids') strongly resist disassembly. Following assembly, some viral shells pass through a sequence of coordinated maturation steps that progressively strengthen the capsid. Nanoindentation measurements by atomic force microscopy enable tests of the strength of individual viral capsids. They show that concepts borrowed from macroscopic materials science are surprisingly relevant to viral shells. For example, viral shells exhibit `materials fatigue' and the theory of thin-shell elasticity can account - in part - for atomic-force-microscopy-measured force-deformation curves. Viral shells have effective Young's moduli ranging from that of polyethylene to that of plexiglas. Some of them can withstand internal osmotic pressures that are tens of atmospheres. Comparisons with thin-shell theory also shed light on nonlinear irreversible processes such as plastic deformation and failure. Finally, atomic force microscopy experiments can quantify the mechanical effects of genome encapsidation and capsid protein mutations on viral shells, providing virological insight and suggesting new biotechnological applications.

  8. Dipeptidyl Peptidase IV Inhibition Does Not Adversely Affect Immune or Virological Status in HIV Infected Men And Women: A Pilot Safety Study

    PubMed Central

    Goodwin, Scott R.; Reeds, Dominic N.; Royal, Michael; Struthers, Heidi; Laciny, Erin

    2013-01-01

    Context: People infected with HIV have a higher risk for developing insulin resistance, diabetes, and cardiovascular disease than the general population. Dipeptidyl peptidase IV (DPP4) inhibitors are glucose-lowering medications with pleiotropic actions that may particularly benefit people with HIV, but the immune and virological safety of DPP4 inhibition in HIV is unknown. Objective: DPP4 inhibition will not reduce CD4+ T lymphocyte number or increase HIV viremia in HIV-positive adults. Design: This was a randomized, placebo-controlled, double-blind safety trial of sitagliptin in HIV-positive adults. Setting: The study was conducted at an academic medical center. Participants: Twenty nondiabetic HIV-positive men and women (9.8 ± 5.5 years of known HIV) taking antiretroviral therapy and with stable immune (625 ± 134 CD4+ T cells per microliter) and virological (<48 copies HIV RNA per milliliter) status. Intervention: The intervention included sitagliptin (100 mg/d) vs matching placebo for up to 24 weeks. Main Outcome Measures: CD4+ T cell number and plasma HIV RNA were measured every 4 weeks; fasting serum regulated upon activation normal T-cell expressed and secreted (RANTES), stromal derived factor (SDF)-1α, Soluble TNF receptor II, and oral glucose tolerance were measured at baseline, week 8, and the end of study. ANOVA was used for between-group comparisons; P < .05 was considered significant. Results: Compared with placebo, sitagliptin did not reduce CD4+ T cell count, plasma HIV RNA remained less than 48 copies/mL, RANTES and soluble TNF receptor II concentrations did not increase. SDF1α concentrations declined (P < .0002) in the sitagliptin group. The oral glucose tolerance levels improved in the sitagliptin group at week 8. Conclusions: Despite lowering SDF1α levels, sitagliptin did not adversely affect immune or virological status, or increase immune activation, but did improve glycemia in healthy, nondiabetic HIV-positive adults. These safety data

  9. Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization, Epidemiological and Virological Aspects

    PubMed Central

    Calvet, Guilherme Amaral; Siqueira, André Machado; Wakimoto, Mayumi; de Sequeira, Patrícia Carvalho; Nobre, Aline; Quintana, Marcel de Souza Borges; de Mendonça, Marco Cesar Lima; Lupi, Otilia; de Souza, Rogerio Valls; Romero, Carolina; Zogbi, Heruza; Bressan, Clarisse da Silveira; Alves, Simone Sampaio; Lourenço-de-Oliveira, Ricardo; Nogueira, Rita Maria Ribeiro; Carvalho, Marilia Sá

    2016-01-01

    Background In 2015, Brazil was faced with the cocirculation of three arboviruses of major public health importance. The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between diseases caused by ZIKV, Dengue (DENV) and Chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. Methodology / Principal Findings The outpatient service for acute febrile illnesses in Fiocruz initiated a syndromic clinical observational study in 2007 to capture unusual presentations of DENV infections. In January 2015, an increase of cases with exanthematic disease was observed. Trained physicians evaluated the patients using a detailed case report form that included clinical assessment and laboratory investigations. The laboratory diagnostic algorithm included assays for detection of ZIKV, CHIKV and DENV. 364 suspected cases of Zika virus disease were identified based on clinical criteria between January and July 2015. Of these, 262 (71.9%) were tested and 119 (45.4%) were confirmed by the detection of ZIKV RNA. All of the samples with sequence information available clustered within the Asian genotype. Conclusions / Significance This is the first report of a ZIKV outbreak in the state of Rio de Janeiro, based on a large number of suspected (n = 364) and laboratory confirmed cases (n = 119). We were able to demonstrate that ZIKV was circulating in Rio de Janeiro as early as January 2015. The peak of the outbreak was documented in May/June 2015. More than half of the patients reported headache, arthralgia, myalgia, non-purulent conjunctivitis, and lower back pain, consistent with the case definition of suspected ZIKV disease issued by the Pan American Health Organization (PAHO). However, fever, when present, was low-intensity and short-termed. In our opinion, pruritus, the second most common clinical sign presented by the confirmed cases, should be added

  10. Virologic and Clinical Outcomes of Hepatitis B Virus Infection in HIV-HBV Coinfected Transplant Recipients

    PubMed Central

    Coffin, C.S.; Stock, P.G.; Dove, L.M.; Berg, C.L.; Nissen, N.N.; Curry, M.P.; Ragni, M.; Regenstein, F.G.; Sherman, K.E.; Roland, M.E.; Terrault, N.A.

    2010-01-01

    Liver transplantation (LT) is the treatment of choice for endstage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-HBV coinfected patients transplanted between 2001–2007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/ml, range 9–789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% vs. 85% in HBV mono- vs coinfected patients (p=0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low level HBV DNA is detectable in ~50% of recipients. PMID:20346065

  11. Human rhinovirus infections in hospitalized children: clinical, epidemiological and virological features.

    PubMed

    Tran, D N; Trinh, Q D; Pham, N T K; Pham, T M H; Ha, M T; Nguyen, T Q N; Okitsu, S; Shimizu, H; Hayakawa, S; Mizuguchi, M; Ushijima, H

    2016-01-01

    Molecular epidemiology and clinical impact of human rhinovirus (HRV) are not well documented in tropical regions. This study compared the clinical characteristics of HRV to other common viral infections and investigated the molecular epidemiology of HRV in hospitalized children with acute respiratory infections (ARIs) in Vietnam. From April 2010 to May 2011, 1082 nasopharyngeal swabs were screened for respiratory viruses by PCR. VP4/VP2 sequences of HRV were further characterized. HRV was the most commonly detected virus (30%), in which 70% were diagnosed as either pneumonia or bronchiolitis. Children with single HRV infections presented with significantly higher rate of hypoxia than those infected with respiratory syncytial virus or parainfluenza virus (PIV)-3 (12·4% vs. 3·8% and 0%, respectively, P < 0·05), higher rate of chest retraction than PIV-1 (57·3% vs. 34·5%, P = 0·028), higher rate of wheezing than influenza A (63·2% vs. 42·3%, P = 0·038). HRV-C did not differ to HRV-A clinically. The genetic diversity and changes of types over time were observed and may explain the year-round circulation of HRV. One novel HRV-A type was discovered which circulated locally for several years. In conclusion, HRV showed high genetic diversity and was associated with significant morbidity and severe ARIs in hospitalized children.

  12. Phylogenetic, virological, and clinical characteristics of genotype C hepatitis B virus with TCC at codon 15 of the precore region.

    PubMed

    Chan, Henry Lik-Yuen; Tse, Chi-Hang; Ng, Eddie Yuen-Tok; Leung, Kwong-Sak; Lee, Kin-Hong; Tsui, Stephen Kwok-Wing; Sung, Joseph Jao-Yiu

    2006-03-01

    Hepatitis B virus (HBV) with T-1856 of the precore region is always associated with C-1858 (i.e., TCC at nucleotides 1856 to 1858), and it is reported only in genotype C HBV isolates. We aimed to investigate the phylogenetic, virological, and clinical characteristics of HBV isolates bearing TCC at nucleotides 1856 to 1858. We have previously reported on the presence of two major subgroups in genotype C HBV, namely, HBV genotype Cs (Southeast Asia) and HBV genotype Ce (Far East). We have designed a novel 5' nuclease technology based on the nucleotide polymorphism (C or A) at nucleotide 2733 to differentiate the two genotype C HBV subgroups. The mutations at the basal core promoter and precore regions were analyzed by direct sequencing. Among 214 genotype C HBV-infected patients, 31% had TCC, 37% had CCC, 3% had CTC, and 29% had CCT at nucleotides 1856 to 1858. All except one HBV strain with TCC at nucleotides 1856 to 1858 belonged to subgroup Cs, which has been reported only in Hong Kong; Guangzhou, China; and Vietnam. HBV with TCC at nucleotides 1856 to 1858 was associated with the G1898A mutation (64%). Patients infected with HBV harboring TCC had more liver cirrhosis than those infected with HBV harboring CCC (18% versus 5%; P = 0.008), and more of the patients infected with HBV harboring TCC were positive for HBeAg (58% versus 36%; P = 0.01) and had higher median alanine aminotransferase levels (65 IU/liter versus 49 IU/liter; P = 0.006); but similar proportions of patients infected with HBV harboring TCC and those infected with HBV harboring CCT had liver cirrhosis (18% versus 13%; P = 0.43). In summary, we report that HBV with TCC at nucleotides 1856 to 1858 of the precore region might represent a specific HBV strain associated with more aggressive liver disease than other genotype C HBV strains.

  13. The human polyomaviruses KI and WU: virological background and clinical implications.

    PubMed

    Babakir-Mina, Muhammed; Ciccozzi, Massimo; Perno, Carlo Federico; Ciotti, Marco

    2013-08-01

    In 2007, two novel polyomaviruses KI and WU were uncovered in the respiratory secretions of children with acute respiratory symptoms. Seroepidemiological studies showed that infection by these viruses is widespread in the human population. Following these findings, different biological specimens and body compartments have been screened by real-time PCR in the attempt to establish a pathogenetic role for KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) in human diseases. Although both viruses have been found mainly in respiratory tract samples of immunocompromised patients, a clear causative link with the respiratory disease has not been established. Indeed, the lack of specific clinical or radiological findings, the frequent co-detection with other respiratory pathogens, the detection in subjects without signs or symptoms of respiratory disease, and the variability of the viral loads measured did not allow drawing a definitive conclusion. Prospective studies carried out on a large sample size including both immunocompromised and immunocompetent patients with and without respiratory symptoms are needed. Standardized quantitative real-time PCR methods, definition of a clear clinical cutoff value, timing in the collection of respiratory samples, are also crucial to understand the pathogenic role, if any, of KIPyV and WUPyV in human pathology.

  14. The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere.

    PubMed

    Murray, K O; Walker, C; Gould, E

    2011-06-01

    West Nile virus (WNV) is now endemic in the USA. After the widespread surge of virus activity across the USA, research has flourished, and our knowledge base has significantly expanded over the past 10 years since WNV was first recognized in New York City. This article provides a review of the virology of WNV, history, epidemiology, clinical features, pathology of infection, the innate and adaptive immune response, host risk factors for developing severe disease, clinical sequelae following severe disease, chronic infection, and the future of prevention.

  15. Virological Surveillance of Influenza A Subtypes Isolated in 2014 from Clinical Outbreaks in Canadian Swine

    PubMed Central

    Grgić, Helena; Gallant, Jackie; Poljak, Zvonimir

    2017-01-01

    Influenza A viruses (IAVs) are respiratory pathogens associated with an acute respiratory disease that occurs year-round in swine production. It is currently one of the most important pathogens in swine populations, with the potential to infect other host species including humans. Ongoing research indicates that the three major subtypes of IAV—H1N1, H1N2, and H3N2—continue to expand in their genetic and antigenic diversity. In this study, we conducted a comprehensive genomic analysis of 16 IAVs isolated from different clinical outbreaks in Alberta, Manitoba, Ontario, and Saskatchewan in 2014. We also examined the genetic basis for probable antigenic differences among sequenced viruses. On the basis of phylogenetic analysis, all 13 Canadian H3N2 viruses belonged to cluster IV, eight H3N2 viruses were part of the IV-C cluster, and one virus belonged to the IV-B and one to the IV-D cluster. Based on standards used in this study, three H3N2 viruses could not be clearly classified into any currently established group within cluster IV (A to F). Three H1N2 viruses were part of the H1α cluster. PMID:28335552

  16. Clinical features and preliminary studies of virological correlates of neurocognitive impairment among HIV-infected individuals in Nigeria.

    PubMed

    Royal, Walter; Cherner, Mariana; Carr, Jean; Habib, Abdulrazaq G; Akomolafe, Abimbola; Abimiku, Alashl'e; Charurat, Manhattan; Farley, John; Oluyemisi, Akinwande; Mamadu, Ibrahim; Johnson, Joyce; Ellis, Ronald; McCutchan, J Allen; McCutchen, J Allen; Grant, Igor; Blattner, William A

    2012-06-01

    In Nigeria, the incidence and prevalence of human immunodeficiency virus (HIV)-related neurocognitive impairment (NCI) are unknown and there currently exists little information related to the viral correlates rates of NCI. Therefore, studies were performed to examine the potential utility of applying an established neuropsychological (NP) screening battery and detailed NP testing to detect NCI and correlations with functional impairment and the presence of specific viral signatures among infected subjects. A total of 60 HIV-1 seropositive antiretroviral-naive individuals and 56 seronegative control subjects were administered the International HIV Dementia Scale (IHDS) and assessed for functional impairment using the Karnofsky performance status scale. Fifteen HIV-infected patients and 11 controls were also administered a detailed NP battery. Blood samples from eight infected subjects, three with evidence of NCI, were obtained for molecular analysis of HIV-1 strain. Unadjusted scores on the IHDS showed that, using a recommended total score cutoff of 10, 28.8% of the HIV-1 seropositive and 16.0% of seropositive individuals scored abnormally. Results from testing using the full NP battery showed that, overall, the HIV seropositive group performed worse than the seronegative group, with effect sizes spanning from small (0.25 on the trail making test A) to large (0.82 on action fluency), and an average effect size across the battery of 0.45, which approaches that which has been recorded in other international settings. Sequencing of partial pol amplicons from viral isolates revealed that two of three patients with NCI were infected with subtype G virus and 1 with the circulating recombinant form (CRF)02_AG; all four individuals without NCI were infected with CRF_02AG. These studies demonstrate the utility of the IHDS in identifying cognitive impairment among HIV infected individuals in Nigeria. Future studies aimed at examining the burden of NCI among the population of

  17. Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects.

    PubMed

    Gessain, A; Mahieux, R

    2012-03-01

    In 1980, Human T cell leukemia/lymphoma virus type 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered. HTLV-1 belongs to the Retroviridae family, the Orthoretrovirinae subfamily and to the deltaretrovirus genus. HTLV-1 preferentially infects CD4(+) lymphoid cells in vivo. Three molecules have been identified for binding and/or entry of HTLV-1: heparan sulfate proteoglycans, neuropilin-1, and glucose transporter 1. An efficient transfer of the virus from an infected cell to a target cell can occur through the formation of a viral synapse and/or by virofilm structure. As for all retroviruses, HTLV-1 genome possesses three major ORFs (gag, pol and env) encoding the structural and enzymatic proteins. HTLV-1 encodes also some regulatory and auxillary proteins including the tax protein with transforming activities and the HBZ protein which plays a role in the proliferation and maintenance of the leukemic cells. HTLV-1 is present throughout the world with clusters of high endemicity including mainly Southern Japan, the Caribbean region, areas in South America and in intertropical Africa. The worldwide HTLV-1 infected population is estimated to be around 10-20 million. HTLV-1 has three modes of transmission: (1): mother to child, mainly linked to prolonged breast-feeding; (2): sexual, mainly occurring from male to female and (3): contaminated blood products. HTLV-1 possesses a remarkable genetic stability. HTLV-1 is the etiological agent of mainly two severe diseases: a malignant T CD4(+) cell lymphoproliferation, of very poor prognosis, named Adult T cell Leukemia/Lymphoma (ATLL), and a chronic neuro-myelopathy named Tropical spastic paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). The lifetime risk among HTLV-1 carriers is estimated to be around 0.25 to 3%. TSP/HAM mainly occurs in adults, with a mean age at onset of 40-50 years and it is more common in women than in men. Blood transfusion is a major risk factor for TSP/HAM development. Clinically

  18. Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014

    PubMed Central

    Kautz, Tiffany F.; Auguste, Albert J.; Erasmus, Jesse H.; Kiaty-Figueroa, Liddy; Gerhardt, Renessa; Lin, David; Hari, Kumar L.; Jain, Ravi; Ruiz, Nicolas; Muruato, Antonio E.; Silfa, Jael; Bido, Franklin

    2016-01-01

    Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection. To obtain a more accurate representation of chikungunya fever (CHIKF) clinical signs and symptoms, and confirm the viral lineage responsible for the DR CHIKV outbreak, we tested 194 serum samples for CHIKV RNA and IgM antibodies from patients seen in a hospital in La Romana, DR using quantitative RT-PCR and IgM capture ELISA, and performed retrospective chart reviews. RNA and antibodies were detected in 49% and 24.7% of participants, respectively. Sequencing revealed that the CHIKV strain responsible for the La Romana outbreak belonged to the Asian/American lineage and grouped phylogenetically with recent Mexican and Trinidadian isolates. Our study shows that, while CHIKV-infected individuals were infrequently diagnosed with CHIKF, uninfected patients were never falsely diagnosed with CHIKF. Participants testing positive for CHIKV RNA were more likely to present with arthralgia, although it was reported in just 20.0% of CHIKF+ individuals. High percentages of respiratory (19.6%) signs and symptoms, especially among children, were noted, though it was not possible to determine whether individuals infected with CHIKV were co-infected with other pathogens. These results suggest that CHIKV may have been underdiagnosed during this outbreak, and that CHIKF should be included in differential diagnoses of diverse undifferentiated febrile syndromes in the

  19. Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014.

    PubMed

    Langsjoen, Rose M; Rubinstein, Rebecca J; Kautz, Tiffany F; Auguste, Albert J; Erasmus, Jesse H; Kiaty-Figueroa, Liddy; Gerhardt, Renessa; Lin, David; Hari, Kumar L; Jain, Ravi; Ruiz, Nicolas; Muruato, Antonio E; Silfa, Jael; Bido, Franklin; Dacso, Matthew; Weaver, Scott C

    2016-12-01

    Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection. To obtain a more accurate representation of chikungunya fever (CHIKF) clinical signs and symptoms, and confirm the viral lineage responsible for the DR CHIKV outbreak, we tested 194 serum samples for CHIKV RNA and IgM antibodies from patients seen in a hospital in La Romana, DR using quantitative RT-PCR and IgM capture ELISA, and performed retrospective chart reviews. RNA and antibodies were detected in 49% and 24.7% of participants, respectively. Sequencing revealed that the CHIKV strain responsible for the La Romana outbreak belonged to the Asian/American lineage and grouped phylogenetically with recent Mexican and Trinidadian isolates. Our study shows that, while CHIKV-infected individuals were infrequently diagnosed with CHIKF, uninfected patients were never falsely diagnosed with CHIKF. Participants testing positive for CHIKV RNA were more likely to present with arthralgia, although it was reported in just 20.0% of CHIKF+ individuals. High percentages of respiratory (19.6%) signs and symptoms, especially among children, were noted, though it was not possible to determine whether individuals infected with CHIKV were co-infected with other pathogens. These results suggest that CHIKV may have been underdiagnosed during this outbreak, and that CHIKF should be included in differential diagnoses of diverse undifferentiated febrile syndromes in the

  20. Non-linear dynamics models characterizing long-term virological data from AIDS clinical trials.

    PubMed

    Verotta, Davide; Schaedeli, Franziska

    2002-04-01

    illustration we demonstrate an application of the models using real AIDS clinical trial data involving patients treated with a combination of anti-retroviral agents using a model which incorporates compliance data.

  1. Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial

    PubMed Central

    Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E.; Wallis, Carol L.; Tripathy, Srikanth; Morgado, Mariza G.; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W.; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G.; Lama, Javier R.; Rassool, Mohammed; Santos, Breno R.; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B.; Eshleman, Susan H.

    2015-01-01

    Background. Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Methods. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance–failure association. Results. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex–treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04–2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22–.98). Conclusions. In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. Clinical Trials

  2. Absence of Effect of Menopause Status at Initiation of First-Line Antiretroviral Therapy on Immunologic or Virologic Responses: A Cohort Study from Rio de Janeiro, Brazil

    PubMed Central

    Calvet, Guilherme Amaral; Velasque, Luciane; Luz, Paula Mendes; Cardoso, Sandra Wagner; Derrico, Monica; Moreira, Ronaldo Ismério; de Andrade, Angela Cristina Vasconcelos; Cytryn, Andrea; Pires, Elaine; Veloso, Valdiléa Gonçalves; Grinsztejn, Beatriz; Friedman, Ruth Khalili

    2014-01-01

    Objective To compare the effectiveness of first-line combination antiretroviral therapy (cART) between premenopausal and postmenopausal women. Methods ART-naïve women initiating cART between January 2000/June 2010 at the Instituto de Pesquisa Clínica Evandro Chagas Cohort were studied. Women were defined as postmenopausal after 12 consecutive months of amenorrhea. CD4 cell counts and HIV-1 RNA viral load (VL) measurements were compared between pre- and postmenopausal at 6, 12 and 24 months after cART initiation. Women who modified/discontinued a drug class or died due to an AIDS defining illness were classified as ART-failures. Variables were compared using Wilcoxon test, χ2 or Fisher’s exact test. The odds of cART effectiveness (VL<400 copies/mL and/or no need to change cART) were compared using logistic regression. Linear model was used to access relationship between CD4 change and menopause. Results Among 383 women, 328 (85%) were premenopausal and 55 (15%) postmenopausal. Median pre cART CD4 counts were 231 and 208 cells/mm3 (p = 0.14) in pre- and postmenopausal women, respectively. No difference in the median pre cART VL was found (both 4.8 copies/mL). Median CD4 changes were similar at 6 and 12 months. At 24 months after cART initiation, CD4 changes among postmenopausal women were significantly lower among premenopausal women (p = 0.01). When the analysis was restricted to women with VL<400 copies/mL, no statistical difference was observed. Overall, 63.7% achieved cART effectiveness at 24 months without differences between groups at 6, 12 and 24 months. Conclusion Menopause status at the time of first-line cART initiation does not impact CD4 cell changes at 24 months among women with a virologic response. No relationship between menopause status and virologic response was observed. PMID:24586673

  3. BCSH/BSBMT/UK clinical virology network guideline: diagnosis and management of common respiratory viral infections in patients undergoing treatment for haematological malignancies or stem cell transplantation.

    PubMed

    Dignan, Fiona L; Clark, Andrew; Aitken, Celia; Gilleece, Maria; Jayakar, Vishal; Krishnamurthy, Pramila; Pagliuca, Antonio; Potter, Michael N; Shaw, Bronwen; Skinner, Roderick; Turner, Andrew; Wynn, Robert F; Coyle, Peter

    2016-05-01

    A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology, the British Society for Bone Marrow Transplantation and the UK Clinical Virology Network has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with haematological malignancies or those undergoing haematopoietic stem cell transplantation. This guideline includes recommendations for the diagnosis, prevention and treatment of respiratory viral infections in adults and children. The suggestions and recommendations are primarily intended for physicians practising in the United Kingdom.

  4. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial

    PubMed Central

    2013-01-01

    . No important differences in tolerability were found. Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital. Registration Clinical Trials NCT00298233 PMID:23723457

  5. Occult HBV infection in HCC and cirrhotic tissue of HBsAg-negative patients: a virological and clinical study

    PubMed Central

    Coppola, Nicola; Onorato, Lorenzo; Iodice, Valentina; Starace, Mario; Minichini, Carmine; Farella, Nunzia; Liorre, Giulia; Filippini, Pietro; Sagnelli, Evangelista; de Stefano, Giorgio

    2016-01-01

    Aim To evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC. Methods HBV DNA was sought and sequenced in plasma, HCC tissue and non-HCC liver tissue by PCRs using primers for HBV core, surface and x regions. OBI was identified by the presence of HBV DNA in at least two different PCRs. Results OBI was detected in HCC tissue of 13 (20%) patients and in non-HCC liver tissue of 3 of these 13. OBI was detected in HCC tissue of 54.5% of 11 anti-HBs- negative/anti-HBc-positive patients, in 29.4% of 17 anti-HBs/anti-HBc-positive and in 5% of 40 anti-HBs/anti-HBc-negative (p < 0.0005). The 13 patients with OBI in HCC tissue more frequently than the 55 without showed Child-B or -C cirrhosis (53.9% vs. 5.5%, p < 0.0001) and BCLC-B or -C stages (46.1% vs. 1.8%, p < 0.0001). The pre-S1, pre-S2 and S region sequences in HCC tissue showed amino acid (AA) substitutions (F19L, P24L, S59F, T131I, Q129H) and deletions (in positions 4,8, 17 and 86) in the S region, AA substitutions (T40S, P124K, L54P, G76A, N222T and I273L) in pre-S1 region and AA substitutions in pre-S2 region (P41H and P66L). In the 3 patients showing OBI also in non-HCC liver tissue the S, pre-S1 and pre-S2 sequencing displayed patterns of mutations different. Conclusions The study showed a significant correlation between OBI and the severity of liver damage, several patterns of mutations in the S, pre-S1 and pre-S2 regions in HCC tissue, some at their first description. PMID:27486882

  6. Twenty-four mini-pool HCV RNA screening in a routine clinical virology laboratory setting: a six-year prospective study.

    PubMed

    Seme, Katja; Mocilnik, Tina; Poljak, Mario

    2011-01-01

    The usefulness of combined anti-HCV and 24 mini-pool HCV RNA screening strategy was re-evaluated after a six-year continuous routine use in a clinical virology laboratory, at which more than half of newly diagnosed hepatitis C patients are intravenous drug users. Pools of 24 samples were prepared from 20,448 anti-HCV negative serum samples and tested using an automated commercial PCR assay with a lower limit of detection of 50 IU/ml. After detection of anti-HCV negative/HCV RNA positive patients, responsible physicians provided follow-up samples. Thirty-eight (0.19%) anti-HCV negative/HCV RNA positive samples from 30 patients (28 intravenous drug users) were detected. Follow-up samples were available for 27/30 patients. Twenty, six and one patient seroconverted in the second, third and fourth available samples, respectively. The interval between the first HCV RNA positive and the first available anti-HCV positive sample was 17-517 days. The costs of detecting a single anti-HCV negative/HCV RNA positive patient were 1227 Euros. Combined anti-HCV and 24 mini-pool HCV RNA screening is a useful and cost effective strategy, not only in blood-transfusion settings but also in a routine clinical virology laboratory, at which a significant proportion of the tested population belongs to a high-risk population.

  7. Clinical and Virological Efficacy of Etravirine Plus Two Active Nucleos(t)ide Analogs in an Heterogeneous HIV-Infected Population

    PubMed Central

    López-Cortés, Luis F.; Viciana, Pompeyo; Girón-González, José A.; Romero-Palacios, Alberto; Márquez-Solero, Manuel; Martinez-Perez, Maria A.; López-Ruz, Miguel A.; de la Torre-Lima, Javier; Téllez-Pérez, Francisco; Delgado-Fernández, Marcial; Garcia-Lázaro, Milagros; Lozano, Fernando; Mohamed-Balghata, Mohamed O.

    2014-01-01

    Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9–92.1%) and 77.4% (CI95, 65.0–89.7%), respectively; the rates reached 97.2% (CI95, 95.1–99.3%) and 90.5% (CI95, 81.7–99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1–2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. Trial registration ClinicalTrials.gov NCT01437241 PMID:24836963

  8. Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens

    PubMed Central

    López-Cortés, Luis F.; Castaño, Manuel A.; López-Ruz, Miguel A.; Rios-Villegas, María J.; Hernández-Quero, José; Merino, Dolores; Jiménez-Aguilar, Patricia; Marquez-Solero, Manuel; Terrón-Pernía, Alberto; Tellez-Pérez, Francisco; Viciana, Pompeyo; Orihuela-Cañadas, Francisco; Palacios-Baena, Zaira; Vinuesa-Garcia, David; Fajardo-Pico, Jose M.; Romero-Palacios, Alberto; Ojeda-Burgos, Guillermo; Pasquau-Liaño, Juan

    2016-01-01

    Background and Objective Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI) -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens. Methods This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure). Results A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on-treatment analysis) at week 96 were 79.3% (CI95, 76.8−81.8) and 91.5% (CI95, 89.6–93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations. Conclusion Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for

  9. Clinical course of chronic hepatitis B patients receiving nucleos(t)ide analogues after virological breakthrough during monotherapy with lamivudine.

    PubMed

    De Francesco, Maria Antonia; Gargiulo, Franco; Spinetti, Angiola; Zaltron, Serena; Giagulli, Cinzia; Caccuri, Francesca; Castelli, Francesco; Caruso, Arnaldo

    2015-01-01

    Little is known about the optimal management of patients with chronic hepatitis B (CHB) who develop drug resistance. The aim of this study was to investigate the effectiveness of different drug regimens in chronically HBV-infected patients. HBV viral load was determined using a bDNA assay and the substitutions in HBV-DNA were studied by polymerase sequencing test. The study involved 38 patients who experienced a therapeutic failure to lamivudine (LAM). The sequential treatments used were: LAM + adefovir (ADV), LAM + tenofovir (TDF), entecavir (ETV) monotherapy, ADV monotherapy and TDF monotherapy. Similar activity against HBV replication was observed with all drug regimens. Of the patients treated with LAM, 44% developed resistance mutations. The rt M204I mutation was observed more frequently. Sequential ADV add-on LAM and TDF therapy induced the appearance of resistance in 3/18 (16.6%) and in 1/8 (5.5%) treated patients, respectively. Genotype D was the most prevalent (78.9%), followed by genotype A (13%), genotype E (5.2%) and genotype C (2.6%). Our study showed that baseline serum HBV DNA is an important predictor of virologic response and that virologic breakthrough is significantly associated with the insurgence of genotypic resistance.

  10. Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses.

    PubMed

    Rojas Sánchez, P; de Mulder, M; Fernandez-Cooke, E; Prieto, L; Rojo, P; Jiménez de Ory, S; José Mellado, M; Navarro, M; Tomas Ramos, J; Holguín, Á

    2015-06-01

    Drug resistance mutations compromise the success of antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected children. We report the virologic and clinical follow-up of the Madrid cohort of perinatally HIV-infected children and adolescents after the selection of triple-class drug-resistant mutations (TC-DRM). We identified patients from the cohort carrying HIV-1 variants with TC-DRM to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors according to IAS-USA-2013. We recovered pol sequences or resistance profiles from 2000 to 2011 and clinical-immunologic-virologic data from the moment of TC-DRM detection until December 2013. Viruses harbouring TC-DRM were observed in 48 (9%) of the 534 children and adolescents from 2000 to 2011, rising to 24.4% among those 197 with resistance data. Among them, 95.8% were diagnosed before 2003, 91.7% were Spaniards, 89.6% carried HIV-1-subtype B and 75% received mono/dual therapy as first regimen. The most common TC-DRM present in ≥50% of them were D67NME, T215FVY, M41L and K103N (retrotranscriptase) and L90M (protease). The susceptibility to darunavir, tipranavir, etravirine and rilpivirine was 67.7%, 43.7%, 33.3% and 33.3%, respectively, and all reported high resistance to didanosine, abacavir and nelfinavir. Despite the presence of HIV-1 resistance mutations to the three main antiretroviral families in our paediatric cohort, some drugs maintained their susceptibility, mainly the new protease inhibitors (tipranavir and darunavir) and nonnucleoside reverse transcriptase inhibitors (etravirine and rilpivirine). These data will help to improve the clinical management of HIV-infected children with triple resistance in Spain.

  11. Clinical Outcome of HIV-Infected Patients with Sustained Virologic Response to Antiretroviral Therapy: Long-Term Follow-Up of a Multicenter Cohort

    PubMed Central

    Gutierrez, Félix; Padilla, Sergio; Masiá, Mar; Iribarren, José A.; Moreno, Santiago; Viciana, Pompeyo; Muñoz, Leopoldo; Sirvent, José L. Gómez; Vidal, Francesc; López-Aldeguer, José; Blanco, José R.; Leal, Manuel; Rodríguez-Arenas, María Angeles; Hoyos, Santiago Perez

    2006-01-01

    Background Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. Methods Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. Results Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9%) patients died (mortality rate 0.86 per 100 person-years), and 40 (5.3%) died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68–10.83]; P = .002), and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02–1.09; P = .001). Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. Conclusions Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected. PMID:17183720

  12. CD127 Expression, Exhaustion Status and Antigen Specific Proliferation Predict Sustained Virologic Response to IFN in HCV/HIV Co-Infected Individuals

    PubMed Central

    Kared, Hassen; Saeed, Sahar; Klein, Marina B.; Shoukry, Naglaa H.

    2014-01-01

    Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-α) remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-α was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-α on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-α therapy with different outcomes including IFN-α non-responders (NR) (n = 9) and patients who achieved sustained virologic response (SVR) (n = 19). We examined the expression of activation (CD38, HLA-DR), functional (CD127) and exhaustion markers (PD1, Tim-3, CD160 and CD244) on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127+ CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-α therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN–based therapies in co-infected individuals. PMID:25007250

  13. RNA and DNA bacteriophages as molecular diagnosis controls in clinical virology: a comprehensive study of more than 45,000 routine PCR tests.

    PubMed

    Ninove, Laetitia; Nougairede, Antoine; Gazin, Celine; Thirion, Laurence; Delogu, Ilenia; Zandotti, Christine; Charrel, Remi N; De Lamballerie, Xavier

    2011-02-09

    Real-time PCR techniques are now commonly used for the detection of viral genomes in various human specimens and require for validation both external and internal controls (ECs and ICs). In particular, ICs added to clinical samples are necessary to monitor the extraction, reverse transcription, and amplification steps in order to detect false-negative results resulting from PCR-inhibition or errors in the technical procedure. Here, we performed a large scale evaluation of the use of bacteriophages as ICs in routine molecular diagnosis. This allowed to propose simple standardized procedures (i) to design specific ECs for both DNA and RNA viruses and (ii) to use T4 (DNA) or MS2 (RNA) phages as ICs in routine diagnosis. Various technical formats for using phages as ICs were optimised and validated. Subsequently, T4 and MS2 ICs were evaluated in routine real-time PCR or RT-PCR virological diagnostic tests, using a series of 8,950 clinical samples (representing 36 distinct specimen types) sent to our laboratory for the detection of a variety of DNA and RNA viruses. The frequency of inefficient detection of ICs was analyzed according to the nature of the sample. Inhibitors of enzymatic reactions were detected at high frequency in specific sample types such as heparinized blood and bone marrow (>70%), broncho-alveolar liquid (41%) and stools (36%). The use of T4 and MS2 phages as ICs proved to be cost-effective, flexible and adaptable to various technical procedures of real-time PCR detection in virology. It represents a valuable strategy for enhancing the quality of routine molecular diagnosis in laboratories that use in-house designed diagnostic systems, which can conveniently be associated to the use of specific synthetic ECs. The high rate of inhibitors observed in a variety of specimen types should stimulate the elaboration of improved technical protocols for the extraction and amplification of nucleic acids.

  14. High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo

    PubMed Central

    Salou, Mounerou; Dagnra, Anoumou Y; Butel, Christelle; Vidal, Nicole; Serrano, Laetitia; Takassi, Elom; Konou, Abla A; Houndenou, Spero; Dapam, Nina; Singo-Tokofaï, Assetina; Pitche, Palokinam; Atakouma, Yao; Prince-David, Mireille; Delaporte, Eric; Peeters, Martine

    2016-01-01

    their current ART regimen. Conclusions Our study provided important information on virological outcome on lifelong ART in perinatally HIV-1-infected children and adolescents who were still on ART and continued to attend antiretroviral (ARV) clinics for follow-up visits. Actual conditions for scaling up and monitoring lifelong ART in children in resource-limited countries can have dramatic long-term outcomes and illustrate that paediatric ART receives inadequate attention. PMID:27125320

  15. Clinical status of benzoporphyrin derivative

    NASA Astrophysics Data System (ADS)

    Levy, Julia G.; Chan, Agnes H.; Strong, H. Andrew

    1996-01-01

    Benzoporphyrin derivative monoacid ring A (BPD) is currently in Phase II clinical trials for the treatment of cutaneous malignancies (basal cell carcinoma and cutaneous metastases) and psoriasis. Results to date suggest that this photosensitizer has potential in both of these areas. Recently, a clinical trial with BPD was initiated for the treatment of age related macular degeneration, a neovascular condition in the eye which leads to blindness. BPD is a lipophilic photosensitizer which is rapidly taken up by activated cells and the vascular endothelium of neovasculature. The PDT effects seen with BPD appear to be a combination of vascular occlusion and direct killing of target cells. Since many diseases involve either activated cells and/or neovasculature, PDT with photosensitizer with characteristics like those of BPD, has applications far wider than oncology. A new area of interest involving photosensitizers is that of immune modulation. A number of photosensitizers have been shown to effect immune modulation in animal models of immune dysfunction including autoimmunity (rheumatoid arthritis, lupus), cutaneous hypersensitivity and allografts. BPD and PHOTOFRINR have both been shown to be effective in ameliorating arthritic symptoms in a number of animal models. The mechanisms by which immune modulation is affected in these studies still remains to be resolved.

  16. Clinical Model for Predicting Hepatocellular Carcinomas in Patients with Post-Sustained Virologic Responses of Chronic Hepatitis C: A Case Control Study

    PubMed Central

    Zeng, Qing-Lei; Li, Bing; Zhang, Xue-Xiu; Chen, Yan; Fu, Yan-Ling; Lv, Jun; Liu, Yan-Min; Yu, Zu-Jiang

    2016-01-01

    Background/Aims No clinical model exists to predict the occurrence of hepatocellular carcinoma in sustained virologic response-achieving (HCC after SVR) patients with chronic hepatitis C (CHC). Methods We performed a case-control study using a clinical database to research the risk factors for HCC after SVR. A predictive model based on risk factors was established, and the area under the receiver operating characteristic curve (AUC) was calculated. Results In the multivariate model, an initial diagnosis of compensated cirrhosis and post-SVR albumin reductions of 1 g/L were associated with 21.7-fold (95% CI, 4.2 to 112.3; p<0.001) and 1.3-fold (95% CI, 1.1 to 1.7; p=0.004) increases in the risk of HCC after SVR, respectively. A predictive model based on an initial diagnosis of compensated cirrhosis (yes, +1; no, 0) and post-SVR albumin ≤36.0 g/L (yes, +1; not, 0) predicted the occurrence of HCC after SVR with a cutoff value of >0, an AUC of 0.880, a sensitivity of 0.833, a specificity of 0.896, and a negative predictive value of 0.956. Conclusions An initial diagnosis of compensated cirrhosis combined with a post-SVR albumin value of ≤36.0 g/L predicts the occurrence of HCC after SVR in patients with CHC. PMID:27257023

  17. Epidemiological, Clinical and Virological Characteristics of Influenza B Virus from Patients at the Hospital Tertiary Care Units in Bangkok during 2011-2014.

    PubMed

    Horthongkham, Navin; Athipanyasilp, Niracha; Pattama, Archiraya; Kaewnapan, Bualan; Sornprasert, Suthatta; Srisurapanont, Surangrat; Kantakamalakul, Wannee; Amaranond, Palanee; Sutthent, Ruengpung

    2016-01-01

    Influenza B virus, which causes acute respiratory infections, has increased in prevalence in recent years. Based on the nucleotide sequence of the hemagglutinin (HA) gene, influenza B virus can be divided into two lineages, Victoria and Yamagata, that co-circulate during the influenza season. However, analysis of the potential association between the clinical and virological characteristic and the lineage of influenza B viruses isolated in Thailand was lacking. To investigate influenza B virus genetically and determine its neuraminidase (NA) inhibitor susceptibility phenotype, a total of 6920 nasopharyngeal-wash samples were collected from patients with influenza-like illness between the years 2011 and 2014 and were screened for influenza B virus by real-time PCR. Of these samples, 3.1% (216/6920) were confirmed to contain influenza B viruses, and 110 of these influenza viruses were randomly selected for nucleotide sequence analysis of the HA and NA genes. Phylogenetic analysis of the HA sequences showed clustering into various clades: Yamagata clade 3 (11/110, 10%), Yamagata clade 2 (71/110, 64.5%), and Victoria clade 1 (28/110, 25.5%). The analysis of clinical characteristic demonstrated that the Victoria lineage was significantly associated with the duration of hospitalization, number of deceased cases, pneumonia, secondary bacterial infection and underlying disease. When combined with phylogenetic analysis of the NA sequences, four samples showed viruses with reassortant sequences between the Victoria and Yamagata lineages. Statistical analysis of the clinical outcomes and demographic data for the reassortant strains did not differ from those of the other strains in circulation. Oseltamivir-resistant influenza B viruses were not detected. Our findings indicated the co-circulation of the Victoria and Yamagata lineages over the past four cold seasons in Bangkok. We also demonstrated differences in the clinical symptoms between these lineages.

  18. [Venezuelan Virology Network].

    PubMed

    Añez, Germán

    2005-03-01

    In November 2004, sponsored by the World Bank, the Venezuelan Foundation of Science, Technology and Innovation (Fonacit) and the Venezuelan Institute of Scientific Research (IVIC), delegates from the different virology research groups of the country, met in Caracas-Venezuela, with the aim to establish the "Venezuelan Virology Network". The symposium entitled "Molecular biology applied to virus of health importance in Venezuela", was divided into three areas, including human and animals viruses related to public health: 1) Dengue, others arboviruses and Hemorrhagic Fevers; 2) diarrhea-related and others veterinary viruses and 3) Hepatitis, HIV and others sexually transmitted viruses. This symposium allowed the delegates to evaluate the current strengths, weaknesses and needs of the different laboratories, becoming evident the necessity of developing collaborative work between the groups that share the same interests or lines of research; and also their need to exchange technical resources, human and bibliographical material and consequently, avoiding the duplication of efforts and the unnecessary cost of resources. One of the main strengths of Venezuelan virology is the presence, in most laboratories, of researchers with studies of fourth level and multidisciplinary teams of work. We aspire to achieve the raised objectives in the event, to the benefit of our virology and even more important, of our people.

  19. Clinical and virologic outcomes after changes in first antiretroviral regimen at 7 sites in the Caribbean, Central and South America Network (CCASAnet)

    PubMed Central

    Wolff, Marcelo; Shepherd, Bryan E.; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Cardoso, Sandra Wagner; Pape, Jean W.; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C.

    2015-01-01

    Background HIV-infected persons in lower income countries may experience high rates of antiretroviral therapy (ART) change, particularly due to toxicity or other non-failure reasons. Few reports address patient outcomes after these modifications. Methods HIV-infected adults from 7 Caribbean, Central and South America network (CCASAnet) clinical cohorts who modified > or = 1 drug from first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. Results 5,565 ART-naïve HAART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 due to toxicity and 11% due to failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4% and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio[aHR]=1.5 vs. failure, 95% confidence interval[CI]=1.0–2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at start of ART-2, and starting ART-2 because of failure (aHR=2.1 vs. toxicity, 95% CI=1.5–2.8). Conclusions Among patients modifying first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success. PMID:26761273

  20. Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS Clinical Trials Group virology laboratories.

    PubMed

    Yen-Lieberman, B; Brambilla, D; Jackson, B; Bremer, J; Coombs, R; Cronin, M; Herman, S; Katzenstein, D; Leung, S; Lin, H J; Palumbo, P; Rasheed, S; Todd, J; Vahey, M; Reichelderfer, P

    1996-11-01

    A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log10 RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons.

  1. Standardization of sensitive human immunodeficiency virus coculture procedures and establishment of a multicenter quality assurance program for the AIDS Clinical Trials Group. The NIH/NIAID/DAIDS/ACTG Virology Laboratories.

    PubMed Central

    Hollinger, F B; Bremer, J W; Myers, L E; Gold, J W; McQuay, L

    1992-01-01

    An independent quality assurance program has been established by the Division of AIDS, National Institute of Allergy and Infectious Diseases, for monitoring virologic assays performed by nearly 40 laboratories participating in multicenter clinical trials in the United States. Since virologic endpoints are important in evaluating the timing and efficacy of therapeutic interventions, it is imperative that virologic measurements be accurate and uniform. When the quality assurance program was initially created, fewer than 40% of the laboratories could consistently recover human immunodeficiency virus (HIV) from peripheral blood mononuclear cells (PBMCs) of HIV-infected patients. By comparing coculture procedures in the more competent laboratories with those in laboratories who were struggling to isolate virus, optimal conditions were established and nonessential reagents and practices were eliminated. Changes were rapidly introduced into a laboratory when experience dictated that such modifications would result in a favorable outcome. Isolation of HIV was enhanced by optimizing the numbers and ratios of patient and donor cells used in cultures, by standardizing PBMC separation procedures, by using fresh rather than frozen donor PBMCs, by processing whole blood within 24 h, and by using natural delectinated interleukin 2 instead of recombinant interleukin 2 products in existence at that time. Delays of more than 8 h in the addition of phytohemagglutinin-stimulated donor cells to freshly separated patient PBMCs reduced recovery. Phytohemagglutinin in cocultures and the addition of Polybrene and anti-human alpha interferon to media were not important in HIV isolation. The introduction of a consensus protocol based on this information brought most laboratories quickly into compliance. In addition, monthly monitoring has successfully maintained proficiency among the laboratories, a process that is critical for the scientific integrity of collaborative multicenter trials

  2. Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study

    PubMed Central

    2013-01-01

    Background Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. Methods A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. Results Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. Conclusions Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments

  3. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java

    PubMed Central

    Kosasih, Herman; Alisjahbana, Bachti; Nurhayati; de Mast, Quirijn; Rudiman, Irani F.; Widjaja, Susana; Antonjaya, Ungke; Novriani, Harli; Susanto, Nugroho H.; Jusuf, Hadi; van der Ven, Andre; Beckett, Charmagne G.; Blair, Patrick J.; Burgess, Timothy H.; Williams, Maya; Porter, Kevin R.

    2016-01-01

    Background Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. Methodology/Principal Findings Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000–2004 and 2006–2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. Conclusions/Significance Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with

  4. Clinical and Virological Characteristics of Chronic Hepatitis B Patients with Coexistence of HBsAg and Anti-HBs.

    PubMed

    Liu, Yong; Zhang, Le; Zhou, Jin-Yong; Pan, Jinshun; Hu, Wei; Zhou, Yi-Hua

    2016-01-01

    Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) comprises an atypical serological profile in patients with chronic hepatitis B virus (HBV) infection. In this study, in total 94 patients with coexisting HBsAg and anti-HBs and 94 age- and sex-matched patients with positive HBsAg were characterized by quantitatively measuring HBsAg and HBV DNA, sequencing large S genes, and observing clinical features. Compared with common hepatitis B patients, the patients with coexisting HBsAg and anti-HBs had lower HBsAg and HBV DNA levels. These two groups had similar rate of pre-S deletion mutations. However, in patients with coexisting HBsAg and anti-HBs, more amino acid substitutions in the a determinant of S gene were observed in HBV genotype C, but not in genotype B. Fourteen patients with coexisting HBsAg and anti-HBs were followed up for an average of 15.5 months. There were no significant changes in the levels of HBsAg, anti-HBs, HBV DNA and ALT over the follow-up period. Compared with the baseline sequences, amino acid substitutions in the MHR of HBsAg occurred in 14.3% (2/14) patients. In conclusion, coexistence of HBsAg and anti-HBs may be associated with higher frequency of mutations in the a determinant of HBV genotype C.

  5. HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study

    PubMed Central

    2014-01-01

    Background An increasing number of people on antiretroviral therapy (ART) in sub-Saharan Africa has led to declines in HIV related morbidity and mortality. However, virologic failure (VF) and acquired drug resistance (ADR) may negatively affect these gains. This study describes the prevalence and correlates of HIV-1 VF and ADR among first-line ART experienced adults at a rural HIV clinic in Coastal Kenya. Methods HIV-infected adults on first-line ART for ≥6 months were cross-sectionally recruited between November 2008 and March 2011. The primary outcome was VF, defined as a one-off plasma viral load of ≥400 copies/ml. The secondary outcome was ADR, defined as the presence of resistance associated mutations. Logistic regression and Fishers exact test were used to describe correlates of VF and ADR respectively. Results Of the 232 eligible participants on ART over a median duration of 13.9 months, 57 (24.6% [95% CI: 19.2 – 30.6]) had VF. Fifty-five viraemic samples were successfully amplified and sequenced. Of these, 29 (52.7% [95% CI: 38.8 – 66.3]) had at least one ADR, with 25 samples having dual-class resistance mutations. The most prevalent ADR mutations were the M184V (n = 24), K103N/S (n = 14) and Y181C/Y/I/V (n = 8). Twenty-six of the 55 successfully amplified viraemic samples (47.3%) did not have any detectable resistance mutation. Younger age (15–34 vs. ≥35 years: adjusted odd ratios [95% CI], p-value: 0.3 [0.1–0.6], p = 0.002) and unsatisfactory adherence (<95% vs. ≥95%: 3.0 [1.5–6.5], p = 0.003) were strong correlates of VF. Younger age, unsatisfactory adherence and high viral load were also strong correlates of ADR. Conclusions High levels of VF and ADR were observed in younger patients and those with unsatisfactory adherence. Youth-friendly ART initiatives and strengthened adherence support should be prioritized in this Coastal Kenyan setting. To prevent unnecessary/premature switches, targeted HIV drug resistance

  6. Status of human monkeypox: clinical disease, epidemiology and research.

    PubMed

    Damon, Inger K

    2011-12-30

    Monkeypox, a vesiculo-pustular rash illness, was initially discovered to cause human infection in 1970 through the World Health Organization (WHO)-sponsored efforts of the Commission to Certify Smallpox Eradication in Western Africa and the Congo Basin. The virus had been discovered to cause a nonhuman primate rash illness in 1958, and was thus named monkeypox. The causative agents of monkeypox and smallpox diseases both are species of Orthopoxvirus. Orthopoxvirus monkeypox, when it infects humans as an epizootic, produces a similar clinical picture to that of ordinary human smallpox. Since 1970, extensive epidemiology, virology, ecology and public health research has enabled better characterization of monkeypox virus and the associated human disease. This work reviews the progress in this body of research, and reviews studies of this "newly" emerging zoonotic disease.

  7. Maintaining Life-saving Testing for Patients With Infectious Diseases: Infectious Diseases Society of America, American Society for Microbiology, and Pan American Society for Clinical Virology Recommendations on the Regulation of Laboratory-developed Tests.

    PubMed

    Caliendo, Angela M; Couturier, Marc R; Ginocchio, Christine C; Hanson, Kimberly E; Miller, Melissa B; Walker, Kimberly E; Frank, Gregory M

    2016-07-15

    In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs.

  8. Individualized treatment strategies and predictors of virological response for chronic hepatitis C: a multicenter prospective study from China.

    PubMed

    Nan, Yue-Min; Zhang, Yu-Guo; Zheng, Huan-Wei; An, Chun-Mian; Li, You-Sheng; Zhang, Ying; Sun, Dian-Xing; Li, Cang-You; Li, Qiang; Tong, Li-Xin; Kong, Ling-Bo; Zhao, Su-Xian; Wang, Rong-Qi; Meng, Ping; Su, Shan-Shan; He, Huan; Niu, Xue-Min

    2015-01-01

    Combination therapy comprising pegylated interferon-alpha (PegIFNα) and ribavirin (RBV) has been the standard of care for the chronic hepatitis C patients for more than a decade. Recently, direct antiviral agents show better efficacy, tolerance, and shorter treatment duration. However, the prohibitive costs of the regimens limit their use in developing countries where most of the HCV infection exists. Optimizing the treatment and understanding the host- and virus-factors associated with viral clearance were necessary for individualizing therapy to maximize sustained virologic response. To explore individualized antiviral strategies with PegIFNα-2a/IFNα-2b plus ribavirin for CHC patients, and to clarify predictive factors for virological response. A cohort of 314 patients were included in this open-label, prospective clinical trial, which received individualized doses of PegIFNα-2a or IFNα-2b combined with RBV according to body weight, disease status and complications, with the duration of 44 weeks after HCV RNA undetectable. All the IL-28B (rs8099917), IL-17A (rs8193036), IL-17B (rs2275913) and PD-1.1 SNPs were genotyped using the TaqMan system. The sustained virological response (SVR) in PegIFNα-2a group was significantly higher than that in IFNα-2b (85.8% vs 75.0%, P = 0.034), especially in HCV genotype 1 (84.0% vs 64.3%, P = 0.022). However, no significant differences were found in rapid virological response (RVR), complete early virological response (cEVR) and SVR between PegIFNα-2a and IFNα-2b according to different doses, respectively. The genotype frequency of IL-28B TT in patients with cEVR, SVR was higher than that in non-responsed patients (93.8% vs 78.1%, χ(2) = 7.827, P = 0.005; 95.9% vs 80.4%, χ(2) = 9.394, P = 0.002). No significant correlation between the genotype distribution of IL-17A, IL-17B and PD-1.1 with virological response. Individualized regimens of PegIFNα-2a/RBV and IFNα-2b/RBV could achieve satisfied virological response in

  9. Status of Clinical Supervision among School Counselors in Southeast Georgia

    ERIC Educational Resources Information Center

    Black, Anna Lila; Bailey, Carrie Lynn; Bergin, James J.

    2011-01-01

    Previous studies have investigated the role of clinical supervision in school counseling practice. This research explored the status and meaning of clinical supervision to school counselors employed in two southeastern Georgia counties. Results indicate that participants value clinical supervision even though their employers did not necessarily…

  10. Clinical and virological predictors of sustained response with an interferon-based simeprevir regimen for patients with chronic genotype 1 hepatitis C virus infection.

    PubMed

    D'Offizi, Gianpiero; Cammà, Calogero; Taibi, Chiara; Schlag, Michael; Weber, Karin; Palma, Maria; DeMasi, Ralph; Janssen, Katrien; Witek, James; Lionetti, Raffaella

    2017-01-01

    Simeprevir plus peg-interferon/ribavirin (PR) is approved to treat chronic hepatitis C (HCV) genotype 1 (GT1) and GT4 infection. This study aimed to assess baseline and on-treatment the factors predictive of sustained virologic response 12-weeks post-treatment (SVR12) in patients receiving 12 weeks of simeprevir plus PR followed by 12 or 36 weeks of PR. Data from participants in four studies (QUEST-1, QUEST-2, ATTAIN and PROMISE) were pooled to examine the efficacy and safety of simeprevir+PR in HCV GT1 patients. The predictive power of baseline variables for SVR12 was assessed using univariate and multivariate logistic regression models while the relationship between early (Week 4) on-treatment response and SVR12 was analyzed by GT1 subtype and treatment experience. Data for 1160 patients were analyzed (overall SVR12: 71%). Baseline factors predictive of SVR12 were: IL28B CC genotype, GT1a/Q80K-negative, treatment-naïve/prior relapser, no cirrhosis, HCV-RNA ≤2,000,000IU/mL, albumin >42g/L, platelets >200x109 /L. Patients with HCV GT1b (86%), IL28B CC genotype (87%), and treatment-naïve patients (83%) were predicted to achieve the highest SVR12 rates and rates of rapid virologic response. Week 4 early on-treatment response identified treatment-naïve and prior relapse patients likely to achieve SVR12. Patients likely to respond to simeprevir+PR can be identified using baseline factors. Early on-treatment response predicts treatment success.

  11. Virological Efficacy in Cerebrospinal Fluid and Neurocognitive Status in Patients with Long-Term Monotherapy Based on Lopinavir/Ritonavir: An Exploratory Study

    PubMed Central

    Santos, José R.; Muñoz-Moreno, José A.; Moltó, José; Prats, Anna; Curran, Adrià; Domingo, Pere; Llibre, Josep M.; McClernon, Daniel R.; Bravo, Isabel; Canet, Jaume; Watson, Victoria; Back, David; Clotet, Bonaventura

    2013-01-01

    Background Data on suppression of HIV replication in the CNS and on the subsequent risk of neurocognitive impairment using monotherapy with boosted protease inhibitors are limited. Methods Ours was an exploratory cross-sectional study in patients on lopinavir/ritonavir-based monotherapy (LPV/r-MT) or standard triple therapy (LPV/r-ART) for at least 96 weeks who maintained a plasma viral load <50 copies/mL. HIV-1 RNA in CSF was determined by HIV-1 SuperLow assay (lower limit of detection, 1 copy/mL). Neurocognitive functioning was assessed using a recommended battery of neuropsychological tests covering 7 areas. Neurocognitive impairment (NCI) was determined and also a global deficit score (GDS) for study comparisons. Results Seventeen patients on LPV/r-MT and 17 on LPV/r-ART were included. Fourteen (82.4%) patients on LPV/r-MT and 16 (94.1%) on LPV/r-ART had HIV-1 RNA <1 copy/mL in CSF (p = 0.601). NCI was observed in 7 patients on LPV/r-MT and in 10 on LPV/r-ART (41% vs 59%; p = 0.494). Mean (SD) GDS was 0.22 (0.20) in patients on LPV/r-MT and 0.47 (0.34) in those on LPV/r-ART (p = 0.012). Conclusions Suppression of HIV in CSF is similar in individuals with durable plasma HIV-1 RNA suppression who are receiving LPV/r-MT or LPV/r-ART for at least 96 weeks. Findings for HIV-1 replication in CSF and neurocognitive status indicate that this strategy seems to be safe for CNS functioning. PMID:23922957

  12. 42 CFR 493.919 - Virology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Virology. 493.919 Section 493.919 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.919 Virology. (a) Types of services offered by laboratories. In virology, there are two types of laboratories for proficiency testing...

