Science.gov

Sample records for clinical status virologic

  1. Ciliocytophthoria in clinical virology.

    PubMed

    Hadziyannis, E; Yen-Lieberman, B; Hall, G; Procop, G W

    2000-08-01

    Direct immunofluorescence assays (DFAs) are used in the clinical virology laboratory for the rapid detection of viruses. An assessment of the cellularity of specimens submitted for DFA is necessary for the most effective use of this assay. This assessment ensures that an adequate number of the appropriate cells are present for examination. During this assessment, clinical virologists may encounter unfamiliar cellular elements or cellular fragments. One of these elements, ciliocytophthoria, has been misinterpreted as a parasite in specimens submitted for cytologic testing. We describe a similar case in which a technologist thought that ciliocytophthoria possibly represented a ciliated parasite in a nasopharyngeal specimen sent for respiratory syncytial virus DFA. After a thorough morphologic examination, the staff dismissed the possibility of a ciliated parasite. We confirmed this entity as ciliocytophthoria using morphologic criteria and the Diff-Quik stain. This near misidentification of ciliocytophthoria as a ciliated parasite affords us the opportunity to raise the awareness of clinical virologists about ciliocytophthoria. Additionally, we briefly review useful features for differentiating ciliocytophthoria from the only ciliate parasitic for humans, Balantidium coli. Finally, we present the utility of a commonly used cytologic stain, the Diff-Quik stain, for the confirmation of ciliocytophthoria.

  2. Ciliocytophthoria in clinical virology.

    PubMed

    Hadziyannis, E; Yen-Lieberman, B; Hall, G; Procop, G W

    2000-08-01

    Direct immunofluorescence assays (DFAs) are used in the clinical virology laboratory for the rapid detection of viruses. An assessment of the cellularity of specimens submitted for DFA is necessary for the most effective use of this assay. This assessment ensures that an adequate number of the appropriate cells are present for examination. During this assessment, clinical virologists may encounter unfamiliar cellular elements or cellular fragments. One of these elements, ciliocytophthoria, has been misinterpreted as a parasite in specimens submitted for cytologic testing. We describe a similar case in which a technologist thought that ciliocytophthoria possibly represented a ciliated parasite in a nasopharyngeal specimen sent for respiratory syncytial virus DFA. After a thorough morphologic examination, the staff dismissed the possibility of a ciliated parasite. We confirmed this entity as ciliocytophthoria using morphologic criteria and the Diff-Quik stain. This near misidentification of ciliocytophthoria as a ciliated parasite affords us the opportunity to raise the awareness of clinical virologists about ciliocytophthoria. Additionally, we briefly review useful features for differentiating ciliocytophthoria from the only ciliate parasitic for humans, Balantidium coli. Finally, we present the utility of a commonly used cytologic stain, the Diff-Quik stain, for the confirmation of ciliocytophthoria. PMID:10923088

  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. 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.

  6. 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.

  7. 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.

  8. 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. PMID:21140798

  9. Clinical Outcome of HIV-Infected Patients with Discordant Virological and Immunological Response to Antiretroviral Therapy

    PubMed Central

    Zoufaly, A.; an der Heiden, M.; Kollan, C.; Bogner, J. R.; Fätkenheuer, G.; Wasmuth, J. C.; Stoll, M.; Hamouda, O.

    2011-01-01

    Background. A subgroup of human immunodeficiency virus type 1 (HIV-1)–infected patients with severe immunodeficiency show persistently low CD4+ cell counts despite sustained viral suppression. It is unclear whether this immuno-virological discordance translates into an increased risk for clinical events. Methods. Data analysis from a large multicenter cohort incorporating 14,433 HIV-1–infected patients in Germany. Treatment-naive patients beginning antiretroviral therapy (ART) with CD4+ cell counts <200 cells/μL who achieved complete and sustained viral suppression <50 copies/mL (n = 1318) were stratified according to the duration of immuno-virological discordance (failure to achieve a CD4+ cell count ≥200 cells/μL). Groups were compared by descriptive and Poisson statistics. The time-varying discordance status was analyzed in a multivariable Cox model. Results. During a total of 5038 person years of follow-up, 42 new AIDS events occurred. The incidence rate of new AIDS events was highest in the initial 6 months of complete viral suppression (immuno-virological discordance group, 55.06; 95% confidence interval [CI], 30.82–90.82; and immune responder group, 24.54; 95% CI, 10.59–48.35) and decreased significantly by 65% per year in patients with immuno-virological discordance (incidence risk ratio, 0.35; 95% CI, 0.14–0.92; P = .03). Immuno-virological discordance and prior AIDS diagnosis were independently associated with new AIDS events (hazard ratio, 3.10; 95% CI, 1.09–8.82; P = .03). Conclusion. Compared with immune responders, patients with immuno-virological discordance seem to remain at increased risk for AIDS. Absolute risk is greatly reduced after the first 6 months of complete viral suppression. PMID:21208929

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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;…

  16. Virological and clinical characterizations of respiratory infections in hospitalized children

    PubMed Central

    2013-01-01

    Background The purpose of this study was to determine the incidence and seasonal distribution of viral etiological agents and to compare their clinical manifestations and disease severity, including single and co infections. Methods Multiplex reverse-transcription PCR was performed for the detection of viruses in nasopharyngeal aspirat. Disease severity was grouped using a categorization index as very mild/mild, and moderate/severe. Clinical and laboratory characteristics of hospitalized children with viral respiratory tract infection were analyzed. Results Viral pathogens were detected in 103/155 (66.5%) of patients. In order of frequency, identified pathogens were respiratory syncytial virus (32.0%), adenovirus (26.2%), parainfluenza viruses type 1–4 (19.4%), rhinovirus (18.4%), influenza A and B (12.6%), human metapneumovirus (12.6%), coronavirus (2.9%), and bocavirus (0.9%). Coinfections were present in 21 samples. Most of the children had very mild (38.8%) and mild disease (37.9%). Severity of illness was not worse with coinfections. The most common discharge diagnoses were "URTI" with or without LRTI/asthma (n=58). Most viruses exhibited strong seasonal patterns. Leukocytosis (22.2%) and neutrophilia (36.6%) were most commonly detected in patients with adenovirus and rhinovirus (p<0.05). Monocytosis was the most remarkable finding in the patients (n=48, 53.3%), especially in patients with adenovirus (p<0.05). Conclusions RSV and RhV were associated with higher severity of illness in hospitalized children. RSV found to account for half of LRTI hospitalizations. In AdV and FluA and B infections, fever lasted longer than in other viruses. Coinfections were detected in 21 of the patients. The presence of coinfections was not associated with increased disease severity. PMID:23536956

  17. 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.

  18. 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

  19. 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.

  20. Clinical observations of virologically confirmed dengue fever in the 1987 outbreak in southern Taiwan.

    PubMed

    Liu, H W; Ho, T L; Hwang, C S; Liao, Y H

    1989-01-01

    Fifty-nine virologically confirmed cases of dengue fever were clinically studied during the 1987 outbreak in southern Taiwan. Viral isolation and serologic studies indicated that type 1 dengue was the cause. Dengue fever has not been on the island of Taiwan for 42 years and nearly all the population under 42 years of age is susceptible. Most patients under age 42 experience primary infection while those over 42 years old experience secondary infection. The majority of 59 cases studied were females in the 21-30-year age group. Classic signs and symptoms ere fever, headache, muscle pain, joint pain, nausea and vomiting, and skin rash. Approximately 80% of the patients had leukopenia (less than 5,000/mm3) and thrombocytopenia (less than 50,000/mm3) and 90% experienced mild to moderate elevation of serum glutamic oxaloacetic transaminase. Hemorrhagic manifestations occurred in 25.4% of patients. No patients under observation in this study developed hypotension or died.

  1. Comparison of adherence monitoring tools and correlation to virologic failure in a pediatric HIV clinical trial.

    PubMed

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

    2014-06-01

    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 log(10)copies/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

  2. 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. PMID:27681154

  3. 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.

  4. 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

  5. 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.

  6. Virologic response and haematologic toxicity of boceprevir- and telaprevir-containing regimens in actual clinical settings

    PubMed Central

    Butt, A. A.; Yan, P.; Shaikh, O. S.; Freiberg, M. S.; Re, V. Lo; Justice, A. C.; Sherman, K. E.

    2016-01-01

    SUMMARY Effectiveness, safety and tolerability of boceprevir (BOC) and telaprevir (TPV) in actual clinical settings remain unknown. We determined rates of sustained virologic response (SVR) and haematologic adverse effects among persons treated with BOC- or TPV-containing regimens, compared with pegylated interferon/ribavirin (PEG/RBV). Using an established cohort of hepatitis C virus (HCV)-infected persons, Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), we identified those treated with a BOC- or TPV-containing regimen and HCV genotype 1-infected controls treated with PEG/RBV. We excluded those with HIV co-infection and missing HCV RNA values to determine SVR. Primary endpoints were SVR (undetectable HCV RNA ≥12 weeks after treatment completion) and haematologic toxicity (grade 3/4 anaemia, neutropenia and thrombocytopenia). We evaluated 2288 persons on BOC-, 409 on TPV-containing regimen and 6308 on PEG/RBV. Among these groups, respectively, 31%, 43% and 9% were treatment-experienced; 17%, 37% and 14% had baseline cirrhosis; 63%, 54% and 48% were genotype 1a. SVR rates among noncirrhotics were as follows: treatment naïve: 65% (BOC), 67% (TPV) and 31% (PEG/RBV); treatment experienced: 57% (BOC), 54% (TPV) and 13% (PEG/RBV); (P-value not significant for BOC vs TPV; P < 0.0001 for BOC or TPV vs PEG/RBV). Haematologic toxicities among BOC-, TPV- and PEG/RBV-treated groups were as follows: grade 3/4 anaemia 7%, 11% and 3%; grade 4 thrombocytopenia 2.2%, 5.4% and 1.7%; grade 4 neutropenia 8.2%, 5.6% and 3.4%. SVR rates are higher and closer to those reported in pivotal clinical trials among BOC- and TPV-treated persons compared with PEG/RBV-treated persons. Haematologic adverse events are frequent, but severe toxicity is uncommon. PMID:25524834

  7. Clinical observations on virologically confirmed fatal dengue infections in Jakarta, Indonesia.

    PubMed

    Sumarmo; Wulur, H; Jahja, E; Gubler, D J; Suharyono, W; Sorensen, K

    1983-01-01

    Thirty virologically confirmed cases of dengue infection with a fatal outcome were studied clinically in Jakarta, Indonesia, from 1975 to 1978. All 4 dengue virus serotypes were isolated from fatal cases, but dengue type 3 was responsible for 21 (70%) of these isolates, compared to only 47% of isolates from all cases of dengue infection. The majority (60%) of these 30 cases were males in the 5-9-year age group. Nonspecific signs and symptoms in the fatal cases were no different from those in patients who survived dengue infection, but 70% of the patients with fatal outcome had one or more signs of encephalitis, primarily convulsions and somnolence; 3 of them developed spastic tetraparesis before death and 2 died of an illness clinically compatible with viral encephalitis. Other unexpected observations were that only 63% of the patients had classical dengue shock syndrome with haemoconcentration, thrombocytopenia and shock. A high percentage (80%) had gastrointestinal haemorrhage, and in 9 patients (30%) this was severe enough to cause shock and death. In these 9 cases, the gastrointestinal haemorrhage and haematemesis began before the onset of shock and there was no evidence of haemoconcentration or pleural effusion at any time during hospitalization. According to certain widely accepted criteria, these patients would not be diagnosed as dengue haemorrhagic fever (DHF). But as they made up nearly one-third of the confirmed fatal dengue infections in this study and had massive gastrointestinal haemorrhages with thrombocytopenia, the definition of DHF should be changed to include this type of patient. It is proposed that the disease should be more realistically classified as dengue fever with or without haemorrhage and dengue shock syndrome.

  8. Some clinical and epidemiological observations on virologically confirmed dengue hemorrhagic fever.

    PubMed

    Samsi, T K; Wulur, H; Sugianto, D; Bartz, C R; Tan, R; Sie, A

    1990-01-01

    This study is a part of a one year prospective study on dengue hemorrhagic fever (DHF) carried out in the Department of Pediatrics, Sumber Waras Hospital in West Jakarta. Viral isolation and serologic analysis for DHF were done by Namru-2 in Jakarta. The subjects were 151 virologically confirmed DHF Patients admitted to the Department of Pediatrics during the period of September 1987-June 1988, consisting of 82 boys and 69 girls of 6 months-15 years old. The predominant age group was 5 to 9 years, representing 49.7% subjects. Dengue virus was isolated from sera during the first 8 days of illness and in 139 (42.1%) during the first 5 days of illness. Dengue virus type 1, 2, 3 and 4 were isolated from 16.6%, 13.2%, 69.5% and 0.7% subjects, respectively. The clinical manifestations revealed no striking differences between dengue 3 and others except for thrombocytopenia and shock. High fever, hemoconcentration and thrombocytopenia on admission was observed in 30.5%, 8.6% and 8.6% of subjects, respectively. Dengue shock syndrome (DSS) were observed in 23 (15.2%) with 3 (2%) fatal cases. Dengue virus serotype 3 was observed in 20 out of 23 DSS cases (86.9%) and all fatal cases were associated with dengue type 2. This study revealed that dengue 3 is the predominant virus circulating during recent epidemics and is associated with more severe clinical manifestation and with a higher incidence rate of living area.

  9. 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

  10. Clinical course of partial virological responders under prolonged entecavir monotherapy in patients with chronic hepatitis B.

    PubMed

    Park, Joo Han; Ahn, Seon Joo; Cho, Hyo Jung; Kim, Soon Sun; Cheong, Jae Youn; Cho, Sung Won

    2016-02-01

    Studies about long-term entecavir (ETV) therapy for partial virological response (PVR) are lacking. This study aimed to assess the clinical course of PVR patients receiving ETV therapy and analyze the efficacy of tenofovir (TDF). We retrospectively evaluated 130 patients who showed a PVR to ETV. Among these patients, 102 were nucleot(s)ide analogue (NUC)-naïve and 28 were lamivudine (LAM)-experienced. The cumulative rates of VR were 54.1%, 70.8%, and 83.7% for the NUC-naïve group and 37.0%, 42.8%, and 42.8% for the LAM-experienced group after 24, 36, and 48 months of ETV therapy, respectively (P  = 0.008). Low HBV DNA level at 12 months (P < 0.001) and absence of a LAM treatment history (P  = 0.031) were significant associated factors for VR. In VR prediction at 36 months of ETV therapy in NUC-naïve patients, HBV DNA level <95 IU/ml at 12 months showed a 92.9% sensitivity and a 78.3% specificity (AUROC, 0.909; P < 0.001). ETV resistance did not develop in NUC-naïve patients with HBV DNA levels <95 IU/ml at 12 months. The cumulative probability of VR in patients who switched to or additionally received TDF was 91.3% at 15 months. Prolonged ETV therapy induced a VR without the risk of ETV resistance in NUC-naïve patients with HBV DNA levels <95 IU/ml at 12 months. All patients with LAM-experienced or NUC-naïve with HBV DNA levels ≥95 IU/ml at 12 months should be switched to TDF rescue therapy.

  11. Clinical and Virological Responses to Clevudine Therapy of Hepatocelluar Carcinoma Patients with Chronic Hepatitis B

    PubMed Central

    Woo, Sang Myung; Lee, Woo Jin; Kim, Chang-Min

    2011-01-01

    Background/Aims The clinical effects of clevudine have been reported in patients with chronic hepatitis B virus infections (CHIs). In this investigation, we assessed whether clevudine induced biochemical and virological improvements in hepatocellular carcinoma (HCC) patients with CHI. Methods Fifty-four patients who received 30 mg clevudine for more than 24 weeks between 2007 and 2009 at the National Cancer Center Hospital, Korea, were enrolled. Among these cases, 39 had HCC (CHI/HCC group) and 15 did not (CHI group). Results In relation to the CHI group, the CHI/HCC group was older (55.5 years.) and had a higher liver cirrhosis rate (79.5%) (p<0.05). Median changes in serum hepatitis B virus (HBV) DNA levels from baseline at weeks 12, 24, and 36 of treatment in the CHI/HCC group were not significantly different from those of the CHI group (-2.3, -2.7, -2.6 vs -1.7, -1.8, -2.4, respectively). HBV DNA <2,000 copies/mL was achieved in 76.5% of the CHI/HCC group at 24 weeks. Rates of ALT normalization in the CHI/HCC and CHI groups were 62.5% and 66.7%, respectively (p>0.05). Liver function was preserved with clevudine treatment in patients displaying response or stable disease under anti-cancer therapy. Four patients (7.4%) developed viral resistance during clevudine therapy. Among these, one was naïve, and three had previously received antiviral therapy. One CHI/HCC patient (1.9%) discontinued clevudine treatment due to symptomatic myopathy. Conclusions Our findings clearly indicate that clevudine has comparable antiviral and biochemical effects in patients with CHI and with CHI/HCC and preserves the underlying liver function in HBV-related HCC patients. PMID:21461078

  12. Clinical & virological study of dengue fever outbreak in Jalore city, Rajasthan 1985.

    PubMed

    Chouhan, G S; Rodrigues, F M; Shaikh, B H; Ilkal, M A; Khangaro, S S; Mathur, K N; Joshi, K R; Vaidhye, N K

    1990-11-01

    An epidemic of acute febrile illness caused by dengue virus occurred in Jalore town, in south-west Rajasthan, in April and May, 1985. Most patients had classical signs and symptoms of dengue fever or had only a mild atypical febrile illness. A few patients had in addition haemorrhagic manifestations/shock or encephalitis. Virological studies (carried out by the National Institute of Virology, Pune) showed that dengue type 3 virus was the main etiological agent. This is the first reported outbreak of dengue in the arid zone in western Rajasthan, that occurred in summer (April-May) in contrast to other parts of India, where such outbreaks are commonly reported after the rains (between August and November).

  13. 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

  14. Clinical and virological outcome of an infection with the Belgian equine arteritis virus strain 08P178.

    PubMed

    Vairo, Sabrina; Vandekerckhove, Annelies; Steukers, Lennert; Glorieux, Sarah; Van den Broeck, Wim; Nauwynck, Hans

    2012-06-15

    Equine viral arteritis (EVA) is an infectious disease with variable clinical outcome. Outbreaks, causing important economic losses, are becoming more frequent. Currently, there is a shortage of pathogenesis studies performed with European strains. In the present study, eight seronegative ponies were experimentally inoculated with the Belgian strain of equine arteritis virus (EAV) 08P178 (EU-1 clade) and monitored daily for clinical signs of EVA. Nasopharyngeal swabs, ocular swabs, bronchoalveolar cells and blood were collected for virological and serological testing. Two ponies were euthanized at 3, 7, 14, and 28 days post infection (DPI). After necropsy, specimens were collected for virus titration and immunofluorescence. EVA symptoms such as fever and lymphadenomegaly were evident from 3 to 10 DPI. Virus was isolated in nasal secretions from 2 to 9 DPI and in bronchoalveolar cells from 3 to 7 DPI. A cell-associated viraemia was detected from 3 to 10 DPI. After replication in the respiratory tract and draining lymph nodes, EAV reached secondary target organs (high virus titers in internal organs sampled at 7 DPI). At 14 DPI, virus titers dropped drastically and, at 28 DPI, only tonsils were positive. Immunofluorescence revealed both individual and clustered EAV-infected cells. Antibodies were detected starting from 7 DPI. It can be concluded that the Belgian strain 08P178 is a European mildly virulent subtype. At present, most European EAV strain infections were thought to run a subclinical course. This study is a proof that mildly virulent European EAV strains do exist in the field.

  15. Clinical and Virological Factors Associated with Viremia in Pandemic Influenza A/H1N1/2009 Virus Infection

    PubMed Central

    Tse, Herman; To, Kelvin K. W.; Wen, Xi; Chen, Honglin; Chan, Kwok-Hung; Tsoi, Hoi-Wah; Li, Iris W. S.; Yuen, Kwok-Yung

    2011-01-01

    Background Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance. Methodology/Principal Findings Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples. Conclusion Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein. PMID:21980333

  16. 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.

  17. 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

  18. 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.

  19. Clinical, epidemiologic, and virologic features of dengue in the 1998 epidemic in Nicaragua.

    PubMed

    Harris, E; Videa, E; Pérez, L; Sandoval, E; Téllez, Y; Pérez, M L; Cuadra, R; Rocha, J; Idiaquez, W; Alonso, R E; Delgado, M A; Campo, L A; Acevedo, F; Gonzalez, A; Amador, J J; Balmaseda, A

    2000-01-01

    From July to December 1998, a hospital- and health center-based surveillance system for dengue was established at selected sites in Nicaragua to better define the epidemiology of this disease. Demographic and clinical information as well as clinical laboratory results were obtained, and virus isolation, reverse transcriptase-polymerase chain reaction, and serologic assays were performed. World Health Organization criteria were used to classify disease severity; however, a number of patients presented with signs of shock in the absence of thrombocytopenia or hemoconcentration. Therefore, a new category was designated as "dengue with signs associated with shock" (DSAS). Of 1,027 patients enrolled in the study, 614 (60%) were laboratory-confirmed as positive cases; of these, 268 (44%) were classified as dengue fever (DF); 267 (43%) as DF with hemorrhagic manifestations (DFHem); 40 (7%) as dengue hemorrhagic fever (DHF); 20 (3%) as dengue shock syndrome (DSS); and 17 (3%) as DSAS. Interestingly, secondary infection was not significantly correlated with DHF/DSS, in contrast to previous studies in Southeast Asia. DEN-3 was responsible for the majority of cases, with a minority due to DEN-2; both serotypes contributed to severe disease. As evidenced by the analysis of this epidemic, the epidemiology of dengue can differ according to geographic region and viral serotype.

  20. Next-generation sequencing in clinical virology: Discovery of new viruses

    PubMed Central

    Datta, Sibnarayan; Budhauliya, Raghvendra; Das, Bidisha; Chatterjee, Soumya; Vanlalhmuaka; Veer, Vijay

    2015-01-01

    Viruses are a cause of significant health problem worldwide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence-independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of next-generation sequencers (NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequence-independent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery. PMID:26279987

  1. Dengue infections in the Philippines: clinical and virological findings in 517 hospitalized patients.

    PubMed

    Hayes, C G; Manaloto, C R; Gonzales, A; Ranoa, C P

    1988-07-01

    From May 1983 to January 1984, 517 patients with laboratory confirmed dengue were studied at a hospital in Manila. Secondary dengue infections were diagnosed in 78% of these cases. Peak admission (28%) occurred towards the end of the rainy season in November. Most patients (78%) were less than 15 years old but only 3 were infants. Although some type of hemorrhagic finding occurred in 460 cases (89%), only 110 were classified as dengue hemorrhagic fever and the remainder as dengue fever with hemorrhagic manifestations. The clinical course was usually mild. Gastrointestinal bleeding was present in 65 cases, but only 2 patients developed shock. No fatalities occurred. Dengue 2 was the predominant serotype with 53 isolates, followed by dengue 1 with 48 isolates, dengue 3 with 39 isolates, and dengue 4 with only 8 isolates. Dengue 2 was the only serotype with more isolates from sera with a homologous HI antibody titer greater than 1:20 (57%) than from sera with a homologous HI titer less than or equal to 1:20 (43%). In contrast, most of the dengue 1 isolates (63%) were from sera with a homologous HI antibody titer less than 1:10, and this serotype was strongly associated with primary infections. This study shows that dengue infections remain an important cause of pediatric hospitalization in the Philippines; however, the occurrence of life-threatening dengue hemorrhagic fever as has been described in several other large urban areas of Southeast Asia appears to be rare.

  2. 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

  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. Dengue 1 epidemic in French Polynesia, 1988-1989: surveillance and clinical, epidemiological, virological and serological findings in 1752 documented clinical cases.

    PubMed

    Chungue, E; Burucoa, C; Boutin, J P; Philippon, G; Laudon, F; Plichart, R; Barbazan, P; Cardines, R; Roux, J

    1992-01-01

    An epidemic of dengue 1 occurred in French Polynesia in December 1988 and June 1989. This paper records (i) the trend of the outbreak and its surveillance and (ii) the clinical, epidemiological and virological data obtained from 1752 documented cases. The epidemic reached its peak in February in Tahiti Island, 7 weeks after its recognition. Among 6034 suspect cases reported by sentinel physicians, 60.3% were < 20 years old. The illness was classical dengue. No fatality or case of dengue haemorrhagic fever/dengue with shock syndrome was reported. Of 4792 patients subjected to laboratory testing, 41% were confirmed as positive. The serological attack rate was c. 40%. The estimated number of dengue infections in the Windward Islands was about 20,000. Transmission was associated with Aedes aegypti. Study of documented cases showed a higher confirmation rate in both the civilian population < 15 years old (46.5%) and the susceptible French military population (47.6%) than in older civilians (31.1%, P < 0.05). Furthermore, primary dengue infections were predominant in both of the first 2 groups. The diagnosis was mostly confirmed (i) by virus isolation on day < 5 of illness and (ii) by detection of immunoglobulin (Ig) M on day > or = 5 of illness. The study showed that adequate surveillance of an epidemic requires both clinically and laboratory-based systems.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. The Clinical Impact of Continuing to Prescribe Antiretroviral Therapy in Patients with Advanced AIDS Who Manifest No Virologic or Immunologic Benefit

    PubMed Central

    Wohl, David A.; Kendall, Michelle A.; Feinberg, Judith; Alston-Smith, Beverly; Owens, Susan; Chafey, Suzette; Marco, Michael; Maxwell, Sharon; Benson, Constance; Keiser, Philip; van der Horst, Charles; Jacobson, Mark A.

    2013-01-01

    Introduction Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized. Methods We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution. Results 233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm3 and lower baseline HIV RNA. Conclusions Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS—improving survival and shifting the causes of death from AIDS- to non

  12. 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.

  13. 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

  14. Efficacy and safety in clinical practice of a rilpivirine, tenofovir and emtricitabine single-tablet regimen in virologically suppressed HIV-positive patients on stable antiretroviral therapy

    PubMed Central

    Gianotti, Nicola; Poli, Andrea; Nozza, Silvia; Spagnuolo, Vincenzo; Tambussi, Giuseppe; Bossolasco, Simona; Cinque, Paola; Maillard, Myriam; Cernuschi, Massimo; Galli, Laura; Lazzarin, Adriano; Castagna, Antonella

    2015-01-01

    Introduction Switching to a rilpivirine, tenofovir and emtricitabine (RTE) single-tablet regimen (STR) has been evaluated in a limited number of virologically suppressed patients. The aim of this study was to describe clinical outcomes in HIV-positive patients switched from a suppressive antiretroviral regimen to RTE STR in routine clinical practice. Methods In this retrospective study of antiretroviral-treated patients with <50 copies of HIV RNA/mL switched to RTE STR, virological failure (VF) was defined as two consecutive measurements of ≥50 copies/mL or a single measurement of ≥50 copies/mL followed by any change in treatment. Treatment failure (TF) was defined as VF or discontinuation of the STR for any reason. Univariate mixed-linear models were used to identify differences in laboratory parameters over time. Results and discussion The analysis involved 307 patients (83% males) with a median age of 45.8 years (interquartile range (IQR 39.3–50.9), who were followed up for a median of 7.4 months (IQR 4.6–10.9). VF occurred in three patients (1%) switched from a protease inhibitor (PI)-based regimen, after a median of 2.6 months (IQR 1.6–3.0), and TF in 34 patients (11%) after a median of three months (IQR 1.4–5.8), 24 of whom (71%) were receiving a PI-based regimen at baseline. Overall, there was a slight but statistically significant improvement in the mean monthly change from baseline in CD4+ cell counts (p=0.027), the CD4+/CD8+ ratio (p=0.0001), and Hb (p=0.024), alanine amino transferase (ALT) (p=0.009), total bilirubin (p<0.0001), indirect bilirubin (p<0.0001), total cholesterol (p<0.0001) and triglyceride (p<0.0001) levels. There was also a slight but statistically significant increase in serum creatinine (p=0.0004), aspartate amino transferase (AST) (p=0.001) and liver fibrosis index (FIB-4) (p=0.002), and a decrease in eGFRcreat (p<0.0001) and high-density lipoprotein (HDL) cholesterol (p<0.0001) values. The study limitations include its

  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 Central

    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. PMID:27387488

  18. Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years.

    PubMed

    Pernas, B; Mena, A; Cañizares, A; Grandal, M; Castro-Iglesias, A; Pértega, S; Pedreira, J D; Poveda, E

    2015-08-01

    To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts < 350 cells/µl and 33.6% had an AIDS defining criteria. Non-B variants were found in 34.4% of patients being subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission.

  19. 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

  20. Clinical, epidemiological and virological characteristics of the first detected human case of avian influenza A(H5N6) virus

    PubMed Central

    Zhang, Rusheng; Chen, Tianmu; Ou, Xinhua; Liu, Ruchun; Yang, Yang; Ye, Wen; Chen, Jingfang; Yao, Dong; Sun, Biancheng; Zhang, Xixing; Zhou, Jianxiang; Sun, Yan; Chen, Faming; Wang, Shi-Ping

    2016-01-01

    A human infection with novel avian influenza A H5N6 virus emerged in Changsha city, China in February, 2014. This is the first detected human case among all human cases identified from 2014 to early 2016. We obtained and summarized clinical, epidemiological, and virological data from this patient. Complete genome of the virus was determined and compared to other avian influenza viruses via the construction of phylogenetic trees using the neighbor-joining approach. A girl aged five and half years developed fever and mild respiratory symptoms on Feb. 16, 2014 and visited hospital on Feb. 17. Throat swab specimens were obtained from the patient and a novel reassortant avian influenza A H5N6 virus was detected. All eight viral gene segments were of avian origin. The hemagglutinin (HA) and neuraminidase (NA) gene segments were closely related to A/duck/Sichuan/NCXN11/2014(H5N1) and A/chicken/Jiangxi/12782/2014(H10N6) viruses, respectively. The six internal genes were homologous to avian influenza A (H5N2) viruses isolated in duck from Jiangxi in China. This H5N6 virus has not gained genetic mutations necessary for human infection and was suggested to be sensitive to neuraminidase inhibitors, but resistant to adamantanes. Epidemiological investigation of the exposure history of the patient found that a live poultry market could be the source place of infection and the incubation period was 2–5 days. This novel reassortant Avian influenza A(H5N6) virus could be low pathogenic in humans. The prevalence and genetic evolution of this virus should be closely monitored. PMID:26973295

  1. Clinical, epidemiological and virological characteristics of the first detected human case of avian influenza A(H5N6) virus.

    PubMed

    Zhang, Rusheng; Chen, Tianmu; Ou, Xinhua; Liu, Ruchun; Yang, Yang; Ye, Wen; Chen, Jingfang; Yao, Dong; Sun, Biancheng; Zhang, Xixing; Zhou, Jianxiang; Sun, Yan; Chen, Faming; Wang, Shi-Ping

    2016-06-01

    A human infection with novel avian influenza A H5N6 virus emerged in Changsha city, China in February, 2014. This is the first detected human case among all human cases identified from 2014 to early 2016. We obtained and summarized clinical, epidemiological, and virological data from this patient. Complete genome of the virus was determined and compared to other avian influenza viruses via the construction of phylogenetic trees using the neighbor-joining approach. A girl aged five and half years developed fever and mild respiratory symptoms on Feb. 16, 2014 and visited hospital on Feb. 17. Throat swab specimens were obtained from the patient and a novel reassortant avian influenza A H5N6 virus was detected. All eight viral gene segments were of avian origin. The hemagglutinin (HA) and neuraminidase (NA) gene segments were closely related to A/duck/Sichuan/NCXN11/2014(H5N1) and A/chicken/Jiangxi/12782/2014(H10N6) viruses, respectively. The six internal genes were homologous to avian influenza A (H5N2) viruses isolated in duck from Jiangxi in China. This H5N6 virus has not gained genetic mutations necessary for human infection and was suggested to be sensitive to neuraminidase inhibitors, but resistant to adamantanes. Epidemiological investigation of the exposure history of the patient found that a live poultry market could be the source place of infection and the incubation period was 2-5days. This novel reassortant Avian influenza A(H5N6) virus could be low pathogenic in humans. The prevalence and genetic evolution of this virus should be closely monitored.

  2. [Nonconvulsive status epilepticus: clinical practice and pathophysiology].

    PubMed

    Nagayama, Masao

    2013-05-01

    The clinical spectrum of nonconvulsive status epilepticus (NCSE) is rapidly expanding from classical manifestations, such as staring, repetitive blinking, chewing, swallowing, and automatism to novel manifestations, such as acute and protracted coma, apnea, cognitive impairment, higher brain dysfunction, and cardiac arrest. It is only in the last decade that these novel NCSE manifestations have been revealed, which is certainly reflective of modern advances in critical care neurology, such as the introduction and spread of continuous electroencephalography (cEEG) monitoring. Although NCSE is a relatively frequent, treatable condition but with a high mortality rate, physicians are still unfamiliar with its clinical manifestations, thus leading to underdiagnosis. In this review, the clinical manifestations, epidemiology, diagnosis, and management of NCSE are critically described using the best available evidence and perspectives, including my hypothesis on epileptic organ dysfunction; in particular, the possible causal relationship between NCSE and cardiac arrhythmia, such as atrial fibrillation is also discussed. PMID:23667121

  3. 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.

  4. Genotypic Resistance Analysis of the Virological Response to Fosamprenavir-Ritonavir in Protease Inhibitor-Experienced Patients in CONTEXT and TRIAD Clinical Trials▿

    PubMed Central

    Marcelin, Anne-Geneviève; Flandre, Philippe; Molina, Jean-Michel; Katlama, Christine; Yeni, Patrick; Raffi, Francois; Antoun, Zeina; Ait-Khaled, Mounir; Calvez, Vincent

    2008-01-01

    The aim of this study was to identify human immunodeficiency virus (HIV) protease mutations associated with virological response (VR) to fosamprenavir-ritonavir (FPV/r) in 113 protease inhibitor (PI)-experienced patients randomized in both CONTEXT and TRIAD clinical trials and receiving the same dose (700/100 mg twice daily) of FPV/r. The impact of each protease mutation on the VR to FPV/r, defined as the decrease in HIV RNA at week 12, was investigated with nonparametric analyses. A step-by-step procedure was done using a Jonckheere-Terpstra (JT) test that retains the group of mutations most strongly associated with the VR. Mutations at the following 14 codons were associated with a reduced VR to FPV/r: 10, 15, 33, 46, 54, 60, 62, 63, 72, 73, 82, 84, 89, and 90. The JT procedure led to selecting the CONTEXT/TRIAD genotypic set of mutations, I15V, M46I/L, I54L/M/V, D60E, L63P/T, and I84V, as providing the strongest association with the VR (P = 1.45 × 10−11). In the nine patients with zero mutations within this set, the median decrease in HIV RNA was −2.63 log copies/ml, and was −2.22 (n = 45), −1.50 (n = 26), −0.58 (n = 23), −0.47 (n = 6), −0.13 (n = 3), and 0.04 (n = 1) log copies/ml in those with one, two, three, four, five, and six mutations, respectively. This study identified six mutations associated with VR to FPV/r. Some of these mutations are shared with the current FPV/r Agence Nationale de Recherches sur le SIDA (ANRS) resistance score, which has been cross-validated in the CONTEXT/TRIAD data set, suggesting that the current ANRS FPV/r score is a useful tool for the prediction of VR to FPV/r in PI-experienced patients. PMID:18852278

  5. Face up to challenge of virology world.

    PubMed

    Pang, Xiaoli Lilly

    2012-02-12

    Welcome to the World Journal of Virology (WJV), a new member of the World Journal Series. The World Journal Series was first launched as a peer-reviewed scientific journal covering aspects of research, diagnostics and clinical practice in biomedicine in 1995. WJV is an online and open-access peer-reviewed periodical focusing on virology. WJV covers a variety of topics in different areas of virology, including advances in basic research, updates in nomenclature, the development of novel diagnostic assays, the epidemiology of viral disorders and, new developments in the clinical management of viral diseases, including new vaccines and antiviral therapeutics. The purpose in launching the WJV is to promote knowledge exchange related to the classic human viruses as well as newly emerging viruses and their associated clinical disorders. Continually updating knowledge in a timely manner in this field where information related to the unceasing evolution of viruses is becoming available at a rapid pace is challenging. Thanks to the World-Wide-Web we are able to provide a podium for all authors and readers of WJV to address this challenge. I would like to acknowledge the Baishideng publisher, the members of the editorial board, and all contributing authors involved in this inaugural issue of the WJV. I sincerely hope all readers, i.e. future contributing authors, will like WJV and we look forward to your input in assisting WJV to grow and mature.

  6. 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. PMID:27118790

  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. The Future of Digital Polymerase Chain Reaction in Virology.

    PubMed

    Vynck, Matthijs; Trypsteen, Wim; Thas, Olivier; Vandekerckhove, Linos; De Spiegelaere, Ward

    2016-10-01

    Driven by its potential benefits over currently available methods, and the recent development of commercial platforms, digital polymerase chain reaction (dPCR) has received increasing attention in virology research and diagnostics as a tool for the quantification of nucleic acids. The current technologies are more precise and accurate, but may not be much more sensitive, compared with quantitative PCR (qPCR) applications. The most promising applications with the current technology are the analysis of mutated sequences, such as emerging drug-resistant mutations. Guided by the recent literature, this review focuses on three aspects that demonstrate the potential of dPCR for virology researchers and clinicians: the applications of dPCR within both virology research and clinical virology, the benefits of the technique over the currently used real-time qPCR, and the importance and availability of specific data analysis approaches for dPCR. Comments are provided on current drawbacks and often overlooked pitfalls that need further attention to allow widespread implementation of dPCR as an accurate and precise tool within the field of virology.

  9. 42 CFR 493.919 - Virology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 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...

  10. 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...

  11. 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,...

  12. 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,...

  13. 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...

  14. 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,...

  15. 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...

  16. 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,...

  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. Clinical status of ten dentin adhesive systems.