  13. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  14. 42 CFR 493.919 - Virology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Virology. 493.919 Section 493.919 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.919 Virology. (a) Types of services offered by laboratories. In virology, there are two types of laboratories for proficiency testing...

  15. 42 CFR 493.919 - Virology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Virology. 493.919 Section 493.919 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.919 Virology. (a) Types of services offered by laboratories. In virology, there are two types of laboratories for proficiency testing...

  16. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  17. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  18. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  19. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  20. [Petit mal status epilepticus with unusual clinical manifestations].

    PubMed

    Savitskaia, O N; Karlov, V A; Gleĭzer, M A; Pmotskaia, E E

    1980-01-01

    A unique observation of an epileptic female examined in detail in a neurological clinic is presented. The patient was later hospitalized 3 times for disturbances of consciousness and extrapyramid disorders characterized by acute onset. An encephalographic examination carried out during such a state showed an epileptic status of atypic absence. The development of the Parkinsonian syndrome is regarded as a proof of the role of the caudate nucleus in the genesis of the petit mal epileptic status.

  1. Clinical decision making in seizures and status epilepticus.

    PubMed

    Teran, Felipe; Harper-Kirksey, Katrina; Jagoda, Andy

    2015-01-01

    Seizures and status epilepticus are frequent neurologic emergencies in the emergency department, accounting for 1% of all emergency department visits. The management of this time-sensitive and potentially life-threatening condition is challenging for both prehospital providers and emergency clinicians. The approach to seizing patients begins with differentiating seizure activity from mimics and follows with identifying potential secondary etiologies, such as alcohol-related seizures. The approach to the patient in status epilepticus and the patient with nonconvulsive status epilepticus constitutes a special clinical challenge. This review summarizes the best available evidence and recommendations regarding diagnosis and resuscitation of the seizing patient in the emergency setting.

  2. Present Status of Radiotherapy in Clinical Practice

    NASA Astrophysics Data System (ADS)

    Duehmke, Eckhart

    Aims of radiation oncology are cure from malignant diseases and - at the same time preservation of anatomy (e.g. female breast, uterus, prostate) and organ functions (e.g. brain, eye, voice, sphincter ani). At present, methods and results of clinical radiotherapy (RT) are based on experiences with natural history and radiobiology of malignant tumors in properly defined situations as well as on technical developments since World War II in geometrical and biological treatment planning in teletherapy and brachytherapy. Radiobiological research revealed tolerance limits of healthy tissues to be respected, effective total treatment doses of high cure probability depending on histology and tumor volume, and - more recently - altered fractionation schemes to be adapted to specific growth fractions and intrinsic radiosensitivities of clonogenic tumor cells. In addition, Biological Response Modifiers (BRM), such as cis-platinum, oxygen and hyperthermia may steepen cell survival curves of hypoxic tumor cells, others - such as tetrachiordekaoxid (TCDO) - may enhance repair of normal tissues. Computer assisted techniques in geometrical RT-planning based on individual healthy and pathologic anatomy (CT, MRT) provide high precision RT for well defined brain lesions by using dedicated linear accelerators (Stereotaxy). CT-based individual tissue compensators help with homogenization of distorted dose distributions in magna field irradiation for malignant lymphomas and with total body irradiation (TBI) before allogeneic bone marrow transplantation, e.g. for leukemia. RT with fast neutrons, Boron Neutron Capture Therapy (BNCT), RT with protons and heavy ions need to be tested in randomized trials before implementation into clinical routine.

  3. Clinical assessment of selenium status of livestock.

    PubMed

    Stowe, H D; Herdt, T H

    1992-12-01

    Assessment of the selenium status of livestock is an important aspect of production medicine, but variations in reported values between laboratories and between methods may be > 30%. Reliable interpretations require considerable experience with an assay and an extensive database from field and research case samples of a variety of species. The Michigan State University Animal Health Diagnostic Laboratory (MSU-ADHL) has offered Se analyses by acid-digestion and fluorometric detection since 1982. This laboratory expects serum Se values (nanograms per milliliter) of livestock to increase gradually with age from starting ranges for neonates of 50 to 80 for calves and sheep and 70 to 90 for foals and pigs. Expected or "normal" values for the adults are in the ranges of 70 to 100 for cattle, 120 to 150 for sheep, 130 to 160 for horses, and 180 to 220 for swine. Normal liver Se concentrations are considered to range between 1.2 and 2.0 micrograms/g on a dry weight basis, regardless of the species or age. Based on samples submitted to MSU-AHDL between September 1990 and August 1991, contemporary feeding practices in the Michigan area resulted in mean serum Se values (nanograms per milliliter) of 75 +/- 19 for adult Holsteins, 170 +/- 27 for adult swine (mixed breeds), and 137 +/- 30 for adult race horses. Within that period of time, two field cases of Se toxicity were diagnosed. One involved feeder pigs with a recorded high serum Se value of 1,525 ng/mL due to a commercial premix manufacturing error.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. [Peliosis hepatis. A clinical status inventory].

    PubMed

    Spech, H J; Liehr, H

    1982-12-01

    Peliosis hepatis is a rare condition, recognizable by macroscopical view. It is characterized by multiple blood-filled cystic spaces in the liver parenchyma. According to 49 out of 152 more recent case reports (1951-1981/82) its spontaneous occurrence is frequently associated with malignant and toxic processes. However, in about 70% peliosis may be induced by the action of certain drugs, especially by 17 alpha-alkylated steroids. Usually peliosis is found by chance at autopsy or peritoneoscopy, as the clinical picture does not provide sufficient conclusive criteria to allow a definite diagnosis. The striking macroscopical appearance contrasts to the dispute on the as yet unestablished natural history. As most important complication spontaneous intraabdominal bleeding can occur in occasional cases. On the other hand, the patients predominantly die of their underlying diseases and not of a peliosis hepatis.

  5. Summary of the 9th annual meeting of the Italian Society for Virology.

    PubMed

    Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Palù, Giorgio

    2011-01-01

    The 9th annual meeting of the Italian Society for Virology (SIV) comprised seven plenary sessions focused on: General virology and viral genetics; Virus-Host interaction and pathogenesis; Viral oncology; Emerging viruses and zoonotic, foodborne, and environmental pathways of transmission; Viral immunology and vaccines; Medical virology and antiviral therapy; Viral biotechnologies and gene therapy. Moreover, four hot topics were discussed in special lectures: the Pioneer in human virology lecture regarding the control of viral epidemics with particular emphasis on the human immunodeficiency virus (HIV), the Pioneer in plant virology lecture focused on cell responses to plant virus infection, a Keynote lecture on the epidemiology and genetic diversity of Crimea-Congo Hemorrhagic Fever virus, and the G.B. Rossi lecture on the molecular basis and clinical implications of human cytomegalovirus tropism for endothelial/epithelial cells. The meeting had an attendance of about 160 virologists. A summary of the plenary lectures and oral selected presentations is reported.

  6. Clinical assessment of nutritional status and feeding programs in horses.

    PubMed

    Becvarova, Iveta; Pleasant, R Scott; Thatcher, Craig D

    2009-04-01

    Veterinarians are a primary source of nutritional information and advice for horse owners. This article reviews methods for clinical assessment of nutritional status and feeding programs that can be applied to an individual horse or group of horses. Physical examination, including measurement of body weight and evaluation of body condition score, estimation of nutrient requirements and the nutrient content of the horse's diet, and evaluation of the feeding method are important components of the assessment. Ongoing clinical assessment of health and body condition will gauge the need for reassessment of the feeding plan. Obvious indications for prompt reevaluation of diet and feeding include changes in health status (eg, body condition), life stage or physiologic state (eg, pregnancy), or performance status.

  7. [The logic of diagnoses used in expert systems. II. Applications in virology].

    PubMed

    Cristea, A; Zaharia, C N

    1988-01-01

    Inference capacity of different clinical or paraclinical examinations are analyzed, whose results allow to establish the definitive diagnosis through gradual integrations. The knowledge of the inference capacity is very useful for the expert systems applied in virology.

  8. General concepts of virology.

    PubMed

    Kennedy, Melissa; Greenacre, Cheryl B

    2005-01-01

    A basic understanding of viruses and how they replicate and produce disease can aid in the management of virus infections. Parameters, such as clinical signs, sample and test selection, prognosis, and control, are implicit in this understanding. Information increases almost daily about known and emerging viruses; this impacts our ability to manage and control infections.

  9. [Virological research on appendicitis].

    PubMed

    Stănescu, D; Sternberg, D; Chirilă, R; Teleguţă, L; Tănase, M; Copelovici, Y

    1988-01-01

    Investigations were conducted on groups of subjects hospitalized in surgery services with a clinical diagnosis of acute or chronic appendicitis, to detect the presence of inframicrobial antibodies and antigens, as well as that of the C reactive protein in these patients as compared with a control group. The results of serological tests and of the examination of pieces of appendix are also presented. The obtained data are used as arguments for the theory of an inframicrobial infection part in some acute and chronic forms of appendicitis.

  10. Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial

    PubMed Central

    Heidrich, Benjamin; Cordes, Hans-Jörg; Klinker, Hartwig; Möller, Bernd; Naumann, Uwe; Rössle, Martin; Kraus, Michael R.; Böker, Klaus H.; Roggel, Christoph; Schuchmann, Marcus; Stoehr, Albrecht; Trein, Andreas; Hardtke, Svenja; Gonnermann, Andrea; Koch, Armin; Wedemeyer, Heiner; Manns, Michael P.; Cornberg, Markus

    2015-01-01

    Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group. Trial Registration ClinicalTrials.gov NCT00803309 PMID:26057627

  11. Updates in immunoassays: virology.

    PubMed

    Josko, Deborah

    2012-01-01

    Virus identification is a challenge to the clinical microbiologist since growing viruses in traditional cell culture is labor intensive, time consuming, and subject to contamination. The advent of rapid and automated immunoassays has eliminated this problem by generating positive results in minutes to hours. For example, testing for infectious mononucleosis can yield a positive result in 3-8 minutes as seen with the Beckman Coulter, Inc. ICON Mono test or in 5-15 minutes with the MONO Mononucleosis Rapid Test Device marketed by ACON Laboratories, Inc. Fully automated immunoassay analyzers provide fast, accurate, sensitive results that aid in a prompt and accurate diagnosis for the patient. Turnaround times are shortened, allowing for timely medical intervention and treatment. The priority in any hospital or medical facility is to treat the patient as quickly and appropriately as possible. By using immunoassays, clinical laboratory professionals are able to report out correct results in a timely manner, ensuring overall positive patient outcomes and improved quality of healthcare.

  12. [Clinical algorithms in the treatment of status epilepticus in children].

    PubMed

    Zubcević, S; Buljina, A; Gavranović, M; Uzicanin, S; Catibusić, F

    1999-01-01

    The clinical algorithm is a text format that is specially suited for presenting a sequence of clinical decisions, for teaching clinical decision making, and for guiding patient care. Clinical algorithms are compared as to their clinical usefulness with decision analysis. We have tried to make clinical algorithm for managing status epilepticus in children that can be applicable to our conditions. Most of the algorithms that are made on this subject include drugs and procedures that are not available at our hospital. We identified performance requirement, defined the set of problems to be solved as well as who would solve them, developed drafts in several versions and put them in the discussion with experts in this field. Algorithm was tested and revised and graphical acceptability was achieved. In the algorithm we tried to clearly define how the clinician should make the decision and to be provided with appropriate feedback. In one year period of experience in working we found this algorithm very useful in managing status epilepticus in children, as well as in teaching young doctors the specifities of algorithms and this specific issue. Their feedback is that they find that it provides the framework for facilitating thinking about clinical problems. Sometimes we hear objection that algorithms may not apply to a specific patient. This objection is based on misunderstanding how algorithms are used and should be corrected by a proper explanation of their use. We conclude that methods should be sought for writing clinical algorithms that represent expert consensus. A clinical algorithm can then be written for many areas of medical decision making that can be standardized. Medical practice would then be presented to students more effectively, accurately and understood better.

  13. Finding our roots and celebrating our shoots: Plant virology in Virology, 1955-1964.

    PubMed

    Scholthof, Karen-Beth G

    2015-05-01

    To celebrate the sixtieth anniversary of Virology a survey is made of the plant viruses, virologists and their institutions, and tools and technology described in the first decade of plant virus publications in Virology. This was a period when plant viruses increasingly became tools of discovery as epistemic objects and plant virology became a discipline discrete from plant pathology and other life sciences.

  14. The History of Tumor Virology

    PubMed Central

    Javier, Ronald T.; Butel, Janet S.

    2012-01-01

    In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. Later identification of mammalian tumor viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by Ludwik Gross, sparked the first intense interest in tumor virology by suggesting the possibility of a similar causal role for viruses in human cancers. This change in attitude opened the door in the 1960s and 1970s for the discovery of the first human tumor viruses—EBV, hepatitis B virus, and the papillomaviruses. Such knowledge proved instrumental to the development of the first cancer vaccines against cancers having an infectious etiology. Tumor virologists additionally recognized that viruses could serve as powerful discovery tools, leading to revolutionary breakthroughs in the 1970s and 1980s that included the concept of the oncogene, the identification of the p53 tumor suppressor, and the function of the retinoblastoma tumor suppressor. The subsequent availability of more advanced molecular technologies paved the way in the 1980s and 1990s for the identification of additional human tumor viruses—human T-cell leukemia virus type 1, hepatitis C virus, and Kaposi’s sarcoma virus. In fact, current estimates suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus, viruses not only have been shown to represent etiologic agents for many human cancers but have also served as tools to reveal mechanisms that are involved in all human malignancies. This rich history promises that tumor virology will continue to contribute to our understanding of cancer and to the development of new therapeutic and preventive measures for this disease in the 21st century. PMID:18829521

  15. The history of tumor virology.

    PubMed

    Javier, Ronald T; Butel, Janet S

    2008-10-01

    In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. Later identification of mammalian tumor viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by Ludwik Gross, sparked the first intense interest in tumor virology by suggesting the possibility of a similar causal role for viruses in human cancers. This change in attitude opened the door in the 1960s and 1970s for the discovery of the first human tumor viruses--EBV, hepatitis B virus, and the papillomaviruses. Such knowledge proved instrumental to the development of the first cancer vaccines against cancers having an infectious etiology. Tumor virologists additionally recognized that viruses could serve as powerful discovery tools, leading to revolutionary breakthroughs in the 1970s and 1980s that included the concept of the oncogene, the identification of the p53 tumor suppressor, and the function of the retinoblastoma tumor suppressor. The subsequent availability of more advanced molecular technologies paved the way in the 1980s and 1990s for the identification of additional human tumor viruses--human T-cell leukemia virus type 1, hepatitis C virus, and Kaposi's sarcoma virus. In fact, current estimates suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus, viruses not only have been shown to represent etiologic agents for many human cancers but have also served as tools to reveal mechanisms that are involved in all human malignancies. This rich history promises that tumor virology will continue to contribute to our understanding of cancer and to the development of new therapeutic and preventive measures for this disease in the 21st century.

  16. Comparative study on the clinical and virological characteristics among patients with single occult hepatitis B virus (HBV), single occult hepatitis C virus (HCV) and occult HBV and HCV dual infection.

    PubMed

    Castillo, Inmaculada; Rodríguez-Iñigo, Elena; López-Alcorocho, Juan Manuel; Bartolomé, Javier; Pardo, Margarita; Carreño, Vicente

    2007-03-01

    Occult hepatitis B virus (HBV) and occult hepatitis C virus (HCV) infection are two recently described different forms of HBV and HCV infections. This work compares the clinical, virologic, and histologic characteristics of patients with occult dual infection to those of patients with single occult HBV or HCV infection. Seventy-six patients with abnormal liver function tests of unknown etiology (serum HBsAg, anti-HCV, HBV-DNA, and HCV-RNA negative) were included in the study. Viral genomes were tested in liver by real-time PCR and confirmed by in situ hybridization. Of the 76 patients, 17 had occult HBV infection (intrahepatic HBV-DNA positive, HCV-RNA negative), 35 had occult HCV infection (intrahepatic HCV-RNA positive, HBV-DNA negative) and 24 occult dual infection (intrahepatic HCV-RNA and HBV-DNA). No differences among the three groups were found regarding clinical and epidemiologic data. The median load of intrahepatic genomic and antigenomic HCV-RNA strands was similar between single occult HCV infection and occult HBV and HCV dual infection. The percentage of HCV-infected hepatocytes did not differ between these groups. In occult single HBV infection, intrahepatic levels of HBV-DNA and percentage of HBV-infected hepatocytes were similar to the group of patients with occult dual infection. Finally, no differences were found in histological liver damage among the three groups. In conclusion, liver disease in patients with occult dual infection was not more severe than in patients with single occult HBV or occult HCV infection. Moreover, in occult dual infection there is no a reciprocal inhibition of the viral genomes.

  17. Nonconvulsive Status Epilepticus Resembling Clinical Absence with Atypical EEG Pattern

    PubMed Central

    Mysore, Channaiah Srikanth; Zabad, Rana; Bertoni, John

    2017-01-01

    Objective. We are reporting two cases: a patient with steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) and another patient with secondary progressive multiple sclerosis (SPMS), both presenting with altered mental status (AMS) and later diagnosed with nonconvulsive atypical absence status epilepticus (AS), with atypical EEG changes. Methods. A report of two cases. Results. A patient with history of SREAT and the other with SPMS had multiple admissions due to AMS. For both, EEG revealed the presence of a high voltage generalized sharply contoured theta activity. A diagnosis of NCSE with clinical features of AS was made based on both clinical and EEG features. There was significant clinical and electrographic improvement with administration of levetiracetam for both patients in addition to sodium valproate and Solumedrol for the SREAT patient. Both patients continued to be seizure free on follow-up few months later. Conclusions. This is a report of two cases of atypical AS, with atypical EEG, in patients with different neurological conditions. Prompt clinical and EEG recovery occurred following appropriate medical treatment. We think that this condition might be underreported and could significantly benefit from prompt treatment when appropriately diagnosed. PMID:28203468

  18. Relationship between clinical and BK virological response in patients with late hemorrhagic cystitis treated with cidofovir: a retrospective study from the European Group for Blood and Marrow Transplantation.

    PubMed

    Cesaro, S; Pillon, M; Tridello, G; Aljurf, M; Martino, R; Schroyens, W; Nozzoli, C; Barba, P; Faraci, M; Fagioli, F; Cappelli, B; Cordonnier, C; Al-Mohareb, F; Floisand, Y; Greil, J; Panizzolo, I S; Santarone, S

    2013-06-01

    To investigate the relationship between clinical response and modification of BK viremia, we assessed retrospectively 32 cases of hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT that were treated with i.v. cidofovir (CDV). They were 22 men (69%) and 10 women (31%) with a median age of 24 years, range 3-62. The median number of CDV doses was 3, range 1-8, and the treatment lasted for a median of 3 weeks, range 1-10. Clinical improvement of HC was observed in 27 patients (84%). In 12 of 32 episodes (37.5%), BK viremia was determined before every CDV administration and a complete clinical response was observed in 10 of 12 patients (83%), the reduction of BK viremia load being 1 log by 2 weeks after starting CDV. Nephrotoxicity related to CDV was observed in nine patients. Among 26 patients with 100-day follow-up, 4 of 4 patients who had a complete clinical response by 30 days were alive vs 16 of 22 (73%) who did not have the resolution of HC in this time frame. We conclude that in patients with HC, the response to CDV treatment is usually associated with a significant reduction of BK viremia load.

  19. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  20. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  1. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  2. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  3. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  4. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  5. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  6. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  7. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  8. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  9. Integrative Virology for Senior Medical Students.

    ERIC Educational Resources Information Center

    Koment, Roger W.

    1991-01-01

    The article describes a senior elective in virology developed at the University of South Dakota School of Medicine. Students work independently through a series of course units, selecting 12 study topics from a catalog of 35 topics in medical virology and discussing their reading daily with the professor. (DB)

  10. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients

    PubMed Central

    Lu, Wei; Mehraj, Vikram; Vyboh, Kishanda; Cao, Wei; Li, Taisheng; Routy, Jean-Pierre

    2015-01-01

    Introduction Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients. Method We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection. Discussion Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults. Conclusion The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials. PMID:26130226

  11. Clinical, virological and serological response of the West African dwarf sheep to experimental infection with different strains of Rift Valley fever virus.

    PubMed

    Tomori, O

    1979-03-01

    West African dwarf sheep were inoculated with three different strains of Rift Valley fever virus (RVFV). Using infective mouse serum as the source of virus classical RVFV disease characterised by sudden onset, a sharp but transient febrile response, viraemia, abortions and the development of specific RVFV antibodies in surviving animals was observed. The severity of clinical response was, however, dependent on the strain of virus used, with animals inoculated with Smithburn's neuroadapted strain showing a milder response than those inoculated with either the Nigerian or Lunyo strain. The inoculation of sheep with RVFV infective mouse brain material of the three different strains resulted in a mild febrile response with low level viraemia. Immune sera from sheep inoculated with both the Nigerian and Smithburn's neurotropic strains did not neutralise the Lunyo virus strain in a mouse intracerebral neutralisation test; the reverse, however, was not the case. The findings indicate that the West African dwarf sheep is highly susceptible to RVFV infection and that previous reports of only a mild clinical response following inoculation with the Nigerian strain were due to infective mouse brain rather than infective mouse serum.

  12. Raltegravir use prospectively assessed in a major HIV outpatient clinic in Italy: sample population, virological-immunological activity, and tolerability profile.

    PubMed

    Manfredi, Roberto; Calza, Leonardo; Marinacci, Ginevra; Cascavilla, Alessandra; Colangeli, Vincenzo; Salvadori, Caterina; Martelli, Giulia; Appolloni, Lucia; Puggioli, Cristina; Viale, Pierluigi

    2014-12-01

    Raltegravir, as the first HIV integrase inhibitor, has been used and prospectively monitored since 2010 in our HIV outpatient centre, where over 1,200 patients are monitored. The aim of our report is to perform an interim assessment of the background, the safety profile and the clinical-laboratory monitoring of all patients treated with a combination antiretroviral therapy (cART) including raltegravir, for at least 12 months. In all, 109 pretreated patients started a raltegravir-containing cART when aged 44.8 plus or minus 19.2 years, with a history of HIV infection lasting 13.4 plus or minus 9.7 years. All subjects were monitored for at least 12 months (mean 17.2 plus or minus 10.3 months). In the vast majority of cases (93 of 109: 85.3%), multiple (3-16) prior cART changes prompted raltegravir introduction in advanced-salvage lines: 72 of 109 (66.1%) patients had even developed a concurrent triple-class resistance to anti-HIV compounds. The most frequent companion antiretroviral agents were: darunavir/ritonavir (75 cases), maraviroc (47 subjects), and etravirine (38 cases). The most common underlying conditions were: AIDS (46 patients), liver cirrhosis (31 cases), AIDS-related or other malignancies (23 cases), and major cardio-cerebro-vascular events (18 cases). A chronic HCV and HBV hepatitis were of concern in 48 and 23 patients, respectively. The adjunct of raltegravir favourably affected all clinical-laboratory markers of HIV disease progression, and those of the broad spectrum of comorbidities, except for two patients who failed the raltegravir-containing cART due to insufficient adherence. Despite the already compromised clinical situation, a minority of subjects experienced mild-transient clinical-laboratory untoward events possibly attributable to raltegravir, such that no patients discontinued raltegravir during the observation period. Only three AIDS-defining conditions became apparent during raltegravir-based cART; chemotherapy and/or radiotherapy

  13. Clinical outcomes and virology of equine influenza in a naïve population and in horses infected soon after receiving one dose of vaccine.

    PubMed

    Kannegieter, N J; Frogley, A; Crispe, E; Kirkland, P D

    2011-07-01

    As part of the control measures of the equine influenza (EI) outbreak, in addition to the strategic use of vaccination to provide buffer zones around infected populations, approval was obtained to vaccinate Thoroughbred racing horses. We review the clinical expression of the disease and virus excretion in a population of racehorses that were exposed to EI approximately 7 days after administration of a single dose of the canarypox-vectored recombinant compared with a similar unvaccinated population of horses at a nearby racetrack. Although this study was undertaken opportunistically and under the difficult field conditions that prevailed during the outbreak, our observations demonstrate that an appropriate vaccine can be effectively used as a disease control measure, even in the face of an outbreak, and therefore should be rapidly implemented as soon as there is evidence of infection in a naïve population.

  14. The origin of phage virology.

    PubMed

    Pennazio, Sergio

    2006-01-01

    The history of bacteriophage (phage) had its start in 1915, when Twort isolated an unusual filterable and infectious agent from excrete of patients struck by diarrhoea; this discovery was followed by an analogous, and probably independent, finding of d'Hérelle in 1917. For several years phage research made scant progress but great attention was paid to the question of phage nature, which saw the contrast between d'Hérelle and Bordet's views (living against chemical nature, respectively). This situation changed with the independent discovery of lysogeny, in 1925, thanks to Bordet and Bail: this phenomenon was considered of genetical origin, a view that Wollman interpreted by assimilating the properties of phage to those of gene (according to a previous idea of Muller). In the 1930s, Burnet's work opened a new era by demonstrating the occurrence of several species of phages and their antigenic property. In the same period, the physical and chemical characteristics of these viruses were disclosed thanks, in particular, to the work of Schlesinger, who first demonstrated that a virus (phage) was constituted of nucleoproteins. The peculiarity of phage was finally shown after the invention of electron microscope: H. Ruska, in 1940, and Anderson and Luria in the next years, obtained the first images of tailed phages, a finding that strongly helped the investigation on the first steps of the infection process. The decisive impulse to phage virology came from Delbrück, a physicist who entered biology giving it a new arrangement. The so-called "phage group" assembled brilliant minds (Luria, Hershey and Delbrück himself, and later a dozen of other scientists): this group faced three fundamental questions of phage virology, i.e., the mechanisms of attack, multiplication and lysis. In ten years' time, phage virology became an integrant part of molecular biology, also thanks to the discovery of the genetical properties of DNA: in such scientific context, Delbrück, Luria and

  15. Diversity of 1,213 hepatitis C virus NS3 protease sequences from a clinical virology laboratory database in Marseille university hospitals, southeastern France.

    PubMed

    Hajji, Hind; Aherfi, Sarah; Motte, Anne; Ravaux, Isabelle; Mokhtari, Saadia; Ruiz, Jean-Marie; Poizot-Martin, Isabelle; Tourres, Christian; Tivoli, Natacha; Gérolami, René; Tamalet, Catherine; Colson, Philippe

    2015-11-01

    Infection with hepatitis C virus (HCV) represents a major public health concern worldwide. Recent therapeutic advances have been considerable, HCV genotype continuing to guide therapeutic management. Since 2008, HCV genotyping in our clinical microbiology laboratory at university hospitals of Marseille, Southeastern France, has been based on NS3 protease gene population sequencing, to allow concurrent HCV genotype and protease inhibitor (PI) genotypic resistance determinations. We aimed, first, to analyze the genetic diversity of HCV NS3 protease obtained from blood samples collected between 2003 and 2013 from patients monitored at university hospitals of Marseille and detect possible atypical sequences; and, second, to identify NS3 protease amino acid patterns associated with decreased susceptibility to HCV PIs. A total of 1,213 HCV NS3 protease sequences were available in our laboratory sequence database. We implemented a strategy based on bioinformatic tools to determine whether HCV sequences are representative of our local HCV genetic diversity, or divergent. In our 2003-2012 HCV NS3 protease sequence database, we delineated 32 clusters representative of the majority HCV genetic diversity, and 61 divergent sequences. Five of these divergent sequences showed less than 85% nucleotide identity with their top GenBank hit. In addition, among the 294 sequences obtained in 2013, three were divergent relative to these 32 previously delineated clusters. Finally, we detected both natural and on-treatment genotypic resistance to HCV NS3 PIs, including a substantial prevalence of Q80K substitutions associated with decreased susceptibility to simeprevir, a second generation PI.

  16. Use of biological knowledge to inform the analysis of gene-gene interactions involved in modulating virologic failure with efavirenz-containing treatment regimens in ART-naïve ACTG clinical trials participants.

    PubMed

    Grady, Benjamin J; Torstenson, Eric S; McLaren, Paul J; DE Bakker, Paul I W; Haas, David W; Robbins, Gregory K; Gulick, Roy M; Haubrich, Richard; Ribaudo, Heather; Ritchie, Marylyn D

    2011-01-01

    Personalized medicine is a high priority for the future of health care. The idea of tailoring an individual's wellness plan to their unique genetic code is one which we hope to realize through the use of pharmacogenomics. There have been examples of tremendous success in pharmacogenomic associations however there are many such examples in which only a small proportion of trait variance has been explained by the genetic variation. Although the increased use of GWAS could help explain more of this variation, it is likely that a significant proportion of the genetic architecture of these pharmacogenomic traits are due to complex genetic effects such as epistasis, also known as gene-gene interactions, as well as gene-drug interactions. In this study, we utilize the Biofilter software package to look for candidate epistasis contributing to risk for virologic failure with efavirenz-containing antiretroviral therapy (ART) regimens in treatment-naïve participants of AIDS Clinical Trials Group (ACTG) randomized clinical trials. A total of 904 individuals from three ACTG trials with data on efavirenz treatment are analyzed after race-stratification into white, black, and Hispanic ethnic groups. Biofilter was run considering 245 candidate ADME (absorption, distribution, metabolism, and excretion) genes and using database knowledge of gene and protein interaction networks to produce approximately 2 million SNP-SNP interaction models within each ethnic group. These models were evaluated within the PLATO software package using pair wise logistic regression models. Although no interaction model remained significant after correction for multiple comparisons, an interaction between SNPs in the TAP1 and ABCC9 genes was one of the top models before correction. The TAP1 protein is responsible for intracellular transport of antigen to MHC class I molecules, while ABCC9 codes for a transporter which is part of the subfamily of ABC transporters associated with multi-drug resistance

  17. USE OF BIOLOGICAL KNOWLEDGE TO INFORM THE ANALYSIS OF GENE-GENE INTERACTIONS INVOLVED IN MODULATING VIROLOGIC FAILURE WITH EFAVIRENZ-CONTAINING TREATMENT REGIMENS IN ART-NAÏVE ACTG CLINICAL TRIALS PARTICIPANTS

    PubMed Central

    Grady, Benjamin J.; Torstenson, Eric S.; Mclaren, Paul J.; De Bakker, Paul I.W.; Haas, David W.; Robbins, Gregory K.; Gulick, Roy M.; Haubrich, Richard; Ribaudo, Heather; Ritchie, Marylyn D.

    2011-01-01

    Personalized medicine is a high priority for the future of health care. The idea of tailoring an individual’s wellness plan to their unique genetic code is one which we hope to realize through the use of pharmacogenomics. There have been examples of tremendous success in pharmacogenomic associations however there are many such examples in which only a small proportion of trait variance has been explained by the genetic variation. Although the increased use of GWAS could help explain more of this variation, it is likely that a significant proportion of the genetic architecture of these pharmacogenomic traits are due to complex genetic effects such as epistasis, also known as gene-gene interactions, as well as gene-drug interactions. In this study, we utilize the Biofilter software package to look for candidate epistasis contributing to risk for virologic failure with efavirenz-containing antiretroviral therapy (ART) regimens in treatment-naïve participants of AIDS Clinical Trials Group (ACTG) randomized clinical trials. A total of 904 individuals from three ACTG trials with data on efavirenz treatment are analyzed after race-stratification into white, black, and Hispanic ethnic groups. Biofilter was run considering 245 candidate ADME (absorption, distribution, metabolism, and excretion) genes and using database knowledge of gene and protein interaction networks to produce approximately 2 million SNP-SNP interaction models within each ethnic group. These models were evaluated within the PLATO software package using pair wise logistic regression models. Although no interaction model remained significant after correction for multiple comparisons, an interaction between SNPs in the TAP1 and ABCC9 genes was one of the top models before correction. The TAP1 protein is responsible for intracellular transport of antigen to MHC class I molecules, while ABCC9 codes for a transporter which is part of the subfamily of ABC transporters associated with multi-drug resistance

  18. Introducing Virological Concepts Using an Insect Virus.

    ERIC Educational Resources Information Center

    Sheppard, Roger F.

    1980-01-01

    A technique is presented which utilizes wax moth larvae in a laboratory investigation of an insect virus. Describes how an insect virus can be used to introduce undergraduate biology students to laboratory work on viruses and several virological concepts. (SA)

  19. Protein bioinformatics applied to virology.

    PubMed

    Mohabatkar, Hassan; Keyhanfar, Mehrnaz; Behbahani, Mandana

    2012-09-01

    Scientists have united in a common search to sequence, store and analyze genes and proteins. In this regard, rapidly evolving bioinformatics methods are providing valuable information on these newly-discovered molecules. Understanding what has been done and what we can do in silico is essential in designing new experiments. The unbalanced situation between sequence-known proteins and attribute-known proteins, has called for developing computational methods or high-throughput automated tools for fast and reliably predicting or identifying various characteristics of uncharacterized proteins. Taking into consideration the role of viruses in causing diseases and their use in biotechnology, the present review describes the application of protein bioinformatics in virology. Therefore, a number of important features of viral proteins like epitope prediction, protein docking, subcellular localization, viral protease cleavage sites and computer based comparison of their aspects have been discussed. This paper also describes several tools, principally developed for viral bioinformatics. Prediction of viral protein features and learning the advances in this field can help basic understanding of the relationship between a virus and its host.

  20. Nutritional Risk, Micronutrient Status and Clinical Outcomes: A Prospective Observational Study in an Infectious Disease Clinic

    PubMed Central

    Dizdar, Oguzhan Sıtkı; Baspınar, Osman; Kocer, Derya; Dursun, Zehra Bestepe; Avcı, Deniz; Karakükcü, Cigdem; Çelik, İlhami; Gundogan, Kursat

    2016-01-01

    Malnutrition has been associated with increased morbidity and mortality. The objective of this study was to determine the nutritional status and micronutrient levels of hospitalized patients in an infectious disease clinic and investigate their association with adverse clinical outcomes. The nutritional status of the study participants was assessed using the Nutritional Risk Screening 2002 (NRS 2002) and micronutrient levels and routine biochemical parameters were tested within the first 24 h of the patient’s admission. The incidence of zinc, selenium, thiamine, vitamin B6, vitamin B12 deficiency were 66.7% (n = 40), 46.6% (n = 29), 39.7% (n = 27), 35.3% (n = 24), 14.1% (n = 9), respectively. Selenium levels were significantly higher in patients with urinary tract infections, but lower in soft tissue infections. Copper levels were significantly higher in patients with soft tissue infections. In the Cox regression models, lower albumin, higher serum lactate dehydrogenase levels and higher NRS-2002 scores were associated with increased death. Thiamine, selenium, zinc and vitamin B6 deficiencies but not chromium deficiencies are common in infectious disease clinics. New associations were found between micronutrient levels and infection type and their adverse clinical outcomes. Hypoalbuminemia and a high NRS-2002 score had the greatest accuracy in predicting death, systemic inflammatory response syndrome and sepsis on admission. PMID:26938553

  1. The status of platinum anticancer drugs in the clinic and in clinical trials.

    PubMed

    Wheate, Nial J; Walker, Shonagh; Craig, Gemma E; Oun, Rabbab

    2010-09-21

    Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, Lipoplatin and ProLindac). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade.

  2. Highlights from the 5th Annual Meeting of the Italian Society of Virology.

    PubMed

    Salata, Cristiano; Calistri, Arianna; Palù, Giorgio

    2006-07-01

    The 5th National Congress of the Italian Society of Virology (SIV) was attended by junior- and senior-level virologists to promote interactions and scientific collaborations among the different areas of Virology and allied sciences. The invited and selected lecturers covered the following topics: General Virology and Viral Genetics; Virus-host Interaction and Pathogenesis; Viral Oncogenesis; Viral Immunology and Vaccines; Anti-viral Therapy; Innovative Diagnostics; Viral Biotechnologies and Cell and Gene Therapy. As in the previous editions (Salata and Palù, 2004; Salata et al., 2005), a specific topic was thoroughly covered in a roundtable. This year the elected subject was "HIV: determinants of pathogenicity and clinical implications." The final program and the abstract book can be found at the web site http://www.siv-virologia.it. This report summarizes the lessons learned from the plenary lectures and the selected oral presentations of the 2005 meeting.

  3. Promoting translational research in human and veterinary medical virology.

    PubMed

    Tang, Yi-Wei

    2013-07-26

    Translational research serves as a bench-to-field "translation" of basic scientific research into practical diagnostic procedures and therapies useful in human and veterinary clinical services. The productivity of translational research involving infectious diseases relevant to both human and animal health (e.g., influenza diagnosis and epidemiology using emerging molecular detection and identification methods) can be maximized when both human and veterinary medical virology disciplines are integrated. Influenza viruses are continually evolving through site-specific mutation and segment reassortment, and these processes occur in all potential carrier species - including birds, humans, and many agriculturally important animals. This evolutionary plasticity occasionally allows "novel" influenzas to move from animal hosts to humans, potentially causing destructive pandemics; therefore, a rapid laboratory technique that can detect and identify "novel" influenza viruses is clinically and epidemiologically desirable. A technique-focused translational research approach is pursued to enhance detection and characterization of emerging influenza viruses circulating in both humans and other animal hosts. The PLEX-ID System, which incorporates multi-locus PCR and electrospray ionization/mass spectrometry, uses deliberately nonspecific primers that amplify all known variants (all H/N subtypes) of influenza virus, including human, other mammalian, and avian influenzas, and is therefore likely to generate analyzable amplicons from any novel influenza that might emerge in any host. Novel technology development and implementation such as the PLEX-ID System forms a key component of human and veterinary medical virology translational research.

  4. Estimates of global research productivity in virology.

    PubMed

    Falagas, Matthew E; Karavasiou, Antonia I; Bliziotis, Ioannis A

    2005-06-01

    The quantity and quality of published research in the field of Virology by different world regions was estimated in this study. Using the PubMed database, articles from journals included in the "Virology" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995-2003 were retrieved. The world was divided into nine regions based on geographic, economic, and scientific criteria. Data on the country of origin of the research was available for 33,425 out of 33,712 articles (99.2% of all articles from the included journals). USA exceeds all other world regions in research production for the period studied (42% of total articles), with Western Europe ranking second (35.7%). The mean impact factor in articles published in Virology journals was highest for the USA (4.60), while it was 3.90 for Western Europe and 3.22 for the rest of the world (seven regions combined). USA and Canada ranked first in research productivity when both gross national income per capita (GNIPC) and population were taken into account. The results of this analysis show a distressing fact; the absolute and relative production of research in the field of Virology by the developing regions is very low, although viral diseases cause considerable morbidity and mortality in these areas. It is evident from this study that developing regions need more help from the developed regions to enhance research infrastructure.

  5. Virological Response after Short-Term CCR5 Antagonist Exposure in HIV-Infected Patients: Frequency of Subjects with Virological Response and Associated Factors▿

    PubMed Central

    Ruiz-Mateos, Ezequiel; González-Serna, Alejandro; Genebat, Miguel; Machmach, Kawthar; Vidal, Francesc; Muñoz-Fernández, Ángeles; Ferrando-Martinez, Sara; Leal, Manuel

    2011-01-01

    The virological response after an 8-day maraviroc monotherapy has been proposed to be an alternative method to determine whether an CCR5 antagonist should be prescribed to HIV-infected patients. The frequency of patients eligible for a combined antiretroviral therapy which includes maraviroc on the basis of the result of this clinical test is not well-known at the moment. In the same way, clinical and immunovirological factors associated with the virological response after antagonist exposure need to be determined. Ninety consecutive HIV-infected patients were exposed to an 8-day maraviroc monotherapy. The virological response was considered positive if either a reduction of ≥1-log10 HIV RNA copies/ml or an undetectable viral load (<40 HIV RNA copies/ml) was achieved. CXCR4- and CCR5-tropic virus levels were determined by using patients' viral isolates and multiple rounds of infection of indicator cell lines (U87-CXCR4 and U87-CCR5). The frequency of patients with a positive virological response was 72.2% (94.7% and 66.2% for treatment-naïve and pretreated patients, respectively). The positive response rates dramatically decreased in patients with lower CD4+ T-cell counts. The CXCR4-tropic virus level was the only variable independently associated with the virological response after short-term maraviroc exposure. Lower CD4+ T-cell strata were associated with higher CXCR4-tropic virus levels. These results support the suggestion that CCR5 antagonists should be an early treatment option before the expansion of CXCR4-tropic strains. PMID:21807977

  6. Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy

    PubMed Central

    2012-01-01

    Background Thymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. Secondary mutations, including thumb subdomain polymorphisms (e.g. R284K) have been identified in association with TAMs. We have identified mutational clusters associated with virological failure during salvage therapy with tenofovir/emtricitabine-based regimens. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex. Results The cross-sectional study carried out with >200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P < 10-10) and TAMs (P < 10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. Clusters of mutations were identified, and among them, the TAM1 complex showed the highest correlation coefficients. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations. Conclusions Our study shows the association

  7. Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

    PubMed Central

    Ruiz-Valderas, Rosa; Sánchez-Rivas, Elena; Lluch, Amparo; Gutierrez-Valencia, Alicia; Torres-Cornejo, Almudena; BenMarzouk-Hidalgo, Omar J.; Viciana, Pompeyo

    2013-01-01

    There is significant intra- and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI95], 75.3 to 89.3%). Virological efficacy was independent of LPV plasma concentrations even when LPVr was given once daily. An adherence of <90% (HR, 4.4 [CI95, 1.78 to 10.8; P = 0.001]) and the presence of blips in the preceding 12 months (HR, 3.06 [CI95, 1.17 to 8.01; P = 0.022]) were the only variables independently associated with time to VF. These findings suggest that the LPV concentrations achieved with the standard doses of LPVr are sufficient to maintain virological control during monotherapy and that measurement of LPV concentrations is not useful for predicting virological outcome. Tight control of viral replication in the previous months and strict adherence throughout the mtLPVr regimen could improve the virological efficacy of this maintenance regimen. PMID:23716055

  8. Oral Health Status and Behaviour of Mauritians Visiting Private Dental Clinics

    ERIC Educational Resources Information Center

    Gunsam, P. Pugo; Banka, S.

    2011-01-01

    Purpose: This paper seeks to assess the oral health status and behaviour of a sample of the Mauritian population visiting private dental clinics. Design/methodology/approach: Oral health status was determined using the World Health Organization (Decayed, Missing, Filled Teeth (DMFT) index indicating the prevalence of caries, and factors associated…

  9. Representation of Functional Status Concepts from Clinical Documents and Social Media Sources by Standard Terminologies.

    PubMed

    Kuang, Jinqiu; Mohanty, April F; Rashmi, V H; Weir, Charlene R; Bray, Bruce E; Zeng-Treitler, Qing

    2015-01-01

    Patient-reported functional status is widely recognized as an important patient-centered outcome that adds value to medical care, research, and quality improvement. Functional status outcomes are, however, not routinely or uniformly collected in the medical record, except in certain small patient populations (e.g. geriatrics, nursing home residents). To utilize patient reported functional status for clinical research and practice, we manually collected 2,763 terms from clinical records and social media sites and modeled them on the widely used Short Form-36 Health Survey. We then examined the coverage of the Unified Medical Language System (UMLS) for these functional status terms through automated mapping. Most terms (85.9%) did not have exact matches in the UMLS. The partial matches were prevalent, however, they typically did not capture the terms' exact semantics. Our study suggests that there is a need to extend existing standard terminologies to incorporate functional status terms used by patients and clinicians.

  10. “Risk factors associated with virologic failure in HIV-infected patients receiving antiretroviral therapy at a public hospital in Peru”

    PubMed Central

    Jorge, Alave R; Jorge, Paz B; Elsa, Gonzalez L; Miguel, Campos S; Rodriguez, Martin; Willig, James; Juan, Echevarría Z

    2013-01-01

    OBJECTIVE To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. MATERIALS AND METHODS An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. RESULTS Of 1 478 records of patients on HAART analized, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. CONCLUSION This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk. PMID:23450408

  11. Current Status and Future Prospects of Clinical Psycholog

    PubMed Central

    Baker, Timothy B.; McFall, Richard M.; Shoham, Varda

    2010-01-01

    SUMMARY The escalating costs of health care and other recent trends have made health care decisions of great societal import, with decision-making responsibility often being transferred from practitioners to health economists, health plans, and insurers. Health care decision making increasingly is guided by evidence that a treatment is efficacious, effective–disseminable, cost-effective, and scientifically plausible. Under these conditions of heightened cost concerns and institutional–economic decision making, psychologists are losing the opportunity to play a leadership role in mental and behavioral health care: Other types of practitioners are providing an increasing proportion of delivered treatment, and the use of psychiatric medication has increased dramatically relative to the provision of psychological interventions. Research has shown that numerous psychological interventions are efficacious, effective, and cost-effective. However, these interventions are used infrequently with patients who would benefit from them, in part because clinical psychologists have not made a convincing case for the use of these interventions (e.g., by supplying the data that decision makers need to support implementation of such interventions) and because clinical psychologists do not themselves use these interventions even when given the opportunity to do so. Clinical psychologists’ failure to achieve a more significant impact on clinical and public health may be traced to their deep ambivalence about the role of science and their lack of adequate science training, which leads them to value personal clinical experience over research evidence, use assessment practices that have dubious psychometric support, and not use the interventions for which there is the strongest evidence of efficacy. Clinical psychology resembles medicine at a point in its history when practitioners were operating in a largely prescientific manner. Prior to the scientific reform of medicine in the

  12. Current status and prospects of HIV treatment.

    PubMed

    Cihlar, Tomas; Fordyce, Marshall

    2016-06-01

    Current antiviral treatments can reduce HIV-associated morbidity, prolong survival, and prevent HIV transmission. Combination antiretroviral therapy (cART) containing preferably three active drugs from two or more classes is required for durable virologic suppression. Regimen selection is based on virologic efficacy, potential for adverse effects, pill burden and dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, social status, and cost. With prolonged virologic suppression, improved clinical outcomes, and longer survival, patients will be exposed to antiretroviral agents for decades. Therefore, maximizing the safety and tolerability of cART is a high priority. Emergence of resistance and/or lack of tolerability in individual patients require availability of a range of treatment options. Development of new drugs is focused on improving safety (e.g. tenofovir alafenamide) and/or resistance profile (e.g. doravirine) within the existing drug classes, combination therapies with improved adherence (e.g. single-tablet regimens), novel mechanisms of action (e.g. attachment inhibitors, maturation inhibitors, broadly neutralizing antibodies), and treatment simplification with infrequent dosing (e.g. long-acting injectables). In parallel with cART innovations, research and development efforts focused on agents that target persistent HIV reservoirs may lead to prolonged drug-free remission and HIV cure.

  13. Clinical research within the chiropractic profession: status, needs and recommendations.

    PubMed

    Sawyer, C; Haas, M; Nelson, C; Elkington, W

    1997-01-01

    In the current climate of accountability, health care financing reform and the demand on all health professions for evidence, there is an urgent need to expand clinical research activity within the profession. Those randomized clinical trials that have been reported in the literature have focused primarily on low back and headache pain. Only recently have studies been initiated to investigate the effectiveness of chiropractic interventions for conditions other than back pain. The ability of chiropractic colleges to develop research infrastructures and productive clinical research programs depends on removing or minimizing a number of impediments. A shortage of chiropractic clinicians who have the experience and training to conduct clinical research is compounded by a dependency on tuition revenue, limited external funding and a lack of institutional emphasis on research. The profession generally, and chiropractic colleges specifically, must address the impediments that limit the growth of research capacity. We present several recommendations and the action steps required to achieve specific outcomes.

  14. Pathologic and virologic study of fatal Lassa fever in man.

    PubMed

    Walker, D H; McCormick, J B; Johnson, K M; Webb, P A; Komba-Kono, G; Elliott, L H; Gardner, J J

    1982-06-01

    Postmortem examination of 21 virologically documented cases of Lassa fever, including 6 complete autopsies, was performed as part of a field study of community-acquired Lassa fever in Sierra Leone. The most consistently observed lesions were hepatocellular, adrenal, and splenic necrosis and adrenal cytoplasmic inclusions. Neither these lesions, nor other milder and less constantly observed lesions such as myocarditis, renal tubular injury, and interstitial pneumonia, appeared severe enough to explain the cause of death in Lassa fever. The central nervous system (CNS) contained no specific lesions. Viral titrations demonstrated high viral content in liver, lung, spleen, kidney, heart, placenta, and mammary gland. Clinical laboratory data included elevation of hepatic enzymes, creatine phosphokinase (CPK), and blood urea nitrogen (BUN). Because of the paucity of pathologic lesions in spite of widely disseminated viral infection, further investigation of humoral inflammatory mechanisms is indicated.

  15. Computerized clinical guidelines: current status & principles for future research.

    PubMed

    Kondylakis, Haridimos; Tsiknakis, Manolis

    2012-01-01

    Although it is widely accepted that the adoption of computerized clinical guidelines would improve the quality of the provided health care, their influence in the daily practice is limited. In this paper we provide insights on the core topics related to computer interpretable clinical guidelines and we present shortly the main approaches in the area. Then we discuss the current limitations, and we present three simple principles that according to our view should be adopted to enhance the penetration of computerized clinical guidelines in the health care organizations. The overall goal of this paper is not only to give readers a quick overview of the works in the area, but also to provide necessary insights for the practical understanding of the issues involved and draw directions for future research and development activities.

  16. Virological diagnosis of Ebolavirus infection

    PubMed Central

    Smith, D. W.; Rawlinson, W. D.; Kok, J.; Dwyer, D. E.; Catton, M.

    2015-01-01

    Summary Ebolaviruses, and the other viral causes of haemorrhagic fevers (VHF) have always posed special problems for diagnostic laboratories. These arise from the rarity of human infections, minimal documented experience with test delivery and interpretation, the paucity of established commercial or in-house assays, the lack of clinical material for test development and validation, the high level containment required for handling live virus, the ongoing evolution of the viruses, and the high personal and public health requirements for accurate diagnosis. This article addresses the current situation and the ongoing challenges associated with delivering timely, high quality and safe testing within Australia for people exposed as part of the current major outbreak of Ebolavirus disease (EVD) in Western Africa. The members of the Public Health Laboratory Network have developed deliverable and reliable nucleic acid detection tests, and also have the laboratory capacity to handle the live viruses if necessary. However delivering and maintaining these services necessitates high levels of experience in developing and applying tests for exotic and emerging infections, strong national and international links and collaborations, ongoing monitoring and reassessment of test design and performance, innovative approaches to generation of positive control material, and a regular quality assurance program. PMID:26126050

  17. Virological diagnosis of Ebolavirus infection.

    PubMed

    Smith, D W; Rawlinson, W D; Kok, J; Dwyer, D E; Catton, M

    2015-08-01

    Ebolaviruses, and the other viral causes of haemorrhagic fevers (VHF) have always posed special problems for diagnostic laboratories. These arise from the rarity of human infections, minimal documented experience with test delivery and interpretation, the paucity of established commercial or in-house assays, the lack of clinical material for test development and validation, the high level containment required for handling live virus, the ongoing evolution of the viruses, and the high personal and public health requirements for accurate diagnosis. This article addresses the current situation and the ongoing challenges associated with delivering timely, high quality and safe testing within Australia for people exposed as part of the current major outbreak of Ebolavirus disease (EVD) in Western Africa. The members of the Public Health Laboratory Network have developed deliverable and reliable nucleic acid detection tests, and also have the laboratory capacity to handle the live viruses if necessary. However delivering and maintaining these services necessitates high levels of experience in developing and applying tests for exotic and emerging infections, strong national and international links and collaborations, ongoing monitoring and reassessment of test design and performance, innovative approaches to generation of positive control material, and a regular quality assurance program.

  18. Current status of quality in Japanese clinical trials.

    PubMed

    Saito, Kazuyuki; Kodama, Yasuo; Ono, Shunsuke; Mutoh, Mizue; Kawashima, Susumu; Fujimura, Akio

    2005-08-01

    The changes in the quality of Japanese clinical trials were evaluated by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year (FY) 1997-1999) with those from April 2001 to March 2002 (FY2001). During both of the periods inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR). The audit findings in the former period were based on the audits that covered 331 hospitals and 775 trials conducted under the old GCP guideline. The audits in the latter period targeted 147 hospitals and 238 trials conducted under the old or new GCP guideline. The total number of deficiencies detected by GCP audits in the former three-year period (FY 1997-1999) was 1529, and the corresponding number in the latter single year (FY 2001) was 912. Two remarkable changes in OPSR's findings were observed between FY 1997-1999 and FY 2001 as follows; the proportion of protocol deviations increased from 14.7% (225/1529) to 53.1% (484/912), while the proportion of errors in case report forms (CRFs) decreased from 43.6% (666/1529) to 15.4% (140/912). The new GCP guideline sets very high standards for a hospital's qualification: to have sufficient equipment and hospital resources, to have capacity for promptly responding to urgent trial-related problems, to have an IRB, and to have appropriate staff including clinical research coordinators (CRCs) assigned to the clinical trial. Our results suggest that the impact of the regulatory changes of applicable standard is large for a hospital's qualification for conducting clinical trials in Japan.

  19. Behavior problems of clinic children: relation to parental marital status, age and sex of child.

    PubMed

    Brady, C P; Bray, J H; Zeeb, L

    1986-07-01

    Behavior problems of 703 children seen in a clinical setting were examined for interactions between and effects of family type (i.e., parental marital status) and age and sex of child. Significant differences were found based on family type, with children of separated, divorced, and remarried parents having more problems. Expected interactions between marital status and age and sex of child were not obtained, although results support prior research with regard to the effects of age and sex.

  20. Cell Therapies in Cardiomyopathy: Current Status of Clinical Trials

    PubMed Central

    Wang, Richard

    2017-01-01

    Because the human heart has limited potential for regeneration, the loss of cardiomyocytes during cardiac myopathy and ischaemic injury can result in heart failure and death. Stem cell therapy has emerged as a promising strategy for the treatment of dead myocardium, directly or indirectly, and seems to offer functional benefits to patients. The ideal candidate donor cell for myocardial reconstitution is a stem-like cell that can be easily obtained, has a robust proliferation capacity and a low risk of tumour formation and immune rejection, differentiates into functionally normal cardiomyocytes, and is suitable for minimally invasive clinical transplantation. The ultimate goal of cardiac repair is to regenerate functionally viable myocardium after myocardial infarction (MI) to prevent or heal heart failure. This review provides a comprehensive overview of treatment with stem-like cells in preclinical and clinical studies to assess the feasibility and efficacy of this novel therapeutic strategy in ischaemic cardiomyopathy. PMID:28194324

  1. Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current status.

    PubMed

    van der Meel, Roy; Vehmeijer, Laurens J C; Kok, Robbert J; Storm, Gert; van Gaal, Ethlinn V B

    2013-10-01

    Since the introduction of Doxil® on the market nearly 20years ago, a number of nanomedicines have become part of treatment regimens in the clinic. With the exception of antibody-drug conjugates, these nanomedicines are all devoid of targeting ligands and rely solely on their physicochemical properties and the (patho)physiological processes in the body for their biodistribution and targeting capability. At the same time, many preclinical studies have reported on nanomedicines exposing targeting ligands, or ligand-targeted nanomedicines, yet none of these have been approved at this moment. In the present review, we provide a concise overview of 13 ligand-targeted particulate nanomedicines (ligand-targeted PNMs) that have progressed into clinical trials. The progress of each ligand-targeted PNM is discussed based on available (pre)clinical data. Main conclusions of these analyses are that (a) ligand-targeted PNMs have proven to be safe and efficacious in preclinical models; (b) the vast majority of ligand-targeted PNMs is generated for the treatment of cancer; (c) contribution of targeting ligands to the PNM efficacy is not unambiguously proven; and (d) targeting ligands do not cause localization of the PNM within the target tissue, but rather provide benefits in terms of target cell internalization and target tissue retention once the PNM has arrived at the target site. Increased understanding of the in vivo fate and interactions of the ligand-targeted PNMs with proteins and cells in the human body is mandatory to rationally advance the clinical translation of ligand-targeted PNMs. Future perspectives for ligand-targeted PNM approaches include the delivery of drugs that are unable or inefficient in passing cellular membranes, treatment of drug resistant tumors, targeting of the tumor blood supply, the generation of targeted vaccines and nanomedicines that are able to cross the blood-brain barrier.

  2. [Clinical research training in dentistry: analysis of the current status].

    PubMed

    Sosa Martínez, J; Deister Mateos, E

    1990-06-01

    The collegiate and university realms--which include lectures, students, clinical and scientific sessions--is open to growth. Furthermore, it has opened gates for new currents of thought and planted hopes for the growth and development of professors who, apart from mastering their specialty, may be familiar with didactics and directly or indirectly engage in full-time research, so that their lecturing and promotions may partially depend on the number and quality of their published works, preferably on scientific research.

  3. The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy.

    PubMed

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; Li, Quanhai; Yan, Baoyong

    2015-01-01

    Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34(+) and CD 133(+) stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future.