    PubMed

    Van Meerbeek, B; Peumans, M; Verschueren, M; Gladys, S; Braem, M; Lambrechts, P; Vanherle, G

    1994-11-01

    Laboratory testing of dentin adhesive systems still requires corroboration by long-term clinical trials for their ultimate clinical effectiveness to be validated. The objective of this clinical investigation was to evaluate, retrospectively, the clinical effectiveness of earlier-investigated dentin adhesive systems (Scotchbond, Gluma, Clearfil New Bond, Scotchbond 2, Tenure, and Tripton), and to compare their clinical results with those obtained with four modern total-etch adhesive systems (Bayer exp. 1 and 2, Clearfil Liner Bond System, and Scotchbond Multi-Purpose). In total, 1177 Class V cervical lesions in the teeth of 346 patients were restored following two cavity designs: In Group A, enamel was neither beveled nor intentionally etched, as per ADA guidelines; in Group B, adjacent enamel was beveled and conditioned. Clinical retention rates definitely indicated the improved clinical efficacy of the newest dentin adhesives over the earlier systems. With regard to adhesion strategy, adhesive systems that removed the smear layer and concurrently demineralized the dentin surface layer performed clinically better than systems that modified the disorderly layer of smear debris without complete removal. Hybridization by resin interdiffusion into the exposed dentinal collagen layer, combined with attachment of resin tags into the opened dentin tubules, appeared to be essential for reliable dentin bonding but might be insufficient by itself. The additional formation of an elastic bonding area as a polymerization shrinkage absorber and the use of a microfine restorative composite apparently guaranteed an efficient clinical result. The perfect one-year retention recorded for Clearfil Liner Bond System and Scotchbond Multi-Purpose must be confirmed at later recalls. PMID:7983255

  19. [Present status of clinical and fundamental threpsology].

    PubMed

    Kostiuchenko, L N; Ruchkina, I N; Kuz'mina, T N

    2009-01-01

    A good nutrition status is one of the impotant prerequisites of good health. Malnutrition in hospital leads to increased complication, morbidity and mortality rates. Whenever the gastrointestinal tract cannot fulfil its function or must be rested (during intestinal desease), parenteral administration of nutrients (or simultative parenteral and enteral alimitation) is necessary. Nowday perspectives of nutrition support in patients whith intestinal deseases, methods of easily diagnosed of malnutrition are the problems of this article. PMID:19552018

  20. 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

  1. Human Immunodeficiency Virus-1 Sequence Changes and Drug Resistance Mutation Among Virologic Failures of Lopinavir/Ritonavir Monotherapy: AIDS Clinical Trials Group Protocol A5230

    PubMed Central

    Vardhanabhuti, Saran; Katzenstein, David; Bartlett, John; Kumarasamy, Nagalingeswaran; Wallis, Carole L.

    2016-01-01

    Background. The mechanism of virologic failure (VF) of lopinavir/ritonavir (LPV/r) monotherapy is not well understood. We assessed sequence changes in human immunodeficiency virus-1 reverse-transcriptase (RT) and protease (PR) regions. Methods. Human immunodeficiency virus-1 pol sequences from 34 participants who failed second-line LPV/r monotherapy were obtained at study entry (SE) and VF. Sequence changes were evaluated using phylogenetic analysis and hamming distance. Results. Human immunodeficiency virus-1 sequence change was higher over drug resistance mutation (DRM) sites (median genetic distance, 2.2%; Q1 to Q3, 2.1%–2.5%) from SE to VF compared with non-DRM sites (median genetic distance, 1.3%; Q1 to Q3, 1.0%–1.4%; P < .0001). Evolution over DRM sites was mainly driven by changes in the RT (median genetic distance, 2.7%; Q1 to Q3, 2.2%–3.2%) compared with PR (median genetic distance, 1.1%; Q1 to Q3, 0.0%–1.1%; P < .0001). Most RT DRMs present at SE were lost at VF. At VF, 19 (56%) and 26 (76%) were susceptible to efavirenz/nevirapine and etravirine (ETV)/rilpivirine (RPV), respectively, compared with 1 (3%) and 12 (35%) at SE. Participants who retained nonnucleoside reverse-transcriptase inhibitor (NNRTI) DRMs and those without evolution of LPV/r DRMs had significantly shorter time to VF. Conclusions. The selection of LPV/r DRMs in participants with longer time to VF suggests better adherence and more selective pressure. Fading NNRTI mutations and an increase in genotypic susceptibility to ETV and RPV could allow for the reuse of NNRTI. Further studies are warranted to understand mechanisms of PR failure. PMID:27704010

  2. 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.

  3. Clinical and virological dynamics of a serotype O 2010 South East Asia lineage foot-and-mouth disease virus in sheep using natural and simulated natural inoculation and exposure systems.

    PubMed

    Stenfeldt, Carolina; Pacheco, Juan M; Singanallur, Nagendrakumar B; Ferreira, Helena C de Carvalho; Vosloo, Wilna; Rodriguez, Luis L; Arzt, Jonathan

    2015-07-01

    Within-host infection dynamics of a recent field isolate of foot-and-mouth disease virus (FMDV), serotype O, topotype South East Asia, lineage Myamar'98 were evaluated in sheep using four different systems for virus exposure. Two novel, simulated natural, inoculation systems consisting of intra-nasopharyngeal (INP) deposition and aerosol inoculation were evaluated in comparison with two conventional systems: coronary band inoculation and direct contact exposure. All four exposure systems were efficient in generating consistently severe, generalized FMD with synchronous clinical characteristics within exposure groups, indicating that this Myanmar98 strain is highly virulent in sheep. Clinical and virological dynamics were similarly rapid following INP- and coronary band inoculation, with both systems leading to significantly earlier detection of virus shedding when compared to aerosol inoculation and contact exposure. The data presented herein support application of the two optimized simulated natural inoculation systems as valid alternatives to conventionally used exposure systems for studies of FMDV pathogenesis and vaccinology in sheep. Furthermore, the data suggest that targeted exposure of the ovine pharynx is highly efficient for generating consistent FMDV infection, which supports critical involvement of this anatomic region as a site of primary virus replication in sheep.

  4. Predictors of Virologic and Clinical Response to Nevirapine versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in Young Children with and without Prior Nevirapine Exposure for the Prevention of Mother-To-Child HIV Transmission

    PubMed Central

    Lindsey, Jane C.; Hughes, Michael D.; Violari, Avy; Eshleman, Susan H.; Abrams, Elaine J.; Bwakura-Dangarembizi, Mutsa; Barlow-Mosha, Linda; Kamthunzi, Portia; Sambo, Pauline M.; Cotton, Mark F.; Moultrie, Harry; Khadse, Sandhya; Schimana, Werner; Bobat, Raziya; Zimmer, Bonnie; Petzold, Elizabeth; Mofenson, Lynne M.; Jean-Philippe, Patrick; Palumbo, Paul

    2014-01-01

    Background In a randomized trial comparing nevirapine (NVP)- versus lopinavir/ritonavir (LPV/r)– based antiretroviral therapy (ART) in HIV-infected children (primary endpoint discontinuation of study treatment for any reason or virologic failure (VF) by week 24) aged two months to three years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of mother-to-child HIV transmission and other covariates. Methods Efficacy was assessed by time to ART discontinuation or VF, VF/death, and death; safety by time to ART discontinuation due to a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height WHO z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates. Results Over a median follow-up of 48 (PrNVP) and 72 (No PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r – based ART was superior to NVP-based ART for efficacy and safety outcomes but those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pre-treatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pre-treatment CD4% with shorter time to ART discontinuation due to a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥3 adverse event. Conclusions Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breastfeeding, sex, HIV-1 subtype, age, pre-treatment CD4%, HIV-1 RNA or WHO disease stage. This finding should be considered when selecting an ART regimen for young children. PMID:25222305

  5. 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

  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. 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.

  8. Aptamers in virology: recent advances and challenges.

    PubMed

    Binning, Jennifer M; Leung, Daisy W; Amarasinghe, Gaya K

    2012-01-01

    Aptamers generated from randomized libraries of nucleic acids have found utility in a wide variety of fields and in the clinic. Aptamers can be used to target both intracellular and extracellular components, including small molecules, proteins, cells, and viruses. With recent technological developments in stringent selection and rapid isolation strategies, it is likely that aptamers will continue to make an impact as useful tools and reagents. Although many recently developed aptamers are intended for use as therapeutic and diagnostic agents, use of aptamers for basic research, including target validation, remains an active area with high potential to impact our understanding of molecular mechanisms and for drug discovery. In this brief review, we will discuss recent aptamer discoveries, their potential role in structural virology, as well as challenges and future prospects.

  9. 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.

  10. 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.

  11. Toward clinical applications of health status measures: sensitivity of scales to clinically important changes.

    PubMed

    Deyo, R A; Inui, T S

    1984-08-01

    While the validity and reliability of many newer health status instruments have been reported, few data are available regarding the sensitivity of these instruments to clinically discernible changes in patient status. We studied this feature of the Sickness Impact Profile (SIP) in a group of patients with rheumatoid arthritis, comparing it with more traditional measures of functional status (the American Rheumatism Association (ARA) functional classification and a patient self-rating scale). Four different approaches were devised to measure "sensitivity to clinical change." These involved comparisons of functional score changes with clinical changes in patient status which were independently agreed upon by both clinician and patient, and also comparisons with several clinical disease severity indicators. When applied to groups of patients, the SIP and the patient self-rating scale were modestly superior to the ARA scale, but neither the SIP nor the self-rating scale was clearly superior to the other. For considering individual patients, all of the scales were relatively insensitive, and predictive accuracy for clinically estimated change was low. New strategies for assessing sensitivity to small changes should be developed and applied to health status and functional scales. Attention to this characteristic should allow refinement of existing scales and may enhance their clinical usefulness.

  12. 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,...

  13. 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,...

  14. 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...

  15. 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...

  16. 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,...

  17. 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)

  18. 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...

  19. 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,...

  20. 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...

  1. 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...

  2. 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,...

  3. 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

  4. Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebo-controlled trial.

    PubMed

    Baeten, Jared M; Reid, Stewart E; Delany-Moretlwe, Sinead; Hughes, James P; Wang, Richard S; Wilcox, Ellen; Limbada, Mohammed; Akpomiemie, Godspower; Corey, Lawrence; Wald, Anna; Celum, Connie

    2012-01-01

    In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (hazard ratio [HR] = 1.48, P = 0.098; mean, 5.1 vs. 6.0 days) and cessation of herpes simplex virus shedding (HR = 1.88, P = 0.008; mean, 3.0 vs. 5.0 days) compared with placebo, similar to results of studies in high-income countries (ClinicalTrials.gov registration NCT00808405).

  5. 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

  6. 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.

  7. Evolution of drug resistance after virologic failure of a first highly active antiretroviral therapy regimen in Uganda

    PubMed Central

    Reynolds, Steven J.; Kityo, Cissy; Mbamanya, Frank; Dewar, Robin; Ssali, Francis; Quinn, Thomas C.; Mugyenyi, Peter; Dybul, Mark

    2009-01-01

    Objective To determine the extent of viral resistance over time among non-clade B HIV-1 infected patients in Uganda maintained on first line highly active antiretroviral therapy (HAART) following virologic failure. Methods Genotyping was performed on sixteen patients with virologic failure who were enrolled in an open label randomized clinical trial of short-cycle treatment interruption. Results All patients receiving efavirenz containing HAART had at least 1 efavirenz resistance mutation develop during follow-up. The majority 13/15 (86%) developed lamivudine resistance during follow-up but no thymidine analogue mutations (TAMS) developed during a median duration of virologic failure of 325.5 days. Conclusions Genotypic resistance to both efavirenz and lamivudine developed early during the course of treatment after virologic failure. TAMs did not emerge early despite moderate exposure time to thymidine analogs during virologic failure. PMID:19430104

  8. 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

  9. 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

  10. Mayo clinic NLP system for patient smoking status identification.

    PubMed

    Savova, Guergana K; Ogren, Philip V; Duffy, Patrick H; Buntrock, James D; Chute, Christopher G

    2008-01-01

    This article describes our system entry for the 2006 I2B2 contest "Challenges in Natural Language Processing for Clinical Data" for the task of identifying the smoking status of patients. Our system makes the simplifying assumption that patient-level smoking status determination can be achieved by accurately classifying individual sentences from a patient's record. We created our system with reusable text analysis components built on the Unstructured Information Management Architecture and Weka. This reuse of code minimized the development effort related specifically to our smoking status classifier. We report precision, recall, F-score, and 95% exact confidence intervals for each metric. Recasting the classification task for the sentence level and reusing code from other text analysis projects allowed us to quickly build a classification system that performs with a system F-score of 92.64 based on held-out data tests and of 85.57 on the formal evaluation data. Our general medical natural language engine is easily adaptable to a real-world medical informatics application. Some of the limitations as applied to the use-case are negation detection and temporal resolution.

  11. 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)

  12. Predictors of virologic response to ritonavir-boosted protease inhibitors.

    PubMed

    Marcelin, Anne-Genevieve; Flandre, Philippe; Peytavin, Gilles; Calvez, Vincent

    2005-01-01

    The primary mechanism of resistance to protease inhibitors involves the stepwise accumulation of mutations that alter and block the substrate binding site of HIV protease. The large degree of cross-resistance among the different protease inhibitors is a source of considerable concern for the management of patients after treatment failure. Although the output of HIV-resistance tests has been based on therapeutically arbitrary criteria, there is now an ongoing move towards correlating test interpretation with virologic outcomes on treatment. This approach is undeniably superior, in principle, for tests intended to guide drug choices. However, the predictive accuracy of a given stratagem that links genotype or phenotype to drug response is strongly influenced by the study design, data capture and the analytical methodology used to derive it. There is no definitively superior methodology for generating a genotype-response association for use in interpreting a resistance test, and the various approaches used to date all have their strengths and weaknesses. Combining the information of therapeutic drug monitoring and resistance tests is likely to be of greatest clinical utility in antiretroviral-experienced patients harboring HIV strains with reduced susceptibility. The combination of pharmacologic and virologic parameters as a predictor of the virologic response has been merged into the parameter known as "inhibitory quotient". This article discusses the potential interest of the use of inhibitory quotients as an approach for enhancing the potency and durability of boosted protease inhibitors against protease inhibitor-resistant viruses. PMID:16425962

  13. 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.

  14. 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

  15. 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. PMID:20593091

  16. [The contribution of the virology laboratory to the diagnosis of neuroinfections].

    PubMed

    Bruj, J; Malináková, J; Struncová, V; Farník, J; Cervenková, H; Hronovský, V

    1990-09-01

    The authors summarizes the results of a virological examination in 1231 patients with neuroinfections hospitalized in 1973-1984 at the Infectious Diseases Clinic in Plzen. The virological diagnosis contributed towards the elucidation of the aetiology in 62.4% of the patients. In the aetiology participated the virus of tick-borne encephalitis in 28.2%, the virus of epidemic parotidis in 15.8% and a group of enteroviruses in 14.9%. The participation of other viral agents was small.

  17. 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.

  18. 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. PMID:15834885

  19. Adherence to Antiretroviral Therapy and Virologic Failure

    PubMed Central

    Bezabhe, Woldesellassie M.; Chalmers, Leanne; Bereznicki, Luke R.; Peterson, Gregory M.

    2016-01-01

    Abstract The often cited need to achieve ≥95% (nearly perfect) adherence to antiretroviral therapy (ART) for successful virologic outcomes in HIV may present a barrier to initiation of therapy in the early stages of HIV. This meta-analysis synthesized 43 studies (27,905 participants) performed across >26 countries, to determine the relationship between cut-off point for optimal adherence to ART and virologic outcomes. Meta-analysis was performed using a random-effect model to calculate pooled odds ratios with corresponding 95% confidence intervals. The mean rate of patients reporting optimal adherence was 63.4%. Compared with suboptimal adherence, optimal adherence was associated with a lower risk of virologic failure (0.34; 95% CI: 0.26–0.44). There were no significant differences in the pooled odds ratios among different optimal adherence thresholds (≥98–100%, ≥95%, ≥80–90%). Study design (randomized controlled trial vs observational study) (regression coefficient 0.74, 95% CI: 0.04–1.43, P < 0.05) and study region (developing vs developed countries; regression coefficient 0.56, 95% CI: 0.01–1.12, P < 0.05) remained as independent predictors of between-study heterogeneity, with more patients with optimal adherence from developing countries or randomized controlled trials experiencing virologic failure. The threshold for optimal adherence to achieve better virologic outcomes appears to be wider than the commonly used cut-off point (≥95% adherence). The cut-off point for optimal adherence could be redefined to a slightly lower level to encourage the prescribing ART at an early stage of HIV infection. PMID:27082595

  20. 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

  1. Single-Cell Genomics for Virology

    PubMed Central

    Ciuffi, Angela; Rato, Sylvie; Telenti, Amalio

    2016-01-01

    Single-cell sequencing technologies, i.e., single cell analysis followed by deep sequencing investigate cellular heterogeneity in many biological settings. It was only in the past year that single-cell sequencing analyses has been applied in the field of virology, providing new ways to explore viral diversity and cell response to viral infection, which are summarized in the present review. PMID:27153082

  2. Single-Cell Genomics for Virology.

    PubMed

    Ciuffi, Angela; Rato, Sylvie; Telenti, Amalio

    2016-01-01

    Single-cell sequencing technologies, i.e., single cell analysis followed by deep sequencing investigate cellular heterogeneity in many biological settings. It was only in the past year that single-cell sequencing analyses has been applied in the field of virology, providing new ways to explore viral diversity and cell response to viral infection, which are summarized in the present review. PMID:27153082

  3. 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…

  4. “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

  5. Feasibility of Automatic Extraction of Electronic Health Data to Evaluate a Status Epilepticus Clinical Protocol.

    PubMed

    Hafeez, Baria; Paolicchi, Juliann; Pon, Steven; Howell, Joy D; Grinspan, Zachary M

    2016-05-01

    Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols.

  6. 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.

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

    PubMed Central

    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. PMID:26958215

  8. 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

  9. Magnitude of Virologic Blips Is Associated With a Higher Risk for Virologic Rebound in HIV-Infected Individuals: A Recurrent Events Analysis

    PubMed Central

    Grennan, J. Troy; Loutfy, Mona R.; Su, DeSheng; Harrigan, P. Richard; Cooper, Curtis; Klein, Marina; Machouf, Nima; Montaner, Julio S. G.; Rourke, Sean; Tsoukas, Christos; Hogg, Bob

    2012-01-01

    (See the editorial commentary by Taiwo and Bosch, on pages 1189–91.) Background. The importance of human immunodeficiency virus (HIV) blip magnitude on virologic rebound has been raised in clinical guidelines relating to viral load assays. Methods. Antiretroviral-naive individuals initiating combination antiretroviral therapy (cART) after 1 January 2000 and achieving virologic suppression were studied. Negative binomial models were used to identify blip correlates. Recurrent event models were used to determine the association between blips and rebound by incorporating multiple periods of virologic suppression per individual. Results. 3550 participants (82% male; median age, 40 years) were included. In a multivariable negative binomial regression model, the Amplicor assay was associated with a lower blip rate than branched DNA (rate ratio, 0.69; P < .01), controlling for age, sex, region, baseline HIV-1 RNA and CD4 count, AIDS-defining illnesses, year of cART initiation, cART type, and HIV-1 RNA testing frequency. In a multivariable recurrent event model controlling for age, sex, intravenous drug use, cART start year, cART type, assay type, and HIV-1 RNA testing frequency, blips of 500–999 copies/mL were associated with virologic rebound (hazard ratio, 2.70; P = .002), whereas blips of 50–499 were not. Conclusions. HIV-1 RNA assay was an important determinant of blip rates and should be considered in clinical guidelines. Blips ≥500 copies/mL were associated with increased rebound risk. PMID:22438396

  10. PHARMACOKINETIC EXPOSURE AND VIROLOGIC RESPONSE IN HIV-1 INFECTED PREGNANT WOMEN TREATED WITH LOPINAVIR/RITONAVIR: AIDS CLINICAL TRIALS GROUP PROTOCOL A5153S: A SUBSTUDY TO A5150

    PubMed Central

    Sha, Beverly E.; Tierney, Camlin; Sun, Xin; Stek, Alice; Cohn, Susan E.; Coombs, Robert W.; Bastow, Barbara; Aweeka, Francesca T.

    2015-01-01

    Objective We studied the pharmacokinetics and pharmacodynamics of boosted soft-gel lopinavir/ritonavir to assess if the area under the plasma concentration versus time curve (AUC) is altered in pregnancy and whether changes in AUC impacted HIV-1 control. Methods We enrolled pregnant women ≥13 years of age between 22 to 30 weeks gestation who expected to be on stable lopinavir/ritonavir for ≥8 weeks pre-delivery and ≥24 weeks post-delivery. Pharmacokinetic evaluations for lopinavir and ritonavir occurred at 36 weeks gestation and 6 and 24 weeks postpartum. Results Ten women underwent intensive pharmacokinetic evaluations for lopinavir and ritonavir at 36 weeks gestation and at 6 and 24 weeks postpartum. Estimated geometric mean (GM) AUC 0–6h (95% CI) for lopinavir were not significantly different at 26.5 (17.0, 41.4) and 41.9 (26.1, 67.5) mcg*hr/mL at 36 weeks gestation and 6 weeks postpartum, respectively (within-subject GM ratio 0.60 (0.25, 1.43); p=0.19). At 36 weeks gestation, 5 of 10 women had viral load <50 copies/mL and at 6 weeks postpartum 5 of 9 had viral load <50 copies/mL. Nine of ten infants for whom data were available were HIV negative. Conclusion Despite below target lopinavir levels (< 52 mcg*hr/mL except at 2 postpartum measurements), women maintained virologic control postpartum. Higher doses of lopinavir/ritonavir during pregnancy may not be necessary in all women. PMID:26878071

  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. Influence of Therapist Gender and Client Gender, Socioeconomic Status and Alcoholic Status on Clinical Judgments.

    ERIC Educational Resources Information Center

    Hardy, Dana M.; Johnson, Mark E.

    1992-01-01

    Psychology graduate students (n=185) responded to case descriptions in which client gender, alcoholism, and socioeconomic status (SES) were manipulated. Found consistent, negative effect of client alcoholism on several prognostic variables, including decision to hospitalize; tendency for female clients to be thought to require more therapy…

  13. Current status of functional gastrointestinal evaluation in clinical practice

    PubMed Central

    Ang, Daphne; Fock, Kwong Ming; Law, Ngai Moh; Ang, Tiing Leong

    2015-01-01

    Neurogastroenterology and motility disorders of the gastrointestinal (GI) tract encompass a broad spectrum of diseases involving the GI tract and central nervous system. They have varied pathophysiology, clinical presentation and management, and make up a substantial proportion of outpatient clinic visits. Typically, patients experience persistent symptoms referable to the GI tract despite normal endoscopic and radiologic findings. An appropriate evaluation is thus important in the patient’s care. Advances in technology and understanding of the disease pathophysiology have provided better insight into the physiological basis of disease and a more rational approach to patient management. While technological advances serve to explain patients’ persistent symptoms, they should be balanced against the costs of diagnostic tests. This review highlights the GI investigative modalities employed to evaluate patients with persistent GI symptoms in the absence of a structural lesion, with particular emphasis on investigative modalities available locally and the clinical impact of such tools. PMID:25715853

  14. Current status of functional gastrointestinal evaluation in clinical practice.

    PubMed

    Ang, Daphne; Fock, Kwong Ming; Law, Ngai Moh; Ang, Tiing Leong

    2015-02-01

    Neurogastroenterology and motility disorders of the gastrointestinal (GI) tract encompass a broad spectrum of diseases involving the GI tract and central nervous system. They have varied pathophysiology, clinical presentation and management, and make up a substantial proportion of outpatient clinic visits. Typically, patients experience persistent symptoms referable to the GI tract despite normal endoscopic and radiologic findings. An appropriate evaluation is thus important in the patient's care. Advances in technology and understanding of the disease pathophysiology have provided better insight into the physiological basis of disease and a more rational approach to patient management. While technological advances serve to explain patients' persistent symptoms, they should be balanced against the costs of diagnostic tests. This review highlights the GI investigative modalities employed to evaluate patients with persistent GI symptoms in the absence of a structural lesion, with particular emphasis on investigative modalities available locally and the clinical impact of such tools.

  15. VITAMIN D STATUS: MEASUREMENT, INTERPRETATION AND CLINICAL APPLICATION

    PubMed Central

    Holick, Michael F.

    2009-01-01

    Vitamin D, the sunshine vitamin, is now recognized not only for its importance of bone health in children and adults, but also for other health benefits including reducing risk of chronic diseases including autoimmune diseases, common cancer and cardiovascular disease. Vitamin D made in the skin or ingested in the diet is biologically inert and requires two successive hydroxylations first in the liver on carbon 25 to form 25-hydroxyvitamin D [25(OH)D], and then in the kidney for a hydroxylation on carbon 1 to form the biologically active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D]. With the identification of 25(OH)D and 1,25(OH)2D, methods were developed to measure these metabolites in the circulation. Serum 25(OH)D is the barometer for vitamin D status. Serum 1,25(OH)2D provides no information about vitamin D status and is often normal or even elevated due to secondary hyperparathyroidism associated with vitamin D deficiency. Most experts agree that 25(OH)D of < 20 ng/ml is considered to be vitamin D deficiency whereas a 25(OH)D of 21-29 ng/ml is considered to be insufficient. The goal should be to maintain both children and adults at a level > 30 ng/ml to take full advantage of all the health benefits that vitamin D provides. PMID:18329892

  16. The current status of targeted radiotherapy in clinical practice.

    PubMed

    Gaze, M N

    1996-10-01

    Biologically targeted radiotherapy in clinical practice requires a molecule which has a relative specificity for tumour tissue--the missile--coupled to a radionuclide with appropriate physical characteristics--the warhead. When administered to a patient this combination should result in selective irradiation of the target tumour cells with relative sparing of normal tissues. Simple ions and small molecules which follow physiological pathways as either the natural substrates or analogues form the best examples of biological targeting. Clinically valuable results are seen with, for instance, iodine uptake by normal and malignant thyroid cells, incorporation of the calci-mimetic element strontium in areas of increased bone metabolism and accumulation of the catecholamine analogue meta-iodobenzylguanidine in neuroblastoma. The use of monoclonal antibodies as targeting vehicles has not proved to be a panacea, yet some patients with lymphoma, hepatoma and ovarian carcinoma have obtained benefit. Current clinical studies in targeted radiotherapy focus on the integration of radionuclide treatment with conventional treatments, and the optimization of such combined approaches. The development of modifications to offset the limitations inherent in the use of crude antibodies also offers an opportunity for improved clinical outcomes.

  17. The status and future of clinical pathology in Korea.

    PubMed

    Cho, H I

    1998-07-01

    Since its introduction half a century ago, modern clinical pathology in Korea has become an essential part of medical practice. The foundations of such fast development are manpower development systems, the government-certified clinical pathologist board system, the medical technologist license system, a medical insurance system providing universal coverage and the decisive introduction of modern technologies. Current issues in clinical pathology are the below cost fee system, the high rate at which claims are rejected, the government's intention to introduce an alternative fee system and 'overheated' competition among commercial laboratories. The 'fee-for-service system' inducing deviated medical practices and low publicity for the discipline-leading to reduction in the number of applications for residency-are serious issues which demand a solution. For continuing success, total laboratory automation (TLA), together with information and core laboratory systems, and an accreditation and audit system must be introduced. Clinical pathologists should, in addition, be trained as laboratory physicians. To extend laboratory usage by developing new demands and needs and expanding the future market for laboratories, effective publicity campaigns through the mass media and internet should be emphasized.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Synthetic Virology: Engineering Viruses for Gene Delivery

    PubMed Central

    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 endeavours will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine. PMID:25195922

  3. Current status of clinical laser applications in periodontal therapy.

    PubMed

    Aoki, Akira; Mizutani, Koji; Takasaki, Aristeo Atsushi; Sasaki, Katia Miyuki; Nagai, Shigeyuki; Schwarz, Frank; Yoshida, Itaru; Eguro, Toru; Zeredo, Jorge Luis; Izumi, Yuichi

    2008-01-01

    Periodontal disease is a chronic inflammatory disorder caused by bacterial infection. Laser treatment demonstrates specific characteristics that may be valuable in managing periodontal disease. In addition, lasers reduce stress and uncomfortable conditions for patients during and after treatment compared to other conventional tools. This article reviews the literature to describe the current clinical applications of lasers for gingival tissue management-including esthetic treatment, non-surgical and surgical periodontal pocket therapy, osseous surgery, and implant therapy.

  4. 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.

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

    PubMed Central

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; 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. PMID:26101528

  6. Measurement equivalence of the Toronto Structured Interview for Alexithymia across language, gender, and clinical status.

    PubMed

    Keefer, Kateryna V; Taylor, Graeme J; Parker, James D A; Inslegers, Ruth; Michael Bagby, R

    2015-08-30

    The Toronto Structured Interview for Alexithymia (TSIA) has been translated into Dutch, German, and Italian and validated in clinical and nonclinical populations. In order to make valid comparisons across different population groups, it is important to establish measurement equivalence across variables such as language, gender, and clinical status. Our objective in this study was to establish measurement equivalence in relation to language (English, Dutch, German, and Italian), gender, and clinical status (non-clinical, psychiatric, and medical) using differential item functioning (DIF). The sample was composed of 842 adults representing the four language groups, all of whom had undergone the TSIA assessment as part of several earlier studies. Ordinal Logistic Regression was employed to explore DIF of the TSIA items. Although several items were found to exhibit DIF for language, gender, or clinical status, all of these effects were within an acceptable range. These findings provide support for the measurement equivalence of the TSIA, and allow researchers to reliably compare results from studies using the TSIA across the four language groups, gender, and clinical status.

  7. 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.

  8. 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…

  9. 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

  10. Current status of transurethral thermotherapy at the Mayo Clinic.

    PubMed

    Blute, M L; Larson, T R; Hanson, K A; King, B F

    1998-06-01

    With the ever-expanding elderly population in the United States, benign prostatic hyperplasia (BPH) has become a widespread condition. Although surgical intervention (open prostatectomy and transurethral resection of the prostate) was the typical management approach for BPH in the past, other options currently include drug therapy and transurethral thermotherapy, a minimally invasive procedure that involves the targeting of heat deep within the prostate transition zone while cooling the surrounding anatomic structures with circulating water. Two thermo-therapy-devices--the Prostatron and the T3 transurethral thermoablation therapy catheter--have been studied in randomized controlled clinical trials at the Mayo Clinic. Both devices were shown to be effective in a substantial subset of patients with BPH: symptom scores decreased, peak urinary flow rates increased, and total serum prostate-specific antigen levels increased, an indication of destruction of adenomatous tissue. All patients were able to complete the treatment without the need for general or regional anesthesia, and thermotherapy was associated with few postprocedural events. Although this therapeutic strategy is currently used selectively in patients with lateral lobe prostatic adenoma, improvements in technology and understanding of the thermoregulatory properties of the prostate should broaden the application of thermotherapy devices in the management of BPH.

  11. Clinical implications of altered thyroid status in male testicular function.

    PubMed

    Wajner, Simone Magagnin; Wagner, Márcia Santos; Maia, Ana Luiza

    2009-11-01

    Thyroid hormones are involved in the development and maintenance of virtually all tissues. Although for many years the testis was thought to be a thyroid-hormone unresponsive organ, studies of the last decades have demonstrated that thyroid dysfunction is associated not only with abnormalities in morphology and function of testes, but also with decreased fertility and alterations of sexual activity in men. Nowadays, the participation of triiodothyronine (T3) in the control of Sertoli and Leydig cell proliferation, testicular maturation, and steroidogenesis is widely accepted, as well as the presence of thyroid hormone transporters and receptors in testicular cells throughout the development process and in adulthood. But even with data suggesting that T3 may act directly on these cells to bring about its effects, there is still controversy regarding the impact of thyroid diseases on human spermatogenesis and fertility, which can be in part due to the lack of well-controlled clinical studies. The current review aims at presenting an updated picture of recent clinical data about the role of thyroid hormones in male gonadal function. PMID:20126850

  12. [Present clinical status of hyperthermia associated with radiotherapy (author's transl)].

    PubMed

    Jaulerry, C; Bataini, J P; Brunin, F; Gaboriaud, G

    1981-01-01

    Improved techniques for inducing heat: ultrasound, microwaves, diathermy with different application modalities, capable of producing localized superficial or deep, regional or total body hyperthermia have been responsible for the multiplication of clinical trials. These studies have confirmed the tumoricidal effect of hyperthermia alone, or more especially when combined with radiotherapy, and the good tolerance of normal tissues to localized temperatures of 42 to 43.5 degrees C even in previously irradiated cases. Localized heating does not seem to increase the incidence of metastasis. Enhancement ratios and therapeutic gain with respect to normal tissues are not yet well documented. Many problems, including the heterogenicity of tissues to be heated, difficulties with temperature monitoring, and selection of appropriate sequential scheduling of radiation and hyperthermia remain unsolved and further investigations are required.

  13. Clinical applications of magnetic resonance imaging - current status

    SciTech Connect

    Cammoun, D.; Hendee, W.R.; Davis, K.A.

    1985-12-01

    Magnetic resonance imaging has far-reaching real and possible clinical applications. Its usefulness has been best explored and realized in the central nervous system, especially the posterior fossa and brain stem, where most abnormalities are better identified than with computed tomography. Its lack of ionizing radiation and extreme sensitivity to normal and abnormal patterns of myelination make magnetic resonance imaging advantageous for diagnosing many neonatal and pediatric abnormalities. New, reliable cardiac gating techniques open the way for promising studies of cardiac anatomy and function. The ability to image directly in three orthogonal planes gives us new insight into staging and follow-up of pelvic tumors and other pelvic abnormalities. Exquisite soft tissue contrast, far above that attainable by other imaging modalities, has made possible the early diagnosis of traumatic ligamentous knee injury, avascular necrosis of the hip and diagnosis, treatment planning and follow-up of musculoskeletal neoplasms. 59 references, 9 figures.

  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. Antiretroviral Treatment Interruptions Induced by the Kenyan Postelection Crisis Are Associated With Virological Failure

    PubMed Central

    Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W.; Sidle, John; Buziba, Nathan; Kantor, Rami

    2014-01-01

    Background Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. Methods We determined effects of unplanned TIs after the 2007–2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Results Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Conclusions Unplanned conflict-related TIs are associated with increased likelihood of virological failure. PMID:24047971

  16. 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

  17. Current status of clinical development of interleukin-10.

    PubMed

    Geissler, K

    1996-05-01

    Communication between cells in the lymphohematopoietic system is mediated by soluble molecules called cytokines. Lymphoid and myeloid cells are the cellular targets and source of these regulatory molecules. Interleukin-10 seems to be a main factor of a negative feedback system that inhibits synthesis of proinflammatory cytokines and of colony-stimulating factors in a variety of cells. Considering the cytokine synthesis-inhibiting action of interleukin-10 in activated macrophages, T cells, neutrophils, and eosinophils, many of the biologic effects of interleukin-10 may result in immunosuppression. Recently, the interleukin-10 receptor and some signal transduction events following interleukin-10 binding have been characterized. Substantial progress has also been made in providing the experimental basis for interleukin-10 therapy in various diseases. In vitro and preclinical studies suggest that interleukin-10 may prove quite useful in clinical settings in which overexpression of cytokines is likely to play an important role in pathogenesis, including inflammatory bowel disease, acute pancreatitis, septic shock, and certain malignancies.

  18. Status and future concerns of clinical and environmental aluminum toxicology.

    PubMed

    Flaten, T P; Alfrey, A C; Birchall, J D; Savory, J; Yokel, R A

    1996-08-30

    A wide range of toxic effects of aluminum (Al) have been demonstrated in plants and aquatic animals in nature, in experimental animals by several routes of exposure, and under different clinical conditions in humans. Aluminum toxicity is a major problem in agriculture, affecting perhaps as much as 40% of arable soils in the world. In fresh waters acidified by acid rain, Al toxicity has led to fish extinction. Aluminum is a very potent neurotoxicant. In humans with chronic renal failure on dialysis, Al causes encephalopathy, osteomalacia, and anemia. There are also reports of such effects in certain patient groups without renal failure. Subtle neurocognitive and psychomotor effects and electroencephalograph (EEG) abnormalities have been reported at plasma Al levels as low as 50 micrograms/L. Infants could be particularly susceptible to Al accumulation and toxicity, reduced renal function being one contributory cause. Recent reports clearly show that Al accumulation occurs in the tissues of workers with long-term occupational exposure to Al dusts or fumes, and also indicate that such exposure may cause subtle neurological effects. Increased efforts should be directed toward defining the full range of potentially harmful effects in humans. To this end, multidisciplinary collaborative research efforts are encouraged, involving scientists from many different specialties. Emphasis should be placed on increasing our understanding of the chemistry of Al in biological systems, and on determining the cellular and molecular mechanisms of Al toxicity.

  19. Epidemiology, pathology and clinical features of genital mycoses--1981 status.

    PubMed

    Senft, H H; Korte, W

    1982-01-01

    The clinical picture of candidal vaginitis was described for the first time in 1792. The connection with yeasts was already discovered in the 19th century. Not until the last 35 years, however, have the epidemiologic aspects of genital mycoses and the diagnostic and therapeutic principles been systematically developed. The rise in the incidence of the disease is due to several factors: the administration of corticosteroids, cystostatic agents, and oral contraceptives as well as socioeconomic circumstances. Two serious complications of vaginal yeast infection in pregnant women should be noted: the amniotic infection syndrome and neonatal contamination at the time of delivery. Vulvovaginitis is one of the most common genital diseases in childhood and adolescence. Mycoses can be diagnosed in daily gynecological practice by simple, reliable methods, but only culture on prepared media or by incubation of standardized plates can be depended upon to establish or rule out a mycosis. Effective antimycotics with a broad spectrum of activity have been developed in the last 15 years. We have been primarily concerned with clotrimazole because of our own investigations and impartial comparisons with other fungicidal drugs. Studies of patient compliance have shown that the diseased women accept short-term therapy most readily. However, appropriate control examinations are needed to document the results of treatment. PMID:6761085

  20. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    PubMed

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma.

  1. [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.

  2. Impact of HIV type 1 drug resistance mutations and phenotypic resistance profile on virologic response to salvage therapy.