  4. Virologic Failure among Children Taking Lopinavir/Ritonavir-Containing First-Line Antiretroviral Therapy in South Africa

    PubMed Central

    Meyers, Tammy; Sawry, Shobna; Wong, Jessica Y.; Moultrie, Harry; Pinillos, Francoise; Fairlie, Lee; van Zyl, Gert

    2014-01-01

    Objective To report the outcomes, clinical management decisions and results of resistance testing among a group of children who developed virologic failure on first line lopinavir/ritonavir (LPV/r)-based therapy from a large cohort of ART-treated children in Soweto. Design Historical cohort study Methods Children with virologic failure were identified from a group of 1692 children <3 years who had initiated first-line LPV/r-containing therapy since 2000 up to end November 2011. Genotyping was conducted in some children and outcomes, management decisions and resistance results were described. Results 152 children with virologic failure on first-line LPV/r-containing ART were included. Resistance testing was performed in 75/152 (49%) and apart from a younger age (11.1 vs 15.1 months, p=0.04), the children with vs those without resistance testing were similar for baseline characteristics (weight, CD4, VL and time to failure). Genotyping revealed that 8/75 (10.7%) had significant LPV/r-associated resistance mutations, including 2 with intermediate DRV resistance. Among 63/75 (84%) children remaining on LPV/r-based therapy, 32/63 (51%) achieved virologic suppression, 2 of these children with significant LPV mutations. 12/152 (8%) children were switched to NNRTI-based therapy in accordance with local guidelines at the time. Of these, 4/12 (33%) resuppressed, and the rest did not achieve virologic suppression including the 2 with LPV mutations. Conclusions Virologic failure of LPV/r-containing first line regimens is associated with accumulation of LPV/r mutations in children. The implications are unclear and surveillance at selected sites is warranted for long-term virologic outcomes and development of resistance. PMID:25741970

  5. Self-Esteem, Oral Health Behaviours, and Clinical Oral Health Status in Chinese Adults: An Exploratory Study

    ERIC Educational Resources Information Center

    Chin, Luzy Siu-Hei; Chan, Joanne Chung-Yan

    2013-01-01

    Objectives: This is an exploratory study to examine the relations among self-esteem, oral health behaviours and clinical oral health status in Chinese adults. In addition, gender differences in clinical oral health status and oral health behaviours were explored. Methods: Participants were 192 patients from a private dental clinic in Hong Kong…

  6. Current Status of Xenotransplantation and Prospects for Clinical Application

    PubMed Central

    Pierson, Richard N.; Dorling, Anthony; Ayares, David; Rees, Michael A.; Seebach, Jörg D.; Fishman, Jay A.; Hering, Bernhard J.; Cooper, David K.C.

    2010-01-01

    Xenotransplantation is one promising approach to bridge the gap between available human cells, tissues, and organs and the needs of patients with diabetes or end-stage organ failure. Based on recent progress using genetically-modified source pigs, improving results with conventional and experimental immunosuppression, and expanded understanding of residual physiologic hurdles, xenotransplantation appears likely to be evaluated in clinical trials in the near future for some select applications. This review offers a comprehensive overview of known mechanisms of xenograft injury, a contemporary assessment of preclinical progress and residual barriers, and our opinions regarding where breakthroughs are likely to occur. PMID:19796067

  7. Current status of clinical particle radiotherapy at Lawrence Berkeley Laboratory

    SciTech Connect

    Castro, J.R.; Quivey, J.M.; Lyman, J.T.; Chen, G.T.Y.; Phillips, T.L.; Tobias, C.A.; Alpen, E.L.

    1980-08-15

    Clinical experience with charged particle irradiation of human cancers has been underway at the University of California Lawrence Berkeley Laboratory. Over 150 patients have been irradiated with heavy charged particle beams including helium, carbon, neon, and argon ions. Pilot studies have included such tumor sites as glioma of the brain, carcinoma of the esophagus, carcinoma of the pancreas, carcinoma of the stomach, ocular melanoma, and carcinoma of the uterine cervix. Prospective studies are planned to investigate the improved dose localization potential (helium) and the enhanced biologic and physical dose potential (carbon, neon) in a controlled trial against the best available megavoltage irradiation techniques.

  8. Raman spectroscopy: the gateway into tomorrow's virology

    PubMed Central

    Lambert, Phelps J; Whitman, Audy G; Dyson, Ossie F; Akula, Shaw M

    2006-01-01

    In the molecular world, researchers act as detectives working hard to unravel the mysteries surrounding cells. One of the researchers' greatest tools in this endeavor has been Raman spectroscopy. Raman spectroscopy is a spectroscopic technique that measures the unique Raman spectra for every type of biological molecule. As such, Raman spectroscopy has the potential to provide scientists with a library of spectra that can be used to unravel the makeup of an unknown molecule. However, this technique is limited in that it is not able to manipulate particular structures without disturbing their unique environment. Recently, a novel technology that combines Raman spectroscopy with optical tweezers, termed Raman tweezers, evades this problem due to its ability to manipulate a sample without physical contact. As such, Raman tweezers has the potential to become an incredibly effective diagnostic tool for differentially distinguishing tissue, and therefore holds great promise in the field of virology for distinguishing between various virally infected cells. This review provides an introduction for a virologist into the world of spectroscopy and explores many of the potential applications of Raman tweezers in virology. PMID:16805914

  9. Raman spectroscopy: the gateway into tomorrow's virology.

    PubMed

    Lambert, Phelps J; Whitman, Audy G; Dyson, Ossie F; Akula, Shaw M

    2006-06-28

    In the molecular world, researchers act as detectives working hard to unravel the mysteries surrounding cells. One of the researchers' greatest tools in this endeavor has been Raman spectroscopy. Raman spectroscopy is a spectroscopic technique that measures the unique Raman spectra for every type of biological molecule. As such, Raman spectroscopy has the potential to provide scientists with a library of spectra that can be used to unravel the makeup of an unknown molecule. However, this technique is limited in that it is not able to manipulate particular structures without disturbing their unique environment. Recently, a novel technology that combines Raman spectroscopy with optical tweezers, termed Raman tweezers, evades this problem due to its ability to manipulate a sample without physical contact. As such, Raman tweezers has the potential to become an incredibly effective diagnostic tool for differentially distinguishing tissue, and therefore holds great promise in the field of virology for distinguishing between various virally infected cells. This review provides an introduction for a virologist into the world of spectroscopy and explores many of the potential applications of Raman tweezers in virology.

  10. Paediatric Virology in the Hippocratic Corpus

    PubMed Central

    Mammas, Ioannis N.; Spandidos, Demetrios A.

    2016-01-01

    Hippocrates (Island of Kos, 460 B.C.-Larissa, 370 B.C.) is the founder of the most famous Medical School of the classical antiquity. In acknowledgement of his pioneering contribution to the new scientific field of Paediatric Virology, this article provides a systematic analysis of the Hippocratic Corpus, with particular focus on viral infections predominating in neonates and children. A mumps epidemic, affecting the island of Thasos in the 5th century B.C., is described in detail. ‘Herpes’, a medical term derived from the ancient Greek word ‘ἕρπειν’, meaning ‘to creep’ or ‘crawl’, is used to describe the spreading of cutaneous lesions in both childhood and adulthood. Cases of children with exanthema ‘resembling mosquito bites’ are presented in reference to varicella or smallpox infection. A variety of upper and lower respiratory tract viral infections are described with impressive accuracy, including rhinitis, pharyngitis, tonsillitis, laryngitis, bronchiolitis and bronchitis. The ‘cough of Perinthos’ epidemic, an influenza-like outbreak in the 5th century B.C., is also recorded and several cases complicated with pneumonia or fatal outcomes are discussed. Hippocrates, moreover, describes conjunctivitis, otitis, lymphadenitis, meningoencephalitis, febrile convulsions, gastroenteritis, hepatitis, poliomyelitis and skin warts, along with proposed treatment directions. Almost 2,400 years later, Hippocrates' systematic approach and methodical innovations can inspire paediatric trainees and future Paediatric Virology subspecialists. PMID:27446241

  11. Paediatric Virology: A rapidly increasing educational challenge

    PubMed Central

    Mammas, Ioannis N.; Theodoridou, Maria; Kramvis, Anna; Thiagarajan, Prakash; Gardner, Sharryn; Papaioannou, Georgia; Melidou, Angeliki; Koutsaki, Maria; Kostagianni, Georgia; Achtsidis, Vassilis; Koutsaftiki, Chryssie; Calachanis, Marcos; Zaravinos, Apostolos; Greenough, Anne; Spandidos, Demetrios A.

    2017-01-01

    The ‘2nd Workshop on Paediatric Virology’, which took place on Saturday the 8th of October 2016 in Athens, Greece, provided an overview on recent views and advances on Paediatric Virology. Emphasis was given to HIV-1 management in Greece, a country under continuous financial crisis, hepatitis B vaccination in Africa, treatment options for hepatitis C virus in childhood, Zika virus in pregnancy and infancy, the burden of influenza on childhood, hand-foot-mouth disease and myocarditis associated with Coxsackie viruses. Other general topics covered included a critical evaluation of Paediatric Accident and Emergency viral infections, multimodality imaging of viral infections in children, surgical approaches of otolaryngologists to complex viral infections, new advances in the diagnosis and treatment of viral conjunctivitis and novel molecular diagnostic methods for HPV in childhood. A brief historical overview of the anti-vaccination movement was also provided, as well as presentations on the educational challenge of Paediatric Virology as a new subspecialty of Paediatrics. This review highlights selected lectures and discussions of the workshop. PMID:28352303

  12. Synthetic virology: engineering viruses for gene delivery.

    PubMed

    Guenther, Caitlin M; Kuypers, Brianna E; Lam, Michael T; Robinson, Tawana M; Zhao, Julia; Suh, Junghae

    2014-01-01

    The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors. The enhanced viral vectors, or 'bionic' viruses, feature engineered components, or 'parts', that are natural (intrinsic to viruses or from other organisms) and synthetic (such as man-made polymers or inorganic nanoparticles). Various design strategies--rational, combinatorial, and pseudo-rational--have been pursued to create the hybrid viruses. The gene delivery vectors of the future will likely criss-cross the boundaries between natural and synthetic domains to harness the unique strengths afforded by the various functional parts that can be grafted onto virus capsids. Such research endeavors will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine.

  13. Virologic Response to Tipranavir-Ritonavir or Darunavir-Ritonavir Based Regimens in Antiretroviral Therapy Experienced HIV-1 Patients: A Meta-Analysis and Meta-Regression of Randomized Controlled Clinical Trials

    PubMed Central

    Berhan, Asres; Berhan, Yifru

    2013-01-01

    Background The development of tipranavir and darunavir, second generation non-peptidic HIV protease inhibitors, with marked improved resistance profiles, has opened a new perspective on the treatment of antiretroviral therapy (ART) experienced HIV patients with poor viral load control. The aim of this study was to determine the virologic response in ART experienced patients to tipranavir-ritonavir and darunavir-ritonavir based regimens. Methods and Findings A computer based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), Medline and Cochrane library. Meta-analysis was performed by including randomized controlled studies that were conducted in ART experienced patients with plasma viral load above 1,000 copies HIV RNA/ml. The odds ratios and 95% confidence intervals (CI) for viral loads of <50 copies and <400 copies HIV RNA/ml at the end of the intervention were determined by the random effects model. Meta-regression, sensitivity analysis and funnel plots were done. The number of HIV-1 patients who were on either a tipranavir-ritonavir or darunavir-ritonavir based regimen and achieved viral load less than 50 copies HIV RNA/ml was significantly higher (overall OR = 3.4; 95% CI, 2.61– 4.52) than the number of HIV-1 patients who were on investigator selected boosted comparator HIV-1 protease inhibitors (CPIs-ritonavir). Similarly, the number of patients with viral load less than 400 copies HIV RNA/ml was significantly higher in either the tipranavir-ritonavir or darunavir-ritonavir based regimen treated group (overall OR = 3.0; 95% CI, 2.15 – 4.11). Meta-regression showed that the viral load reduction was independent of baseline viral load, baseline CD4 count and duration of tipranavir-ritonavir or darunavir-ritonavir based regimen. Conclusions Tipranavir and darunavir based regimens were more effective in patients who were ART experienced and had poor viral load control. Further studies are

  14. The current status and trend of clinical pharmacology in developing countries

    PubMed Central

    2013-01-01

    Background Several international forums for promoting clinical pharmacology in developing countries have been held since 1980, and several clinical pharmacology programmes targeting developing countries were instituted such that the status of clinical pharmacology in developing countries is not where it was 50 years ago. Therefore, a survey and an appraisal of the literature on the current status of clinical pharmacology in developing countries were undertaken with a hope that it would enable development of appropriate strategies for further promotion of clinical pharmacology in these countries. Methods First, nine determinants (or enabling factors) for running a successful clinical pharmacology programme were identified, i.e., disease burden, drug situation, economic growth, clinical pharmacology activities, recognition, human capital, government support, international collaboration, and support for traditional/alternative medicines. These factors were then evaluated with regard to their current status in the developing countries that responded to an electronic questionnaire, and their historical perspective, using the literature appraisal. From these, a projected trend was constructed with recommendations on the way forward. Results Clinical pharmacology services, research and teaching in developing countries have improved over the past 50 years with over 90% of countries having the appropriate policies for regulation and rational use of medicines in place. Unfortunately, policy implementation remains a challenge, owing to a worsening disease burden and drug situation, versus fewer clinical pharmacologists and other competing priorities for the national budgets. This has led to a preference for training ‘a physician clinical pharmacologist’ in programmes emphasizing local relevancy and for a shorter time, and the training of other professionals in therapeutics for endemic diseases (task shifting), as the most promising strategies of ensuring rational use of

  15. Design rules for nanomedical engineering: from physical virology to the applications of virus-based materials in medicine.

    PubMed

    Wen, Amy M; Rambhia, Pooja H; French, Roger H; Steinmetz, Nicole F

    2013-03-01

    Physical virology seeks to define the principles of physics underlying viral infections, traditionally focusing on the fundamental processes governing virus assembly, maturation, and disassembly. A detailed understanding of virus structure and assembly has facilitated the development and analysis of virus-based materials for medical applications. In this Physical Virology review article, we discuss the recent developments in nanomedicine that help us to understand how physical properties affect the in vivo fate and clinical impact of (virus-based) nanoparticles. We summarize and discuss the design rules that need to be considered for the successful development and translation of virus-based nanomaterials from bench to bedside.

  16. Virological and serological features of acute hepatitis B in adults

    PubMed Central

    Du, Xiaofei; Liu, Yali; Ma, Lina; Lu, Junfeng; Jin, Yi; Ren, Shan; He, Zhimin; Chen, Xinyue

    2017-01-01

    Abstract Various viral kinetics among patients with acute hepatitis B (AHB) have been observed in clinical practice. This study investigated the virological, biochemical, and serological characteristics of AHB in adults. A total of 192 adult patients with AHB were recruited between December 2010 and January 2014. The quantification of biochemical and serologic markers for hepatitis B virus (HBV) infection was monitored from the onset. Of the 192 patients, 113 patients were followed up. One patient died due to acute liver failure, 2 developed chronic HBV infection. Clinical recovery was observed in 110 patients; 92.7% (102/110) achieved clinical recovery within 24 weeks, and 7.3% (8/110) between 24 and 44 weeks. There were 3 different viral kinetics patterns among the patients with AHB: the clearance of HBV DNA preceded hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg), the clearance of HBeAg preceded HBV DNA and HBsAg, the clearance of HBsAg preceded HBV DNA and HBeAg. In the absence of HBV DNA clearance within 13 weeks, the risk of development of chronic HBV infection increased. The serologic HBV markers clearance occurred between 24 and 44 weeks (6–11 months) from the onset in 8 of the AHB patients, which was longer than 6 months. Thus, AHB may be redefined as HBV DNA undetectable, HBsAg and HBeAg seroconversion within 44 weeks. PMID:28207518

  17. Research in the field of antiviral chemotherapy performed in the "Stefan S. Nicolau" Institute of Virology.

    PubMed

    Eşanu, V

    1984-01-01

    A brief review is made of the research in the field of antiviral chemotherapy performed in the "Stefan S. Nicolau" Institute of Virology during the 35 years since its foundation. The investigations have mainly focused on influenza and herpes virus, but the chemotherapy of other viral infections (mumps, vaccinia, Coxsackie, etc.) has also been approached. Most of the chemotherapy agents assayed have been represented by natural preparations: immunoglobulins, interferon, hormones, vitamins, plant extracts (garlic, horse radish), bee products (propolis, royal jelly); attempts have also been made with numerous synthetic compounds. Stress is laid on the preparations already tested with a view to application in human clinic, and the prospects of chemotherapy research in the Institute of Virology are discussed.

  18. Current views and advances on Paediatric Virology: An update for paediatric trainees.

    PubMed

    Mammas, Ioannis N; Greenough, Anne; Theodoridou, Maria; Kramvis, Anna; Christaki, Iliana; Koutsaftiki, Chryssie; Koutsaki, Maria; Portaliou, Dimitra M; Kostagianni, Georgia; Panagopoulou, Paraskevi; Sourvinos, George; Spandidos, Demetrios A

    2016-01-01

    Paediatric Virology is a bold new scientific field, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, Clinical Governance, Quality Improvement, Pharmacology and Immunology. The Workshop on Paediatric Virology, which took place on Saturday October 10, 2015 in Athens, Greece, provided an overview of recent views and advances on viral infections occurring in neonates and children. It was included in the official programme of the 20th World Congress on Advances in Oncology and the 18th International Symposium on Molecular Medicine, which attracted over 500 delegates from the five continents. During the Workshop, the topics covered included the challenges of vaccine implementation against human papillomaviruses in countries under financial crisis, strategies for eradicating poliomyelitis and its 60th vaccine anniversary, as well as the debate on the association between autism and vaccination against measles, mumps and rubella. Among the non-vaccine related topics, emphasis was given to viral infections in prematurely born infants and their long-term outcomes, new paediatric intensive care management options for bronchiolitis related to respiratory syncytial virus, the clinical implications of hepatitis B virus and cytomegalovirus genotyping, the Ebola virus threat and preparedness in Paediatric Emergency Departments, oral, oropharynx, laryngeal, nasal and ocular viral infections and Merkel cell polyomavirus as a novel emerging virus of infancy and childhood. In this review, we provide selected presentations and reports discussed at the Workshop.

  19. Current views and advances on Paediatric Virology: An update for paediatric trainees

    PubMed Central

    MAMMAS, IOANNIS N.; GREENOUGH, ANNE; THEODORIDOU, MARIA; KRAMVIS, ANNA; CHRISTAKI, ILIANA; KOUTSAFTIKI, CHRYSSIE; KOUTSAKI, MARIA; PORTALIOU, DIMITRA M.; KOSTAGIANNI, GEORGIA; PANAGOPOULOU, PARASKEVI; SOURVINOS, GEORGE; SPANDIDOS, DEMETRIOS A.

    2016-01-01

    Paediatric Virology is a bold new scientific field, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, Clinical Governance, Quality Improvement, Pharmacology and Immunology. The Workshop on Paediatric Virology, which took place on Saturday October 10, 2015 in Athens, Greece, provided an overview of recent views and advances on viral infections occurring in neonates and children. It was included in the official programme of the 20th World Congress on Advances in Oncology and the 18th International Symposium on Molecular Medicine, which attracted over 500 delegates from the five continents. During the Workshop, the topics covered included the challenges of vaccine implementation against human papillomaviruses in countries under financial crisis, strategies for eradicating poliomyelitis and its 60th vaccine anniversary, as well as the debate on the association between autism and vaccination against measles, mumps and rubella. Among the non-vaccine related topics, emphasis was given to viral infections in prematurely born infants and their long-term outcomes, new paediatric intensive care management options for bronchiolitis related to respiratory syncytial virus, the clinical implications of hepatitis B virus and cytomegalovirus genotyping, the Ebola virus threat and preparedness in Paediatric Emergency Departments, oral, oropharynx, laryngeal, nasal and ocular viral infections and Merkel cell polyomavirus as a novel emerging virus of infancy and childhood. In this review, we provide selected presentations and reports discussed at the Workshop. PMID:26889211

  20. T cell virological synapses and HIV-1 pathogenesis.

    PubMed

    Chen, Benjamin K

    2012-12-01

    Human immunodeficiency virus type 1 is the cause of a modern global pandemic associated with progressive acquired immune deficiency. The infection is characterized by the loss of the primary target of viral infection, the CD4+ T cell. The measurement of plasma viremia in patients can predict the rate of CD4+ cell decline; however, it is not clear whether this cell-free plasma virus represents the engine that drives viral spread. Active viral replication is mainly observed within lymphoid tissues that are hotbeds of cell-cell interactions that initiate and organize immune responses. It is well established that cell-cell interactions enhance viral spread in vitro. Dendritic cell-T cell interactions, which lie at the heart of adaptive immune responses, enhance viral infection in vitro. Interactions between infected and uninfected CD4+ T cells are a dominant route of viral spread in vitro and are likely to play a central role in viral dissemination in vivo. Future studies will test existing paradigms of HIV-1 dissemination to determine whether virus-transmitting contacts between infected and uninfected T cells called virological synapses are the dominant mode of viral spread in vivo. Here, we review the status of our understanding of this mode of infection with a focus on T cell-T cell interactions and examine how it may explain resistance to neutralizing antibodies and or the generation of genetic diversity of HIV.

  1. The influence of individual socioeconomic status on the clinical outcomes in ischemic stroke patients with different neighborhood status in Shanghai, China

    PubMed Central

    Yan, Han; Liu, Baoxin; Meng, Guilin; Shang, Bo; Jie, Qiqiang; Wei, Yidong; Liu, Xueyuan

    2017-01-01

    Objective: Socioeconomic status (SES) is being recognized as an important factor in both social and medical problems. The aim of present study is to examine the relationship between SES and ischemic stroke and investigate whether SES is a predictor of clinical outcomes among patients with different neighborhood status from Shanghai, China. Methods: A total of 471 first-ever ischemic stroke patients aged 18-80 years were enrolled in this retrospective study. The personal SES of each patient was evaluated using a summed score derived from his or her educational level, household income, occupation, and medical reimbursement rate. Clinical adverse events and all-cause mortality were analyzed to determine whether SES was a prognostic factor, its prognostic impact was then assessed based on different neighborhood status using multivariable Cox proportional hazard models after adjusting for other covariates. Results: The individual SES showed a significant positive correlation with neighborhood status (r = 0.370; P < 0.001). The incidence of clinical adverse events and mortality were significantly higher in low SES patients compared with middle and high SES patients (P = 0.001 and P = 0.037, respectively). After adjusting other risk factors and neighborhood status, Kaplan-Meier analysis showed clinical adverse events and deaths were still higher in the low SES patients (all P < 0.05). Multivariate Cox regression analysis demonstrated that both personal SES and neighborhood status are independent prognostic factors for ischemic stroke (all P < 0.05). Besides, among patients with low and middle neighborhood status, lower individual SES was significantly associated with clinical adverse events and mortality (all P < 0.05). Conclusion: Both individual SES and neighborhood status are significantly associated with the prognosis after ischemic stroke. A lower personal SES as well as poorer neighborhood status may significantly increase risk for adverse clinical outcomes among

  2. The influence of individual socioeconomic status on the clinical outcomes in ischemic stroke patients with different neighborhood status in Shanghai, China.

    PubMed

    Yan, Han; Liu, Baoxin; Meng, Guilin; Shang, Bo; Jie, Qiqiang; Wei, Yidong; Liu, Xueyuan

    2017-01-01

    Objective: Socioeconomic status (SES) is being recognized as an important factor in both social and medical problems. The aim of present study is to examine the relationship between SES and ischemic stroke and investigate whether SES is a predictor of clinical outcomes among patients with different neighborhood status from Shanghai, China. Methods: A total of 471 first-ever ischemic stroke patients aged 18-80 years were enrolled in this retrospective study. The personal SES of each patient was evaluated using a summed score derived from his or her educational level, household income, occupation, and medical reimbursement rate. Clinical adverse events and all-cause mortality were analyzed to determine whether SES was a prognostic factor, its prognostic impact was then assessed based on different neighborhood status using multivariable Cox proportional hazard models after adjusting for other covariates. Results: The individual SES showed a significant positive correlation with neighborhood status (r = 0.370; P < 0.001). The incidence of clinical adverse events and mortality were significantly higher in low SES patients compared with middle and high SES patients (P = 0.001 and P = 0.037, respectively). After adjusting other risk factors and neighborhood status, Kaplan-Meier analysis showed clinical adverse events and deaths were still higher in the low SES patients (all P < 0.05). Multivariate Cox regression analysis demonstrated that both personal SES and neighborhood status are independent prognostic factors for ischemic stroke (all P < 0.05). Besides, among patients with low and middle neighborhood status, lower individual SES was significantly associated with clinical adverse events and mortality (all P < 0.05). Conclusion: Both individual SES and neighborhood status are significantly associated with the prognosis after ischemic stroke. A lower personal SES as well as poorer neighborhood status may significantly increase risk for adverse clinical outcomes among

  3. Illness Representations of HIV Positive Patients Are Associated with Virologic Success

    PubMed Central

    Leone, Daniela; Borghi, Lidia; Lamiani, Giulia; Barlascini, Luca; Bini, Teresa; d’Arminio Monforte, Antonella; Vegni, Elena

    2016-01-01

    Introduction: It is important for HIV positive patients to be engaged in their care and be adherent to treatment in order to reduce disease progression and mortality. Studies found that illness representations influence adherence through the mediating role of coping behaviors. However, no study has ever tested if patient engagement to the visits mediate the relationship between illness perceptions and adherence. This study aimed to explore illness representations of HIV positive patients and test the hypothesis that illness representations predict adherence through the mediating role of a component of behavioral engagement. Methods: HIV-positive patients treated with highly active antiretroviral therapy (HAART) for at least one year and presenting to a check-up visit were eligible to participate in the study. Patients completed the Illness Perception Questionnaire-Revised. Behavioral engagement was measured based on the patients’ clinical attendance to the check-up visits; adherence to HAART was measured by viral load. Undetectable viral load or HIV-RNA < 40 copies/ml were considered indexes of virologic success. Results: A total of 161 patients participated in the study. Most of them coherently attributed the experienced symptoms to HIV/HAART; perceived their condition as chronic, stable, coherent, judged the therapy as effective, and attributed their disease to the HIV virus and to their behavior or bad luck. The majority of patients (80.1%) regularly attended check-up visits and 88.5% of them reached virologic success. The mediation model did not show good fit indexes. However, a significant direct effect of two independent variables on virologic success was found. Specifically, the perception that the disease does not have serious consequences on patient’s life and the prevalence of negative emotions toward HIV were associated with virologic success. On the contrary, the patient’s perception that the disease has serious consequences on his/her life and

  4. [Comments on influence of different functional status of the body on clinical effects of acupuncture therapy].

    PubMed

    Li, Zheng-Jie; Zeng, Fang; Yang, Jie; Ren, Yu-Lan; Liang, Fan-Rang

    2013-10-01

    Functional status is an important factor affecting clinical therapeutic effect of acupuncture therapy. Authors of the present article make an analysis on the related descriptions of ancient classical books about the patient's body constitution, age, duration of disease, type of disease or clinical conditions, psychological state, etc. which determine the functional state of patients. Moreover, the authors also make some comments on the results of modern clinical trials and experimental studies. However, till now, the results of many related modern studies were lower in reliability due to unreliable methodology. Fewer clinical trials involve the patient's psychological state, and constitution from the viewpoint of Chinese medicine. Correspondingly, the related experimental studies are fewer. The authors suggest that in the coming days clinical trials should be greatly improved in quality and the mutual interference among the influential factors should be excluded. At the same time, experimental studies on the related biochemical mechanisms should be strengthened.

  5. The role, responsibilities and status of the clinical medical physicist in AFOMP.

    PubMed

    Ng, K H; Cheung, K Y; Hu, Y M; Inamura, K; Kim, H J; Krisanachinda, A; Leung, J; Pradhan, A S; Round, H; van Doomo, T; Wong, T J; Yi, B Y

    2009-12-01

    This document is the first of a series of policy statements being issued by the Asia-Oceania Federation of Organizations for Medical Physics (AFOMP). The document was developed by the AFOMP Professional Development Committee (PDC) and was endorsed for official release by AFOMP Council in 2006. The main purpose of the document was to give guidance to AFOMP member organizations on the role and responsibilities of clinical medical physicists. A definition of clinical medical physicist has also been provided. This document discusses the following topics: professional aspects of education and training; responsibilities of the clinical medical physicist; status and organization of the clinical medical physics service and the need for clinical medical physics service.

  6. Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

    PubMed

    Miyake, Hidehiko; Yamada, Shigehito; Fujii, Yosuke; Sawai, Hideaki; Arimori, Naoko; Yamanouchi, Yasuko; Ozasa, Yuka; Kanai, Makoto; Sago, Haruhiko; Sekizawa, Akihiko; Takada, Fumio; Masuzaki, Hideaki; Matsubara, Yoichi; Hirahara, Fumiki; Kugu, Koji

    2016-10-01

    Prenatal testing has been provided in Japan over the past several decades. However, it is difficult to assess the clinical status of amniocentesis (AC) and maternal serum markers (MSM) because obstetricians can perform these tests without registration. This study aims to investigate the current clinical status of AC and MSM in Japan. We conducted a questionnaire study that was intended for a total of 5622 Japanese obstetrics/gynecology facilities during October 2013 to January 2014. The response rate was 40.8% (2295/5622). Of the 2295 facilities, 864 performed MSM (37.7%), 619 performed AC (27.0%) and 412 performed both (18.0%). The average number of MSM tests was 2.0 per month (range 0-52), and the average number of AC tests was 2.4 per month (range 0-30). Involvement of genetic professionals, such as clinical geneticists (CGs) and certified genetic counselors (CGCs), contribute to a content-rich explanation and management of difficult issues and lengthened the explanation time. Nevertheless, relatively few facilities employed these specialists (MSM: 96/864 and AC: 128/619). This is the first study to highlight the current clinical status of AC and MSM tests in Japan. Active involvement of CGs and CGCs can provide more appropriate genetic counseling for prenatal tests.

  7. Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG Task Force.

    PubMed

    Baughman, R P; Nagai, S; Balter, M; Costabel, U; Drent, M; du Bois, R; Grutters, J C; Judson, M A; Lambiri, I; Lower, E E; Muller-Quernheim, J; Prasse, A; Rizzato, G; Rottoli, P; Spagnolo, P; Teirstein, A

    2011-07-01

    The clinical outcome of sarcoidosis is quite variable. Several scoring systems have been used to assess the level of disease and clinical outcome. The definition of clinical phenotypes has become an important goal as genetic studies have identified distinct genotypes associated with different clinical phenotypes. In addition, treatment strategies have been developed for patients with resolving versus non resolving disease. A task force was established by the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) to define clinical phenotypes of the disease based on the clinical outcome status (COS). The committee chose to examine patients five years after diagnosis to determine the COS. Several features of the disease were incorporated into the final nine categories of the disease. These included the current or past need for systemic therapy, the resolution of the disease, and current status of the condition. Sarcoidosis patients who were African American or older were likely to have a higher COS, indicating more chronic disease. The COS may be useful in future studies of sarcoidosis.

  8. Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

    PubMed Central

    El-Khatib, Ziad; Katzenstein, David; Marrone, Gaetano; Laher, Fatima; Mohapi, Lerato; Petzold, Max; Morris, Lynn; Ekström, Anna Mia

    2011-01-01

    Background Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa. Methods In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12–99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO). Results After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2–6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2–3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02). Conclusion One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure. PMID:21408071

  9. Clinical Variables Associated with Hydration Status in Acute Ischemic Stroke Patients with Dysphagia.

    PubMed

    Crary, Michael A; Carnaby, Giselle D; Shabbir, Yasmeen; Miller, Leslie; Silliman, Scott

    2016-02-01

    Acute stroke patients with dysphagia are at increased risk for poor hydration. Dysphagia management practices may directly impact hydration status. This study examined clinical factors that might impact hydration status in acute ischemic stroke patients with dysphagia. A retrospective chart review was completed on 67 ischemic stroke patients who participated in a prior study of nutrition and hydration status during acute care. Prior results indicated that patients with dysphagia demonstrated elevated BUN/Cr compared to non-dysphagia cases during acute care and that BUN/Cr increased selectively in dysphagic patients. This chart review evaluated clinical variables potentially impacting hydration status: diuretics, parenteral fluids, tube feeding, oral diet, and nonoral (NPO) status. Exposure to any variable and number of days of exposure to each variable were examined. Dysphagia cases demonstrated significantly more NPO days, tube fed days, and parenteral fluid days, but not oral fed days, or days on diuretics. BUN/Cr values at discharge were not associated with NPO days, parenteral fluid days, oral fed days, or days on diuretics. Patients on modified solid diets had significantly higher mean BUN/Cr values at discharge (27.12 vs. 17.23) as did tube fed patients (28.94 vs. 18.66). No difference was noted between these subgroups at baseline (regular diet vs. modified solids diets). Any modification of solid diets (31.11 vs. 17.23) or thickened liquids (28.50 vs. 17.81) resulted in significantly elevated BUN/Cr values at discharge. Liquid or diet modifications prescribed for acute stroke patients with dysphagia may impair hydration status in these patients.

  10. 1st Workshop of the Canadian Society for Virology

    PubMed Central

    McCormick, Craig; Grandvaux, Nathalie

    2017-01-01

    The 1st Workshop of the Canadian Society for Virology (CSV2016) was a Special Workshop of the 35th Annual Meeting for the American Society for Virology, held on 18 June 2016 on the beautiful Virginia Tech campus in Blacksburg, Virginia. The workshop provided a forum for discussion of recent advances in the field, in an informal setting conducive to interaction with colleagues. CSV2016 featured two internationally-renowned Canadian keynote speakers who discussed translational virology research; American Society for Virology President Grant McFadden (then from University of Florida, now relocated to Arizona State University) who presented his studies of oncolytic poxviruses, while Matthew Miller (McMaster University) reviewed the prospects for a universal influenza vaccine. The workshop also featured a variety of trainee oral and poster presentations, and a panel discussion on the topic of the future of the CSV and virus research in Canada. PMID:28335511

  11. [Virological diagnosis and follow-up of HIV infection. State of the art and situation in Tunisia].

    PubMed

    Ben Mamou, Myriam; Slim, Amine; Garbouj, Mounira; Ben Redjeb, Saida

    2006-07-01

    Human immunodeficiency virus (HIV) is a retrovirus infecting approximatively 40 million people worldwide. HIV is characterized by a great variability with epidemiological, diagnostic and therapeutic implications. The course of infection goes through three stages (acute infection, clinical latency and AIDS) with the evolution of virological markers (anti-HIV antibodies, p24 antigenemia, plasma RNA and proviral DNA). Direct virological diagnosis is mainly based on molecular tools allowing viral genome detection and amplification with specific primers and nucleic probes besides p24 antigenemia detection, and more rarely viral culture. Antigenic properties of viral proteins elicit in infected patients antibody synthesis, which is detected using serology (ELISA and Western blot tests). The follow-up of infected patients is carried out with plasma HIV-1 RNA quantitation and phenotypic or genotypic characterization of variant isolates. Virological tests are prescribed according to clinical presentation (screening, acute infection, newborn from HIV-infected mother). Most of these virological tools are available in Tunisia, allowing both diagnosis of HIV infection and monitoring of infected individuals. Regarding diagnostic tests indication and interpretation, multidisciplinary concertation is hopeful in order to optimize patient management.

  12. Immunization Status of Young People Attending a Youth Clinic in Geneva, Switzerland.

    PubMed

    Meynard, Anne; Genequand, Lydia Markham; Jeannot, Emilien; Wyler-Lazarevic, Claire-Anne; Cerutti, Bernard; Narring, Françoise

    2016-04-01

    Adolescent vaccination coverage is very variable in European countries and data are scarce. The aim of this study was to assess immunization status and analyze potential variations according to sociodemographic variables in a youth clinic in Geneva, Switzerland. Immunization status was assessed retrospectively: Tetanus (number of doses or in absence of data tetanus antibodies) and measles as indicators of childhood coverage as well as hepatitis B and human papillomavirus. All new patients (N = 390) of Geneva University Hospital's youth clinic were included between January 2010 and June 2011. Vaccine coverage was low for all vaccines regardless of sex or origin. 89% of young people tested (mostly recent immigrants with no available data) had tetanus antibodies indicating adequate childhood immunization but hepatitis B and HPV coverage was low especially in recent immigrants. Systematic assessment allows better adolescent vaccine coverage and can improve safety by avoiding unnecessary dosis.

  13. Virological diagnosis of African swine fever--comparative study of available tests.

    PubMed

    Oura, C A L; Edwards, L; Batten, C A

    2013-04-01

    The rapid and reliable detection of African swine fever virus (ASFV) is essential both for timely implementation of control measures to prevent the spread of disease, and to differentiate African swine fever (ASF) from other pig disease with similar clinical presentations. Many virological tests are currently available for the detection of ASFV (live virus), antigen and genome, including virus isolation, ELISA, fluorescent antibody, polymerase chain reaction (PCR) and isothermal assays. In recent years real-time PCR (rPCR) has become one of the most widely used formats for virological diagnosis providing sensitive, specific and swift detection and quantification of ASFV DNA. The ability to integrate rPCR into automated platforms increases sample throughput and decreases the potential for cross-contamination. In more recent years isothermal assays, which are a lower-cost alternative to PCR more suitable for use in non-specialised or mobile laboratories, have been developed for the detection of ASFV, however these assays have not been fully validated for routine use in the field. The performance of all virological detection assays in ASF diagnostics, as well as prospects for improving diagnostic strategies in the future, are discussed and reviewed in this chapter.

  14. [Epilepsies with electric status epilepticus in sleep: peculiarities of clinical course and rational approaches to treatment].

    PubMed

    Ermolenko, N A; Ermakov, A Iu; Buchneva, I A; Zakharova, E I; Kalikina, T A

    2011-01-01

    We studied 52 patients with electric status epilepticus in slow sleep (EESSS) during 3-5 years. Age-dependent peculiarities of clinical course of the disease, risk factors for EESSS and rational approaches to antiepileptic treatment for these cases were singled out. Symptomatic and idiopathic EESSS variants were revealed. Combinations of valproates, levetiracetam and ethosuximidum were the most effective antiepileptic drugs in the treatment of EESSS.

  15. Clinical evolution and nutritional status in asthmatic children and adolescents enrolled in Primary Health Care

    PubMed Central

    Morishita, Rosinha Yoko Matsubayaci; Strufaldi, Maria Wany Louzada; Puccini, Rosana Fiorini

    2015-01-01

    Objective: To evaluate the clinical evolution and the association between nutritional status and severity of asthma in children and adolescents enrolled in Primary Health Care. Methods: A retrospective cohort study of 219 asthmatic patients (3-17 years old) enrolled in Primary Care Services (PCSs) in Embu das Artes (SP), from 2007 to 2011. Secondary data: gender, age, diagnosis of asthma severity, other atopic diseases, family history of atopy, and body mass index. To evaluate the clinical outcome of asthma, data were collected on number of asthma exacerbations, number of emergency room consultations and doses of inhaled corticosteroids at follow-up visits in the 6th and 12th months. The statistical analysis included chi-square and Kappa agreement index, with 5% set as the significance level. Results: 50.5% of patients started wheezing before the age of 2 years, 99.5% had allergic rhinitis and 65.2% had a positive family history of atopy. Regarding severity, intermittent asthma was more frequent (51.6%) and, in relation to nutritional status, 65.8% of patients had normal weight. There was no association between nutritional status and asthma severity (p=0.409). After 1 year of follow-up, 25.2% of patients showed reduction in exacerbations and emergency room consultations, and 16.2% reduced the amount of inhaled corticosteroids. Conclusions: The monitoring of asthmatic patients in Primary Care Services showed improvement in clinical outcome, with a decreased number of exacerbations, emergency room consultations and doses of inhaled corticosteroids. No association between nutritional status and asthma severity was observed in this study. PMID:26316387

  16. Preoperative Nutritional Status and Clinical Complications in the Postoperative Period of Cardiac Surgeries

    PubMed Central

    Gonçalves, Luciana de Brito; de Jesus, Natanael Moura Teixeira; Gonçalves, Maiara de Brito; Dias, Lidiane Cristina Gomes; Deiró, Tereza Cristina Bomfim de Jesus

    2016-01-01

    Objective This study aims to assess the preoperative nutritional status of patients and the role it plays in the occurrence of clinical complications in the postoperative period of major elective cardiac surgeries. Methods Cross-sectional study comprising 72 patients aged 20 years or older, who underwent elective cardiac surgery. The preoperative nutritional assessment consisted of nutritional screening, anthropometry (including the measurement of the adductor pollicis muscle thickness) and biochemical tests. The patients were monitored for up to 10 days after the surgery in order to control the occurrence of postoperative complications. The R software, version 3.0.2, was used to statistically analyze the data. Results Clinical complications were found in 62.5% (n=42) of the studied samples and complications of non-infectious nature were most often found. Serum albumin appeared to be associated with renal complications (P=0.026) in the nutritional status indicators analyzed herein. The adductor pollicis muscle thickness was associated with infectious complications and presented mean of 9.39±2.32 mm in the non-dominant hand (P=0.030). No significant correlation was found between the other indicators and the clinical complications. Conclusion The adductor pollicis muscle thickness and the serum albumin seemed be associated with clinical complications in the postoperative period of cardiac surgeries. PMID:27982346

  17. Gender-specific risk factors for virologic failure in KwaZulu-Natal: automobile ownership and financial insecurity.

    PubMed

    Hare, Anna Q; Ordóñez, Claudia E; Johnson, Brent A; Del Rio, Carlos; Kearns, Rachel A; Wu, Baohua; Hampton, Jane; Wu, Peng; Sunpath, Henry; Marconi, Vincent C

    2014-11-01

    We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line ART, defined as viral load >1,000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p < 0.05) were used in multivariate models and all models were stratified by gender. Of 158 cases and 300 controls, 35 % were male and median age was 40 years. Gender stratification of models revealed automobile ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis.

  18. Gender-specific risk factors for virologic failure in KwaZulu-Natal: Automobile ownership and financial insecurity

    PubMed Central

    HARE, Anna Q.; ORDÓÑEZ, Claudia E.; JOHNSON, Brent A.; RIO, Carlos DEL; KEARNS, Rachel A.; WU, Baohua; HAMPTON, Jane; WU, Peng; SUNPATH, Henry; MARCONI, Vincent C.

    2014-01-01

    We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line antiretroviral therapy (ART), defined as viral load > 1000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p<.05) were used in multivariate models and all models were stratified by gender. Of 158 cases and 300 controls, 35% were male and median age was 40 years. Gender stratification of models revealed automobile ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis. PMID:25037488

  19. Assessment of demographic and clinical characteristics on functional status and disability of patients with stroke

    PubMed Central

    Memis, Derya; Kozanoglu, Erkan; Kelle, Bayram; Goncu, Mustafa K.

    2016-01-01

    Objective: To determine the effects of demographic and clinical characteristics on mobility, disability, and activities of daily life of patients with stroke. Methods: This cross-sectional clinical study was performed in the Department of Physical Medicine and Rehabilitation in Cukurova University Faculty of Medicine in Adana, Turkey, between February 2011 and December 2011. The study included 126 patients with stroke. The Brunnstrom recovery scale (BRS), functional ambulation classification scale (FACS), modified Barthel index (MBI), modified Rankin scale (MRS), and Rivermead mobility index (RMI) were used in the evaluation of the functional status of stroke patients. Correlations between each scale and parameters including age, etiology, and duration of hemiplegia were assessed. Results: The major etiology of stroke was found as ischemic (77%). Hypertension was a major risk factor in both genders (72% for males, 85% for females). Statistically significant differences were found between ischemic and hemorrhagic stroke patients regarding the RMI, MBI, BRS, and the FACS (p<0.001). Age had a poor negative correlation with the FACS and RMI. Conclusion: It is suggested that age is an important risk factor for the development of stroke, but it has no strong effect on functional status and disability in patients with stroke. The BRS, FACS, MBI, MRS, and RMI scales can be used in stroke patients whether they are under or over 65 years old in order to evaluate functional status and disability. PMID:27744465

  20. Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status.

    PubMed

    Schöpke, K; Gomez, A; Dunbar, K A; Swalve, H H; Döpfer, D

    2015-11-01

    Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (±0.11) and 0.52 (±0

  1. Relationship between radiological grading and clinical status in knee osteoarthritis. a multicentric study

    PubMed Central

    2012-01-01

    Background Controversy exists regarding the relationship between radiographic findings and clinical status in knee osteoarthritis. Although the surgical indication for total knee arthroplasty (TKA) should be based on pain, clinical status, and the deterioration of quality of life, the radiographic study is the most commonly used criterion for preoperative evaluation. The objective of this study is to find out the relationship between the Ahlbäck classification and clinical status in patients undergoing TKA. Methods 1329 protocols were collected from preoperative studies in four multicentric working groups (the Interax, Duracon, Scorpio, and Triathlon Spanish groups) in 30 Spanish hospitals. Mean age was 70.4 years (SD: 6.8; range: 35 to 98); 76.3% of patients were women. Patients entered the study whenever the surgeon found that medical treatment was insufficient to control pain and functional limitation. Data were collected using electronic Case Report Forms, and included Ahlbäck grading scores, Hospital for Special Surgery Knee Score (HSS), SF-12, and other clinical and epidemiologic variables. Results According to the Ahlbäck grading system, patients were divided as follows: 243 grade I (18.3%), 358 grade II (26.9%), 416 grade III (31.3%), 241 grade IV (18.1%), and 71 grade V (5.3%). As for HSS, the following scores were obtained: <60 points in 925 patients (69.6%), 60 to 69 points in 286 patients (21.5%), 70 to 84 points in 112 patients (8.4%) and 85 to 100 points in 6 patients (0.5%). Scores showed a statistically significant difference depending on Ahlbäck grade, with a clear tendency towards decrease in HSS scores as the Ahlbäck grade increases (p<0.001). However, the HSS score difference between Ahlbäck grades I and V was of 9.56 points only. Comparing the status of the patients at the start (1994) and at the end (2010) of the data collection process, we observed that patients who underwent surgery in the last years were older and showed a lower Ahlb

  2. Variation in serum biomarkers with sex and female hormonal status: implications for clinical tests

    PubMed Central

    Ramsey, Jordan M.; Cooper, Jason D.; Penninx, Brenda W. J. H.; Bahn, Sabine

    2016-01-01

    Few serum biomarker tests are implemented in clinical practice and recent reports raise concerns about poor reproducibility of biomarker studies. Here, we investigated the potential role of sex and female hormonal status in this widespread irreproducibility. We examined 171 serum proteins and small molecules measured in 1,676 participants from the Netherlands Study of Depression and Anxiety. Concentrations of 96 molecules varied with sex and 66 molecules varied between oral contraceptive pill users, postmenopausal females, and females in the follicular and luteal phases of the menstrual cycle (FDR-adjusted p-value <0.05). Simulations of biomarker studies yielded up to 40% false discoveries when patient and control groups were not matched for sex and up to 41% false discoveries when premenopausal females were not matched for oral contraceptive pill use. High accuracy (over 90%) classification tools were developed to label samples with sex and female hormonal status where this information was not collected. PMID:27240929

  3. Application perspectives of localization microscopy in virology.

    PubMed

    Cremer, C; Kaufmann, R; Gunkel, M; Polanski, F; Müller, P; Dierkes, R; Degenhard, S; Wege, C; Hausmann, M; Birk, U

    2014-07-01

    Localization microscopy approaches allowing an optical resolution down to the single-molecule level in fluorescence-labeled biostructures have already found a variety of applications in cell biology, as well as in virology. Here, we focus on some perspectives of a special localization microscopy embodiment, spectral precision distance/position determination microscopy (SPDM). SPDM permits the use of conventional fluorophores or fluorescent proteins together with standard sample preparation conditions employing an aqueous buffered milieu and typically monochromatic excitation. This allowed superresolution imaging and studies on the aggregation state of modified tobacco mosaic virus particles on the nanoscale with a single-molecule localization accuracy of better than 8 nm, using standard fluorescent dyes in the visible spectrum. To gain a better understanding of cell entry mechanisms during influenza A virus infection, SPDM was used in conjunction with algorithms for distance and cluster analyses to study changes in the distribution of virus particles themselves or in the distribution of infection-related proteins, the hepatocyte growth factor receptors, in the cell membrane on the single-molecule level. Not requiring TIRF (total internal reflection) illumination, SPDM was also applied to study the molecular arrangement of gp36.5/m164 glycoprotein (essentially associated with murine cytomegalovirus infection) in the endoplasmic reticulum and the nuclear membrane inside cells with single-molecule resolution. On the basis of the experimental evidence so far obtained, we finally discuss additional application perspectives of localization microscopy approaches for the fast detection and identification of viruses by multi-color SPDM and combinatorial oligonucleotide fluorescence in situ hybridization, as well as SPDM techniques for optimization of virus-based nanotools and biodetection devices.

  4. Sexual Risk Behavior Among Virologically Detectable Human Immunodeficiency Virus–Infected Young Men Who Have Sex With Men

    PubMed Central

    Wilson, Patrick A.; Kahana, Shoshana Y.; Fernandez, Maria Isabel; Harper, Gary W.; Mayer, Kenneth; Wilson, Craig M.; Hightow-Weidman, Lisa B.

    2016-01-01

    Importance Human immunodeficiency virus (HIV) diagnoses continue to increase among young men who have sex with men (YMSM). Many YMSM living with HIV engage in sexual risk behaviors, and those who have a detectable viral load can transmit HIV to sex partners. Understanding factors that are related to sexual risk taking among virologically detectable (VL+) YMSM can inform prevention and treatment efforts. Objectives To describe differences between virologically suppressed (VL−) and VL+ YMSM living with HIV and to identify correlates of condomless anal intercourse (CAI) and serodiscordant CAI among VL+ YMSM. Design, Setting, and Participants In this cross-sectional survey conducted from December 1, 2009, through June 30, 2012, we studied 991 HIV-infected YMSM 15 to 26 years of age at 20 adolescent HIV clinics in the United States. Data analysis was conducted December 1, 2013, through July 31, 2015. Main Outcomes and Measures Demographic, behavioral, and psychosocial assessments obtained using audio computer-assisted self-interviews. Viral load information was obtained via blood draw or medical record abstraction. Results Of the 991 participants, 688 (69.4%) were VL+ and 458 (46.2%) reported CAI, with 310 (31.3%) reporting serodiscordant CAI in the past 3 months. The VL+ YMSM were more likely than the VL− YMSM to report CAI (detectable, 266 [54.7%]; suppressed, 91 [44.4%]; P = .01) and serodiscordant CAI (detectable, 187 [34.9%]; suppressed, 57 [25.0%]; P < .01). Multivariable analyses indicated that among VL+ YMSM, those reporting problematic substance use were more likely to report CAI (adjusted odds ratio [AOR], 1.46; 95% CI, 1.02-2.10) and serodiscordant CAI (AOR, 1.45; 95% CI, 1.06-1.99). Black VL+ YMSM were less likely to report CAI (AOR, 0.63; 95% CI, 0.44-0.90) or serodiscordant CAI (AOR, 0.66; 95% CI, 0.46-0.94) compared with other VL+ YMSM. In addition, VL+ YMSM who disclosed their HIV status to sex partners were more likely to report CAI compared with

  5. Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov.

    PubMed

    Cihoric, Nikola; Tsikkinis, Alexandros; Minniti, Giuseppe; Lagerwaard, Frank J; Herrlinger, Ulrich; Mathier, Etienne; Soldatovic, Ivan; Jeremic, Branislav; Ghadjar, Pirus; Elicin, Olgun; Lössl, Kristina; Aebersold, Daniel M; Belka, Claus; Herrmann, Evelyn; Niyazi, Maximilian

    2017-01-03

    The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

  6. Impact of smoking status on clinical outcome in oral cavity cancer patients.

    PubMed

    Kawakita, Daisuke; Hosono, Satoyo; Ito, Hidemi; Oze, Isao; Watanabe, Miki; Hanai, Nobuhiro; Hasegawa, Yasuhisa; Tajima, Kazuo; Murakami, Shingo; Tanaka, Hideo; Matsuo, Keitaro

    2012-02-01

    The association between smoking status and survival in oral cavity squamous cell carcinoma (OSCC) patients remains unclear. Therefore, we evaluated the association between smoking status before treatment and clinical outcome in OSCC patients. We conducted a retrospective cohort study of 222 OSCC patients who were treated at Aichi Cancer Center in Japan. Of these, 82 patients (36.9%) were non-smokers, 65 (29.3%) were light smokers (pack-years smoking (PY) <30), 54 (24.3%) were moderate smokers (30≤PY<60), and 21 (9.5%) were heavy smokers (60≤PY). The survival impact of pre-treatment smoking status was evaluated using multivariate proportional hazard models. Five-year overall survival for non-, light, moderate, and heavy smokers was 72.9% (95% confidence interval CI): (61.4-81.5), 85.5% (74.0-92.2), 59.9% (44.3-72.4) and 69.0% (42.8-85.0). Adjusted hazard ratios (HRs) for moderate and heavy smokers in comparison with light smokers were 2.44 (1.07-5.57, P=0.034) and 2.66 (0.97-7.33, P=0.058) and the dose-response relationship among smokers was statistically significance (P(trend)=0.024). In addition, adjusted HR for non-smokers relative to light smokers was 2.27 (0.84-6.15, P=0.108). We observed a suggestive heterogeneity in the impact of smoking status by treatment method (P for heterogeneity=0.069). Effect of smoking was evident only among the chemoradiotherapy or radiotherapy group. In this study, we found the significant positive dose-response relationship among smokers on clinical outcome in OSCC patients and that non-smokers were worse prognosis than light smokers. In addition, this effect might differ by treatment method.

  7. Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma.

    PubMed

    Mandel, Jacob J; Cachia, David; Liu, Diane; Wilson, Charmaine; Aldape, Ken; Fuller, Greg; de Groot, John F

    2016-08-01

    IDH1 mutated glioblastoma (GB) has a better prognosis than IDH1 wildtype GB. However, it remains unknown whether patients (pts) with IDH1 mutated GB have a higher 6-month progression free survival (PFS6) or radiographic response (RR) rate on clinical trials for recurrence. Retrospective review of GB pts at MDACC between 2006 and 2012 identified 330 patients in recurrent GB trials. 93 patients (28 %) had either PFS6 or a complete/partial RR per RANO criteria. 49/93 (53 %) patients with PFS6 or a complete/partial RR had tumor tissue for IDH1 testing. A matched cohort of 49 patients on recurrent GB clinical trials that failed to achieve PFS6 or RR (also with tissue for IDH1 testing) was identified for comparison. IDH1 status was obtained in 92/98 (94 %) patients of which 17 (18 %) had an IDH1 mutation. PFS6 was seen in 26/49 (53 %) patients. IDH status was unknown in two of these patients. 5/24 (21 %) were IDH1 mutated compared to 5/24 (21 %) of their matched cohort without PFS6. RR was found in 47/49 (94 %) patients. IDH status was unknown in four of these patients. IDH1 mutation was present in 7/43 (16 %) patients with RR compared to 10/43 (23 %) in the matched cohort without RR (p = 0.48). Median OS for trials at first recurrence was 9.8 months for IDH1 wildtype GB vs. 19.32 months for IDH1 mutated GB (p = 0.14). IDH1 mutation status was not predictive of PFS6 or RR in recurrent GB trials for this data set. However, further examination in larger randomized prospective studies is needed.

  8. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia.

    PubMed

    Tobón-Castaño, Alberto; Mesa-Echeverry, Esteban; Miranda-Arboleda, Andrés Felipe

    2015-01-01

    Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%), 313 with P. vivax infection (35.2%), and 19 with mixed infection by these species (2.1%). Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54%) followed by monocytosis (11%); the differential granulocyte count in 298 patients revealed eosinophilia (15%) and high basophil counts (8%). Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response.

  9. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia

    PubMed Central

    Tobón-Castaño, Alberto; Mesa-Echeverry, Esteban; Miranda-Arboleda, Andrés Felipe

    2015-01-01

    Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%), 313 with P. vivax infection (35.2%), and 19 with mixed infection by these species (2.1%). Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54%) followed by monocytosis (11%); the differential granulocyte count in 298 patients revealed eosinophilia (15%) and high basophil counts (8%). Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response. PMID:26664413

  10. Non-convulsive status epilepticus: usefulness of clinical features in selecting patients for urgent EEG

    PubMed Central

    Husain, A; Horn, G; Jacobson, M

    2003-01-01

    Background: Non-convulsive status epilepticus (NCSE) is status epilepticus without obvious tonic–clonic activity. Patients with NCSE have altered mental state. An EEG is needed to confirm the diagnosis, but obtaining an EEG on every patient with altered mental state is not practical. Objective: To determine whether clinical features could be used to predict which patients were more likely to be in NCSE and thus in need of an urgent EEG. Methods: Over a six month period, all patients for whom an urgent EEG was ordered to identify NCSE were enrolled. Neurology residents examined the patients and filled out a questionnaire without knowledge of the EEG results. The patients were divided into two groups, NCSE and non-NCSE, depending on the EEG result. The clinical features were compared between the two groups. The sensitivity and specificity of the features were calculated. Results: 48 patients were enrolled, 12 in NCSE and 36 not in NCSE. Remote risk factors for seizures, severely impaired mental state, and ocular movement abnormalities were seen significantly more often in the NCSE group. The combined sensitivity of remote risk factors for seizures and ocular movement abnormalities was 100%. Conclusions: There are certain clinical features that are more likely to be present in patients in NCSE compared with other types of encephalopathy. Either remote risk factors for seizures or ocular movement abnormalities were seen in all patients in NCSE. These features may be used to select which patients should have an urgent EEG. PMID:12531946

  11. Immunological/virological peripheral blood biomarkers and distinct patterns of sleeping quality in chronic hepatitis C patients.