    PubMed

    Ross, L; Liao, Q; Gao, H; Pham, S; Tolson, J; Hertogs, K; Larder, B; Saag, M S

    2001-10-10

    This study examines the association between presence of drug resistance mutations and phenotypic resistance at baseline to virologic response to salvage therapy in a community setting. The study population consisted of 58 antiretroviral drug-experienced patients with HIV-1 infection who had recently switched therapy because of virologic failure. Drug resistance mutations in the reverse transcriptase- and protease-coding regions and phenotypic susceptibility to 13 antiretroviral drugs were assessed at baseline. Plasma HIV-1 RNA levels were assessed at baseline and at subsequent clinic visits. Results showed that three variables were significant in predicting virologic response: HIV-1 levels at baseline, number of protease mutations, and phenotypic sensitivity score for the regimen at baseline. For four drugs there was a significant association between the presence of specific drug resistance mutations and >10-fold phenotypic resistance to that drug. With phenotypic resistance defined as >4-fold resistance, the association between specific drug resistance mutations and phenotypic resistance was significant for seven drugs. Overall, these data show that phenotypic susceptibility and absence of drug resistance mutations, particularly protease mutations, are significant predictors of virologic response. For several drugs, specific combinations of drug resistance mutations are associated with decreased phenotypic susceptibility and might provide useful clinical guidelines in selecting therapeutic options.

  3. Cautionary tales in the clinical interpretation of trials assessing therapy-induced changes in health status.

    PubMed

    Scott, I A

    2011-05-01

    Trials assessing the effects of therapies on symptoms, functional capacity, health-related quality of life and other aspects of health status are becoming more common in an era of chronic disease management. Such trials involve instruments for measuring health status whose reliability, validity and responsiveness need to be understood by clinicians and policy-makers in interpreting trial results. Deciding whether a treatment is clinically efficacious requires prior determination, based on empirical evidence, of what constitutes a minimal important difference (MID) between active treatment and control groups in the change in health status between study start and end. This MID should be used to calculate the sample size that will confer adequate power to detect a treatment effect if it truly exists. Many trials assessing health status have major methodological flaws: use of inappropriate or psychometrically unsound measurement instruments, lack of specification of MID, assumption that statistically significant results represent clinically significant treatment effects, and statement of conclusions inconsistent with observed results. This article provides guidance to clinicians in interpreting results of such trials in regard to clinical decision-making. PMID:21489078

  4. Epidemiology of dengue and dengue haemorrhagic fever in Malaysia. III. A comparative study of clinical features seen in virologically confirmed cases for periods between 1963-1987--a review.

    PubMed

    Shekhar, K C; Senan, P

    1992-01-01

    Dengue fever, Dengue hemorrhagic fever and Dengue shock syndrome within the dengue complex is a sinister disease of great public health importance and continues to ravage children, young adults and the aged in Malaysia. The history of the disease is traced for over the years and the changing pattern of clinical presentation are noted. Various hospital based studies have been compared and the pathognomonic features of the disease in Malaysia are highlighted.

  5. Virology, Immunology and Pathology of Human Rabies During Treatment

    PubMed Central

    Caicedo, Yolanda; Paez, Andres; Kuzmin, Ivan; Niezgoda, Michael; Orciari, Lillian A.; Yager, Pamela A.; Recuenco, Sergio; Franka, Richard; Velasco-Villa, Andres; Willoughby, Rodney E.

    2016-01-01

    Background Rabies is an acute fatal encephalitis caused by all members of the Lyssavirus genus. The first human rabies survivor without benefit of prior vaccination was reported from Milwaukee in 2005. We report a second unvaccinated patient who showed early recovery from rabies and then died accidentally during convalescence, providing an unparalleled opportunity to examine the histopathology as well as immune and virological correlates of early recovery from human rabies. Methods Case report, rapid fluorescent focus inhibition test, enzyme-linked immunosorbent assay, indirect and direct fluorescent antibody assays, reverse-transcriptase polymerase chain reaction, phylogenetic reconstruction, isolation in tissue culture, pathology and immunohistochemistry. Results The 9 year old died 76 days after presenting with rabies of vampire bat phylogeny transmitted by cat bite. Antibody response in serum and cerebrospinal fluid was robust and associated with severe cerebral edema. No rabies virus was cultured at autopsy. Rabies virus antigen was atypical in size and distribution. Rabies virus genome was present in neocortex but absent in brainstem. Conclusions Clinical recovery was associated with detection of neutralizing antibody and clearance of infectious rabies virus in the central nervous system by 76 days but not clearance of detectable viral subcomponents such as nucleoprotein antigen or RNA in brain. PMID:25405805

  6. The clinical impact of HPV tumor status upon head and neck squamous cell carcinomas

    PubMed Central

    Benson, Eleni; Li, Ryan; Eisele, David; Fakhry, Carole

    2015-01-01

    SUMMARY Human papillomavirus (HPV) is etiologically responsible for a distinct subset of head and neck squamous cell cancers (HNSCCs). HPV-positive HNSCCs (HPV-HNSCCs) most commonly arise from the oropharynx and are responsible for the increasing incidence of oropharyngeal SCC (OSCC) in the United States (US) and abroad. HPV-positive OSCC (HPV-OSCC) has a unique demographic and risk factor profile and tumor biology. HPV-OSCC patients tend to be white, younger, and have a higher cumulative exposure to sexual behaviors as compared with HPV-negative OSCC patients. HPV-positive tumor status also significantly improves survival, and is indeed the single strongest prognostic factor for OSCC. The mechanisms that underlie the improved prognosis conferred by HPV-positive disease are unknown. The purpose of this review is to describe the clinical impact of HPV status in HNSCC, particularly in OSCC, both in terms of the unique clinic-demographic profile and prognostic implications. PMID:24134947

  7. The status of hypnosis as an empirically validated clinical intervention: a preamble to the special issue.

    PubMed

    Nash, M R

    2000-04-01

    In his introductory remarks to this Journal's special issue on the status of hypnosis as an empirically supported clinical intervention, the editor briefly describes the dawn of clinical hypnosis research, the logic of the natural science model, the importance of an inspired but tough-minded clinical science, and the auspicious confluence of practice and research purpose in this enterprise. The progenitor of this effort was indeed the Report of the Royal Commission coauthored by Benjamin Franklin and Antoine Lavoisier, among others, more than 215 years ago--a report noted as one of the most important documents in the history of human reason. The ethos and logic of this special issue is grounded on the legacy of that document. Eschewing the conflicting mental health agendas of managed-care, government, patient rights, and professional guild interests, this special issue seeks to present a frank, evenhanded, informed, and dispassionate assessment of what science knows and does not know about clinical hypnosis. PMID:10769979

  8. The status of hypnosis as an empirically validated clinical intervention: a preamble to the special issue.

    PubMed

    Nash, M R

    2000-04-01

    In his introductory remarks to this Journal's special issue on the status of hypnosis as an empirically supported clinical intervention, the editor briefly describes the dawn of clinical hypnosis research, the logic of the natural science model, the importance of an inspired but tough-minded clinical science, and the auspicious confluence of practice and research purpose in this enterprise. The progenitor of this effort was indeed the Report of the Royal Commission coauthored by Benjamin Franklin and Antoine Lavoisier, among others, more than 215 years ago--a report noted as one of the most important documents in the history of human reason. The ethos and logic of this special issue is grounded on the legacy of that document. Eschewing the conflicting mental health agendas of managed-care, government, patient rights, and professional guild interests, this special issue seeks to present a frank, evenhanded, informed, and dispassionate assessment of what science knows and does not know about clinical hypnosis.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. How the American Society for Virology was founded.

    PubMed

    Joklik, Wolfang K; Grossberg, Sidney E

    2006-01-01

    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.

  16. 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

  17. 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

  18. Impact of immune status on the clinical characteristics and treatment outcomes of nocardiosis.

    PubMed

    Kim, Yong Kyun; Sung, Heungsup; Jung, Jiwon; Yu, Shi Nae; Lee, Ju Young; Kim, Sung-Han; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Lee, Sang-Oh; Chong, Yong Pil

    2016-08-01

    Nocardiosis occurs in both immunocompromised and immunocompetent patients. We aimed to assess how its characteristics differ depending on patients' immune status. Of a total of 54 patients with culture-proven nocardiosis diagnosed over 13 years, 18 (33%) were immunocompetent. Half of immunocompetent patients had chronic lung disease and were not receiving systemic corticosteroid. There were no significant differences in clinical, radiographic, and microbiologic characteristics, and treatment outcomes according to immune status, except that pulmonary cavitation (47% vs. 8%) and coexisting infections (17% vs. 0%) were more frequent in immunocompromised hosts. Nocardia farcinica, the most commonly identified isolates at the species level (51%), was highly susceptible to trimethoprim-sulfamethoxazole (100%) and highly resistant to ceftriaxone (94%). Nocardiosis should be considered in differential diagnosis of pneumonia, brain abscess, or soft tissue infection that does not respond to conventional antibiotic therapy such as ceftriaxone, regardless of whether the patient is immunocompromised or not. PMID:27241370

  19. Super-refractory status epilepticus: an approach to therapy in this difficult clinical situation.

    PubMed

    Shorvon, Simon

    2011-10-01

    Super-refractory status epilepticus (SE) is a stage of refractory SE characterized by unresponsiveness to initial anesthetic therapy. It is a new concept that has been the focus of recent basic and therapeutic work, and is defined as "SE that continues or recurs 24 hours or more after the onset of anesthesia, including those cases in which SE recurs on the reduction or withdrawl of anesthesia." It is encountered typically, but not exclusively, in two quite distinctive clinical situations: (1) in patients with severe acute brain injury, and (2) in patients with no history of epilepsy in whom status epilepticus develops out of the blue with no overt cause. There are a variety of treatments used, almost entirely based on open observational studies or case reports. Therapy includes anesthesia, antiepileptic drug therapy, hypothermia and ICU therapy, other medical, immunological, and physical therapies. In this review, the range of possible therapies is outlined and an approach to therapy is discussed.

  20. 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.

  1. 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

  2. Clinical presentation and visual status of retinitis pigmentosa patients: a multicenter study in southwestern Nigeria

    PubMed Central

    Onakpoya, Oluwatoyin Helen; Adeoti, Caroline Olufunlayo; Oluleye, Tunji Sunday; Ajayi, Iyiade Adeseye; Majengbasan, Timothy; Olorundare, Olayemi Kolawole

    2016-01-01

    Background To review the visual status and clinical presentation of patients with retinitis pigmentosa (RP). Methodology Multicenter, retrospective, and analytical review was conducted of the visual status and clinical characteristics of patients with RP at first presentation from January 2007 to December 2011. Main outcome measure was the World Health Organization’s visual status classification in relation to sex and age at presentation. Data analysis by SPSS (version 15) and statistical significance was assumed at P<0.05. Results One hundred and ninety-two eyes of 96 patients with mean age of 39.08±18.5 years and mode of 25 years constituted the study population; 55 (57.3%) were males and 41 (42.7%) females. Loss of vision 67 (69.8%) and night blindness 56 (58.3%) were the leading symptoms. Twenty-one (21.9%) patients had a positive family history, with RP present in their siblings 15 (71.4%), grandparents 11 (52.3%), and parents 4 (19.4%). Forty (41.7%) were blind at presentation and 23 (24%) were visually impaired. Blindness in six (15%) patients was secondary to glaucoma. Retinal vascular narrowing and retinal pigmentary changes of varying severity were present in all patients. Thirty-five (36.5%) had maculopathy, 36 (37.5%) refractive error, 19 (20%) lenticular opacities, and eleven (11.5%) had glaucoma. RP was typical in 85 patients (88.5%). Older patients had higher rates of blindness at presentation (P=0.005); blindness and visual impairment rate at presentation were higher in males than females (P=0.029). Conclusion Clinical presentation with advanced diseases, higher blindness rate in older patients, sex-related difference in blindness/visual impairment rates, as well as high glaucoma blindness in RP patients requires urgent attention in southwestern Nigeria.

  3. 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.

  4. Clinical presentation and visual status of retinitis pigmentosa patients: a multicenter study in southwestern Nigeria

    PubMed Central

    Onakpoya, Oluwatoyin Helen; Adeoti, Caroline Olufunlayo; Oluleye, Tunji Sunday; Ajayi, Iyiade Adeseye; Majengbasan, Timothy; Olorundare, Olayemi Kolawole

    2016-01-01

    Background To review the visual status and clinical presentation of patients with retinitis pigmentosa (RP). Methodology Multicenter, retrospective, and analytical review was conducted of the visual status and clinical characteristics of patients with RP at first presentation from January 2007 to December 2011. Main outcome measure was the World Health Organization’s visual status classification in relation to sex and age at presentation. Data analysis by SPSS (version 15) and statistical significance was assumed at P<0.05. Results One hundred and ninety-two eyes of 96 patients with mean age of 39.08±18.5 years and mode of 25 years constituted the study population; 55 (57.3%) were males and 41 (42.7%) females. Loss of vision 67 (69.8%) and night blindness 56 (58.3%) were the leading symptoms. Twenty-one (21.9%) patients had a positive family history, with RP present in their siblings 15 (71.4%), grandparents 11 (52.3%), and parents 4 (19.4%). Forty (41.7%) were blind at presentation and 23 (24%) were visually impaired. Blindness in six (15%) patients was secondary to glaucoma. Retinal vascular narrowing and retinal pigmentary changes of varying severity were present in all patients. Thirty-five (36.5%) had maculopathy, 36 (37.5%) refractive error, 19 (20%) lenticular opacities, and eleven (11.5%) had glaucoma. RP was typical in 85 patients (88.5%). Older patients had higher rates of blindness at presentation (P=0.005); blindness and visual impairment rate at presentation were higher in males than females (P=0.029). Conclusion Clinical presentation with advanced diseases, higher blindness rate in older patients, sex-related difference in blindness/visual impairment rates, as well as high glaucoma blindness in RP patients requires urgent attention in southwestern Nigeria. PMID:27601870

  5. 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

  6. 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

  7. Clinical and virological characterization of imported cases of Chikungunya fever.

    PubMed

    Pfeffer, Martin; Zöller, Gudrun; Essbauer, Sandra; Tomaso, Herbert; Behrens-Riha, Nicole; Löscher, Thomas; Dobler, Gerhard

    2008-01-01

    A Chikungunya virus (CHIKV) epidemic emerged in the Indian Ocean islands of the Comores, Reunion, Mayotte, Mauritius, the Seychelles and Madagascar in 2005 resulting in the infection of about 250.000 inhabitants and travellers in only one year. Beginning in March 2006 increasing numbers of CHIKV-like febrile illnesses were reported from various parts of India. We investigated 70 consecutive German travellers returning from the affected areas and presenting with arthralgia and/or fever suggestive of CHIKV infection. Eleven patients had serological evidence of CHIKV infection. Real-time RT-PCR for CHIKV was positive in two cases, one who returned from Mauritius and the other who came back from Rajasthan, Northern India. In both cases CHIKV was isolated and sequencing of the entire viral genome was performed. The nucleotide sequence data obtained for both CHIKV strains revealed a high level of identity to CHIKV isolates from the ongoing epidemic. In detail, we found only 18 nucleotide exchanges between the isolates from Mauritius and Rajasthan, resulting in only six amino acid changes (nsP1 T128K, T376M, nsP3 S472N, capsid P23S, V27I and E1-protein A226V). Although the excessive dimension of the 2005/2006 outbreak in the Indian Ocean islands was at least in part accounted to the naïve population affected, our results of the Rajasthan isolate support that the emergence of this CHIKV subtype may rather be a result of a better viral fitness. This has been previously accounted to a A226V change in the E1 protein of the new CHIKV variant when compared to other CHIKV data available. This mutation, supposedly resulting in high-titred viremia in humans and/or an enhanced adaptation to the vector population resulting in increased transmission rates, was also found in our CHIKV isolate from Mauritius. The spread of an African CHIKV to Asia further demonstrates how fast viruses can emerge and establish in places where competent vectors are prevalent.

  8. 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

  9. [Anogenital warts: a clinical, pathological and virological study].

    PubMed

    Mataix Díaz, J; Betlloch Mas, I; Pastor Tomás, N; Bañuls Roca, J; Martínez, M T

    2008-12-01

    The objective of this study was to investigate the possible relationship between the presence of anogenital warts (AGW) in children and the sexual abuse as mode of transmission. Our series includes 8 patients with AGW who were treated in our hospital during the year 2007. A complete physical examination was carried out, including colposcopy or anoscopy, and samples were taken for histopathological examination and human papiloma virus (HPV) subtyping. We considered perinatal transmission as a possible route in two cases. Although sexual abuse was definitively confirmed in only one case, we observed some findings in four cases that led us to consider the possibility of sexual abuse. We did not consider the possibility of heteroinoculation or autoinoculation from common warts in any case. Our results have demonstrated the difficulty in assessing with certainty the source of HPV contamination in children with AGW.

  10. [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.

  11. [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. PMID:15619815

  12. 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

  13. 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.

  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. PMID:26244516

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

    PubMed Central

    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. PMID:26244516

  16. 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.

  17. 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…

  18. Identifying and extracting patient smoking status information from clinical narrative texts in Spanish.

    PubMed

    Figueroa, Rosa L; Soto, Diego A; Pino, Esteban J

    2014-01-01

    In this work we present a system to identify and extract patient's smoking status from clinical narrative text in Spanish. The clinical narrative text was processed using natural language processing techniques, and annotated by four people with a biomedical background. The dataset used for classification had 2,465 documents, each one annotated with one of the four smoking status categories. We used two feature representations: single word token and bigrams. The classification problem was divided in two levels. First recognizing between smoker (S) and non-smoker (NS); second recognizing between current smoker (CS) and past smoker (PS). For each feature representation and classification level, we used two classifiers: Support Vector Machines (SVM) and Bayesian Networks (BN). We split our dataset as follows: a training set containing 66% of the available documents that was used to build classifiers and a test set containing the remaining 34% of the documents that was used to test and evaluate the model. Our results show that SVM together with the bigram representation performed better in both classification levels. For S vs NS classification level performance measures were: ACC=85%, Precision=85%, and Recall=90%. For CS vs PS classification level performance measures were: ACC=87%, Precision=91%, and Recall=94%. PMID:25570550

  19. Identifying and extracting patient smoking status information from clinical narrative texts in Spanish.

    PubMed

    Figueroa, Rosa L; Soto, Diego A; Pino, Esteban J

    2014-01-01

    In this work we present a system to identify and extract patient's smoking status from clinical narrative text in Spanish. The clinical narrative text was processed using natural language processing techniques, and annotated by four people with a biomedical background. The dataset used for classification had 2,465 documents, each one annotated with one of the four smoking status categories. We used two feature representations: single word token and bigrams. The classification problem was divided in two levels. First recognizing between smoker (S) and non-smoker (NS); second recognizing between current smoker (CS) and past smoker (PS). For each feature representation and classification level, we used two classifiers: Support Vector Machines (SVM) and Bayesian Networks (BN). We split our dataset as follows: a training set containing 66% of the available documents that was used to build classifiers and a test set containing the remaining 34% of the documents that was used to test and evaluate the model. Our results show that SVM together with the bigram representation performed better in both classification levels. For S vs NS classification level performance measures were: ACC=85%, Precision=85%, and Recall=90%. For CS vs PS classification level performance measures were: ACC=87%, Precision=91%, and Recall=94%.

  20. 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.

  1. Concise Review: The Clinical Application of Mesenchymal Stem Cells for Musculoskeletal Regeneration: Current Status and Perspectives

    PubMed Central

    Steinert, Andre F.; Rackwitz, Lars; Gilbert, Fabian; Nöth, Ulrich

    2012-01-01

    Regenerative therapies in the musculoskeletal system are based on the suitable application of cells, biomaterials, and/or factors. For an effective approach, numerous aspects have to be taken into consideration, including age, disease, target tissue, and several environmental factors. Significant research efforts have been undertaken in the last decade to develop specific cell-based therapies, and in particular adult multipotent mesenchymal stem cells hold great promise for such regenerative strategies. Clinical translation of such therapies, however, remains a work in progress. In the clinical arena, autologous cells have been harvested, processed, and readministered according to protocols distinct for the target application. As outlined in this review, such applications range from simple single-step approaches, such as direct injection of unprocessed or concentrated blood or bone marrow aspirates, to fabrication of engineered constructs by seeding of natural or synthetic scaffolds with cells, which were released from autologous tissues and propagated under good manufacturing practice conditions (for example, autologous chondrocyte implantation). However, only relatively few of these cell-based approaches have entered the clinic, and none of these treatments has become a “standard of care” treatment for an orthopaedic disease to date. The multifaceted reasons for the current status from the medical, research, and regulatory perspectives are discussed here. In summary, this review presents the scientific background, current state, and implications of clinical mesenchymal stem cell application in the musculoskeletal system and provides perspectives for future developments. PMID:23197783

  2. 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.

  3. 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

  4. Teaching medical students a clinical approach to altered mental status: simulation enhances traditional curriculum

    PubMed Central

    Sperling, Jeremy D.; Clark, Sunday; Kang, Yoon

    2013-01-01

    Introduction Simulation-based medical education (SBME) is increasingly being utilized for teaching clinical skills in undergraduate medical education. Studies have evaluated the impact of adding SBME to third- and fourth-year curriculum; however, very little research has assessed its efficacy for teaching clinical skills in pre-clerkship coursework. To measure the impact of a simulation exercise during a pre-clinical curriculum, a simulation session was added to a pre-clerkship course at our medical school where the clinical approach to altered mental status (AMS) is traditionally taught using a lecture and an interactive case-based session in a small group format. The objective was to measure simulation's impact on students’ knowledge acquisition, comfort, and perceived competence with regards to the AMS patient. Methods AMS simulation exercises were added to the lecture and small group case sessions in June 2010 and 2011. Simulation sessions consisted of two clinical cases using a high-fidelity full-body simulator followed by a faculty debriefing after each case. Student participation in a simulation session was voluntary. Students who did and did not participate in a simulation session completed a post-test to assess knowledge and a survey to understand comfort and perceived competence in their approach to AMS. Results A total of 154 students completed the post-test and survey and 65 (42%) attended a simulation session. Post-test scores were higher in students who attended a simulation session compared to those who did not (p<0.001). Students who participated in a simulation session were more comfortable in their overall approach to treating AMS patients (p=0.05). They were also more likely to state that they could articulate a differential diagnosis (p=0.03), know what initial diagnostic tests are needed (p=0.01), and understand what interventions are useful in the first few minutes (p=0.003). Students who participated in a simulation session were more likely

  5. 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

  6. [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.

  7. [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. PMID:20084925

  8. Clinical status of anti-cancer agents derived from marine sources.

    PubMed

    Singh, Ram; Sharma, Mukul; Joshi, Penny; Rawat, Diwan S

    2008-08-01

    The chemical, biological and ecological diversity of the marine ecosystem has contributed immensely in the discovery of extremely potent compounds that have shown potent activities in antitumor, analgesia, antiinflammatory, immunomodulation, allergy, anti-viral etc. The compounds of marine origin are diverse in structural class from simple linear peptides to complex macrocyclic polyethers. The recent advances in the sophisticated instruments for the isolation and characterization of marine natural products and development of high-throughput screening, have substantially increased the rate of discovery of various compounds of biomedical application. Didemnin was the first marine peptide that entered in human clinical trials in US for the treatment of cancer and other compounds such as dolastatin-10, soblidotin, didemnin B, ecteinascidin 743, girolline, aplidine, cryptophycins (also arenastatin A), bryostatin 1, ILX 651, kahalalide F, E7389, discodermolide, ES-285 (spisulosine), HTI-286 (hemiasterlin derivative), squalamine, KRN-7000, vitilevuamide, Laulimalide, Curacin A, diazonamide, peloruside A, eleutherobin, sarcodictyin, thiocoraline, salicylihalimides A, ascididemnin, CGX-1160, CGX-1007dictyodendrins, GTS-21 (aka DMBX), manoalide, IPL-576,092 (aka HMR-4011A) have entered in the clinical trials. This article summarize clinical status and synthetic advances of some of these compounds. PMID:18690825

  9. Self-reported non-adherence to ART and virological outcome in a multiclinic UK study.

    PubMed

    Sherr, L; Lampe, F C; Clucas, C; Johnson, M; Fisher, M; Leake Date, H; Anderson, J; Edwards, S; Smith, C J; Hill, T; Harding, R

    2010-08-01

    Adherence is of fundamental importance to ART success. We examined the association of self-reported non-adherence with demographic factors, health and behaviour issues, and virological outcome, in a multi-clinic study. Seven hundred and seventy-eight HIV patients in five clinics in London and Brighton completed a questionnaire on adherence and HIV/health issues at baseline in 2005/6. For 486 subjects taking ART, non-adherence in the past week was defined as: (A)>or=1 dose missed or taken incorrectly (wrong time/circumstances); (B)>or=1 dose missed; (C)>or=2 doses missed. Questionnaire data were matched with routine treatment and virology data for consenting subjects (61.4%). We assessed four virological outcomes in 307 of 486 patients: (i) VL>50c/mL using latest VL at the questionnaire and excluding patients starting HAART<24 weeks ago; (ii) VL>50c/mL using the first VL from 6 to 12 months post-questionnaire; (iii) any VL>50c/mL from 6 to 12 months post-questionnaire; (iv) among patients with VL<50c/mL at questionnaire, time to first subsequent VL>50c/mL over two years follow up. Non-adherence was reported by 278 (57.2%), 102 (21.0%) and 49 (10.1%) of 486 patients, for definitions A, B and C, respectively. Non-adherence declined markedly with older age, and tended to be more commonly reported by Black patients, those born outside the UK, those with greater psychological symptoms and those with suicidal thoughts. There was a weaker association with physical symptoms and no association with gender/sexuality, education, unemployment, or risk behaviour (p>0.1). In logistic regression analyses, younger age, non-UK birth and psychological variables were independent predictors of non-adherence [e.g., for non-adherence B: odds ratios (95% CI) were 0.95 (0.92, 0.98) for every year older age; 1.6 (1.0, 2.5) for non-UK born; 2.3 (1.5, 3.7) for suicidal thoughts]. Non-adherence was associated with poorer virological outcome; the most consistent association was for definition C

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

    PubMed

    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; Koelsch, Kersten K; Kelleher, Anthony D; Phillips, Rodney E; Frater, John

    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. PMID:25217531

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

    PubMed

    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; Koelsch, Kersten K; Kelleher, Anthony D; Phillips, Rodney E; Frater, John

    2014-09-12

    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.

  12. 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

  13. Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review).

    PubMed

    Zinner, Ralph; Visseren-Grul, Carla; Spigel, David R; Obasaju, Coleman

    2016-01-01

    Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make treatment decisions. Advanced NSCLC patients with an Eastern Cooperative Oncology Group PS of 2 have poor prognoses and are frequently excluded from clinical trials. This article reviews the efficacy and safety of pemetrexed in this patient group. We identified English-language literature (through March 2015) involving completed and ongoing studies through searches of PubMed, meeting abstracts, ClinicalTrials.gov and the European Clinical Trials Register; search terms included 'pemetrexed,' 'NSCLC' and 'PS2'. Only studies reporting ≥1 subset analysis of PS2 patients receiving pemetrexed were chosen. Our search identified a total of ten pemetrexed studies in PS2 patients. Eight studies included only chemonaive patients, one study included both chemonaive patients and patients with one prior chemotherapy regimen and one study included only patients with one prior regimen. In subset analyses in these studies, PS2 patients had worse outcomes than PS0-1 patients regardless of treatment. In a phase 3 study, chemonaive advanced NSCLC patients with PS2 receiving pemetrexed‑carboplatin versus pemetrexed experienced improved overall survival [hazard ratio (HR)=0.62; P=0.001], progression-free survival (HR=0.46; P<0.001) and response (P=0.032). This review confirms the poorer outcomes in PS2 vs. PS0-1 patients. Although it is not an approved combination therapy, in clinical studies, PS2 patients treated with pemetrexed plus carboplatin as first-line therapy had improved response rates and survival. Additional research on PS2 patients is needed.

  14. One hundred years of virology: a chief's perspective.

    PubMed

    Foster, J R

    2002-03-01

    The ubiquitous nature of viruses has had its impact throughout the living world. Virus disease can be found in higher animals, birds, plants, arthropods, protozoa and bacteria. Viruses are no modern phenomenon, although it is only in the last 50 or so years that a fuller knowledge of their biological, chemical and physical properties has emerged. This short account recalls the development of human virology in particular, from the first discovery of a 'filterable virus' in 1892 to the spectacular technological breakthroughs during the 1950's and 1960's, leading to the molecular virology of today. This account was written to accompany an exhibition of artefacts displayed during the IBMS Congress in Birmingham in September 2001.

  15. Comparison of Diffusion Tensor Tractography and Motor Evoked Potentials for the Estimation of Clinical Status in Subacute Stroke

    PubMed Central

    Chun, Kwang-Soo; Lee, Yong-Taek; Park, Jong-Wan; Lee, Joon-Youn; Park, Chul-Hyun

    2016-01-01

    Objective To compare diffusion tensor tractography (DTT) and motor evoked potentials (MEPs) for estimation of clinical status in patients in the subacute stage of stroke. Methods Patients with hemiplegia due to stroke who were evaluated using both DTT and MEPs between May 2012 and April 2015 were recruited. Clinical assessments investigated upper extremity motor and functional status. Motor status was evaluated using Medical Research Council grading and the Fugl-Meyer Assessment of upper limb and hand (FMA-U and FMA-H). Functional status was measured using the Modified Barthel Index (MBI). Patients were classified into subgroups according to DTT findings, MEP presence, fractional anisotropy (FA) value, FA ratio (rFA), and central motor conduction time (CMCT). Correlations of clinical assessments with DTT parameters and MEPs were estimated. Results Fifty-five patients with hemiplegia were recruited. In motor assessments (FMA-U), MEPs had the highest sensitivity and negative predictive value (NPV) as well as the second highest specificity and positive predictive value (PPV). CMCT showed the highest specificity and PPV. Regarding functional status (MBI), FA showed the highest sensitivity and NPV, whereas CMCT had the highest specificity and PPV. Correlation analysis showed that the resting motor threshold (RMT) ratio was strongly associated with motor status of the upper limb, and MEP parameters were not associated with MBI. Conclusion DTT and MEPs could be suitable complementary modalities for analyzing the motor and functional status of patients in the subacute stage of stroke. The RMT ratio was strongly correlated with motor status. PMID:26949679

  16. Pharmacist-managed clinics for patient education and counseling in Japan: current status and future perspectives.

    PubMed

    Yamada, Kiyofumi; Nabeshima, Toshitaka

    2015-01-01

    To improve the adherence to and knowledge about pharmacotherapy in outpatients and to maximize the efficacy and minimize the adverse drug events, the first pharmacist-managed clinic (PMC) in Japan was established for anticoagulation therapy at Nagoya University Hospital in 2000. Since then, various PMCs such as for asthma/chronic obstructive pulmonary disease, Alzheimer's disease, hypercholesterolemia, chronic hepatitis C, cancer chemotherapy, palliative care, chronic kidney disease, and continuous ambulatory peritoneal dialysis have been established and expanded to many hospitals in Japan. Accumulating evidences suggest that PMCs have some beneficial effects on patients' adherence to and knowledge about their pharmacotherapy as well as the clinical outcome, besides being cost-effective. Notably, PMCs for cancer chemotherapy have been approved as a new medical service in hospitals in 2014, which is covered by the universal health coverage in Japan. In this review article, the current status of PMCs for patient education and counseling in Japan and their impact on pharmaceutical care and management are critically reviewed. Furthermore, future perspectives on PMCs are discussed. PMID:26819713

  17. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    PubMed Central

    Ishii, Tetsuya

    2014-01-01

    Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS) cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART) that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions. PMID:26237592

  18. Nodal Status Assessment in Breast Cancer: Strategies of Clinical Grounds and Quality of Life Implications

    PubMed Central

    Vanni, Gianluca; Granai, Alessandra Vittoria; Petrella, Giuseppe; Buonomo, Oreste Claudio

    2014-01-01

    Even in the era of gene-expression profiling, the nodal status still remains the primary prognostic discriminant in breast cancer patients. The exclusion of node involvement using noninvasive methods could reduce the rate of axillary surgery, thereby preventing from suffering complications. However, lymphatic mapping with sentinel node biopsy (SNB) is one of the most interesting recent developments in surgical oncology. Optimization of procedure could be implemented by dual mapping injection site skills, resection of all hot or blue nodes through tracer combination, and improvement in atypical drainage patterns mapping. This anatomical analysis suggests safety measures in patients with high probability of node metastasis through a renewed interest in surgical management. The perspective of a guided axillary sampling (GAS) could represent a potential development of recent anatomical and functional acquisitions, offering a dynamic technique shared according to clinical and anatomical disease parameters. Furthermore, the surgical staging procedures may adopt a conservative approach through the evaluation of upper arm lymphatics, thus defining a functional model aimed at the reduction of short- and long-term adverse events. Quality results in breast cancer surgery need to generate oncological safety devoid of complications through renewed clinical experience. PMID:24672730

  19. Anemia and iron status of Malay women attending an antenatal clinic in Kubang Kerian, Kelantan, Malaysia.

    PubMed

    Hassan, Rosline; Abdullah, Wan Zaidah; Nik Hussain, Nik Hazlina

    2005-09-01

    The purpose of this study was to detect the frequency of iron deficiency anemia in women attending their first antenatal clinic at a Maternal and Child Health Clinic in Kubang Kerian, a district of Kelantan that is located on the East coast of Malaysia. A cross-sectional study was done over a two-month period and fifty-two Malay women were enrolled in this study. Red blood cell indices and serum ferritin were used as a screening tool for anemia and iron status. Eighteen patients (34.6%) were anemic. The majority were classified as having mild anemia (90%). Four of them had hypochromic microcytic anemia. Of 52 women, 7 had iron deficient erythropoiesis and 11 (61.1%) had iron deficient anemia. The prevalence of iron deficiency anemia in pregnant women was 21.2%, which is similar to other developing countries. The serum ferritin level was significantly associated with the hemoglobin level (p=0.003). Other red blood cell indices were not useful in predicting iron deficient erythropoiesis. It is important to detect iron deficient erythropoiesis during the first antenatal check-up, as it is an early manifestation of iron deficiency anemia. In conclusion, screening for iron deficient is recommended during first antenatal visit because iron deficiency anemia is still the leading cause of nutritional deficiency in pregnant women. This will initiate an early therapeutic intervention so as to reduce public health problem.

  20. Degree of Glutathione Deficiency and Redox Imbalance Depend on Subtype of Mitochondrial Disease and Clinical Status

    PubMed Central

    Enns, Gregory M.; Moore, Tereza; Le, Anthony; Atkuri, Kondala; Shah, Monisha K.; Cusmano-Ozog, Kristina; Niemi, Anna-Kaisa; Cowan, Tina M.

    2014-01-01

    Mitochondrial disorders are associated with decreased energy production and redox imbalance. Glutathione plays a central role in redox signaling and protecting cells from oxidative damage. In order to understand the consequences of mitochondrial dysfunction on in vivo redox status, and to determine how this varies by mitochondrial disease subtype and clinical severity, we used a sensitive tandem mass spectrometry assay to precisely quantify whole blood reduced (GSH) and oxidized (GSSG) glutathione levels in a large cohort of mitochondrial disorder patients. Glutathione redox potential was calculated using the Nernst equation. Compared to healthy controls (n = 59), mitochondrial disease patients (n = 58) as a group showed significant redox imbalance (redox potential −251 mV±9.7, p<0.0001) with an increased level of oxidation by ∼9 mV compared to controls (−260 mV±6.4). Underlying this abnormality were significantly lower whole blood GSH levels (p = 0.0008) and GSH/GSSG ratio (p = 0.0002), and significantly higher GSSG levels (p<0.0001) in mitochondrial disease patients compared to controls. Redox potential was significantly more oxidized in all mitochondrial disease subgroups including Leigh syndrome (n = 15), electron transport chain abnormalities (n = 10), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (n = 8), mtDNA deletion syndrome (n = 7), mtDNA depletion syndrome (n = 7), and miscellaneous other mitochondrial disorders (n = 11). Patients hospitalized in metabolic crisis (n = 7) showed the greatest degree of redox imbalance at −242 mV±7. Peripheral whole blood GSH and GSSG levels are promising biomarkers of mitochondrial dysfunction, and may give insights into the contribution of oxidative stress to the pathophysiology of the various mitochondrial disorders. In particular, evaluation of redox potential may be useful in monitoring of clinical status or response to redox

  1. HIV DNA loads, plasma residual viraemia and risk of virological rebound in heavily treated, virologically suppressed HIV-infected patients.

    PubMed

    Gianotti, N; Canducci, F; Galli, L; Cossarini, F; Salpietro, S; Poli, A; Nozza, S; Spagnuolo, V; Clementi, M; Sampaolo, M; Ceresola, E R; Racca, S; Lazzarin, A; Castagna, A

    2015-01-01

    In this single-centre, retrospective study, we analyzed data of 194 patients receiving antiretroviral therapy with <50 human immunodeficiency virus (HIV) RNA copies/mL in plasma and 318 HIV RNA/DNA paired samples. By kinetic polymerase chain reaction (kPCR) molecular system analysis, 104 (54%) subjects had undetectable HIV RNA and 90 (46%) had residual viraemia. Median (interquartile range) HIV DNA load was 780 (380-1930) copies/10(6) peripheral blood lymphocytes (PBL), and HIV DNA loads were independently associated with residual viraemia (p 0.002). Virological rebound occurred in 29/194 (15%) patients over a median (interquartile range) follow-up of 17.5 (13.5-31.5) months. Residual viraemia (p 0.002), but not HIV DNA load, was independently associated with virological rebound.

  2. 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

  3. Nutritional status and clinical outcomes among institutionalized elderly Chinese in Taiwan.

    PubMed

    Chen, Liang-Kung; Lin, Ming-Hsien; Hwang, Shinn-Jang; Wang, Pein; Chwang, Leh-Chii

    2007-01-01

    Nutrition is an important issue in institutional care, and is related to clinical outcomes in many aspects. Although Taiwan is marching to an aged society, related studies were lacking. Elderly residents in two long-term care facilities (LTCF) were enrolled for study. Nutritional status including anthropometric measurements and laboratory examinations was assessed every 3 months for 12 months. Age, sex-matched community-dwelling elderly participating in the annual health check-up was randomly selected as the control subjects. In total, 66 subjects in LTCF and 870 age, sex-matched community-dwelling elderly were enrolled. Body mass index, serum levels of albumin, and total cholesterol were significantly poorer in LTCF residents than the community-dwelling elderly. Triceps skinfold thickness, hemoglobin, serum albumin, and total cholesterol were progressively deteriorated among the institutionalized elderly during the 6-month follow-up. Thirteen subjects of the study group had been hospitalized during the follow-up. Body mass index, triceps skinfold thickness, mid-arm circumference, serum albumin at screening were significantly poorer and unintentional weight loss within 6 months was significantly greater in subjects who had been hospitalized. By using multivariate logistic regression model, only weight loss >5% within 6-month follow-up was the significant independent predictive factors to hospitalization. In conclusion, nutritional status of institutionalized elderly Chinese was significantly poorer than the community-dwelling elderly. Nutritional markers were progressively deteriorated in LTCF residents during the follow-up period. Unintentional weight loss >5% within 6 months was the only significantly independent predictive factor for hospitalization among the institutionalized elderly Chinese.