    PubMed

    de Almeida, C M O; de Lima, T A; Castro, D B; Torres, K L; da Silva Braga, W; Peruhype-Magalhães, V; Teixeira-Carvalho, A; Martins-Filho, O A; Malheiro, A

    2011-05-01

    The rational of this study we intended to investigate whether the peripheral blood immunological/virological biomarkers were associated with distinct patterns of sleeping quality in patients with chronic hepatitis C-(HCV). Distinct well-established indexes/scores were used to categorize the sleeping quality of HCV patients, including the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale and Fatigue Severity Scores. Our findings demonstrated that HCV patients classified as 'good sleeper' displayed an enhanced frequency of circulating CD8(+) T cells, lower frequency of activated (CD69(+)) neutrophils and eosinophils but enhanced frequency of activated lymphocytes besides lower seric levels of IL-4/IL-8/IL-10 but higher levels of IL-12, besides lower HCV virus load and lower anti-HCV IgG levels. In contrast, HCV patients classified as 'poor sleeper' displayed enhanced levels of activated neutrophils and eosinophils but lower frequency of activated lymphocytes, higher seric levels of IL-6/TNF-α/IL-10 but lower levels of IL-12 besides higher HCV virus load and increased anti-HCV IgG levels. Positive correlation was further confirmed by the relationship between the leucocyte activation status, the cytokine levels, the HCV viral load and the anti-HCV IgG reactivity with the PSQI indexes. Analysis of cytokine signature curves demonstrated that lower frequency of IL-10 was observed in HCV patients classified as 'good sleepers', whereas enhanced frequency of IL-6 was found HCV patients classified as 'poor sleepers'. In conclusion, our data suggest that immunological biomarkers (leucocytes activation status and seric cytokines levels) are likely to be associated with sleeping quality patterns in HCV patients, suggesting their putative use for clinical monitoring purposes.

  12. A text mining approach to the prediction of disease status from clinical discharge summaries.

    PubMed

    Yang, Hui; Spasic, Irena; Keane, John A; Nenadic, Goran

    2009-01-01

    OBJECTIVE The authors present a system developed for the Challenge in Natural Language Processing for Clinical Data-the i2b2 obesity challenge, whose aim was to automatically identify the status of obesity and 15 related co-morbidities in patients using their clinical discharge summaries. The challenge consisted of two tasks, textual and intuitive. The textual task was to identify explicit references to the diseases, whereas the intuitive task focused on the prediction of the disease status when the evidence was not explicitly asserted. DESIGN The authors assembled a set of resources to lexically and semantically profile the diseases and their associated symptoms, treatments, etc. These features were explored in a hybrid text mining approach, which combined dictionary look-up, rule-based, and machine-learning methods. MEASUREMENTS The methods were applied on a set of 507 previously unseen discharge summaries, and the predictions were evaluated against a manually prepared gold standard. The overall ranking of the participating teams was primarily based on the macro-averaged F-measure. RESULTS The implemented method achieved the macro-averaged F-measure of 81% for the textual task (which was the highest achieved in the challenge) and 63% for the intuitive task (ranked 7(th) out of 28 teams-the highest was 66%). The micro-averaged F-measure showed an average accuracy of 97% for textual and 96% for intuitive annotations. CONCLUSIONS The performance achieved was in line with the agreement between human annotators, indicating the potential of text mining for accurate and efficient prediction of disease statuses from clinical discharge summaries.

  13. Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer.

    PubMed

    Fernández-Marcelo, Tamara; Sánchez-Pernaute, Andrés; Pascua, Irene; De Juan, Carmen; Head, Jacqueline; Torres-García, Antonio-José; Iniesta, Pilar

    2016-01-01

    The role of telomeres and telomerase in colorectal cancer (CRC) is well established as the major driving force in generating chromosomal instability. However, their potential as prognostic markers remains unclear. We investigated the outcome implications of telomeres and telomerase in this tumour type. We considered telomere length (TL), ratio of telomere length in cancer to non-cancer tissue (T/N ratio), telomerase activity and TERT levels; their relation with clinical variables and their role as prognostic markers. We analyzed 132 CRCs and paired non-cancer tissues. Kaplan-Meier curves for disease-free survival were calculated for TL, T/N ratio, telomerase activity and TERT levels. Overall, tumours had shorter telomeres than non-tumour tissues (P < 0.001) and more than 80% of CRCs displayed telomerase activity. Telomere lengths of non-tumour tissues and CRCs were positively correlated (P < 0.001). Considering telomere status and clinical variables, the lowest degree of telomere shortening was shown by tumours located in the rectum (P = 0.021). Regarding prognosis studies, patients with tumours showing a mean TL < 6.35 Kb experienced a significantly better clinical evolution (P < 0.001) and none of them with the highest degree of tumour telomere shortening relapsed during the follow-up period (P = 0.043). The mean TL in CRCs emerged as an independent prognostic factor in the Cox analysis (P = 0.017). Telomerase-positive activity was identified as a marker that confers a trend toward a poor prognosis. In CRC, our results support the use of telomere status as an independent prognostic factor. Telomere status may contribute to explaining the different molecular identities of this tumour type.

  14. Thermal biology and physiology in clinical hyperthermia: current status and future needs.

    PubMed

    Li, G C

    1984-10-01

    The current status and needs of thermal biology and physiology as related to clinical hyperthermia are summarized. Emphasis is placed on heat-induced modification of blood flow and microenvironment in tissues, on the biological effects of heat and X-rays, and on the relationship between drug resistance, heat resistance, and thermotolerance in thermochemotherapy. Results from recent studies investigating the relationships between thermotolerance and heat shock proteins in tissue culture cell lines, in rodent tumors, and in normal tissues are presented. These data strongly suggest that the levels of Mr 70,000 heat shock protein can be used as an assay to predict the thermal sensitivity of tissues during fractionated hyperthermia.

  15. Genetics of Autism Spectrum Disorder: Current Status and Possible Clinical Applications

    PubMed Central

    2015-01-01

    Autism spectrum disorder (ASD) is one of the most complex behavioral disorders with a strong genetic influence. The objectives of this article are to review the current status of genetic research in ASD, and to provide information regarding the potential candidate genes, mutations, and genetic loci possibly related to pathogenesis in ASD. Investigations on monogenic causes of ASD, candidate genes among common variants, rare de novo mutations, and copy number variations are reviewed. The current possible clinical applications of the genetic knowledge and their future possibilities are highlighted. PMID:26713075

  16. Context: An Algorithm for Determining Negation, Experiencer, and Temporal Status from Clinical Reports

    PubMed Central

    Harkema, Henk; Dowling, John N.; Thornblade, Tyler; Chapman, Wendy W.

    2009-01-01

    In this paper we describe an algorithm called ConText for determining whether clinical conditions mentioned in clinical reports are negated, hypothetical, historical, or experienced by someone other than the patient. The algorithm infers the status of a condition with regard to these properties from simple lexical clues occurring in the context of the condition. The discussion and evaluation of the algorithm presented in this paper address the questions of whether a simple surface-based approach which has been shown to work well for negation can be successfully transferred to other contextual properties of clinical conditions, and to what extent this approach is portable among different clinical report types. In our study we find that ConText obtains reasonable to good performance for negated, historical, and hypothetical conditions across all report types that contain such conditions. Conditions experienced by someone other than the patient are very rarely found in our report set. A comprehensive solution to the problem of determining whether a clinical condition is historical or recent requires knowledge above and beyond the surface clues picked up by ConText. PMID:19435614

  17. Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis

    PubMed Central

    Beck, Julia; Urnovitz, Howard B.; Saresella, Marina; Caputo, Domenico; Clerici, Mario; Mitchell, William M.; Schütz, Ekkehard

    2010-01-01

    Using recently available mass sequencing and assembly technologies, we have been able to identify and quantify unique cell-free DNA motifs in the blood of patients with multiple sclerosis (MS). The most common MS clinical syndrome, relapsing-remitting MS (RRMS), is accompanied by a unique fingerprint of both inter- and intragenic cell-free circulating nucleic acids as specific DNA sequences that provide significant clinical sensitivity and specificity. Coding genes that are differentially represented in MS serum encode cytoskeletal proteins, brain-expressed regulators of growth, and receptors involved in nervous system signal transduction. Although coding genes distinguish RRMS and its clinical activity, several repeat sequences, such as the L1M family of LINE elements, are consistently different in all MS patients and clinical status versus the normal database. These data demonstrate that DNA motifs observed in serum are characteristic of RRMS and disease activity and are promising as a clinical tool in monitoring patient responses to treatment modalities. PMID:20228264

  18. How the American Society for Virology was founded.

    PubMed

    Joklik, Wolfang K; Grossberg, Sidney E

    2006-01-05

    The American Society for Virology, the very first such Society to be formed anywhere, was founded at a meeting of some 40 virologists at Chicago O'Hare International airport on June 9, 1981. They met after a decade and a half of intense discussion that originated at the 9th International Congress of Microbiology in Moscow in 1966 when a small group of virologists requested the International Association of Microbiological Societies to form a Virology Section within IAMS, and this request was rejected. Virologists therefore held their own First International Congress of Virology in Helsinki in 1968 which was very successful and generated intense informal discussion among leading virologists in this country as to the desirability of founding an American society for virologists. Proposals were circulated and discussed which resulted in the informal Chicago meeting that created the mechanism for founding the ASV and organizing its 1st Annual Meeting at Cornell in Ithaca in August 1982.

  19. Thank you to Virology Journal's peer reviewers in 2013

    PubMed Central

    2014-01-01

    The editors of Virology Journal would like to thank all our reviewers who have contributed to the journal in Volume 10 (2013). The success of any scientific journal depends on an effective and strict peer review process and Virology Journal could not operate without your contribution. We are grateful to the large number of reviewers (1026 to be exact!), who have done a great job in not only lifting the quality of the journal’s scientific peer reviewing process, but also helped us to achieve our goal of a median time to first decision of just 35 days. Our record time from submission to online, open access, publication in 2013 was 22 days for a Research Article [1] and 28 days for a Review [2]. This is a great achievement by any standard. We look forward to your continuous support of Virology Journal either as an invited reviewer or a contributing author in the years to come.

  20. The Theory and Fundamentals of Bioimpedance Analysis in Clinical Status Monitoring and Diagnosis of Diseases

    PubMed Central

    Khalil, Sami F.; Mohktar, Mas S.; Ibrahim, Fatimah

    2014-01-01

    Bioimpedance analysis is a noninvasive, low cost and a commonly used approach for body composition measurements and assessment of clinical condition. There are a variety of methods applied for interpretation of measured bioimpedance data and a wide range of utilizations of bioimpedance in body composition estimation and evaluation of clinical status. This paper reviews the main concepts of bioimpedance measurement techniques including the frequency based, the allocation based, bioimpedance vector analysis and the real time bioimpedance analysis systems. Commonly used prediction equations for body composition assessment and influence of anthropometric measurements, gender, ethnic groups, postures, measurements protocols and electrode artifacts in estimated values are also discussed. In addition, this paper also contributes to the deliberations of bioimpedance analysis assessment of abnormal loss in lean body mass and unbalanced shift in body fluids and to the summary of diagnostic usage in different kinds of conditions such as cardiac, pulmonary, renal, and neural and infection diseases. PMID:24949644

  1. The theory and fundamentals of bioimpedance analysis in clinical status monitoring and diagnosis of diseases.

    PubMed

    Khalil, Sami F; Mohktar, Mas S; Ibrahim, Fatimah

    2014-06-19

    Bioimpedance analysis is a noninvasive, low cost and a commonly used approach for body composition measurements and assessment of clinical condition. There are a variety of methods applied for interpretation of measured bioimpedance data and a wide range of utilizations of bioimpedance in body composition estimation and evaluation of clinical status. This paper reviews the main concepts of bioimpedance measurement techniques including the frequency based, the allocation based, bioimpedance vector analysis and the real time bioimpedance analysis systems. Commonly used prediction equations for body composition assessment and influence of anthropometric measurements, gender, ethnic groups, postures, measurements protocols and electrode artifacts in estimated values are also discussed. In addition, this paper also contributes to the deliberations of bioimpedance analysis assessment of abnormal loss in lean body mass and unbalanced shift in body fluids and to the summary of diagnostic usage in different kinds of conditions such as cardiac, pulmonary, renal, and neural and infection diseases.

  2. Role of the virology laboratory in diagnosis and management of patients with central nervous system disease.

    PubMed Central

    Chonmaitree, T; Baldwin, C D; Lucia, H L

    1989-01-01

    A number of viruses cause acute central nervous system disease. The two major clinical presentations are aseptic meningitis and the less common meningoencephalitis. Clinical virology laboratories are now more widely available than a decade ago; they can be operated on a modest scale and can be tailored to the needs of the patients they serve. Most laboratories can provide diagnostic information on diseases caused by enteroviruses, herpesviruses, and human immunodeficiency virus. Antiviral therapy for herpes simplex virus is now available. By providing a rapid diagnostic test or isolation of the virus or both, the virology laboratory plays a direct role in guiding antiviral therapy for patients with herpes simplex encephalitis. Although there is no specific drug available for enteroviruses, attention needs to be paid to these viruses since they are the most common cause of nonbacterial meningitis and the most common pathogens causing hospitalization for suspected sepsis in young infants in the United States during the warm months of the year. When the virology laboratory maximizes the speed of viral detection or isolation, it can make a significant impact on management of these patients. Early viral diagnosis benefits patients with enteroviral meningitis, most of whom are hospitalized and treated for bacterial sepsis or meningitis or both; these patients have the advantage of early withdrawal of antibiotics and intravenous therapy, early hospital discharge, and avoidance of the risks and costs of unnecessary tests and treatment. Enteroviral infection in young infants also is a risk factor for possible long-term sequelae. For compromised patients, the diagnostic information helps in selecting specific immunoglobulin therapy. Good communication between the physician and the laboratory will result in the most benefit to patients with central nervous system viral infection. PMID:2644021

  3. Vitamin D Status of Clinical Practice Populations at Higher Latitudes: Analysis and Applications

    PubMed Central

    Genuis, Stephen J.; Schwalfenberg, Gerry K.; Hiltz, Michelle N.; Vaselenak, Sharon A.

    2009-01-01

    Background: Inadequate levels of vitamin D (VTD) throughout the life cycle from the fetal stage to adulthood have been correlated with elevated risk for assorted health afflictions. The purpose of this study was to ascertain VTD status and associated determinants in three clinical practice populations living in Edmonton, Alberta, Canada - a locale with latitude of 53°30’N, where sun exposure from October through March is often inadequate to generate sufficient vitamin D. Methods: To determine VTD status, 1,433 patients from three independent medical offices in Edmonton had levels drawn for 25(OH)D as part of their medical assessment between Jun 2001 and Mar 2007. The relationship between demographic data and lifestyle parameters with VTD status was explored. 25(OH)D levels were categorized as follows: (1) Deficient: <40 nmol/L; (2) Insufficient (moderate to mild): 40 to <80 nmol/L; and (3) Adequate: 80–250 nmol/L. Any cases <25 nmol/L were subcategorized as severely deficient for purposes of further analysis. Results: 240 (16.75% of the total sample) of 1,433 patients were found to be VTD ‘deficient’ of which 48 (3.35% of the overall sample) had levels consistent with severe deficiency. 738 (51.5% of the overall sample) had ‘insufficiency’ (moderate to mild) while only 31.75% had ‘adequate’ 25(OH)D levels. The overall mean for 25(OH) D was 68.3 with SD=28.95. VTD status was significantly linked with demographic and lifestyle parameters including skin tone, fish consumption, milk intake, sun exposure, tanning bed use and nutritional supplementation. Conclusion: A high prevalence of hypovitaminosis-D was found in three clinical practice populations living in Edmonton. In view of the potential health sequelae associated with widespread VTD inadequacy, strategies to facilitate translation of emerging epidemiological information into clinical intervention need to be considered in order to address this public health issue. A suggested VTD supplemental

  4. Improved virologic suppression with HIV subspecialty care in a large prison system using telemedicine: an observational study with historical controls.

    PubMed

    Young, Jeremy D; Patel, Mahesh; Badowski, Melissa; Mackesy-Amiti, Mary Ellen; Vaughn, Pyrai; Shicker, Louis; Puisis, Michael; Ouellet, Lawrence J

    2014-07-01

    Correctional populations have an elevated human immunodeficiency virus (HIV) prevalence, yet many individuals lack access to subspecialty care. Our study showed that HIV-infected inmates had significantly greater virologic suppression and higher CD4 T-lymphocyte counts when managed by a multidisciplinary team of subspecialists conducting clinics via telemedicine. In other studies, these outcomes have been associated with reductions on HIV-related morbidity and mortality, as well as HIV transmission.

  5. Impact of postoperative glycemic control and nutritional status on clinical outcomes after total pancreatectomy

    PubMed Central

    Shi, Hao-Jun; Jin, Chen; Fu, De-Liang

    2017-01-01

    AIM To evaluate the impact of glycemic control and nutritional status after total pancreatectomy (TP) on complications, tumor recurrence and overall survival. METHODS Retrospective records of 52 patients with pancreatic tumors who underwent TP were collected from 2007 to 2015. A series of clinical parameters collected before and after surgery, and during the follow-up were evaluated. The associations of glycemic control and nutritional status with complications, tumor recurrence and long-term survival were determined. Risk factors for postoperative glycemic control and nutritional status were identified. RESULTS High early postoperative fasting blood glucose (FBG) levels (OR = 4.074, 95%CI: 1.188-13.965, P = 0.025) and low early postoperative prealbumin levels (OR = 3.816, 95%CI: 1.110-13.122, P = 0.034) were significantly associated with complications after TP. Postoperative HbA1c levels over 7% (HR = 2.655, 95%CI: 1.299-5.425, P = 0.007) were identified as one of the independent risk factors for tumor recurrence. Patients with postoperative HbA1c levels over 7% had much poorer overall survival than those with HbA1c levels less than 7% (9.3 mo vs 27.6 mo, HR = 3.212, 95%CI: 1.147-8.999, P = 0.026). Patients with long-term diabetes mellitus (HR = 15.019, 95%CI: 1.278-176.211, P = 0.031) and alcohol history (B = 1.985, SE = 0.860, P = 0.025) tended to have poor glycemic control and lower body mass index levels after TP, respectively. CONCLUSION At least 3 mo are required after TP to adapt to diabetes and recover nutritional status. Glycemic control appears to have more influence over nutritional status on long-term outcomes after TP. Improvement in glycemic control and nutritional status after TP is important to prevent early complications and tumor recurrence, and improve survival. PMID:28127200

  6. Predicting Cognitive Function from Clinical Measures of Physical Function and Health Status in Older Adults

    PubMed Central

    Bolandzadeh, Niousha; Kording, Konrad; Salowitz, Nicole; Davis, Jennifer C.; Hsu, Liang; Chan, Alison; Sharma, Devika; Blohm, Gunnar; Liu-Ambrose, Teresa

    2015-01-01

    Introduction Current research suggests that the neuropathology of dementia—including brain changes leading to memory impairment and cognitive decline—is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies. Methods We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1–L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation. Results Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year. Discussion We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a

  7. Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis.

    PubMed

    Barr, Helen L; Halliday, Nigel; Cámara, Miguel; Barrett, David A; Williams, Paul; Forrester, Douglas L; Simms, Rebecca; Smyth, Alan R; Honeybourne, David; Whitehouse, Joanna L; Nash, Edward F; Dewar, Jane; Clayton, Andrew; Knox, Alan J; Fogarty, Andrew W

    2015-10-01

    Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection.A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable.Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability (p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline (p=0.02) and NHQ concentrations (p<0.01) decreased significantly.In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection.

  8. Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis

    PubMed Central

    Halliday, Nigel; Cámara, Miguel; Barrett, David A.; Williams, Paul; Forrester, Douglas L.; Simms, Rebecca; Smyth, Alan R.; Honeybourne, David; Whitehouse, Joanna L.; Nash, Edward F.; Dewar, Jane; Clayton, Andrew; Knox, Alan J.; Fogarty, Andrew W.

    2015-01-01

    Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection. A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable. Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability (p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline (p=0.02) and NHQ concentrations (p<0.01) decreased significantly. In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection. PMID:26022946

  9. SMOKING STATUS IS A CLINICAL INDICATOR FOR ALCOHOL MISUSE IN US ADULTS

    PubMed Central

    McKee, Sherry A.; Falba, Tracy; O’Malley, Stephanie S.; Sindelar, Jody; O’Connor, Patrick G.

    2010-01-01

    Context Screening for alcohol use in primary care settings is recommended by clinical care guidelines, but is not adhered to as strongly as screening for smoking. It has been proposed that smoking status could be used to enhance the identification of alcohol misuse in primary and other medical settings but national data are lacking. Objective To investigate smoking status as a clinical indicator for alcohol misuse in a national sample of US adults, following clinical care guidelines for the assessment of these behaviors. Design, Setting, and Participants Analyses are based on a sample of 42,565 US adults from the National Epidemiological Survey on Alcohol and Related Conditions (Wave I, 2001–2002). Main Outcome Measures Odds ratios (O.R.) and test characteristics (sensitivity, specificity, positive and negative predictive value [PPV, NPV], and likelihood ratio [LR] of smoking behavior (daily, occasional, former) were determined for the detection of hazardous drinking behavior and alcohol-related diagnoses, assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. Results Daily, occasional, and ex-smokers were more likely than never smokers to be hazardous drinkers (O.R.3.23 [95% CI 3.02–3.46]; O.R.5.33 [95% CI 4.70–6.04]; O.R.1.19 [95% CI 1.10–1.28], respectively). Daily and occasional smokers were more likely to meet criteria for alcohol diagnoses (O.R.3.52 [95% CI 3.19–3.90], O.R.5.39 [95% CI 4.60–6.31]; respectively). For the detection of hazardous drinking by current smoking (occasional + daily), sensitivity was 42.5%; specificity 81.9%, PPV 45.3% (vs. population rate of 26.1%), and LR+ 2.34. For the detection of alcohol diagnoses by current smoking; sensitivity was 51.4%; specificity 78.0%, PPV 17.8% (vs. population rate of 8.5%), and LR+ 2.33. Conclusions Occasional and daily smokers were at heightened risk for hazardous drinking and alcohol use diagnoses. Smoking status can be used as a clinical indicator for alcohol

  10. Is long-term virological response related to CCR5 Δ32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

    PubMed Central

    Laurichesse, Jean-Jacques; Taieb, Audrey; Capoulade-Metay, Corinne; Katlama, Christine; Villes, Virginie; Drobacheff-Thiebaud, Marie-Christine; Raffi, François; Chêne, Genevieve; Theodorou, Ioannis; Leport, Catherine

    2010-01-01

    Objective To examine whether CCR5 Δ32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1 infected patients. Methods The genetic sub-study of ANRS CO8 APROCO-COPILOTE cohort included 609 patients who started a protease inhibitor-containing cART in 1997–99. Patients were considered to have a sustained virological response if all plasma HIV-RNA measurements between month 4 and years 3–5 were <500 copies/ml, allowing for a single blip. Virological response was compared between patients heterozygous for CCR5 Δ32 (Δ32/wt) and wild-type patients (wt/wt) from month 4 to year 3 and month 4 to year 5. Logistic regression analysis was used to adjust for baseline demographical data, HIV-RNA, CD4 cell counts, antiretroviral naive status, time spent on antiretroviral therapy at year 3 and 5 and adherence to treatment (month 4 to year 3 and 5). Results Sustained virological response was better in Δ32/wt than in wt/wt patients: 66% versus 52% up to year 3 (p=0.02), nearly significant after adjustment to potential cofounders (p=0.07). Δ32/wt patients had a better virological response, up to year 5, 48% versus 35% (p=0.01), and remained significantly better, after adjustment, associated with a better virological response up to 5 years post initiation of cART (p=0.04). There was no association with CD4 response. Conclusion Δ32/wt deletion is associated with a beneficial virological response to cART on the long-term. Whether this association can be a direct effect of Δ32/wt deletion remains questionable and needs confirmation in other observational studies. PMID:20050936

  11. A Serious Game for Clinical Assessment of Cognitive Status: Validation Study

    PubMed Central

    Chignell, Mark; Tierney, Mary C.; Lee, Jacques

    2016-01-01

    Background We propose the use of serious games to screen for abnormal cognitive status in situations where it may be too costly or impractical to use standard cognitive assessments (eg, emergency departments). If validated, serious games in health care could enable broader availability of efficient and engaging cognitive screening. Objective The objective of this work is to demonstrate the feasibility of a game-based cognitive assessment delivered on tablet technology to a clinical sample and to conduct preliminary validation against standard mental status tools commonly used in elderly populations. Methods We carried out a feasibility study in a hospital emergency department to evaluate the use of a serious game by elderly adults (N=146; age: mean 80.59, SD 6.00, range 70-94 years). We correlated game performance against a number of standard assessments, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Confusion Assessment Method (CAM). Results After a series of modifications, the game could be used by a wide range of elderly patients in the emergency department demonstrating its feasibility for use with these users. Of 146 patients, 141 (96.6%) consented to participate and played our serious game. Refusals to play the game were typically due to concerns of family members rather than unwillingness of the patient to play the game. Performance on the serious game correlated significantly with the MoCA (r=–.339, P <.001) and MMSE (r=–.558, P <.001), and correlated (point-biserial correlation) with the CAM (r=.565, P <.001) and with other cognitive assessments. Conclusions This research demonstrates the feasibility of using serious games in a clinical setting. Further research is required to demonstrate the validity and reliability of game-based assessments for clinical decision making. PMID:27234145

  12. Clinical and Virological Outcome of European Patients Infected With HIV

    ClinicalTrials.gov

    2016-02-29

    HIV; Hepatitis B; Hepatitis C; AIDS; Coinfection; Cardiovascular Diseases; Diabetes Mellitus; Acidosis, Lactic; Renal Insufficiency; Fractures, Bone; End Stage Liver Disease; Kidney Failure, Chronic; Proteinuria

  13. [Virological and clinical features of patients with sporadic hepatitis C].

    PubMed

    Tang, Z; Wang, Y; Yu, Z; Yang, D; Hao, L

    1997-06-01

    In this study, the transmission route in 16 sporadic hepatitis C (SHC) patients was investigated. Three of them were surgeons who had often had occupational needlestick accidents, another 3 had close household contact with their spouses who had been diagnosed as chronic posttransfusion viral hepatitis C (PTHC), and the remaining 5 had potential parenteral exposure such as tooth extraction, injection or inoculation and so on. Five patients with SHC didn't have such history, their transmission route was not determined. Our result showed a lower viremia level in patients with SHC when compared to PTHC patients (the serum dilutions for HCV RNA detection was 10-100 times in the former and 100-10000 times in the latter. P<0.01). Only 1 patient with SHC was anti-HCV positive. Comparing to PTHC, the patients with SHC in our study had milder liver demage and lower ALT levels, and most of them (10/16) were symptomless.

  14. Factors Influencing Antiretroviral Adherence and Virological Outcomes in People Living with HIV in the Highlands of Papua New Guinea.

    PubMed

    Gare, Janet; Kelly-Hanku, Angela; Ryan, Claire E; David, Matthew; Kaima, Petronia; Imara, Ulato; Lote, Namarola; Crowe, Suzanne M; Hearps, Anna C

    2015-01-01

    Adherence to antiretroviral therapy (ART) is paramount for virological suppression and positive treatment outcomes. ART has been rapidly scaled up in Papua New Guinea (PNG) in recent years, however clinical monitoring of HIV+ individuals on ART is limited. A cross-sectional study was conducted at two major sexual health clinics in high HIV prevalence provinces in the Highlands Region of PNG to assess ART adherence, factors affecting adherence and the relationship between ART adherence and virological outcomes. Ninety-five HIV+ individuals were recruited and administered a questionnaire to gather demographic and ART adherence information whilst clinical data and pill counts were extracted from patient charts and blood was collected for viral load testing. Bivariate analysis was performed to identify independent predictors of ART adherence. Fourteen percent (n = 12) of participants showed evidence of virological failure. Although the majority of participants self-reported excellent ART adherence in the last seven days (78.9%, 75/91), pill count measurements indicated only 40% (34/84) with >95% adherence in the last month. Taking other medications while on ART (p = 0.01) and taking ART for ≥1 year (p = 0.037) were positively associated with adherence by self-report and pill count, respectively. Participants who had never heard of drug resistance were more likely to show virological failure (p = 0.033). Misconception on routes of HIV transmission still persists in the studied population. These findings indicate that non-adherence to ART is high in this region of PNG and continued education and strategies to improve adherence are required to ensure the efficacy of ART and prevent HIV drug resistance.

  15. Are three generations of quantitative molecular methods sufficient in medical virology? Brief review.

    PubMed

    Clementi, Massimo; Bagnarelli, Patrizia

    2015-10-01

    In the last two decades, development of quantitative molecular methods has characterized the evolution of clinical virology more than any other methodological advancement. Using these methods, a great deal of studies has addressed efficiently in vivo the role of viral load, viral replication activity, and viral transcriptional profiles as correlates of disease outcome and progression, and has highlighted the physio-pathology of important virus diseases of humans. Furthermore, these studies have contributed to a better understanding of virus-host interactions and have sharply revolutionized the research strategies in basic and medical virology. In addition and importantly from a medical point of view, quantitative methods have provided a rationale for the therapeutic intervention and therapy monitoring in medically important viral diseases. Despite the advances in technology and the development of three generations of molecular methods within the last two decades (competitive PCR, real-time PCR, and digital PCR), great challenges still remain for viral testing related not only to standardization, accuracy, and precision, but also to selection of the best molecular targets for clinical use and to the identification of thresholds for risk stratification and therapeutic decisions. Future research directions, novel methods and technical improvements could be important to address these challenges.

  16. Integrated Design of a Virology Course Develops Lifelong Learners

    ERIC Educational Resources Information Center

    Mester, Joseph C.

    2009-01-01

    This article describes the author's first attempt at integrated course design. Students in the author's virology course helped set the learning goals, and the design and content of the exams, and developed rubrics for individual and group projects. The result was that they learned how to direct their own learning. Integrated course design and…

  17. Factors Associated With Smoking Status among HIV-Positive Patients in Routine Clinical Care

    PubMed Central

    Zyambo, Cosmas M; Willig, James H; Cropsey, Karen L; Carson, April P; Wilson, Craig; Tamhane, Ashutosh R; Westfall, Andrew O; Burkholder, Greer A

    2015-01-01

    Background Treatment-related reductions in morbidity and mortality among human immunodeficiency virus (HIV)-positive patients have been attenuated by cigarette smoking, which increases risk of cardiovascular, respiratory, and neoplastic diseases. This study investigated factors associated with smoking status among HIV-positive patients. Methods This cross-sectional study included 2,464 HIV-positive patients attending the HIV Clinic at the University of Alabama at Birmingham between April 2008 and December 2013. Smoking status (current, former, never), psychosocial factors, and clinical characteristics were assessed. Multinomial logistic regression was used to obtain unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association of the various factors with smoking status. Results Among HIV-positive patients (mean age 45 years, 75% male, 55% African-American), the majority reported a history of smoking (39% current and 22% former smokers). In adjusted models, patient characteristics associated with increased odds of current smoking were male gender (OR for heterosexual men, 1.8 [95% CI: 1.3–2.6]; for men who have sex with men, 1.5 [1.1–1.9]), history of respiratory diseases (1.5 [1.2–1.9]), unsuppressed HIV viral load (>50 copies/mL) (1.5 [1.1–1.9]), depression (1.6 [1.3–2.0]), anxiety (1.6 [1.2–2.1]), and prior and current substance abuse (4.7 [3.6–6.1] and 8.3 [5.3–13.3] respectively). Male gender, anxiety, and substance abuse were also associated with being a former smoker. Conclusions Smoking was common among HIV-positive patients, with several psychosocial factors associated with current and former smoking. This suggests smoking cessation programs in HIV clinic settings may achieve greater impact by integrating interventions that also address illicit substance abuse and mental health. PMID:26767146

  18. Clinical and Taxonomic Status of Pathogenic Nonpigmented or Late-Pigmenting Rapidly Growing Mycobacteria

    PubMed Central

    Brown-Elliott, Barbara A.; Wallace, Richard J.

    2002-01-01

    The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of disease are also described. Special emphasis is on the Mycobacterium fortuitum group, including M. fortuitum, M. peregrinum, and the unnamed third biovariant complex with its recent taxonomic changes and newly recognized species (including M. septicum, M. mageritense, and proposed species M. houstonense and M. bonickei). The clinical and taxonomic status of M. chelonae, M. abscessus, and M. mucogenicum is also detailed, along with that of the closely related new species, M. immunogenum. Additionally, newly recognized species, M. wolinskyi and M. goodii, as well as M. smegmatis sensu stricto, are included in a discussion of the M. smegmatis group. Laboratory diagnosis of RGM using phenotypic methods such as biochemical testing and high-performance liquid chromatography and molecular methods of diagnosis are also discussed. The latter includes PCR-restriction fragment length polymorphism analysis, hybridization, ribotyping, and sequence analysis. Susceptibility testing and antibiotic susceptibility patterns of the RGM are also annotated, along with the current recommendations from the National Committee for Clinical Laboratory Standards (NCCLS) for mycobacterial susceptibility testing. PMID:12364376

  19. Current Clinical Status of Telehealth in Korea: Categories, Scientific Basis, and Obstacles

    PubMed Central

    Kim, Hun-Sung; Kim, Hyunah; Lee, Suehyun; Lee, Kye Hwa

    2015-01-01

    Objectives Through telehealth, medical services have expanded beyond spatial boundaries and are now available in living spaces outside of hospitals. It can also contribute to patient medical knowledge improvement because patients can access their hospital records and data from home. However, concepts of telehealth are rather vague in Korea. Methods We refer to several clinical reports to determine the current clinical status of and obstacles to telehealth in Korea. Results Patients' health conditions are now reported regularly to doctors remotely, and patients can receive varied assistance. Self-improvement based on minute details that are beyond medical staff's reach is another possible benefit that may be realized with the help of a variety of medical equipment (sensors). The feasibility, clinical effect, and cost-benefit of telehealth have been verified by scientific evidence. Conclusions Patients will be able to improve their treatment adherence by receiving help from various professionals, such as doctors, nurses, nutritionists, and sports therapists. This means that the actual treatment time per patient will increase as well. Ultimately, this will increase the quality of patients' self-administration of care to impede disease progression and prevent complications. PMID:26618030

  20. Low socioeconomic status, adverse gene expression profiles, and clinical outcomes in hematopoietic stem cell transplant recipients

    PubMed Central

    Knight, Jennifer M.; Rizzo, J. Douglas; Logan, Brent R.; Wang, Tao; Arevalo, Jesusa M.G.; Ma, Jeffrey; Cole, Steve W.

    2015-01-01

    Purpose Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biological mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I IFN response and antibody synthesis. Experimental Design We compared pre-transplant leukocyte CTRA gene expression between a group of 78 high vs. low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes. Results Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA up-regulation compared to matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival. Conclusions Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT. PMID:26286914

  1. [ISO 15189 accreditation in clinical microbiology laboratory: general concepts and the status in our laboratory].

    PubMed

    Akyar, Işin

    2009-10-01

    One important trend in the laboratory profession and quality management is the global convergence of laboratory operations. The goal of an accredited medical laboratory is to continue "offering useful laboratory service for diagnosis and treatment of the patients and also aid to the health of the nation". An accredited clinical laboratory is managed by a quality control system, it is competent technically and the laboratory service meets the needs of all its patients and physicians by taking the responsibility of all the medical tests and therapies. For this purpose, ISO 15189 international standard has been prepared by 2003. ISO 15189 standard is originated from the arrangement of ISO 17025 and ISO 9001:2000 standards. Many countries such as England, Germany, France, Canada and Australia have preferred ISO 15189 as their own laboratory accreditation programme, meeting all the requirements of their medical laboratories. The accreditation performance of a clinical microbiology laboratory is mainly based on five essential points; preanalytical, analytical, postanalytical, quality control programmes (internal, external, interlaboratory) and audits (internal, external). In this review article, general concepts on ISO 15189 accreditation standards for the clinical microbiology laboratories have been summarized and the status of a private laboratory (Acibadem LabMed, Istanbul) in Turkey has been discussed.

  2. Vitamin K status and vascular calcification: evidence from observational and clinical studies.

    PubMed

    Shea, M Kyla; Holden, Rachel M

    2012-03-01

    Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients.

  3. Vitamin K Status and Vascular Calcification: Evidence from Observational and Clinical Studies12

    PubMed Central

    Shea, M. Kyla; Holden, Rachel M.

    2012-01-01

    Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients. PMID:22516723

  4. Canine visceral leishmaniasis: relationships between oxidative stress, liver and kidney variables, trace elements, and clinical status.

    PubMed

    Heidarpour, M; Soltani, S; Mohri, M; Khoshnegah, J

    2012-10-01

    The aim of this study was to investigate the role of oxidative stress in the pathology of canine visceral leishmaniasis (CVL). We therefore studied the relationships between oxidative stress markers, liver and kidney variables, trace elements, and clinical status in dogs naturally infected with Leishmania infantum. Two groups of Leishmania-infected dogs [asymptomatic (AD, n = 14) and symptomatic (SD, n = 16)] were assessed and compared with a group of non-infected control dogs (CD, n = 30). A significant decrease (p < 0.001) in serum total antioxidant status (TAS) and albumin concentration (p < 0.05) and a significant increase in serum malondialdehyde (MDA) and blood urea nitrogen (BUN) concentrations (p < 0.001), in the SD group, were observed when compared to CD and AD groups. Dogs of the AD group presented a significant decrease in copper (p < 0.01) and zinc (p < 0.001) concentrations, when compared to CD group, while the SD group presented a significant decrease (p < 0.001) in copper and zinc concentrations, when compared to CD and AD groups. Oxidative stress markers (MDA and TAS) showed significant correlations (p < 0.001) with trace elements (copper and zinc) and liver (alanine aminotransferase) and kidney (BUN and creatinine) variables. The results of the present study revealed that symptomatic dogs showed more severe oxidative stress than asymptomatic and non-infected dogs and enhanced lipid peroxidation may be linked to liver and kidney damage in canine visceral leishmaniasis.

  5. Current Status and Clinical Studies of Oriental Herbs in Sexual Medicine in Korea

    PubMed Central

    Shin, Yu Seob; Zhao, Chen; Zhang, Li Tao

    2015-01-01

    Erectile dysfunction (ED) is one of the most common diseases among aging men. Although previous studies have shown that type 5 phosphodiesterase inhibitors (PDE5-Is) are very effective for the treatment of ED, many researchers are currently attempting to identify therapeutic agents from natural sources with comparable or better effects than PDE5-Is. Herbal medicine is thought to be advantageous because it is natural; moreover, it not only treats isolated symptoms, but also maintains general well-being. Furthermore, since newly created chemical compound libraries have limited structural diversity with regard to pharmaceutical agents, more attention has recently been paid to the ability of oriental herbs to enhance physical health, including sexual function. Herein, we review the current status of Korean preclinical or clinical studies of the application of oriental herbs to sexual medicine. PMID:26331122

  6. Clinical and demographic characteristics and functional status of the patients with fibromyalgia syndrome

    PubMed Central

    Sahin, Nilay; Atik, Aziz; Dogan, Erdal

    2014-01-01

    OBJECTIVE: To investigate the clinical and demographic characteristics and functional status of the patients with fibromyalgia syndrome (FMS). METHODS: Ninety-four patients with the diagnosis of FMS were included in the study. All patients were evaluated with short form 36 for quality of life (SF-36), pain, depression, benign joint hypermobility syndrome (BJHS), myofacial pain syndrome (MPS), and demogrophic characteristics. End-point measurements were SF-36 for quality of life, visual analogue scale, Beck Depression Index, anamnesis, and physical examination. RESULTS: The majority of the patients were women who were suffering from generalised pain with a median age of 40.4. Mostly depression and sleep disorders were accompanying the syndrome. Physical examination revealed MPS and BJHS in most of the patients. CONCLUSION: BJHS and MPS must also be investigated in patients with the diagnosis of FMS. PMID:28058309

  7. Cationic liposomal vaccine adjuvants in animal challenge models: overview and current clinical status.

    PubMed

    Korsholm, Karen Smith; Andersen, Peter Lawætz; Christensen, Dennis

    2012-05-01

    Cationic liposome formulations can function as efficient vaccine adjuvants. However, due to the highly diverse nature of lipids, cationic liposomes have different physical-chemical characteristics that influence their adjuvant mechanisms and their relevance for use in different vaccines. These characteristics can be further manipulated by incorporation of additional lipids or stabilizers, and inclusion of carefully selected immunostimulators is a feasible strategy when tailoring cationic liposomal adjuvants for specific disease targets. Thus, cationic liposomes present a plasticity, which makes them promising adjuvants for future vaccines. This versatility has also led to a vast amount of literature on different experimental liposomal formulations in combination with a wide range of immunostimulators. Here, we have compiled information about the animal challenge models and administration routes that have been used to study vaccine adjuvants based on cationic liposomes and provide an overview of the applicability, progress and clinical status of cationic liposomal vaccine adjuvants.

  8. New-Onset Refractory Status Epilepticus with Claustrum Damage: Definition of the Clinical and Neuroimaging Features

    PubMed Central

    Meletti, Stefano; Giovannini, Giada; d’Orsi, Giuseppe; Toran, Lisa; Monti, Giulia; Guha, Rahul; Kiryttopoulos, Andreas; Pascarella, Maria Grazia; Martino, Tommaso; Alexopoulos, Haris; Spilioti, Martha; Slonkova, Jana

    2017-01-01

    New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic–clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases, extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies.

  9. Clinical knee findings in floor layers with focus on meniscal status

    PubMed Central

    Rytter, Søren; Jensen, Lilli Kirkeskov; Bonde, Jens Peter

    2008-01-01

    Background The aim of this study was to examine the prevalence of self-reported and clinical knee morbidity among floor layers compared to a group of graphic designers, with special attention to meniscal status. Methods We obtained information about knee complaints by questionnaire and conducted a bilateral clinical and radiographic knee examination in 134 male floor layers and 120 male graphic designers. After the exclusion of subjects with reports of earlier knee injuries the odds ratio (OR) with 95% confidence intervals (CI) of knee complaints and clinical findings were computed among floor layers compared to graphic designers, using logistic regression. Estimates were adjusted for effects of body mass index, age and knee straining sports. Using radiographic evaluations, we conducted side-specific sensitivity analyses regarding clinical signs of meniscal lesions after the exclusion of participants with tibiofemoral (TF) osteoarthritis (OA). Results Reports of knee pain (OR = 2.7, 95% CI = 1.5–4.6), pain during stair walking (OR = 2.2, 95% CI = 1.3–3.9) and symptoms of catching of the knee joint (OR = 2.9, 95% CI = 1.4–5.7) were more prevalent among floor layers compared to graphic designers. Additionally, significant more floor layers than graphic designers had clinical signs suggesting possible meniscal lesions: a positive McMurray test (OR = 2.4, 95% CI = 1.1–5.0) and TF joint line tenderness (OR = 5.4, 95% CI = 2.4–12.0). Excluding floor layers (n = 22) and graphic designers (n = 15) with radiographic TF OA did not alter this trend between the two study groups: a positive McMurray test (OR = 2.2, 95% CI = 1.0–4.9), TF joint line tenderness (OR = 5.0, 95% CI = 2.0–12.5). Conclusion Results indicate that floor layers have a high prevalence of both self-reported and clinical knee morbidity. Clinical knee findings suggesting possible meniscal lesions were significant more prevalent among floor layers compared to a group of low-level exposed graphic

  10. On-treatment HBV DNA dynamics predict virological breakthrough in entecavir-treated HBeAg-positive chronic hepatitis B

    PubMed Central

    Huang, Yi-Jie; Chang, Chi-Sen; Yeh, Hong-Zen; Yang, Sheng-Shun

    2017-01-01

    Background & aims Virological breakthrough (VBT) could be a manifestation of chronic hepatitis B (CHB) in patients treated with long-term nucleot(s)ide analogues. We aimed to determine the association of on-treatment serum hepatitis B virus (HBV) DNA with VBT in HBeAg-positive CHB patients receiving entecavir (ETV) treatment. Methods A retrospective cohort study, including 162 consecutive patients (95 men and 67 women; mean age, 43.1±13.4 years) with HBeAg-positive CHB treated with ETV for at least 48 weeks between August 2008 and May 2015, was conducted. Univariate and multivariate cox regression analysis were used to identify associations with VBT and clinical factors, including HBV DNA and HBeAg serum status. Results Among the 162 ETV-treated HBeAg-positive CHB patients, eighteen patients (11.1%) experienced VBT (VBT group), whereas the other 144 patients were without VBT (non-VBT group). The cumulative rate of HBV DNA < 100 IU/mL in the VBT group and the non-VBT group at week 48 were 44.44% and 70.14%, and at week 96 were 58.33% and 92.56%, respectively (p = 0.015). The cumulative rate of HBeAg seroclearance in the VBT group and non-VBT group at week 48 and week 96 were statistically significant (p = 0.014). Multivariate analysis disclosed that failure to achieve HBeAg seroclearance were the factors significantly associated with VBT. Conclusions Our results demonstrated that on-treatment HBV DNA could probably predict VBT in ETV-treated HBeAg-positive chronic hepatitis B patients. Failure to achieve HBeAg seroclearance was associated with VBT in ETV-treated HBeAg-positive CHB patients. HBV DNA >100IU/mL at 48 weeks is potentially a predictor for VBT. PMID:28350873

  11. On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings.

    PubMed

    Rutstein, S E; Golin, C E; Wheeler, S B; Kamwendo, D; Hosseinipour, M C; Weinberger, M; Miller, W C; Biddle, A K; Soko, A; Mkandawire, M; Mwenda, R; Sarr, A; Gupta, S; Mataya, R

    2016-01-01

    Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider

  12. Impact of New Regulations On Assessing Driving Status (INROADS): a South Australian seizure clinic cohort.

    PubMed

    Hafner, Jessica; Horn, Sharon; Robinson, Martin; Purdie, Grant; Jannes, Jim

    2014-11-01

    The ability to drive is important to patients and driving restriction often leads to restriction of employment and social opportunities. In March 2012, Austroads released revised Assessing Fitness to Drive Guidelines (AFTDG) with significant changes for drivers with seizures and epilepsy. Our study aimed to assess the impact of the 2012 AFTDG on a Seizure Clinic cohort compared to the previous 2003 AFTDG and an individual's current driving status. We also aimed to quantify the difference in AFTDG interpretation between expert and non-expert doctors. We performed a retrospective observational audit of case notes for all patients managed in a public hospital outpatient Seizure Clinic between 1 March 2010 and 1 March 2012. A total of 142 patients were included in the analysis. Comparison between the 2003 and 2012 AFTDG resulted in reduced eligibility to drive a private vehicle by 2.1% (52.5% versus 50.4%) and commercial vehicle by 2.2% (4.5% versus 2.3%). The proportion of those currently driving against guideline recommendations increased (private 8.8% versus 19%; commercial 50% versus 100%) and the non-expert assessor was more likely to agree with the experts with the 2012 AFTDG. In summary, the 2012 AFTDG has had a measurable impact on driving eligibility in individuals with seizure although it is easier to interpret for non-expert doctors. Greater awareness of the 2012 AFTDG is required to reduce the proportion of patients driving against current recommendations.

  13. Current status of clinical trials assessing oncolytic virus therapy for urological cancers.

    PubMed

    Taguchi, Satoru; Fukuhara, Hiroshi; Homma, Yukio; Todo, Tomoki

    2017-03-21

    Oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. Oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. Notably, T-VEC (talimogene laherparepvec, formerly called OncoVEX(GM)(-)(CSF) ), an oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in October 2015, and was subsequently approved in Europe and Australia in 2016. The efficacies of many types of oncolytic viruses against urological cancers have been investigated in preclinical studies during the past decade, and some have already been tested in clinical trials. For example, a phase I trial of the third-generation oncolytic Herpes simplex virus type 1, G47Δ, in patients with prostate cancer was completed in 2016. We summarize the current status of clinical trials of oncolytic virus therapy in patients with the three major urological cancers: prostate, bladder and renal cell cancers. In addition to Herpes simplex virus type 1, adenoviruses, reoviruses, vaccinia virus, Sendai virus and Newcastle disease virus have also been used as parental viruses in these trials. We believe that oncolytic virus therapy is likely to become an important and major treatment option for urological cancers in the near future.

  14. Sociodemographic disparities and behavioral factors in clinical oral health status during pregnancy

    PubMed Central

    Chung, Lisa H.; Gregorich, Steven E.; Armitage, Gary C.; Gonzalez-Vargas, Judy; Adams, Sally H.

    2013-01-01

    Objective Although oral health (OH) problems are common during pregnancy, little is known about individual characteristics or behaviors relating to clinically assessed OH during pregnancy. This cross-sectional study describes the clinical OH status of a sample of pregnant women, examines relationships between sociodemographic factors and OH, behavioral factors and OH, and the influence of behavior on the relationships between sociodemographic clusters and OH. Baseline data were utilized from a pilot intervention study promoting OH during pregnancy. Methods Participants (n=99), recruited from CenteringPregnancy® prenatal care groups completed: questionnaires addressing race/ethnicity, income, education, dental insurance, oral hygiene practices, and dental care utilization; and clinical examinations for periodontal probing depths (PD), bleeding on probing (BOP), plaque assessment, and visual detection of untreated decay. Chi-squares and one-way ANOVAs with Tukey’s Studentized Range Test of planned comparisons were conducted to examine bivariable relationships between both sociodemographic and behavioral characteristics to OH status. Multivariable logistic regression analyses tested whether the effects of sociodemographic variables on OH status might be mediated by behaviors, including self-reported oral hygiene and recent dental visits. Results Forty-five percent of the sample had untreated decay and the mean percentage of sites with BOP=18%. Bivariable analyses of sociodemographic factors indicated that compared to Whites, Hispanic women had greater % of sites with: BOP, PD ≥5mm plus BOP, and Plaque Index (PI) scores of ≥2, all p=0.05; and greater untreated decay (Chi-square 13.3, p<0.001). Lower income was related to greater untreated decay (Chi-square 7.6, p<0.01). Compared to the highest education level, the lowest level group had higher % BOP, p<0.05. Public dental insurance (versus private) was associated with greater % BOP, PD ≥5mm plus BOP, both p<0

  15. Mechanisms and Clinical Application of Tetramethylpyrazine (an Interesting Natural Compound Isolated from Ligusticum Wallichii): Current Status and Perspective

    PubMed Central

    Chen, Keji

    2016-01-01

    Tetramethylpyrazine, a natural compound from Ligusticum wallichii (Chuan Xiong), has been extensively used in China for cardiovascular and cerebrovascular diseases for about 40 years. Because of its effectiveness in multisystems, especially in cardiovascular, its pharmacological action, clinical application, and the structural modification have attracted broad attention. In this paper its mechanisms of action, the clinical status, and synthetic derivatives will be reviewed briefly. PMID:27668034

  16. Virologic Tools for HCV Drug Resistance Testing

    PubMed Central

    Fourati, Slim; Pawlotsky, Jean-Michel

    2015-01-01

    Recent advances in molecular biology have led to the development of new antiviral drugs that target specific steps of the Hepatitis C Virus (HCV) lifecycle. These drugs, collectively termed direct-acting antivirals (DAAs), include non-structural (NS) HCV protein inhibitors, NS3/4A protease inhibitors, NS5B RNA-dependent RNA polymerase inhibitors (nucleotide analogues and non-nucleoside inhibitors), and NS5A inhibitors. Due to the high genetic variability of HCV, the outcome of DAA-based therapies may be altered by the selection of amino-acid substitutions located within the targeted proteins, which affect viral susceptibility to the administered compounds. At the drug developmental stage, preclinical and clinical characterization of HCV resistance to new drugs in development is mandatory. In the clinical setting, accurate diagnostic tools have become available to monitor drug resistance in patients who receive treatment with DAAs. In this review, we describe tools available to investigate drug resistance in preclinical studies, clinical trials and clinical practice. PMID:26690198

  17. Enzyme immunoassays and related procedures in diagnostic medical virology

    PubMed Central

    Kurstak, Edouard; Tijssen, Peter; Kurstak, Christine; Morisset, Richard

    1986-01-01

    This review article describes several applications of the widely used enzyme immunoassay (EIA) procedure. EIA methods have been adapted to solve problems in diagnostic virology where sensitivity, specificity, or practicability is required. Concurrent developments in hybridoma and conjugation methods have increased significantly the use of these assays. A general overview of EIA methods is given together with typical examples of their use in diagnostic medical virology; attention is drawn to possible pitfalls. Recent advances in recombinant DNA technology have made it possible to produce highly specific nucleic acid probes that have a sensitivity approximately 100 times greater than that of EIA. Some applications of these probes are described. Although the non-labelled nucleic acid probes for use in the field are not as refined as non-labelled immunoassays, their range of applications is expected to expand rapidly in the near future. ImagesFig. 4 PMID:3533302

  18. Importance and impact of veterinary virology in Germany.

    PubMed

    Horzinek, M C

    1999-01-01

    The causative agent of tobacco mosaic and of foot and mouth disease (FMD) were recognized in 1898 as "filterable" or "invisible"--and eventually termed "virus". Four years later the viral aetiology of yellow fever was established, and the new discipline took off. Thus animal virology started with a veterinary problem, and Germany's contribution during the following decades came mainly from the chairs of veterinary teaching and research establishments in Giessen, Munich and Hanover, the Riems Institute, and the Federal Research Institute for Animal Virus Diseases in Tübingen. From a superficial bibliometric analysis, a wide divergence in impact figures is noted, with excellent contributions in international virology journals and lesser papers in German veterinary journals. The publications in the observed time frame reveal a fascination by virion structure, physical characteristics and structure-function relationships with little work published in journals dedicated to immunology and pathogenesis.

  19. Relationship between psychiatric status, self-reported outcome measures, and clinical parameters in axial spondyloarthritis.

    PubMed

    Kilic, Gamze; Kilic, Erkan; Ozgocmen, Salih

    2014-12-01

    This article aims to compare the risks of depression and anxiety in patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) and investigate the relationship among self-reported outcome measures, clinical parameters, and physical variables of patients with axSpA. Patients with axSpA were recruited from Erciyes Spondyloarthritis Cohort. The patients met Assessment of Spondyloarthritis International Society classification criteria for axial SpA and were assessed in a cross-sectional study design for visual analog scale (VAS) pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life questionnaire (ASQoL), and Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP). Psychological status was evaluated using the hospital anxiety and depression scale (HADS). Multivariate logistic regression analysis was applied to determine the associations between psychological variables and clinical parameters after adjusting for confounding variables. Of the 316 patients (142 nr-axSpA, 174 AS), 139 (44%) had high risk for depression (HADS-D score ≥ 7) and 71 (22.5%) for anxiety (HADS-A score ≥ 10). HADS-D and HADS-A scores were similar between patients with AS and nr-axSpA. Patients with high risk for depression and anxiety had higher scores in BASDAI, BASFI, and ASDAS-CRP, and also poorer scores in VAS pain and ASQoL. Multivariate logistic regression analysis showed that the ASDAS-CRP, ASQoL, BASDAI, as well as educational level were factors associated with the risk of depression whereas the ASQoL and educational level were factors associated with the risk of anxiety. Patients with nr-axSpA and AS have similar burden of psychological distress. The quality of life (ASQoL) and educational level were factors associated with the risk of both depression and anxiety whereas disease activity (BASDAI and ASDAS-CRP) was the

  20. A meta-analysis of adherence to antiretroviral therapy and virologic responses in HIV-infected children, adolescents, and young adults.

    PubMed

    Kahana, Shoshana Y; Rohan, Jennifer; Allison, Susannah; Frazier, Thomas W; Drotar, Dennis

    2013-01-01

    The relationship between adherence to antiretroviral therapy (ART) and virologic outcomes in HIV+ children, adolescents, and young adults has been notably understudied, with much of the extant research focused on specific sub-literatures, such as resource-limited regions, specific clinical outcomes and time frames. The authors sought to better characterize the relationship between adherence to ART and virologic functioning along various sample and methodological factors. The authors conducted a meta-analysis of thirty-seven studies and utilized a random effects model to generate weighted mean effect sizes. In addition, the authors conducted meta-ANOVAs to examine potential factors influencing the relationship between adherence and three categories of clinical outcomes, specifically Viral Load (VL) <100, VL < 400, and continuously measured VL. The analyses included 5,344 HIV+ children, adolescents, and young adults. The relationship between adherence behaviors and virologic outcomes varied across different methods of measurement and analysis. The relationship between adherence and continuously measured VL was significantly larger than for dichotomously-coded VL < 400 at Qb (20.69(1), p < .0005). Caregiver self-report indices elicited very small to small magnitude effects across both VL < 100 and VL < 400 outcomes and combined informant reporting (youth/adolescent and parent) produced significantly larger effects than caregiver report alone with adherence and VL < 400 outcomes at Qb (9.28(1), p < .005). More recently published trials reported smaller relationships between adherence and categorical clinical outcomes, such that year of publication significantly negatively correlated with VL < 100 (r = -.71(14), p < .005) and VL < 400 (r = -.43(26), p < .02). The data suggest that the magnitude of the relationship between ART adherence and virologic outcomes among heterogeneous samples of HIV+ children, adolescents and young adults varies across virologic outcomes and

  1. Health status instruments for patients with COPD in pulmonary rehabilitation: defining a minimal clinically important difference

    PubMed Central

    Alma, Harma; de Jong, Corina; Jelusic, Danijel; Wittmann, Michael; Schuler, Michael; Blok, Bertine Flokstra-de; Kocks, Janwillem; Schultz, Konrad; Molen, Thys van der

    2016-01-01

    The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28–0.61 (CCQ), 1.46–3.08 (CAT) and 6.86–9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD. PMID:27597571

  2. Health status instruments for patients with COPD in pulmonary rehabilitation: defining a minimal clinically important difference.

    PubMed

    Alma, Harma; de Jong, Corina; Jelusic, Danijel; Wittmann, Michael; Schuler, Michael; Flokstra-de Blok, Bertine; Kocks, Janwillem; Schultz, Konrad; van der Molen, Thys

    2016-09-01

    The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George's Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.

  3. The relationship between religious involvement and clinical status of patients with bipolar disorder

    PubMed Central

    Cruz, Mario; Pincus, Harold Alan; Welsh, Deborah E; Greenwald, Devra; Lasky, Elaine; Kilbourne, Amy M

    2009-01-01

    Objective Religion and spirituality are important coping strategies in depression but have been rarely studied within the context of bipolar disorder. The present study assessed the association between different forms of religious involvement and the clinical status of individuals treated for bipolar disorder. Methods A cross-sectional observation study of follow-up data from a large cohort study of patients receiving care for bipolar disorder (n = 334) at an urban Veterans Affairs mental health clinic was conducted. Bivariate and multivariate analyses were performed to assess the association between public (frequency of church attendance), private (frequency of prayer/meditation), as well as subjective forms (influence of beliefs on life) of religious involvement and mixed, manic, depressed, and euthymic states when demographic, anxiety, alcohol abuse, and health indicators were controlled. Results Multivariate analyses found significant associations between higher rates of prayer/meditation and participants in a mixed state [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.10-1.52, chi square = 9.42, df = 14, p < 0.05], as well as lower rates of prayer/meditation and participants who were euthymic (OR = 0.84; 95% CI = 0.72-0.99, chi square = 4.60, df = 14, p < 0.05). Depression and mania were not associated with religious involvement. Conclusions Compared to patients with bipolar disorder in depressed, manic, or euthymic states, patients in mixed states have more active private religious lives. Providers should assess the religious activities of individuals with bipolar disorder in mixed states and how they may complement/deter ongoing treatment. Future longitudinal studies linking bipolar states, religious activities, and treatment-seeking behaviors are needed. PMID:20148868

  4. Heart Failure Medications Detection and Prescription Status Classification in Clinical Narrative Documents

    PubMed Central

    Meystre, Stéphane M.; Kim, Youngjun; Heavirland, Julia; Williams, Jenifer; Bray, Bruce E.; Garvin, Jennifer

    2016-01-01

    Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB) are two common medication classes used for heart failure treatment. The ADAHF (Automated Data Acquisition for Heart Failure) project aimed at automatically extracting heart failure treatment performance metrics from clinical narrative documents, and these medications are an important component of the performance metrics. We developed two different systems to detect these medications, rule-based and machine learning-based. The rule-based system uses dictionary lookups with fuzzy string searching and showed successful performance even if our corpus contains various misspelled medications. The machine learning-based system uses lexical and morphological features and produced similar results. The best performance was achieved when combining the two methods, reaching 99.3% recall and 98.8% precision. To determine the prescription status of each medication (i.e., active, discontinued, or negative), we implemented a SVM classifier with lexical features and achieved good performance, reaching 95.49% accuracy, in a five-fold cross validation evaluation. PMID:26262123

  5. GH improves growth and clinical status in children with cystic fibrosis -- a review of published studies.

    PubMed

    Hardin, Dana S

    2004-08-01

    Children with cystic fibrosis (CF) have problems with poor linear growth and inadequate weight gain. Nutritional augmentation has been the mainstay of therapy for improving both weight and height in CF; however, inadequate growth continues to be a problem. Furthermore, protein catabolism has been documented even in non-acutely ill adults and children with CF, and could adversely affect longitudinal growth. Human recombinant GH has positive effects on nitrogen balance, and multiple studies have demonstrated improved height and weight in children treated with GH. The purpose of this article is to summarize studies evaluating GH use in children with CF. All published studies of GH use in children with CF have demonstrated significant improvement in height velocity and height Z score. All studies but one, in which subjects were treated only three times per week with GH, have demonstrated improvement in weight as reported by weight velocity and/or weight Z score, and one trial has demonstrated a substantial improvement when GH was used to augment nutritional therapy. Several reports suggest that GH treatment results in improved forced vital capacity, and multiple studies have found improved clinical status as measured by decreased hospitalizations and courses of intravenous antibiotics. Furthermore studies to date also suggest that GH results in improvement in exercise tolerance and bone accumulation. To date significant side effects, including glucose intolerance, have not been reported. Thus mounting evidence suggests that human recombinant GH provides safe and effective therapy in children with CF.

  6. Thyroid function status and its impact on clinical outcome in patients admitted to critical care

    PubMed Central

    Qari, Faiza A.

    2015-01-01

    Objective: To analyze alterations in thyroid function and the correlation between results of thyroid function test and mortality in medical and surgical intensive care unit (ICU) patients. It also aimed to evaluate the effect of thyroid dysfunction in ICU patients and their need for mechanical ventilation (MV). Methods: A single-center, prospective, observational study was conducted on patients admitted to medical and surgical ICU between 2013-2014.. Clinical and paraclinical findings (free triiodothyronine, free thyroxine and thyroid stimulating hormone) were documented for all patients. Regression analysis and chi-square were used for death and MV outcome variables. Results: We included 502 patients. Of these, 340 (67.7%) were admitted to the medical ICU. Results of thyroid function tests were normal in 320 (64%) and 162 (32.3%) medical and surgical ICU patients, respectively. Euthyroid sick syndrome (ESS) was documented in 86 patients (17%). Mortality was twice higher among surgical ICU patients with ESS compared to those with normal thyroid function (p=0.085), which is not statistically significant. Based on thyroid function status, no differences in the risk to be mechanically ventilated was found between medical or surgical ICU patients. Conclusion: There is a significant association between ESS and mortality in ICU patients. Future studies should determine whether abnormal thyroid function increases the risk for MV in ICU patients. PMID:26430429

  7. Turner syndrome: review of clinical, neuropsychiatric, and EEG status: an experience of tertiary center.

    PubMed

    Saad, Khaled; Abdelrahman, Ahmed A; Abdel-Raheem, Yasser F; Othman, Essam R; Badry, Reda; Othman, Hisham A K; Sobhy, Karema M

    2014-03-01

    We reviewed the clinical, neuropsychiatric, and EEG status of 53 turner syndrome (TS) females, aged 3-16 years, in Assiut university hospitals, Upper Egypt. The diagnosis and care of patients with TS in Egypt is still in the developing stage. Hence this study was undertaken to review the details of patients with TS with respect to the pattern of cognitive, psychiatric, and motor dysfunction. We aimed to provide a comprehensive data about the experience of our center comparable to previous studies, which have been published in this field. This will contribute to a better definition of the neuropsychiatric features that may be specific to TS that allows early and better detection and management of these cases. We found FSIQ and verbal IQ that seem to be at a nearly normal level and a decreased performance IQ. ADHD and autistic symptoms were found in 20.70 and 3.77 % of our cohort, respectively. The motor performance in TS was disturbed, with some neurological deficits present in 17 % (reduced muscle tone and reduced muscle power). In addition, females with TS in our study exhibit social and emotional problems, including anxiety (5.66 %) and depression (11.30 %). The EEG results revealed abnormalities in seven patients (13.20 %). One patient presenting with generalized tonic-clonic seizures showed generalized epileptiform activity, and six patients presenting with intellectual disabilities showed abnormal EEG background activity.

  8. Clinical value of nutritional status in neurodegenerative diseases: What is its impact and how it affects disease progression and management?

    PubMed

    Tsagalioti, Eftyhia; Trifonos, Christina; Morari, Aggeliki; Vadikolias, Konstantinos; Giaginis, Constantinos

    2016-11-30

    Neurodegenerative diseases constitute a major problem of public health that is associated with an increased risk of mortality and poor quality of life. Malnutrition is considered as a major problem that worsens the prognosis of patients suffering from neurodegenerative diseases. In this aspect, the present review is aimed to critically collect and summarize all the available existing clinical data regarding the clinical impact of nutritional assessment in neurodegenerative diseases, highlighting on the crucial role of nutritional status in disease progression and management. According to the currently available clinical data, the nutritional status of patients seems to play a very important role in the development and progression of neurodegenerative diseases. A correct nutritional evaluation of neurodegenerative disease patients and a right nutrition intervention is essential in monitoring their disease.

  9. Influence of Peritoneal Transport Characteristics on Nutritional Status and Clinical Outcome in Chinese Diabetic Nephropathy Patients on Peritoneal Dialysis

    PubMed Central

    Guan, Ji-Chao; Bian, Wei; Zhang, Xiao-Hui; Shou, Zhang-Fei; Chen, Jiang-Hua

    2015-01-01

    Background: High peritoneal transport status was previously thought to be a poor prognostic factor in peritoneal dialysis (PD) patients. However, its effect on diabetic nephropathy PD patients is unclear in consideration of the adverse impact of diabetes itself. The purpose of this study was to investigate the influence of peritoneal transport characteristics on nutritional status and clinical outcome in diabetic nephropathy patients on PD. Methods: One hundred and two diabetic nephropathy patients on PD were enrolled in this observational cohort study. According to the initial peritoneal equilibration test result, patients were divided into two groups: Higher transport group (HT, including high and high average transport) and lower transport group (LT, including low and low-average transport). Demographic characteristics, biochemical data, dialysis adequacy, and nutritional status were evaluated. Clinical outcomes were compared. Risk factors for death-censored technique failure and mortality were analyzed. Results: Compared with LT group (n = 37), serum albumin was significantly lower and the incidence of malnutrition by subjective global assessment was significantly higher in HT group (n = 65) (P < 0.05). Kaplan–Meier analyses showed that death-censored technique failure and mortality were significantly increased in HT group compared with that in LT group. On multivariate Cox analyses, higher peritoneal transport status and lower residual renal function (RRF) were independent predictors of death-censored technique failure when adjusted for serum albumin and total weekly urea clearance (Kt/V). Independent predictors of mortality were advanced age, anemia, hypoalbuminemia, and lower RRF, but not higher peritoneal transport status. Conclusions: Higher peritoneal transport status has an adverse influence on nutrition for diabetic nephropathy patients on PD. Higher peritoneal transport status is a significant independent risk factor for death-censored technique

  10. Viral vectors: from virology to transgene expression

    PubMed Central

    Bouard, D; Alazard-Dany, N; Cosset, F-L

    2009-01-01

    In the late 1970s, it was predicted that gene therapy would be applied to humans within a decade. However, despite some success, gene therapy has still not become a routine practise in medicine. In this review, we will examine the problems, both experimental and clinical, associated with the use of viral material for transgenic insertion. We shall also discuss the development of viral vectors involving the most important vector types derived from retroviruses, adenoviruses, herpes simplex viruses and adeno-associated viruses. This article is part of a themed section on Vector Design and Drug Delivery. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 PMID:18776913

  11. Impact of Lymph Node Status on Clinical Outcomes After Accelerated Partial Breast Irradiation

    SciTech Connect

    Shah, Chirag; Wilkinson, J. Ben; Shaitelman, Simona; Grills, Inga S.; Chen, Peter Y.; Dekhne, Nayana; Jaiyesimi, Ishmael; Wallace, Michelle; Mitchell, Christina K.; Vicini, Frank A.

    2012-03-01

    Purpose: To compare outcomes after accelerated partial breast irradiation (APBI) between node-negative and node-positive patients. Methods and Materials: A total of 534 patients with early-stage breast cancer received APBI including 39 node-positive (N+) cases. Clinical, pathologic, and treatment-related factors were compared between node-negative (N-) and N+ cohorts. Local recurrence (LR), regional recurrence (RR), axillary failure (AF), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: N+ patients were younger (p = 0.04), had larger tumors (p < 0.001), and were more likely to receive chemotherapy (p < 0.001). Mean follow-up was 7.8 years for N+ patients and 6.3 years for N- patients (p = 0.06). No differences were seen in 5-year actuarial rates of LR (2.2% vs. 2.6%, p = 0.86), AF (0% vs. 0%, p = 0.69), DFS (90.0% vs. 88.0%, p = 0.79), or OS (91.0 vs. 84.0%, p = 0.65) between the two groups, whereas higher rates of RR (0% vs. 6.1%, p < 0.001) and DM (2.2% vs. 8.9%, p = 0.005) were noted in N+ patients. A trend for improved CSS (p = 0.06), was seen in N- patients. Age, tumor size, receptor status, T-stage, chemotherapy, APBI technique, and nodal status (p = 0.86) were not associated with LR, while a trend for an association with LR was noted with close/positive margins, (p = 0.07), and failure to receive adjuvant hormonal therapy (p = 0.06). Conclusions: No differences were seen in the rates of LR or AF between N- and N+ patients after APBI. These results support the continued enrollment of node-positive patients in Phase III trials evaluating the efficacy of APBI including the National Surgical Adjuvant Breast and Bowel Project-B39/Radiation Therapy Oncology Group 0413.

  12. [Current status of adjuvant chemotherapy for resected lung cancer at our institute--focus on clinical trial enrollment].

    PubMed

    Sawada, Shigeki; Yamashita, Motohiro; Komori, Eisaku; Suehiro, Hiroshi; Ogino, Atsuko; Nogami, Hiroyuki; Segawa, Yoshihiko; Shinkai, Tetsu

    2010-03-01

    Adjuvant chemotherapy after complete resection in Stage I B-III A non-small cell lung cancer is recommended. Several clinical trials of adjuvant chemotherapy are now underway in Japan. Our institute also participates in adjuvant clinical trials, but slow patient recruitment is a problem. In this paper, we reported the current status of adjuvant chemotherapy and recruitment for clinical trials at our institute. Between August 2001 and December 2008, candidates for adjuvant chemotherapy were 315 patients. Among them 186 who received adjuvant chemotherapy were younger and had less co-morbidity than those who did not receive adjuvant chemotherapy. Twenty-five of the 186 patients participated in the clinical trials. The major reason of refusal of a clinical trial was that patients preferred to choose their own treatment and disliked randomized trials.

  13. Virology: The Next Generation from Digital PCR to Single Virion Genomics

    SciTech Connect

    White, Richard A.; Brazelton De Cardenas, Jessica N.; Hayden, Randall T.

    2015-10-01

    In the past 25 years, virology has had major technology breakthroughs stemming first from the introduction of nucleic acid amplification testing, but more recently from the use of next-generation sequencing, digital PCR, and the possibility of single virion genomics. These technologies have and will improve diagnosis and disease state monitoring in clinical settings, aid in environmental monitoring, and reveal the vast genetic potential of viruses. Using the principle of limiting dilution, digital PCR amplifies single molecules of DNA in highly partitioned endpoint reactions and reads each of those reactions as either positive or negative based on the presence or absence of target fluorophore. In this review, digital PCR will be highlighted along with current studies, advantages/disadvantages, and future perspectives with regard to digital PCR, viral load testing, and the possibility of single virion genomics.

  14. Assessing Nutrient Intake and Nutrient Status of HIV Seropositive Patients Attending Clinic at Chulaimbo Sub-District Hospital, Kenya

    PubMed Central

    Onyango, Agatha Christine; Walingo, Mary Khakoni; Mbagaya, Grace; Kakai, Rose

    2012-01-01

    Background. Nutritional status is an important determinant of HIV outcomes. Objective. To assess the nutrient intake and nutrient status of HIV seropositive patients attending an AIDS outpatient clinic, to improve the nutritional management of HIV-infected patients. Design. Prospective cohort study. Setting. Comprehensive care clinic in Chulaimbo Sub-District Hospital, Kenya. Subjects. 497 HIV sero-positive adults attending the clinic. Main Outcome Measures. Evaluation of nutrient intake using 24-hour recall, food frequency checklist, and nutrient status using biochemical assessment indicators (haemoglobin, creatinine, serum glutamate pyruvate (SGPT) and mean corpuscular volume (MCV)). Results. Among the 497 patients recruited (M : F sex ratio: 1.4, mean age: 39 years ± 10.5 y), Generally there was inadequate nutrient intake reported among the HIV patients, except iron (10.49 ± 3.49 mg). All the biochemical assessment indicators were within normal range except for haemoglobin 11.2 g/dL (11.4 ± 2.60 male and 11.2 ± 4.25 female). Conclusions. Given its high frequency, malnutrition should be prevented, detected, monitored, and treated from the early stages of HIV infection among patients attending AIDS clinics in order to improve survival and quality of life. PMID:22997571

  15. HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b

    PubMed Central

    2012-01-01

    Background The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin. Methods For 48 weeks, 388 “naïve”genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000–1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR). Results The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR. Conclusion Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance. Trial registration ClinicalTrials.gov Identifier: NCT01342003 PMID:23157720

  16. Correlation of serum lead levels with inflammation, nutritional status, and clinical complications in hemodialysis patients.

    PubMed

    Pouresmaeil, Rahmat; Razeghi, Effat; Ahmadi, Farokhlagha

    2012-01-01

    The aim of this study was to determine blood lead level (BLL) in hemodialysis (HD) patients and their relation with high-sensitivity C-reactive protein (hsCRP) and albumin which are inflammatory and nutritional biomarkers, respectively, and clinical complications. A total of 93 patients, who were dialyzed at least for 3 months, were included in the study. Blood samples were collected before HD and BLL was measured and categorized as three equal groups: low normal (BLL < 8 μg/dL), middle normal (BLL = 8-10.6 μg/dL), and high normal (BLL > 10.6 μg/dL). All patients had normal BLL, 9.7 ± 3.4 g/dL. Patients with abnormal hsCRP level (>3 mg/L) had higher BLL than other patients (16.4 ± 0.8 vs. 11.5 ± 2.7 mg/L, p = 0.003). Patients with BLL > 10.6 μg/dL had significantly lower hemoglobin, ferritin, iron, and albumin levels and higher hsCRP and intact parathyroid hormone (iPTH) levels than the patients with BLL < 8 μg/dL. In addition, BLL revealed a significant positive correlation with duration of dialysis. We concluded that BLL associated to inflammation, malnutritional status, iron-deficiency condition, and high iPTH level in HD patients.

  17. Clinical Neuropathology practice news 1-2014: pyrosequencing meets clinical and analytical performance criteria for routine testing of MGMT promoter methylation status in glioblastoma.

    PubMed

    Preusser, Matthias; Berghoff, Anna S; Manzl, Claudia; Filipits, Martin; Weinhäusel, Andreas; Pulverer, Walter; Dieckmann, Karin; Widhalm, Georg; Wöhrer, Adelheid; Knosp, Engelbert; Marosi, Christine; Hainfellner, Johannes A

    2014-01-01

    Testing of the MGMT promoter methylation status in glioblastoma is relevant for clinical decision making and research applications. Two recent and independent phase III therapy trials confirmed a prognostic and predictive value of the MGMT promoter methylation status in elderly glioblastoma patients. Several methods for MGMT promoter methylation testing have been proposed, but seem to be of limited test reliability. Therefore, and also due to feasibility reasons, translation of MGMT methylation testing into routine use has been protracted so far. Pyrosequencing after prior DNA bisulfite modification has emerged as a reliable, accurate, fast and easy-to-use method for MGMT promoter methylation testing in tumor tissues (including formalin fixed and paraffin-embedded samples). We performed an intra- and inter-laboratory ring trial which demonstrates a high analytical performance of this technique. Thus, pyrosequencing- based assessment of MGMT promoter methylation status in glioblastoma meets the criteria of high analytical test performance and can be recommended for clinical application, provided that strict quality control is performed. Our article summarizes clinical indications, practical instructions and open issues for MGMT promoter methylation testing in glioblastoma using pyrosequencing.

  18. View and present status of personnel involved in clinical trials: a survey of participants from the First Symposium of the Shikoku Collaborative Group for Promotion of Clinical Trials.

    PubMed

    Yanagawa, Hiroaki; Irahara, Minoru; Houchi, Hitoshi; Kakehi, Yoshiyuki; Moritoyo, Takashi; Nomoto, Masahiro; Miyamura, Mitsuhiko; Shuin, Taro

    2011-02-01

    Clinical trials leading to drug approval (registration trials) play a central role in the drug development process. Since the introduction of the Good Clinical Practice (GCP) standard in 1997, the Japanese infrastructure for registration trials has improved. The contribution of support staff, including clinical research coordinators (CRCs), to clinical trials is now widely recognized in Japan. Quality issues and career development for these support staff are being increasingly emphasized. The Shikoku Collaborative Group for Promotion of Clinical Trials was organized in 2008 to address these issues through communication with the personnel involved in clinical trials in regional areas of Japan. To understand the views and present status of personnel involved in clinical trials, we used questionnaires to survey the participants of the First Symposium of the Shikoku Collaborative Group for Promotion of Clinical Trials held in August 2009. Group discussions and special lectures occurred at the symposium. The questionnaire began with questions about basic patient characteristics, followed by practical questions. Of 110 participants, there were 68 respondents (62%), including clinical trial support staff (clinical research coordinators [n=36, 53%], administrative officers [n=9, 13%]), and medical staff [n=23, 34%]). Among the support staff, 36 (80%) had more than 5 years of experience. The most common questionnaire answer selected for participation in the symposium was "willing to contact staff from other medical institutions or organizations" for support staff and "to obtain further knowledge concerning clinical trials" for medical staff. The overall view of the discussion ("Was the discussion satisfactory?") was favorable for 36 (53%) respondents. This survey revealed that the group discussion in the present symposium appears to be valuable for participants, using overall satisfaction as a surrogate. Based on the information obtained in the present study, further

  19. The use of health status questionnaires in the management of chronic obstructive pulmonary disease patients in clinical practice.

    PubMed

    van der Molen, Thys; Diamant, Zuzana; Kocks, Jan Willem H; Tsiligianni, Ioanna G

    2014-08-01

    Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone. Both questionnaires are designed to provide the clinician information enabling a more personalized disease approach and subsequent management. Although both Clinical COPD Questionnaire and COPD Assessment Test have good discriminate properties, their use as prognostic markers of severity and their ability to modify disease management has not yet been fully established. New studies are needed to further determine their value on several disease outcomes.

  20. Validation of the HIV Tropism Test TROCAI Using the Virological Response to a Short-Term Maraviroc Monotherapy Exposure

    PubMed Central

    Genebat, M.; De Luna-Romero, M.; Tarancon-Diez, L.; Dominguez-Molina, B.; Pacheco, Y. M.; Muñoz-Fernández, M. A.; Leal, M.

    2016-01-01

    TROCAI is a phenotypic tropism test developed using the virological response to a short-term exposure to maraviroc monotherapy (Maraviroc Clinical Test [MCT]). It was found that with TROCAI, a cutoff of <0.5% of dual/mixed viruses was needed to predict R5 HIV tropism. Here, we have validated TROCAI, using this cutoff, in a new cohort of 42 patients, finding a very high concordance between TROCAI and MCT (98%), and a good concordance (71 to 87%) with other genotypic/phenotypic methods. PMID:27480849

  1. Next-Generation Sequencing and Genome Editing in Plant Virology

    PubMed Central

    Hadidi, Ahmed; Flores, Ricardo; Candresse, Thierry; Barba, Marina

    2016-01-01

    Next-generation sequencing (NGS) has been applied to plant virology since 2009. NGS provides highly efficient, rapid, low cost DNA, or RNA high-throughput sequencing of the genomes of plant viruses and viroids and of the specific small RNAs generated during the infection process. These small RNAs, which cover frequently the whole genome of the infectious agent, are 21–24 nt long and are known as vsRNAs for viruses and vd-sRNAs for viroids. NGS has been used in a number of studies in plant virology including, but not limited to, discovery of novel viruses and viroids as well as detection and identification of those pathogens already known, analysis of genome diversity and evolution, and study of pathogen epidemiology. The genome engineering editing method, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been successfully used recently to engineer resistance to DNA geminiviruses (family, Geminiviridae) by targeting different viral genome sequences in infected Nicotiana benthamiana or Arabidopsis plants. The DNA viruses targeted include tomato yellow leaf curl virus and merremia mosaic virus (begomovirus); beet curly top virus and beet severe curly top virus (curtovirus); and bean yellow dwarf virus (mastrevirus). The technique has also been used against the RNA viruses zucchini yellow mosaic virus, papaya ringspot virus and turnip mosaic virus (potyvirus) and cucumber vein yellowing virus (ipomovirus, family, Potyviridae) by targeting the translation initiation genes eIF4E in cucumber or Arabidopsis plants. From these recent advances of major importance, it is expected that NGS and CRISPR-Cas technologies will play a significant role in the very near future in advancing the field of plant virology and connecting it with other related fields of biology. PMID:27617007

  2. Adherence to Hepatitis C Virus Therapy and Early Virologic Outcomes

    PubMed Central

    Re, Vincent Lo; Amorosa, Valerianna K.; Localio, A. Russell; O’Flynn, Rose; Teal, Valerie; Dorey-Stein, Zachariah; Kostman, Jay R.; Gross, Robert

    2009-01-01

    Background Suboptimal drug exposure attributable to physician-directed dosage reductions of pegylated interferon and/or ribavirin are associated with decreased sustained virologic response rates. However, data are limited with regard to suboptimal drug exposure that is attributable to missed doses by patients with chronic hepatitis C virus (HCV) infection. We examined the relationship between adherence to pegylated interferon and ribavirin therapy, measured by pharmacy refill, and HCV suppression during the initial 12 weeks of therapy. Methods We conducted a cohort study involving 188 patients with chronic HCV infection who were treated with pegylated interferon plus ribavirin. Adherence was calculated using pharmacy refill data and could exceed 100%. The primary outcome was decrease in HCV load at 12 weeks; early virologic response was a secondary outcome. Mixed-effects regression models estimated the association between adherence and HCV suppression during the initial 12 weeks. Subanalyses were performed among patients who received optimal weight-based dosages. Results The mean decrease in HCV load at 12 weeks was 0.66 log IU/mL greater for patients with ⩾85% adherence than for those with <85% adherence (3.23 vs. 2.57 log IU/mL; P = 04). When patients who received a suboptimal ribavirin dosage were excluded, the decrease in viral load was 1.00 log IU/mL greater for persons with <85% adherence (3.32 vs. 2.32 log IU/mL; P = 01). Early virologic response was more common among patients with ⩾85% adherence than it was among those with <85% adherence to treatment with pegylated interferon (73% vs. 29%; P = 02) and ribavirin (73% vs. 55%; P = 08). Conclusions Adherence of ⩾85% to pegylated interferon and ribavirin treatment was associated with increased HCV suppression. Decreases in HCV load became greater when patients with ⩾85% adherence to their regimen continued to receive their recommended weight-based ribavirin dosage. PMID:19086908

  3. Next-Generation Sequencing and Genome Editing in Plant Virology.

    PubMed

    Hadidi, Ahmed; Flores, Ricardo; Candresse, Thierry; Barba, Marina

    2016-01-01

    Next-generation sequencing (NGS) has been applied to plant virology since 2009. NGS provides highly efficient, rapid, low cost DNA, or RNA high-throughput sequencing of the genomes of plant viruses and viroids and of the specific small RNAs generated during the infection process. These small RNAs, which cover frequently the whole genome of the infectious agent, are 21-24 nt long and are known as vsRNAs for viruses and vd-sRNAs for viroids. NGS has been used in a number of studies in plant virology including, but not limited to, discovery of novel viruses and viroids as well as detection and identification of those pathogens already known, analysis of genome diversity and evolution, and study of pathogen epidemiology. The genome engineering editing method, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been successfully used recently to engineer resistance to DNA geminiviruses (family, Geminiviridae) by targeting different viral genome sequences in infected Nicotiana benthamiana or Arabidopsis plants. The DNA viruses targeted include tomato yellow leaf curl virus and merremia mosaic virus (begomovirus); beet curly top virus and beet severe curly top virus (curtovirus); and bean yellow dwarf virus (mastrevirus). The technique has also been used against the RNA viruses zucchini yellow mosaic virus, papaya ringspot virus and turnip mosaic virus (potyvirus) and cucumber vein yellowing virus (ipomovirus, family, Potyviridae) by targeting the translation initiation genes eIF4E in cucumber or Arabidopsis plants. From these recent advances of major importance, it is expected that NGS and CRISPR-Cas technologies will play a significant role in the very near future in advancing the field of plant virology and connecting it with other related fields of biology.

  4. Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression

    PubMed Central

    Llibre, Josep M.; Cozzi-Lepri, Alessandro; Pedersen, Court; Ristola, Matti; Losso, Marcelo; Mocroft, Amanda; Mitsura, Viktar; Falconer, Karolin; Maltez, Fernando; Beniowski, Marek; Vullo, Vincenzo; Hassoun, Gamal; Kuzovatova, Elena; Szlavik, János; Kuznetsova, Anastasiia; Stellbrink, Hans-Jürgen; Duvivier, Claudine; Edwards, Simon; Laut, Kamilla; Paredes, Roger

    2016-01-01

    Abstract Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant. We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50 copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL. We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42–0.93] per 100 cells higher), time with pVL ≤50 copies/mL (HR 0.87 [95% CI: 0.79–0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28–6.04]). Resistance selection at failure was uncommon. A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure. PMID:27749561

  5. [Environmental virology and sanitation in Brazil: a narrative review].

    PubMed

    Prado, Tatiana; Miagostovich, Marize Pereira

    2014-07-01

    Sanitation services play a critical role in controlling transmission of numerous waterborne pathogens, especially viruses that cause acute gastroenteritis and hepatitis. The viral agents with the greatest public health impact are hepatitis A virus, rotaviruses and noroviruses, adenoviruses, and enteroviruses, contaminating many Brazilian aquatic ecosystems. Heavy circulation of viruses in the environment has been related to inadequate local sanitary conditions, including incomplete coverage of services or inefficacy of conventional technologies in eliminating or reducing the viral load in water or sewage. This study reviews the relations between virology, health, and sanitation, emphasizing the epidemiology of waterborne viral infections and their public health impact.

  6. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

    PubMed Central

    Fairlie, Lee; Karalius, Brad; Patel, Kunjal; van Dyke, Russell B.; Hazra, Rohan; Hernán, Miguel A.; Siberry, George K.; Seage, George R.; Agwu, Allison; Wiznia, Andrew

    2015-01-01

    Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) −1.01 to 2.19], not different than those who continued failing cART (71%) (−0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline −3.18 percentage points (95% CI −5.25 to −1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (−1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. PMID:26182197

  7. Evaluation of Humoral Immunity to Mycobacterium tuberculosis-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development

    PubMed Central

    Niki, Mamiko; Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Ohta, Ken; Inoue, Manabu; Niki, Makoto; Kaneko, Yukihiro; Morimoto, Kozo; Kurashima, Atsuyuki; Kitada, Seigo; Matsumoto, Sohkichi; Suzuki, Koichi; Hoshino, Yoshihiko

    2015-01-01

    Although tuberculosis remains a major global health problem, Bacille Calmette-Guérin (BCG) is the only available vaccine. However, BCG has limited applications, and a more effective vaccine is needed. Cellular mediated immunity (CMI) is thought to be the most important immune response for protection against Mycobacterium tuberculosis (Mtb). However, the recent failure of a clinical trial for a booster BCG vaccine and increasing evidence of antibody-mediated immunity prompted us to evaluate humoral immunity to Mtb-specific antigens. Using Enzyme-Linked ImmunoSpot and Enzyme-Linked ImmunoSorbent Assays, we observed less correlation of both CMI and IgG titers with patient clinical status, including serum concentration of C reactive protein. However, IgA titers against Mtb were significantly correlated with clinical status, suggesting that specific IgA antibodies protect against Mtb proliferation. In addition, in some cases, IgA antibody titers were significantly associated with the serum concentration of total albumin, which supports the idea that humoral immunity can be influenced by the nutritional status. Based on these observations, we propose that the induction of humoral immunity should be included as an option in TB vaccine development strategies. PMID:26568961

  8. Simultaneous Modeling of Disease Status and Clinical Phenotypes To Increase Power in Genome-Wide Association Studies.

    PubMed

    Bilow, Michael; Crespo, Fernando; Pan, Zhicheng; Eskin, Eleazar; Eyheramendy, Susana

    2017-03-01

    Genome-wide association studies have identified thousands of variants implicated in dozens of complex diseases. Most studies collect individuals with and without disease and search for variants with different frequencies between the groups. For many of these studies, additional disease traits are also collected. Jointly modeling clinical phenotype and disease status is a promising way to increase power to detect true associations between genetics and disease. In particular, this approach increases the potential for discovering genetic variants that are associated with both a clinical phenotype and a disease. Standard multivariate techniques fail to effectively solve this problem, because their case-control status is discrete and not continuous. Standard approaches to estimate model parameters are biased due to the ascertainment in case-control studies. We present a novel method that resolves both of these issues for simultaneous association testing of genetic variants that have both case status and a clinical covariate. We demonstrate the utility of our method using both simulated data and the Northern Finland Birth Cohort data.

  9. Correlation of the Virological Response to Short-Term Maraviroc Monotherapy with Standard and Deep-Sequencing-Based Genotypic Tropism Prediction Methods

    PubMed Central

    Gonzalez-Serna, A.; McGovern, R. A.; Harrigan, P. R.; Vidal, F.; Poon, A. F. Y.; Ferrando-Martinez, S.; Abad, M. A.; Genebat, M.; Leal, M.

    2012-01-01

    Genotypic tropism testing methods are emerging as the first step before prescription of the CCR5 antagonist maraviroc (MVC) to HIV-infected patients in Europe. Studies validating genotypic tests have included other active drugs that could have potentially convoluted the effects of MVC. The maraviroc clinical test (MCT) is an in vivo drug sensitivity test based on the virological response to a short-term exposure to MVC monotherapy. Thus, our aim was to compare the results of genotypic tropism testing methods with the short-term virological response to MVC monotherapy. A virological response in the MCT was defined as a ≥1-log10 decrease in HIV RNA or undetectability after 8 days of drug exposure. Seventy-three patients undergoing the MCT were included in this study. We used both standard genotypic methods (n = 73) and deep sequencing (n = 27) on MCT samples at baseline. For the standard methods, the most widely used genotypic algorithms for analyzing the V3 loop sequence, geno2pheno and PSSM, were used. For deep sequencing, the geno2pheno algorithm was used with a false-positive rate cutoff of 3.5. The discordance rates between the standard genotypic methods and the virological response were approximately 20% (including mostly patients without a virological response). Interestingly, these discordance rates were similar to that obtained from deep sequencing (18.5%). The discordance rates between the genotypic methods (tropism assays predictive of the use of the CCR5 coreceptor) and the MCT (in vivo MVC sensitivity assay) indicate that the algorithms used by genotypic methods are still not sufficiently optimized. PMID:22143533

  10. The Effects of Socioeconomic Status, Clinical Factors, and Genetic Ancestry on Pulmonary Tuberculosis Disease in Northeastern Mexico

    PubMed Central

    Young, Bonnie N.; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M.; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L.

    2014-01-01

    Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

  11. The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

    PubMed

    Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

    2014-01-01

    Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

  12. [Research on antiviral chemotherapy at the Stefan S. Nicolau Institute of Virology in 1984-1989].

    PubMed

    Eşanu, V

    1989-01-01

    The paper is a review of researches done at the "Stefan S. Nicolau" Institute of Virology, in Bucharest, the last five years, in the antiviral chemotherapy field, as well as of the chemotherapeutical implications of studies conducted about other aspects of virology.

  13. L-Carnitine supplementation improved clinical status without changing oxidative stress and lipid profile in women with knee osteoarthritis.

    PubMed

    Malek Mahdavi, Aida; Mahdavi, Reza; Kolahi, Sousan; Zemestani, Maryam; Vatankhah, Amir-Mansour

    2015-08-01

    Considering the pathologic importance of oxidative stress and altered lipid metabolism in osteoarthritis (OA), this study aimed to investigate the effect of l-carnitine supplementation on oxidative stress, lipid profile, and clinical status in women with knee OA. We hypothesized that l-carnitine would improve clinical status by modulating serum oxidative stress and lipid profile. In this randomized double-blind, placebo-controlled trial, 72 overweight or obese women with mild to moderate knee OA were randomly allocated into 2 groups to receive 750 mg/d l-carnitine or placebo for 8 weeks. Dietary intake was evaluated using 24-hour recall for 3 days. Serum malondialdehyde (MDA), total antioxidant capacity (TAC) and lipid profile, visual analog scale for pain intensity, and patient global assessment of severity of disease were assessed before and after supplementation. Only 69 patients (33 in the l-carnitine group and 36 in the placebo group) completed the study. l-Carnitine supplementation resulted in significant reductions in serum MDA (2.46 ± 1.13 vs 2.16 ± 0.94 nmol/mL), total cholesterol (216.09 ± 34.54 vs 206.12 ± 39.74 mg/dL), and low-density lipoprotein cholesterol (129.45 ± 28.69 vs 122.05 ± 32.76 mg/dL) levels compared with baseline (P < .05), whereas these parameters increased in the placebo group. Serum triglyceride, high-density lipoprotein cholesterol, and TAC levels did not change significantly in both groups (P > .05). No significant differences were observed in dietary intake, serum lipid profile, MDA, and TAC levels between groups after adjusting for baseline values and covariates (P > .05). There were significant intragroup and intergroup differences in pain intensity and patient global assessment of disease status after supplementation (P < .05). Collectively, l-carnitine improved clinical status without changing oxidative stress and lipid profile significantly in women with knee OA.

  14. Update from the 7th annual meeting of the Italian Society of Virology.

    PubMed

    Salata, Cristiano; Calistri, Arianna; Palù, Giorgio

    2008-07-01

    The Italian Society of Virology (SIV) held a meeting in Orvieto (June 24-26, 2007) aimed at promoting interactions and collaborations between scientists in the field of Virology. The meeting had an attendance of about 170 virologists from Italy. In accordance with the normal format of the SIV National Meeting the conference transcended all areas of Virology. Sessions included invited speakers together with selected oral presentation. Covered topics included: General Virology and Viral Genetics, Medical Virology and Antiviral Therapy, Viral Biotechnologies and Gene Therapy, Viral Oncogenesis and Vaccines, Virus-Host Interactions and Pathogenesis, Emerging and Zoonotic Viral Infections. In this edition, a special effort was addressed to the HPV infection and prevention and to the guidelines for the preemptive (presymptomatic) therapy of human cytomegalovirus infections in transplant recipients. A summary of the main topics are reported.

  15. Current status of ex vivo gene therapy for hematological disorders: a review of clinical trials in Japan around the world.

    PubMed

    Tani, Kenzaburo

    2016-07-01

    Gene therapies are classified into two major categories, namely, in vivo and ex vivo. Clinical trials of human gene therapy began with the ex vivo techniques. Based on the initial successes of gene-therapy clinical trials, these approaches have spread worldwide. The number of gene therapy trials approved worldwide increased gradually starting in 1989, reaching 116 protocols per year in 1999, and a total of 2210 protocols had been approved by 2015. Accumulating clinical evidence has demonstrated the safety and benefits of several types of gene therapy, with the exception of serious adverse events in several clinical trials. These painful experiences were translated backward to basic science, resulting in the development of several new technologies that have influenced the recent development of ex vivo gene therapy in this field. To date, six gene therapies have been approved in a limited number of countries worldwide. In Japan, clinical trials of gene therapy have developed under the strong influence of trials in the US and Europe. Since the initial stages, 50 clinical trials have been approved by the Japanese government. In this review, the history and current status of clinical trials of ex vivo gene therapy for hematological disorders are introduced and discussed.

  16. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS

    PubMed Central

    Kong, Byung Soo; Lee, Jung-Eun; Kim, Kyoung Heon; Lee, Do Yup; Kim, Ho Jin

    2016-01-01

    Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (ITM). Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF) metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls). Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs. PMID:27855220

  17. The Correspondence Between Magnetic Resonance Images and the 
Clinical and Intraoperative Status of Patients with Spinal Tumors

    PubMed Central

    Guzik, Grzegorz

    2016-01-01

    Abstract: Introduction Surgical treatment of tumors, particularly metastases to the spine, has become increasingly common owing to the progress in anesthesiology and spinal surgery and greater detectability. The patients qualified for surgeries are those with mechanical pain, fracture or at risk of vertebral fracture or neurological complications. The basis for qualification for different types of surgeries is clinical and imaging examination, particularly MRI and CT. Qualification should always be multidisciplinary and requires understanding and knowledge of its most essential aspects. When carrying out imaging examinations, it is necessary to assess the size and the type of the tumor, taking into account of differential diagnosis. One should also consider the factors indicating spinal instability or the onset of neurological deficits. The criteria developed by Kostiuk-Weinstain and Taneichi are used for that purpose. The aim of the present study was to evaluate the correspondence between the most essential elements of clinical and MRI examination of the spine and the intraoperative status of patients with spinal tumors. Materials and Methods We carried out prospective examination assessing the correspondence between the clinical status and MR images and the intraoperative spine. We introduced algorithm to describe the morphology of neoplastic lesions within the spine. Results The information obtained from the clinical examination and the intraoperative status of the spine corresponded with the MRI examination with the exception of the assessment of neoplastic infiltration to soft tissues, dura mater and nerve roots. It was also found that there are no clear-cut MRI features allowing differentiation of metastatic lesions from primary tumors and osteitis. Furthermore, MRI examination does not allow for the assessment of the quality of bone tissue in the vicinity of the tumor. PMID:27853411

  18. Case report: successful retreatment of hepatitis C genotype 1b infection with sofosbuvir + simeprevir in a patient with cirrhosis who had prior virologic relapse after treatment with daclatasvir and asunaprevir.

    PubMed

    Safadi, Rifaat; Noviello, Stephanie; Boparai, Navdeep; McPhee, Fiona

    2016-07-01

    There is currently minimal clinical experience regarding retreatment options for patients failing direct-acting antiviral combination regimens. Here, we report the outcomes of a HCV genotype 1b-infected patient with virologic failure following treatment with daclatasvir and asunaprevir, who was successfully retreated with sofosbuvir plus simeprevir.

  19. HIV-1 DNA predicts disease progression and post-treatment virological control

    PubMed Central

    Williams, James P; Hurst, Jacob; Stöhr, Wolfgang; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Carrington, Mary; Babiker, Abdel; Weber, Jonathan

    2014-01-01

    In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 PMID:25217531

  20. The Serological and Virological Investigation of Canine Adenovirus Infection on the Dogs

    PubMed Central

    Bulut, Oya; Yapici, Orhan; Avci, Oguzhan; Simsek, Atilla; Atli, Kamil; Dik, Irmak; Yavru, Sibel; Hasircioglu, Sibel; Kale, Mehmet; Mamak, Nuri

    2013-01-01

    Two types of Canine Adenovirus (CAVs), Canine Adenovirus type 1 (CAV-1), the virus which causes infectious canine hepatitis, and Canine Adenovirus type 2 (CAV-2), which causes canine infectious laryngotracheitis, have been found in dogs. In this study, blood samples taken from 111 dogs, which were admitted to the Internal Medicine Clinic of Selcuk University, Faculty of Veterinary Medicine, with clinical symptoms. Seventy-seven dogs were sampled from Isparta and Burdur dog shelters by random sampling, regardless of the clinical findings. Dogs showed a systemic disease, characterized by fever, diarrhea, vomiting, oculonasal discharge, conjunctivitis, severe moist cough, signs of pulmonary disease and dehydration. Two dogs had corneal opacity and photophobia. In serological studies, 188 serum samples were investigated on the presence of CAV antibodies by ELISA. Total 103 (103/188–54.7%) blood samples were detected to be positive for CAV antibodies by ELISA. However, 85 (85/188–45.2%) blood samples were negative. Blood leukocyte samples from dogs were processed and inoculated onto confluent monolayers of MDCK cells using standard virological techniques. After third passage, cells were examined by direct immunoflourescence test for virus isolation. But positive result was not detected. In conclusion, this study clearly demonstrates the high prevalence of CAV infection in dogs. PMID:24223508

  1. Progressive outer retinal necrosis syndrome: a comprehensive review of its clinical presentation, relationship to immune system status, and management.

    PubMed

    Austin

    2000-12-01

    Progressive outer retinal necrosis (PORN) syndrome is a form of the Varicella zoster virus (VZV) chorioretinitis found almost exclusively in people with the acquired immunodeficiency syndrome (AIDS). This destructive infection has an extremely rapid course that may lead to no light perception in affected eyes within days or weeks. Attempts at its treatment have had limited success. Rhegmatogenous retinal detachments often occur after the development of atrophic retinal holes, and silicone oil temponade has been found to be the most successful reattachment procedure. Unfortunately, cataract formation is common after such surgery. PORN needs to be differentiated from acute retinal necrosis (ARN) syndrome, a necrotizing retinitis that can also be caused by VZV. PORN and ARN are found at opposite ends of the spectrum of necrotizing herpetic retinopathies (NHR), where its clinical presentation depends upon immune system status. After a brief case presentation, the distinguishing clinical characteristics of PORN, its differentiation from ARN, attempts at its treatment, the role of the immune system status on its clinical appearance and treatment, and management of complications such as retinal detachment and subsequent cataracts are discussed.

  2. Current status on clinical applications of magnesium-based orthopaedic implants: A review from clinical translational perspective.

    PubMed

    Zhao, Dewei; Witte, Frank; Lu, Faqiang; Wang, Jiali; Li, Junlei; Qin, Ling

    2017-01-01

    As a new generation of medical metallic material, magnesium (Mg) and its alloys with or without surface coating have attracted a great deal of attention due to its biodegradability and potential for avoiding a removal operation after the implant has fulfilled its function for surgical fixation of injured musculoskeletal tissues. Although a few clinical cases on Mg-based orthopaedic implants were reported more than a century ago, it was not until recently that clinical trials using these implants with improved physicochemical properties were carried out in Germany, China and Korea for bone fracture fixation. The promising results so far suggest a bright future for biodegradable Mg-based orthopaedic implants and would warrant large scale phase II/III studies. Given the increasing interest on this emerging biomaterials and intense effort to improve its properties for various clinical applications, this review covers the evolution, current strategies, and future perspectives in the development of Mg-based orthopaedic implants. We also highlight a few clinical cases performed in China that may be unfamiliar to the general orthopaedic community.

  3. Hepatitis B e Antigen Status and Hepatitis B DNA Levels in Women of Childbearing Age with Chronic Hepatitis B Infection Screening for Clinical Trials

    PubMed Central

    Tran, Tram T.; Gordon, Stuart C.; Fung, Scott; Dinh, Phillip; Yee, Leland; Martins, Eduardo Bruno; Buti, Maria; Marcellin, Patrick

    2015-01-01

    Background Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load. Aim To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials. Methods Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18–69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive. Results Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>108 copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load. Conclusions Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load. PMID:25789483

  4. Dynamics of hepatitis B virus quasispecies heterogeneity and virologic response in patients receiving low-to-moderate genetic barrier nucleoside analogs.

    PubMed

    Peveling-Oberhag, J; Herrmann, E; Kronenberger, B; Farnik, H; Susser, S; Sarrazin, C; Zeuzem, S; Hofmann, W-P

    2013-04-01

    We characterized the early dynamics of hepatitis B virus (HBV) quasispecies evolution during the first weeks of antiviral therapy with low-to-moderate genetic barrier antiviral drugs and associated these data with antiviral response patterns. Fifteen chronic hepatitis B patients (men, 10; mean age, 34; HBeAg positive, 6) who received lamivudine or telbivudine for at least 52 weeks were included. HBV DNA was extracted from serum, and a 910-bp fragment covering domains A-F of the reverse transcriptase region was amplified, cloned and sequenced. Parameters of quasispecies heterogeneity, genetic diversity and complexity were calculated and were correlated with complete virologic response, defined as undetectable HBV DNA at week 52. Nine patients achieved complete virologic response during the observational period. While baseline HBV DNA levels and HBeAg status were associated with virologic response, baseline quasispecies complexity and diversity of responders showed no significant difference to those of nonresponders (P > 0.05). However, at week 4, quasispecies complexity of nonresponders was significantly higher compared with that of responders on the nucleotide level (P = 0.01) and the aa level (P = 0.04). The number of synonymous substitutions per synonymous site dropped significantly in responders at week 4 (P = 0.04), while there was no difference in nonresponders. The HBV quasispecies complexity at the early stage of antiviral therapy (week 4) with the low-to-moderate genetic barrier nucleoside analogs lamivudine or telbivudine was associated with subsequent virologic response. Further studies are needed to confirm HBV quasispecies evolution as additional predictive marker for beneficial treatment outcome.

  5. Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy

    PubMed Central

    Zhou, Bin; Dong, Hui; He, Yungang; Sun, Jian; Jin, Weirong; Xie, Qing; Fan, Rong; Wang, Minxian; Li, Ran; Chen, Yangyi; Xie, Shaoqing; Shen, Yan; Huang, Xin; Wang, Shengyue; Lu, Fengming; Jia, Jidong; Zhuang, Hui; Locarnini, Stephen; Zhao, Guo-Ping; Jin, Li; Hou, Jinlin

    2015-01-01

    Reverse transcriptase (RT) mutations contribute to hepatitis B virus resistance during antiviral therapy with nucleos(t)ide analogs. However, the composition of the RT quasispecies and their interactions during antiviral treatment have not yet been thoroughly defined. In this report, 10 patients from each of 3 different virological response groups, i.e., complete virological response, partial virological response and virological breakthrough, were selected from a multicenter trial of Telbivudine treatment. Variations in the drug resistance-related critical RT regions in 107 serial serum samples from the 30 patients were examined by ultra-deep sequencing. A total of 496,577 sequence reads were obtained, with an average sequencing coverage of 4,641X per sample. The phylogenies of the quasispecies revealed the independent origins of two critical quasispecies, i.e., the rtA181T and rtM204I mutants. Data analyses and theoretical modeling showed a cooperative-competitive interplay among the quasispecies. In particular, rtM204I mutants compete against other quasispecies, which eventually leads to virological breakthrough. However, in the absence of rtM204I mutants, synergistic growth of the drug-resistant rtA181T mutants with the wild-type quasispecies could drive the composition of the viral population into a state of partial virological response. Furthermore, we demonstrated that the frequency of drug-resistant mutations in the early phase of treatment is important for predicting the virological response to antiviral therapy. PMID:26599443

  6. Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy.

    PubMed

    Zhou, Bin; Dong, Hui; He, Yungang; Sun, Jian; Jin, Weirong; Xie, Qing; Fan, Rong; Wang, Minxian; Li, Ran; Chen, Yangyi; Xie, Shaoqing; Shen, Yan; Huang, Xin; Wang, Shengyue; Lu, Fengming; Jia, Jidong; Zhuang, Hui; Locarnini, Stephen; Zhao, Guo-Ping; Jin, Li; Hou, Jinlin

    2015-11-24

    Reverse transcriptase (RT) mutations contribute to hepatitis B virus resistance during antiviral therapy with nucleos(t)ide analogs. However, the composition of the RT quasispecies and their interactions during antiviral treatment have not yet been thoroughly defined. In this report, 10 patients from each of 3 different virological response groups, i.e., complete virological response, partial virological response and virological breakthrough, were selected from a multicenter trial of Telbivudine treatment. Variations in the drug resistance-related critical RT regions in 107 serial serum samples from the 30 patients were examined by ultra-deep sequencing. A total of 496,577 sequence reads were obtained, with an average sequencing coverage of 4,641X per sample. The phylogenies of the quasispecies revealed the independent origins of two critical quasispecies, i.e., the rtA181T and rtM204I mutants. Data analyses and theoretical modeling showed a cooperative-competitive interplay among the quasispecies. In particular, rtM204I mutants compete against other quasispecies, which eventually leads to virological breakthrough. However, in the absence of rtM204I mutants, synergistic growth of the drug-resistant rtA181T mutants with the wild-type quasispecies could drive the composition of the viral population into a state of partial virological response. Furthermore, we demonstrated that the frequency of drug-resistant mutations in the early phase of treatment is important for predicting the virological response to antiviral therapy.

  7. Bite Injuries to the Hand: Microbiology, Virology and Management

    PubMed Central

    Malahias, M.; Jordan, D.; Hughes, O.; Khan, Wasim S.; Hindocha, S.

    2014-01-01

    Bites to the human hand, be it from a pet, a stray animal or even a fellow human, may often have dire consequences for the person suffering the insult. Bites by mammals are a common problem and they account for up to 1% of all visits to hospital emergency rooms, in the UK. Clenched fist injuries to the mouth (‘fight bite’) are notorious for being the worst human bites. Bite injuries of the hand and their related infections must be monitored vigilantly and managed proactively, by experts in this field of surgery. In this review article we discuss the associated microbiology and virology of these injuries as well as their management. PMID:25067969

  8. Virological Mechanisms in the Coinfection between HIV and HCV.

    PubMed

    Liberto, Maria Carla; Zicca, Emilia; Pavia, Grazia; Quirino, Angela; Marascio, Nadia; Torti, Carlo; Focà, Alfredo

    2015-01-01

    Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV) is common in patients infected by Human Immunodeficiency Virus (HIV). The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

  9. Establishment of the European College of Veterinary Clinical Pathology (ECVCP) and the current status of veterinary clinical pathology in Europe.

    PubMed

    O'Brien, P J; Fournel-Fleury, C; Bolliger, A P; Freeman, K P; Braun, J-P; Archer, J; Paltrinieri, S; Tvedten, H; Polizopoulou, Z S; Jensen, A L; Pastor, J; Lanevschi-Pietersma, A; Thoren-Tolling, K; Schwendenwien, I; Thoresen, S I; Bauer, N B; Ledieu, D; Cerón, J J; Palm, M; Papasouliotis, K; Gaál, T; Vajdovich, P

    2007-12-01

    After 5 years of development, the European College of Veterinary Clinical Pathology (ECVCP) was formally recognized and approved on July 4, 2007 by the European Board of Veterinary Specialisation (EBVS), the European regulatory body that oversees specialization in veterinary medicine and which has approved 23 colleges. The objectives, committees, basis for membership, constitution, bylaws, information brochure and certifying examination of the ECVCP have remained unchanged during this time except as directed by EBVS. The ECVCP declared full functionality based on the following criteria: 1) a critical mass of 65 members: 15 original diplomates approved by the EBVS to establish the ECVCP, 37 de facto diplomates, 7 diplomates certified by examination, and 5 elected honorary members; 2) the development and certification of training programs, laboratories, and qualified supervisors for residents; currently there are 18 resident training programs in Europe; 3) administration of 3 annual board-certifying examinations thus far, with an overall pass rate of 70%; 4) European consensus criteria for assessing the continuing education of specialists every 5 years; 5) organization of 8 annual scientific congresses and a joint journal (with the American Society for Veterinary Clinical Pathology) for communication of scientific research and information; the College also maintains a website, a joint listserv, and a newsletter; 6) collaboration in training and continuing education with relevant colleges in medicine and pathology; 7) development and strict adherence to a constitution and bylaws compliant with the EBVS; and 8) demonstration of compelling rationale, supporting data, and the support of members and other colleges for independence as a specialty college. Formal EBVS recognition of ECVCP as the regulatory body for the science and practice of veterinary clinical pathology in Europe will facilitate growth and development of the discipline and compliance of academic

  10. Data standards for clinical research data collection forms: current status and challenges.

    PubMed

    Richesson, Rachel L; Nadkarni, Prakash

    2011-05-01

    Case report forms (CRFs) are used for structured-data collection in clinical research studies. Existing CRF-related standards encompass structural features of forms and data items, content standards, and specifications for using terminologies. This paper reviews existing standards and discusses their current limitations. Because clinical research is highly protocol-specific, forms-development processes are more easily standardized than is CRF content. Tools that support retrieval and reuse of existing items will enable standards adoption in clinical research applications. Such tools will depend upon formal relationships between items and terminological standards. Future standards adoption will depend upon standardized approaches for bridging generic structural standards and domain-specific content standards. Clinical research informatics can help define tools requirements in terms of workflow support for research activities, reconcile the perspectives of varied clinical research stakeholders, and coordinate standards efforts toward interoperability across healthcare and research data collection.

  11. Effect of Phosphodiesterase-5 Inhibition on Exercise Capacity and Clinical Status in Heart Failure with Preserved Ejection Fraction: A Randomized Clinical Trial

    PubMed Central

    Redfield, Margaret M; Chen, Horng H; Borlaug, Barry A; Semigran, Marc J.; Lee, Kerry L.; Lewis, Gregory; LeWinter, Martin M.; Rouleau, Jean L.; Bull, David A.; Mann, Douglas L.; Deswal, Anita; Stevenson, Lynne W.; Givertz, Michael M.; Ofili, Elizabeth O.; O’Connor, Christopher M.; Felker, G. Michael; Goldsmith, Steven R.; Bart, Bradley A.; McNulty, Steven E; Ibarra, Jenny C.; Lin, Grace; Oh, Jae K.; Patel, Manesh R.; Kim, Raymond J.; Tracy, Russell P.; Velazquez, Eric J.; Anstrom, Kevin J.; Hernandez, Adrian F.; Mascette, Alice M.; Braunwald, Eugene

    2013-01-01

    Importance Studies in experimental and human heart failure suggest that phosphodiesterase type-5 inhibitors may enhance cardiovascular function, and thus, exercise capacity in heart failure with preserved ejection fraction. Objective To determine the effect of the phosphodiesterase type-5 inhibitor, sildenafil, in comparison to placebo on exercise capacity and clinical status in heart failure with preserved ejection fraction. Design, setting, and patients Multicenter, double-blind, placebo-controlled, parallel design, randomized clinical trial of 216 stable outpatients with heart failure, ejection fraction ≥ 50%, elevated N-terminal pro-brain natriuretic peptide or elevated invasively-measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in the United States and Canada. Intervention Sildenafil (n=113) or placebo (n=103) administered orally at 20 mg three times daily for 12 weeks followed by 60 mg three times daily for 12 weeks. Main outcome measures Primary endpoint was change in peak oxygen consumption after 24 weeks of therapy. Secondary endpoints included change in six-minute walk distance and a three tier hierarchical composite clinical status score where patients were ranked (range 1-N) based on time to death, time to cardiovascular or cardiorenal hospitalization and change in quality of life for participants alive without cardiovascular or cardiorenal hospitalization at 24 weeks. Results Median age was 69 years and 48% of patients were female. At baseline, median peak oxygen consumption (11.7 ml/kg/min) and six-minute walk distance (308 meters) were reduced and median E/e′ (16), left atrial volume index (44 ml/m2) and pulmonary artery systolic pressure (41 mmHg) were consistent with chronically-elevated left ventricular filling pressures. At 24 weeks, median (interquartile range) changes in peak oxygen consumption (ml/kg/min) in patients who received placebo [−0

  12. 100 years of virology: from vitalism via molecular biology to genetic engineering.