  4. Unboosted atazanavir with lamivudine/emtricitabine for patients with long-lasting virological suppression

    PubMed Central

    Carbone, Alessia; Galli, Laura; Bigoloni, Alba; Bossolasco, Simona; Guffanti, Monica; Maillard, Miriam; Carini, Elisabetta; Salpietro, Stefania; Spagnuolo, Vincenzo; Gianotti, Nicola; Lazzarin, Adriano; Castagna, Antonella

    2014-01-01

    Introduction Unboosted atazanavir (ATV) including regimens have been investigated as a ritonavir-sparing simplification strategy. No data are available on removal of one NRTI in subjects effectively treated with unboosted atazanavir+2NRTIs. We present the 48-week virological efficacy and safety of unboosted atazanavir plus lamivudine (3TC) or emtricitabine (FTC) (lamivudine/emtricitabine/Reyataz©, LAREY Study). Materials and Methods Single arm, prospective, pilot study on HIV-treated patients, HBsAg negative, with HIV-RNA<50 cps/mL since at least 2 years, who switched from ATV+2NRTIs to ATV 400 mg QD +3TC or FTC. Virological failure was defined as 2 consecutive values of HIV-RNA>50 cps/ml; viral blip was defined as a single HIV-RNA value>50 cps/ml not subsequently confirmed. Results as median (IQR). Changes between baseline (BL) and week 48 assessed by the Wilcoxon signed rank test. Results Forty patients enrolled: 75% males, 51 (47–54) years, 14% HCV co-infected, infected with HIV since 16 (9–21) years, on antiretroviral therapy since 13 (5–16) years, with a nadir CD4+ of 254 (157–307) cells/mm3, virologically suppressed since 4.2 (2.2–5.4) years; 53 patients switched from a tenofovir (TDF)-based regimens; ATV was associated with 3TC in 83% patients. No virological failures or discontinuations were observed; three patients had a single viral blip in the range 50–250 copies/mL; CD4+ increased from 610 (518–829) cells/mm3 at BL to 697 (579–858) cells/mm3 at week 48 [48-week change: 39 (−63/+160) cells/mm3 p=0.081]. Three clinical events were observed (one herpes zoster, one pneumonia, one syphilis) in absence of renal lithiasis, AIDS-defining or drug-related events or death. Overall, significant 48-week amelioration of ALP [BL: 83 (71–107) mg/dL; 48-week change: −15 (−27/−8) mg/dL p<0.0001] and CKD-EPI [BL: 100 (86–108) ml/min/1.73 m2; 48-week change: 1.5 (−3/+8) ml/min/1.73 m2, p=0.042] were observed. Patients switching from TDF

  5. Construction of Multi-dimensional Arterial Health Status Map based on Molecular and Clinical Measurements, Fuzzy System and Data Cubes

    PubMed Central

    Chan, Lawrence W.C.; Benzie, Iris F.F.; Lau, Thomas Y.H.; Zheng, Yongping; Wong, Alex K.S.; Liu, Y.; Chan, Phoebe S.T.

    2008-01-01

    Atherosclerosis results from inflammatory processes involving biomarkers, such as lipid profile, haemoglobin A1C, oxidative stress, coronary artery calcium score and flow-mediated endothelial response through nitric oxide. This paper proposes a health status coefficient, which comprehends molecular and clinical measurements concerning atherosclerosis to provide a measure of arterial health. An arterial health status map is produced to map the multi-dimensional measurements to the health status coefficient. The mapping is modeled by a fuzzy system embedded with the health domain expert knowledge. The measurements obtained from the pilot study are used to tune the fuzzy system. The inferred arterial health coefficients are stored into the data cubes of a multi-dimensional database. Due to this adaptability and transparency of fuzzy system, the health status map can be easily updated when the refinement of fuzzy rule base is needed or new measurements are obtained. PMID:21347120

  6. 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

  7. 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

  8. 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; 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

  9. 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; 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.

  10. 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.

  11. Influence of socioeconomic status on clinical outcomes and quality of life after percutaneous coronary intervention

    PubMed Central

    Denvir, M A; Lee, A J; Rysdale, J; Walker, A; Eteiba, H; Starkey, I R; Pell, J P

    2006-01-01

    Objectives To determine whether socioeconomic status (SES) influences clinical outcomes and quality of life after percutaneous coronary intervention (PCI). Design Prospective observational study. Setting Two interventional cardiac centres. Participants 1346 consecutive patients undergoing PCI over a 12‐month period. Outcomes Self reported health‐related quality of life (HRQoL; EuroQol‐5 Dimensions (EQ‐5D); EuroQol Visual Analogue Scale (EQ‐VAS)), repeat angiography, revascularisation, hospital admission, myocardial infarction and death within 12 months, by SES derived using postal address code. Main results No significant differences were found between patients with high and low SES in the occurrence of repeat angiography (p = 0.55), repeat revascularisation (PCI, p = 0.81, CAEG, p = 0.27), total cardiac hospitalisation (p = 0.10), myocardial infarction (p = 0.97) or death 12 months after PCI (p = 0.88). Non‐procedure‐related readmissions were higher in patients with low SES (18.6% v 13.7%; p = 0.025). After adjustment for confounding factors, patients with low SES had lower HRQoL scores at baseline (95% CI for difference 0.01 to 0.14; p = 0.003) and at 12 months (95% CI 0.07 to 0.17; p<0.001) compared with those with high SES. Conclusions Clinical outcomes were similar for patients in different SES groups. Patients with low SES had considerably more non‐procedure‐related readmissions and lower quality‐of‐life scores. Future studies on HRQoL after coronary revascularisation should take account of these important differences related to SES. PMID:17108307

  12. The current status and future of multiple myeloma in the clinic.

    PubMed

    Jagannath, Sundar; Kyle, Robert A; Palumbo, Antonio; Siegel, David S; Cunningham, Sonia; Berenson, James

    2010-02-01

    It is now recognized that all cases of multiple myeloma (MM) are preceded by the premalignant condition of monoclonal gammopathy of undetermined significance (MGUS). Although patients with MGUS are generally asymptomatic and currently managed by "watch and wait," the identification of high-risk patients whose disease will progress more rapidly to smoldering MM (SMM) and MM aids in timely intervention. The immunomodulatory agents thalidomide and lenalidomide and the proteasome inhibitor bortezomib are now routine components of MM therapy in both first-line and relapsed/ refractory settings. These targeted agents are used in various combinations with chemotherapy for the treatment of both transplantation-ineligible and transplantation-eligible patients. More recently, a trend toward evaluation of 3- and 4-drug multiagent combinations before transplantation and prolongation of primary therapy has generated new treatment paradigms. Ultimately, the physician's choice of therapy and treatment strategy requires consideration of regimen-associated toxicities and integration of the patient's risk, comorbid status, and response and tolerability of previous treatment regimens. Particular attention needs to be paid to baseline and/or treatment-emergent peripheral neuropathy, thrombotic risk, changes in renal function, and bone health. Despite recent advances, all patients with MM eventually relapse, and efforts to identify novel synergistic combinations and new agents are ongoing. This review highlights challenges in the clinic and newer approaches under evaluation for the treatment and/or management of patients with MGUS, SMM, and MM. PMID:20223727

  13. 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.

  14. Status and potential clinical value of a transthoracic evaluation of the coronary arteries.

    PubMed

    Labombarda, Fabien; Castelnuovo, Samuela; Goularas, Dionysis; Sirtori, Cesare R

    2016-01-01

    The growing need for coronary evaluation has raised interest in non-radioactive, non-invasive monitoring systems. In particular, radiation exposure during coronary investigations has been shown to be a possible cause of an enhanced risk of secondary tumors. Literature search has indicated that transthoracic echocardiography (TTE) has been widely applied to coronary arteries up to 2003, following which the lack of adequate equipment and the increased availability of invasive diagnostics, has reduced interest in this low cost, low-risk technology. The more recent availability of newer, more sensitive machines, allows evaluation of a larger number of arterial trees, including the aorta in newborns, the prenatal aortic intima-media thickness, as well as the detection of coronary artery anomalies in the adult. Improved technology for this highly operator sensitive technique may thus predict a possible evolution toward the clinical diagnostics of coronary disease and, eventually, also of the progression/regression of disease. We sought to evaluate the present status of this seldom quoted non-invasive technology. PMID:26787070

  15. 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. PMID:27617007

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. The usefulness of holotranscobalamin in predicting vitamin B12 status in different clinical settings.

    PubMed

    Herrmann, Wolfgang; Obeid, Rima; Schorr, Heike; Geisel, Jürgen

    2005-02-01

    Serum concentrations of homocysteine (Hcy) and methylmalonic acid (MMA) become increased in B12-deficient subjects and are therefore, considered specific markers of B12 deficiency. Serum level of holotranscobalamin (holoTC) becomes decreased before the development of the metabolic dysfunction. We investigated the usefulness of holoTC in diagnosing B12 deficiency in some clinical settings. We measured serum concentrations of holoTC, MMA, Hcy and total B12 in omnivores, vegetarians, elderly people and haemodialysis patients. Our results indicated that the incidence of holoTC <35 pmol/L was highest in the vegans (76%). Low holoTC and elevated MMA were detected in 64% of the vegans and 43% of the lacto- and lacto-ovovegetarians. An elevated MMA and a low holoTC were found in subjects with total serum B12 as high as 300 pmol/L. The distribution of holoTC in elderly people was similar to that in younger adults (median holoTC 55 pmol/L in both groups). A low holoTC and an elevated MMA were found in 16% of the elderly group. An elevated MMA and a normal holoTC were found in 20% of the elderly group who had a relatively high median serum concentration of creatinine (106.1 micromol/L). Serum concentrations of holoTC in dialysis patients were considerably higher than all other groups (median 100 pmol/L). This was also associated with severely increased serum levels of MMA (median 987 nmol/L). From these results it can be concluded that serum concentration of holoTC is a much better predictor of B12 status than total B12. This was particularly evident in case of dietary B12 deficiency. Serum concentrations of holoTC as well as MMA can be affected by renal dysfunction. Elevated MMA and normal holoTC in patients with renal insufficiency may not exclude vitamin B12 deficiency. HoloTC seems not to be a promising marker in predicting B12 status in renal patients.

  1. 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.

  2. [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. PMID:25166934

  3. 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

  4. 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. PMID:24359605

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

    PubMed Central

    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. PMID:24359605

  6. 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.

  7. 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.

  8. 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.

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

    PubMed

    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

  10. 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

  11. A Randomized, Placebo-Controlled Trial of Abacavir Intensification in HIV-1–Infected Adults With Virologic Suppression on a Protease Inhibitor–Containing Regimen

    PubMed Central

    Hammer, Scott M.; Ribaudo, Heather; Bassett, Roland; Mellors, John W.; Demeter, Lisa M.; Coombs, Robert W.; Currier, Judith; Morse, Gene D.; Gerber, John G.; Martinez, Ana I.; Spreen, William; Fischl, Margaret A.; Squires, Kathleen E.

    2011-01-01

    Background and Objective Maximizing the durability of viral suppression is a key goal of antiretroviral therapy. The objective of AIDS Clinical Trials Group Study 372A was to determine whether the intensification strategy of adding abacavir to an effective indinavir-dual nucleoside regimen would delay the time to virologic failure. Methods Zidovudine-experienced subjects (n=229) on therapy with indinavir + zidovudine + lamivudine with plasma HIV-1 RNA levels <500 copies/mL were randomized to abacavir 300 mg twice daily or placebo. The primary endpoint was the time to treatment failure, defined as a composite of confirmed virologic failure (2 consecutive HIV-1 RNAs >200 copies/mL) and treatment discontinuation. Results At baseline, the study population was 88% male with a median age of 41 years and median CD4 cell count of 250/mm3. Median follow-up was 4.4 years. The primary endpoint was reached in 61/116 of abacavir versus 62/113 of placebo recipients (P = .77); virologic failure occurred in 34/116 and 42/113 patients, respectively (P = .22). There were no differences in the proportions of subjects with plasma HIV-1 RNA levels below 50 copies/mL, in CD4 cell count increases, nor adverse events between the arms. In the study, 17% of subjects developed nephrolithiasis, 2% experienced abacavir hypersensitivity, and 4.8% experienced at least 1 serious cardiovascular event (7 [6%] in the abacavir arm, 4 [3.5%] in the placebo arm). In additional secondary and post hoc analyses, rates of intermittent viremia, suppression below a plasma HIV-1 RNA level of 6 copies/mL, and HIV-1 proviral DNA levels in peripheral blood mononuclear cells were not significantly different in the 2 arms. Conclusions The strategy of intensification with abacavir in patients who are virologically suppressed on a stable antiretroviral regimen does not confer a clinical or virologic benefit. As antiretroviral regimens have become more potent since this trial was completed, it will be even more

  12. Correlation of clinical features and methylation status of MGMT gene promoter in glioblastomas.

    PubMed

    Blanc, J L; Wager, M; Guilhot, J; Kusy, S; Bataille, B; Chantereau, T; Lapierre, F; Larsen, C J; Karayan-Tapon, L

    2004-07-01

    In an effort to extend the potential relationship between the methylation status of MGMT promoter and response to CENU therapy, we examined the methylation status of MGMT promoter in 44 patients with glioblastomas. Tumor specimens were obtained during surgery before adjuvant treatment, frozen and stored at -80 degrees C until for DNA extraction process. DNA methylation patterns in the CpG island of the MGMT gene were determined in every tumor by methylation specific PCR (MSP). These results were then related to overall survival and response to alkylating agents using statistical analysis. Methylation of the MGMT promoter was detected in 68% of tumors, and 96.7% of methylated tumors exhibited also an unmethylated status. There was no relationship between the methylation status of the MGMT promoter and overall survival and response to alkylating agents. Our observations do not lead us to consider promoter methylation of MGMT gene as a prognostic factor of responsiveness to alkylating agents in glioblastomas. PMID:15332332

  13. 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

  14. 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

  15. Profile and correlates of functional status in elderly patients presenting at a primary care clinic in Nigeria

    PubMed Central

    Adebusoye, Lawrence A.; Ogunbode, Adetola M.; Akinyemi, Joshua O.; Adebayo, Ayodeji M.

    2015-01-01

    Background Assessing the functional status of elderly patients is central in measuring their health outcome. Little is known about the functional status of elderly patients attending our primary care clinic in Nigeria. Objective To assess the correlates of functional status in elderly patients presenting at the General Outpatient Clinic of the University College Hospital, Ibadan, Nigeria. Method A cross-sectional study of 360 randomly selected patients aged 60 years and above was undertaken to assess their functional status by scoring their basic activities of daily living (BADL) using the Modified Bathel Index. An interviewer-administered questionnaire was used to obtain the socio-demographic data, anthropometric measurements and morbidities of each patient. Results The mean age was 69.1 ± 6.6 years with a female-to-male ratio of 1.9: 1. The prevalence of overall functional disability (defined as when assistance was sought in the performance of at least one of the components of BADL) was 88.3%. The highest prevalence of functional disability was experienced in the area of personal hygiene and grooming (95.3%) and transferring from bed to chair (95.3%). Overall functional disability significantly increased with increasing age (χ2 for trend=14.004, p < 0.0001), living in a polygamous family unit (p = 0.025), and lack of formal education (p = 0.020). Conclusion Functional disability was high amongst the elderly in this setting. Age, education, and living in a polygamous type of family unit had significant influence on the functional status. High premium should, therefore, be placed on considering these factors in reducing functional disability in the elderly. PMID:26245617

  16. 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.

  17. Clinical Pharmacokinetic Service and Research--Present Status and Future Goals at SUNY-Buffalo

    ERIC Educational Resources Information Center

    Koup, Jeffrey R.

    1976-01-01

    Two Clinical Pharmacokinetics Laboratories at Buffalo are described: one at the Millard Fillmore Hospital and the other at the Buffalo Children's Hospital. Their research efforts are reviewed and their scientific contributions to clinical therapeutics and pharmaceutical research are noted. (LBH)

  18. The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-Infected Children in Tororo, Uganda

    PubMed Central

    Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

    2014-01-01

    Background Malnutrition may impact the pharmacokinetics (PK) of antiretroviral medications and virologic responses in HIV-infected children. We therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Methods Sparse dried blood spot (DBS) samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from three resource-rich countries (RRC) were utilized to develop the PK models. Results Concentrations in 330 DBS from 163 Ugandan children aged 0.7–7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5–12 years. Among Ugandan children 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008) respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (P<0.001) with a trend towards greater bioavailability when malnourished. Children receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z-scores were associated with reduced risk of virologic failure (p=0.034, p=0.068 respectively). Conclusions Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessements, to further assess causes of virologic failure in Ugandan children. PMID:25742090

  19. Virological course of herpes zoster in otherwise normal hosts.

    PubMed

    Cevenini, R; Donati, M; Rumpianesi, F; Moroni, A; Tosti, A; Patrizi, A; Varotti, C; Negosanti, M

    1983-08-01

    The virological course of herpes zoster infection in 42 otherwise normal hosts was studied by virus isolation and antibody titration. Varicella-zoster virus (VZV) was isolated from vesicle fluid from all three patients examined on the first day of the vesicular eruption and from five out of six examined on the second day. The isolation rate fell to one out of six patients on the seventh day of illness and VZV was not isolated from patients at a later stage of the illness. IgG antibodies were detected by IFAMA and ELISA, in sera from all the patients by the end of the first week of illness; IgG antibody titres were highest during the second and the third weeks. IgM antibodies to VZV were detected in sera from six of the 42 patients with herpes zoster after fractionation by ion-exchange chromatography.

  20. 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

  1. Software library with applications in virology and molecular biology.

    PubMed

    Campione-Piccardo, J

    1986-06-01

    A menu-driven interactive package of computer programs has been developed to help in calculations commonly required in laboratories using virological and molecular biological techniques. Two of the programs use two of the most accurate methods available for determining viral titers, several programs were designed to optimize experimental parameters and others help in the analysis of recombinant DNA data. All of the programs use specially developed original algorithms which in some cases are based also on equations originally derived. The programs were written in Microsoft BASIC using mostly hardware independent commands and functions and should run without major modifications in most microcomputers with BASIC interpreters or compilers. The programs are menu-driven and fully interactive. PMID:3755444

  2. Relationship between energy expenditure, nutritional status and clinical severity before starting enteral nutrition in critically ill children.

    PubMed

    Botrán, Marta; López-Herce, Jesús; Mencía, Santiago; Urbano, Javier; Solana, Maria José; García, Ana; Carrillo, Angel

    2011-03-01

    The objective of the present study was to investigate the relationship between energy expenditure (EE), biochemical and anthropometric nutritional status and severity scales in critically ill children. We performed a prospective observational study in forty-six critically ill children. The following variables were recorded before starting nutrition: age, sex, diagnosis, weight, height, risk of mortality according to the Paediatric Risk Score of Mortality (PRISM), the Revised Paediatric Index of Mortality (PIM2) and the Paediatric Logistic Organ Dysfunction (PELOD) scales, laboratory parameters (albumin, total proteins, prealbumin, transferrin, retinol-binding protein, cholesterol and TAG, and nitrogen balance) and EE measured by indirect calorimetry. The results showed that there was no relationship between EE and clinical severity evaluated using the PRISM, PIM2 and PELOD scales or with the anthropometric nutritional status or biochemical alterations. Finally, it was concluded that neither nutritional status nor clinical severity is related to EE. Therefore, EE must be measured individually in each critically ill child using indirect calorimetry.

  3. Virologic Cure of Hepatitis C: Impact on Hepatic Fibrosis and Patient Outcomes.

    PubMed

    Gonzalez, Humberto C; Duarte-Rojo, Andrés

    2016-07-01

    Treatment with direct-acting antiviral agents has revolutionized the approach to hepatitis C. We are now able to obtain high sustained virological response (SVR) rates, even in the historically difficult-to-treat patient populations. SVR translates into improved clinical outcomes, particularly overall and liver-related mortality, and benefits are more striking in patients with cirrhosis. A 2.5- to 5-fold risk reduction in the incidence of hepatocellular carcinoma and improvement in complications derived from portal hypertension have been reported as well. It is hypothesized that the benefits from SVR occur largely due to regression of fibrosis, which arises from the halt on the fibrogenic stimuli and activation of extracellular matrix reabsorption signals. Non-invasive markers of fibrosis are being utilized to assess regression, but it is still unclear how accurate they are in this clinical scenario. Interventions aiming to improve liver wellness and screening for cirrhosis-related complications should continue to be the norm after SVR. PMID:27177638

  4. Association Between Nutritional Status, Inflammatory Condition, and Prognostic Indexes with Postoperative Complications and Clinical Outcome of Patients with Gastrointestinal Neoplasia.

    PubMed

    Costa, Milena Damasceno de Souza; Vieira de Melo, Camila Yandara Sousa; Amorim, Ana Carolina Ribeiro de; Cipriano Torres, Dilênia de Oliveira; Dos Santos, Ana Célia Oliveira

    2016-10-01

    The aim of this study is to describe and relate nutritional and inflammatory status and prognostic indexes with postoperative complications and clinical outcome of patients with gastrointestinal malignancies. Twenty-nine patients were evaluated; nutritional assessment was carried out by subjective and objective parameters; albumin, pre-albumin, C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP) were determined. To assess prognosis, the Glasgow scale, the Prognostic Inflammatory Nutritional Index (PINI), and CRP/albumin ratio were used; the clinical outcomes considered were hospital discharge and death. A high Subjective Global Assessment (SGA) score was associated with the occurrence of postoperative complications: 73% of the patients with postoperative complications had the highest SGA score, but only 6% of those without postoperative complications had the highest SGA score (P < 0.001). Greater occurrence of death was observed in patients with a high SGA score, low serum albumin, increased CRP, PINI > 1, and Glasgow score 2. There was a positive correlation between weight loss percentage with serum CRP levels (P = 0.002), CRP/albumin (P = 0.002), PINI (P = 0.002), and Glasgow score (P = 0.000). This study provides evidence that the assessment of the nutritional status and the use of prognostic indexes are good tools for predicting postoperative complications and clinical outcome in patients with gastrointestinal neoplasia.

  5. 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.

  6. Influence of Clinical Status and Parasite Load on Erythropoiesis and Leucopoiesis in Dogs Naturally Infected with Leishmania (Leishmania) chagasi

    PubMed Central

    Trópia de Abreu, Raquel; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Coura-Vital, Wendel; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

    2011-01-01

    Background The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). Methodology/Principal Findings The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. Conclusions Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL. PMID:21572995

  7. 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

  8. Current status and future prospects of the development of clinical Pharmacy in China: A SWOT analysis.

    PubMed

    Rao, Yuefeng; Zhao, Qingwei; Zhang, Xiangyi; Yang, Hongyu; Lou, Yan; Zhang, Xingguo

    2016-03-01

    In many industrialized countries, clinical pharmacy has developed into a separate discipline and become a vital part of inpatient care in hospitals. However, as compared to many established branches of medicine, clinical pharmacy is still in its infancy, with much room for growth, improvement, and recognition by both the medical community and patients. In this study, a widely-recognized development strategy analysis tool, Strength, Weakness, Opportunity and Threat (SWOT), was used to systematically address several key issues to the development of clinical pharmacy in China. This analysis aims to provide feasible recommendations for the development of clinical pharmacy in China by identifying current problems and growth opportunities. Full development of clinical pharmacy as a mature clinical discipline will help promote the rational use of drugs by both clinicians and patients and lead to enhanced drug efficacy and safety. PMID:27087089

  9. Current status and future prospects of the development of clinical Pharmacy in China: A SWOT analysis.

    PubMed

    Rao, Yuefeng; Zhao, Qingwei; Zhang, Xiangyi; Yang, Hongyu; Lou, Yan; Zhang, Xingguo

    2016-03-01

    In many industrialized countries, clinical pharmacy has developed into a separate discipline and become a vital part of inpatient care in hospitals. However, as compared to many established branches of medicine, clinical pharmacy is still in its infancy, with much room for growth, improvement, and recognition by both the medical community and patients. In this study, a widely-recognized development strategy analysis tool, Strength, Weakness, Opportunity and Threat (SWOT), was used to systematically address several key issues to the development of clinical pharmacy in China. This analysis aims to provide feasible recommendations for the development of clinical pharmacy in China by identifying current problems and growth opportunities. Full development of clinical pharmacy as a mature clinical discipline will help promote the rational use of drugs by both clinicians and patients and lead to enhanced drug efficacy and safety.

  10. 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

  11. Effect of Habits and Nutritional Status on Clinical Grading and Histopathological Staging in Patients with Oral Sub Mucous Fibrosis

    PubMed Central

    Lanke, Rama Brahmam; Shetty, Rakhith; Akifuddin, Syed; Sahu, Manish; Singh, Navneet; Kaur, Gagandeep; Goyal, Garish

    2015-01-01

    Background Oral submucous fibrosis (OSMF) is a chronic progressive debilitating disease affecting the oral, oropharyngeal and sometimes the oesophageal mucosa resulting in inability to eat due to burning, ulcers and stiffness. Aim The study was undertaken, to evaluate the correlation of clinical staging, histological grading and nutritional status using body mass index (BMI) with gutkha (habit) index in OSMF patients. Materials and Methods The study group comprised of 50 patients clinically diagnosed and histopathologically confirmed cases of OSMF. Habit (gutkha) index was calculated by multiplying duration and frequency. Body mass index was calculated by dividing weight in kilograms and height in centimetres of the patient. Results Male to female ratio was 2.8:1. Clinical grading increased with increase in gutkha index, patients with gutkha index 1-50, maximum were in mild stage; with gutkha index 51-100, maximum in moderate and patients with gutkha index 101-150, all were in severe stage. Histological staging showed direct correlation with gutkha index, it increased with increase in gutkha index with p <0.05. Site analysis showed that buccal mucosa and retromolar area were involved in all the patient and floor of mouth in 46% of patients Body mass index analysis revealed that out of 27 patients with moderate clinical staging 3 was underweight; out of 3 with severe clinical staging, 2 was underweight. Conclusion The duration and frequency of areca nut product use effects on the incidence and severity of OSMF and the patient becomes unable to eat due to burning, ulcers and inability to open mouth which affect the health of the individual. Thus it is important to access the nutritional status to improve the survival rate of patients. PMID:26557616

  12. 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

  13. 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.

  14. Contributions to variability of clinical measures for use as indicators of udder health status in a clinical protocol.

    PubMed

    Fossing, C; Vaarst, M; Houe, H; Enevoldsen, C

    2006-08-22

    A cross-sectional observational study with repeated observations was conducted on 16 Danish dairy farms to quantify the influence of observer, parity, time (stage in lactation) and farm on variables routinely selected for inclusion in clinical protocols, thereby to enable a more valid comparison of udder health between different herds. During 12 months, participating herds were visited 5 times by project technicians, who examined 20 cows and scored the selected clinical variables. The estimates of effect on variables were derived from a random regression model procedure. Statistical analyses revealed that, although estimates for occurrence of several the variables, e.g. degree of oedema, varied significantly between observers, the effects on many of these estimates were similar in size. Almost all estimates for occurrences of variables were significantly affected either parity and lactation stage, or by both e.g. udder tissue consistency. Some variables, e.g. mange, had high estimates for the farm component, and others e.g. teat skin quality had a high individual component. Several of the variables, e.g. wounds on warts, had a high residual component indicating that a there still was a major part of the variation in data, which was unexplained. It was concluded that most of the variables were relevant for implementation in herd health management, but that adjustments need to be made to improve reliability.

  15. The effective evaluation of thyroid status in patients on phenytoin, carbamazepine or sodium valproate attending an epilepsy clinic.

    PubMed Central

    Connacher, A. A.; Borsey, D. Q.; Browning, M. C.; Davidson, D. L.; Jung, R. T.

    1987-01-01

    To assess the most efficient means of monitoring thyroid status in an epilepsy clinic, total thyroxine (T4), free thyroxine stimulating hormone (TSH) were measured in 71 adult patients treated long-term with either phenytoin (DPH), carbamazepine (CBZ) or sodium valproate (VAL). Twenty-seven patients with one or more abnormal thyroid hormone results were further investigated by a thyrotrophin releasing hormone (TRH) test and clinical assessment. T4 was found to be normal in 85% on VAL, 40% on CBZ and 39% on DPH. FT4 was normal in more patients, namely 95% on VAL, 70% on CBZ and 65% on DPH. The TRH tests indicated that FT4 was the most efficient screening test for hypothyroidism in this epileptic population. We estimate that the use of FT4 alone as a screening test would have reduced by 60% the number of TRH tests required. PMID:3128778

  16. Clinical implications of changes in the modern diet: iron intake, absorption and status.

    PubMed

    Heath, Anne-Louise M; Fairweather-Tait, Susan J

    2002-06-01

    The modern British diet contains less red meat and is lower in iron than that consumed 30 years ago. This is in spite of the fact that fortification of foods, particularly breakfast cereals, with iron has become more widespread. Although there is no clear relationship between dietary iron intake and iron status, isotope studies have identified multiple dietary factors that influence iron absorption, such as ascorbic acid, animal tissue, phytates and polyphenols. There is no evidence to suggest that current dietary changes will have a major impact on iron status in the general population; however, effects on the incidence of iron overload in individuals with HFE mutations and iron deficiency in children and premenopausal women remain to be determined.

  17. Clinical relevance of optimizing vitamin D status in soldiers to enhance physical and cognitive performance.

    PubMed

    Wentz, Laurel M; Eldred, Jerad D; Henry, Michael D; Berry-Cabán, Cristóbal S

    2014-01-01

    Vitamin D deficiency initiates a loss of combat effectiveness by impairing physical and cognitive functioning of combat Operators. Synthesized in response to sunlight and consumed in the diet, vitamin D functions as a hormone and regulates gene expression for nearly 300 genes throughout the human body. These target genes are involved processes essential to combat operations, such as immune function, response to stress, inflammation, and regulation of calcium movement. Since widespread vitamin D deficiency is observed across the U.S. population, poor vitamin D status is expected in Servicemembers. Physical conditions linked to vitamin D deficiency include increased risk for muscle or bone injury, muscle weakness, and reduced neuromuscular function. Hormonally, vitamin D levels have been positively correlated with testosterone levels. Vitamin D deficiency is also associated with cognitive decline, depression, and may prolong recovery following mild traumatic brain injury (mTBI). Since vitamin D deficiency elevates systemic inflammation, poor vitamin D status at the time of brain injury may prolong the inflammatory response and exacerbate postconcussive symptoms. Furthermore, veterans with mTBI experience chronic endocrine dysfunction. While vitamin D status has not been assessed post-mTBI, it is plausible that vitamin D levels are altered along with testosterone and growth hormone, raising the question of whether vitamin D deficiency results from trauma-related hormonal abnormalities or whether vitamin D deficiency increases the risk for endocrine dysfunction. Through its association with testosterone production, vitamin D deficiency may increase the risk for posttraumatic stress disorder (PTSD) since testosterone levels are altered in veterans with PTSD. Therefore, vitamin D status has a significant impact on Operator health and performance. Supplementing vita-min D to deficient Operators provides a noninvasive and low-cost intervention to maintain combat force

  18. 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.

  19. 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.

  20. 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. PMID:26149189

  1. 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

  2. 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

  3. The validity and reproducibility of clinical assessment of nutritional status in the elderly.

    PubMed

    Duerksen, D R; Yeo, T A; Siemens, J L; O'Connor, M P

    2000-09-01

    Malnutrition is an important predictor of morbidity and mortality. In the non-elderly, a subjective global assessment (SGA) has been developed. It has a high inter-rater agreement, correlates with other measures of nutritional status, and predicts subsequent morbidity. The purpose of this study was to determine the validity and reproducibility of the SGA in a group of patients older than 70 y of age. Consecutive patients from four geriatric/rehabilitation units were considered for the study. Each patient underwent independent nutritional assessments by a geriatrician and senior medical resident. At the completion of the assessment, skinfold caliper measurements were obtained and the patient reclassified according to the results, which were then compared with objective measures of nutritional status. Six-month follow-up was obtained on all patients. The agreement between the two clinicians was 0.48 +/- 0.17 (unweighted kappa), which represents moderate agreement and is less than the reported agreement in nonelderly subjects. Skin calipers improved the agreement between clinicians but did not improve the correlation with other nutritional markers or prediction of morbidity and mortality. There was a correlation between a patient's severely malnourished state and mortality. In addition, patients with a body mass index (BMI) of <75% or >150% age/sex standardized norms had an increased mortality. The SGA is a reproducible and valid tool for determining nutritional status in the elderly. The reproducibility is less than in the nonelderly, which may relate to changes in body composition or ability to obtain an accurate nutritional history.

  4. Nutritional status and clinical outcome of children on continuous renal replacement therapy: a prospective observational study

    PubMed Central

    2012-01-01

    Background No studies on continuous renal replacement therapy (CRRT) have analyzed nutritional status in children. The objective of this study was to assess the association between mortality and nutritional status of children receiving CRRT. Methods Prospective observational study to analyze the nutritional status of children receiving CRRT and its association with mortality. The variables recorded were age, weight, sex, diagnosis, albumin, creatinine, urea, uric acid, severity of illness scores, CRRT-related complications, duration of admission to the pediatric intensive care unit, and mortality. Results The sample comprised 174 critically ill children on CRRT. The median weight of the patients was 10 kg, 35% were under percentile (P) 3, and 56% had a weight/P50 ratio of less than 0.85. Only two patients were above P95. The mean age for patients under P3 was significantly lower than that of the other patients (p = 0.03). The incidence of weight under P3 was greater in younger children (p = 0.007) and in cardiac patients and in those who had previous chronic renal insufficiency (p = 0.047). The mortality analysis did not include patients with pre-existing renal disease. Mortality was 38.9%. Mortality for patients with weight < P3 was greater than that of children with weight > P3 (51% vs 33%; p = 0.037). In the univariate and multivariate logistic regression analyses, the only factor associated with mortality was protein-energy wasting (malnutrition) (OR, 2.11; 95% CI, 1.067-4.173; p = 0.032). Conclusions The frequency of protein-energy wasting in children who require CRRT is high, and the frequency of obesity is low. Protein-energy wasting is more frequent in children with previous end-stage renal disease and heart disease. Underweight children present a higher mortality rate than patients with normal body weight. PMID:23016957

  5. 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

  6. Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications.

    PubMed

    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

  7. Are clinical criteria just proxies for socioeconomic status? A study of low birth weight in Jamaica.

    PubMed Central

    Peabody, J W; Gertler, P J

    1997-01-01

    OBJECTIVE: To determine if the clinical risk factors for low birth weight are independent of socioeconomic risk factors in a population based sample from a developing country. DESIGN: Survey data from patient reported socioeconomic measures and their most recent pregnancy history. SETTING: A national sample of randomly selected households in Jamaica. SUBJECTS: All women aged 14-50 in the household who had a pregnancy lasting seven months in the past five years (n = 952). MAIN OUTCOME MEASURE: Birth weight. RESULTS: Clinical risk factors for low birth weight, such as parity age, are independent of socioeconomic determinants, such as consumption and where a mother lives. Women who are nulliparous, 35 or older, poor, or living in certain areas are more likely to have lower birth weight children than those that do not have these characteristics (t statistics > 2.0). The addition of socioeconomic factors to the multiple regression does not alter the estimates for the clinical risk factors for low birth weight. Thus, the effect of being nulliparous can be offset by being in the highest consumption quintile and, conversely, the risk of being older will be compounded if women are poor. CONCLUSIONS: Both clinical and socioeconomic risk factors should be used to target women at risk. In terms of the quality of care, this study links clinical and socioeconomic risk factors to poor outcomes. Further studies are needed, however, to link the quality of care at various locations to these outcomes. Images PMID:9135795

  8. [Experimental data on the virological study of pasteurized milk].

    PubMed

    Kalitina, T A

    1975-01-01

    Virological analyses of sterile milk per se enabled the poliovirus to be disclosed with a concentration of 30 infection units in 1 ml. To determine such doses of the viruses in pasteurized milk the viruses have to be concentrated, for prior to cytopathogenic manifestations subsequent to these viral doses there occurs bacterial germination. In achieving poliovirus concentration in pasteurized milk are suitable polyethyleneglycol, molecular weight 15 000, and polyvinylpyrolidon, molecular weight 10 000, in a 10% concentration. Dilution of milk with Hanks' solution in the ratio of 1:4 and 1:9 improves the process of the poliovirus sorption-eluation with the polymer, enabling it to detect 3 BOU of the virus in 1 ml of milk. The AB-17-8 anionite and Ky-21-8 cationite are capable of adequately sorbing the poliovirus in pasteurized milk, but it is only from the cationite, and then only in a small amount, that eluation of the virus can be accomplished.

  9. HIV Treatment Adherence, Drug Resistance, Virologic Failure: Evolving Concepts

    PubMed Central

    Nachega, Jean B.; Marconi, Vincent C.; van Zyl, Gert U.; Gardner, Edward M.; Preiser, Wolfgang; Hong, Steven Y.; Mills, Edward J.; Gross, Robert

    2016-01-01

    Poor adherence to combined antiretroviral therapy (cART) has been shown to be a major determinant of virologic failure, emergence of drug resistant virus, disease progression, hospitalizations, mortality, and health care costs. While high adherence levels can be achieved in both resource-rich and resource-limited settings following initiation of cART, long-term adherence remains a challenge regardless of available resources. Barriers to optimal adherence may originate from individual (biological, socio-cultural, behavioral), pharmacological, and societal factors. Although patients and providers should continuously strive for maximum adherence to cART, there is accumulating evidence that each class of antiretroviral therapy has specific adherence-drug resistance relationship characteristics allowing certain regimens more flexibility than others. There is not a universally accepted measure for cART adherence, since each method has distinct advantages and disadvantages including cost, complexity, accuracy, precision, intrusiveness and bias. Development of a real-time cART adherence monitoring tool will enable the development of novel, pre-emptive adherence-improving strategies. The application of these strategies may ultimately prove to be the most cost-effective method to reduce morbidity and mortality for the individual and decrease the likelihood of HIV transmission and emergence of resistance in the community. PMID:21406048

  10. 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.