    PubMed

    Bos, L

    2000-02-01

    The identification of the causative agent of tobacco mosaic disease as a novel pathogen by the Dutch microbiologist Beijerinck is now acknowledged as being the foundation of virology as a discipline distinct from bacteriology. However, as this was contrary to the prevailing theories of the time, it took many years for virology to become firmly established as a separate discipline. The history of virology illustrates how accepted concepts in science evolve by trial and error and the need for a balanced approach when manipulating natural systems.

  13. Sleep Apnea Cardiovascular Clinical Trials-Current Status and Steps Forward: The International Collaboration of Sleep Apnea Cardiovascular Trialists.

    PubMed

    Gottlieb, Daniel J; Craig, Sonya E; Lorenzi-Filho, Geraldo; Heeley, Emma; Redline, Susan; McEvoy, R Doug; Durán-Cantolla, Joaquín

    2013-07-01

    Sleep apnea is a common chronic disease that is associated with coronary heart disease, stroke, heart failure and mortality, although the ability of sleep apnea treatment to reduce cardiovascular morbidity and mortality has not been demonstrated. In contrast to patients seeking treatment in sleep disorders centers, as many as half of individuals with moderate to severe sleep apnea in the general population do not report excessive sleepiness; however, if treatment of sleep apnea were shown to reduce cardiovascular disease risk, this would provide a strong rationale for treatment of sleep apnea even in the absence of daytime sleepiness. This article summarizes the status of clinical trials evaluating the potential cardiovascular benefits of sleep apnea treatment and discusses the challenges of conducting such trials, and introduces the International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT), a clinical research collaboration formed to foster cardiovascular sleep research.

  14. Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases.

    PubMed

    Peretz, A; Nève, J; Jeghers, O; Pelen, F

    1993-05-01

    The effects of zinc supplementation on zinc status and on clinical and biological indicators of inflammation were investigated in 18 patients with chronic inflammatory rheumatic diseases and in 9 healthy control subjects. Patients with mild and recent onset disease were assigned to a 60-d trial to receive either 45 mg Zn (as gluconate)/d or a placebo, while control subjects received the zinc supplement. Baseline mean plasma zinc of the patients was low whereas mononuclear cell zinc content was elevated, suggesting a redistribution of the element related to the inflammatory process rather than to a zinc-deficient state. Zinc supplementation increased plasma zinc to a similar extent in patients and in control subjects, which suggested no impairment of zinc intestinal absorption as a result of the inflammatory process. On the contrary, erythrocyte and leukocyte zinc concentrations were not modified in the two groups examined. No beneficial effect of zinc treatment could be demonstrated on either clinical or inflammation indexes.

  15. Current status of psychology and clinical psychology in India - an appraisal.

    PubMed

    Virudhagirinathan, Baboo Sankar; Karunanidhi, Subbiah

    2014-10-01

    This paper provides an overview of the social and cultural context for the emergence and development of psychology in India and also more specifically of the development of clinical psychology. It details the range of universities offering psychology programmes and the various bodies involved in supporting the development of the psychology. The paper also describes the development of clinical psychology in India and the variety of roles undertaken by clinical psychologists. Finally, it raises a number of issues facing the development of Indian psychology into the future.

  16. Status of interagency cooperation between interdisciplinary clinics or hospitals and the public schools.

    PubMed

    Rotberg, J; Forness, S R; Lynch, E W; Gardner, T P; Urbano, R; Bender, M

    1982-01-01

    Since public schools are now mandated to provide a large and varied range of clinical services to handicapped school children, a survey was conducted of 26 interdisciplinary UAF clinics and hospitals in regard to the types of services which they offer to public school children and the extent in which coordination of such services has been developed. Results suggest that diagnosis of evaluation is the primary reason for referral but that a wide variety of community outreach services are both requested by the schools and offered by interdisciplinary hospital and clinic staff. These services are described and the implications for future interagency cooperation are discussed.

  17. HIV testing and clinical status upon admission to a specialized health care unit in Pará, Brazil

    PubMed Central

    Abati, Paulo Afonso Martins; Segurado, Aluisio Cotrim

    2015-01-01

    OBJECTIVE To analyze the clinical and laboratory characteristics of HIV-infected individuals upon admission to a reference health care center. METHODS This cross-sectional study was conducted between 1999 and 2010 on 527 individuals with confirmed serological diagnosis of HIV infection who were enrolled in an outpatient health care service in Santarém, PA, Northern Brazil. Data were collected from medical records and included the reason for HIV testing, clinical status, and count of peripheral CD4+ T lymphocytes upon enrollment. The data were divided into three groups, according to the patient’s year of admission – P1 (1999-2002), P2 (2003-2006), and P3 (2007-2010) – for comparative analysis of the variables of interest. RESULTS In the study group, 62.0% of the patients were assigned to the P3 group. The reason for undergoing HIV testing differed between genders. In the male population, most tests were conducted because of the presence of symptoms suggesting infection. Among women, tests were the result of knowledge of the partner’s seropositive status in groups P1 and P2. Higher proportion of women undergoing testing because of symptoms of HIV/AIDS infection abolished the difference between genders in the most recent period. A higher percentage of patients enrolling at a more advanced stage of the disease was observed in P3. CONCLUSIONS Despite the increased awareness of the number of HIV/AIDS cases, these patients have identified their serological status late and were admitted to health care units with active disease. The HIV/AIDS epidemic in Pará presents specificities in its progression that indicate the complex characteristics of the epidemic in the Northern region of Brazil and across the country. PMID:25741647

  18. Oncologic Photodynamic Therapy: Basic Principles, Current Clinical Status and Future Directions

    PubMed Central

    van Straten, Demian; Mashayekhi, Vida; de Bruijn, Henriette S.; Oliveira, Sabrina; Robinson, Dominic J.

    2017-01-01

    Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells and/or vasculature, and induce inflammatory and immune responses. PDT is a two-stage procedure, which starts with photosensitizer administration followed by a locally directed light exposure, with the aim of confined tumor destruction. Since its regulatory approval, over 30 years ago, PDT has been the subject of numerous studies and has proven to be an effective form of cancer therapy. This review provides an overview of the clinical trials conducted over the last 10 years, illustrating how PDT is applied in the clinic today. Furthermore, examples from ongoing clinical trials and the most recent preclinical studies are presented, to show the directions, in which PDT is headed, in the near and distant future. Despite the clinical success reported, PDT is still currently underutilized in the clinic. We also discuss the factors that hamper the exploration of this effective therapy and what should be changed to render it a more effective and more widely available option for patients. PMID:28218708

  19. ICU nurses and physicians dialogue regarding patients clinical status and care options—a focus group study

    PubMed Central

    Kvande, Monica; Lykkeslet, Else; Storli, Sissel Lisa

    2017-01-01

    ABSTRACT Nurses and physicians work side-by-side in the intensive care unit (ICU). Effective exchanges of patient information are essential to safe patient care in the ICU. Nurses often rate nurse-physician communication lower than physicians and report that it is difficult to speak up, that disagreements are not resolved and that their input is not well received. Therefore, this study explored nurses’ dialogue with physicians regarding patients’ clinical status and the prerequisites for effective and accurate exchanges of information. We adopted a qualitative approach, conducting three focus group discussions with five to six nurses and physicians each (14 total). Two themes emerged. The first theme highlighted nurses’ contributions to dialogues with physicians; nurses’ ongoing observations of patients were essential to patient care discussions. The second theme addressed the prerequisites of accurate and effective dialogue regarding care options, comprising three subthemes: nurses’ ability to speak up and present clinical changes, establishment of shared goal and clinical understanding, and open dialogue and willingness to listen to each other. Nurses should understand their essential role in conducting ongoing observations of patients and their right to be included in care-related decision-making processes. Physicians should be willing to listen to and include nurses’ clinical observations and concerns.

  20. VE1 immunohistochemistry predicts BRAF V600E mutation status and clinical outcome in colorectal cancer

    PubMed Central

    Schafroth, Christian; Galván, José A.; Centeno, Irene; Koelzer, Viktor H.; Dawson, Heather E.; Sokol, Lena; Rieger, Gregor; Berger, Martin D.; Hädrich, Marion; Rosenberg, Robert; Nitsche, Ulrich; Schnüriger, Beat; Langer, Rupert; Inderbitzin, Daniel; Lugli, Alessandro; Zlobec, Inti

    2015-01-01

    Aim VE1 is a monoclonal antibody detecting mutant BRAFV600E protein by immunohistochemistry. Here we aim to determine the inter-observer agreement and concordance of VE1 with mutational status, investigate heterogeneity in colorectal cancers and metastases and determine the prognostic effect of VE1 in colorectal cancer patients. Methods Concordance of VE1 with mutational status and inter-observer agreement were tested on a pilot cohort of colorectal cancers (n = 34), melanomas (n = 23) and thyroid cancers (n = 8). Two prognostic cohorts were evaluated (n = 259, Cohort 1 and n = 226, Cohort 2) by multiple-punch tissue microarrays. VE1 staining on preoperative biopsies (n = 118 patients) was compared to expression in resections. Primary tumors and metastases from 13 patients were tested for VE1 heterogeneity using a tissue microarray generated from all available blocks (n = 100 blocks). Results Inter-observer agreement was 100% (kappa = 1.0). Concordance between VE1 and V600E mutation was 98.5%. Cohort 1: VE1 positivity (seen in 13.5%) was associated with older age (p = 0.0175) and MLH1 deficiency (p < 0.0001). Cohort 2: VE1 positivity (seen in 12.8%) was associated with female gender (p = 0.0016), right-sided tumor location (p < 0.0001), higher tumor grade (p < 0.0001) and mismatch repair (MMR)-deficiency (p < 0.0001). In survival analysis, MMR status and postoperative therapy were identified as possible confounding factors. Adjusting for these features, VE1 was an unfavorable prognostic factor. Preoperative biopsy staining matched resections in all cases except one. No heterogeneity was found across any primary/metastatic tumor blocks. Conclusion VE1 is highly concordant for V600E and homogeneously expressed suggesting staining can be analysed on resection specimens, preoperative biopsies, metastatic lesions and tissue microarrays. PMID:26496026

  1. News and views from the 8th annual meeting of the Italian Society of Virology.

    PubMed

    Sartori, Elena; Salata, Cristiano; Calistri, Arianna; Palù, Giorgio; Parolin, Cristina

    2009-06-01

    The 8th annual meeting of the Italian Society of Virology (SIV) took place in Orvieto, Italy from the 21st to the 23rd of September 2008. The meeting covered different areas of Virology and the scientific sessions focused on: general virology and viral genetics; viral oncology, virus-host interaction and pathogenesis; emerging viruses and zoonotic, foodborne and environmental pathways of transmission; viral immunology and vaccines; viral biotechnologies and gene therapy; medical virology and antiviral therapy. The meeting had an attendance of about 160 virologists from all Italy. In this edition, a satellite workshop on "Viral biotechnologies" was organized in order to promote the role of virologists in the biotechnological research and teaching fields. A summary of the plenary lectures and oral selected presentations is reported. J. Cell. Physiol. 219: 797-799, 2009. (c) 2009 Wiley-Liss, Inc.

  2. Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications

    PubMed Central

    Pak, Jaewoo; Lee, Jung Hun; Kartolo, Wiwi Andralia; Lee, Sang Hee

    2016-01-01

    Osteoarthritis (OA) is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs) in the form of stromal vascular fraction (SVF) may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP), have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA. PMID:26881220

  3. Kidney stones diseases and glycaemic statuses: focus on the latest clinical evidences.

    PubMed

    Spatola, Leonardo; Angelini, Claudio; Badalamenti, Salvatore; Maringhini, Silvio; Gambaro, Giovanni

    2016-12-05

    Diabetes and obesity are already recognized as potential risk factors for nephrolithiasis, especially for uric acid stones. Insulin resistance and hyperinsulinemia actively contribute to impaired ability to excrete an acid load and altered ammonium production, leading to a lower urinary pH compared to non-diabetic controls. All these electrolytic disorders play an important role in stone formation and aggregation, especially in uric acid stones. There are still missing points in scientific evidence if the increased risk in stone formation is already existing even in the prediabetic statuses (isolated impaired glucose tolerance, isolated impaired fasting glucose, and associated impaired glucose tolerance/impaired fasting glucose) as well as it is worth to consider the same level of risk. Urolithiasis is the most frequent urological cause of hospitalization in diabetic patients and its cost is usually higher compared to non-diabetic patients, but less is known in others altered glycaemic diseases. The aim of this review article is to focus on the association between stone formation and altered glycaemic statuses, beyond the already known link between nephrolithiasis and diabetes mellitus.

  4. Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases.

    PubMed

    Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

    2015-01-01

    In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and 62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread.

  5. Thank you to Virology Journal’s peer reviewers in 2012

    PubMed Central

    2013-01-01

    Contributing reviewers The editors of Virology Journal would like to thank all our reviewers who have contributed to the journal in Volume 9 (2012). The success of any scientific journal depends on an effective and strict peer review process and Virology Journal could not operate without your contribution. We look forward to your continuous support to this journal either as an invited reviewer or a contributing author in the years to come.

  6. Latest status of the clinical and industrial applications of cell sheet engineering and regenerative medicine.

    PubMed

    Egami, Mime; Haraguchi, Yuji; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

    2014-01-01

    Cell sheet engineering, which allows tissue engineering to be realized without the use of biodegradable scaffolds as an original approach, using a temperature-responsive intelligent surface, has been applied in regenerative medicine for various tissues, and a number of clinical studies have been already performed for life-threatening diseases. By using the results and findings obtained from the initial clinical studies, additional investigative clinical studies in several tissues with cell sheet engineering are currently in preparation stage. For treating many patients effectively by cell sheet engineering, an automated system integrating cell culture, cell-sheet fabrication, and layering is essential, and the system should include an advanced three-dimensional suspension cell culture system and an in vitro bioreactor system to scale up the production of cultured cells and fabricate thicker vascularized tissues. In this paper, cell sheet engineering, its clinical application, and further the authors' challenge to develop innovative cell culture systems under newly legislated regulatory platform in Japan are summarized and discussed.

  7. Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials.

    PubMed

    Aguirre, T A S; Teijeiro-Osorio, D; Rosa, M; Coulter, I S; Alonso, M J; Brayden, D J

    2016-11-15

    The development of oral dosage forms that allows absorption of therapeutic peptides to the systemic circulation is one of the greatest challenges for the pharmaceutical industry. Currently, a number of technologies including either mixtures of penetration enhancers or protease inhibitors and/or nanotechnology-based products are under clinical development. Typically, these formulations are presented in the form of enteric-coated tablets or capsules. Systems undergoing preclinical investigation include further advances in nanotechnology, including intestinal microneedle patches, as well as their combination with regional delivery to the colon. This review critically examines four selected promising oral peptide technologies at preclinical stage and the twelve that have progressed to clinical trials, as indicated in www.clinicaltrials.gov. We examined these technologies under the criteria of peptide selection, formulation design, system components and excipients, intestinal mechanism of action, efficacy in man, and safety issues. The conclusion is that most of the technologies in clinical trials are incremental rather than paradigm-shifting and that even the more clinically advanced oral peptide drugs examples of oral bioavailability appear to yield oral bioavailability values of only 1-2% and are, therefore, only currently suitable for a limited range of peptides.

  8. [Acupuncture in diseases of the locomotor system. Status of research and clinical applications].

    PubMed

    Molsberger, A; Böwing, G; Haake, M; Meier, U; Winkler, J; Molsberger, F

    2002-06-01

    Acupuncture has been used for over 2000 years for a wide variety of complaints with minimal side effects. Based on the experience in Chinese medicine and the anticipated positive effects, acupuncture has been widely accepted in Western medicine as well. Some clinical evidence supports the efficacy of acupuncture treatment, but randomized controlled trials have been conducted for only a few of all possible locomotive disorder indications, and the results have been equivocal. Other indications have not yet been systematically studied, and application is based on clinical experience and consensus among practitioners. One of the outcomes on which consensus appears to exist is that 10-20 sessions are generally necessary, and that initial improvement can be expected to occur by the 10th treatment. Rigorous trials should be conducted to improve clinical validity and provide scientific proof of the efficacy of acupuncture. Clinical trials like the German Acupuncture Trials (gerac), funded by the German health insurance companies, have been launched with the aim of furthering knowledge in this area.

  9. Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status

    PubMed Central

    Xu, Yan; Zheng, Yi-Zi; Liu, Yi-Rong; Lang, Guan-Tian; Qiao, Feng; Hu, Xin; Shao, Zhi-Ming

    2016-01-01

    In this study we sought to correlate androgen receptor (AR) expression with tumor progression and disease-free survival (DFS) in breast cancer patients. We investigated AR expression in 450 breast cancer patients. We found that breast cancers expressing the estrogen receptor (ER) are more likely to co-express AR compared to ER-negative cancers (56.0% versus 28.1%, P < 0.001). In addition, we found that AR expression is correlated with increased DFS in patients with luminal breast cancer (P < 0.001), and decreased DFS in TNBC (triple negative breast cancer, P = 0.014). In addition, patients with HR+ tumors (Hormone receptor positive tumors) expressing low levels of AR have the lowest DFS among all receptor combinations. We also propose a novel prognostic model using AR receptor status, BRCA1, and present data showing that our model is more predictive of disease free survival compared to the traditional TMN staging system. PMID:27285752

  10. HER2 status in molecular apocrine breast cancer: associations with clinical, pathological, and molecular features

    PubMed Central

    Guo, Wenwen; Wang, Wei; Zhu, Yun; Zhu, Xiaojing; Shi, Zhongyuan; Wang, Yan

    2015-01-01

    Molecular apocrine breast cancer (MABC) is a distinct subtype of breast cancer. The purpose of this study was to investigate the relationship between HER2 status and clinicopathologic characteristics of MABCs from Chinese Han cohort. A cohort of 90 MABC patients were enrolled. Immunohistochemical method was performed to analyze the molecular expression, and the human epidermal growth factor receptor 2 (HER2) amplification was verified by fluorescence in situ hybridization (FISH). By studying these 90 MABC cases, the majority of studied patients were premenopausal young women (median age 48 yr) with high grade tumors. We also found that MABCs had high positive expression rates of HER2, CK8, CD44, CD166, p53 and BRCA1, the elevated Ki-67 labeling index, and favorable prognosis. There was a significantly higher incidence of lymph node metastasis and lower CD166 positive rate in HER2-negative patients compared to HER2-positive patients (54.5% vs. 37.0%, P = 0.044 and 72.7% vs. 91.3%, P = 0.021, respectively). The CK5/6 and EGFR expression rates were significant higher in HER2-negative cases than in HER2-positive cases, suggesting that there is overlap between MABC with HER2-negative phenotype and basal-like breast cancer. In addition, HER2 positive was found to be significantly associated a poor overall survival in MABCs. In conclusion, HER2 are highly expressed, and HER2 positivity could be considered as a significant biomarker of poor prognosis in MABC. The results also suggest that a subtype tumor with distinct patterns of molecule expression depending on HER2 status presented in MABC. PMID:26339367

  11. HER2 status in molecular apocrine breast cancer: associations with clinical, pathological, and molecular features.

    PubMed

    Guo, Wenwen; Wang, Wei; Zhu, Yun; Zhu, Xiaojing; Shi, Zhongyuan; Wang, Yan

    2015-01-01

    Molecular apocrine breast cancer (MABC) is a distinct subtype of breast cancer. The purpose of this study was to investigate the relationship between HER2 status and clinicopathologic characteristics of MABCs from Chinese Han cohort. A cohort of 90 MABC patients were enrolled. Immunohistochemical method was performed to analyze the molecular expression, and the human epidermal growth factor receptor 2 (HER2) amplification was verified by fluorescence in situ hybridization (FISH). By studying these 90 MABC cases, the majority of studied patients were premenopausal young women (median age 48 yr) with high grade tumors. We also found that MABCs had high positive expression rates of HER2, CK8, CD44, CD166, p53 and BRCA1, the elevated Ki-67 labeling index, and favorable prognosis. There was a significantly higher incidence of lymph node metastasis and lower CD166 positive rate in HER2-negative patients compared to HER2-positive patients (54.5% vs. 37.0%, P = 0.044 and 72.7% vs. 91.3%, P = 0.021, respectively). The CK5/6 and EGFR expression rates were significant higher in HER2-negative cases than in HER2-positive cases, suggesting that there is overlap between MABC with HER2-negative phenotype and basal-like breast cancer. In addition, HER2 positive was found to be significantly associated a poor overall survival in MABCs. In conclusion, HER2 are highly expressed, and HER2 positivity could be considered as a significant biomarker of poor prognosis in MABC. The results also suggest that a subtype tumor with distinct patterns of molecule expression depending on HER2 status presented in MABC.

  12. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status

    NASA Astrophysics Data System (ADS)

    Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey

    1996-04-01

    Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.

  13. Clinically relevant determinants of body composition, function and nutritional status as mortality predictors in lung cancer patients.

    PubMed

    Kovarik, Miroslav; Hronek, Miloslav; Zadak, Zdenek

    2014-04-01

    Lung cancer belongs to the type of tumors with a relatively high frequency of malnutrition, sarcopenia and cachexia, severe metabolic syndromes related to impairment of physical function and quality of life, resistance to therapy and short survival. Inexpensive and accessible methods of evaluating changes in body composition, physical function and nutrition status are for this reason of great importance for clinical practice to enable the early identification, monitoring, preventing and treatment of these nutritional deficiencies. This could lead to improved outcomes in the quality of life, physical performance and survival of patients with lung cancer. The aim of this article is to summarize the recent knowledge for the use of such methods, their predictability for patient outcomes and an association with other clinically relevant parameters, specifically with lung cancer patients, because such an article collectively describing their practical application in clinical practice is lacking. The interest of this article is in the use of anthropometry, handgrip dynamometry, bioelectrical impedance analysis derived phase angle and nutritional screening questionnaires in lung cancer patients.

  14. Outcome of Sustained Virological Responders with Histologically Advanced Chronic Hepatitis C

    PubMed Central

    Morgan, Timothy R.; Ghany, Marc G.; Kim, Hae-Young; Snow, Kristin K.; Shiffman, Mitchell L.; De Santo, Jennifer L.; Lee, William M.; Di Bisceglie, Adrian M.; Bonkovsky, Herbert L.; Dienstag, Jules L.; Morishima, Chihiro; Lindsay, Karen L.; Lok, Anna S.F.

    2010-01-01

    Background & Aims Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR) and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C Trial. Methods Laboratory and/or clinical outcome data were available for 140 of the 180 SVR patients. Nonresponders (n=309) or BT/R (N=77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Results Median follow-up for SVR, BT/R, and NR patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that in NR (21.3% and 27.2%, p<0.001 for both) but not the BT/R (4.4% and 8.7%). The adjusted hazard ratio [HR] for time to death/liver transplantation (HR=0.17, 95% CI: 0.06–0.46), or development of liver-related morbidity/mortality (HR=0.15, 95% CI: 0.06–0.38) or HCC (HR=0.19, 95% CI: 0.04–0.80) was significant for SVR compared to NR. Laboratory tests related to liver-disease severity improved following SVR. Conclusions Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC. PMID:20564351

  15. Disclosure of amyloid status is not a barrier to recruitment in preclinical Alzheimer's disease clinical trials.

    PubMed

    Grill, Joshua D; Zhou, Yan; Elashoff, David; Karlawish, Jason

    2016-03-01

    Preclinical Alzheimer's disease (AD) clinical trials may require participants to learn if they meet biomarker enrollment criteria. To examine whether this requirement will impact trial recruitment, we presented 132 older community volunteers who self-reported normal cognition with 1 of 2 hypothetical informed consent forms (ICFs) describing an AD prevention clinical trial. Both ICFs described amyloid Positron Emission Tomography scans. One ICF stated that scan results would not be shared with the participants (blinded enrollment); the other stated that only persons with elevated amyloid would be eligible (transparent enrollment). Participants rated their likelihood of enrollment and completed an interview with a research assistant. We found no difference between the groups in willingness to participate. Study risks and the requirement of a study partner were reported as the most important factors in the decision whether to enroll. The requirement of biomarker disclosure may not slow recruitment to preclinical AD trials.

  16. Structural properties of fracture haematoma: current status and future clinical implications.

    PubMed

    Wang, Xin; Friis, Thor; Glatt, Vaida; Crawford, Ross; Xiao, Yin

    2016-07-12

    Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright © 2016 John Wiley & Sons, Ltd.

  17. The full metallic double-pigtail ureteral stent: Review of the clinical outcome and current status

    PubMed Central

    Kallidonis, Panagiotis S.; Georgiopoulos, Ioannis S.; Kyriazis, Iason D.; Kontogiannis, Stavros; Al-Aown, Abdulrahman M.; Liatsikos, Evangelos N.

    2015-01-01

    The full metallic double-J ureteral stent (MS) was introduced as a method for providing long-term drainage in malignant ureteral obstruction. Experimental evaluation of the MS revealed that its mechanical features allow efficient drainage in difficult cases, which could not be managed by the insertion of a standard polymeric double-J stent. Clinical experience with the MS showed controversial results. Careful patient selection results in efficient long-term management of malignant ureteral obstruction. The use of the MS should also be considered in selected benign cases. Major complications are uncommon and the minor complications should not hinder its use. Experience in pediatric patients is limited and warrants additional study. The cost-effectiveness of the MS seems to be appropriate for long-term treatment. Further investigation with comparative clinical trials would document the outcome more extensively and establish the indications as well as the selection criteria for the MS. PMID:25624569

  18. Role of antibodies in diagnosis and treatment of ovarian cancer: Basic approach and clinical status.

    PubMed

    Bhatt, Priyanka; Vhora, Imran; Patil, Sushilkumar; Amrutiya, Jitendra; Bhattacharya, Chandrali; Misra, Ambikanandan; Mashru, Rajashree

    2016-03-28

    Ovarian cancer is the second most leading gynecological cancer after endometrial cancer in women. Chemotherapy and cyto-reductive surgery are currently the mainstays for treatment of ovarian cancer in early stages. However, the overall 5years of survival rate in advanced stage is just 20-30%. The main reasons behind therapeutic failures and a low survival rate are challenges in early diagnosis, frequent recurrence, chemo-resistance development and lack of targeting. Antibodies have evolved as a rationale therapeutic approach to overcome these hurdles and to engender significant clinical applications. Detection of cancer associated antibodies and radiolabeled antibody conjugates are forming the basis for early diagnosis of ovarian cancer. Besides this, antibodies when given alone act as an anti-angiogenic agent or utilize the protective role of immune system against ovarian cancer. This high specificity and selectivity of action is also accompanied by development of tumor antigen-specific memory T cells, which can prevent cancer recurrence. In addition, when given in combination with chemotherapy, antibodies have turned out to sensitize chemo-resistant tumors. Antibodies are also playing cardinal role in design of highly potent class of targeted therapies, such as antibody-drug conjugates and clinically viable tumor targeted drug nanocarriers. This article aims to explore the fundamentals in development of antibody based therapeutics and multitude ways of clinical applications in diagnosis and treatment of ovarian cancer. Focus is given on the recent advances made in preclinical and clinical settings with an overview to unmet challenges so as to develop better immunotherapeutics in future.

  19. The influence of modern nuclear technologies on immune status in clinic and experiment

    SciTech Connect

    Ivanov, A.A.; Smirnova, O.V.; Ulanova, A.M.

    1993-12-31

    It is known that the immune system is extremly sensitive to ionizing radiation. This report described results of investigations pertaining to experimental and clinical data on the character and dynamics of changes in the immune system as under external radiation influence (x-rays, gamma-irradiation, neutrons) as in the result of radionuclides entering an organism. The influence of ionizing radiation on man was studied by data from nuclear accidents such as from people exposed from the Chernobyl accident.

  20. [Security Management in Clinical Laboratory Departments and Facilities: Current Status and Issues].

    PubMed

    Ishida, Haku; Nakamura, Junji; Yoshida, Hiroshi; Koike, Masaru; Inoue, Yuji

    2014-11-01

    We conducted a questionnaire survey regarding the current activities for protecting patients' privacy and the security of information systems (IS) related to the clinical laboratory departments of university hospitals, certified training facilities for clinical laboratories, and general hospitals in Yamaguchi Prefecture. The response rate was 47% from 215 medical institutions, including three commercial clinical laboratory centers. The results showed that there were some differences in management activities among facilities with respect to continuing education, the documentation or regulation of operational management for paper records, electronic information, remaining samples, genetic testing, and laboratory information for secondary use. They were suggested to be caused by differences in functions between university and general hospitals, differences in the scale of hospitals, or whether or not hospitals have received accreditation or ISO 15189. Regarding the IS, although the majority of facilities had sufficiently employed the access control to IS, there was some room for improvement in the management of special cases such as VIPs and patients with HIV infection. Furthermore, there were issues regarding the login method for computers shared by multiple staff, the showing of the names of personnel in charge of reports, and the risks associated with direct connections to systems and the Internet and the use of portable media such as USB memory sticks. These results indicated that further efforts are necessary for each facility to continue self-assessment and make improvements.

  1. Cutaneous leishmaniasis in Syria: clinical features, current status and the effects of war.

    PubMed

    Hayani, Kinan; Dandashli, Anwar; Weisshaar, Elke

    2015-01-01

    Cutaneous leishmaniasis (CL) is a worldwide disease caused by an infection with the protozoan parasite Leishmania transmitted via sand flies. It is endemic in many of the poorest countries of all continents. "Aleppo boil" is one of the recognised names given to this disease in the medical literature. Although CL used to be well-controlled and well-documented in Syria, its incidence has dramatically increased since the beginning of the war; however, there is lack of documentation. Here, we present the past and current epidemiological situation of the disease in Syria. We also draw attention to gross and highly unusual clinical variants of CL presented to the Department of Dermatology in Aleppo covering the important differential clinical diagnoses, since this disease is already known to mimic other conditions. Diagnostic procedures and treatment as well as prevention are summarised. Due to the increased ability to travel, and especially the flight of Syrians to neighbouring countries, as well as to Europe, CL may become a new threat in formerly unaffected regions. Through this account, we hope to give weight to the aspiration that CL does not remain a neglected and often clinically overlooked tropical dermatosis.

  2. Current status of flow convergence for clinical applications: is it a leaning tower of "PISA"?

    PubMed

    Simpson, I A; Shiota, T; Gharib, M; Sahn, D J

    1996-02-01

    Spatial appreciation of flow velocities using Doppler color flow mapping has led to quantitative evaluation of the zone of flow convergence proximal to a regurgitant orifice. Based on the theory of conservation of mass, geometric analysis, assuming a series of hemispheric shells of increasing velocity as flow converges on the orifice--the so-called proximal isovelocity surface area (PISA) effect--has yielded methods promising noninvasive measurement of regurgitant flow rate. When combined with conventional Doppler ultrasound to measure orifice velocity, regurgitant orifice area, the major predictor of regurgitation severity, can also be estimated. The high temporal resolution of color M-mode can be used to evaluate dynamic changes in orifice area, as seen in many pathologic conditions, which enhances our appreciation of the pathophysiology of regurgitation. The PISA methodology is potentially applicable to any restrictive orifice and has gained some credibility in the quantitative evaluation of other valve pathology, particularly mitral and tricuspid regurgitation, and in congenital heart disease. Although the current limitations of PISA estimates of regurgitation have tempered its introduction as a valuable clinical tool, considerable efforts in in vitro and clinical research have improved our understanding of the problems and limitations of the PISA methodology and provided a firm platform for continuing research into the accurate quantitative assessment of valve regurgitation and the expanding clinical role of quantitative Doppler color flow mapping.

  3. Application of next-generation sequencing technologies in virology.

    PubMed

    Radford, Alan D; Chapman, David; Dixon, Linda; Chantrey, Julian; Darby, Alistair C; Hall, Neil

    2012-09-01

    The progress of science is punctuated by the advent of revolutionary technologies that provide new ways and scales to formulate scientific questions and advance knowledge. Following on from electron microscopy, cell culture and PCR, next-generation sequencing is one of these methodologies that is now changing the way that we understand viruses, particularly in the areas of genome sequencing, evolution, ecology, discovery and transcriptomics. Possibilities for these methodologies are only limited by our scientific imagination and, to some extent, by their cost, which has restricted their use to relatively small numbers of samples. Challenges remain, including the storage and analysis of the large amounts of data generated. As the chemistries employed mature, costs will decrease. In addition, improved methods for analysis will become available, opening yet further applications in virology including routine diagnostic work on individuals, and new understanding of the interaction between viral and host transcriptomes. An exciting era of viral exploration has begun, and will set us new challenges to understand the role of newly discovered viral diversity in both disease and health.

  4. Application of next-generation sequencing technologies in virology

    PubMed Central

    Chapman, David; Dixon, Linda; Chantrey, Julian; Darby, Alistair C.; Hall, Neil

    2012-01-01

    The progress of science is punctuated by the advent of revolutionary technologies that provide new ways and scales to formulate scientific questions and advance knowledge. Following on from electron microscopy, cell culture and PCR, next-generation sequencing is one of these methodologies that is now changing the way that we understand viruses, particularly in the areas of genome sequencing, evolution, ecology, discovery and transcriptomics. Possibilities for these methodologies are only limited by our scientific imagination and, to some extent, by their cost, which has restricted their use to relatively small numbers of samples. Challenges remain, including the storage and analysis of the large amounts of data generated. As the chemistries employed mature, costs will decrease. In addition, improved methods for analysis will become available, opening yet further applications in virology including routine diagnostic work on individuals, and new understanding of the interaction between viral and host transcriptomes. An exciting era of viral exploration has begun, and will set us new challenges to understand the role of newly discovered viral diversity in both disease and health. PMID:22647373

  5. Vitamin D status among immigrant mothers from Pakistan, Turkey and Somalia and their infants attending child health clinics in Norway.

    PubMed

    Madar, Ahmed A; Stene, Lars C; Meyer, Haakon E

    2009-04-01

    High prevalences of vitamin D deficiency have been reported in non-Western immigrants moving to Western countries, including Norway, but there is limited information on vitamin D status in infants born to immigrant mothers. We aimed to describe the vitamin D status and potentially correlated factors among infants aged 6 weeks and their mothers with Pakistani, Turkish or Somali background attending child health clinics in Norway. Eighty-six healthy infants and their mothers with immigrant background were recruited at the routine 6-week check-up at nine centres between 2004 and 2006. Venous or capillary blood was collected at the clinics from the mother and infant, and serum separated for analysis of 25-hydroxyvitamin D (s-25(OH)D) and intact parathyroid hormone (s-iPTH). The mean maternal s-25(OH)D was 25.8 nmol/l, with 57 % below 25 nmol/l and 15 % below 12.5 nmol/l. Of the mothers, 26 % had s-iPTH>5.7 pmol/l. For infants, mean s-25(OH)D was 41.7 nmol/l, with 47 % below 25 nmol/l and 34 % below 12.5 nmol/l. s-25(OH)D was considerably lower in the thirty-one exclusively breast-fed infants (mean 11.1 nmol/l; P < 0.0001). Use of vitamin D supplements and education showed a positive association with maternal s-25(OH)D. There was no significant association between mother's and child's s-25(OH)D, and no significant ethnic or seasonal variation in s-25(OH)D for mothers or infants. In conclusion, there is widespread vitamin D deficiency in immigrant mothers and their infants living in Norway. Exclusively breast-fed infants who did not receive vitamin D supplements had particularly severe vitamin D deficiency.

  6. Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

    PubMed Central

    Ghamari, Shiva; Alavian, Seyed Moayed; Rizzetto, Mario; Olivero, Antonella; Smedile, Antonina; Khedive, Abulfazl; Alavian, Seyed Ehsan; Zolfaghari, Mohammad Reza; Jazayeri, Seyed Mohammad

    2013-01-01

    Background Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone. Objectives The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates. Patients and Methods 81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations. Results 12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients. Conclusions HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group. PMID:24098308

  7. Clinical applications of PET/MRI: current status and future perspectives.

    PubMed

    Nensa, Felix; Beiderwellen, Karsten; Heusch, Philipp; Wetter, Axel

    2014-01-01

    Fully integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners have been available for a few years. Since then, the number of scanner installations and published studies have been growing. While feasibility of integrated PET/MRI has been demonstrated for many clinical and preclinical imaging applications, now those applications where PET/MRI provides a clear benefit in comparison to the established reference standards need to be identified. The current data show that those particular applications demanding multiparametric imaging capabilities, high soft tissue contrast and/or lower radiation dose seem to benefit from this novel hybrid modality. Promising results have been obtained in whole-body cancer staging in non-small cell lung cancer and multiparametric tumor imaging. Furthermore, integrated PET/MRI appears to have added value in oncologic applications requiring high soft tissue contrast such as assessment of liver metastases of neuroendocrine tumors or prostate cancer imaging. Potential benefit of integrated PET/MRI has also been demonstrated for cardiac (i.e., myocardial viability, cardiac sarcoidosis) and brain (i.e., glioma grading, Alzheimer's disease) imaging, where MRI is the predominant modality. The lower radiation dose compared to PET/computed tomography will be particularly valuable in the imaging of young patients with potentially curable diseases.However, further clinical studies and technical innovation on scanner hard- and software are needed. Also, agreements on adequate refunding of PET/MRI examinations need to be reached. Finally, the translation of new PET tracers from preclinical evaluation into clinical applications is expected to foster the entire field of hybrid PET imaging, including PET/MRI.

  8. RNA-targeted therapeutics in cancer clinical trials: Current status and future directions.

    PubMed

    Barata, Pedro; Sood, Anil K; Hong, David S

    2016-11-01

    Recent advances in RNA delivery and target selection provide unprecedented opportunities for cancer treatment, especially for cancers that are particularly hard to treat with existing drugs. Small interfering RNAs, microRNAs, and antisense oligonucleotides are the most widely used strategies for silencing gene expression. In this review, we summarize how these approaches were used to develop drugs targeting RNA in human cells. Then, we review the current state of clinical trials of these agents for different types of cancer and outcomes from published data. Finally, we discuss lessons learned from completed studies and future directions for this class of drugs.

  9. Gender differences in clinical status at time of coronary revascularisation in Spain

    PubMed Central

    Aguilar, M; Lazaro, P; Fitch, K; Luengo, S

    2002-01-01

    Design: Retrospective study of clinical records. Two stage stratified cluster sampling was used to select a nationally representative sample of patients receiving a coronary revascularisation procedure in 1997. Setting: All of Spain. Main outcome measures: Odds ratios (OR) in men and women for different clinical and diagnostic variables related with coronary disease. A logistic regression model was developed to estimate the association between coronary symptoms and gender. Results: In the univariate analysis the prevalence of the following risk factors for coronary heart disease was higher in women than in men: obesity (OR=1.8), hypertension (OR=2.9) and diabetes (OR=2.1). High surgical risk was also more prevalent among women (OR=2.6). In the logistic regression analysis women's risk of being symptomatic at the time of revascularisation was more than double that of men (OR=2.4). Conclusions: Women have more severe coronary symptoms at the time of coronary revascularisation than do men. These results suggest that women receive revascularisation at a more advanced stage of coronary disease. Further research is needed to clarify what social, cultural or biological factors may be implicated in the gender differences observed. PMID:12080167

  10. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

    PubMed

    Kawakami, Kohsaku

    2009-09-01

    Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

  11. An algorithm for the clinical assessment of nutritional status in hospitalized patients.

    PubMed

    de Kruif, J Th C M; Vos, A

    2003-10-01

    Upon admission to hospital, 30-50 % of patients either are or become malnourished. There is no generally accepted definition of malnutrition or guidelines on the best way to establish nutritional status. We consider it self-evident that the nursing staff have an important role in screening patients at risk of malnutrition on admission and thereafter at regular times. This is why we developed the nursing nutritional screening form (NNSF). The NNSF was tested by nurses, dietitians and clinicians, in pairs, to establish the extent of agreement in two phases on sixty-nine and forty patients. Later, the form was used in practice by nursing staff on five wards (334 patients). Based on the results of the NNSF, patients were referred to a dietitian. The dietitian established whether the patient was indeed at risk, or was actually malnourished, using a complete nutritional history. The degree of concurrence within pairs was reasonable to good. The same applied to the concurrence between nursing staff and dietitians, but concurrence between clinicians and nursing staff was less. In total, 334 patients were screened and sixty-nine of them were referred to the dietitian. It was established that 86 % of the referred patients were potentially at risk of malnutrition or were malnourished. Without the NNSF, 39 % (n 27) of the patients referred to the dietitian would not have been referred, or would have been referred much later. The NNSF makes it possible for nurses to detect malnourished patients or patients at risk of malnutrition at an early stage of their hospitalization.

  12. Status and Perspectives of Clinical Modes in Surgical Patients With Lung Cancer: A Retrospective Study.

    PubMed

    Lai, Yutian; Du, Heng; Wang, Xin; Shen, Cheng; Huang, Jian; Li, Weiming; Che, Guowei

    2016-01-01

    To investigate the association between the clinical characteristics and clinical modes of surgically treated lung cancer patients, we conducted a retrospective study with 1097 lung cancer patients receiving pulmonary resection between 2012 and 2013.A physical examination or screening (PES) group (n = 267) and a symptomatic (SY) group (n = 830) were established depending on the new clinical mode (sequence of physical examination, early detection and sequential medical treatment) and the conventional mode (hospitalization due to occurrence of relevant symptoms), respectively.A higher proportion of patients referred to our unit directly form a junior medical unit is found in PES group (43.8%, 117/267 vs 13.6%, 113/830) (P < 0.001) and 37.5% (100/267) patients in PES group spent <1 months from detection or first medical visit to diagnosis compared with 15.4% (128/830) patient in SY group (P < 0.001). A significantly higher proportion of PES patients versus SY patients received video-assisted thoracoscopic surgery (VATS) resection (67.8%, 183/267 vs 42.6%, 352/830; P < 0.001). A significantly higher proportion of PES patients versus SY patients chose sublobar resection (16.9%, 45/267 vs 7.6%, 63/830; P < 0.001). A significantly higher proportion of PES patients versus SY patients are at stage 0 or I (64.4%, 172/267 vs 40.7%, 338/830; P < 0.000). The postoperative incidence rate of complications in 30 days is significantly higher in SY group than in PES group (34.9% vs 27.3%; P = 0.022).Helping to early diagnosis and surgical treatment, early tumor detection via PES may contribute to significantly higher proportions of early-stage lung cancer, use of VATS pulmonary resection, and sublobectomy as well as lower complication rate.

  13. The efficacy, pharmacokinetics, and safety of a nevirapine to rilpivirine switch in virologically suppressed HIV-1-infected patients.

    PubMed

    Rokx, Casper; Blonk, Maren; Verbon, Annelies; Burger, David; Rijnders, Bart J A

    2015-01-01

    : This prospective, open-label nonrandomized controlled trial evaluated the efficacy, safety, and pharmacokinetics of substituting nevirapine/emtricitabine/tenofovir for rilpivirine/emtricitabine/tenofovir in 50 suppressed HIV-1 switchers. One hundred thirty-nine nonswitchers remained on nevirapine as controls. Week 12 HIV-1 RNA was <50 copies per milliliter in 92.0% of switchers and was <50 copies per milliliter at week 24 in 88.0% of switchers and 90.6% of nonswitchers (difference 2.6%, 95% confidence interval: -7.6% to 12.8%). Week 3 geometric mean nevirapine concentration was undetectable and week 1 geometric mean rilpivirine concentration (0.083 mg/L) was comparable with phase 3 trial (P = 0.747). Substituting nevirapine for rilpivirine resulted in ongoing virological suppression and did not have clinically relevant pharmacokinetic effects by cytochrome P450 interactions.

  14. Best Practice No 175. Guidelines for virological and non-viral serological examination of specimens in routine diagnostic microbiological laboratories.

    PubMed

    Francis, J; Barrett, S P; Ogilvie, M M; Sutherland, S

    2004-01-01

    Viral examination is routinely carried out in most routine diagnostic microbiology laboratories. Most often, this comprises the detection of viral antigens and antibodies, and less commonly the isolation of viruses and the detection of viral nucleic acids. However, there are no standards or guidelines available for processing these specimens in routine diagnostic laboratories or for referral to specialist virology centres or units. Clinical Pathology Accreditation (CPA) has defined standards for assessing the quality of service provided by laboratories, but these do not include the scientific and technical aspects of provision of service. The Association of Medical Microbiologists has recently published Standards for Laboratory practice in medical microbiology, which covers scientific and technical aspects of provision of microbiology service, mainly bacteriological examination of specimens in routine diagnostic microbiology laboratories. These guidelines are complementary to the CPA guidelines and aim to ensure a consistent and high quality service. This article presents guidelines for the examination of specimens for the diagnosis of viral infections.

  15. A Model Predicting Lymph Node Status for Patients with Clinical Stage T1aN0-2M0 Nonsmall Cell Lung Cancer

    PubMed Central

    Zang, Ruo-Chuan; Qiu, Bin; Gao, Shu-Geng; He, Jie

    2017-01-01

    Background: Lymph node status of patients with early-stage nonsmall cell lung cancer has an influence on the choice of surgery. To assess the lymph node status more correspondingly and accurately, we evaluated the relationship between the preoperative clinical variables and lymph node status and developed one model for predicting lymph node involvement. Methods: We collected clinical and dissected lymph node information of 474 patients with clinical stage T1aN0-2M0 nonsmall cell lung cancer (NSCLC). Logistic regression analysis of clinical characteristics was used to estimate independent predictors of lymph node metastasis. The prediction model was validated by another group. Results: Eighty-two patients were diagnosed with positive lymph nodes (17.3%), and four independent predictors of lymph node disease were identified: larger consolidation size (odds ratio [OR] = 2.356, 95% confidence interval [CI]: 1.517–3.658, P < 0.001,), central tumor location (OR = 2.810, 95% CI: 1.545–5.109, P = 0.001), abnormal status of tumor marker (OR = 3.190, 95% CI: 1.797–5.661, P < 0.001), and clinical N1–N2 stage (OR = 6.518, 95% CI: 3.242–11.697, P < 0.001). The model showed good calibration (Hosmer–Lemeshow goodness-of-fit, P < 0.766) with an area under the receiver operating characteristics curve (AUC) of 0.842 (95% [CI]: 0.797–0.886). For the validation group, the AUC was 0.810 (95% CI: 0.731–0.889). Conclusions: The model can assess the lymph node status of patients with clinical stage T1aN0-2M0 NSCLC, enable surgeons perform an individualized prediction preoperatively, and assist the clinical decision-making procedure. PMID:28218211

  16. Influence of Clinical Status on the Association Between Plasma Total and Unbound Bilirubin and Death or Adverse Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants

    PubMed Central

    Oh, William; Stevenson, David K.; Tyson, Jon E.; Morris, Brenda H.; Ahlfors, Charles E.; Bender, G. Jesse; Wong, Ronald J.; Perritt, Rebecca; Vohr, Betty R.; Van Meurs, Krista P.; Vreman, Hendrik J.; Das, Abhik; Phelps, Dale L.; O’Shea, T. Michael; Higgins, Rosemary D.

    2010-01-01

    Objectives To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method Total plasma biirubin and unbound biirubin were measured in 1,101 extremely low birth weight infants at 5±1 day of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma and unbound bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants. PMID:20105142

  17. Ingenol Mebutate Topical Gel A Status Report On Clinical Use Beyond Actinic Keratosis

    PubMed Central

    Del Rosso, James Q.

    2016-01-01

    Ingenol mebutate is available as a topical gel formulation approved for the treatment of actinic keratosis. Two different concentrations are available for treatment of actinic keratoses at specific anatomic sites with the advantages of short durations of therapy and limited “down time” related to visible inflammation as compared to other topical agents. Due to the various modes of action of ingenol mebutate, it has also been used for treatment of disease states other than actinic keratosis. This manuscript discusses the suggested modes of action of ingenol mebutate and reviews publications on the use of ingenol mebutate gel for cutaneous disorders other than actinic keratosis, including squamous cell carcinoma in-situ, basal cell carcinoma, actinic cheilitis, anogenital warts, and others. Author commentaries are also included with the goal of providing relevant clinical insights. PMID:28224020

  18. Current status of single-balloon enteroscopy: Insertability and clinical applications

    PubMed Central

    Kawamura, Takuji; Uno, Koji; Tanaka, Kiyohito; Yasuda, Kenjiro

    2015-01-01

    The single-balloon enteroscopy (SBE) system was launched in 2007, proposed as a simpler method than double-balloon enteroscopy (DBE). Controversy surrounds whether the SBE system has the same insertability as DBE. However, many methods have been proposed to improve the depth of insertion with the SBE system, involving several techniques and endoscopic accessories. SBE is used for investigating not only small bowel diseases, but also diseases of the pancreatobiliary and colonic structures. SBE is a necessary advancement for many endoscopic procedures and applications in modern clinical practice. In our review, we summarized the current literature concerning the insertability of SBE and described the technical aspects of improving the rate of deep insertion in SBE procedures. In addition, the recent applications of SBE to diseases besides those of the small bowel are described. PMID:25610535

  19. The use of psychometrists in clinical neuropsychology: history, current status, and future directions.

    PubMed

    Malek-Ahmadi, Michael; Erickson, Tom; Puente, Antonio E; Pliskin, Neil; Rock, Rachel

    2012-01-01

    In recent years, the National Academy of Neuropsychology and other professional neuropsychological organizations have published a number of articles and position papers regarding the use, education, and training of psychometrists ("technicians"). Although these documents provide guidelines for the suggested qualifications and training procedures of psychometrists, none make any mention of the need for a standardized credentialing process, which is commonly required of technicians in similar fields, especially in medical settings. Given the recent changes in current procedural Terminology codes used to bill for neuropsychological services and the interpretation of legislation disallowing the use of psychometrists in New York, the need for a standard credential for psychometrists is apparent. This article will review the history and current use of psychometrists in clinical neuropsychology and highlight the need and rationale for the credentialing of psychometrists.

  20. Scaling-up recombinant plasmid DNA for clinical trial: current concern, solution and status.

    PubMed

    Ismail, Ruzila; Allaudin, Zeenathul Nazariah; Lila, Mohd-Azmi Mohd

    2012-09-07

    Gene therapy and vaccines are rapidly developing field in which recombinant nucleic acids are introduced in mammalian cells for enhancement, restoration, initiation or silencing biochemical function. Beside simplicity in manipulation and rapid manufacture process, plasmid DNA-based vaccines have inherent features that make them promising vaccine candidates in a variety of diseases. This present review focuses on the safety concern of the genetic elements of plasmid such as propagation and expression units as well as their host genome for the production of recombinant plasmid DNA. The highlighted issues will be beneficial in characterizing and manufacturing plasmid DNA for save clinical use. Manipulation of regulatory units of plasmid will have impact towards addressing the safety concerns raised in human vaccine applications. The gene revolution with plasmid DNA by alteration of their plasmid and production host genetics will be promising for safe delivery and obtaining efficient outcomes.

  1. MRI experience with multiple sclerosis - Comparison to CT and clinical status

    SciTech Connect

    Reese, L.; Carr, T.; Nicholson, R.L.

    1985-05-01

    A Multiple Sclerosis (M.S.) Protocol was set--SEB (1000/60) volume acquisition and selected single slices SEC (1000/120) and IR (1500/450). Single slices SE 500/30, 1500/30 and 1530/60 were obtained for T1 and T2 calculation. New software and coils permitted multi-slice multi-echo acquisition so the Protocol was changed to multi-slice multi-echo transaxial SE 2120/60-120, and the T1 and T2 sets. The study consisted of 62 known M.S. patients and 35 controls. Of the 62 M.S. patients, 58 (94%) were positive on NMR. Thirty-two of these patients had CT scans of which 17 (53%) were positive. Of the 35 controls, 2 were positive on NMR for a false positive rate of 6%. The relative sensitivity of NMR, Double Dose Delayed CT(DDD) and contrast CT in the clinically early progressive group is 87%, 60% and 45% respectively. In the chronic stable group, the sensitivity is 100% for NMR and 55% for DDD. The NMR lesions were graded on a scale of 1 - 4 and the authors found poor correlation with either duration of disease or Kurtzke Functional Scale. The T1, T2 values showed good differentiation between white matter and lesions, although differentiation between lesions and grey matter was poor. White matter has T1 of 328 +- 28 and T2 of 85 +- 22, grey matter T1 of 515 +- 37 and T2 of 96 +- 32 and lesions T1 of 530 +- 76 and T2 of 106 +- 27. They conclude that multi-slice SE 2120/60-120 NMR imaging has proven to be a valuable tool in the clinical diagnosis of Multiple Sclerosis. Most of the lesions seen are asymptomatic and the number, size and distribution of lesions have little correlation with severity or acuity of the disease.

  2. The Negligible Influence of Chronic Obesity on Hospitalization, Clinical Status, and Complications in Elective Posterior Lumbar Interbody Fusion

    PubMed Central

    Kombos, Theodoros; Bode, Frank

    2016-01-01

    Background. Posterior lumbar interbody fusion (PLIF) is a common surgical treatment for degenerative spinal instability, but many surgeons consider obesity a contraindication for elective spinal fusion. The aim of this study was to analyze whether obesity has any influence on hospitalization parameters, change in clinical status, or complications. Methods. In this prospective study, regression analysis was used to analyze the influence of the body mass index (BMI) on operating time, postoperative care, hospitalization time, type of postdischarge care, change in paresis or sensory deficits, pain level, wound complications, cerebrospinal fluid leakage, and implant complications. Results. Operating time increased only 2.5 minutes for each increase of BMI by 1. The probability of having a wound complication increased statistically with rising BMI. Nonetheless, BMI accounted for very little of the variation in the data, meaning that other factors or random chances play a much larger role. Conclusions. Obesity has to be considered a risk factor for wound complications in patients undergoing elective PLIF for degenerative instability. However, BMI showed no significant influence on other kinds of peri- or postoperative complications, nor clinical outcomes. So obesity cannot be considered a contraindication for elective PLIF. PMID:27478866

  3. Chicken infectious anemia virus infection in Israeli commercial flocks: virus amplification, clinical signs, performance, and antibody status.

    PubMed

    Davidson, I; Kedem, M; Borochovitz, H; Kass, N; Ayali, G; Hamzani, E; Perelman, B; Smith, B; Perk, S

    2004-01-01

    The impact of chicken infectious anemia virus (CIAV) infection on commercial chicken flocks in Israel was examined by analyzing flocks with or without typical CIAV signs, signs of other diseases, or apparently healthy flocks. In 23 flocks (broilers and layers) of ages up to 8 wk, typical signs of CIAV infection (stunting, gangrenous dermatitis, and secondary bacterial infections) were recorded. When permitted by flock owners, in several cases among these 23 flocks the morbidity, mortality, and performance parameters were recorded; the presence of CIAV was detected by polymerase chain reaction (PCR); and the antibody status of parents and broilers was measured. In addition, total mortality, number of birds sold, total kilograms of meat sold, density (kg/m2), mean age at slaughter, daily growth rate in grams, total kilogram of food consumed, food conversion rate, and the European Index were calculated. We also surveyed flocks affected by other diseases, such as tumors, respiratory diseases, or coccidiosis, and flocks with no apparent clinical signs. The latter flocks were negative by CIAV-PCR, indicating that typical CIAV clinical signs are associated with one-step PCR-CIAV amplification. However, a small amount of CIAV might still be present in these flocks, acting to induce the subclinical effects of CIAV infection. These data indicate a link between the presence of virus sequences and typical CIAV signs and strengthen the concept that CIAV infection has a negative economic impact on the chicken industry.