  11. [The Clinical Application Status and Development Trends of Hydrogen Peroxide Low Temperature Plasma Sterilizers].

    PubMed

    Zhuang, Min; Zheng, Yunxin; Chen, Ying; Hou, Bin; Xu, Zitian

    2016-01-01

    The hydrogen peroxide low temperature plasma sterilization technology solved the problems of thermo-sensitive materials' disinfection and sterilization based on its development and unique characteristics. This paper introduced the researches of clinical application quality control, and showed the hydrogen peroxide low temperature plasma sterilizers were being widely used in hospitals and highly recognized. According to the clinical data and the literatures of the domestic equipment in preliminary application, it could be concluded that the technology maturity of domestic hydrogen peroxide low temperature plasma sterilizers was in a high level. The advantages of using domestic hydrogen peroxide low temperature plasma sterilizers to do disinfection and sterilization included lower cost, safer, faster and non-toxic, etc. Also the management system should be improved and the clinical staff should master the technical essentials, obey the procedures strictly, verify periodically and offer full monitoring to upgrade the quality of sterilization. PMID:27197500

  12. [The Clinical Application Status and Development Trends of Hydrogen Peroxide Low Temperature Plasma Sterilizers].

    PubMed

    Zhuang, Min; Zheng, Yunxin; Chen, Ying; Hou, Bin; Xu, Zitian

    2016-01-01

    The hydrogen peroxide low temperature plasma sterilization technology solved the problems of thermo-sensitive materials' disinfection and sterilization based on its development and unique characteristics. This paper introduced the researches of clinical application quality control, and showed the hydrogen peroxide low temperature plasma sterilizers were being widely used in hospitals and highly recognized. According to the clinical data and the literatures of the domestic equipment in preliminary application, it could be concluded that the technology maturity of domestic hydrogen peroxide low temperature plasma sterilizers was in a high level. The advantages of using domestic hydrogen peroxide low temperature plasma sterilizers to do disinfection and sterilization included lower cost, safer, faster and non-toxic, etc. Also the management system should be improved and the clinical staff should master the technical essentials, obey the procedures strictly, verify periodically and offer full monitoring to upgrade the quality of sterilization.

  13. Densitometric analysis of Western blot (immunoblot) assays for human immunodeficiency virus antibodies and correlation with clinical status.

    PubMed Central

    Schmidt, G; Amiraian, K; Frey, H; Stevens, R W; Berns, D S

    1987-01-01

    Western blot assays for antibodies directed against components of human immunodeficiency virus (HIV) associated with acquired immunodeficiency syndrome (AIDS) were examined with a densitometer and integrator. Antibody responses to seven HIV proteins were determined from the areas under the peaks of bands on blots from 430 seropositive individuals. Antibody responses corresponded qualitatively and quantitatively with clinical status. The Western blot assays examined were done on single specimens from individuals in one of four clinical states: asymptomatic with no risk factor identified, asymptomatic with risk factor(s) identified, AIDS-related complex, and AIDS. The ratios of gp41 antibody to p24 antibody and of gp41 antibody to total HIV antibodies increased, and the number of total HIV antibodies decreased progressively in these populations. Parameters were assigned to characterize the typical response found in AIDS: gp41 antibody/p24 antibody ratio, greater than or equal to 2.0; gp41 antibody/total HIV antibodies ratio, greater than or equal to 0.30; and number of total HIV antibodies, less than or equal to 25.0 signal units. Parameter match increased with progression of clinical status. These parameters were applied in a brief follow-up study of 34 HIV-infected asymptomatic individuals who developed AIDS-related complex or AIDS. Initial specimens showed a stronger correlation than our population data base had predicted, suggesting that the parameters have prognostic value. Densitometric analysis of antibody responses on Western blot assays of single or serial specimens should prove useful to physicians in staging and monitoring HIV-infected individuals and in predicting which individuals will progress to AIDS. Images PMID:2444624

  14. 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.

  15. Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

    PubMed Central

    Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M.; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R.; Cardoso, Sandra W.; Sugandhavesa, Patcharaphan; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

    2014-01-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

  16. Pre-antiretroviral therapy serum selenium concentrations predict WHO stages 3, 4 or death but not virologic failure post-antiretroviral therapy.

    PubMed

    Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

    2014-11-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28-99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86-95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30-9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

  17. Pre-antiretroviral therapy serum selenium concentrations predict WHO stages 3, 4 or death but not virologic failure post-antiretroviral therapy.

    PubMed

    Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

    2014-11-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28-99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86-95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30-9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.

  18. Proactive tobacco cessation outreach to smokers of low socioeconomic status: a randomized clinical trial

    PubMed Central

    Haas, Jennifer S.; Linder, Jeffrey A.; Park, Elyse R.; Gonzalez, Irina; Rigotti, Nancy A.; Klinger, Elissa V.; Kontos, Emily Z.; Zaslavsky, Alan M.; Brawarsky, Phyllis; Marinacci, Lucas X.; Hubert, Stella St.; Fleegler, Eric W.; Williams, David R.

    2015-01-01

    Importance Widening socioeconomic disparities in mortality in the United States are largely explained by slower declines in tobacco use between low- and high-socioeconomic status (SES) groups, suggesting the need for targeted tobacco cessation interventions. Documentation of smoking status in electronic health records (EHRs), provides health systems with an opportunity to proactively offer tobacco treatment to disadvantaged smokers. Objective To evaluate a proactive strategy to provide tobacco treatment that addresses socio-contextual mediators of tobacco use for low-SES smokers. Design, Setting, Participants Prospective, randomized controlled trial for low-SES adult smokers who described their race/ethnicity as black, Hispanic or white and received primary care at one of 13 practices in greater-Boston (intervention n=399, control n=308). Intervention We used interactive voice response (IVR)-facilitated outreach to eligible individuals using EHR-coded smoking status. Consenting patients were randomized to a control group which received usual care from their health care team or to an intervention group that included a treatment program of: (1) telephone-based motivational counseling, (2) 6-weeks of free nicotine replacement therapy (NRT), (3) access to community-based referrals to address socio-contextual mediators of tobacco use, and (4) integration of this program with an individual’s care team through the EHR. Main Outcome Self-reported past 7-day tobacco abstinence 9-months after randomization (“quitting”), assessed by automated caller or blinded study staff. Results The intervention group had a higher quit rate than the usual care group (17.8% vs. 8.1%, odds ratio 2.5, 95% confidence interval 1.5-4.0, number-needed-to-treat=10). We examined whether use of intervention components was associated with quitting among individuals in the intervention group; individuals who participated in the telephone counseling were more likely to quit compared to those who

  19. The discrepancy between clinical and ultrasonographic remission in rheumatoid arthritis is not related to therapy or autoantibody status.

    PubMed

    Spinella, Amelia; Sandri, Gilda; Carpenito, Giacomo; Belletti, Lorenza; Mascia, Maria Teresa

    2012-12-01

    To evaluate the clinical remission by means of power Doppler ultrasonographic (PDUS) monitoring in a group of patients with rheumatoid arthritis (RA) in clinical remission (DAS28 < 2.6). The study included 54 patients with RA in therapy with DMARDS, anti-TNF, or no therapy in clinical remission according to ACR criteria and DAS 28 < 2.6 for at least 6 months. All patients had active wrist or hand inflammation in the past. US examination evaluated the presence of active synovitis, power Doppler signal, and synovial hypertrophy on the following bilateral joints: metacarpophalangeal-proximal interphalangeal joints-flexor tendons (on 2°-3° fingers) and wrist (radiocarpal and midcarpal joints). In 19 patients, there was an agreement between clinical and US parameters. However, 35 patients with clinical remission showed a positive ultrasonographic assessment and at least an active parameter. No statistic correlation was found between US examination and antibody assessment (anti-CCP and/or RF). Patients in therapy with anti-TNF or other therapies showed similar US assessment without significant statistical differences. Among eleven patients that presented swollen and tender joints at the latest physical examination, which preceded US exam, just 5 patients had an US confirmation too. In the other patients, the PDUS did not confirm the presence of inflammation in the corresponding swollen and tender joints or showed a positive ultrasonographic assessment in other locations. The remission state is a great therapy target and not only through the biological therapy. Synovial inflammation could persist independently from type of therapy or autoantibody status.

  20. Clinical and EEG analysis of initial status epilepticus during infancy in patients with mesial temporal lobe epilepsy.

    PubMed

    Ohtsu, Mayu; Oguni, Hirokazu; Awaya, Yutaka; Osawa, Makiko

    2002-06-01

    This study investigated the clinical and EEG characteristics of initial status epilepticus (SE) during infancy in patients with mesial temporal lobe epilepsy (MTLE). The subjects were six patients who had been brought to our emergency clinic and treated for their initial SE between 1977 and 1988, and later developed MTLE. We reviewed the medical records and laboratory findings at the time of the initial SE, and the clinical evolution up to the development of MTLE. The six patients included four females and two males. The initial SE developed at ages ranging from 7 months to 2 years and 9 months with a mean of 1 year and 2 months. These episodes were characterized by an elevated temperature of more than 38 degrees C (4/6 cases), clusters of prolonged seizures during one episode of SE (4/6 cases), long-lasting SE (120-380 min, mean 227 min, 6/6 cases), postictal prolonged loss of consciousness (median 5 h, 6/6 cases), and the presence of Todd's paralysis (3/6 cases). The lateralization of the ictal or postictal EEGs of the SE in five of the six cases was identical to that of the hippocampal atrophy later confirmed by MRI. Follow-up EEG examinations at a 6 month interval demonstrated temporal spike discharges appearing only after the onset of complex partial seizures. Two patients, who had no fever at the initial SE, were characterized by a very early appearance of epileptic EEG abnormality and a short interval between the initial SE and the development of complex partial seizures, suggesting that the SE was the first epileptic manifestation. The result of this study showed that SE progressing to MTLE tends to have complicated clinical manifestations characterized by clusters of unilateral or generalized SE followed by prolonged postictal unconsciousness, generalized clinical manifestations despite lateralized ictal EEG discharges, and the Todd's paresis in addition to the prolonged seizure duration. PMID:12015166

  1. Oxidative stress in multiple sclerosis patients in clinical remission: association with the expanded disability status scale.

    PubMed

    Oliveira, Sayonara Rangel; Kallaur, Ana Paula; Simão, Andréa Name Colado; Morimoto, Helena Kaminami; Lopes, Josiane; Panis, Carolina; Petenucci, Diego Lima; da Silva, Eloisa; Cecchini, Rubens; Kaimen-Maciel, Damácio Ramon; Reiche, Edna Maria Vissoci

    2012-10-15

    Increased levels of oxidative stress markers and/or decreased levels of antioxidant molecules have been described in patients with multiple sclerosis (MS). This imbalance has been implicated in demyelination and axonal damage. The aims of this study were to evaluate oxidative stress in MS patients and to verify its correlation with disability as assessed by the expanded disability status scale (EDSS). This case-controlled study included 91 patients with relapsing-remitting multiple sclerosis (RR-MS) and 196 healthy individuals matched by age, gender, ethnicity, smoking status, and body mass index. Oxidative stress was evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), sulfhydryl groups of proteins and serum uric acid levels. MS patients exhibited higher plasma levels of CL-LOOH (p<0.0001) and carbonyl protein (p=0.0081), and lower plasma levels of NOx (p<0.0001), TRAP (p=0.0088), and sulfhydryl groups (p=0.0003) compared to the control subjects. A multivariate analysis showed an association between oxidative markers and the presence of MS. Patients with an EDSS >3.5 showed higher CL-LOOH than control subjects (p=0.0093). A positive correlation was observed between CL-LOOH and EDSS (r=0.3244, p=0.0026) and between carbonyl protein and EDSS (r=0.3012, p=0.0041). These results demonstrate that oxidative stress plays an important role in the physiopathology of MS progression. PMID:22883481

  2. Clinical Implication of Performance Status in Patients with Hepatocellular Carcinoma Complicating with Cirrhosis

    PubMed Central

    Nishikawa, Hiroki; Kita, Ryuichi; Kimura, Toru; Ohara, Yoshiaki; Sakamoto, Azusa; Saito, Sumio; Nishijima, Norihiro; Nasu, Akihiro; Komekado, Hideyuki; Osaki, Yukio

    2015-01-01

    Background and aims: The aims of our study were to elucidate the relationship between baseline characteristics of hepatocellular carcinoma (HCC) patients complicating with liver cirrhosis (LC) and performance status (PS) and to investigate the impact of PS on survival in patients with HCC complicating with LC. Methods: In a total of 1003 patients diagnosed with HCC complicating with LC, we divided into two groups of PS ≥1 (n=251) and PS 0 (n=752) as evaluated by using the Eastern Cooperative Oncology Group criteria at the time of HCC diagnosis. Baseline characteristics between these two groups were compared. We also performed univariate and multivariate analyses of factors contributing to overall survival (OS). Results: The median follow-up period was 1.6 years in the PS ≥1 group and 3.1 years in the PS 0 group. The 1-, 3- and 5-year OS rates after each initial therapy for HCC were 90.3%, 67.4% and 49.8%, respectively, in the PS 0 group and 73.4%, 42.0% and 17.7%, respectively, in the PS ≥1 group (P<0.001). A worse PS was significantly associated with age, gender, Child-Pugh classification, HCC stage, Japan Integrated Staging score, initial treatment option for HCC, maximum tumor size, alanine aminotransferase value, hypoalbuminemia, hyperbilirubinemia, renal insufficiency, hyponatremia, prothrombin time prolongation, platelet count and tumor marker level. In multivariate analyses, poorer PS was an independent predictor linked to OS with a hazard ratio of 1.773 (P<0.001). Conclusions: PS was closely associated with status of HCC patients with LC and could be an important predictor for these populations. PMID:25767611

  3. 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.

  4. Demographics features, clinical findings and functional status in a group of subjects with cervical myofascial pain syndrome.

    PubMed

    Sahin, Nilay; Karataş, Omer; Ozkaya, Murat; Cakmak, Ayşegül; Berker, Ender

    2008-07-01

    Subjects with myofascial pain of muscles of the neck region may present with various clinical symptoms. The aim of this study was to explore the demographics features, clinical findings and functional status in a group of patients presenting with myofascial pain of the cervical muscles. 94 cervical myofascial pain syndrome patients were recruited from the out-patient clinic. Evaluated of patient short form health survey (SF-36), pain, depression, patient demographics and physical examinations. Outcome measures; SF-36 Health Survey, visual analog scale, Beck Depression Inventory, history, physical examination. A total of 82 patients with a diagnosis of cervical myofascial syndrome were included in the study. All patients were in the young age group 37.4+/-9, and 87.8% were females. 53.1% had trigger points in the trapezius muscle with high percentage of autonomic phenomena like skin reddening, lacrimation, tinnitus and vertigo. 58.5% of the series had suffered from former cervical trauma and 40.2% also had fibromyalgia syndrome and 18.5% had benign Joint hypermobility syndrome. Younger female patients presenting with autonomic phenomena and early onset cervical injury should be examined for cervical myofascial pain syndrome and also for fibromyalgia syndrome since this study demonstrated a high percentage of fibromyalgia syndrome in these patients.

  5. Status of stem cell based clinical trials in the treatment for diabetes.

    PubMed

    Viswanathan, Chandra; Sarang, Shabari

    2013-11-01

    Rapidly increasing number of diabetic patients across the world is a great challenge to the current therapeutic approach. Although the traditional method of rendering exogenous insulin is an established method of treatment, it is not sufficient and often causes lethal hypoglycemia. There is also a good amount of success with whole organ transplantation or Islet cells' transplantation. But this technique is limited with regards the availability of donors. Currently, many clinicians and researchers are involved in clinical studies using various different stem cells from embryonic as well as adult sources for the treatment of diabetes. In this review we have tried to discuss the results of various clinical trials using stem cells. We have also tried to look at various stem cell types and the routes of injections that are currently being followed world wide.

  6. Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice.

    PubMed

    Gatopoulou, A; Papanas, N; Maltezos, E

    2012-09-01

    Gastrointestinal symptoms occur frequently among patients with diabetes mellitus and are associated with considerable morbidity. Diabetic gastrointestinal autonomic neuropathy represents a complex disorder with multifactorial pathogenesis, which is still not well understood. It appears to involve a spectrum of metabolic and cellular changes that affect gastrointestinal motor and sensory control. It may affect any organ in the digestive system. Clinical manifestations are often underestimated, and therefore autonomic neuropathy should be suspected in all diabetic patients with unexplained gastrointestinal symptoms. Advances in technology have now enabled assessment of gastrointestinal motor function. Moreover, novel pharmacological approaches, along with endoscopic and surgical treatment options, contribute to improved outcomes. This review summarises the progress achieved in diabetic gastrointestinal autonomic neuropathy during the last years, focusing on clinical issues of practical importance to the everyday clinician. PMID:22863425

  7. Superparamagnetic iron oxide based MRI contrast agents: Current status of clinical application.

    PubMed

    Wang, Yi-Xiang J

    2011-12-01

    Superparamagnetic iron oxide (SPIO) MR contrast agents are composed of nano-sized iron oxide crystals coated with dextran or carboxydextran. Two SPIO agents are clinically approved, namely: ferumoxides (Feridex in the USA, Endorem in Europe) with a particle size of 120 to 180 nm, and ferucarbotran (Resovist) with a particle size of about 60 nm. The principal effect of the SPIO particles is on T2* relaxation and thus MR imaging is usually performed using T2/T2*-weighted sequences in which the tissue signal loss is due to the susceptibility effects of the iron oxide core. Enhancement on T1-weighted images can also be seen with the smaller Resovist. Both Feridex and Resovist are approved specifically for MRI of the liver. The difference being that Resovist can be administered as a rapid bolus (and thus can be used with both dynamic and delayed imaging), whereas Feridex needs to be administered as a slow infusion and is used solely in delayed phase imaging. In the liver, these particles are sequestered by phagocytic Kupffer cells in normal reticuloendothelial system (RES), but are not retained in lesions lacking Kupffer cells. Consequently, there are significant differences in T2/T2* relaxation between normal tissue and lesions, resulting in increased lesion conspicuity and detectability. SPIO substantially increase the detectability of hepatic metastases. For focal hepatocellular lesions, SPIO-enhanced MR imaging exhibits slightly better diagnostic performance than dynamic CT. A combination of dynamic and static MR imaging technique using T1- and T2 imaging criteria appears to provide clinically more useful patterns of enhancement. Feridex and Resovist are also used for evaluating macrophage activities in some inflammatory lesions, but their clinical values remain to be further confirmed. The clinical development of Ferumoxtran (Combidex in the USA, Sinerem in Europe), designed for lymph node metastasis evaluation, is currently stopped.

  8. Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis

    PubMed Central

    Taylor, A; Bush, A; Thomson, A; Oades, P; Marchant, J; Bruce-Morgan, C; Holly, J; Ahmed, L; Dunger, D

    1997-01-01

    Accepted 26 October 1996
 OBJECTIVES—Despite improved nutrition and intensive treatment, subjects with cystic fibrosis have difficulty in maintaining anabolism during intercurrent infections, which can result in reduced body mass index and impaired skeletal growth. Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP3 are sensitive to changes in nutritional status. The aim of this study was to determine the relation between circulating concentrations of these peptides, body mass index, and clinical status in cystic fibrosis.
METHODS—Serum concentrations of IGF-I and IGFBP3 were measured in 197 subjects (108 males, 89 females; mean age 9.69 years, range 0.41-17.9 years) and these data were analysed with respect to body mass index, pubertal stage, and clinical status as assessed by Shwachman score and forced expiratory volume in one second (FEV1 ).
RESULTS—The mean height SD score of the children studied was −0.2 (SD 1.14) and the body mass index SD score −0.26 (1.4). The body mass index SD score declined with increasing age (r=−0.18) and paralleled changes in IGF-I concentrations, which also declined. The IGF-I SD score (calculated from control data) correlated with age (r=−0.53). The abnormalities were most obvious during late puberty, when IGF-I and IGFBP3 concentrations were significantly reduced compared with those in control subjects matched for pubertal stage. The IGF-I SD score correlated with height SD score (r=0.14) and the decline in IGF-I concentrations with the fall in body mass index SD score (r=0.42). IGF-I SD scores also correlated with the Shwachman score (r=0.33) and FEV1 (r=0.17).
CONCLUSIONS—The close relation between declining IGF-I and IGFBP3 concentrations and body mass index in patients with cystic fibrosis may simply reflect poor nutritional status and insulin hyposecretion. Nevertheless, IGF-I deficiency could also contribute towards the catabolism observed in these patients, and IGF-I SD scores

  9. [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. PMID:27509732

  10. [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.

  11. 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.

  12. [Clinical status and outcome biomarkers in schizophrenia: a review for near-infrared spectroscopy studies].

    PubMed

    Koike, Shinsuke

    2013-01-01

    Neuroimaging technologies have seen enormous progress during the past two decades, and are now able to provide detailed illustrations of brain structure and activity. As a result, our understanding of the pathophysiology of mental illnesses such as schizophrenia has expanded, and potential clinical applications are becoming apparent. Unlike most physical illnesses, mental illnesses often lack objective markers, and this is one of the reasons why some patients and their family members experience difficulty in understanding symptoms and disabilities. In some cases, this leads to delays in patients seeking treatment, discontinuation of treatment, and relapse. If biological markers can be utilized as aids in differential diagnosis, selection of treatment options, and assessment of severity and treatment response in clinical settings, they may lead to improved treatment quality and clinical outcomes. Near-infrared spectroscopy (NIRS) is a functional neuroimaging technique that may be a candidate for clinical application in psychiatry. Advantages of NIRS include: 1) its non-invasive nature, with no harmful impact resulting from repeated measurement, even in infants; 2) high temporal resolution (> 10 Hz); 3) compact size, enabling easy movement; and 4) no required restraint position: people undergoing testing may take a natural position, such as sitting or standing, and may converse and perform manual tasks during measurement. Previous NIRS studies have revealed different characteristic waveform patterns during verbal fluency tasks among patients with major depression, bipolar disorder, and schizophrenia, which led to government approval in 2009 as an "advanced medical technology to aid in the differential diagnosis of depressive symptoms." This was the first approval in the field of psychiatry in Japan. Future NIRS studies will focus more on clinical applications, and multi-site studies are needed to assess the impact of non-illness factors such as age, sex, and head

  13. Association of SCARB1 Gene Polymorphisms with Virological Response in Chronic Hepatitis C Patients Receiving Pegylated Interferon plus Ribavirin Therapy.

    PubMed

    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

  14. 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

  15. The role of stem cell therapy in multiple sclerosis: An overview of the current status of the clinical studies.

    PubMed

    Meamar, Rokhsareh; Nematollahi, Shahrzad; Dehghani, Leila; Mirmosayyeb, Omid; Shayegannejad, Vahid; Basiri, Keivan; Tanhaei, Amir Pouya

    2016-01-01

    The complexity of multiple sclerosis (MS) and the incompetence of a large number of promised treatments for MS urge us to plan new and more effective therapeutic approaches that aim to suppress ongoing autoimmune responses and induction of local endogenous regeneration. Emerging data propose that hematopoietic, mesenchymal, and neural stem cells have the potential to restore self-tolerance, provide in situ immunomodulation and neuroprotection, as well as promote regeneration. Thus, in this article, we will first provide an overview of the cell sources for proposed mechanisms that contribute to the beneficial effects of stem cell transplantation, the ideal route and/or timing of stem cell-based therapies for each main stem cell group, and finally, an overview of the current status of stem cell research in clinical trial stages in MS by comparable and healthy therapeutic effects of different stem cell therapies for MS patients. PMID:27110543

  16. The role of stem cell therapy in multiple sclerosis: An overview of the current status of the clinical studies

    PubMed Central

    Meamar, Rokhsareh; Nematollahi, Shahrzad; Dehghani, Leila; Mirmosayyeb, Omid; Shayegannejad, Vahid; Basiri, Keivan; Tanhaei, Amir Pouya

    2016-01-01

    The complexity of multiple sclerosis (MS) and the incompetence of a large number of promised treatments for MS urge us to plan new and more effective therapeutic approaches that aim to suppress ongoing autoimmune responses and induction of local endogenous regeneration. Emerging data propose that hematopoietic, mesenchymal, and neural stem cells have the potential to restore self-tolerance, provide in situ immunomodulation and neuroprotection, as well as promote regeneration. Thus, in this article, we will first provide an overview of the cell sources for proposed mechanisms that contribute to the beneficial effects of stem cell transplantation, the ideal route and/or timing of stem cell-based therapies for each main stem cell group, and finally, an overview of the current status of stem cell research in clinical trial stages in MS by comparable and healthy therapeutic effects of different stem cell therapies for MS patients. PMID:27110543

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Clinical assessment of acid-base status. Strong ion difference theory.

    PubMed

    Constable, P D

    1999-11-01

    The traditional approach to evaluating acid-base balance uses the Henderson-Hasselbalch equation to categorize four primary acid-base disturbances: respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2), metabolic acidosis (decreased extracellular base excess), or metabolic alkalosis (increased extracellular base excess). The anion gap is calculated to detect the presence of unidentified anions in plasma. This approach works well clinically and is recommended for use whenever serum total protein, albumin, and phosphate concentrations are approximately normal; however, when their concentrations are markedly abnormal, the Henderson-Hasselbalch equation frequently provides erroneous conclusions as to the cause of an acid-base disturbance. Moreover, the Henderson-Hasselbalch approach is more descriptive than mechanistic. The new approach to evaluating acid-base balance uses the simplified strong ion model to categorize eight primary acid-base disturbances: respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2), strong ion acidosis (decreased [SID+]) or strong ion alkalosis (increased [SID+]), nonvolatile buffer ion acidosis (increased [ATOT]) or nonvolatile buffer ion alkalosis (decreased [ATOT]), and temperature acidosis (increased body temperature) or temperature alkalosis (decreased body temperature). The strong ion gap is calculated to detect the presence of unidentified anions in plasma. This simplified strong ion approach works well clinically and is recommended for use whenever serum total protein, albumin, and phosphate concentrations are markedly abnormal. The simplified strong ion approach is mechanistic and is therefore well suited for describing the cause of any acid-base disturbance. The new approach should therefore be valuable in a clinical setting and in research studies investigating acid-base balance. The presence of unmeasured strong ions in plasma or serum (such as lactate, ketoacids, and uremic anions

  2. 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. PMID:25010371

  3. Current status of midinfrared quantum and interband cascade lasers for clinical breath analysis

    NASA Astrophysics Data System (ADS)

    Risby, Terence H.; Tittel, Frank K.

    2010-11-01

    State-of-the-art quantum- and interband-cascade-based chemical sensors may be effective new tools for the identification and quantification of trace gases in human breath for clinical uses. Increased or decreased concentrations of these molecules are associated with the pathogenesis of a large number of diseases. Current technologies enable breath analyses to be performed on a single breath and the results are available in real time. Critical parameters including sensor sensitivity, selectivity, real-time monitoring capability, robustness, cost, size, and weight determine the progress made toward the development and availability of commercial diagnostic material.

  4. Methylation status of IGFBP-3 as a useful clinical tool for deciding on a concomitant radiotherapy

    PubMed Central

    Pernía, Olga; Belda-Iniesta, Cristobal; Pulido, Veronica; Cortes-Sempere, María; Rodriguez, Carlos; Vera, Olga; Soto, Javier; Jiménez, Julia; Taus, Alvaro; Rojo, Federico; Arriola, Edurne; Rovira, Ana; Albanell, Joan; Macías, M Teresa; de Castro, Javier; Perona, Rosario; Ibañez de Caceres, Inmaculada

    2014-01-01

    The methylation status of the IGFBP-3 gene is strongly associated with cisplatin sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we found in vitro evidence that linked the presence of an unmethylated promoter with poor response to radiation. Our data also indicate that radiation might sensitize chemotherapy-resistant cells by reactivating IGFBP-3-expression through promoter demethylation, inactivating the PI3K/AKT pathway. We also explored the IGFBP-3 methylation effect on overall survival (OS) in a population of 40 NSCLC patients who received adjuvant therapy after R0 surgery. Our results indicate that patients harboring an unmethylated promoter could benefit more from a chemotherapy schedule alone than from a multimodality therapy involving radiotherapy and platinum-based treatments, increasing their OS by 2.5 y (p = .03). Our findings discard this epi-marker as a prognostic factor in a patient population without adjuvant therapy, indicating that radiotherapy does not improve survival for patients harboring an unmethylated IGFBP-3 promoter. PMID:25482372

  5. Challenges and opportunities for the implementation of virological testing in resource-limited settings

    PubMed Central

    Roberts, Teri; Bygrave, Helen; Fajardo, Emmanuel; Ford, Nathan

    2012-01-01

    Though the advantages of routine virological monitoring for patients on anti-retroviral therapy have been established, cost and complexity limit its full implementation. Monitoring is important for diagnosing virological failure early on, before the development of drug resistance mutations, and to trigger early adherence interventions. Simple and cost-effective viral load tests that facilitate simplification and decentralization of testing and strategies, such as the use of dried blood spots and pooled sample testing, which further aid simplification, are becoming available. In addition, replacing immunological monitoring with virological monitoring in non-viremic patients in a phased manner will reduce the costs associated with dual immuno-virological monitoring. Going forward, the simplification of testing paired with price reducing strategies that will allow for healthy competition between multiple manufacturers will enable the implementation of viral load testing in resource-poor settings. It is important that future HIV and AIDS treatment guidelines provide clear recommendations for routine virological monitoring and that governments and donors fund the implementation of accurate and operationally proven testing platforms in a comprehensive manner. PMID:23078767

  6. Classifying risk status of non-clinical adolescents using psychometric indicators for psychosis spectrum disorders.

    PubMed

    Fonseca-Pedrero, Eduardo; Gooding, Diane C; Ortuño-Sierra, Javier; Pflum, Madeline; Paino, Mercedes; Muñiz, José

    2016-09-30

    This study is an attempt to evaluate extant psychometric indicators using latent profile analysis for classifying community-derived individuals based on a set of clinical, behavioural, and personality traits considered risk markers for psychosis spectrum disorders. The present investigation included four hundred and forty-nine high-school students between the ages of 12 and 19. We used the following to assess risk: the Prodromal Questionnaire-Brief (PQ-B), Oviedo Schizotypy Assessment Questionnaire (ESQUIZO-Q), Anticipatory and Consummatory Interpersonal Pleasure Scale-Adolescent version (ACIPS-A), and General Health Questionnaire 12 (GHQ-12). Using Latent profile analysis six latent classes (LC) were identified: participants in class 1 (LC1) displayed little or no symptoms and accounted for 38.53% of the sample; class 2 (LC2), who accounted for 28.06%, also produced low mean scores across most measures though they expressed somewhat higher levels of subjective distress; LC3, a positive schizotypy group (10.24%); LC4 (13.36%), a psychosis high-risk group; LC5, a high positive and negative schizotypy group (4.45%); and LC6, a very high distress, severe clinical high-risk group, comprised 5.34% of the sample. The current research indicates that different latent classes of early individuals at risk can be empirically defined in adolescent community samples using psychometric indicators for psychosis spectrum disorders. These findings may have implications for early detection and prevention strategies in psychosis spectrum disorders. PMID:27423122

  7. 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.

  8. 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

  9. Longitudinal study on clinical and microbial analysis of periodontal status in pregnancy.

    PubMed

    Machado, Fernanda Campos; Cesar, Dionéia Evangelista; Apolônio, Ana Carolina Morais; Ribeiro, Luiz Claudio; Ribeiro, Rosangela Almeida

    2016-01-01

    This study was aimed to provide a longitudinal overview of the subgingival bacterial microbiome using fluorescence in situ hybridization (FISH) technique, in women in the second trimester of pregnancy (between 14 and 24 weeks), and 48 h and 8 weeks postpartum. Of 31 women evaluated during pregnancy, 24 returned for the 48-h and 18 for their 8-week exams postpartum. Probing depth (PD), bleeding on probing, clinical attachment level, and presence of calculus were recorded. Subgingival plaque samples were collected, and FISH was used to identify the numbers of eight periodontal pathogens. Friedman test was used to compare differences between follow-up examinations, followed by a multiple comparison test for a post hoc pairwise comparison. Clinically, a significantly greater number of teeth with PD = 4-5 mm were found during pregnancy than on postpartum examinations. Microbial analysis showed a statistically significant decrease in cell count over the study period for Prevotella nigrescens. P. intermedia, Campylobacter rectus, and Porphyromonas gingivalis also decrease, although not significantly, and Aggregatibacter actinomycetemcomitans increased. No significant changes were found for Fusobacterium nucleatum, Treponema denticola, or Tannerella forsythia. Our data demonstrate a change in the subgingival microbiota during pregnancy, at least for P. nigrescens. PMID:27556678

  10. 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. PMID:26765424

  11. Status and Perspectives of Clinical Modes in Surgical Patients With Lung Cancer

    PubMed Central

    Lai, Yutian; Du, Heng; Wang, Xin; Shen, Cheng; Huang, Jian; Li, Weiming; Che, Guowei

    2016-01-01

    Abstract 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. PMID:26765424

  12. 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

  13. 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.

  14. Current status of patient recall in U.S. predoctoral dental school clinics.

    PubMed

    Afshari, Fatemeh S; Schelkopf, Stuart; Yuan, Judy Chia-Chun; Marinis, Aristotelis; Syros, George; Campbell, Stephen D; Sukotjo, Cortino

    2014-10-01

    The Commission on Dental Accreditation (CODA)'s revised standard 2-23, which went into effect in July 2013, requires U.S. dental graduates to be competent in "evaluation of the outcomes of treatment, recall strategies, and prognosis." To assess the way dental schools are implementing this revised recommendation, a survey was conducted to assess the existence of recall systems in the schools' clinics and factors enhancing or hindering the formation of an effective recall system. Surveys were returned from thirty-five dental schools (54.7 percent response rate). Results showed that most institutions had active recall systems and the respondents believed that program effectiveness can be further improved. Suggested improvements included patient education and tracking patient recall appointments. The results indicate that recall systems exist in predoctoral dental education programs, have high student involvement, and vary among schools. PMID:25281670

  15. 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.

  16. Antioxidant and Anticoagulant Status Were Improved by Personalized Dietary Intervention Based on Biochemical and Clinical Parameters in Cancer Patients.

    PubMed

    Lee, Ga-Yi; Lee, Jong Jyun; Lee, Seung-Min

    2015-01-01

    We investigated whether personalized dietary intervention could improve clinical measurements such as immune cell-mediated cytotoxicity, serum albumin, derivatives of reactive oxygen metabolites (D-ROMS), D-dimer, and fibrinogen. Cancer patients received either a treatment support diet (TD, for those with chemotherapy), or a remission support diet (RD; for those in remission) for at least 3 wk (21-61 days). Both diets were low glycemic, low fat, and high plant protein diets; the diet for the TD group contained an additional 0.5 servings of protein. Based on clinical values, additional amounts of garlic, onion, tomato, shiitake, rice bran, kale, blueberry, pineapples, and/or turmeric powder were provided in regular meals. Estimated daily intake of protein, plant fat, garlic, onion, allicin, and quercetin was greater in the TD compared to the RD. An increased intake of vitamin A, vitamin C, vitamin E and selenium and a reduction in D-dimer were noted compared to baseline diets in both groups. A decrease in D-ROMS in the RD and an increase in albumin and an increased tendency in cytotoxicity in the TD were observed. In conclusion, personalized diets with supplemented functional ingredients improved antioxidant status and/or anticoagulant activity in cancer patients undergoing chemotherapy and in remission.

  17. 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

  18. Antioxidant and Anticoagulant Status Were Improved by Personalized Dietary Intervention Based on Biochemical and Clinical Parameters in Cancer Patients.

    PubMed

    Lee, Ga-Yi; Lee, Jong Jyun; Lee, Seung-Min

    2015-01-01

    We investigated whether personalized dietary intervention could improve clinical measurements such as immune cell-mediated cytotoxicity, serum albumin, derivatives of reactive oxygen metabolites (D-ROMS), D-dimer, and fibrinogen. Cancer patients received either a treatment support diet (TD, for those with chemotherapy), or a remission support diet (RD; for those in remission) for at least 3 wk (21-61 days). Both diets were low glycemic, low fat, and high plant protein diets; the diet for the TD group contained an additional 0.5 servings of protein. Based on clinical values, additional amounts of garlic, onion, tomato, shiitake, rice bran, kale, blueberry, pineapples, and/or turmeric powder were provided in regular meals. Estimated daily intake of protein, plant fat, garlic, onion, allicin, and quercetin was greater in the TD compared to the RD. An increased intake of vitamin A, vitamin C, vitamin E and selenium and a reduction in D-dimer were noted compared to baseline diets in both groups. A decrease in D-ROMS in the RD and an increase in albumin and an increased tendency in cytotoxicity in the TD were observed. In conclusion, personalized diets with supplemented functional ingredients improved antioxidant status and/or anticoagulant activity in cancer patients undergoing chemotherapy and in remission. PMID:26333154

  19. 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. PMID:27450028

  20. 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.

  1. 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.

  2. Clinical assessment of acid-base status: comparison of the Henderson-Hasselbalch and strong ion approaches.

    PubMed

    Constable, Peter D.

    2000-01-01

    The traditional approach for clinically assessing acid-base status uses the Henderson-Hasselbalch equation to categorize 4 primary acid-base disturbances: respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2), metabolic acidosis (decreased extracellular base excess or actual HCO3- concentration), and metabolic alkalosis (increased extracellular base excess or actual HCO3- concentration). The anion gap is calculated to detect unidentified anions in plasma. This approach works well clinically and is recommended for use whenever serum total protein, albumin, and phosphate concentrations are approximately normal. However, because the Henderson-Hasselbalch approach is more descriptive than mechanistic, when these concentrations are markedly abnormal the Henderson-Hasselbalch equation frequently provides erroneous information as to the cause of an acid-base disturbance. The new quantitive physicochemical approach to evaluating acid-base balance uses the simplified strong ion model to categorize 6 primary acid-base disturbances: respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2), strong ion acidosis (decreased strong ion difference), strong ion alkalosis (increased strong ion difference), nonvolatile buffer ion acidosis (increased plasma concentrations of albumin, globulins, or phosphate), and nonvolatile buffer ion alkalosis (decreased plasma concentrations of albumin, globulins, or phosphate). The strong ion gap is calculated to detect unidentified anions in plasma. The simplified strong ion approach works well clinically and is recommended for use whenever serum total protein, albumin, or phosphate concentrations are markedly abnormal. The simplified strong ion approach is mechanistic and is therefore well suited for describing the cause of any acid-base disturbance.

  3. Clinically Determined and Self-Reported Dental Caries Status During and After Pregnancy Among Low-Income Hispanic Women

    PubMed Central

    Weintraub, Jane A.; Gansky, Stuart A.; Santo, William; Ramos-Gomez, Francisco

    2014-01-01

    Objectives This analysis assessed, during and one-year after pregnancy: 1) the prevalence of and relationship between self-reported and clinically determined dental caries and oral health status, and whether self-reports are a potential proxy for professional determination; 2) factors associated with high levels of professionally determined or self-reported oral disease. Methods Data are from a randomized clinical trial of 301 pregnant, low-income Hispanic women at the California-Mexico border to compare two interventions to prevent early childhood caries. Interviews and dental examinations were conducted at enrollment (second trimester) and one-year post-partum (PP). Results During pregnancy and PP, 93% had untreated caries and most had gingival inflammation. Sensitivity and specificity of self-reported measures compared to dentists’ determinations were modest (ranging from 45–80% for sensitivity and 41–77% for specificity at both time points); positive predictive values for women reporting current tooth decay or fair/poor oral health were high (>94%), but negative predictive values were low (<23%). In a bivariate GEE model, factors associated with fair/poor self-reported oral health during and after pregnancy included self-reported dental symptoms (current tooth decay, bleeding gums without brushing), dental behaviors (not flossing) and number of decayed tooth surfaces. In a logistic regression model, the only significant factor PP associated with less extensive untreated disease was if women ever had their teeth cleaned professionally (OR=0.44). Conclusions There is a great need for dental treatment in this underserved population both during pregnancy and PP. Women may not be able to accurately recognize or act on their treatment needs. At baseline and PP, few demographic or behavioral factors were associated with either self-reported or clinically-determined oral disease (e.g., being less educated or acculturated and not flossing) in the bivariate

  4. 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

  5. [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. PMID:20408446

  6. The Clinical Trials Program at the ESRF Biomedical Beamline ID17: Status and Remaining Steps

    SciTech Connect

    Requardt, H.; Bravin, A.; Prezado, Y.; Braeuer-Krisch, E.; Renier, M.; Brochard, Th.; Berkvens, P.; Nemoz, C.; Berruyer, G.; Esteve, F.; Elleaume, H.; Adam, J.-F.; Blattmann, H.; Laissue, J. A.; Kaser-Hotz, B.

    2010-06-23

    For several years the ID17 Biomedical beamline at the ESRF has developed synchrotron radiation therapy preclinical programmes to treat aggressive brain tumours. Two techniques have been developed at the ESRF:a) The Microbeam Radiation Therapy (MRT) using spatially fractionated 'white beam' (energies 50-300 keV) irradiation (beam widths 25-100 {mu}m, spacing between beams 200-400 {mu}m ) with extremely high dose rates (up to about 20 kGy/s) and depositing very high doses (300-1000 Gy) in the targeted tissue.b) The Stereotactic Synchrotron Radiation Therapy (SSRT) using spatially homogeneous monochromatic beam with the energy closely above that of the K-edge of a contrast- or chemotherapeutical agent (iodine, gadolinium, platinum) loaded into the tumour volume for obtaining a dose-enhancement. In 2005 an International review panel of oncology experts has recommended to move to clinical trials on humans in SSRT and on large animals in MRT. The works required for this program were launched in autumn 2007 with constructing a new, dedicated experimental hutch for MRT and a major upgrade of the existing sample-positioning station to a patient-positioning station for SSRT. In parallel, safety systems are developed and progressively implemented and a patient treatment-planning system developed.

  7. Ivermectin in human medicine, an overview of the current status of its clinical applications.

    PubMed

    González, P; González, F A; Ueno, K

    2012-05-01

    Ivermectin is a broad spectrum antiparasitic veterinary drug introduced in human medicine in 1987. It is considered the drug of choice in onchocerciasis and strongyloidiasis infections, and remains as a therapeutic option for mass treatment in lymphatic filariasis, for which it has widely proved its efficacy. While research continued for human use, new therapeutic targets for ivermectin have emerged. It is currently the better therapeutic option in the treatment of gnathostomiasis and crusted scabies, and could be an alternative option in ascariasis and Mansonella infections. Although these uses are already included in clinical guidelines, more trials are needed to increase their grade of evidence and to obtain their official approval. Concerning other minor uses such as the treatment of enterobiasis or against Trichuris trichiura, more research is still needed in order to test the real activity of ivermectin. The use of ivermectin in human medicine has shown an outstanding low rate of adverse reactions, with the exception of treatment of loiasis and onchocerciasis, where the death of a high microfilarial load may cause severe encephalopathy. However special attention must be paid to the emergence of the first documented cases of resistance in treatment of scabies. PMID:22039800

  8. Abacavir/Lamivudine Versus Tenofovir/Emtricitabine in Virologically Suppressed Patients Switching from Ritonavir-Boosted Protease Inhibitors to Raltegravir

    PubMed Central

    d'Albuquerque, Polyana M.; Pérez, Ignacio; Pich, Judit; Gatell, José M.

    2013-01-01

    Abstract There are few clinical data on the combination abacavir/lamivudine plus raltegravir. We compared the outcomes of patients from the SPIRAL trial receiving either abacavir/lamivudine or tenofovir/emtricitabine at baseline who had taken at least one dose of either raltegravir or ritonavir-boosted protease inhibitors. For the purpose of this analysis, treatment failure was defined as virological failure (confirmed HIV-1 RNA ≥50 copies/ml) or discontinuation of abacavir/lamivudine or tenofovir/emtricitabine because of adverse events, consent withdrawal, or lost to follow-up. There were 143 (72.59%) patients with tenofovir/emtricitabine and 54 (27.41%) with abacavir/lamivudine. In the raltegravir group, there were three (11.11%) treatment failures with abacavir/lamivudine and eight (10.96%) with tenofovir/emtricitabine (estimated difference 0.15%; 95% CI −17.90 to 11.6). In the ritonavir-boosted protease inhibitor group, there were four (14.81%) treatment failures with abacavir/lamivudine and 12 (17.14%) with tenofovir/emtricitabine (estimated difference −2.33%; 95% CI −16.10 to 16.70). Triglycerides decreased and HDL cholesterol increased through the study more pronouncedly with abacavir/lamivudine than with tenofovir/emtricitabine and differences in the total-to-HDL cholesterol ratio between both combinations of nucleoside reverse transcriptase inhibitors (NRTIs) tended to be higher in the raltegravir group, although differences at 48 weeks were not significant. While no patient discontinued abacavir/lamivudine due to adverse events, four (2.80%) patients (all in the ritonavir-boosted protease inhibitor group) discontinued tenofovir/emtricitabine because of adverse events (p=0.2744). The results of this analysis do not suggest that outcomes of abacavir/lamivudine are worse than those of tenofovir/emtricitabine when combined with raltegravir in virologically suppressed HIV-infected adults. PMID:22916715

  9. Abacavir/lamivudine versus tenofovir/emtricitabine in virologically suppressed patients switching from ritonavir-boosted protease inhibitors to raltegravir.

    PubMed

    Martínez, Esteban; d'Albuquerque, Polyana M; Pérez, Ignacio; Pich, Judit; Gatell, José M

    2013-02-01

    There are few clinical data on the combination abacavir/lamivudine plus raltegravir. We compared the outcomes of patients from the SPIRAL trial receiving either abacavir/lamivudine or tenofovir/emtricitabine at baseline who had taken at least one dose of either raltegravir or ritonavir-boosted protease inhibitors. For the purpose of this analysis, treatment failure was defined as virological failure (confirmed HIV-1 RNA ≥50 copies/ml) or discontinuation of abacavir/lamivudine or tenofovir/emtricitabine because of adverse events, consent withdrawal, or lost to follow-up. There were 143 (72.59%) patients with tenofovir/emtricitabine and 54 (27.41%) with abacavir/lamivudine. In the raltegravir group, there were three (11.11%) treatment failures with abacavir/lamivudine and eight (10.96%) with tenofovir/emtricitabine (estimated difference 0.15%; 95% CI -17.90 to 11.6). In the ritonavir-boosted protease inhibitor group, there were four (14.81%) treatment failures with abacavir/lamivudine and 12 (17.14%) with tenofovir/emtricitabine (estimated difference -2.33%; 95% CI -16.10 to 16.70). Triglycerides decreased and HDL cholesterol increased through the study more pronouncedly with abacavir/lamivudine than with tenofovir/emtricitabine and differences in the total-to-HDL cholesterol ratio between both combinations of nucleoside reverse transcriptase inhibitors (NRTIs) tended to be higher in the raltegravir group, although differences at 48 weeks were not significant. While no patient discontinued abacavir/lamivudine due to adverse events, four (2.80%) patients (all in the ritonavir-boosted protease inhibitor group) discontinued tenofovir/emtricitabine because of adverse events (p=0.2744). The results of this analysis do not suggest that outcomes of abacavir/lamivudine are worse than those of tenofovir/emtricitabine when combined with raltegravir in virologically suppressed HIV-infected adults. PMID:22916715

  10. 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.

  11. Association of clinical complications with nutritional status and the prevalence of leukopenia among arsenic patients in Bangladesh.

    PubMed

    Islam, Laila N; Nabi, A H M Nurun; Rahman, M Mahfuzur; Khan, Monsur A; Kazi, Azizul I

    2004-09-01

    This study conducted in Bangladesh reports the relationship of clinical complications with nutritional status and the prevalence of leukopenia among arsenic exposed patients living in the rural villages. A total of 115 exposed individuals diagnosed as arsenicosis patients were randomly selected from four known arsenic endemic villages, and age-matched 120 unexposed subjects were enrolled in the study program. The duration of arsenic exposure in about 37% of the patients was at least 10 yrs, while the population mean and range were 7.6 +/- 5.2 yrs, and 1 - 25 yrs, respectively. The mean arsenic concentrations in the drinking water for the exposed and unexposed (control) population were 218.1 microg/L and 11.3 microg/L, respectively. The spot urine sample of the arsenicosis patients contained an average of 234.6 microg/L arsenic. Although very few patients showed elevated WBC count, 16% had leukopenia (below normal count), and the whole population had significantly low WBC count than the control subjects. Prevalences of neutropenia and lymphocytosis were observed in patients with chronic exposure to high levels of arsenic in water. The body mass index was found to be lower than 18.5, the cut-off point for malnutrition (underweight), in about 28% of the arsenicosis cases compared to 15% of the controls. The monthly income and total calorie consumption per day showed the patients were underprivileged than the controls. Arsenical symptoms and complications were more severe in the nutritionally vulnerable (underweight) patients than the overweight ones. Also, the incidences of leukopenia and anaemia were more common in the female patients who were underweight. The findings of this research demonstrate that the poor nutritional status of patients increases the complications of chronic arsenic toxicity; suggest the possibility of other sources of arsenic contamination different from drinking water in the study area; and establish a higher prevalence of leukopenia and

  12. Slower Fibrosis Progression Among Liver Transplant Recipients With Sustained Virological Response After Hepatitis C Treatment

    PubMed Central

    Habib, Shahid; Meister, Edward; Habib, Sana; Murakami, Traci; Walker, Courtney; Rana, Abbas; Shaikh, Obaid S.

    2015-01-01

    Background The natural course of hepatic fibrosis in HCV allograft recipients with sustained virological response (SVR) after anti-HCV therapy remains debatable. The aim of this study was to examine the progression of fibrosis in a cohort of patients who achieved SVR compared with those without treatment. Methods The 167 patients who met the inclusion and exclusion criteria were chosen from a transplant database. All patients were required to have histological evidence of recurrent HCV infection post-liver transplantation and a follow-up biopsy. The 140 of these patients had received anti-viral therapy. Twenty-seven patients were identified as controls and were matched with the treatment group in all respects. The patients were categorized into four groups based on treatment response: 1) no treatment (control) (n = 27); 2) non-responders (n = 81); 3) relapsers (n = 32); and 4) SVR (n = 27). The endpoint was the stage of fibrosis on the follow-up liver biopsy. Results The treated and untreated groups were similar in clinical characteristics at the time of transplantation and prior to the initiation of treatment. The 72% of the cohort showed a fibrosis progression of ≥ 1 stage; this change did not significantly differ between the patient groups. Nonetheless, the fibrosis progression rate was the highest in the untreated group and lowest in the patients who achieved SVR. A coefficient of determination was used. Improvements in fibrosis scores were found with greater treatment duration. These improvements were most evident with the achievement of SVR. Conclusions In conclusion, SVR after anti-viral therapy for recurrent hepatitis C infection post-transplantation was associated with slower fibrosis progression and significantly improved graft survival.

  13. 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…

  14. Clinical validation of the WMS-IV-NL brief cognitive status exam (BCSE) in older adults with MCI or dementia.

    PubMed

    Bouman, Zita; Hendriks, Marc P H; Aldenkamp, Albert P; Kessels, Roy P C

    2014-07-31

    ABSTRACT Background: The Brief Cognitive Status Exam (BCSE) is a new, optional subtest of the Wechsler Memory Scale-IV (WMS-IV) developed for rapid detection of cognitive deficits. We examined the clinical validation of the Dutch version of the BCSE in older adults with mild cognitive impairment (MCI) or dementia, comparing it to the Mini-Mental State Examination (MMSE). Method: BCSE and MMSE were administered in 39 older adults with MCI, 51 with dementia and 96 matched healthy controls. Results: Our results show that the BCSE is a valid screening instrument, with psychometric properties similar to the widely used MMSE. High correlations were found between the BCSE and MMSE (r = 0.79, n = 183, p < 0.001). Furthermore, a BCSE cut-off score ≤ 42 revealed a sensitivity of 96% a specificity of 92%, a positive predictive value of 86% and a negative predictive value of 97%, whereas the MMSE cut-off score of ≤ 24 showed values of 84%, 96%, 91%, and 92%, respectively. Sensitivity, specificity, positive and negative predictive values to detect MCI compared to controls was 81%, 80%, 61%, and 92%, respectively, on the BCSE, with a cut-off score of ≤ 46, and 84%, 76%, 57%, and 92%, respectively, on the MMSE, with a cut-off score of ≤ 27. Conclusions: The Dutch version of the BCSE is a clinically valid screening instrument for the detection of cognitive impairment in patients with dementia. Nevertheless, for distinguishing older adults with MCI from healthy controls both the BCSE and MMSE have limitations.

  15. Improvement of periodontal status by green tea catechin using a local delivery system: a clinical pilot study.

    PubMed

    Hirasawa, Masatomo; Takada, Kazuko; Makimura, Masaharu; Otake, Shigeo

    2002-12-01

    The purpose of this study was to determine the usefulness of green tea catechin for the improvement of periodontal disease. The minimum inhibitory concentration (MIC) and bactericidal activity of green tea catechin against black-pigmented, Gram-negative anaerobic rods (BPR) were measured. Hydroxypropylcellulose strips containing green tea catechin as a slow release local delivery system were applied in pockets in patients once a week for 8 weeks. The clinical, enzymatic and microbiological effects of the catechin were determined. Green tea catechin showed a bactericidal effect against Porphyromonas gingivalis and Prevotella spp. in vitro with an MIC of 1.0 mg/ml. In the in vivo experiment, the pocket depth (PD) and the proportion of BPR were markedly decreased in the catechin group with mechanical treatment at week 8 compared with the baseline with significant difference. In contrast, PD and BPR were similar to the baseline and the value at the end of the experimental period in the placebo sites of scaled groups. The peptidase activities in the gingival fluid were maintained at lower levels during the experimental period in the test sites, while it reached 70% of that at baseline in the placebo sites. No morbidity was observed in the placebo and catechin groups without mechanical treatment. Green tea catechin showed a bactericidal effect against BPR and the combined use of mechanical treatment and the application of green tea catechin using a slow release local delivery system was effective in improving periodontal status.

  16. Adding point of care ultrasound to assess volume status in heart failure patients in a nurse-led outpatient clinic. A randomised study

    PubMed Central

    Gundersen, Guri Holmen; Norekval, Tone M; Haug, Hilde Haugberg; Skjetne, Kyrre; Kleinau, Jens Olaf; Graven, Torbjorn; Dalen, Havard

    2016-01-01

    Objectives Medical history, physical examination and laboratory testing are not optimal for the assessment of volume status in heart failure (HF) patients. We aimed to study the clinical influence of focused ultrasound of the pleural cavities and inferior vena cava (IVC) performed by specialised nurses to assess volume status in HF patients at an outpatient clinic. Methods HF outpatients were prospectively included and underwent laboratory testing, history recording and clinical examination by two nurses with and without an ultrasound examination of the pleural cavities and IVC using a pocket-size imaging device, in random order. Each nurse worked in a team with a cardiologist. The influence of the different diagnostic tests on diuretic dosing was assessed descriptively and in linear regression analyses. Results Sixty-two patients were included and 119 examinations were performed. Mean±SD age was 74±12 years, EF was 34±14%, and N-terminal pro-brain natriuretic peptide (NT-proBNP) value was 3761±3072 ng/L. Dosing of diuretics differed between the teams in 31 out of 119 consultations. Weight change and volume status assessed clinically with and without ultrasound predicted dose adjustment of diuretics at follow-up (p<0.05). Change of oedema, NT-proBNP, creatinine, and symptoms did not (p≥0.10). In adjusted analyses, only volume status based on ultrasound predicted dose adjustments of diuretics at first visit and follow-up (all ultrasound p≤0.01, all other p≥0.2). Conclusions Ultrasound examinations of the pleural cavities and IVC by nurses may improve diagnostics and patient care in HF patients at an outpatient clinic, but more studies are needed to determine whether these examinations have an impact on clinical outcomes. Trial registration number NCT01794715. PMID:26438785

  17. 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.

  18. Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

    PubMed Central

    Goetz, Matthew Bidwell; Ferguson, Monique R.; Han, Xueliang; McMillan, Greg; St. Clair, Marty; Pappa, Keith A.; McClernon, Daniel R.; O’Brien, William A.

    2007-01-01

    Objective We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure. Design Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure. Results The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4+ cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue–containing regimens, whether lamivudine was or was not used. Conclusions Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine. PMID:17075391

  19. 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.

  20. 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

  1. Performance of HIV-1 Drug Resistance Testing at Low-Level Viremia and Its Ability to Predict Future Virologic Outcomes and Viral Evolution in Treatment-Naive Individuals

    PubMed Central

    Gonzalez-Serna, A.; Min, J. E.; Woods, C.; Chan, D.; Lima, V. D.; Montaner, J. S. G.; Harrigan, P. R.; Swenson, L. C.

    2014-01-01

    Background. Low-level viremia (LLV; human immunodeficiency virus [HIV-1] RNA 50–999 copies/mL) occurs frequently in patients receiving antiretroviral therapy (ART), but there are few or no data available demonstrating that HIV-1 drug resistance testing at a plasma viral load (pVL) <1000 copies/mL provides potentially clinically useful information. Here, we assess the ability to perform resistance testing by genotyping at LLV and whether it is predictive of future virologic outcomes in patients beginning ART. Methods. Resistance testing by genotyping at LLV was attempted on 4915 plasma samples from 2492 patients. A subset of previously ART-naive patients was analyzed who achieved undetectable pVL and subsequently rebounded with LLV (n = 212). A genotypic sensitivity score (GSS) was calculated based on therapy and resistance testing results by genotyping, and stratified according to number of active drugs. Results. Eighty-eight percent of LLV resistance assays produced useable sequences, with higher success at higher pVL. Overall, 16 of 212 (8%) patients had pretherapy resistance. Thirty-eight of 196 (19%) patients without pretherapy resistance evolved resistance to 1 or more drug classes, primarily the nucleoside reverse transcriptase (14%) and/or nonnucleoside reverse transcriptase (9%) inhibitors. Patients with resistance at LLV (GSS <3) had a 2.1-fold higher risk of virologic failure (95% confidence interval, 1.2- to 3.7-fold) than those without resistance (P = .007). Progressively lower GSS scores at LLV were associated with a higher increase in pVL over time (P < .001). Acquisition of additional resistance mutations to a new class of antiretroviral drugs during LLV was not found in a subset of patients. Conclusions. Routine HIV-1 genotyping of LLV samples can be performed with a reasonably high success rate, and the results appear predictive of future virologic outcomes. PMID:24429436

  2. 25-Hydroxyvitamin D Insufficiency and Deficiency is Associated With HIV Disease Progression and Virological Failure Post-Antiretroviral Therapy Initiation in Diverse Multinational Settings

    PubMed Central

    Havers, Fiona; Smeaton, Laura; Gupte, Nikhil; Detrick, Barbara; Bollinger, Robert C.; Hakim, James; Kumarasamy, Nagalingeswaran; Andrade, Adriana; Christian, Parul; Lama, Javier R.; Campbell, Thomas B.; Gupta, Amita

    2014-01-01

    Background. Low 25-hydroxyvitamin D (25(OH)D) has been associated with increased HIV mortality, but prospective studies assessing treatment outcomes after combination antiretroviral therapy (cART) initiation in resource-limited settings are lacking. Methods. A case-cohort study (N = 411) was nested within a randomized cART trial of 1571 cART-naive adults in 8 resource-limited settings and the United States. The primary outcome (WHO stage 3/4 disease or death within 96 weeks of cART initiation) was met by 192 cases, and 152 and 29 cases met secondary outcomes of virologic and immunologic failure. We studied prevalence and risk factors for baseline low 25(OH)D (<32 ng/mL) and examined associated outcomes using proportional hazard models. Results. Low 25(OH)D prevalence was 49% and ranged from 27% in Brazil to 78% in Thailand. Low 25(OH)D was associated with high body mass index (BMI), winter/spring season, country-race group, and lower viral load. Baseline low 25(OH)D was associated with increased risk of human immunodeficiency virus (HIV) progression and death (adjusted hazard ratio (aHR) 2.13; 95% confidence interval [CI], 1.09–4.18) and virologic failure (aHR 2.42; 95% CI, 1.33–4.41). Conclusions. Low 25(OH)D is common in diverse HIV-infected populations and is an independent risk factor for clinical and virologic failure. Studies examining the potential benefit of vitamin D supplementation among HIV patients initiating cART are warranted. PMID:24799602

  3. Lack of association between plasma levels of non-nucleoside reverse transcriptase inhibitors & virological outcomes during rifampicin co-administration in HIV-infected TB patients

    PubMed Central

    Ramachandran, Geetha; Kumar, A.K. Hemanth; Ponnuraja, C.; Ramesh, K.; Rajesh, Lakshmi; Chandrasekharan, C.; Swaminathan, Soumya

    2013-01-01

    Background & objectives: Among patients with HIV-associated tuberculosis (TB), reduced plasma non-nucleoside reverse transcriptase inhibitors (NNRTI) concentrations during rifampicin (RMP) co-administration could lead to HIV treatment failure. This study was undertaken to examine the association between plasma nevirapine (NVP) and efavirenz (EFV) concentrations and virological outcomes in patients infected with HIV-1 and TB. Methods: This was a nested study undertaken in a clinical trial of patients with HIV-1 and TB, randomized to two different once-daily antiretroviral treatment (ART) regimens along with anti-TB treatment (ATT). Trough concentrations of plasma NVP and EFV were estimated at months 1 (during ATT and ART) and 6 months (ART only) by HPLC. Plasma HIV-1 RNA level >400 copies/ml or death within 6 months of ART were considered as unfavourable outcomes. Genotyping of CYP2B6 516G>T polymorphism was performed. Results: Twenty nine per cent of patients in NVP arm had an unfavourable outcome at 6 months compared to 9 per cent in EFV arm (P<0.08). The mean NVP and EFV levels estimated at 1 and 6 months did not significantly differ between favourable and unfavourable responders. Logistic regression analysis showed CYP2B6 516G>T polymorphism significantly associated with virologic outcome in patients receiving EFV–based regimen. Interpretation & conclusions: Trough plasma concentrations of NVP and EFV did not show any association with response to ART in patients on ATT and once-daily ART. CYP2B6 516G>T polymorphism was associated with virologic outcome among patients on EFV. PMID:24521642

  4. Serological and clinical surveillance studies to validate reported foot-and-mouth disease free status in Tsirang district of Bhutan.

    PubMed

    Dukpa, Kinzang; Robertson, Ian D; Ellis, Trevor M

    2012-04-01

    Serological and clinical studies were conducted between March 2009 and August 2010 to validate the foot-and-mouth disease free status of Tsirang district of Bhutan as determined by the country's passive surveillance system. Randomised (first survey) and targeted (third survey) samplings, with subsequent follow-up samplings (second and fourth), were conducted on FMD-susceptible animals to detect the disease at a design prevalence of 25% and 20% at the individual animal-level and village-level, respectively. Sera from cattle, goats, pigs, and sheep were tested for the presence of non-structural protein (NSP) antibodies using two commercial (PrioCHECK(®) FMDV NS and CHEKIT(®)-FMD-3ABC-bo-ov) and one in-house NSP kit (c-ELISA, AAHL, Australia). The overall seropositivity (all species) at the animal-level was 3% (95% CI: 1.7, 4.8) and 3.5% (95% CI: 2.1, 5.4), for the randomised and targeted surveys, respectively. Except for one goat from the first survey, none of the small ruminants and pigs had NSP antibodies. The seropositives from the first and targeted surveys were distributed among 13 and 16 of 20 villages sampled, respectively. All repeat testing from the initial seropositive animals and their herd mates, for both the first and third surveys, were negative in the NSP tests 6-8 months later. Using the hypergeometric exact probability formula for two-stage analyses, the results enabled rejection of the null hypothesis and supported conclusion that the population was free from disease at the minimum expected prevalence of 20% at the 95.53% and 99.46% confidence levels, for the randomised and targeted surveys, respectively. Clinical surveillance also showed absence of disease or clinical signs suggestive of FMD. The few seropositives were likely to be false positives due to factors such as imperfect specificities of the tests and possible NSP-residues in the vaccines. The study has paved the way for initiation of zoning approaches for the progressive control of FMD

  5. Vitamin D status in children with systemic lupus erythematosus and its association with clinical and laboratory parameters.

    PubMed

    AlSaleem, Alhanouf; AlE'ed, Ashwaq; AlSaghier, Afaf; Al-Mayouf, Sulaiman M

    2015-01-01

    To assess serum 25-hydroxyvitamin D (25-OH vitamin D) status in Saudi children with systemic lupus erythematosus (SLE) and determined its association with clinical, laboratory variables and disease activity. This cross-sectional study comprised children with SLE who are followed at Pediatric Lupus Clinic. All patients reviewed for demographic data, age of first disease manifestations, and disease duration. All included patients evaluated for disease activity, which is completed by using the SLE Disease Activity Index (SLEDAI) and laboratory parameters included a vitamin D profile, bone markers at enrollment and 3 months later. All patients treated with Cholecalciferol (vitamin D3 2000 IU daily) and calcium supplement (Caltrate 600 mg twice daily). Twenty-eight patients (26 female) with mean age of 9.7 years completed the evaluation. Fifteen patients had more than one major organ involvement. Most of the patients are on daily vitamin D3 supplement (800 IU) prior enrollment. The baseline assessment revealed 24 patients had low levels of serum 25-OH vitamin D levels, with a mean of 51.1 ± 33.6 nmol/L; 25 patients had high autoantibodies; and 18 patients had high protein/creatinine ratio, with a mean of 0.9 ± 1.7. Bone density was subnormal with a mean of 0.9 ± 1. The mean disease activity was 6 ± 5.6. Levels of 25-OH vitamin D correlated inversely with autoantibodies and SLEDAI and positively with bone density but not statistically significant. After 3 months, treatment of vitamin D3 (2000 IU daily) and Caltrate (600 mg twice daily), 17 patients had improvement in SLEDAI score and autoimmune markers. Disease activity of childhood SLE is probably linked with low serum 25-OH vitamin D levels. Accordingly, high daily vitamin D3 supplement could potentially impact disease activity of childhood SLE. Further follow up and more patients needed to confirm this finding.

  6. Characterisation of swabbing for virological analysis in the Spanish Influenza Sentinel Surveillance System during four influenza seasons in the period 2002-2006.

    PubMed

    Larrauri, A; de Mateo, S

    2007-05-01

    This study sought to characterise the swabbing pattern in the Spanish Influenza Sentinel Surveillance System (SISSS) and ascertain to what extent the system meets the guidelines currently being drafted by The European Influenza Surveillance Scheme (EISS). Data on seasons 2002/2003 to 2005/2006 were drawn from SISSS. The study analysed collection and dispatch of swab specimens for virological analysis by reference to variables relating to patient sex, age group, vaccination status, specimen collection period, period of influenza activity, time of swabbing and epidemiological season. SISSS adapts to EISS recommendations with respect to the specimen collection period and period of influenza activity, but there is a tendency to collect fewer specimens than recommended as the age of patients increases, and in the case of elderly patients (65 years and older), frequency of collection is clearly insufficient. Furthermore, sentinel physicians collect a higher percentage of specimens in cases where patients have received the influenza vaccine. PMID:17991396

  7. Two Year Virologic Outcomes of an Alternative AIDS Care Model: Evaluation of a Peer Health Worker and Nurse-Staffed Community-Based Program in Uganda

    PubMed Central

    Chang, Larry W.; Alamo, Stella; Guma, Samuel; Christopher, Jason; Suntoke, Tara; Omasete, Richard; Montis, Jennifer P.; Quinn, Thomas C.; Juncker, Margrethe; Reynolds, Steven J

    2009-01-01

    Background There is growing concern about the human resources needed to care for increasing numbers of patients receiving antiretroviral therapy in resource-limited settings. We evaluated an alternative model, community-based, comprehensive antiretroviral program staffed primarily by peer health workers and nurses. Methods We conducted a retrospective cohort study of patients receiving antiretroviral therapy during the first 10 months of program enrollment beginning in late 2003. Virologic, immunologic, clinical, and adherence data were collected. Results Of 360 patients started on treatment, 258 (72%) were active and on therapy approximately two years later. Viral load testing demonstrated that 86% of active patients (211 of 246 tested) had a viral load <400 copies/mL. The median CD4 increase for active patients was 197 cells/mm3 (IQR, 108–346). Patients with either a history of antiretroviral use or lack of CD4 response were more likely to experience virologic failure. Survival was 84% at one year and 82% at two years. WHO stage 4 was predictive of both not sustaining therapy and increased mortality. Conclusions A community-based antiretroviral treatment program in a resource-limited setting can provide excellent AIDS care over at least a two year period. A comprehensive program based upon peer health workers and nurses provides an effective alternative model for AIDS care. PMID:19194316

  8. 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. PMID:26621909

  9. Association of Efavirenz Hypersusceptibility with Virologic Response in ACTG 368, a Randomized Trial of Abacavir (ABC) in Combination with Efavirenz (EFV) and Indinavir (IDV) in HIV-infected Subjects with Prior Nucleoside Analog Experience

    PubMed Central

    Demeter, Lisa M.; DeGruttola, Victor; Lustgarten, Stephanie; Bettendorf, Daniel; Fischl, Margaret; Eshleman, Susan; Spreen, William; Nguyen, Bach-Yen; Koval, Christine E.; Eron, Joseph J.; Hammer, Scott; Squires, Kathleen

    2010-01-01

    Purpose To evaluate the association of efavirenz hypersusceptibility (EFV-HS) with clinical outcome in a double-blind, placebo-controlled, randomized trial of EFV plus indinavir (EFV+IDV) vs. EFV+IDV plus abacavir (ABC) in 283 nucleoside-experienced HIV-infected patients. Methods and Results Rates of virologic failure were similar in the 2 arms at week 16 (p=0.509). Treatment discontinuations were more common in the ABC arm (p=0.001). Using logistic regression, there was no association between virologic failure and either baseline ABC resistance or regimen sensitivity score. Using 3 different genotypic scoring systems, EFV-HS was significantly associated with reduced virologic failure at week 16, independent of treatment assignment. In some patients on the nucleoside-sparing arm, the nucleoside-resistant mutant L74V was selected for in combination with the uncommonly occurring EFV-resistant mutant K103N+L100I; L74V was not detected as a minority variant, using clonal sequence analysis, when the nucleoside-sparing regimen was initiated. Conclusions Premature treatment discontinuations in the ABC arm and the presence of EFV-hypersusceptible HIV variants in this patient population likely made it difficult to detect a benefit of adding ABC to EFV+IDV. In addition, L74V, when combined with K103N+L100I, may confer a selective advantage to the virus that is independent of its effects on nucleoside resistance. PMID:18215978

  10. 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

  11. 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.

  12. 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.

  13. Research in the field of nucleic acids performed in the "Stefan S. Nicolau" Institute of Virology.

    PubMed

    Popa, L M; Repanovici, R; Iliescu, R

    1985-01-01

    A review is made of the research in the field of nucleic acids performed in the "Stefan S. Nicolau" Institute of Virology. The results obtained as regards the infectivity of viral nucleic acids, the oncogenic capacity of nucleic acids extracted from tumors, the isolation, characterization, physicochemical and biological activity of viral and cellular nucleic acids, as well as some achievements in recombinant DNA technology, are briefly presented. PMID:3907119

  14. HIV controllers with different viral load cut-off levels have distinct virologic and immunologic profiles

    PubMed Central

    Bello, Gonzalo; Teixeira, Sylvia LM; Vorsatz, Carla; Babic, Dunja; Sharkey, Mark; Grinsztejn, Beatriz; Veloso, Valdilea; Stevenson, Mario; Morgado, Mariza G

    2015-01-01

    Background The mechanisms behind natural control of HIV replication are still unclear, and several studies pointed that elite controllers are a heterogeneous group. Methods We performed analyses of virologic, genetic and immunologic parameters of HIV-1 controllers groups: 1) Elite Controllers (EC; VL <80 copies/mL); 2) Ebbing Elite Controllers (EEC; transient viremia/blips); and Viremic Controllers (VC; detectable viremia <5,000 copies/mL). Untreated non-controllers (NC), patients under suppressive HAART and HIV-1 negative individuals were analyzed as controls. Results Total and integrated HIV-1 DNA for EC were significantly lower than for NC and HAART groups. 2-LTR circles were detected in EEC (3/5) and VC (6/7) but not in EC. While EC and EEC maintain normal T cell counts over time, some VC displayed negative CD4+ T cells slopes. VC and EEC showed a higher percentage of activated CD8+ T cells and microbial translocation than HIV-1 negative controls. EC displayed a weaker Gag/Nef IFN-γ T cell response and a significantly lower proportion of anti-HIV IgG antibodies than EEC, VC and NC groups. Conclusion Transient/persistent low level viremia in HIV controllers may have an impact on immunologic and virologic profiles. Classify HIV controllers patients taking into account their virologic profile may decrease the heterogeneity of HIV controllers cohorts, which may help to clarify the mechanisms associated to the elite control of HIV. PMID:25564106

  15. 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.

  16. 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

  17. Less than 3 doses of the HPV vaccine - Review of efficacy against virological and disease end points.

    PubMed

    Basu, Partha; Bhatla, Neerja; Ngoma, Twalib; Sankaranarayanan, Rengaswamy

    2016-06-01

    World Health Organization (WHO) recommended 2 doses of the Human Papillomavirus (HPV) vaccine for girls below 15 y on the basis of the immune-bridging studies demonstrating non-inferior immune response of 2 doses in the adolescent girls compared to 3 doses in the young adult women in whom the efficacy against disease is established. The biological nature of the antigens (virus-like particles) constituting the HPV vaccine is responsible for the vigorous antibody response that may make the third dose redundant. The protection offered by 2 doses has been demonstrated in non-randomized clinical trials to be comparable to that offered by 3 doses against incident and persistent infections of vaccine targeted HPV types. However, results emerging from the ecological and nested case-control studies embedded in the population based screening programs of different countries indicate reduced efficacy of 2 doses against virological and disease end points. Some recent studies observed the protective effect of single dose of the vaccine against incident and persistent infections of the vaccine targeted HPV types to be similar to 3 doses in spite of immunological inferiority. The sample size, duration of follow-ups and number of events were limited in these studies. Longer follow ups of the less than 3 doses cohorts in the ongoing studies as well as appropriately designed and ethically justifiable randomized studies are needed to establish the protection offered by the alternative schedules at least beyond 10 y of vaccination. PMID:26933961

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Epidemiological and Virological Characterization of Influenza B Virus Infections.

    PubMed

    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

  3. Multiplex PCR: Optimization and Application in Diagnostic Virology

    PubMed Central

    Elnifro, Elfath M.; Ashshi, Ahmed M.; Cooper, Robert J.; Klapper, Paul E.

    2000-01-01

    PCR has revolutionized the field of infectious disease diagnosis. To overcome the inherent disadvantage of cost and to improve the diagnostic capacity of the test, multiplex PCR, a variant of the test in which more than one target sequence is amplified using more than one pair of primers, has been developed. Multiplex PCRs to detect viral, bacterial, and/or other infectious agents in one reaction tube have been described. Early studies highlighted the obstacles that can jeopardize the production of sensitive and specific multiplex assays, but more recent studies have provided systematic protocols and technical improvements for simple test design. The most useful of these are the empirical choice of oligonucleotide primers and the use of hot start-based PCR methodology. These advances along with others to enhance sensitivity and specificity and to facilitate automation have resulted in the appearance of numerous publications regarding the application of multiplex PCR in the diagnosis of infectious agents, especially those which target viral nucleic acids. This article reviews the principles, optimization, and application of multiplex PCR for the detection of viruses of clinical and epidemiological importance. PMID:11023957

  4. 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

  5. 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

  6. Development of a learning-oriented computer assisted instruction designed to improve skills in the clinical assessment of the nutritional status: a pilot evaluation.

    PubMed

    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.