  4. Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

    PubMed Central

    García-Samaniego, Javier; Romero, Miriam; Granados, Rafael; Alemán, Remedios; Jorge Juan, Miguel; Suárez, Dolores; Pérez, Ramón; Castellano, Gregorio; González-Portela, Carlos

    2013-01-01

    AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to peginterferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d). RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventy-eight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41

  5. Association of SCARB1 Gene Polymorphisms with Virological Response in Chronic Hepatitis C Patients Receiving Pegylated Interferon plus Ribavirin Therapy

    PubMed Central

    Hsu, Ching-Sheng; Hsu, Shih-Jer; Liu, Wei-Liang; Chen, Ding-Shinn; Kao, Jia-Horng

    2016-01-01

    The scavenger receptor type B class I(SR-BI) is a receptor for high-density lipoproteins(HDL) and one of entry factors for hepatitis C virus(HCV). We examined the association of single nucleotide polymorphisms(SNPs) of the SCARB1 gene, which encodes SR-BI, with virologic responses to pegylated interferon-based treatment in Asian chronic hepatitis C(CHC) patients. Human genomic and clinical data were collected from 156 consecutive Taiwanese HCV genotype 1 or 2 patients who received pegylated interferon plus ribavirin therapy and 153 non-HCV healthy subjects. Three SNPs(rs10846744, rs5888, and rs3782287) of the SCARB1 gene that have been linked to humans diseases were investigated. rs10846744 rather than rs5888 or rs3782287 was associated with serum HCV RNA level and sustained virologic response(SVR) to pegylated interferon plus ribavirin therapy in CHC patients(GG vs. non-GG genotype, Adjusted Odds Ratio, 95% CI: 0.32, 0.11–0.95, P = 0.039). Among patients with IL28B rs8099917 non-TT genotypes, those with rs10846744 non-GG genotype had a higher SVR rate than those with GG genotypes. In addition, patients with GG genotype had a higher fasting blood glucose level than those with CC genotype. In conclusion, SCARB1 gene polymorphisms may serve as a potential predictor of treatment responses in CHC patients receiving interferon-based therapy. (ClinicalTrials.gov number, NCT02714712). PMID:27561198

  6. Virological control of groundwater quality using biomolecular tests.

    PubMed

    Carducci, A; Casini, B; Bani, A; Rovini, E; Verani, M; Mazzoni, F; Giuntini, A

    2003-01-01

    Deep groundwater, even if generally protected, could be contaminated by surface or rain water infiltration through soil fractures, septic tanks, cesspits, land irrigation, disposal of wastewater and disposal of muds from depuration systems. The sanitary importance of such possible contamination is related to the different uses of the water and it is at the maximum level when it is intended for human use. Routine microbiological analyses do not consider viruses, only bacterial parameters, as contamination indicators. However, it is known that enteric viruses can survive a long time in deep aquifers and that they may not always be associated with bacterial indicators. The virological analysis of waters intended for drinking use is provided only as an occasional control exercised at the discretion of the sanitary authority. Technological difficulties with obtaining data about groundwater viral contamination led to a study to devise rapid and efficient methods for their detection and the application of these methods to samples from different sources. Four acid nucleic extraction techniques have been tested (classic proteinase K- phenol/chloroform, QIAamp Viral RNA Kit (Qiagen), SV Total RNA Isolation System (Promega) and NucleoSpin Virus L (Macherey-Nagel). Sensitivity and specificity of RT-PCR protocols for entero- (EV), hepatitis A (HAV) and small round structured (SRSV) viruses have been verified. Deep groundwater samples (100 L) were concentrated (2-step tangential flow ultrafiltration) and the concentrate contaminated with serial 10-fold dilutions of a known titre of poliovirus type 3. Extracted RNA was concentrated (microcon-100) and analysed by RT-PCR using specific EV primers and visualising amplification products by agarose gel electrophoresis. In addition, two different methods of RT-PCR for non-cultivable viruses have been tested: (a) RT-PCR and nested RT-PCR for HAV and (b) RT-PCR with generic primers and RT-PCR with specific primers for SRSV. Different

  7. Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

    PubMed Central

    Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P.; Pape, Jean W.; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

    2015-01-01

    Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923. PMID:26520929

  8. Comparative clinicoradiographical evaluation of effect of aminobisphosphonate (sodium alendronate) on peri-implant bone status: Controlled clinical trial

    PubMed Central

    Aggarwal, Rajni; Babaji, Prashant; Nathan, S. Senthil; Attokaran, George; Santosh Kumar, S. M.; Sathnoorkar, Sharanpriya

    2016-01-01

    Aim: The present study aims to compare the peri-implant bone status around immediately loaded dental implants treated with aminobisphosphonate solution and untreated control implants in terms of clinical and radiographical parameters. Materials and Methods: A total of 24 patients were randomly divided equally into two groups. This study was conducted in accordance to the Helsinki's declaration of 1975, revised in 2000, and with the approval of the institutional ethical committee. In the control group after preparation, osteotomy sites were irrigated with normal saline solution, whereas in the test group osteotomy sites were irrigated with modified bisphosphonate solution and then TRX-OP, Hi-Tec dental implants were inserted. Clinical parameters, such as modified plaque and gingival index, probing depth, mobility, and radiographic parameters were recorded at baseline (0), 3, 6, and 9 months. Data analysis was performed using the Statistical Package for the Social Sciences version 17 for windows, and the statistical techniques employed were repeated measures analysis of variance, independent sample t-test, and paired sample t-test. Results: Reduction in mean radiographic bone levels (height) was observed on the mesial and distal aspect of the control group in comparison to its baseline at all intervals. In the test group, there was reduction in mean radiographic bone levels on mesial and distal aspect of the implant site in comparison to its baseline till 6-month follow up, however, at 9 month, there was gain in bone level on both mesial and distal aspect of implant. This represents the effectiveness of sodium alendronate in enhancing the bone formation. On comparison, between both groups on mesial and distal aspect of implants, statistically significant differences were observed at 3 and 9 months on mesial and distal aspect, respectively, without any clinical evidence of mobility in the test group. Conclusion: Implant site treated with aminobisphosphonate solution

  9. [Akita University Graduate School of Medicine: status of clinical laboratory medicine education].

    PubMed

    Ito, Wataru; Chihara, Junichi

    2010-03-01

    Education in laboratory medicine is important. However, many medical students and doctors cannot understand this importance. This problem may be caused by the unclear character of laboratory medicine in research as well as hospital work, resulting in a lack of staff in the Department of Laboratory Medicine. One of the characters of laboratory medicine is its all-inclusive actions unrestrained by medical specialty. Thus, we tell medical students that the staff of laboratory medicine are suitable members of the infection control team (ICT) and nutrition support team (NST) in lectures. Moreover, we also teach allergy, immunology, infection, and sex-specific medicine, which are some subjects the topics of research. Many students in Akita University recognize that the staff of the Department of Laboratory Medicine are specialists of infection and allergy. On the other hand, young doctors can also receive postgraduate clinical training and conduct research not restricted to allergy and infection. We have a policy whereby the Department of Laboratory Medicine always opens its door widely to everyone including students and doctors. Nine staff joined the Department of Laboratory Medicine of Akita University about ten years, and now, can fully provide students with medical education. To solve some problems regarding education in laboratory medicine, we should promote our roles in medical education as well as in hospitals, and increase the number of staff.

  10. Homocysteine, methylenetetrahydrofolate reductase, folate status and atherothrombosis: A mechanistic and clinical perspective.

    PubMed

    Santilli, Francesca; Davì, Giovanni; Patrono, Carlo

    2016-03-01

    Observational studies consistently reported an association between plasma total homocysteine concentrations and the risk of vascular events. In contrast, data from randomized trials largely support the hypothesis that mild elevations in homocysteine level have a modest effect on cardiovascular risk. A substantial body of evidence suggests that platelet activation is, at least in part, a transducer of the effects of high homocysteine in promoting atherothrombosis. The larger treatment effect recorded in several supplementation trials by subjects not on antiplatelet agents may support this hypothesis and justify, at least in part, the success of folate therapy in primary prevention. Circulating folate and homocysteine levels as well as MTHFR genotype, while emerging as major predictors of the risk of vascular events and of the efficacy of folic acid therapy, have also proved to be determinants of an interindividual variability in the degree of lipid peroxidation and platelet activation, and of the extent of their downregulation by folic acid. This may justify a variability in folate requirements, to be further characterized with dose-finding studies using biochemical endpoints. The combination of low-dose aspirin and low-dose folate would appear to be ideally suited for the primary prevention of both coronary and cerebrovascular events, and additional clinical trials should assess the efficacy and safety of these agents.

  11. [Monogenic obesity - current status of molecular genetic research and clinical importance].

    PubMed

    Aldhoon-Hainerová, Irena; Včelák, Josef; Zamrazilová, Hana

    2014-01-01

    Obesity and its comorbidities represent one of the major health problems worldwide. A positive energy balance due to inappropriate life-style changes plays a key role in the current obesity epidemic. The influence of genetic factors is also significant - several studies concluded that genes contribute to the development of obesity by 40-70%. Genetic variability predisposes an individual to tendency or resistance to increase body weight in obesogenic environment. Polygenic type of inheritance is responsible in most of obese individuals. However, an intensive research of the past 20 years has led to an identification of several genes causing monogenic forms of obesity. To date, several monogenic genes (leptin, leptin receptor, prohormon convertase 1, proopiomelanocortin, melanocortin 4 receptor, single-minded homolog 1, brain-derived neurotrophic factor, neurotrophic tyrosine kinase receptor type 2) that are either involved in the neuronal differentiation of the paraventricular nucleus or in the leptin-melanocortin pathway are known to cause obesity. Mutation carriers apart from severe early onset obesity manifest with additional phenotypic characteristics as adrenal insufficiency, impaired immunity and impaired fertility. This review provides an overview of molecular-genetic and clinical research in the field of monogenic obesities including therapeutical approaches.

  12. Review: capsule colonoscopy—a concise clinical overview of current status

    PubMed Central

    Yung, Diana E.; Rondonotti, Emanuele

    2016-01-01

    The colon capsule endoscopy (CCE) was first introduced in 2007. Currently, the main clinical indications for CCE are completion of incomplete colonoscopy, polyp detection and investigation of inflammatory bowel disease (IBD). Although conventional colonoscopy is the gold standard in bowel cancer screening, incomplete colonoscopy remains a problem as lesions are missed. CCE compares favourably to computer tomography colonography (CTC) in adenoma detection and has therefore been proposed as a method for completing colonoscopy. However the data on CCE remains sparse and current evidence does not show its superiority over CTC or conventional colonoscopy in bowel cancer screening. CCE also seems to show good correlation with conventional colonoscopy when used to evaluate IBD, but there are not many published studies at present. Other significant limitations include the need for aggressive bowel preparation and the labour-intensiveness of CCE reading. Therefore, much further software and hardware development is required to enable CCE to fulfill its potential as a minimally-invasive and reliable method of colonoscopy. PMID:27867950

  13. Probiotic foods and drugs: impact of US regulatory status on design of clinical trials.

    PubMed

    Hibberd, Patricia L; Davidson, Lisa

    2008-02-01

    Probiotics have been in widespread use since ancient times and are increasingly being consumed to maintain health and to prevent and treat a wide range of conditions. In the United States, probiotics are considered to be foods or biologics, depending on their intended use. This article addresses the similarities and differences between approaches to conducting clinical trials of probiotics as foods (which leads to health claims) or as biologics (which leads to therapeutic claims). Most probiotics are manufactured as foods, which makes it challenging for academic investigators in the United States to meet the requirements of an Investigational New Drug application that enables them to study the therapeutic effects of these novel agents. Although it is important to ensure the safety and quality of probiotic products, there also may be value in adapting the US Food and Drug Administration's Guidance for Industry for Botanical Products to probiotic products, in part to allow the research agenda to move forward with products for which there are no safety concerns.

  14. Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response

    PubMed Central

    Welsch, Christoph; Efinger, Mira; von Wagner, Michael; Herrmann, Eva; Zeuzem, Stefan

    2017-01-01

    Background Novel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts. Methods This post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493). Results We observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens. Conclusion This is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR. PMID:28196130

  15. Clinical performance of two visual scoring systems in detecting and assessing activity status of occlusal caries in primary teeth.

    PubMed

    Braga, M M; Ekstrand, K R; Martignon, S; Imparato, J C P; Ricketts, D N J; Mendes, F M

    2010-01-01

    This study aimed to compare the clinical performance of two sets of visual scoring criteria for detecting caries severity and assessing caries activity status in occlusal surfaces. Two visual scoring systems--the Nyvad criteria (NY) and the ICDAS-II including an adjunct system for lesion activity assessment (ICDAS-LAA)--were compared using 763 primary molars of 139 children aged 3-12 years. The examinations were performed by 2 calibrated examiners. A subsample (n = 50) was collected after extraction and histology with 0.1% red methyl dye was performed to validate lesion depth and activity. The reproducibility of the indices was calculated (kappa test) and ROC analysis was performed to assess their validity and related parameters were compared using McNemar's test. The association between the indices and with the histological examination was evaluated using Spearman's correlation coefficient (r(s)). Visual criteria showed excellent reproducibility both regarding severity (NY: 0.94; ICDAS-II: 0.91) and activity (NY: 0.90; LAA: 0.91). The NY and LAA showed good association in caries activity assessment (r(s) = 0.88; 95% CI = 0.86-0.89; p < 0.001). Nevertheless, considering only cavitated lesions, this association was not significant (p > 0.05). Concerning the severity, both indices presented similar validity parameters. At D2 threshold, the sensitivity was higher for NY (NY = 0.87; ICDAS = 0.61, p < 0.05). Regarding activity status, NY showed higher specificities and accuracies. In conclusion, NY and ICDAS-II criteria are comparable and present good reproducibility and validity to detect caries lesions and estimate their severities, but the LAA seems to overestimate the caries activity assessment of cavitated lesions compared to NY.

  16. Deep brain stimulation for Parkinson disease in Australia: current scientific and clinical status.

    PubMed

    Poortvliet, P C; Silburn, P A; Coyne, T J; Chenery, H J

    2015-02-01

    There is currently no cure for Parkinson disease (PD). Disease management is directed primarily at motor symptom relief, but the impact of non-motor symptoms associated with PD should not be underestimated. Medical and surgical treatment options aim to increase functional independence and quality of life. Deep brain stimulation (DBS) has proven to be a safe, effective and cost-efficient surgical treatment option. In 2009, the Australian referral guidelines, developed to provide a synopsis of DBS therapy for PD, were introduced, and since then novel findings have been reported regarding the timing of intervention, target selection and symptom management. Our aim is to provide an update of DBS for PD in Australia. Intervention at earlier stages of the disease can potentially improve quality of life over a longer period with greater possibilities for meaningful social and professional contributions. For less responsive motor symptoms (e.g. freezing of gait, postural instability), the pedunculopontine nucleus has emerged as a promising new surgical target. Traditional PD treatment is focused on improvement of motor symptoms, but the disorder is also characterised by non-motor symptoms, often undiagnosed or undisclosed, that have the potential to impact quality of life to a greater extent than motor symptoms. It is essential to identify and routinely monitor for non-motor symptoms as they can emerge at all stages of the disease or can result from treatment. Many of these current advances require long-term monitoring of treatment outcomes to improve future clinical practice, refine patient selection and ensure best patient outcomes.

  17. Alternating hemiplegia of childhood in Denmark: clinical manifestations and ATP1A3 mutation status.

    PubMed

    Hoei-Hansen, Christina E; Dali, Christine Í; Lyngbye, Troels J B; Duno, Morten; Uldall, Peter

    2014-01-01

    Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder characterized by early-onset recurrent distinctive hemiplegic episodes commonly accompanied by other paroxysmal features and developmental impairment. De novo mutations in ATP1A3 were recently identified as a genetic cause of AHC. To describe the entire Danish cohort of paediatric AHC patients we approached neuropaediatricians nationwide. All currently acknowledged Danish patients ≤16 years with AHC were genetically tested and seen by the same child neurologist (PU). Ten patients; seven girls and three boys were identified. Mean present age was 10.0 years (range 1-16). Mean age at presentation was 7.4 months (range 1-18 months). Sequencing of ATP1A3 in all ten patients revealed a pathogenic mutation in seven. Two females with moderate psychomotor impairment were heterozygous for the known p.G947R mutation, whereas one severely retarded boy was heterozygous for the common p.E815K mutation. The prevalent p.D801N mutation was identified in two moderate to severely retarded children. Interestingly, in a set of monochorionic male twins a novel p.D801E mutation was identified, underscoring that the asparagine at position 801 is a mutation hotspot. Three girls aged 5-13 years did not reveal any ATP1A3 mutations. They were rather mildly clinically affected and displayed a normal or near-normal psychomotor development. This is the first study of AHC in the Danish paediatric population. The patients harboured a wide range of psychomotor difficulties. Patients with no mutation detected tended to be less severely affected. Prevalence was approximately 1 per 100,000 children.

  18. A Comparison between Older Persons with Down Syndrome and a Control Group: Clinical Characteristics, Functional Status and Sensori-Motor Function

    ERIC Educational Resources Information Center

    Carmeli, Eli; Kessel, Shlomo; Merrick, Joav; Bar-Chad, Shmuel

    2004-01-01

    The increase in life expectancy within the general population has resulted in an increasing number of elderly adults with intellectual disability, and this is reflected in the increased life expectancy in persons with Down syndrome, currently about 56 years. The aim of this study was to study the clinical characteristics, the functional status and…

  19. Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression: A prospective cohort study.

    PubMed

    Llibre, Josep M; Cozzi-Lepri, Alessandro; Pedersen, Court; Ristola, Matti; Losso, Marcelo; Mocroft, Amanda; Mitsura, Viktar; Falconer, Karolin; Maltez, Fernando; Beniowski, Marek; Vullo, Vincenzo; Hassoun, Gamal; Kuzovatova, Elena; Szlavik, János; Kuznetsova, Anastasiia; Stellbrink, Hans-Jürgen; Duvivier, Claudine; Edwards, Simon; Laut, Kamilla; Paredes, Roger

    2016-10-01

    Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50 copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells higher), time with pVL ≤50 copies/mL (HR 0.87 [95% CI: 0.79-0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28-6.04]). Resistance selection at failure was uncommon.A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure.

  20. Sustained Virologic Response to a Dual Peginterferon alfa-2a and Ribavirin in Treating Chronic hepatitis C Infection

    PubMed Central

    Naing, Cho; Sitt, Than; Aung, Aye TD; Aung, Kyan

    2015-01-01

    Abstract In Myanmar, hepatitis C virus (HCV) infection prevalence is 2%. A combination therapy of pegylated interferon alfa-2a and ribavirin (PEG-IFNa/RBV) is a standard treatment, but the effect of this antiviral therapy needs evaluation as to determine the efficacy and safety of dual PEG-IFNa/RBV therapy in treating patients infected with HCV in Myanmar. This was a retrospective analysis of data from a single clinic exclusively for gastrointestinal diseases in Yangon, Myanmar. We assessed treatment responses at the defined time points and stratified by genotypes of HCV. We also determined incidences of adverse events (AEs). We investigated independent predictors of sustained virologic response (SVR) in the participants. A total of 362 HCV-infected cases were included in this study. The majority were females (51.7%) with mean age of 47.12 years (±11.6) and noncirrhosis patients (82%). Rapid virologic response (RVR), early virologic response (EVR), end of treatment response (ETR), and SVR 24 weeks after completion of the dual treatment were 50.3% (178/362), 88% (314/357), 80.1% (286/357), and 85.6% (167/195), respectively. The most frequently reported AEs were nausea/anorexia (72.8%) and flu-like symptoms (62.4%). In multivariate analysis, 4 factors were independently associated with SVR; SVR to genotype 3 (odds ratio [OR] 2.4, 95% CI: 1.24–4.62), EVR (OR 0.54, 95% CI: 0.3–0.95), and duration of treatment (OR 1.52, 95% CI: 1.18–1.98). Study limitations were acknowledged. The efficacy and safety of the dual therapy in treating HCV-infected patient in Myanmar was acceptable. We recommend a prospective randomized control trial looking at duration of therapy and rates of achieving SVR, which could significantly impact the care of HCV-infected patients in Myanmar and perhaps other countries as well. PMID:26222859

  1. Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort

    PubMed Central

    Welzel, Tania M; Petersen, Jörg; Herzer, Kerstin; Ferenci, Peter; Gschwantler, Michael; Wedemeyer, Heiner; Berg, Thomas; Spengler, Ulrich; Weiland, Ola; van der Valk, Marc; Rockstroh, Jürgen; Peck-Radosavljevic, Markus; Zhao, Yue; Jimenez-Exposito, Maria Jesus; Zeuzem, Stefan

    2016-01-01

    Objective We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease. Design Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). Results Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related. Conclusions DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease. Trial registration number NCT0209966. PMID:27605539

  2. Rapid virological response assessment by Abbott RealTime hepatitis C virus assay for predicting sustained virological responses in patients with hepatitis C virus genotype 1 treated with pegylated-interferon and ribavirin.

    PubMed

    Su, Pei-Yuan; Yen, Hsu-Heng; Hsu, Yu-Chun; Wu, Shun-Sheng; Kor, Chew-Teng; Su, Wei-Wen

    2016-07-01

    The lower limits of virus detection of hepatitis C virus (HCV) RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4(th) week viral load [rapid virological response (RVR)] in predicting sustained virological response (SVR) in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN) and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4(th) week viral load as follows: undetectable (n = 90) and detectable but not quantifiable (< 12 IU/mL, n = 27). All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA) HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4(th) week viral load, respectively. The between-group difference in SVR was significant (p < 0.001). We determined 4(th) week viral load was independently associated with SVR (odds ratio = 19.28; p = 0.002) and a good predictor of SVR [area under the curve (AUC) = 0.775; p = 0.001]. ART HCV assays had a stronger SVR predictive value in HCV genotype 1 patients, indicating that only the undetectable group of 4(th) week viral load patients measured by ART HCV assay should be considered for shorter treatment time (24 weeks) with PEG-IFN and ribavirin.

  3. Proceedings of the fourth National Congress of the Italian Society of Virology.

    PubMed

    Salata, Cristiano; Parolin, Cristina; Palù, Giorgio

    2005-09-01

    The aim of the yearly National Congress of the Italian Society of Virology (SIV) is to promote the discussion between senior and younger researchers to improve the knowledge and scientific collaboration among the various areas of Virology. The invited and selected lecturers of the fourth National Congress of SIV covered the following topics: general Virology and viral Genetics; virus host interactions and pathogenesis; viral immunology and vaccines; emerging and re-emerging viral diseases; antiviral therapy; innovative diagnostics; viral biotechnologies and gene therapy. As in the previous edition (Salata and Palù, 2004 J Cell Physiol 199:171-173), a specific topic was thoroughly covered in a roundtable. In this edition the overviewed topic was HCV, from epidemiology and genetic variability to immunology and antiviral therapy. The final program can be found at the web site http://www.siv-virologia.it. A summary of the oral presentations of the 2004 meeting is reported.

  4. Report of the 2011 annual meeting of the Italian Society for Virology.

    PubMed

    Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Palù, Giorgio

    2012-07-01

    The 10th annual meeting of the Italian Society for Virology (SIV) comprised seven plenary sessions focused on: General virology and viral genetics; Virus-Host interaction and pathogenesis; Viral oncology; Emerging viruses and zoonotic, foodborne and environmental pathways of transmission; Viral immunology and vaccines; Medical virology and antiviral therapy; Viral biotechnologies and gene therapy. The meeting had an attendance of 143 virologists, about 60% were senior, and the other were young scientists. The submitted abstracts amounted to 88 and the abstracts selected for oral presentation were 41. Complete abstracts of oral and poster presentations are available at the web site www.siv-virologia.it. A summary of the plenary lectures and oral selected presentations is reported.

  5. Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial

    PubMed Central

    Badrasawi, M; Shahar, Suzana; Zahara, AM; Nor Fadilah, R; Singh, Devinder Kaur Ajit

    2016-01-01

    Background Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. Methodology This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. Results The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine (P<0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. Conclusion L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults. PMID:27895474

  6. Acute-phase protein concentration and metabolic status affect the outcome of treatment in cows with clinical and subclinical endometritis.

    PubMed

    Heidarpour, M; Mohri, M; Fallah-Rad, A H; Dehghan Shahreza, F; Mohammadi, M

    2012-09-01

    The aim of this study was to investigate the role of acute-phase protein concentration and metabolic status in the establishment and resistance of clinical endometritis (CE) and subclinical endometritis (SE) in dairy cows. We also characterised the treatment-related changes in the concentration of acute-phase proteins and metabolic variables in dairy cows affected by CE and SE. Cows of the SE and CE groups presented a significantly higher β-hydroxybutyrate (BHB), haptoglobin and total sialic acid (TSA) concentrations compared with a healthy group of animals. A significantly lower serum calcium concentration, and a significantly higher serum aspartate aminotransferase activity in the CE group, were observed when compared with SE and healthy groups. The comparison of parameters before treatment indicated that cows suffering from CE or SE with lower concentrations of hepatic and inflammatory markers showed a better response to further treatment, and endometritis was not detected in the second examination. Moreover, decreased concentrations of BHB, acute-phase proteins and hepatic markers were observed after successful treatment for endometritis in CE and SE cows. The results obtained in this study suggest that improved liver function and a decrease in the acute-phase protein concentration might favour the resolution of endometritis after treatment.

  7. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes.

    PubMed

    Rumi, Elisa; Pietra, Daniela; Ferretti, Virginia; Klampfl, Thorsten; Harutyunyan, Ashot S; Milosevic, Jelena D; Them, Nicole C C; Berg, Tiina; Elena, Chiara; Casetti, Ilaria C; Milanesi, Chiara; Sant'antonio, Emanuela; Bellini, Marta; Fugazza, Elena; Renna, Maria C; Boveri, Emanuela; Astori, Cesare; Pascutto, Cristiana; Kralovics, Robert; Cazzola, Mario

    2014-03-06

    Patients with essential thrombocythemia may carry JAK2 (V617F), an MPL substitution, or a calreticulin gene (CALR) mutation. We studied biologic and clinical features of essential thrombocythemia according to JAK2 or CALR mutation status and in relation to those of polycythemia vera. The mutant allele burden was lower in JAK2-mutated than in CALR-mutated essential thrombocythemia. Patients with JAK2 (V617F) were older, had a higher hemoglobin level and white blood cell count, and lower platelet count and serum erythropoietin than those with CALR mutation. Hematologic parameters of patients with JAK2-mutated essential thrombocythemia or polycythemia vera were related to the mutant allele burden. While no polycythemic transformation was observed in CALR-mutated patients, the cumulative risk was 29% at 15 years in those with JAK2-mutated essential thrombocythemia. There was no significant difference in myelofibrotic transformation between the 2 subtypes of essential thrombocythemia. Patients with JAK2-mutated essential thrombocythemia and those with polycythemia vera had a similar risk of thrombosis, which was twice that of patients with the CALR mutation. These observations are consistent with the notion that JAK2-mutated essential thrombocythemia and polycythemia vera represent different phenotypes of a single myeloproliferative neoplasm, whereas CALR-mutated essential thrombocythemia is a distinct disease entity.

  8. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes

    PubMed Central

    Rumi, Elisa; Pietra, Daniela; Ferretti, Virginia; Klampfl, Thorsten; Harutyunyan, Ashot S.; Milosevic, Jelena D.; Them, Nicole C. C.; Berg, Tiina; Elena, Chiara; Casetti, Ilaria C.; Milanesi, Chiara; Sant’Antonio, Emanuela; Bellini, Marta; Fugazza, Elena; Renna, Maria C.; Boveri, Emanuela; Astori, Cesare; Pascutto, Cristiana; Kralovics, Robert

    2014-01-01

    Patients with essential thrombocythemia may carry JAK2 (V617F), an MPL substitution, or a calreticulin gene (CALR) mutation. We studied biologic and clinical features of essential thrombocythemia according to JAK2 or CALR mutation status and in relation to those of polycythemia vera. The mutant allele burden was lower in JAK2-mutated than in CALR-mutated essential thrombocythemia. Patients with JAK2 (V617F) were older, had a higher hemoglobin level and white blood cell count, and lower platelet count and serum erythropoietin than those with CALR mutation. Hematologic parameters of patients with JAK2-mutated essential thrombocythemia or polycythemia vera were related to the mutant allele burden. While no polycythemic transformation was observed in CALR-mutated patients, the cumulative risk was 29% at 15 years in those with JAK2-mutated essential thrombocythemia. There was no significant difference in myelofibrotic transformation between the 2 subtypes of essential thrombocythemia. Patients with JAK2-mutated essential thrombocythemia and those with polycythemia vera had a similar risk of thrombosis, which was twice that of patients with the CALR mutation. These observations are consistent with the notion that JAK2-mutated essential thrombocythemia and polycythemia vera represent different phenotypes of a single myeloproliferative neoplasm, whereas CALR-mutated essential thrombocythemia is a distinct disease entity. PMID:24366362

  9. Systems virology: host-directed approaches to viral pathogenesis and drug targeting.

    PubMed

    Law, G Lynn; Korth, Marcus J; Benecke, Arndt G; Katze, Michael G

    2013-07-01

    High-throughput molecular profiling and computational biology are changing the face of virology, providing a new appreciation of the importance of the host in viral pathogenesis and offering unprecedented opportunities for better diagnostics, therapeutics and vaccines. Here, we provide a snapshot of the evolution of systems virology, from global gene expression profiling and signatures of disease outcome, to geometry-based computational methods that promise to yield novel therapeutic targets, personalized medicine and a deeper understanding of how viruses cause disease. To realize these goals, pipettes and Petri dishes need to join forces with the powers of mathematics and computational biology.

  10. GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients.

    PubMed

    Cox, David G; Curtit, Elsa; Romieu, Gilles; Fumoleau, Pierre; Rios, Maria; Bonnefoi, Hervé; Bachelot, Thomas; Soulié, Patrick; Jouannaud, Christelle; Bourgeois, Hugues; Petit, Thierry; Tennevet, Isabelle; Assouline, David; Mathieu, Marie-Christine; Jacquin, Jean-Philippe; Lavau-Denes, Sandrine; Darut-Jouve, Ariane; Ferrero, Jean-Marc; Tarpin, Carole; Lévy, Christelle; Delecroix, Valérie; Trillet-Lenoir, Véronique; Cojocarasu, Oana; Meunier, Jérôme; Pierga, Jean-Yves; Faure-Mercier, Céline; Blanché, Hélène; Sahbatou, Mourad; Boland, Anne; Bacq, Delphine; Besse, Céline; Deleuze, Jean-François; Pauporté, Iris; Thomas, Gilles; Pivot, Xavier

    2016-11-22

    Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46×10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16×10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors.

  11. GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

    PubMed Central

    Cox, David G.; Curtit, Elsa; Romieu, Gilles; Fumoleau, Pierre; Rios, Maria; Bonnefoi, Hervé; Bachelot, Thomas; Soulié, Patrick; Jouannaud, Christelle; Bourgeois, Hugues; Petit, Thierry; Tennevet, Isabelle; Assouline, David; Mathieu, Marie-Christine; Jacquin, Jean-Philippe; Lavau-Denes, Sandrine; Darut-Jouve, Ariane; Ferrero, Jean-Marc; Tarpin, Carole; Lévy, Christelle; Delecroix, Valérie; Trillet-Lenoir, Véronique; Cojocarasu, Oana; Meunier, Jérôme; Pierga, Jean-Yves; Faure-Mercier, Céline; Blanché, Hélène; Sahbatou, Mourad; Boland, Anne; Bacq, Delphine; Besse, Céline; Deleuze, Jean-François; Pauporté, Iris; Thomas, Gilles; Pivot, Xavier

    2016-01-01

    Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46×10−12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16×10−11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors. PMID:27764800

  12. The Prevalence of Only-Child Status Among Children and Adolescents Referred to a Gender Identity Service Versus a Clinical Comparison Group.

    PubMed

    Hughes, S Kathleen; VanderLaan, Doug P; Blanchard, Ray; Wood, Hayley; Wasserman, Lori; Zucker, Kenneth J

    2016-07-11

    Several studies indicate that homosexual males have a high proportion of older brothers compared to heterosexual males. Natal males with gender dysphoria who are likely to be homosexual also display this sibship pattern. Until recently, there was little evidence linking homosexuality and/or gender dysphoria in females to unique sibship characteristics. Two studies have indicated that natal female youth clinically referred for gender dysphoria are more likely to be only children (Schagen, Delemarre-van de Waal, Blanchard, & Cohen-Kettenis, 2012; VanderLaan, Blanchard, Wood, & Zucker, 2014). However, these studies did not include control groups of youth clinically referred for other reasons. Thus, it is unclear whether the increased likelihood of only-child status is specific to gender-referred natal females. This study compared only-child status among youth referred to a mental health service for gender dysphoria (778 males, 245 females) versus other reasons (783 males, 281 females). Prehomosexual gender-referred males were less likely to be only children than clinical controls. Contrary to previous findings, gender-referred females were not more likely to be only children, indicating that increased likelihood of only-child status is not specific to gender-referred females, but is characteristic of clinic-referred females more generally.

  13. Writing the history of virology in the twentieth century: Discovery, disciplines, and conceptual change.

    PubMed

    Méthot, Pierre-Olivier

    2016-10-01

    Concerned with the study of viruses and the diseases they cause, virology is now a well-established scientific discipline. Whereas aspects of its history from the late nineteenth to the mid-twentieth century have often been recounted through a number of detailed case studies, few general discussions of the historiography of virology have been offered. Looking at the ways in which the history of virology has been told, this article examines a number of debates among scientists and historians of biology and show how they are based on a different understanding of notions such as "discipline", of processes such as "scientific discovery" as well as on distinct views about what the history of science is and how it should be written (the opposition between "longue durée" and "micro-history" or between history of "concepts" versus "experimental methods"). The analysis provided here also suggests that a richer historiography of virology will require looking at the variations over time of the relations between conceptual, technological, and institutional factors that fostered its development at the intersection of several other scientific fields in the life sciences.

  14. Adherence to antiretroviral therapy, virological response, and time to resistance in the Dakar cohort

    PubMed Central

    Tournoud, M.; Etard, J. F.; Ecochard, R.; DeGruttola, V.

    2012-01-01

    In 1998, with the launch of the Senegalese Initiative for Antiretroviral Access (ISAARV), Senegal became one of the first African countries to propose an antiretroviral access program. Our objective in this paper is to study the time to any first drug resistance, as well as predictors of the time to resistance. We propose a joint model to study the effect of adherence to the HAART therapy, and virological response on the time to resistance mutations. A logistic mixed model is used to model the time-dependent adherence process; and a Markov model is used to study the virological response. Given the presence of missing data in the adherence process and in the virological response, the latent adherence and virological states are then included in the linear predictor of the time to resistance model. The proposed time to resistance model takes into account interval-censored data as well as null hazard periods, during which the viral replication is very low. A Bayesian approach is used for accommodating with missing data and for prediction. We also propose model checking tools to study model adequacy. PMID:19941299

  15. 76 FR 27327 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Virologic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Virologic Evaluation of the Modes of Influenza Virus...

  16. Environmental Virology Workshop Summary, Tucson, Arizona, Jan 7-12, 2013

    SciTech Connect

    Sullivan, Matthew

    2015-02-17

    Full Text of the report: A total of 66 researchers participated in this workshop, including 44 attendees, 3 program officers from private and federal funding agencies, and 19 workshop teachers. The workshop was incredibly productive and focused on identifying knowledge-gaps critical for predictive modeling, and developing the framework (experimental, informatic, theoretical) needed to obtain the data. All attendees developed a strong foundation in cutting-edge methods and a network of researchers that are now aiding in advancing environmental virology research. To more broadly reach Environmental Virologists, a subset of the attendees since proposed and ran a viromics workshop at the American Society of Microbiology meeting in 2014 in Boston, MA where the workshop sold-out. The workshop proposal was accepted again by ASM and is scheduled to occur at the New Orleans meeting in May, 2015. Additionally, PI Sullivan is co-convening a ''Viromics: Tools and Concepts'' session at the FEMS meeting in the Netherlands in June 2015 to continue getting the word out about Environmental Virology. A second formal Environmental Virology Workshop is being planned to occur in Scotland in summer 2016, likely held jointly with the Aquatic Virology Workshop. I wish to thank DOE for their critical support for this workshop which has helped galvanize the field.

  17. Isotype patterns of immunoglobulins: hallmarks for clinical status and tissue parasite density in Brazilian dogs naturally infected by Leishmania (Leishmania) chagasi.

    PubMed

    Reis, Alexandre B; Teixeira-Carvalho, Andréa; Vale, André M; Marques, Marcos J; Giunchetti, Rodolfo C; Mayrink, Wilson; Guerra, Luanda Liboreiro; Andrade, Renata A; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo A

    2006-08-15

    The role of anti-leishmanial immune response underlying the susceptibility/resistance during canine visceral leishmaniasis (CVL) has been recognized throughout ex vivo and in vitro investigations. Recently, we demonstrated that immunoglobulin levels (Igs), as well as the parasite load are relevant hallmarks of distinct clinical status of CVL. To further characterize and upgrade the background on this issue, herein, we have evaluated, in Leishmania (Leishmania) chagasi naturally infected dogs, the relationship between tissue parasitism (skin, bone marrow, spleen, liver and lymph node), the CVL clinical status (asymptomatic (AD), with no suggestive signs of the disease; oligosymptomatic (OD), with maximum three clinical signs-opaque bristles; localized alopecia and moderate loss of weight; symptomatic (SD), serologically positive with severe clinical signs of visceral leishmaniasis), and the humoral immunological profile of anti-Leishmania immunoglobulins (IgG, IgG1, IgG2, IgM, IgA and IgE). Our major statistically significant findings revealed distinct patterns of tissue parasite density within L. chagasi-infected dogs despite their clinical status, pointing out the spleen and skin as the most relevant sites of high parasitism during ongoing CVL. Parasite density of bone marrow and spleen were the most reliable parasitological markers to decode the clinical status of CVL. Moreover, the parasite density of bone marrow better correlates with most anti-Leishmania Igs reactivity. Additionally, a prognostic hallmark for canine visceral leishmaniasis was found, highlighting strong correlation between IgG1 and asymptomatic disease, but with IgA, IgE and IgG2 displaying better association with symptomatic disease. The new aspects of this study highlighted pioneer findings that correlated the degree of tissue parasite density (low (LP), medium (MP) and high (HP) parasitism) with distinct patterns of anti-Leishmania Igs reactivity. In this scope, our data re-enforce the anti

  18. Hepatitis C virus/human T lymphotropic virus 1/2 co-infection: Regional burden and virological outcomes in people who inject drugs

    PubMed Central

    Castro, Erika; Roger, Elena

    2016-01-01

    This review analyses current data concerning co-infection with hepatitis C virus (HCV) and human T lymphotropic virus (HTLV)-1/2 in people who inject drugs (PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the ongoing and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the PubMed literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes. PMID:27175351

  19. Association of tumor location, extent of resection, and neurofibromatosis status with clinical outcomes for 221 spinal nerve sheath tumors.

    PubMed

    Safaee, Michael; Parsa, Andrew T; Barbaro, Nicholas M; Chou, Dean; Mummaneni, Praveen V; Weinstein, Philip R; Tihan, Tarik; Ames, Christopher P

    2015-08-01

    OBJECT Intradural extramedullary spine tumors represent two-thirds of all primary spine neoplasms. Approximately half of these are peripheral nerve sheath tumors, mainly neurofibromas and schwannomas. Given the rarity of this disease and, thus, the limited analyses of clinical outcomes, the authors examined the association of tumor location, extent of resection, and neurofibromatosis (NF) status with clinical outcomes. METHODS Patients were identified through a search of the University of California, San Francisco, neuropathology database and a separate review of current procedural terminology codes. Data recorded included patient age, patient sex, clinical presentation, presence of NF, tumor type, tumor location, extent of resection (gross-total resection [GTR] or subtotal resection [STR]), and clinical follow-up. RESULTS Of 221 tumors in 199 patients (mean age 45 years), 53 were neurofibromas, 163 were schwannomas, and 5 were malignant peripheral nerve sheath tumors. The most common presenting symptom was spinal pain (76%), followed by weakness (36%) and sensory abnormalities (34%). Mean symptom duration was 16 months. In terms of spinal location, neurofibromas were more common in the cervical spine (74% vs 27%, p < 0.001), and schwannomas were more common in the thoracic and lumbosacral spine (73% vs 26%, p < 0.001). Rates of GTR were lower for neurofibromas than schwannomas (51% vs 83%, p < 0.001), regardless of location. Rates of GTR were lower for cervical (54%) than thoracic (90%) and lumbosacral (86%) lesions (p < 0.001). NF was associated with lower rates of GTR among all tumors (43% vs 86%, p < 0.001). The mean follow-up time was 32 months. Recurrence/progression was more common for neurofibromas than schwannomas (17% vs 7%, p = 0.03), although the mean time to recurrence/progression did not differ according to tumor type (45 vs 53 months, p = 0.63). As expected, GTR was associated with lower recurrence rates (4% vs 22%, p < 0.001). According to

  20. A history of plant virology. Mendelian genetics and resistance of plants to viruses.

    PubMed

    Pennazio, S; Roggero, P; Conti, M

    2001-10-01

    Virology was borne at the end of the nineteenth century, some years before the re-discovery of the so-called "Mendel's Laws". The rapid development of genetics was helpful to horticulturists and plant pathologists to produce hybrids of important cropping species resistant to several virus diseases. The concepts of Mendelian genetics were applied to plant virology by Francis Oliver Holmes, an American scientist who must be considered a pioneer in several fields of modern plant virology. During the Thirties, Holmes studied in particular the hypersensitive response of solanaceous plants to TMV and discovered the N dominant gene of tobacco hypersensitive to this virus. After the Second World War, the theoretic and practical support given by geneticists assisted plant virologists in better understanding the mechanism of inheritance of the character "resistance". The major problems posed by breeding for plant resistance were detected and critically discussed in several reviews published between the Fifties and the Sixties. These results, together with the discovery of the genetic functions of RNA virus raised interest on the possible relations between viral and plant genes. This fundamental subject saw the entry into the virological scene of molecular genetics, and in 1970 the Russian virologist Joseph Atabekov introduced host specificity to viruses as a central point of plant virology. From the mid 1980s, this point attracted the interest of several virologists, and many results led to several theoretic models of genetic interactions between plant and virus products. In the last fifteen years, the introduction of transgenic plants has given a remarkable contribution to the question of host specificity, which, however, still awaits a general explanation.

  1. Functional status and well being in chronic obstructive pulmonary disease with regard to clinical parameters and smoking: a descriptive and comparative study.

    PubMed Central

    Engström, C. P.; Persson, L. O.; Larsson, S.; Rydén, A.; Sullivan, M.

    1996-01-01

    BACKGROUND: Self-assessment questionnaires which measure the functional and affective consequences of chronic obstructive pulmonary disease (COPD) give valuable information about the effects of the disease and may serve as important tools with which to evaluate treatment. METHODS: A cross sectional comparative study was performed between patients with COPD (n = 68), stratified according to pulmonary function, and a healthy control group (n = 89). A battery of well established clinical and quality of life measures (the Sickness Impact Profile (SIP), Mood Adjective Check List (MACL), and Hospital Anxiety and Depression scale (HAD)) was used to examine in which functional and affective aspects the patient group differed from the control group and how these measures related to pulmonary function and smoking habits. RESULTS: Compared with the controls, COPD affected functional status in most areas, not just those requiring physical activity. Forty six patients with forced expiratory volume in one second (FEV1) below 50% predicted showed particularly high levels of dysfunction in ambulation, eating, home management, and recreation/ pastimes (SIP). Despite this, their level of psychosocial functioning and mood status was little different from that of the healthy controls. Among the patients, a subgroup reported substantial psychological distress, but mood status was only weakly, or not at all, related to pulmonary function. Smoking habits did not affect functional status or well being. CONCLUSIONS: Quality of life is not significantly affected in patients with mild to moderate loss of pulmonary function, possibly due to coping and/or pulmonary reserve capacity. This suggests that generic self-assessment questionnaires are of limited value for detecting the early consequences of COPD. However, in later stages of the disease they are sensitive enough to discriminate between patients with different levels of pulmonary dysfunction. The low correlations between the indices of

  2. High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic: A cross-sectional study.

    PubMed

    Mossoro-Kpinde, Christian Diamant; Gody, Jean-Chrysostome; Mboumba Bouassa, Ralph-Sydney; Mbitikon, Olivia; Jenabian, Mohammad-Ali; Robin, Leman; Matta, Mathieu; Zeitouni, Kamal; Longo, Jean De Dieu; Costiniuk, Cecilia; Grésenguet, Gérard; Touré Kane, Ndèye Coumba; Bélec, Laurent

    2017-03-01

    A large cohort of 220 HIV-1-infected children (median [range] age: 12 [4-17] years) was cared and followed up in the Central African Republic, including 198 in 1st-line and 22 in 2nd-line antiretroviral regimens. Patients were monitored clinically and biologically for HIV-1 RNA load and drug resistance mutations (DRMs) genotyping. A total of 87 (40%) study children were virological responders and 133 (60%) nonresponders. In children with detectable viral load, the majority (129; 97%) represented a virological failure. In children receiving 1st-line regimens in virological failure for whom genotypic resistance test was available, 45% displayed viruses harboring at least 1 DRM to NNRTI or NRTI, and 26% showed at least 1 major DRM to NNRTI or NRTI; more than half of children in 1st-line regimens were resistant to 1st-generation NNRTI and 24% of the children in 1st-line regimens had a major DRMs to PI. Virological failure and selection of DRMs were both associated with poor adherence. These observations demonstrate high rate of virological failure after 3 to 5 years of 1st-line or 2nd-line antiretroviral treatment, which is generally associated with DRMs and therapeutic failure. Overall, more than half (55%) of children receiving 1st-line antiretroviral treatment for a median of 3.4 years showed virological failure and antiretroviral-resistance and thus eligible to 2nd-line treatment. Furthermore, two-third (64%) of children under 2nd-line therapy were eligible to 3rd-line regimen. Taken together, these observations point the necessity to monitor antiretroviral-treated children by plasma HIV-1 RNA load to diagnose as early as possible the therapeutic failure and operate switch to a new therapeutic line.

  3. High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

    PubMed Central

    Mossoro-Kpinde, Christian Diamant; Gody, Jean-Chrysostome; Mboumba Bouassa, Ralph-Sydney; Mbitikon, Olivia; Jenabian, Mohammad-Ali; Robin, Leman; Matta, Mathieu; Zeitouni, Kamal; Longo, Jean De Dieu; Costiniuk, Cecilia; Grésenguet, Gérard; Touré Kane, Ndèye Coumba; Bélec, Laurent

    2017-01-01

    Abstract A large cohort of 220 HIV-1-infected children (median [range] age: 12 [4–17] years) was cared and followed up in the Central African Republic, including 198 in 1st-line and 22 in 2nd-line antiretroviral regimens. Patients were monitored clinically and biologically for HIV-1 RNA load and drug resistance mutations (DRMs) genotyping. A total of 87 (40%) study children were virological responders and 133 (60%) nonresponders. In children with detectable viral load, the majority (129; 97%) represented a virological failure. In children receiving 1st-line regimens in virological failure for whom genotypic resistance test was available, 45% displayed viruses harboring at least 1 DRM to NNRTI or NRTI, and 26% showed at least 1 major DRM to NNRTI or NRTI; more than half of children in 1st-line regimens were resistant to 1st-generation NNRTI and 24% of the children in 1st-line regimens had a major DRMs to PI. Virological failure and selection of DRMs were both associated with poor adherence. These observations demonstrate high rate of virological failure after 3 to 5 years of 1st-line or 2nd-line antiretroviral treatment, which is generally associated with DRMs and therapeutic failure. Overall, more than half (55%) of children receiving 1st-line antiretroviral treatment for a median of 3.4 years showed virological failure and antiretroviral-resistance and thus eligible to 2nd-line treatment. Furthermore, two-third (64%) of children under 2nd-line therapy were eligible to 3rd-line regimen. Taken together, these observations point the necessity to monitor antiretroviral-treated children by plasma HIV-1 RNA load to diagnose as early as possible the therapeutic failure and operate switch to a new therapeutic line. PMID:28272247

  4. Structured Treatment Interruptions and Low Doses of IL-2 in Patients with Primary HIV Infection. Inflammatory, Virological and Immunological Outcomes

    PubMed Central

    Nicolás, David; Manzardo, Christian; Agüero, Fernando; Claramonte, Xavier; Plana, Montserrat; Tuset, Montserrat; Pumarola, Tomás; Gallart, Teresa; Gatell, José María; Miró, José María

    2015-01-01

    Background Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of interleukin-2 (IL-2) in treated PHI patients is unknown. Methods Twelve PHI patients with viral load (VL) <20 copies/mL, CD4 cells >500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL <20 copies/mL ('final stop'). Primary endpoints were VL<3000 copies/mL and CD4 cells >500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 <350 cells/mm3 or AIDS) after ‘final stop’, compared between groups. Results Ten out of 12 patients were males, median age was 35 years and the main risk was men-who-have-sex-with-men. Only one out of 12 patients (in the STI group) maintained VL<3000 copies/mL and CD4 cells >500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19). Conclusions STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials. Trial Registration ClinicalTrials.gov NCT02300623 PMID:26186440

  5. Immunologic and Virologic Progression in HIV Controllers: The Role of Viral "Blips" and Immune Activation in the ANRS CO21 CODEX Study.

    PubMed

    Noel, Nicolas; Lerolle, Nathalie; Lécuroux, Camille; Goujard, Cécile; Venet, Alain; Saez-Cirion, Asier; Avettand-Fenoël, Veronique; Meyer, Laurence; Boufassa, Faroudy; Lambotte, Olivier

    2015-01-01

    Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm(3) or more than 200/mm(3) with a baseline count below 600/mm(3). Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations. Clinical characteristics, immune activation, ultrasensitive HIV VL and total HIV DNA were analyzed. Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5). Progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e. 1-2 years before progression) than non-progressors. ImmP had also lower CD4+T cell nadir and CD4+T cell count at inclusion, and VirP had higher HIV DNA levels in blood. T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors. In summary, the lasting loss of CD4+T cells, residual HIV replication and basal levels of immune activation appear to be major determinants of progression in HICs. These factors should be considered for adjusting their follow-up.

  6. Persistently Elevated C-Reactive Protein Level in the First Year of Antiretroviral Therapy, Despite Virologic Suppression, Is Associated With HIV Disease Progression in Resource-Constrained Settings.

    PubMed

    Shivakoti, Rupak; Yang, Wei-Teng; Berendes, Sima; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Santos, Breno; Poongulali, Selvamuthu; Tripathy, Srikanth; Riviere, Cynthia; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Balagopal, Ashwin; Gupte, Nikhil; Semba, Richard D; Campbell, Thomas B; Bollinger, Robert C; Gupta, Amita

    2016-04-01

    A case-cohort analysis of human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) was performed within a multicountry randomized trial (PEARLS) to assess the prevalence of persistently elevated C-reactive protein (CRP) levels, based on serial measurements of CRP levels, and their association with HIV clinical failure. A persistently elevated CRP level in plasma (defined as ≥ 5 mg/L at both baseline and 24 weeks after ART initiation) was observed in 50 of 205 individuals (24%). A persistently elevated CRP level but not an elevated CRP level only at a single time point was independently associated with increased clinical failure, compared with a persistently low CRP level, despite achievement of virologic suppression. Serial monitoring of CRP levels could identify individuals who are at highest risk of HIV progression and may benefit from future adjunct antiinflammatory therapies.

  7. Long-term immunologic and virologic responses on raltegravir-containing regimens among ART-experienced participants in the HIV Outpatient Study

    PubMed Central

    Buchacz, Kate; Wiegand, Ryan; Armon, Carl; Chmiel, Joan S.; Wood, Kathleen; Brooks, John T.; Palella, Frank J.

    2015-01-01

    Objectives Raltegravir (RAL)-containing antiretroviral therapy (ART) produced better immunologic and virologic responses than optimized background ART in clinical trials of heavily ART-experienced patients, but few data exist on long-term outcomes in routine HIV care. Methods We studied ART-experienced HIV outpatient study (HOPS) participants seen at 10 US HIV-specialty clinics during 2007–2011. We identified patients who started (baseline date) either continuous ≥30 days of RAL-containing or RAL-sparing ART, and used propensity score (PS) matching methods to account for baseline clinical and demographic differences. We used Kaplan–Meier methods and log-rank tests for the matched subsets to evaluate probability of death, achieving HIV RNA <50 copies/ml, and CD4 cell count (CD4) increase of ≥50 cells mm−3 during follow-up. Results Among 784 RAL-exposed and 1062 RAL-unexposed patients, 472 from each group were matched by PS. At baseline, the 472 RAL-exposed patients (mean nadir CD4, 205 cells mm−3; mean baseline CD4, 460 cells mm−3; HIV RNA <50 copies ml−1 in 61%; mean years on prescribed ART, 7.5) were similar to RAL unexposed. During a mean follow-up of over 3 years, mortality rates and immunologic and virologic trajectories did not differ between the two groups. Among patients with detectable baseline HIV RNA levels, 76% of RAL-exposed and 63% of RAL-unexposed achieved HIV RNA <50 copies ml−1 (P=0.51); 69 and 58%, respectively, achieved a CD4 increase ≥50 cells mm−3 (P=0.70). Discussion In our large cohort of US ART-experienced patients with a wide spectrum of clinical history, similar outcomes were observed when prescribed RAL containing versus other contemporary ART. PMID:26126549

  8. Lamivudine Concentration in Hair and Prediction of Virologic Failure and Drug Resistance among HIV Patients Receiving Free ART in China

    PubMed Central

    Wang, Zhe; Wu, Jianjun; Zhang, Jiafeng; Ruan, Yuhua; Hsi, Jenny; Liao, Lingjie; Shao, Yiming; Xing, Hui

    2016-01-01

    Background The assessment of adherence to antiretroviral therapy (ART) is important in order to predict treatment outcomes. Lamivudine (3TC) is one of the most widely used NRTIs in China, but its concentrations in hair and association with virologic failure and drug resistance have not been studied. Methods We conducted a cross-sectional survey to investigate 3TC concentrations in hair as a predictor of virologic failure and drug resistance among HIV patients receiving free ART. We also compared the capacity of hair 3TC concentrations with self-reported adherence in predicting virologic responses. Hair 3TC concentrations were detected through the LC-MS/MS system. Results In patients without HIV drug resistance (HIVDR), with a threshold hair 3TC concentration of 260 ng/g, the sensitivity and specificity in predicting virologic suppression were 76.9% and 89.9%, respectively. Some factors, including CD4+ cell counts, initial treatment regimens with 3TC, and current regimens with second-line drugs, influenced the association between hair 3TC concentrations and virologic suppression. In patients who experienced virologic failure with HIVDR, with a threshold of 180 ng/g, the sensitivity and specificity were 70.0% and 74.4%, respectively. Hair 3TC concentrations had higher sensitivity and specificity in predicting virologic failure and drug resistance than self-reported adherence. Conclusions The hair 3TC concentration was a stronger indicator than self-reported adherence in predicting virologic failure and drug resistance in HIV patients receiving free ART. PMID:27119346

  9. Historical perspective, development and applications of next-generation sequencing in plant virology.

    PubMed

    Barba, Marina; Czosnek, Henryk; Hadidi, Ahmed

    2014-01-06

    Next-generation high throughput sequencing technologies became available at the onset of the 21st century. They provide a highly efficient, rapid, and low cost DNA sequencing platform beyond the reach of the standard and traditional DNA sequencing technologies developed in the late 1970s. They are continually improved to become faster, more efficient and cheaper. They have been used in many fields of biology since 2004. In 2009, next-generation sequencing (NGS) technologies began to be applied to several areas of plant virology including virus/viroid genome sequencing, discovery and detection, ecology and epidemiology, replication and transcription. Identification and characterization of known and unknown viruses and/or viroids in infected plants are currently among the most successful applications of these technologies. It is expected that NGS will play very significant roles in many research and non-research areas of plant virology.

  10. Atomic Force Microscopy as a Tool for Applied Virology and Microbiology

    NASA Astrophysics Data System (ADS)

    Zaitsev, Boris

    2003-12-01

    Atomic force microscope (AFM) can be successfully used for simple and fast solution of many applied biological problems. In this paper the survey of the results of the application of atomic force microscope SolverP47BIO (NT-MDT, Russia) in State Research Center of Virology and Biotechnology "Vector" is presented. The AFM has been used: - in applied virology for the counting of viral particles and examination of virus-cell interaction; - in microbiology for measurements and indication of bacterial spores and cells; - in biotechnology for control of biotechnological processes and evaluation of the distribution of particle dimension for viral and bacterial diagnostic assays. The main advantages of AFM in applied researches are simplicity of the processing of sample preparation and short time of the examination.

  11. Historical Perspective, Development and Applications of Next-Generation Sequencing in Plant Virology

    PubMed Central

    Barba, Marina; Czosnek, Henryk; Hadidi, Ahmed

    2014-01-01

    Next-generation high throughput sequencing technologies became available at the onset of the 21st century. They provide a highly efficient, rapid, and low cost DNA sequencing platform beyond the reach of the standard and traditional DNA sequencing technologies developed in the late 1970s. They are continually improved to become faster, more efficient and cheaper. They have been used in many fields of biology since 2004. In 2009, next-generation sequencing (NGS) technologies began to be applied to several areas of plant virology including virus/viroid genome sequencing, discovery and detection, ecology and epidemiology, replication and transcription. Identification and characterization of known and unknown viruses and/or viroids in infected plants are currently among the most successful applications of these technologies. It is expected that NGS will play very significant roles in many research and non-research areas of plant virology. PMID:24399207

  12. 3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

    PubMed Central

    Felts, Richard L.; Narayan, Kedar; Estes, Jacob D.; Shi, Dan; Trubey, Charles M.; Fu, Jing; Hartnell, Lisa M.; Ruthel, Gordon T.; Schneider, Douglas K.; Nagashima, Kunio; Bess, Julian W.; Bavari, Sina; Lowekamp, Bradley C.; Bliss, Donald; Lifson, Jeffrey D.; Subramaniam, Sriram

    2010-01-01

    The efficiency of HIV infection is greatly enhanced when the virus is delivered at conjugates between CD4+ T cells and virus-bearing antigen-presenting cells such as macrophages or dendritic cells via specialized structures known as virological synapses. Using ion abrasion SEM, electron tomography, and superresolution light microscopy, we have analyzed the spatial architecture of cell-cell contacts and distribution of HIV virions at virological synapses formed between mature dendritic cells and T cells. We demonstrate the striking envelopment of T cells by sheet-like membrane extensions derived from mature dendritic cells, resulting in a shielded region for formation of virological synapses. Within the synapse, filopodial extensions emanating from CD4+ T cells make contact with HIV virions sequestered deep within a 3D network of surface-accessible compartments in the dendritic cell. Viruses are detected at the membrane surfaces of both dendritic cells and T cells, but virions are not released passively at the synapse; instead, virus transfer requires the engagement of T-cell CD4 receptors. The relative seclusion of T cells from the extracellular milieu, the burial of the site of HIV transfer, and the receptor-dependent initiation of virion transfer by T cells highlight unique aspects of cell-cell HIV transmission. PMID:20624966

  13. Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology

    PubMed Central

    Li, Yongfeng; Li, Lian-Feng; Yu, Shaoxiong; Wang, Xiao; Zhang, Lingkai; Yu, Jiahui; Xie, Libao; Li, Weike; Ali, Razim; Qiu, Hua-Ji

    2016-01-01

    Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time. Notably, the development of replicating-competent reporter-expressing viruses (RCREVs) has provided an excellent option to detect directly viral replication without the use of secondary labeling, which represents a significant advance in virology. This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others. However, there remain various challenges associated with RCREVs, including pathogenicity alterations due to the insertion of a reporter gene, instability or loss of the reporter gene expression, or attenuation of reporter signals in vivo. Despite all these limitations, RCREVs have become powerful tools for both basic and applied virology with the development of new technologies for generating RCREVs, the inventions of novel reporters and the better understanding of regulation of viral replication. PMID:27164126

  14. Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology.