  7. The status of clinic-based STD patient education: the need for a commitment to innovation in health communication.

    PubMed

    DeJong, W; O'Donnell, L; San Doval, A D; Juhn, G

    1996-01-01

    Although knowledge of safer sex practices is increasing in high-risk populations, such as STD clinic patients, this knowledge does not often translate into behavior change. As a result, STD reinfection rates among clinic patients remain high, resulting in large numbers of return patient visits. As part of a study to evaluate strategies for improving clinic-based education for patients with STDs, we conducted formative research interviews with inner-city clinic managers or other key staff to identify opportunities for and barriers to enhancing STD patient education. These interviews revealed that most of the inner-city clinics had not introduced any new or innovative health communication strategies in the last several years. A primary barrier to innovation appeared to be the belief that patient needs were sufficiently addressed through one-on-one counseling, an assumption that does not take into account the limitations of this form of provider-patient communication. Another barrier was the emphasis placed on maintaining clinic flow, with little consideration given to how it might be altered to accommodate new educational approaches. We offer recommendations to encourage STD clinics to experiment with new and potentially more powerful health communication methods and to encourage the CDC and other funders to alter their STD service priorities toward improvements in health communication and education. We also offer steps that health communication specialists can take in helping clinics and funders move toward these goals.

  8. The Status of Psychological Testing in Clinical Psychology: Relationships Between Test Use and Professional Activities and Orientations

    ERIC Educational Resources Information Center

    Wade, Terry C.; And Others

    1978-01-01

    The occupational specializations and therapeutic orientations of clinical psychologists were related to their use and opinion of testing. The two tests clinicians considered most important to clinical practice were the Rorschach and the Thematic Apperception Test. Among the 10 most frequently recommended test, projective measures were listed 30…

  9. 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.

  10. A description of patient characteristics, insurance status and travel distance at a free inner-city clinic.

    PubMed

    Carranti, Barbara; Myers, Gina; Bowers, Leanne; Satterly, Lynn-Beth

    2012-01-01

    This study was designed to investigate patient characteristics at Amaus Health Services at Cathedral, a free medical clinic in Syracuse, New York which provides interim primary health care to the underserved and uninsured populations in the downtown area of Syracuse. The mission of the clinic is to serve an inner-city population. This study found that the clinic sees equal numbers of men and women and half of the visits were for chronic disease management. Patients traveled from 33 different zip codes, most of which were outside of the intended service area. In addition, of the 278 visits, 50 clinic users reported having some form of insurance. These findings can help Amaus leadership direct volunteers and donations to enhance the services provided, and may assist other areas of the country to identify needs for enhanced access as changes occur in the health care system.

  11. 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.

  12. Comparable sustained virologic suppression between community and academic-based HIV care settings

    PubMed Central

    Chu, Carolyn; Heo, Moonseong; Peshansky, Alex; Umanski, Galina; Meissner, Paul; Voss, Cindy; Selwyn, Peter A.

    2015-01-01

    Purpose The HIV/AIDS epidemic in the United States is evolving due to factors including aging and geographical diffusion. Provider shortages are also driving the restructuring of HIV care delivery away from specialized settings, and family medicine providers may play a larger role in the future. We attempted to compare the effectiveness of HIV treatment delivered at community versus hospital care settings. Methods The outcome of interest was sustained virologic suppression defined as two consecutive HIV-1 RNA measurements ≤ 400 copies/mL within one year after antiretroviral initiation. We used data from the multi-state HIV Research Network cohort to compare sustained virologic suppression outcomes among 15,047 HIV-infected adults followed from 2000–2008 at five community- and eight academic hospital-based ambulatory care sites. Community-based sites were mostly staffed by family medicine and general internal medicine physicians with HIV expertise whereas hospital sites were primarily staffed by infectious disease subspecialists. Multivariate mixed-effects logistic regression controlling for potential confounding variables was applied to account for clustering effects of study sites. Results In an unadjusted analysis, the rate of sustained virologic suppression was significantly higher among subjects treated in the community-based care settings: 1,646/2,314 (71.1%) vs. 8,416/12,733 (66.1%) (p < 0.01). In the adjusted multivariate model with potential confounding variables, the rate was higher, although not statistically significant, in the community-based settings (AOR = 1.26, 95% CI 0.73–2.16). Conclusion Antiretroviral therapy can be delivered effectively through community-based treatment settings. This finding is potentially important for new program development to shift HIV care into community-based settings as the landscape of accountable care, health reform, and HIV funding and resources evolves. PMID:25567825

  13. Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India.

    PubMed

    Karade, Santosh K; Ghate, Manisha V; Chaturbhuj, Devidas N; Kadam, Dileep B; Shankar, Subramanian; Gaikwad, Nitin; Gurav, Shraddha; Joshi, Rajneesh; Sane, Suvarna S; Kulkarni, Smita S; Kurle, Swarali N; Paranjape, Ramesh S; Rewari, Bharat B; Gangakhedkar, Raman R

    2016-09-01

    The free antiretroviral therapy (ART) program in India has scaled up to register second largest number of people living with HIV/AIDS across the globe. To assess the effectiveness of current first-line regimen we estimated virological suppression on completion of 1 year of ART. The study describes the correlates of virological failure (VF) and multinucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations (DRMs).In this cross-sectional study conducted between June and August 2014, consecutive adults from 4 State sponsored ART clinics of western India were recruited for plasma viral load screening at 12 ± 2 months of ART initiation. Individuals with plasma viral load >1000 copies/mL were selected for HIV drug resistance (HIVDR) genotyping. Logistic regression analyses were performed to assess factors associated with VF and multi-NRTI resistance mutations. Criteria adopted for multi-NRTI resistance mutation were either presence of K65R or 3 or more thymidine analog mutations (TAMs) or presence of M184V along with 2 TAMs.Of the 844 study participants, virological suppression at 1 year was achieved in 87.7% of individuals. Factors significantly associated with VF (P < 0.005) were 12 months CD4 count of ≤100 cells/μL (adjusted OR -7.11), low reported adherence (adjusted OR -4.44), and those living without any partner (adjusted OR -1.98). In patients with VF, the prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) DRM (78.75%) were higher as compared to NRTI (58.75%). Multi-NRTI DRMs were present in 32.5% of sequences and were significantly associated with CD4 count of ≤100 cells/μL at baseline (adjusted OR -13.00) and TDF-based failing regimen (adjusted OR -20.43). Additionally, low reported adherence was negatively associated with multi-NRTI resistance (adjusted OR -0.11, P = 0.015). K65R mutation was significantly associated with tenofovir (TDF)-based failing regimen (P < 0.001).The study supports early

  14. 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. PMID:26350662

  15. 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.

  16. 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

  17. Clinical consequences of new diagnostic tools for intestinal parasites.

    PubMed

    van Lieshout, L; Roestenberg, M

    2015-06-01

    Following the success of nucleic acid-based detection in virology and bacteriology, multiplex real-time PCRs are increasingly used as first-line diagnostics in clinical parasitology, replacing microscopy. The detection and quantification of parasite-specific DNA in faeces is highly sensitive and specific and allows for cost-effective high-throughput screening. In this paper we discuss the clinical consequences of this radical change in diagnostic approach, as well as its potential drawbacks. In the Netherlands, routine diagnostic laboratories have been pioneering the implementation of multiplex real-time PCR for the detection of pathogenic intestinal protozoa and this has resulted in increased detection rates of Giardia lamblia and Cryptosporidium spp. As a consequence of this new diagnostic approach, expertise in the field of parasite morphology by conventional light microscopy seems to be disappearing in most of the high-throughput microbiological laboratories. As a result, to maintain a high standard of care, a formalized exchange of critical information between clinicians and laboratory staff is necessary to determine the most appropriate testing either in local laboratories or in reference centres, based on clinical signs and symptoms, exposure and immune status. If such a diagnostic algorithm is lacking, important infections in travellers, immigrants and immunocompromised patients may be missed.

  18. Gender, ethnicity and graduate status, and junior doctors’ self-reported preparedness for clinical practice: national questionnaire surveys

    PubMed Central

    Svirko, Elena; Lambert, Trevor; Goldacre, Michael J

    2014-01-01

    Objectives Medical schools need to ensure that graduates feel well prepared for their first medical job. Our objective was to report on differences in junior doctors’ self-reported preparedness for work according to gender, ethnicity and graduate status. Design Postal and electronic questionnaires. Setting UK. Participants Medical graduates of 2008 and 2009, from all UK medical schools, one year after graduation. Main outcome measures The main outcome measure was the doctors’ level of agreement with the statement that ‘My experience at medical school prepared me well for the jobs I have undertaken so far’, to which respondents were asked to reply on a scale from ‘strongly agree’ to ‘strongly disagree’. Results Women were slightly less likely than men to agree that they felt well prepared for work (50% of women agreed or strongly agreed vs. 54% of men), independently of medical school, ethnicity, graduate entry status and intercalated degree status, although they were no more likely than men to regard lack of preparedness as having been a problem for them. Adjusting for the other subgroup differences, non-white respondents were less likely to report feeling well prepared than white (44% vs. 54%), and were more likely to indicate that lack of preparedness was a problem (30% non-white vs. 24% white). There were also some gender and ethnic differences in preparedness for specific areas of work. Conclusions The identified gender and ethnic differences need to be further explored to determine whether they are due to differences in self-confidence or in actual preparedness. PMID:24108533

  19. 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

    2016-01-01

    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. PMID:27503138

  20. Clinical Significance of Human Metapneumovirus in Refractory Status Epilepticus and Encephalitis: Case Report and Review of the Literature

    PubMed Central

    Vehapoglu, Aysel; Turel, Ozden; Uygur Sahin, Turkan; Kutlu, Nurettin Onur; Iscan, Akın

    2015-01-01

    Encephalitis is a complex neurological disease that is associated with significant morbidity and mortality, and the etiology of the disease is often not identified. Human metapneumovirus (hMPV) is a common cause of upper and lower respiratory tract infections in children. Few reports are available showing possible involvement of hMPV in development of neurologic complications. Here, we describe an infant, the youngest case in literature, with refractory status epilepticus and severe encephalitis in whom hMPV was detected in respiratory samples and review diagnostic workup of patient with encephalitis. PMID:26664779

  1. Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

    PubMed Central

    2010-01-01

    Background Various clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations. Results Based on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations. Conclusions The findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign

  2. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study

    PubMed Central

    Caniglia, Ellen C.; Sabin, Caroline; Robins, James M.; Logan, Roger; Cain, Lauren E.; Abgrall, Sophie; Mugavero, Michael J.; Hernandez-Diaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, Francois; Moore, Richard R.; Reiss, Peter; van Sighem, Ard; Mathews, William C.; del Amo, Julia; Moreno, Santiago; Deeks, Steven G.; Muga, Roberto; Boswell, Stephen L.; Ferrer, Elena; Eron, Joseph J.; Napravnik, Sonia; Jose, Sophie; Phillips, Andrew; Olson, Ashley; Justice, Amy C.; Tate, Janet P.; Bucher, Heiner C.; Egger, Matthias; Touloumi, Giota; Sterne, Jonathan A.; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A.

    2016-01-01

    Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9–12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9–12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were −5.3 (−18.6 to 7.9) and −31.7 (−52.0 to −11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question. PMID:26895294

  3. 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.

  4. Mortality and virologic outcomes following access to antiretroviral therapy among a cohort of HIV-infected women who received single-dose nevirapine in Lusaka, Zambia

    PubMed Central

    Kuhn, Louise; Semrau, Katherine; Ramachandran, Shobana; Sinkala, Moses; Scott, Nancy; Kasonde, Prisca; Mwiya, Mwiya; Kankasa, Chipepo; Decker, Don; Thea, Donald M.; Aldrovandi, Grace M.

    2009-01-01

    Objectives Single-dose nevirapine (SDNVP) for prevention of mother-to-child HIV transmission selects mutations conferring resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy. We investigated mortality and virologic and clinical outcomes following introduction of antiretroviral treatment (ART) among a cohort of women given SDNVP. Methods When ART programs were introduced in 2004 in Lusaka, Zambia, we were completing a trial of infant feeding which involved following HIV-infected women who received SDNVP between 2001 and 2005. Women still in follow-up or who could be contacted were evaluated for eligibility for ART (CD4 count <200 or <350 and WHO stage ≥ 3) and started on NNRTI-based therapy if eligible. We compared mortality in the cohort of women before and after ART access, and examined, among women initiating ART, whether virologic response was better allowing a longer time to elapse between SDNVP and treatment initiation. Results In the cohort of 872 women, mortality more than halved after ART became available (relative hazard [RH] = 0.46 95% CI: 0.23–0.91 p=0.03). Of 161 SDNVP-exposed women followed on NNRTI-based ART, 70.8% suppressed (viral load <400 copies/ml). Only 3/8 (37.5%) women SDNVP-exposed <6 months of starting therapy suppressed compared to 13/22 (59.1%) who started 6–12 months, 44/61 (72.1 %) 12–24 months, and 54/70 (77.1%) >24 months post-exposure (chi-square trend p=0.01). Conclusions Most SDNVP-exposed women respond well to NNRTI-based therapy but there was an attenuation of therapy efficacy that persisted to 12 months after exposure. Women should be screened for ART eligibility during pregnancy and started on effective regimens before delivery. PMID:19506483

  5. 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.

  6. Marital Status and Satisfaction Five Years Following a Randomized Clinical Trial Comparing Traditional versus Integrative Behavioral Couple Therapy

    ERIC Educational Resources Information Center

    Christensen, Andrew; Atkins, David C.; Baucom, Brian; Yi, Jean

    2010-01-01

    Objective: To follow distressed married couples for 5 years after their participation in a randomized clinical trial. Method: A total of 134 chronically and seriously distressed married couples were randomly assigned to approximately 8 months of either traditional behavioral couple therapy (TBCT; Jacobson & Margolin, 1979) or integrative…

  7. 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 ...

  8. 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

  9. An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses

    PubMed Central

    Vandegrift, Kurt J.; Wale, Nina; Epstein, Jonathan H.

    2011-01-01

    The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues. PMID:21994738

  10. An ecological and conservation perspective on advances in the applied virology of zoonoses.

    PubMed

    Vandegrift, Kurt J; Wale, Nina; Epstein, Jonathan H

    2011-04-01

    The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today's globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues.

  11. Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.

    PubMed

    Yu, Xinwei; Xu, Fangda; Ramirez, Nora-Guadalupe P; Kijewski, Suzanne D G; Akiyama, Hisashi; Gummuluru, Suryaram; Reinhard, Björn M

    2015-01-01

    Next-generation nanoparticle-based drug delivery systems require the ability to target specific organelles or subcellular regions in selected target cells. Human immunodeficiency virus type I (HIV-1) particles are evolutionarily optimized nanocarriers that have evolved to avoid intracellular degradation and achieve enrichment at the synapse between mature dendritic cells (mDCs) and T cells by subverting cellular trafficking mechanisms. This study demonstrates that integration of the glycosphingolipid, GM3, in a membrane around a solid nanoparticle (NP) core is sufficient to recapitulate key aspects of the virus particle trafficking in mDCs. GM3-presenting artificial virus NPs (GM3-AVNs) accumulate in CD169(+) and CD81(+) nonlysosomal compartments in an actin-dependent process that mimics the sequestration of HIV-1. Live-cell optical tracking studies reveal a preferential recruitment and arrest of surface scanning CD4(+) T cells in direct vicinity to the AVN-enriched compartments. The formed mDC-T cell conjugates exhibit strong morphological similarities between the GM3-AVN-containing mDC-T cell synapse and the HIV-1 virological synapse, indicating that GM3-CD169 interactions alone are sufficient for establishing the mDC-T cell virological synapse. These results emphasize the potential of the GM3-AVN approach for providing therapeutic access to a key step of the host immune response--formation of the synaptic junction between an antigen-presenting cell (mDC) and T cells--for modulating and controlling immune responses.

  12. 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.

  13. 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.

  14. Description and status update on GELLO: a proposed standardized object-oriented expression language for clinical decision support.

    PubMed

    Sordo, Margarita; Boxwala, Aziz A; Ogunyemi, Omolola; Greenes, Robert A

    2004-01-01

    A major obstacle to sharing computable clinical knowledge is the lack of a common language for specifying expressions and criteria. Such a language could be used to specify decision criteria, formulae, and constraints on data and action. Al-though the Arden Syntax addresses this problem for clinical rules, its generalization to HL7's object-oriented data model is limited. The GELLO Expression language is an object-oriented language used for expressing logical conditions and computations in the GLIF3 (GuideLine Interchange Format, v. 3) guideline modeling language. It has been further developed under the auspices of the HL7 Clinical Decision Support Technical Committee, as a proposed HL7 standard., GELLO is based on the Object Constraint Language (OCL), because it is vendor-independent, object-oriented, and side-effect-free. GELLO expects an object-oriented data model. Although choice of model is arbitrary, standardization is facilitated by ensuring that the data model is compatible with the HL7 Reference Information Model (RIM).

  15. Clinical utility of chimerism status assessed by lineage-specific short tandem repeat analysis: experience from four cases of allogeneic stem cell transplantation.

    PubMed

    Goh, Ri-Young; Cho, Sung-Suk; Song, Yoo-Jeong; Heo, Kyeong; Oh, Sung-Yong; Kim, Sung-Hyun; Kwon, Hyeok-Chan; Kim, Hyo-Jin; Han, Jin-Yeong

    2009-08-01

    Chimerism testing permits early prediction and documentation of successful engraftment, and also facilitates detection of impending graft rejection. In this study, we serially monitored chimerism status by short tandem repeat-based PCR in nucleated cells (NC), T cells and natural killer (NK) cells after myeloablative allogeneic stem cell transplantation (SCT). Four patients with myeloid malignancies showed discrepant chimerism results among those three fractions. Three patients had mixed chimerism (MC) of donor/host T cells at a time point around the onset of chronic graft-versus-host disease (GVHD). In two patients with disease relapse, MC of NK cells preceded a morphological relapse or NK cells showed a higher percentage of patient cells compared to NC. Therefore, our study shows that chimerism analysis in lineage-specific cells might be useful in predicting clinical outcome after allogeneic SCT in certain patients.

  16. The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features

    PubMed Central

    Wang, Lu; Cui, Yun; Zhang, Lian; Sheng, Jindong; Yang, Yang; Kuang, Guanyu; Fan, Yu; Zhang, Qian; Jin, Jie

    2016-01-01

    Cyclin D2 (CCND2) is a member of the D-type cyclins, which plays a pivotal role in cell cycle regulation, differentiation and malignant transformation. However, its expression status and relative regulation mechanism remains unclear in renal cell cancer (RCC). In our study, the mRNA expression level of CCND2 is down-regulated in 22/23 paired RCC tissues (p<0.05). In addition, its protein expression level is also decreased in 43/43 RCC tumor tissues compared with its corresponding non-malignant tissues (p<0.001). We further detected that CCND2 was down-regulated or silenced in 6/7 RCC cell lines, but expressed in “normal” human proximal tubular (HK-2) cell line. Subsequently, MSP and BGS results showed that the methylation status in CCND2 promoter region is closely associated with its expression level in RCC cell lines. Treatment with 5-Aza with or without TSA restored CCND2 expression in several methylated RCC cell lines. Among the 102 RCC tumors, methylation of CCND2 was detected in 29/102 (28%) cases. Only 2/23 (8.7%) adjacent non-malignant tissues showed methylation. We then analyzed the correlation of clinical features and its promoter methylation. Collectively, our data suggested that loss of CCND2 expression is closely associated with the promoter aberrant methylation. PMID:27583477

  17. The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features.

    PubMed

    Wang, Lu; Cui, Yun; Zhang, Lian; Sheng, Jindong; Yang, Yang; Kuang, Guanyu; Fan, Yu; Zhang, Qian; Jin, Jie

    2016-01-01

    Cyclin D2 (CCND2) is a member of the D-type cyclins, which plays a pivotal role in cell cycle regulation, differentiation and malignant transformation. However, its expression status and relative regulation mechanism remains unclear in renal cell cancer (RCC). In our study, the mRNA expression level of CCND2 is down-regulated in 22/23 paired RCC tissues (p<0.05). In addition, its protein expression level is also decreased in 43/43 RCC tumor tissues compared with its corresponding non-malignant tissues (p<0.001). We further detected that CCND2 was down-regulated or silenced in 6/7 RCC cell lines, but expressed in "normal" human proximal tubular (HK-2) cell line. Subsequently, MSP and BGS results showed that the methylation status in CCND2 promoter region is closely associated with its expression level in RCC cell lines. Treatment with 5-Aza with or without TSA restored CCND2 expression in several methylated RCC cell lines. Among the 102 RCC tumors, methylation of CCND2 was detected in 29/102 (28%) cases. Only 2/23 (8.7%) adjacent non-malignant tissues showed methylation. We then analyzed the correlation of clinical features and its promoter methylation. Collectively, our data suggested that loss of CCND2 expression is closely associated with the promoter aberrant methylation. PMID:27583477

  18. Virulence of Escherichia coli Clinical Isolates in a Murine Sepsis Model in Relation to Sequence Type ST131 Status, Fluoroquinolone Resistance, and Virulence Genotype

    PubMed Central

    Porter, Stephen B.; Zhanel, George; Kuskowski, Michael A.; Denamur, Erick

    2012-01-01

    Escherichia coli sequence type ST131 (O25b:H4) has emerged over the past decade as a globally disseminated, multidrug-resistant pathogen. Unlike traditional antimicrobial-resistant E. coli, ST131 derives from virulence-associated phylogenetic group B2 and exhibits extraintestinal virulence factors. This, plus preliminary evidence of virulence in experimental animals, has suggested that ST131's epidemic emergence may be due to high virulence potential, compared with other E. coli types. To test this hypothesis, we compared a large number of matched ST131 and non-ST131 E. coli clinical isolates, both fluoroquinolone resistant and susceptible, plus isolates from classic extraintestinal pathogenic E. coli (ExPEC) sequence types (STs) and case report ST131 household transmission isolates, for virulence in a mouse subcutaneous sepsis model. Overall, in mice, the study isolates produced a wide range of lethality and clinical illness. However, neither ST131 status nor fluoroquinolone phenotype correlated with this diversity of illness severity, which occurred within each of the 6 study groups. In contrast, multiple known or suspected ExPEC virulence genes, including pap (P fimbriae), vat (vacuolating toxin), kpsM II (group 2 capsule), ibeA (invasion of brain endothelium), and clbB/N (colibactin synthesis), plus molecularly defined ExPEC status, were significantly associated with virulence. These findings point away from ST131 isolates as having higher virulence potential compared with other E. coli types in causing invasive extraintestinal infections and suggest instead that ST131's epidemiological success may reflect enhanced fitness for upstream steps in pathogenesis or in colonization and transmission. Additionally, the extensive within-ST virulence diversity suggests an opportunity to compare closely related strains to identify the responsible genetic determinants. PMID:22311928

  19. Sustained virological response to peginterferon therapy in patients infected with HCV (genotypes 2 and 3), with or without HIV

    PubMed Central

    2014-01-01

    Background HIV infection leads to a faster progression of liver disease in subjects infected with HCV, as compared with HCV mono-infected patients. Previous reports suggest that sustained virological response (SVR) rates are lower in HIV/HCV coinfection than in HCV monoinfection. We aimed to compare SVR rates of these two populations. Methods We retrospectively analyzed clinical, biochemical and virological data of HCV and HIV/HCV infected patients with HCV genotypes 2 and 3 who started anti-HCV treatment between March 2004 and November 2012, at a single large center. Intention-to-treat (ITT) and per-protocol (PP) analysis were performed. Univariate and multivariate logistic regression analyses were performed to assess predictors of SVR. Results 461 patients were analyzed: 307 (66.6%) males, 76 (16.5%) infected with HIV. Several differences at baseline between HCV monoinfected and HIV/HCV coinfected patients were observed. HCV monoinfected group was characterized by higher prevalence of genotype 2 (53% vs 5.3%), higher baseline HCV viral load (50% vs 35%), shorter mean duration of treatment (19 vs 41 weeks), more frequent use of peginterferon alfa-2a (84.5% vs 69.7%), lower prevalence of cirrhosis (6% vs 31.6%). Globally, SVR was achieved by 353 (76.6%) patients and 321 (83.8%) in the PP analysis. No statistically relevant differences were found in SVR rates between the two groups, either in ITT [78.2% (n = 301/385) vs 68.4% (n = 52/76), p =0.066, respectively] than in PP analysis [83.6% (n = 276/330) vs 84.9% (n = 45/53), p = 0.8]. ITT analysis At univariate and multivariate analysis, baseline HCV-RNA >500.000 IU/ml [OR 0.4 (0.24-0.66), p = 0.0004], use of peginterferon alfa-2b [OR 0.5 (0.27-0.93) p = 0.033], platelets count <130.000/mm3 [OR 0.45 (0.2-0.99), p = 0.045], interruption of peginterferon therapy [OR 0.2 (0.1-0.4), p<0.0001], interruption of ribavirin treatment [OR 0.34 (0.17-0.69), p = 0.0026] were related with lower rate of SVR. PP analysis Only HCV

  20. The Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Androgen Status in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials.

    PubMed

    Hajishafiee, M; Askari, G; Iranj, B; Ghiasvand, R; Bellissimo, N; Totosy de Zepetnek, J; Salehi-Abargouei, A

    2016-05-01

    The anti-androgenic role of n-3 polyunsaturated fatty acids (PUFAs) among patients with polycystic ovary syndrome (PCOS) has recently been proposed. The present study aimed to systematically review clinical trials assessing the effects of n-3 PUFAs consumption on androgen status among adult females with PCOS. PubMed, ISI Web of Science, Google Scholar, and Scopus were searched up to December 2015. Clinical investigations assessing the effect of n-3 PUFAs on adult females with PCOS were included. Mean±standard deviation of change in serum total testosterone, sex hormone binding globulin (SHBG), and dehydroepiandrostrone sulfate (DHEAS) were extracted. Eight clinical trials with 298 participants were eligible. Meta-analysis showed that n-3 PUFAs supplementation marginally reduces total testosterone (mean difference [MD]: - 0.19 nmol/l; 95% CI: - 0.39 to 0.00; p=0.054), but not SHBG (MD: 1.75 nmol/l; 95% CI: -0.51 to 4.01; p=0.129) or serum DHEAS levels (Hedes' g: -0.11 nmol/l; 95% CI: -0.29 to 0.06; p=0.19) among adult females with PCOS. Subgroup analyses showed that only before-after studies (Hedges' g: 0.15; 95% CI: -0.27 to -0.04; p=0.01) and long-term interventions (>6 weeks) (Hedges' g: -0.17; 95% CI, -0.29 to -0.05; p=0.004) had reducing effects on serum DHEAS levels. The majority of long-term trials utilized a single group design (no control group). It does not appear that n-3 PUFAs supplementation significantly affects the androgenic profile of females with PCOS; however, some before-after and long-term intervention studies show reduced DHEAS levels. Future studies incorporating double blinded placebo controlled clinical trials with long follow-up periods are warranted. PMID:27077458

  1. Migration status in relation to clinical characteristics and barriers to care among youth with diabetes in the US.

    PubMed

    Jaacks, Lindsay M; Oza-Frank, Reena; D'Agostino, Ralph; Dolan, Lawrence M; Dabelea, Dana; Lawrence, Jean M; Pihoker, Catherine; O'Connor, M Rebecca; Linder, Barbara; Imperatore, Giuseppina; Seid, Michael; Narayan, K M Venkat; Mayer-Davis, Elizabeth J

    2012-12-01

    Migration status and the accompanying diversity in culture, foods and family norms, may be an important consideration for practitioners providing individualized care to treat and prevent complications among youth with diabetes. Approximately 20 % of youth in the US have ≥1 foreign-born parent. However, the proportion and characteristics of youth with diabetes and ≥1 foreign-born parent have yet to be described. Study participants (n = 3,086) were from SEARCH for Diabetes in Youth, a prospective multi-center study in the US. Primary outcomes of interest included HbA1c, body mass index and barriers to care. Multivariable analyses were carried out using logistic regression and analysis of covariance. Approximately 17 % of participants with type 1 diabetes (T1D) and 22 % with type 2 diabetes (T2D) had ≥1 foreign-born parent. Youth with T1D and ≥1 foreign-born parent were less likely to have poor glycemic control [adjusted odds ratio (OR) (95 % confidence interval): 0.70 (0.53, 0.94)]. Among youth with T2D, those with ≥1 foreign-born parent had lower odds of obesity [adjusted OR (95 % CI): 0.35 (0.17, 0.70)]. This is the first study to estimate the proportion and characteristics of youth with diabetes exposed to migration in the US. Research into potential mechanisms underlying the observed protective effects is warranted.

  2. Diagnostic virology practices for respiratory syncytial virus and influenza virus among children in the hospital setting: a national survey.

    PubMed

    Jafri, Hasan S; Ramilo, Octavio; Makari, Doris; Charsha-May, Deborah; Romero, José R

    2007-10-01

    A survey was sent to the emergency room and laboratory directors of 400 randomly selected US hospitals to assess the diagnostic testing practices for respiratory syncytial virus and influenza virus in children. The results demonstrate that the majority of hospitals routinely perform viral testing for both viruses and use virology testing practices appropriate for the reasons reported for testing.

  3. Hepatitis C virus (HCV) genotype 2a has a better virologic response to antiviral therapy than HCV genotype 1b

    PubMed Central

    Wang, Meng; Zhang, Yi; Li, Zhiqin; Zhang, Hongyu; Zhang, Zhen; Yue, Dongli; Zhou, Rong; Li, Xiaogang; Wu, Shuhuan; Li, Jiansheng

    2015-01-01

    The standard treatment, pegylated interferon (PEG-IFN) plus ribavirin (RBV), for patients with chronic hepatitis C (CHC), does not provide a sustained virologic response (SVR) in a large majority of patients. In the present study, 211 treatment-naïve patients with the hepatitis C virus (HCV) genotype 1b and 2a were recruited and treated weekly with PEG-IFN plus RBV to determine the response of HCV genotype 1b and 2a patients to standard antiviral treatment. Virologic responses were assessed by TaqMan at week 4, 12, 24, 48 and 24 weeks of treatment. Patients with HCV genotype 2a had a significantly higher rapid virologic response (RVR), early virologic response, end-of-treatment response and SVR, and a lower relapse rate than patients with HCV genotype 1b. Multivariate logistic regression analysis showed that the HCV genotype 2a patients had a HCV RNA level ≤ 5.70 log10 IU/ml, a fibrosis stage < S3, and that HLA-A02 expression and RVR were independent factors of SVR that may improve HCV clearance. PMID:26221288

  4. Undergraduate Virology Exercises Demonstrate Conventional and Real-Time PCR Using Commercially Available HIV Primers and Noninfectious Target

    ERIC Educational Resources Information Center

    Sulzinski, Michael A.; Wasilewski, Melissa A.; Farrell, James C.; Glick, David L.

    2009-01-01

    It is an extraordinary challenge to offer an undergraduate laboratory course in virology that teaches hands-on, relevant molecular biology techniques using nonpathogenic models of human virus detection. To our knowledge, there exists no inexpensive kits or reagent sets that are appropriate for demonstrating real-time PCR (RT-PCR) in an…

  5. Baseline prognostic factors and statistic model to predict early virological response in lamivudine-treated patients with chronic hepatitis B.

    PubMed

    Zhou, Rui; Pan, Fan; Lin, Chun; Lin, Xiuquan; Gao, Haibing; Huang, Shuiwen; Huang, Zuxiong; Lin, Yong; Pan, Chen; Zhou, Yuanping

    2015-01-01

    Lamivudine is a potent nucleoside analogue used in treating chronic hepatitis B (CHB). However, resistance to the drug remains a problem. We analyzed all lamivudine recipients in this trial to determine the baseline characteristics and a model to predict early virological response reflecting the long-term effect of lamivudine. In this prospective trial, 230 patients who had not treated with nucleotide analogue with chronic HBV infection were assigned to receive 100 mg of lamivudine once daily for 24 weeks at least. All patients were followed up every 2 week. Cox proportional hazard regression model analyses were employed to evaluate baseline variables and to develop a statistical model. Female (P = 0.042), baseline higher serum aspartate aminotransferase (AST) (P = 0.002), and lower level of HBV-DNA (P = 0.016) were identified to be associated with higher possibility of early virological response. A model was established based on these variables to calculate the risk scores (R) for CHB patients. R > -0.45 suggested early virological response to lamivudine. The model was validated among an independent set of 40 patients. The gender as well as baseline AST and HBV-DNA levels can predict early virological response. The model provides a better tool for response prediction based on the three prognostic factors.

  6. Temporary treatment during primary HIV infection does not affect virologic response to subsequent long-term treatment.

    PubMed

    Grijsen, Marlous L; Wit, Ferdinand W N M; Jurriaans, Suzanne; Kroon, Frank P; Schippers, Emile F; Koopmans, Peter; Gras, Luuk; Lange, Joep M A; Prins, Jan M

    2014-01-01

    Temporary cART during primary HIV-infection (PHI) did not select for drug resistance mutations after treatment interruption and did not affect the subsequent virological response to long-term cART. Our data demonstrate that fear of drug resistance development is not a valid argument to refrain from temporary early treatment during PHI.

  7. Impact of Interleukin 28B Genotype on the Virological Responses in Chronic Hepatitis C Treatment

    PubMed Central

    Aygen, Bilgehan; Yildiz, Orhan; Akhan, Sila; Gunal, Ozgur; Taheri, Serpil; Zararsiz, Gokmen; Sayan, Murat; Rustemoglu, Aydin; Altinok, Elif Sargin

    2014-01-01

    Background Interleukin (IL) 28B single nucleotide polymorphisms may play a role in the clearance of hepatitis C virus (HCV). We aimed to evaluate the treatment response of chronic HCV infection patients to pegile interferon (pegIFN) and ribavirin treatment with regard to IL28B rs12979860 C/T polymorphism. Methods A total of 186 patients (mean age, 55.6 ± 10 years; 65.1% female) who underwent pegIFN and ribavirin treatment for chronic HCV infection were studied. We analyzed demographics, HCV genotype, baseline alanine aminotransferase (ALT) levels, histopathological data, viral load before treatment and at 4, 12, 24, 48, and 72 weeks from the treatment start, and IL28B genotype. IL28B polymorphism was genotyped using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in all the subjects. Results One hundred forty-five (86.8%) patients were infected with viral genotype 1b, and 13.2% were infected with viral genotype 4. The rates of C/C, C/T, and T/T genotypes were 22.6%, 52.7%, and 24.7% respectively. The percentage of patients with a viral load over 400,000 IU/mL was higher in the C/T group (P = 0.020). Of the patients, 44.6% provided sustained virological response (SVR) to pegIFN and ribavirin combination treatment. The frequency of T allele was 41% in patients with SVR, whereas 59% patients provided no response (P < 0.001). SVR was obtained in 66.7%, 42.9%, and 28.3% of CC, CT, and TT groups (P = 0.001). The rates of rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and SVR were higher in the CC group than other groups (P = 0.216, P < 0.001, P = 0.001, P = 0.001, respectively). The relapse and null response (NR) rates were higher in TT group and partial response rate (PR) was higher in CT group. Conclusions IL28B rs12979860 C/T gene polymorphism affects the response to antiviral treatment in the patients with chronic HCV genotypes 1b and 4 infections.

  8. Contributions of Early Cortical Processing and Reading Ability to Functional Status in Individuals at Clinical High Risk for Psychosis

    PubMed Central

    Carrión, Ricardo E.; Cornblatt, Barbara A.; McLaughlin, Danielle; Chang, Jeremy; Auther, Andrea M.; Olsen, Ruth H.; Javitt, Daniel C.

    2015-01-01

    Background There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. Methods The sample consisted of 34 CHR individuals and 33 healthy comparisons subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning. Results CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively. Conclusions Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function. PMID:25728833

  9. Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial

    PubMed Central

    Hossein-nezhad, Arash; Spira, Avrum; Holick, Michael F.

    2013-01-01

    Background Although there have been numerous observations of vitamin D deficiency and its links to chronic diseases, no studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. The objective of this study was to determine the effect of vitamin D status and subsequent vitamin D supplementation on broad gene expression in healthy adults. (Trial registration: ClinicalTrials.gov NCT01696409). Methods and Findings A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults in the winter. Microarrays of the 16 buffy coats from eight subjects passed the quality control filters and normalized with the RMA method. Vitamin D3 supplementation that improved serum 25-hydroxyvitamin D concentrations was associated with at least a 1.5 fold alteration in the expression of 291 genes. There was a significant difference in the expression of 66 genes between subjects at baseline with vitamin D deficiency (25(OH)D<20 ng/ml) and subjects with a 25(OH)D>20 ng/ml. After vitamin D3 supplementation gene expression of these 66 genes was similar for both groups. Seventeen vitamin D-regulated genes with new candidate vitamin D response elements including TRIM27, CD83, COPB2, YRNA and CETN3 which have been shown to be important for transcriptional regulation, immune function, response to stress and DNA repair were identified. Conclusion/Significance Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the

  10. Prevalence, Clinical Profile, Iron Status, and Subject-Specific Traits for Excessive Erythrocytosis in Andean Adults Living Permanently at 3,825 Meters Above Sea Level

    PubMed Central

    De Ferrari, Aldo; Miranda, J. Jaime; Gilman, Robert H.; Dávila-Román, Victor G.; León-Velarde, Fabiola; Rivera-Ch, Maria; Huicho, Luis; Bernabé-Ortiz, Antonio; Wise, Robert A.

    2014-01-01

    BACKGROUND: Excessive erythrocytosis (EE) is a prevalent condition in populations living at high altitudes (> 2,500 m above sea level). Few large population-based studies have explored the association between EE and multiple subject-specific traits including oxygen saturation, iron status indicators, and pulmonary function. METHODS: We enrolled a sex-stratified and age-stratified sample of 1,065 high-altitude residents aged ≥ 35 years from Puno, Peru (3,825 m above sea level) and conducted a standardized questionnaire and physical examination that included spirometry, pulse oximetry, and a blood sample for multiple clinical markers. Our primary objectives were to estimate the prevalence of EE, characterize the clinical profile and iron status indicators of subjects with EE, and describe subject-specific traits associated with EE. RESULTS: Overall prevalence of EE was 4.5% (95% CI, 3.3%-6.0%). Oxygen saturation was significantly lower among EE than non-EE group subjects (85.3% vs 90.1%, P < .001) but no difference was found in iron status indicators between both groups (P > .09 for all values). In multivariable logistic regression, we found that age ≥ 65 years (OR = 2.45, 95% CI, 1.16-5.09), male sex (3.86, 1.78-9.08), having metabolic syndrome (2.66, 1.27-5.75) or being overweight (5.20, 1.95-16.77), pulse oximetry < 85% (14.90, 6.43-34.90), and % predicted FVC < 80% (13.62, 4.40-41.80) were strongly associated with EE. Attributable fractions for EE were greatest for being overweight (26.7%), followed by male sex (21.5%), pulse oximetry < 85% (16.4%), having metabolic syndrome (14.4%), and % predicted FVC < 80% (9.3%). CONCLUSIONS: We found a lower prevalence of EE than in previous reports in the Peruvian Andes. Although the presence of hypoxemia and decreased vital capacity were strongly associated with excessive erythrocytosis, being overweight or having metabolic syndrome were associated with an important fraction of cases in our study population. PMID

  11. [A new objective clinical method in the evaluation of the status of blood flow in conjunctival vessels].