    PubMed

    Li, Yongfeng; Li, Lian-Feng; Yu, Shaoxiong; Wang, Xiao; Zhang, Lingkai; Yu, Jiahui; Xie, Libao; Li, Weike; Ali, Razim; Qiu, Hua-Ji

    2016-05-06

    Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time. Notably, the development of replicating-competent reporter-expressing viruses (RCREVs) has provided an excellent option to detect directly viral replication without the use of secondary labeling, which represents a significant advance in virology. This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others. However, there remain various challenges associated with RCREVs, including pathogenicity alterations due to the insertion of a reporter gene, instability or loss of the reporter gene expression, or attenuation of reporter signals in vivo. Despite all these limitations, RCREVs have become powerful tools for both basic and applied virology with the development of new technologies for generating RCREVs, the inventions of novel reporters and the better understanding of regulation of viral replication.

  15. Effect of Bevacizumab Plus Temozolomide-Radiotherapy for Newly Diagnosed Glioblastoma with Different MGMT Methylation Status: A Meta-Analysis of Clinical Trials

    PubMed Central

    Du, Chigang; Ren, Junquan; Zhang, Rui; Xin, Tao; Li, Zhongmin; Zhang, Zhiti; Xu, Xinghua; Pang, Qi

    2016-01-01

    Background MGMT methylation status can influence the therapeutic effect and prognosis of glioblastoma (GBM). There are conflicting results from studies evaluating the efficacy of bevacizumab (BV) when it is combined with temozolomide (TMZ) and radiotherapy (RT) in patients diagnosed with GBM with different MGMT methylation status. Material/Methods Data were extracted from publications in PubMed, Embase, and The Cochrane Library, with the last search performed March 23, 2016. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained. Results Data from 3 clinical trials for a total of 1443 subjects were used for this meta-analysis. MGMT methylated and unmethylated patients showed improved PFS in the BV group (pooled HRs, 0.769, 95% CIs 0.604–0.978, P=0.032; 0.675, 95%CIs 0.466–0.979, P=0.038). For patients with either type of GBM, BV did not improve the OS based on the pooled HRs 1.132 (95% CIs 0.876–1.462; P=0.345) for methylated and 1.018 (95% CIs 0.879–1.179; P=0.345) for unmethylated. Conclusions Bevacizumab combined with temozolomide-radiotherapy correlated with improved PFS for treatment of patients with different MGMT methylation status of newly diagnosed GBM. There was insufficient evidence to determine the synergistic effects of combining BV with TMZ and RT on improving survival in patients with different MGMT methylation status. PMID:27684457

  16. Use of human immunodeficiency virus (HIV) human hyperimmune immunoglobulin in HIV type 1-infected children (Pediatric AIDS clinical trials group protocol 273).

    PubMed

    Stiehm, E R; Fletcher, C V; Mofenson, L M; Palumbo, P E; Kang, M; Fenton, T; Sapan, C V; Meyer, W A; Shearer, W T; Hawkins, E; Fowler, M G; Bouquin, P; Purdue, L; Sloand, E M; Nemo, G J; Wara, D; Bryson, Y J; Starr, S E; Petru, A; Burchett, S

    2000-02-01

    The clinical, immunologic, and virologic effects and the pharmacokinetics of human immunodeficiency virus (HIV) human hyperimmune immunoglobulin (HIVIG) were assessed in 30 HIV-infected children aged 2-11 years. All had moderately advanced disease with an immune complex-dissociated (ICD) p24 antigen >70 pg/mL and were on stable antiviral therapy. Three groups of 10 children received 6 monthly infusions of 200, 400, or 800 mg/kg of HIVIG, and serial immunologic and virologic assays were performed. HIVIG doses as high as 800 mg/kg were safe and well tolerated. The half-life of HIVIG, determined by serial p24 antibody titers, was 13-16 days, the volume of distribution was 102-113 mL/kg, and clearance was 5.6-6.0 mL/kg/day. Plasma ICD p24 decreased during the infusions, but CD4 cell levels, plasma RNA copy number, cellular virus, immunoglobulin levels, and neutralizing antibody titers were minimally affected by the infusions. Clinical status did not change during the 6-month infusion and 3-month follow-up periods.

  17. Translational HIV-1 research: from routine diagnostics to new virology insights in Amsterdam, the Netherlands during 1983-2013

    PubMed Central

    2013-01-01

    An HIV-1 diagnostic laboratory was established in the Academic Medical Center (AMC) of the University of Amsterdam after the discovery of human immunodeficiency virus (HIV) as the cause of the acquired immunodeficiency syndrome (AIDS). The first AIDS patients were diagnosed here in 1981 and since 1983 we have tested the samples of 50992 patients using a variety of assays that greatly improved over the years. We will describe some of the basic results from this diagnostic laboratory and then focus on the spin-off in terms of the development of novel virus assays to detect super-infections and ultra-sensitive assays to measure the intracellular HIV-1 RNA load. We also review several original research findings in the field of HIV-1 virology that stem from initial observations made in the diagnostic unit. This includes the study of genetic defects in the HIV-1 genome and time trends of the replication fitness over 30 years of viral evolution, but also the description of novel HIV-1 variants in difficult-to-diagnose clinical specimen. PMID:23985078

  18. Discordance between genotypic resistance and pseudovirus phenotypic resistance in AIDS patients after long-term antiretroviral therapy and virological failure.

    PubMed

    Yang, Jing; Geng, Wenqing; Zhang, Min; Han, Xiaoxu; Shang, Hong

    2014-10-01

    Sixteen original recombinant pseudoviruses were generated by cloning the reverse transcriptase and protease genes of human immunodeficiency virus (HIV)-1 from patients into a plasmid vector (pNL4-3-ΔE-EGFP). By site-directed mutagenesis two restriction endonuclease sites, ApaI and AgeI, were inserted into pNL4-3-ΔE-EGFP. Phenotypic susceptibility of recombinant pseudoviruses to five different classes of antiretroviral drugs was determined using a luciferase reporter assay system. The results were subjected to comparative analyses to detect genotype-phenotype associations. Among 16 strains tested, 12 strains had a discordant genotype-phenotype resistance pattern to at least one drug. In five strains resistance to two, in two strains to three, and in one strain resistance to four drugs was detected. HIV resistance genotyping could predict the phenotype for nevirapine and azidothymidine. For lamivudine, 2'-3'-didehydro-2'-3'dideoxythymidine and didanosine, phenotypic resistance testing was necessary. The study showed that in patients who experienced long-term highly active antiretroviral therapy and virological failure, there is some discordance between genotypic and phenotypic HIV drug resistance. To address the issue of limited resources in China, genotypic and phenotypic resistance testing should be done for different drugs in order to guide clinical therapy more effectively.

  19. [Focal epithelial hyperplasia. An unusual clinical aspect].

    PubMed

    Bodokh, I; Lacour, J P; Rainero, C; Orth, G; Perrin, C; Hoffman, P; Santini, J; Ortonne, J P

    1993-01-01

    We report a case of focal epithelial hyperplasia in a child born in France of Algerian parents. The clinical appearance was unusual in that certain lesions were verrucous and pediculate. A virological study revealed the presence of papillomavirus 32, one of the two types of HPV specifically associated with this entity.

  20. Development and Evaluation of an Affordable Real-Time Qualitative Assay for Determining HIV-1 Virological Failure in Plasma and Dried Blood Spots

    PubMed Central

    Kliphuis, Aletta; Bronze, Michelle; Wallis, Carole L.; Kityo, Cissy; Balinda, Sheila; Stevens, Wendy; Spieker, Nicole; de Oliveira, Tulio; Rinke de Wit, Tobias F.; Schuurman, Rob

    2013-01-01

    Virological failure (VF) has been identified as the earliest, most predictive determinant of HIV-1 antiretroviral treatment (ART) failure. Due to the high cost and complexity of virological monitoring, VF assays are rarely performed in resource-limited settings (RLS). Rather, ART failure is determined by clinical monitoring and to a large extent immunological monitoring. This paper describes the development and evaluation of a low-cost, dried blood spot (DBS)-compatible qualitative assay to determine VF, in accordance with current WHO guideline recommendations for therapy switching in RLS. The assay described here is an internally controlled qualitative real-time PCR targeting the conserved long terminal repeat domain of HIV-1. This assay was applied to HIV-1 subtypes A to H and further evaluated on HIV-1 clinical plasma samples from South Africa (n = 191) and Tanzania (n = 42). Field evaluation was performed in Uganda using local clinical plasma samples (n = 176). Furthermore, assay performance was evaluated for DBS. This assay is able to identify VF for all major HIV-1 group M subtypes with equal specificity and has a lower detection limit of 1.00E+03 copies/ml for plasma samples and 5.00E+03 copies/ml for DBS. Comparative testing yielded accurate VF determination for therapy switching in 89% to 96% of samples compared to gold standards. The assay is robust and flexible, allowing for “open platform” applications and producing results comparable to those of commercial assays. Assay design enables application in laboratories that can accommodate real-time PCR equipment, allowing decentralization of testing to some extent. Compatibility with DBS extends access of sampling and thus access to this test to remote settings. PMID:23596235

  1. Development and evaluation of an affordable real-time qualitative assay for determining HIV-1 virological failure in plasma and dried blood spots.

    PubMed

    Aitken, Susan C; Kliphuis, Aletta; Bronze, Michelle; Wallis, Carole L; Kityo, Cissy; Balinda, Sheila; Stevens, Wendy; Spieker, Nicole; de Oliveira, Tulio; Rinke de Wit, Tobias F; Schuurman, Rob

    2013-06-01

    Virological failure (VF) has been identified as the earliest, most predictive determinant of HIV-1 antiretroviral treatment (ART) failure. Due to the high cost and complexity of virological monitoring, VF assays are rarely performed in resource-limited settings (RLS). Rather, ART failure is determined by clinical monitoring and to a large extent immunological monitoring. This paper describes the development and evaluation of a low-cost, dried blood spot (DBS)-compatible qualitative assay to determine VF, in accordance with current WHO guideline recommendations for therapy switching in RLS. The assay described here is an internally controlled qualitative real-time PCR targeting the conserved long terminal repeat domain of HIV-1. This assay was applied to HIV-1 subtypes A to H and further evaluated on HIV-1 clinical plasma samples from South Africa (n = 191) and Tanzania (n = 42). Field evaluation was performed in Uganda using local clinical plasma samples (n = 176). Furthermore, assay performance was evaluated for DBS. This assay is able to identify VF for all major HIV-1 group M subtypes with equal specificity and has a lower detection limit of 1.00E+03 copies/ml for plasma samples and 5.00E+03 copies/ml for DBS. Comparative testing yielded accurate VF determination for therapy switching in 89% to 96% of samples compared to gold standards. The assay is robust and flexible, allowing for "open platform" applications and producing results comparable to those of commercial assays. Assay design enables application in laboratories that can accommodate real-time PCR equipment, allowing decentralization of testing to some extent. Compatibility with DBS extends access of sampling and thus access to this test to remote settings.

  2. Burkholderia cepacia Complex Bacteria from Clinical and Environmental Sources in Italy: Genomovar Status and Distribution of Traits Related to Virulence and Transmissibility

    PubMed Central

    Bevivino, Annamaria; Dalmastri, Claudia; Tabacchioni, Silvia; Chiarini, Luigi; Belli, Maria L.; Piana, Sandra; Materazzo, Alberto; Vandamme, Peter; Manno, Graziana

    2002-01-01

    Sixty-eight Burkholderia cepacia complex isolates recovered from the sputum of 53 cystic fibrosis patients and 75 isolates collected from the maize rhizosphere were compared to each other to assess their genomovar status as well as some traits related to virulence such as antibiotic susceptibility, proteolytic and hemolytic activities, and transmissibility, in which transmissibility is determined by detection of the esmR and cblA genes. Among the clinical isolates, B. cepacia genomovar III comprised the majority of isolates examined and only a very few isolates were assigned to B. cepacia genomovar I, B. stabilis, and B. pyrrocinia; among the environmental isolates a prevalence of B. cepacia genomovar III and B. ambifaria was observed, whereas few environmental isolates belonging to B. cepacia genomovar I and B. pyrrocinia were found. Antibiotic resistance analysis revealed a certain degree of differentiation between clinical and environmental isolates. Proteolytic activity and onion tissue maceration ability were found to be spread equally among both clinical and environmental isolates, whereas larger percentages of environmental isolates than clinical isolates had hemolytic activity. The esmR gene was found exclusively among isolates belonging to B. cepacia genomovar III, with a marked prevalence in clinical isolates, whereas only one clinical isolate belonging to B. cepacia genomovar III was found to bear the cblA gene. In conclusion, the results of the present study show that the species compositions of the clinical and environmental B. cepacia complex populations examined are quite different and that some of the candidate determinants related to virulence and transmissibility are not confined solely to clinical isolates but are also spread among environmental isolates belonging to different species of the B. cepacia complex. PMID:11880403

  3. Virological and serological findings in dogs with naturally occurring distemper.

    PubMed

    Elia, Gabriella; Camero, Michele; Losurdo, Michele; Lucente, Maria Stella; Larocca, Vittorio; Martella, Vito; Decaro, Nicola; Buonavoglia, Canio

    2015-03-01

    Canine distemper virus (CDV) is the cause of a severe and highly contagious disease in dogs. The unpredictable and variable course of CDV-related disease may hamper correct diagnosis of infection and makes it crucial the collection of samples suitable for laboratory confirmation. In the present study we were able to follow the disease in two dogs infected naturally, collecting different biological matrices during the entire period of infection. By real time RT-PCR, viral RNA was detected and quantified, suggesting that urine and rectal swabs would be useful for ante-mortem diagnosis of distemper in dogs, regardless of the clinical stage and form of the illness.

  4. Development of a Learning-Oriented Computer Assisted Instruction Designed to Improve Skills in the Clinical Assessment of the Nutritional Status: A Pilot Evaluation

    PubMed Central

    García de Diego, Laura; Cuervo, Marta; Martínez, J. Alfredo

    2015-01-01

    Computer assisted instruction (CAI) is an effective tool for evaluating and training students and professionals. In this article we will present a learning-oriented CAI, which has been developed for students and health professionals to acquire and retain new knowledge through the practice. A two-phase pilot evaluation was conducted, involving 8 nutrition experts and 30 postgraduate students, respectively. In each training session, the software developed guides users in the integral evaluation of a patient’s nutritional status and helps them to implement actions. The program includes into the format clinical tools, which can be used to recognize possible patient’s needs, to improve the clinical reasoning and to develop professional skills. Among them are assessment questionnaires and evaluation criteria, cardiovascular risk charts, clinical guidelines and photographs of various diseases. This CAI is a complete software package easy to use and versatile, aimed at clinical specialists, medical staff, scientists, educators and clinical students, which can be used as a learning tool. This application constitutes an advanced method for students and health professionals to accomplish nutritional assessments combining theoretical and empirical issues, which can be implemented in their academic curriculum. PMID:25978456

  5. Sociodemographic factors in a pediatric chronic pain clinic: The roles of age, sex and minority status in pain and health characteristics

    PubMed Central

    Evans, Subhadra; Taub, Rebecca; Tsao, Jennie CI; Meldrum, Marcia; Zeltzer, Lonnie K

    2011-01-01

    Little is known about how sociodemographic factors relate to children’s chronic pain. This paper describes the pain, health, and sociodemographic characteristics of a cohort of children presenting to an urban tertiary chronic pain clinic and documents the role of age, sex and minority status on pain-related characteristics. A multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Two hundred and nineteen patients and their parents were given questionnaire packets to fill out prior to their intake appointment which included demographic information, clinical information, Child Health Questionnaire – Parent Report, Functional Disability Index – Parent Report, Child Somatization Index – Parent Report, and a Pain Intensity Scale. Additional clinical information was obtained from patients’ medical records via chart review. This clinical sample exhibited compromised functioning in a number of domains, including school attendance, bodily pain, and health compared to normative data. Patients also exhibited high levels of functional disability. Minority children evidenced decreased sleep, increased somatization, higher levels of functional disability, and increased pain intensity compared to Caucasians. Caucasians were more likely to endorse headaches than minorities, and girls were more likely than boys to present with fibromyalgia. Younger children reported better functioning than did teens. The results indicate that sociodemographic factors are significantly associated with several pain-related characteristics in children with chronic pain. Further research must address potential mechanisms of these relationships and applications for treatment. PMID:21686073

  6. Favorable Outcomes of Chinese HCV-Related Cirrhotic Patients with Sustained Virological Response after Pegylated Interferon Plus Ribavirin Treatment

    PubMed Central

    Chen, You-ming; Zhang, Ting; Cai, Qing-xian; Zhang, Xiao-hong; Zhao, Zhi-xing

    2017-01-01

    Few studies have conducted follow-up investigations of the clinical course in HCV-related cirrhotic patients who achieved a sustained virological response (SVR) with pegylated interferon plus ribavirin treatment (PegIFN + RBV). We investigated the clinical course and laboratory data in a prospective cohort study enrolling HCV-related cirrhotic patients who received PegIFN + RBV between August 2008 and July 2013 in China. Complete blood counts, liver function tests, and HCV-RNA were serially examined. Liver-related complications were recorded. To detect hepatocellular carcinoma (HCC), alpha-fetoprotein assays, and ultrasound scans were repeated at 6-month intervals. Twenty-five patients were enrolled, including 8 patients with decompensation events before treatment. Eighteen patients achieved SVR with a mean follow-up period of 25.78 months. During the follow-up period, only one patient exhibited HCV-RNA positivity and no decompensation events were detected, but 4 patients developed HCC after SVR. APRI decreased more in patients with SVR than in patients with non-SVR (median, −1.33 versus 0.86, P < 0.001). The albumin levels and platelet counts significantly increased during the follow-up period after SVR (44.27 ± 4.09 versus 42.63 ± 4.37, P = 0.037 and 173.89 ± 87.36 versus 160.11 ± 77.97, P = 0.047). These data indicated that HCV-related cirrhotic patients with SVR after PegIFN + RBV may have a favorable clinical course and improvements in laboratory data. Moreover, HCC should be monitored. PMID:28232944

  7. Virological pattern of hepatitis B infection in an HIV-positive man with fatal fulminant hepatitis B: a case report

    PubMed Central

    2009-01-01

    Introduction There seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis. Case presentation A 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission. He developed fatal fulminant hepatitis and was found to be heavily immunocompromised due to HIV-1 infection. He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2 domain showed the presence of mixed infection with D and F genotypes. Analysis of the point mutations within this region revealed the presence of HBV strains with amino acid substitutions at the immunodominant epitopes involved in B or T cell recognition. A homogeneous population of a pre-core mutant strain harbouring the A1896G and A1899G affecting HBeAg expression was invariably found in the liver tissue, plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it was the dominant strain in the liver only, and was characterised by the presence of two point mutations in the direct repeat 1 domain involved in HBV replication activity. Taken together, these mutations are indicative of a highly replicative virus capable of evading immune responses. Conclusion This case report provides clinical evidence of a possible association between the rapid spread of highly replicative escape mutants and the development of fulminant hepatitis in a heavily immunocompromised patient. Virological surveillance of severe acute hepatitis B may be important in establishing an early treatment strategy involving antiviral drugs capable of preventing liver failure, especially in individuals for whom liver transplantation is not accepted as a standard indication. PMID:19946588

  8. Causes of virological failure in a population of 1895 HIV-infected patients: the experience of an infectious diseases service in Lisbon, Portugal

    PubMed Central

    Moneti, V; Luís, N; Rijo, J; Miranda, A; Baptista, T; Farinha, H; Mansinho, K

    2012-01-01

    Despite the increasing optimization of combined antiretroviral therapy (cART) regimens in the last decades, a significant percentage of patients still do not achieve viral replication control. We present a retrospective analysis focusing on human immunodeficiency virus (HIV)-infected population on cART, followed at our ambulatory care clinic between 1st January and 31st December 2011, in order to identify the causes of virological failure. From the 1895 patients in our population we included 1854 in the study. Ten percent (187) of the included patients had detectable HIV RNA (≥40 cp/mL) at the time of last laboratory evaluation: 70,1% were males, mean age was 46 years and 72,7% were Portuguese. Patients with detectable HIV RNA were divided into group A (HIV RNA <200 cp/mL) - 78 (41,7%) patients and group B (HIV RNA ≥200 cp/mL) 109 (58,3%) patients. The comparison of both groups revealed an higher mean count of TCD4+ (568 vs 334 cells/mm3; p<0,001) in group A, although similar mean TCD4+ count at time of cART initiation (276 vs 262 cells/mm3; p=0,412). Group A patients experienced longer exposure to cART (10 vs 8 years; p<0,05) and have undergone, on average, 3 previous regimens (p<0,05). With regard to cARV current regimen: 32,1% patients in group A and 30,3% in group B were prescribed non-nucleoside reverse transcriptase inhibitors based regimes and 51,3% patients in Group A and 59,6% in group B were under cARV based on Protease inhibitors. The identified causes of virologic failure for patients with detectable HIV RNA were: poor adherence (54%); unsuccessful retention in care (14,4%); sporadic detectable HIV RNA (40≤viral load<200), “blips” (14,4%); mutations of resistance to ARVs (13,4%); intolerance to the current regimen (2,1%) and pharmacokinetics drug interactions (1,6%). The estimated rate of virological failure was 10,1% in this population. Insufficient adherence and unsuccessful retention in care were identified in 68,4% of treatment failed

  9. Relationship of smoking status to genomic profile, chemotherapy response and clinical outcome in patients with advanced urothelial carcinoma

    PubMed Central

    Joshi, Monika; Vasekar, Monali; Grivas, Petros; Emamekhoo, Hamid; Hsu, JoAnn; Miller, Vincent A.; Stephens, Philip J.; Ali, Siraj M.; Ross, Jeffrey S.; Zhu, Junjia; Warrick, Joshua; Drabick, Joseph J.; Holder, Sheldon L.; Kaag, Matthew; Li, Min; Pal, Sumanta Kumar

    2016-01-01

    Smoking has been linked to urothelial carcinoma (UC), but the implications on genomic profile and therapeutic response are poorly understood. To determine how smoking history impacts genomic profile and chemotherapy response, clinicopathologic data was collected for patients with metastatic UC (mUC) across 3 academic medical centers and comprehensive genomic profiling (CGP) was performed through a CLIA-certified lab. Unsupervised hierarchical clustering based on smoking status was used to categorize the frequency of genomic alterations (GAs) amongst current smokers (CS), ex-smokers (ES) and non-smokers (NS), and survival was compared in these subsets. Fisher's exact test identified significant associations between GAs and smoking status. Amongst 83 patients, 23%, 55% and 22% were CS, ES, and NS, respectively, and 95% of patients had stage IV disease. With a median follow up of 14.4 months, the median overall survival (OS) was significantly higher in NS and ES (combined) as compared to CS (51.6 vs 15.6 months; P = 0.04). Of 315 cancer-related genes and 31 genes often related to rearrangement tested, heatmaps show some variations amongst the subsets. GAs in NSD1 were more frequent in CS as compared to other groups (P < 0.001). CS status negatively impacts OS in patients with mUC and is associated with genomic alterations that could have therapeutic implications. PMID:27213592

  10. Patients with electrical status epilepticus in sleep share similar clinical features regardless of their focal or generalized sleep potentiation of epileptiform activity.

    PubMed

    Fernández, Iván Sánchez; Peters, Jurriaan; Takeoka, Masanori; Rotenberg, Alexander; Prabhu, Sanjay; Gregas, Matt; Riviello, James J; Kothare, Sanjeev; Loddenkemper, Tobias

    2013-01-01

    The study objective was to compare qualitatively the clinical features of patients with electrical status epilepticus in sleep with focal versus generalized sleep potentiated epileptiform activity. We enrolled patients 2 to 20 years of age, studied between 2001 and 2009, and with sleep potentiated epileptiform activity defined as an increase of epileptiform activity of 50% or more during non-rapid eye movement sleep compared with wakefulness. Eighty-five patients met the inclusion criteria, median age was 7.3 years, and 54 (63.5%) were boys. Sixty-seven (78.8%) patients had focal sleep potentiated epileptiform activity, whereas 18 (21.2%) had generalized sleep potentiated epileptiform activity. The 2 groups did not differ with respect to sex, age, presence of a structural brain abnormality, epilepsy, or other qualitative cognitive, motor, or behavioral problems. Our data suggest that there are no qualitative differences in the clinical features of patients with focal versus generalized sleep potentiated epileptiform activity.

  11. Effect of hepatitis C virus on immunological and virological responses in HIV-infected patients initiating highly active antiretroviral therapy: a meta-analysis.

    PubMed

    Tsiara, C G; Nikolopoulos, G K; Dimou, N L; Bagos, P G; Saroglou, G; Velonakis, E; Hatzakis, A

    2013-10-01

    Co-infection of human immunodeficiency virus (HIV) with hepatitis C virus (HCV) is rather common. In the era of highly active antiretroviral therapy (HAART), viral hepatitis could result in adverse outcomes in HIV+ patients. The current meta-analysis aims to evaluate the impact of HCV on immunological and virological responses after HAART initiation in HIV/HCV co-infected individuals by synthesizing the existing scientific evidence. A comprehensive search of electronic databases was performed. Eligible studies were analysed using univariate and multivariate meta-analytic methods. Totally, 21 studies involving 22533 individuals were eligible. The estimated summary difference in CD4 cell counts increase between HIV and HIV/HCV co-infected subjects after 3-12 months on HAART was 34.86 cells/mm(3) [95% confidence interval (CI): 16.82-52.89]. The difference was more prominent in patients with baseline CD4 counts below 350 cells/mm(3) (38.97, 95% CI: 20.00-57.93) and attenuated 2 years later (13.43, 95% CI: 0.83-26.04). The analysis of ratio measures yielded similar findings. The virological control remained unaffected by the presence of HCV (adjusted Hazard Ratio for co-infected patients vs those with HIV alone: 0.99, 95% CI: 0.91-1.07). The bivariate meta-analytic method confirmed the results of the univariate approaches. This meta-analysis supports the adverse effect of HCV on immune recovery of HIV+ patients initiating HAART, especially of those with initially impaired immunologic status. Although this effect diminishes over time, early administration of HAART in the setting of co-infection seems to be justified.

  12. Zika virus infections imported to Italy: clinical, immunological and virological findings, and public health implications.

    PubMed

    Zammarchi, Lorenzo; Stella, Giulia; Mantella, Antonia; Bartolozzi, Dario; Tappe, Dennis; Günther, Stephan; Oestereich, Lisa; Cadar, Daniel; Muñoz-Fontela, César; Bartoloni, Alessandro; Schmidt-Chanasit, Jonas

    2015-02-01

    We report the first two cases of laboratory confirmed Zika virus (ZIKV) infections imported into Italy from French Polynesia. Both patients presented with low grade fever, malaise, conjunctivitis, myalgia, arthralgia, ankle oedema, and axillary and inguinal lymphadenopathy. One patient showed leukopenia with relative monocytosis and thrombocytopenia. The diagnosis was based on ZIKV seroconversion in both cases and on ZIKV RNA detection in one patient from acute serum sample. Sera from both patients exhibited cross-reactivity with dengue virus antigens. Our immunological analysis demonstrated that recovery from ZIKV infection is associated with restoration of normal numbers of immune cells in the periphery as well as with normal function of antigen-presenting cells. ZIKV is an emerging arbovirus, which has recently spread extensively in tourist destinations on several West Pacific islands. Returning viremic travelers may ignite autochthonous infections in countries like Italy, which are infested by Aedes albopictus, a suitable vector for ZIKV. The role of clinicians is crucial and includes early diagnosis and timely notification of public health authorities in order to quickly implement adequate focal vector control measurements.

  13. Clinical, Virologic, and Epidemiologic Characteristics of Dengue Outbreak, Dar es Salaam, Tanzania, 2014

    PubMed Central

    Mboera, Leonard E.G.; De Nardo, Pasquale; Oriyo, Ndekya M.; Meschi, Silvia; Rumisha, Susan F.; Colavita, Francesca; Mhina, Athanas; Carletti, Fabrizio; Mwakapeje, Elibariki; Capobianchi, Maria Rosaria; Castilletti, Concetta; Di Caro, Antonino; Nicastri, Emanuele; Malecela, Mwelecele N.; Ippolito, Giuseppe

    2016-01-01

    We investigated a dengue outbreak in Dar es Salaam, Tanzania, in 2014, that was caused by dengue virus (DENV) serotype 2. DENV infection was present in 101 (20.9%) of 483 patients. Patient age and location of residence were associated with infection. Seven (4.0%) of 176 patients were co-infected with malaria and DENV. PMID:27088845

  14. Clinical, Virologic, and Epidemiologic Characteristics of Dengue Outbreak, Dar es Salaam, Tanzania, 2014.

    PubMed

    Vairo, Francesco; Mboera, Leonard E G; De Nardo, Pasquale; Oriyo, Ndekya M; Meschi, Silvia; Rumisha, Susan F; Colavita, Francesca; Mhina, Athanas; Carletti, Fabrizio; Mwakapeje, Elibariki; Capobianchi, Maria Rosaria; Castilletti, Concetta; Di Caro, Antonino; Nicastri, Emanuele; Malecela, Mwelecele N; Ippolito, Giuseppe

    2016-05-01

    We investigated a dengue outbreak in Dar es Salaam, Tanzania, in 2014, that was caused by dengue virus (DENV) serotype 2. DENV infection was present in 101 (20.9%) of 483 patients. Patient age and location of residence were associated with infection. Seven (4.0%) of 176 patients were co-infected with malaria and DENV.

  15. [Varicella and herpes zoster. Part 1: virology, epidemiology, clinical picture, laboratory diagnostics].

    PubMed

    Wittek, Miriam; Doerr, Hans Wilhelm; Allwinn, Regina

    2010-05-01

    Varicella-zoster virus (VZV), known as one of the eight human herpesviridae, shows a ubiquitous distribution and is the cause for acute exanthema in childhood (chickenpox). VZV is highly infectious, spread by respiratory droplets and direct contact with fluid in vesicles. As a characteristic of the alpha-herpesviridae, VZV establishes latency in the nucleus of the paraspinal cells. Reactivation of VZV (zoster) is possible in all infected persons, but becomes more common with increasing age and a decline of VZV-specific cell-mediated immunity. Immunocompromised patients and older people (> 50 years) have an increased risk for a severe course of disease. The postherpetic neuralgia (PHN), as one of the most common and feared complications, is defined as a neuropathic pain (burning character), which persists for > 6 weeks after onset of disease and needs adequate antiviral and pain treatment.

  16. Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry

    PubMed Central

    Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

    2016-01-01

    Objective Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. Methods A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. Results A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Conclusions Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. PMID:27881517

  17. Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa

    PubMed Central

    Petersen, Maya L.; Tran, Linh; Geng, Elvin H.; Reynolds, Steven J.; Kambugu, Andrew; Wood, Robin; Bangsberg, David R.; Yiannoutsos, Constantin T.; Deeks, Steven G.; Martin, Jeffrey N.

    2015-01-01

    Objective Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa. Design A cohort. Methods We examined patients with confirmed virologic failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27–33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1 –4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99–5.8) to that of the entire cohort, although of borderline statistical significance. Conclusion Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality. PMID:24977440

  18. Current status of nuclear cardiology in Japan: Ongoing efforts to improve clinical standards and to establish evidence.

    PubMed

    Yoshinaga, Keiichiro; Tamaki, Nagara

    2015-08-01

    Nuclear cardiology imaging tests are widely performed in Japan as clinical practice. The Japanese nuclear cardiology community has developed new diagnostic imaging tests using (123)I-beta-methyl-p-iodophenyl-pentadecanoic acid, (123)I-metaiodobenzylguanidine, and (18)F-fluorodeoxyglucose PET for detecting cardiac involvement in sarcoidosis. These tests have become popular worldwide. The Japanese Circulation Society and the Japanese Society of Nuclear Cardiology have published clinical imaging guidelines showing indications and standards for the new imaging tests. JSNC is currently striving to improve the standard of clinical practice and is promoting research activities.

  19. Chromophore based analyses of steady-state diffuse reflectance spectroscopy: current status and perspectives for clinical adoption.

    PubMed

    Bydlon, Torre M; Nachabé, Rami; Ramanujam, Nimmi; Sterenborg, Henricus J C M; Hendriks, Benno H W

    2015-01-01

    Diffuse reflectance spectroscopy is a rapidly growing technology in the biophotonics community where it has shown promise in its ability to classify different tissues. In the steady-state domain a wide spectrum of clinical applications is supported with this technology ranging from diagnostic to guided interventions. Diffuse reflectance spectra provide a wealth of information about tissue composition; however, extracting biologically relevant information from the spectra in terms of chromophores may be more useful to gain acceptance into the clinical community. The chromophores that absorb light in the visible and near infrared wavelengths can provide information about tissue composition. The key characteristics of these chromophores and their relevance in different organs and clinical applications is the focus of this review, along with translating their use to the clinic.

  20. Comparison between Ultrasound and Pathologic Status of Axillary Lymph Nodes in Clinically Node-negative Breast Cancer Patients.

    PubMed

    Bailey, Amanda; Layne, Ginger; Shahan, Cimmie; Zhang, Jianjun; Wen, Siji; Radis, Sarah; Richmond, Bryan; Partin, Jessica; Hazard, Hannah

    2015-09-01

    Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative breast cancer patients. Ultrasound (US) has shown promise when used to assess axillary lymph nodes preoperatively, thus aiding surgical decision making. We examined the correlation between preoperative US and SLNB results to further clarify the role of US in clinicopathologic staging of breast cancer when the axilla is clinically negative on physical examination. Our institutional cancer registry was used to identify clinically node-negative patients diagnosed with breast cancer from January 1, 2009 to December 31, 2012. Variables including age, body mass index, date of surgery, date of diagnosis, US results, US-directed biopsy results, SLNB results, and final pathology were recorded. Incomplete charts were excluded. In all, 249 patients were included. Sensitivity/specificity of US in the clinically negative axilla were 7.4 per cent and 91.8 per cent, respectively. The false-positive rate was 80 per cent, whereas the negative predictive value was 78 per cent. The effect of time from diagnosis/US to SLNB, interpreting radiologist, year in which US was performed, and body mass index were not statistically significant. US in the clinically node-negative patient, although useful when it leads to a positive needle biopsy result, is unlikely to replace SLNB owing to its low sensitivity and a high false-positive rate. Further prospective study into the role of US in the evaluation of the clinically negative axilla is warranted.

  1. Epidemiological and Virological Characterization of Influenza B Virus Infections

    PubMed Central

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011–2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  2. Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti–Hepatitis C Virus Therapy in Patients With Advanced Liver Disease

    PubMed Central

    Kattakuzhy, Sarah; Wilson, Eleanor; Sidharthan, Sreetha; Sims, Zayani; McLaughlin, Mary; Price, Angie; Silk, Rachel; Gross, Chloe; Akoth, Elizabeth; McManus, Maryellen; Emmanuel, Benjamin; Shrivastava, Shikha; Tang, Lydia; Nelson, Amy; Teferi, Gebeyehu; Chavez, Jose; Lam, Brian; Mo, Hongmei; Osinusi, Anuoluwapo; Polis, Michael A.; Masur, Henry; Kohli, Anita; Kottilil, Shyamasundaran

    2016-01-01

    Background. Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8–24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis. Methods. Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged ≥18 years, had chronic HCV genotype 1 infection (serum HCV RNA ≥2000 IU/mL), and stage 3–4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay. Results. Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%–85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P = .51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen. Conclusions. Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy. Chinese Clinical Trials Registration. CT01805882. PMID:26503379

  3. Good Laboratory Practice (GLP) status of Asian countries and its implementation in non-clinical safety studies in pharmaceutical drug development.

    PubMed

    Sasaki, Madoka; Hinotsu, Shiro; Kawakami, Koji

    2009-10-01

    Non-clinical animal studies to assess the safety of compounds under development have to comply with Good Laboratory Practice (GLP). The Organization for Economic Co-operation and Development (OECD) has established the Mutual Acceptance of Data (MAD) system in OECD member countries for the mutual acceptance of non-clinical safety study data. Since 1997 non-OECD-member countries have also been able to participate in the MAD system, if the country meets the level of standardized compliance with OECD GLP. Thus, several Asian non-OECD countries are trying to develop their GLP standards in order to become official members of the MAD system. Pharmaceutical companies face significant expense in the drug-development process, including the cost of non-clinical safety studies; in response, companies in Asian countries are seeking to establish GLP facilities to provide cost-effective services for drug development. To assess the quality and cost of GLP performance in Asian countries, in this study we approached GLP facilities in a number of Asian countries to obtain price and quality information on a 'virtual compound' to be assessed in non-clinical safety studies. Also, the development status of GLP in Asian countries in terms of policy and infrastructure was analyzed. We found that, among Asian countries, India and Singapore may be candidates for participation in te MAD system in terms of their compliance with GLP, language, and costs. These findings will be beneficial to pharmaceutical companies planning GLP studies in Asian countries.

  4. A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas.

    PubMed

    Arita, Hideyuki; Yamasaki, Kai; Matsushita, Yuko; Nakamura, Taishi; Shimokawa, Asanao; Takami, Hirokazu; Tanaka, Shota; Mukasa, Akitake; Shirahata, Mitsuaki; Shimizu, Saki; Suzuki, Kaori; Saito, Kuniaki; Kobayashi, Keiichi; Higuchi, Fumi; Uzuka, Takeo; Otani, Ryohei; Tamura, Kaoru; Sumita, Kazutaka; Ohno, Makoto; Miyakita, Yasuji; Kagawa, Naoki; Hashimoto, Naoya; Hatae, Ryusuke; Yoshimoto, Koji; Shinojima, Naoki; Nakamura, Hideo; Kanemura, Yonehiro; Okita, Yoshiko; Kinoshita, Manabu; Ishibashi, Kenichi; Shofuda, Tomoko; Kodama, Yoshinori; Mori, Kanji; Tomogane, Yusuke; Fukai, Junya; Fujita, Koji; Terakawa, Yuzo; Tsuyuguchi, Naohiro; Moriuchi, Shusuke; Nonaka, Masahiro; Suzuki, Hiroyoshi; Shibuya, Makoto; Maehara, Taketoshi; Saito, Nobuhito; Nagane, Motoo; Kawahara, Nobutaka; Ueki, Keisuke; Yoshimine, Toshiki; Miyaoka, Etsuo; Nishikawa, Ryo; Komori, Takashi; Narita, Yoshitaka; Ichimura, Koichi

    2016-08-08

    The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients' treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P < 0.0001). To investigate the association between TERT mutations and MGMT methylation on survival of patients with GBM, samples from a combined cohort of 453 IDH-wild-type GBM cases treated with radiation and temozolomide were analyzed. A multivariate Cox regression model revealed that the interaction between TERT and MGMT was significant for OS (P = 0.0064). Compared with TERT mutant-MGMT unmethylated GBMs, the hazard ratio (HR) for OS incorporating the interaction was the lowest in the TERT mutant-MGMT methylated GBM (HR, 0.266), followed by the TERT wild-type-MGMT methylated (HR, 0.317) and the TERT wild-type-MGMT unmethylated GBMs (HR, 0.542). Thus, patients with TERT mutant-MGMT unmethylated GBM have the poorest prognosis. Our findings suggest that a combination of IDH, TERT, and MGMT refines the classification of grade II-IV diffuse gliomas.

  5. Comparison of clinical and radiographic status around immediately loaded versus conventional loaded implants placed in patients with type 2 diabetes: 12- and 24-month follow-up results.

    PubMed

    Al Amri, M D; Alfarraj Aldosari, A M; Al-Johany, S S; Al Baker, A M; Al Rifaiy, M Q; Al-Kheraif, A A

    2017-03-01

    There are no studies that have compared the clinical and radiographic status around immediately loaded (IL) and conventional loaded (CL) implants placed in patients with type 2 diabetes mellitus (T2DM). The aim was to compare the clinical and radiographic status around IL and CL implants placed in T2DM patients. One hundred and eight diabetic patients [55 with IL implants (Group 1) and 53 with CL implants (Group 2)] were included in this cross-sectional study. All implants were placed in healed sites in the maxillary and mandibular premolar and molar regions and supported single restorations. All patients underwent full mouth mechanical debridement biannually. Haemoglobin A1c (HbA1c) levels, clinical [bleeding on probing (BOP) and probing depth (PD) ≥ 4 mm] and radiographic [crestal bone loss (CBL)] peri-implant parameters were measured for both groups at 12- and 24-month follow-up. Group comparisons were performed using the Mann-Whitney U-test (P < 0·05). The mean age and duration of T2DM in groups 1 and 2 were 50·6 ± 2·2 and 51·8 ± 1·7 years, and 9·2 ± 2·4 and 8·5 ± 0·4 years, respectively. At 12- and 24-month follow-up, the mean HbA1c levels in groups 1 and 2 were 5·4% (4·8-5·5%) and 5·1% (4·7-5·4%) and 5·1% (4·7-5·2%) and 4·9% (4·5-5·2%), respectively. At 12- and 24-month follow-up, there was no statistically significant difference in peri-implant BOP, PD and CBL in both groups. It was concluded that clinical and radiographic status is comparable around IL and CL implants placed in patients with T2DM. The contribution of careful case selection, oral hygiene maintenance and glycaemic control is emphasised.

  6. The Effect of Photodynamic Therapy and Diode Laser as Adjunctive Periodontal Therapy on the Inflammatory Mediators Levels in Gingival Crevicular Fluid and Clinical Periodontal Status

    PubMed Central

    Teymouri, Faraz; Farhad, Shirin Zahra; Golestaneh, Hedayatollah

    2016-01-01

    Statement of the Problem The presence of bacterial biofilms is the major cause of gingivitis and periodontitis, their mechanical removal is not often enough. Therefore, laser therapy and photodynamic therapy can be effective as adjunctive treatment. Purpose This study aimed to evaluate the impact of these treatments on the level of gingival crevicular fluid (GCF), inflammatory mediators, and periodontal clinical status. Materials and Method In this clinical trial, three quadrants were studied in 12 patients with chronic periodontitis aged 30-60 years. The clinical parameters were recorded and GCF samples were taken. After the first phase of periodontal treatment, one of the three quadrants was determined as the control group, one was treated by diode laser, and one underwent photodynamic therapy. The clinical parameters were recorded 2 and 6 weeks later. The data were statistically analyzed by using Friedman, ANOVA, and LSD post-test. Results Significant reduction was observed over time in the level of Interleukin-1β (IL-1β), Interleukin-17 (IL-17), clinical attachment loss, and pocket depth in the three treatment groups (p< 0.000). The three treatment methods significantly reduced the IL-1β and IL-17 at the baseline, up to 2 weeks, and 2-6 weeks (p< 0.05). Diode laser and photodynamic therapy significantly decreased the average bleeding on probing over time (p< 0.000 and p< 0.002, respectively). Conclusion Laser and photodynamic therapy reduced the inflammatory mediators (IL-1β and IL-17) and improved the clinical symptoms. PMID:27602399

  7. Role of MRD status in relation to clinical outcomes in newly diagnosed multiple myeloma patients: a meta-analysis.

    PubMed

    Landgren, O; Devlin, S; Boulad, M; Mailankody, S

    2016-12-01

    Driven by access to better drugs, on average, newly diagnosed multiple myeloma patients have over 10 years overall survival. Using modern combination therapies-with or without the addition of high-dose melphalan and autologous stem cell transplantation-up to 80% of patients reach a complete response. As a logical and necessary step forward, clinical studies have explored strategies to detect minimal residual disease (MRD) and its correlation with clinical outcomes. In this context, MRD has been proposed as a regulatory end point for drug approval in newly diagnosed multiple myeloma. To better define the role of MRD negativity in relation to clinical outcomes, we undertook a meta-analysis including published clinical trials of newly diagnosed multiple myeloma patients. We applied a random effects model which weighted studies using the inverse-variance method. Studies were combined on the scale of the logarithm of the hazard ratio (HR) and the corresponding s.d. We found that MRD negativity (versus positivity) was associated with better PFS (HR=0.35; 95% confidence interval (CI) 0.27-0.46; P<0.001) and overall survival (HR=0.48; 95% CI 0.33-0.70; P<0.001). Our results show that MRD negativity is a strong predictor of clinical outcomes, supportive of MRD becoming a regulatory end point for drug approval in newly diagnosed multiple myeloma.

  8. An update on HDV: virology, pathogenesis and treatment.

    PubMed

    Alvarado-Mora, Mónica V; Locarnini, Stephen; Rizzetto, Mario; Pinho, João R Rebello

    2013-01-01

    Hepatitis delta is an inflammatory liver disease caused by infection with HDV. HDV is a single-stranded circular RNA pathogen with a diameter of 36 nm. HDV is classified in the genus Deltavirus and is still awaiting a final taxonomic classification up to the family level. HDV shares similarities with satellite RNA and viroids including a small circular single-stranded RNA with secondary structure that replicates through the 'double rolling circle' mechanism. The HDV RNA genome is capable of self-cleavage through a ribozyme and encodes only one structural protein, the hepatitis delta antigen (HDAg), from the antigenomic RNA. There are two forms of HDAg, a shorter (S; 22 kDa) and a longer (L; 24 kDa) form, the latter generated from an RNA editing mechanism. The S form is essential for viral genomic replication. The L form participates in the assembly and formation of HDV. For complete replication and transmission, HDV requires the hepatitis B surface antigen (HBsAg). Thus, HDV infection only occurs in HBsAg-positive individuals, either as acute coinfection in treatment-naive HBV-infected persons, or as superinfection in patients with pre-existing chronic hepatitis B (CHB). HDV is found throughout the world, but its prevalence, incidence, clinical features and epidemiological characteristics vary by geographic region. There are eight genotypes (1 to 8) distributed over different geographic areas: HDV-1 is distributed worldwide, whereas HDV-2 to 8 are seen more regionally. Levels of HDV viraemia change over the course of HDV infection, being significantly higher in patients with early chronic hepatitis than in cirrhosis. Chronic HDV infection leads to more severe liver disease than chronic HBV monoinfection with an accelerated course of fibrosis progression, an increased risk of hepatocellular carcinoma and early decompensation in the setting of established cirrhosis. Current treatments include pegylated interferon-α and liver transplantation; the latter of which can

  9. Current status of matrix-assisted laser desorption ionisation-time of flight mass spectrometry in the clinical microbiology laboratory.

    PubMed

    Kok, Jen; Chen, Sharon C A; Dwyer, Dominic E; Iredell, Jonathan R

    2013-01-01

    The integration of matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) into many clinical microbiology laboratories has revolutionised routine pathogen identification. MALDI-TOF MS complements and has good potential to replace existing phenotypic identification methods. Results are available in a more clinically relevant timeframe, particularly in bacteraemic septic shock. Novel applications include strain typing and the detection of antimicrobial resistance, but these are not widely used. This review discusses the technical aspects, current applications, and limitations of MALDI-TOF MS.

  10. Repeated HIV-1 resistance genotyping external quality assessments improve virology laboratory performance.

    PubMed

    Descamps, Diane; Delaugerre, Constance; Masquelier, Bernard; Ruffault, Annick; Marcelin, Anne-Geneviève; Izopet, Jacques; Chaix, Marie-Laure; Calvez, Vincent; Brun-Vézinet, Françoise; Costagliola, Dominique

    2006-02-01

    The performance of French virology laboratories belonging to the ANRS network has been assessed annually for 3 years. The performance of these laboratories was compared between the years 2002 and 2003. Ten and 7 coded samples were sent to 38 virology laboratories in 2002 and 45 virology laboratories in 2003, respectively. Each panel of coded samples included at least one HIV-negative control, a pair of duplicate specimens, samples with a wide range of viral loads, and samples with a large number of resistance mutations. The laboratories used their standard sequencing procedures and were asked to report the amino acids at codons associated with resistance mutations, based on the IAS-USA expert panel list. The reference amino acid sequences were defined as those most frequently reported by the participants. The specificity of detection of RT mutations was significantly better in 2003 (99.9%) than in 2002 (99.7%) (P = 0.05). There was no difference between 2002 and 2003 in the specificity of detection of protease mutations (99.6% and 99.8%) or the sensitivity of detection of RT mutations (98.8% and 98.2%). The sensitivity of detection of protease mutations improved significantly between 2002 and 2003 (97.6% and 99.0%, respectively; P = 0.037). The proportion of laboratories reporting fully accurate results, in terms of amplification, specificity, sensitivity, and reproducibility, tended to increase between 2002 and 2003 (P = 0.077). No errors were made by 19% of laboratories in 2002, compared to 42% in 2003. These results show the value of repeated external quality assessments.

  11. The response of medical virology laboratories to the influenza A(H1N1)pdm09 outbreak in Paris Île-de-France region.

    PubMed

    Seringe, E; Agut, H

    2013-10-01

    The outbreak of influenza A(H1N1)pdm09 was a challenge for the laboratories of Paris Île-de-France region in charge of virological diagnosis. In order to evaluate the quality of their response to this challenge, a retrospective survey based on a self-administered standardized questionnaire was undertaken among the 18 hospital laboratories involved in A(H1N1)pdm09 virus detection over a period of 10 months from April 2009 to January 2010. All concerned laboratories responded to the survey. Due to imposed initial biosafety constraints and indications, virological diagnosis was performed in only two laboratories at the start of the studied period. Step by step, it was further settled in the other laboratories starting from June to November 2009. From the beginning, A(H1N1)pdm09-specific RT-PCR was considered the reference method while the use of rapid influenza detection tests remained temporary and concerned a minority of these laboratories. Among the overall 21,656 specimens received, a positive diagnosis of influenza A(H1N1)pdm09 was obtained in 5,390 cases (25%), the positivity range being significantly higher among women as compared to men (P<0.0001) and subjects below 45 years of age as compared to those over 65 years (P<0.0001). Two peaks in positivity frequency were observed at weeks 24 (30%, 8-12 June 2009) and 44 (50%, 26-30 October 2009) respectively, the latter one occurring 2 weeks earlier than the peak of epidemic at the national level. In contrast, a low positivity rate was detected at weeks 38-40 in relationship with other respiratory virus infections which were clinically misinterpreted as a peak of influenza epidemic. These data demonstrate the ability of medical virology laboratories of Paris Île-de-France region to provide in real time a valuable diagnosis of A(H1N1)pdm09 virus infection and a relevant view of outbreak evolution, suggesting they will be a crucial component in the management of future influenza epidemics.

  12. Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

    PubMed Central

    Limsreng, Setha; Him, Sovanvatey; Nouhin, Janin; Hak, Chanroeurn; Srun, Chanvatey; Viretto, Gerald; Ouk, Vara; Delfraissy, Jean Francois; Ségéral, Olivier

    2014-01-01

    Introduction In resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. Methods This retrospective study, conducted in 2010–2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. Results On a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30–194) and 279 cells/mm3 (IQR: 103–455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6–18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations. Conclusion In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for

  13. Detection and analysis of nanoparticles in patients: A critical review of the status quo of clinical nanotoxicology.

    PubMed

    Bitounis, Dimitrios; Pourchez, Jérémie; Forest, Valérie; Boudard, Delphine; Cottier, Michèle; Klein, Jean-Philippe

    2016-01-01

    On the cusp of massive commercialization of nanotechnology-enhanced products and services, the physical and chemical analysis of nanoparticles in human specimens merits immediate attention from the research community as a prerequisite for a confident clinical interpretation of their occurrence in the human organism. In this review, we describe the caveats in current practices of extracting and isolating nanoparticles from clinical samples and show that they do not help truly define the clinical significance of detected exogenous nano-sized objects. Finally, we suggest a systematic way of tackling these demanding scientific tasks. More specifically, a precise and true qualitative evaluation of nanoparticles in human biological samples is still hindered by various technical reasons. Such a procedure is more refined when the nature of the pollutants is known, like in the case of nano-sized wear debris originating from biomedical prostheses. Nevertheless, nearly all available analytical methods provide unknown quantitative accuracy and qualitative precision due to the challenging physical and chemical nature of nanoparticles. Without trustworthy information to describe the nanoparticulate load of clinical samples, it is impossible to accurately assess its pathological impact on isolated cases or allow for relevant epidemiological surveys on large populations. Therefore, we suggest that the many and various specimens stored in hospitals be used for the refinement of methods of exhaustive quantitative and qualitative characterization of prominent nanoparticles in complex human milieu.

  14. The Effects of Plasmodium vivax Gestational Malaria on the Clinical and Immune Status of Pregnant Women in Northwestern Colombia

    PubMed Central

    Perkins, Douglas Jay; Corredor, Mauricio; Yanow, Stephanie; Carmona-Fonseca, Jaime; Maestre, Amanda

    2013-01-01

    Objetive: The study explored the effects of Plasmodium vivax infection on the balance of pro- versus anti- inflammatory cytokines and chemokines and their relationship with some clinical and epidemiology outcomes. Methods: Thirty-five pregnant women were recruited. Of these, 15 subjects had malaria at delivery (GM+), and 20 had no exposition to infection throughout the pregnancy (GM-) and at delivery. Epidemiological and clinical data were recorded after reviewing the clinical records. At delivery, whole blood from the mother as well as placental tissue was collected. Diagnosis of infection was performed by thick smear and a polymerase chain reaction (PCR). Expression of pro-inflammatory and anti-inflammatory cytokines and chemokines was measured by a real time PCR. Results: The clinical and epidemiological variables explored were similar in both groups, with the exception of gestational age. When comparing the GM+ group with the GM- group, it is clear that although the differences generally are not significant, pro- inflammatory cytokines are elevated in both maternal blood and placental; anti-inflammatory ones are elevated in the mother and reduced in the placenta, and the chemokines are reduced in both compartments, except for MCP-1 which is elevated in all. Conclusion: The results appear to be strongly affected by the small number of women with GM by P. vivax at childbirth. Additional studies are needed with larger groups in this and other regions of the country PMID:24892615

  15. Impact of environmental chemicals, sociodemographic variables, depression, and clinical indicators of health and nutrition on self-reported health status

    EPA Science Inventory

    Public health researchers ideally integrate social, environmental, and clinical measures to identify predictors of poor health. Chemicals measured in human tissues are often evaluated in relation to intangible or rare health outcomes, or are studied one chemical at a time. Using ...

  16. [A virological description of serous meningitis in children immunized with vaccine against epidemic parotitis].

    PubMed

    Goleva, O V; Kharit, S M; Cherniaeva, T V; Aksenov, O A; Davidkin, I; Kolyshkin, V M

    2004-01-01

    The morbidity structure was analyzed in children vaccinated against epidemic parotitis in 1993-2002. Eight children (4 with serous meningitis and 4 with lesions of the salivary glands) underwent virologic and immunologic examinations. The molecular typing of the SH-gene fragment of the parotitis virus showed the process in 7 cases to be provoked by the vaccination strain. Presumedly, progressing vaccine-associated meningitis inhibits antibody formation. The total incidence of vaccine-associated meningitis was shown, according to Saint Petersburg data, to be not high, which testifies to a low reactogenicity of the Russian vaccine strain.

  17. 2013 Pharmacology Risk SRP Status Review Comments to Chief Scientist. The Risk of Clinically Relevant Unpredicted Effects of Medication

    NASA Technical Reports Server (NTRS)

    2014-01-01

    On December 5, 2013, the Pharmacology Risk SRP, participants from the JSC, HQ, the NSBRI, and NRESS participated in a WebEx/teleconference. The purpose of the call (as stated in the Statement of Task) was to allow the SRP members to: 1. Receive an update by the HRP Chief Scientist or Deputy Chief Scientist on the status of NASA's current and future exploration plans and the impact these will have on the HRP. 2. Receive an update on any changes within the HRP since the 2012 SRP meeting. 3. Receive an update by the Element or Project Scientist(s) on progress since the 2012 SRP meeting. 4. Participate in a discussion with the HRP Chief Scientist, Deputy Chief Scientist, and the Element regarding possible topics to be addressed at the next SRP meeting.

  18. Day-night variations in thyroid stimulating hormone and its relation with clinical status and metabolic parameters in patients with cirrhosis of the liver.

    PubMed

    Atalay, Roni; Ersoy, Reyhan; Demirezer, Aylin Bolat; Akın, Fatma Ebru; Polat, Sefika Burcak; Cakir, Bekir; Ersoy, Osman

    2015-04-01

    To investigate day-night variations in thyroid stimulating hormone (TSH) and its relation with clinical status and metabolic parameters in patients with cirrhosis. Forty-one patients with negative thyroid antibodies and normal thyroid function tests who were diagnosed with cirrhosis were included. Thirty-five age- and gender-matched healthy subjects were included in control group.TSH, fT3, and fT4 levels, which were measured both in the morning and late evening. The difference between nocturnal TSH and morning TSH (ΔTSH) were compared between groups. Relation between Child-Turcotte-Pugh, model for End-Stage Liver Disease (MELD) and MELD-Na scores and levels of thyroid hormones, ΔTSH and serum sodium (Na) levels was investigated. Relation between ΔTSH and clinical status and metabolic parameters was also evaluated. The mean morning fT3, nocturnal fT3, nocturnal TSH, and ΔTSH levels were significantly lower, morning and nocturnal fT4 levels were higher in patients with cirrhosis (p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001). As the ROC analysis, day-night variation was detected to be impaired in the event that difference between nocturnal TSH level and morning TSH level was lower than 1 uIU/mL in patients with cirrhosis with a sensitivity of 92.7% and specificity of 71.4% (p<0.001).A significant positive correlation was found between serum Na levels and fT3 in patients with cirrhosis (r=0.479, p=0.001), and a significant negative correlation was found between the severity of clinical status and low levels of fT3 in patients with cirrhosis (p<0.001).Nocturnal TSH increase does not occur in cases of cirrhosis without known thyroid disease and with normal thyroid function tests, which may be an early finding of impaired thyroid functions in patients with cirrhosis.

  19. [Comparison of human papilloma virus infection status between men who have sex with men recruited from gay bathhouses and HIV voluntary counseling and testing clinics respectively in Urumqi].