    PubMed

    Polunin, G S; Pirogova, E P; Iarovaia, L D

    1989-01-01

    The suggested method for assessment of the blood aggregation characteristics in the conjunctival vessels is based on microdensitometry of the blood stream microphotographs. The method permits a graphic recording of the blood stream. The potentialities of the developed technique have been studied in comparison of the blood aggregation in patients with diabetic retinopathy and in normal subjects. The data evidence an increased coagulation activity of the blood in patients with diabetes mellitus vs. normal subjects, this correlating with the biochemical findings in examinations of these patients' hemostasis. The clinical method for assessment of the blood aggregation characteristics may be useful for the prognosis of the course of various diseases and for monitoring the treatment efficacy.

  12. Canagliflozin-current status in the treatment of type 2 diabetes mellitus with focus on clinical trial data

    PubMed Central

    Bhatia, Jagriti; Gamad, Nanda; Bharti, Saurabh; Arya, Dharamvir Singh

    2014-01-01

    Canagliflozin (CFZ) is a member of new class of glucose lowering agents, sodium-glucose co-transporter (SGLT) inhibitors, which got approval by food and drug administration. It has insulin independent action by blocking the transporter protein SGLT2 in the kidneys, resulting in urinary glucose excretion and reduction in blood glucose levels. In clinical trials, CFZ significantly decreased HbA1c level when administered either as monotherapy or as combined therapy with other anti-diabetic drugs. Intriguingly, it showed additional benefits like weight reduction and lowering of blood pressure. The commonly observed side effects were urinary and genital infections. It has exhibited favorable pharmacokinetic and pharmacodynamic profiles even in patients with renal and hepatic damage. Hence, this review purports to outline CFZ as a newer beneficial drug for type 2 diabetes mellitus. PMID:24936262

  13. A focus on the preclinical development and clinical status of the histone deacetylase inhibitor, romidepsin (depsipeptide, Istodax(®)).

    PubMed

    Harrison, Simon J; Bishton, Mark; Bates, Susan E; Grant, Steven; Piekarz, Richard L; Johnstone, Ricky W; Dai, Yun; Lee, Becki; Araujo, Maria E; Prince, H Miles

    2012-10-01

    Romidepsin (Istodax(®), depsipeptide, FR901228, FK228, NSC 630176) is a cyclic peptide, broad-spectrum, potent histone deacetylase inhibitor, with activity mainly against class I histone deacetylase enzymes. In this article, we give an overview of the putative modes of action, such as effects on gene expression, cell cycle regulation, apoptosis induction, DNA repair, protein acetylation and induction of autophagy. Romidepsin has mainly been developed as a therapy for hematologic malignancies and is approved by the US FDA for the treatment of cutaneous T-cell lymphomas. This report outlines the laboratory and clinical development of the compound as a single agent that has more recently been evaluated in combination with other anticancer therapeutics, such as proteasome inhibitors.

  14. The conundrum of causality in tumor virology: the cases of KSHV and MCV.

    PubMed

    Moore, Patrick S; Chang, Yuan

    2014-06-01

    Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch's postulates, work poorly or not at all for these viruses. Kaposi's sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology.

  15. A brief review on dengue molecular virology, diagnosis, treatment and prevalence in Pakistan

    PubMed Central

    2012-01-01

    Dengue virus infection is a serious health problem infecting 2.5 billion people worldwide. Dengue is now endemic in more than 100 countries, including Pakistan. Each year hundreds of people get infected with dengue in Pakistan. Currently, there is no vaccine available for the prevention of Dengue virus infection due to four viral serotypes. Dengue infection can cause death of patients in its most severity, meanwhile many antiviral compounds are being tested against dengue virus infection to eradicate this disease but still there is a need to develop an efficient, low-cost and safe vaccine that can target all the four serotypes of dengue virus. This review summarizes dengue molecular virology, important drug targets, prevalence in Pakistan, diagnosis, treatment and medicinal plant inhibitors against dengue. PMID:22929369

  16. HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT

    PubMed Central

    de MATTOS, Angelo Alves; MARCON, Patrícia dos Santos; de ARAÚJO, Fernanda Schild Branco; CORAL, Gabriela Perdomo; TOVO, Cristiane Valle

    2015-01-01

    Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil. PMID:27049708

  17. The Impact of Mass Spectrometry-Based Proteomics on Fundamental Discoveries in Virology.

    PubMed

    Greco, Todd M; Diner, Benjamin A; Cristea, Ileana M

    2014-11-01

    In recent years, mass spectrometry has emerged as a core component of fundamental discoveries in virology. As a consequence of their coevolution, viruses and host cells have established complex, dynamic interactions that function either in promoting virus replication and dissemination or in host defense against invading pathogens. Thus, viral infection triggers an impressive range of proteome changes. Alterations in protein abundances, interactions, posttranslational modifications, subcellular localizations, and secretion are temporally regulated during the progression of an infection. Consequently, understanding viral infection at the molecular level requires versatile approaches that afford both breadth and depth of analysis. Mass spectrometry is uniquely positioned to bridge this experimental dichotomy. Its application to both unbiased systems analyses and targeted, hypothesis-driven studies has accelerated discoveries in viral pathogenesis and host defense. Here, we review the contributions of mass spectrometry-based proteomic approaches to understanding viral morphogenesis, replication, and assembly and to characterizing host responses to infection.

  18. The Conundrum of Causality in Tumor Virology: The Cases of KSHV and MCV

    PubMed Central

    Moore, Patrick S.; Chang, Yuan

    2014-01-01

    Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch’s postulates, work poorly or not at all for these viruses. Kaposi’s sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology. PMID:24304907

  19. Rising to the challenge: accelerated pace of discovery transforms marine virology.

    PubMed

    Brum, Jennifer R; Sullivan, Matthew B

    2015-03-01

    Marine viruses have important roles in microbial mortality, gene transfer, metabolic reprogramming and biogeochemical cycling. In this Review, we discuss recent technological advances in marine virology including the use of near-quantitative, reproducible metagenomics for large-scale investigation of viral communities and the emergence of gene-based viral ecology. We also describe the reprogramming of microbially driven processes by viral metabolic genes, the identification of novel viruses using cultivation-dependent and cultivation-independent tools, and the potential for modelling studies to provide a framework for studying virus-host interactions. These transformative advances have set a rapid pace in exploring and predicting how marine viruses manipulate and respond to their environment.

  20. HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT.

    PubMed

    Mattos, Angelo Alves de; Marcon, Patrícia dos Santos; Araújo, Fernanda Schild Branco de; Coral, Gabriela Perdomo; Tovo, Cristiane Valle

    2015-12-01

    Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil. PMID:27049708

  1. Epidemic dengue hemorrhagic fever in rural Indonesia. I. Virological and epidemiological studies.

    PubMed

    Gubler, D J; Suharyono, W; Lubis, I; Eram, S; Sulianti Saroso, J

    1979-07-01

    Virological studies were carried out during an epidemic of dengue hemorrhagic fever in Central Java, Indonesia in 1976. Dengue virus was isolated from the acute sera of 45 of 69 patients (65%). The isolation rate was higher in primary than secondary cases. Dengue 3 was the predominant serotype being transmitted (27 isolates), but both dengue 1 (8 isolates) and dengue 4 (10 isolates) were also being transmitted. A composite picture of magnitude and duration of viremia showed that many patients were circulating over 10(8) MID50 per milliliter dengue 3 virus for the first 3 days of illness and that viremia persisted for 5-6 days in some persons. If all shock cases were considered, there was no relationship between dengue serotype and severity of disease. All three confirmed fatal cases, however, were associated with dengue type 3 infections.

  2. Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities.

    PubMed

    Gish, Robert G; Given, Bruce D; Lai, Ching-Lung; Locarnini, Stephen A; Lau, Johnson Y N; Lewis, David L; Schluep, Thomas

    2015-09-01

    The host immune system plays an important role in chronic hepatitis B (CHB), both in viral clearance and hepatocellular damage. Advances in our understanding of the natural history of the disease have led to redefining the major phases of infection, with the "high replicative, low inflammatory" phase now replacing what was formerly termed the "immune tolerant" phase, and the "nonreplicative phase" replacing what was formerly termed the "inactive carrier" phase. As opposed to the earlier view that HBV establishes chronic infection by exploiting the immaturity of the neonate's immune system, new findings on trained immunity show that the host is already somewhat "matured" following birth, and is actually very capable of responding immunologically, potentially altering future hepatitis B treatment strategies. While existing therapies are effective in reducing viral load and necroinflammation, often restoring the patient to near-normal health, they do not lead to a cure except in very rare cases and, in many patients, viremia rebounds after cessation of treatment. Researchers are now challenged to devise therapies that will eliminate infection, with a particular focus on eliminating the persistence of viral cccDNA in the nuclei of hepatocytes. In the context of chronic hepatitis B, new definitions of 'cure' are emerging, such as 'functional' and 'virological' cure, defined by stable off-therapy suppression of viremia and antigenemia, and the normalization of serum ALT and other liver-related laboratory tests. Continued advances in the understanding of the complex biology of chronic hepatitis B have resulted in the development of new, experimental therapies targeting viral and host factors and pathways previously not accessible to therapy, approaches which may lead to virological cures in the near term and functional cures upon long term follow-up. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia

  3. Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives

    PubMed Central

    Beg, Sarwar; Swain, Suryakanta; Hasan, Hameed; Barkat, M Abul; Hussain, Md Sarfaraz

    2011-01-01

    Many synthetic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Since the last few decades, herbal drugs have regained their popularity in treatment against several human ailments. Herbals containing anti-inflammatory activity (AIA) are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA. The basic aim of this review is to give updated knowledge regarding plants which will be valuable for the scientists working in the field of anti-inflammatory natural chemistry. PMID:22279370

  4. Clinical status in adolescents: is its impact on oral health-related quality of life influenced by psychological characteristics?

    PubMed

    Foster Page, Lyndie A; Thomson, W Murray; Ukra, Ali; Baker, Sarah R

    2013-06-01

    The objective of this study was to examine, using structural equation modelling, the relationships among clinical characteristics (such as caries experience and malocclusion), oral health-related quality of life (OHRQoL), and psychological characteristics (mental health, self-esteem, somatisation, and social perception of body image) in adolescents in New Zealand. Adolescents were examined for malocclusion using the Dental Aesthetic Index (DAI) and for dental caries. Among the 353 (58.8%) 12- and 13-yr-old adolescents who took part in this cross-sectional study, the overall mean ± SD decayed, missing, or filled surfaces (DMFS) value was 1.6 ± 3.0, with slightly more than 50% of being caries-free; the mean ± SD DAI was 31.5 ± 7.6, with one-quarter of subjects having a 'handicapping' malocclusion. The structural equation modelling analysis showed that the structural model was a good fit to the data. As hypothesized, the DAI score significantly predicted OHRQoL. There was no direct relationship between caries experience (DMFS) and OHRQoL, but there was an indirect effect of DMFS on OHRQoL mediated through psychological characteristics. The amount of OHRQoL variance accounted for in the model was substantial, at 62%. It appears that investigating OHRQoL in adolescents is not straightforward; while malocclusion directly affects OHRQoL, the influence of dental caries experience is less direct.

  5. Virological and molecular epidemiological investigations into the role of wild birds in the epidemiology of influenza A/H5N1 in central Thailand.

    PubMed

    Siengsanan-Lamont, J; Robertson, I; Blacksell, S D; Ellis, T; Fenwick, S; Saengchoowong, S; Suwanpukdee, S; Yongyuttawichai, P; Sariya, L; Prompiram, P; Chaichoun, K; Wiriyarat, W; Pothieng, D; Ratanakorn, P

    2011-03-24

    A serological and virological surveillance program to investigate the HPAI H5N1 virus in wild bird populations was undertaken from February 2007 to October 2008. The purpose of the survey was to investigate the infection status in free ranging wild birds in Banglane district, Nakhon Pathom province, central Thailand. Samples from wild birds were collected every two months. Choanal and cloacal swabs, serum and tissue samples were collected from 421 birds comprising 44 species. Sero-prevalence of the virus tested by H5N1 serum neutralization test (using a H5N1 virus clade 1; A/chicken/Thailand/vsmu-3-BKK/2004) was 2.1% (8 out of 385 samples; 95% CI 0.7, 3.5). Species that were antibody positive included rock pigeons (Columba livia), Asian pied starling (Gracupica contra), spotted dove (Streptopelia chinensis), oriental magpie robin (Copsychus saularis), blue-tailed bee-eater (Merops philippinus), myna (Acridotheres spp.), and pond heron (Ardeola spp.). Prevalence by H5N1 virus isolation was 0.5% (2 out of 421 samples; 95% CI 0.0, 1.1); the two H5N1 virus-positive samples were from Asian pied starling (Gracupica contra) and white vented myna (Acridotheres grandis). Positive virological samples were collected in June 2007 while all positive serology samples were collected between May and August except for one sample collected in December 2007. No positive samples were collected in 2008. Molecular studies revealed that the wild bird H5N1 viruses were closely related to poultry viruses isolated in other parts of Thailand. However, there was no poultry H5N1 prevalence study performed in the study site during the time of this wild bird survey. Interpretation of source of virus isolates would include spill-over of H5N1 viruses from contaminated sources due to movement of domestic poultry and/or fomites from other areas; or infection of wild birds within the outbreak locations and then translocation by wild bird movement and interaction with wild birds inhabiting distant

  6. Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting

    PubMed Central

    Revell, Andrew D.; Wang, Dechao; Pozniak, Anton; Montaner, Julio S.; Lane, H. Clifford; Larder, Brendan A.

    2013-01-01

    Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%). Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings. PMID:24175292

  7. Clinical characteristics and the diagnosis and treatment status of headaches in the Department of Gerontology of a university hospital in China.

    PubMed

    Wang, Xin; Li, Wang-Wen; Duan, Jing-Xi; Deng, Yong-Tao; Pan, Lin; Zhou, Ji-Ying

    2014-10-01

    Headache is a common problem among the population, many factors may impact the headache characteristics and medical consultation behaviors in different age groups. The purpose of this study was to evaluate the clinical characteristics and the diagnosis and treatment status of headaches in elderly patients hospitalized in a gerontologic department. Consecutive patients hospitalized in the Department of Gerontology eligible for this study were registered. All the patients underwent a comprehensive evaluation of their whole health status, performed by three gerontologists initially. Then headache was evaluated by two physicians experienced in headache studies. Headache diagnosis was made according to the criteria of the second edition of the International Classification of Headache Disorders. In this study, 20% of the participants reported at least one headache attack in the previous year. Sixty percent of the migraineurs and 79·7% of the tension type headache (TTH) patients reported bilateral pain. Throbbing/pulsating and tightness/pressing were the most frequently described pain quality by the migraineurs and TTH patients, respectively. The migraineurs reported the most severe pain (P < 0·001). The frequency of headache attacks was not significantly different in the three subgroups (P  =  0·053). About 76·2% of the migraineurs, 68·8% of the TTH, and 80% of the other type headache patients had consulted a physician for their headaches in the previous year. Taking acute analgesics for headache was more common in migraineurs (P < 0·001). The results showed that headache remained under-recognized and under-treated in the geriatrics department.

  8. Determining the status of non-transferred embryos in Ireland: a conspectus of case law and implications for clinical IVF practice

    PubMed Central

    Sills, Eric Scott; Murphy, Sarah Ellen

    2009-01-01

    The development of in vitro fertilisation (IVF) as a treatment for human infertilty was among the most controversial medical achievements of the modern era. In Ireland, the fate and status of supranumary (non-transferred) embryos derived from IVF brings challenges both for clinical practice and public health policy because there is no judicial or legislative framework in place to address the medical, scientific, or ethical uncertainties. Complex legal issues exist regarding informed consent and ownership of embryos, particularly the use of non-transferred embryos if a couple separates or divorces. But since case law is only beginning to emerge from outside Ireland and because legislation on IVF and human embryo status is entirely absent here, this matter is poised to raise contractual, constitutional and property law issues at the highest level. Our analysis examines this medico-legal challenge in an Irish context, and summarises key decisions on this issue rendered from other jurisdictions. The contractual issues raised by the Roche case regarding informed consent and the implications the initial judgment may have for future disputes over embryos are also discussed. Our research also considers a putative Constitutional 'right to procreate' and the implications EU law may have for an Irish case concerning the fate of frozen embryos. Since current Medical Council guidelines are insufficient to ensure appropriate regulation of the advanced reproductive technologies in Ireland, the report of the Commission on Assisted Human Reproduction is most likely to influence embryo custody disputes. Public policy requires the establishment and implementation of a more comprehensive legislative framework within which assisted reproductive medical services are offered. PMID:19589140

  9. KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

    SciTech Connect

    Kim, Sun Young; Shim, Eun Kyung; Yeo, Hyun Yang; Baek, Ji Yeon; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seock-Ah; Jung, Kyung Hae; Chang, Hee Jin

    2013-01-01

    Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with

  10. Relationships between serum aminotransferase levels, liver histologies and virological status in patients with chronic hepatitis C in Taiwan.

    PubMed

    Luo, J C; Hwang, S J; Lai, C R; Lu, C L; Li, C P; Tsay, S H; Wu, J C; Chang, F Y; Lee, S D

    1998-07-01

    In patients with chronic hepatitis C, the relationships between serum alanine aminotransferase (ALT) levels, histological liver injury and serum hepatitis C virus (HCV) RNA titres remain controversial. To evaluate these relationships, 93 Chinese patients with histological diagnosis of chronic hepatitis C were enrolled for this study. Serum ALT levels, HCV-RNA titres and HCV genotypes were examined. The histology was evaluated according to a modified histological activity score based on the degree of periportal necro-inflammation, intralobular necro-inflammation, portal inflammation, total necro-inflammation and fibrosis. The mean serum ALT level was significantly higher in patients with severe intralobular necro-inflammation activity than in patients with mild or no activity (P = 0.013). However, scores of intralobular activity were only weakly correlated with serum ALT levels (r = 0.27) and could not be used to adequately predict ALT values. Serum ALT levels showed no significant correlation with the scores of portal inflammation, periportal necro-inflammation, total necro-inflammation and fibrosis. Also, there was no significant difference in the mean serum ALT level among different serum HCV-RNA levels and HCV genotypes. Serum HCV-RNA titres and genotypes showed no significant correlation with liver histology and serum HCV-RNA titres were only weakly correlated with the total necro-inflammatory score (r = 0.27). In conclusion, although serum ALT levels were higher in patients with more severe intralobular necro-inflammatory activity, the correlation was not strong enough to adequately predict ALT values. Serum HCV-RNA titres and genotypes also showed no significant correlation with serum ALT levels and liver histologies.

  11. Relationships Among Neurocognitive Status, Medication Adherence Measured by Pharmacy Refill Records, and Virologic Suppression in HIV-infected Persons

    PubMed Central

    Andrade, Adriana S.A.; Deutsch, Reena; Celano, Shivaun; Duarte, Nichole A.; Marcotte, Thomas D.; Umlauf, Anya; Atkinson, J. Hampton; McCutchan, J. Allen; Franklin, Donald; Alexander, Terry J.; McArthur, Justin; Marra, Christina; Grant, Igor; Collier, Ann C

    2013-01-01

    Background Optimal antiretroviral therapy (ART) effectiveness depends upon medication adherence, which is a complex behavior with many contributing factors including neurocognitive function. Pharmacy refill records offer a promising and practical tool to assess adherence. Methods A substudy of the CHARTER (CNS HIV Anti-Retroviral Therapy Effects Research) study was conducted at the Johns Hopkins University (JHU) and the University of Washington (UW). Pharmacy refill records were the primary method to measure ART adherence, indexed to a “sentinel” drug with the highest central nervous system penetration effectiveness score. Standardized neuromedical, neuropsychological, psychiatric and substance use assessments were performed at enrollment and at 6 months. Regression models were used to determine factors associated with adherence and the relationships between adherence and change in plasma and cerebrospinal fluid HIV RNA concentrations between visits. Results Among 80 (33 JHU, 47 UW) participants, the mean adherence score was 86.4% with no difference by site. In the final multivariable model, better neurocognitive function was associated with better adherence, especially among participants who were at JHU, male, and HIV-infected for a longer time-period. Worse performance on working memory tests was associated with worse adherence. Better adherence predicted greater decreases in cerebrospinal fluid HIV RNA between visits. Conclusion Poorer global neurocognitive functioning and deficits in working memory were associated with lower adherence defined by a pharmacy refill record measure, suggesting that assessments of cognitive function, and working memory in particular, may identify patients at risk for poor ART adherence who would benefit from adherence support. PMID:23202813

  12. Diagnostic tests in HIV management: a review of clinical and laboratory strategies to monitor HIV-infected individuals in developing countries.

    PubMed Central

    Kimmel, April D.; Losina, Elena; Freedberg, Kenneth A.; Goldie, Sue J.

    2006-01-01

    We conducted a systematic review on the performance of diagnostic tests for clinical and laboratory monitoring of HIV-infected adults in developing countries. Diagnostic test information collected from computerized databases, bibliographies and the Internet were categorized as clinical (non-laboratory patient information), immunologic (information from immunologic laboratory tests), or virologic (information from virologic laboratory tests). Of the 51 studies selected for the review 28 assessed immunologic tests, 12 virologic tests and seven clinical and immunologic tests. Methods of performance evaluation were primarily sensitivity and specificity for the clinical category and correlation coefficients for immunologic and virologic categories. In the clinical category, the majority of test performance measures was reported as >70% sensitive and >65% specific. In the immunologic category, correlation coefficients ranged from r=0.54 to r=0.99 for different CD4 count enumeration techniques, while correlation for CD4 and total lymphocyte counts was between r=0.23 and r=0.74. In the virologic category, correlation coefficients for different human immunodeficiency virus (HIV) ribonucleic acid (RNA) quantification techniques ranged from r=0.54 to r=0.90. Future research requires consensus on designing studies, and collecting and reporting data useful for decision-makers. We recommend classifying information into clinically relevant categories, using a consistent definition of disease across studies and providing measures of both association and accuracy. PMID:16878233

  13. Age at Virologic Control Influences Peripheral Blood HIV Reservoir Size and Serostatus in Perinatally-Infected Adolescents

    PubMed Central

    Persaud, Deborah; Patel, Kunjal; Karalius, Brad; Rainwater-Lovett, Kaitlin; Ziemniak, Carrie; Ellis, Angela; Chen, Ya Hui; Richman, Douglas; Siberry, George K.; Van Dyke, Russell B.; Burchett, Sandra; Seage, George R.; Luzuriaga, Katherine

    2014-01-01

    Importance Combination antiretroviral therapy (cART) initiated within several weeks of HIV infection in adults limits proviral reservoirs that preclude HIV cure. Biomarkers of restricted proviral reservoirs may aid in the monitoring of HIV remission or cure. Objectives To quantify peripheral blood proviral reservoir size in perinatally HIV-infected adolescents and to identify correlates of limited proviral reservoirs. Design, Setting, and Participants A cross-sectional study including 144 perinatally HIV-infected (PHIV+) youth (median age: 14.3 years), enrolled in the US-based Pediatric HIV/AIDS Cohort Study, on durable (median: 10.2 years) cART, stratified by age at virologic control. Main Outcome and Measures The primary endpoint was peripheral blood mononuclear cell (PBMC) proviral load following virologic control at different ages. Correlations between proviral load and markers of active HIV production (HIV-specific antibodies, 2-long terminal repeat (2-LTR) circles), and markers of immune activation and inflammation were also assessed. Results Proviral reservoir size was markedly reduced in the PHIV+ youth who achieved virologic control by age 1 year (4.2 [interquartile range, 2.6-8 6] copies per 1 million PBMCs) compared to those who achieved virologic control between 1-5 years of age (19.4 [interquartile range, 5.5-99.8] copies per 1 million PBMCs) or after age 5 years (−(70.7 [interquartile range, 23.2-209.4] copies per 1 million PBMCs; P < .00l). A proviral burden <10 copies/million PBMCs was measured in 11 (79%), 20 (40%), and 13 (18%) participants with virologic control at ages <1 year, 1-5 years, and >5 years, respectively (p<0.001). Lower proviral load was associated with undetectable 2-LTR circles (p<0.001) and HIV negative or indeterminate serostatus (p<0.001), but not with concentrations of soluble immune activation markers CD14 and CD163. Conclusions and Relevance Early effective cART along with prolonged virologic suppression after perinatal HIV

  14. Effect of a dedicated oral care program on periodontal status of medically compromised patients at the Toronto Rehabilitation Institute Dental Clinic.

    PubMed

    Schlosser, Robert; Hebbes, Trudy

    2016-01-01

    Medically compromised patients attending the dental clinic at the Toronto Rehabilitation Institute have considerable gingival inflammation and breath odor. The objective of this study was to evaluate the effect of toothbrushing on the periodontal status of these patients and to determine if there were any additional benefit in combining brushing with an application of an antibiotic rinse. During the first 7 days of the study, the teeth of 11 participants were brushed twice a day by a dental hygienist using a soft-bristle suction toothbrush without toothpaste. Soft interproximal brushes were used to clean interproximal surfaces from the facial aspect. During the second week, facial and interproximal cleaning were repeated in the same patients, but the toothbrush and interproximal brush were dipped in 10-mL of a solution consisting of water and 40 mg/mL of metronidazole with nystatin. Each patient underwent an oral examination and biofilm sampling at baseline, after brushing without toothpaste (week 1), and after brushing with antibiotic solution (week 2). After week 1, tissues improved substantially, and there was a notable change in the biofilm on the teeth. The addition of an antibiotic solution increased healing and resulted in a further decrease in oral biofilm. Medically compromised patients would benefit considerably from a treatment regimen of antibiotic solution to decrease oral infection followed by a daily oral care program of brushing and interdental cleaning to maintain healthy oral tissues. PMID:27367641

  15. A model international partnership for community-based research on vaccine-preventable diseases: the Kamphaeng Phet-AFRIMS Virology Research Unit (KAVRU).

    PubMed

    Gibbons, Robert V; Nisalak, Ananda; Yoon, In-Kyu; Tannitisupawong, Darunee; Rungsimunpaiboon, Kamchai; Vaughn, David W; Endy, Timothy P; Innis, Bruce L; Burke, Donald S; Mammen, Mammen P; Scott, Robert McNair; Thomas, Stephen J; Hoke, Charles H

    2013-09-23

    This paper describes an international collaboration to carry out studies that contributed to the understanding of pathogenesis, diagnosis, treatment, and prevention of several diseases of public health importance for Thailand and the United States. In Kamphaeng Phet Province, Thailand, febrile syndromes, including encephalitis, hepatitis, hemorrhagic fever, and influenza-like illnesses, occurred commonly and were clinically diagnosed, but the etiology was rarely confirmed. Since 1982, the Kamphaeng Phet Provincial Hospital, the Thai Ministry of Public Health, and the US Army Component of the Armed Forces Research Institute of Medical Sciences, along with vaccine manufacturers and universities, have collaborated on studies that evaluated and capitalized on improved diagnostic capabilities for infections caused by Japanese encephalitis, hepatitis A, dengue, and influenza viruses. The collaboration clarified clinical and epidemiological features of these infections and, in large clinical trials, demonstrated that vaccines against Japanese encephalitis and hepatitis A viruses were over 90% efficacious, supporting licensure of both vaccines. With the introduction of Japanese encephalitis vaccines in Thailand's Expanded Program on Immunization, reported encephalitis rates dropped substantially. Similarly, in the US, particularly in the military populations, rates of hepatitis A disease have dropped with the use of hepatitis A vaccine. Studies of the pathogenesis of dengue infections have increased understanding of the role of cellular immunity in responding to these infections, and epidemiological studies have prepared the province for studies of dengue vaccines. Approximately 80 publications resulted from this collaboration. Studies conducted in Kamphaeng Phet provided experience that contributed to clinical trials of hepatitis E and HIV vaccines, conducted elsewhere. To provide a base for continuing studies, The Kamphaeng Phet-AFRIMS Virology Research Unit (KAVRU) was

  16. LFA-1 Engagement Triggers T Cell Polarization at the HIV-1 Virological Synapse

    PubMed Central

    Starling, Shimona

    2016-01-01

    ABSTRACT HIV-1 efficiently disseminates by cell-cell spread at intercellular contacts called virological synapses (VS), where the virus preferentially assembles and buds. Cell-cell contact triggers active polarization of organelles and viral proteins within infected cells to the contact site to support efficient VS formation and HIV-1 spread; critically, however, which cell surface protein triggers contact-induced polarization at the VS remains unclear. Additionally, the mechanism by which the HIV-1 envelope glycoprotein (Env) is recruited to the VS remains ill defined. Here, we use a reductionist bead-coupled antibody assay as a model of the VS and show that cross-linking the integrin LFA-1 alone is sufficient to induce active T cell polarization and recruitment of the microtubule organizing center (MTOC) in HIV-1-infected cells. Mutant cell lines coupled with inhibitors demonstrated that LFA-1-induced polarization was dependent on the T cell kinase ZAP70. Notably, immunofluorescent staining of viral proteins revealed an accumulation of surface Env at sites of LFA-1 engagement, with intracellular Env localized to a Golgi compartment proximal to the polarized MTOC. Furthermore, blocking LFA-1-induced MTOC polarization through ZAP70 inhibition prevented intracellular Env polarization. Taken together, these data reveal that LFA-1 is a key determinant in inducing dynamic T cell remodeling to the VS and suggest a model in which LFA-1 engagement triggers active polarization of the MTOC and the associated Env-containing secretory apparatus to sites of cell-cell contact to support polarized viral assembly and egress for efficient cell-cell spread. IMPORTANCE HIV-1 causes AIDS by spreading within immune cells and depletion of CD4 T lymphocytes. Rapid spread between these cells occurs by highly efficient cell-cell transmission that takes place at virological synapses (VS). VS are characterized by striking T cell remodeling that is spatially associated with polarized virus

  17. Medication possession ratio associated with short-term virologic response in individuals initiating antiretroviral therapy in Namibia.

    PubMed

    Hong, Steven Y; Jerger, Logan; Jonas, Anna; Badi, Alfons; Cohen, Steven; Nachega, Jean B; Parienti, Jean-Jacques; Tang, Alice M; Wanke, Christine; Terrin, Norma; Pereko, Dawn; Blom, Abraham; Trotter, Andrew B; Jordan, Michael R

    2013-01-01

    The visual-analogue scale (VAS), Likert item (rating scale), pills identification test (PIT), and medication possession ratio (MPR) provide estimates of antiretroviral therapy (ART) adherence which correlate with HIV viral suppression. These simple adherence measures are inexpensive and easy to administer; however, require validation and adjustment prior to implementation. The objective of this study was to define the optimal adherence assessment measure in Namibia to identify patients at risk for sub-optimal adherence and poor virologic response 6 months after ART initiation. We conducted a cross-sectional survey in HIV-infected adults receiving ART for 6-12 months prior to the adherence assessment. Adherence measures included 30-day VAS, 30-day Likert item, self-reported treatment interruptions, PIT, and MPR. Association of adherence measures with 6-month HIV-1 RNA level was assessed using two thresholds (1000 copies/mL and 5000 copies/mL). Adherence was assessed in 236 patients, mean age 37.3 years, 54% female. Mean adherence was 98.1% by 30-day VAS, 84.7% by 30-day Likert item, 97.0% by self-reported treatment interruptions, 90.6% by PIT, and 98.8% by MPR. Agreement between adherence measures was poor using kappa statistic. 76% had HIV-1 RNA <1000 copies/ml, and 88% had HIV-1 RNA <5000 copies/ml. MPR (continuous) was associated with viral suppression <5000 copies/ml (p = 0.036). MPR <75% was associated with virologic failure at ≥5000 copies/ml with OR 3.89 (1.24, 12.21), p = 0.013. Adherence was high with all measures. Only MPR, was associated with short-term virologic response, suggesting its cross-culturally utility for early identification of patients at high risk for virologic failure.

  18. Some trends of research in the domain of viral neuroinfections approached in the "Stefan S. Nicolau" Institute of Virology.

    PubMed

    Drăgănescu, N

    1985-01-01

    The main directions of research in the field of viral neuroinfections approached during 35 years in the Institute of Virology are briefly outlined. After some considerations on terminology and on the classification of viral encephalitides, mention is made of the studies in the domain of herpes infections, rabies, meningitis, encephalitis and slow virus infections of the central nervous system (subacute sclerosing panencephalitis, multiple sclerosis, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, etc.).

  19. Investigations in the field of recombinant DNA technology performed in the "Stefan S. Nicolau" Institute of Virology.

    PubMed

    Popa, L M; Repanovici, R; Iliescu, R

    1984-01-01

    A brief review is provided of the investigations in the field of recombinant DNA technology started in 1979 in the Central Laboratory for Nucleic Acids within the "Stefan S. Nicolau" Institute of Virology. The research efforts have been focused on the following main objectives: optimization of vector extraction, isolation and purification of restriction enzymes and of DNA ligase T4, transformation and transfection experiments, construction of recombinant DNA. PMID:6097023

  20. Low Pretreatment Acoustic Radiation Force Impulse Imaging (ARFI) Values Predict Sustained Virological Response in Antiviral Hepatitis C Virus (HCV) Therapy

    PubMed Central

    Zopf, Steffen; Rösch, Lara; Konturek, Peter C.; Goertz, Ruediger S.; Neurath, Markus F.; Strobel, Deike

    2016-01-01

    Background Non-invasive procedures such as acoustic radiation force impulse imaging (ARFI) shear-wave elastography are currently used for the assessment of liver fibrosis. In the course of chronic hepatitis C, significant liver fibrosis or cirrhosis develops in approximately 25% of patients, which is a negative predictor of antiviral treatment response. Cirrhosis can be prevented by successful virus elimination. In this prospective study, a pretreatment ARFI cutoff value of 1.5 m/s was evaluated in relation to sustained virological response to anti-HCV therapy. Material/Methods In 23 patients with chronic hepatitis C, liver stiffness was examined with ARFI at defined times before and under antiviral triple therapy (peginterferon, ribavirin in combination with a first-generation protease inhibitor, and telaprevir or boceprevir). Patients were stratified into 2 groups based on pretreatment ARFI values (<1.5 m/s and ≥1.5 m/s) for the assessment of virological response. Results The liver stiffness at baseline for all patients was 1.57±0.79 m/s (ARFI median ± standard deviation; margin: 0.81 m/s to 3.45 m/s). At week 4 of triple therapy, patients with low pretreatment ARFI values had higher rates of HCV-RNA negativity (69% vs. 43%), reflecting an early rapid virological response (eRVR). Sustained virological response (SVR) was found in 75% (12/16) of patients with an ARFI value <1.5 m/s and only 57% (4/7) of patients with ARFI value ≥1.5 m/s. Conclusions Patients with chronic hepatitis C and pretreatment ARFI <1.5 m/s showed earlier virus elimination and better response to treatment. PMID:27690214

  1. Sex differences in atazanavir pharmacokinetics and associations with time to clinical events: AIDS Clinical Trials Group Study A5202

    PubMed Central

    Venuto, Charles S.; Mollan, Katie; Ma, Qing; Daar, Eric S.; Sax, Paul E.; Fischl, Margaret; Collier, Ann C.; Smith, Kimberly Y.; Tierney, Camlin; Morse, Gene D.

    2014-01-01

    Objectives It is uncertain whether HIV-1 antiretroviral exposure and clinical response varies between males and females or different race/ethnic groups. We describe ritonavir-enhanced atazanavir pharmacokinetics in relation to virological failure, safety and tolerability in treatment-naive individuals to investigate potential differences. Methods Plasma samples were collected from participants in AIDS Clinical Trials Group Study A5202 for measurement of antiretroviral concentrations. Individual estimates of apparent oral clearance of atazanavir (L/h) were calculated from a one-compartment model and divided into tertiles as slow (<7), middle (7 to <9; reference group) and fast (≥9). Associations between atazanavir clearance and clinical outcomes were estimated with a hazard ratio (HR) from Cox proportional hazards models. Interactions between atazanavir clearance and sex, race/ethnicity and NRTIs were investigated for each of the outcomes. Results Among 786 participants, average atazanavir clearance was slower in females (n = 131) than males (n = 655). Atazanavir clearance was associated with time to virological failure (P = 0.053) and this relationship differed significantly by sex (P = 0.003). Females in the fast atazanavir clearance group had shorter time to virological failure (HR 3.49; 95% CI 1.24–9.84) compared with the middle (reference) atazanavir clearance group. Among males, the slow atazanavir clearance group had a higher risk of virological failure (HR 2.10; 95% CI 1.16–3.77). Conclusions Atazanavir clearance differed by sex. Females with fast clearance and males with slow clearance had increased risk of virological failure. PMID:25159623

  2. VIROLOGICAL AND SEROLOGICAL DIAGNOSIS OF RABIES IN BATS FROM AN URBAN AREA IN THE BRAZILIAN AMAZON.

    PubMed

    Oliveira, Rubens Souza de; Costa, Lanna Jamile Corrêa da; Andrade, Fernanda Atanaena Gonçalves de; Uieda, Wilson; Martorelli, Luzia Fátima Alves; Kataoka, Ana Paula de Arruda Geraldes; Rosa, Elizabeth Salbé Travassos da; Vasconcelos, Pedro Fernando da Costa; Pereira, Armando de Souza; Carmo, Antônio Ismael Barros do; Fernandes, Marcus Emanuel Barroncas

    2015-12-01

    The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a priority area for studies on this zoonosis. Given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (RABV) among bat species in Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and dry seasons. Samples of brain tissue and blood were collected for virological and serological survey, respectively. None of the 153 brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus planirostris was the most common species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested positive for infection, the high proportion of seropositive specimens indicates that RABV may be widespread in this urban area. PMID:27049703

  3. In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection

    PubMed Central

    Zhang, Xiaonan; Lu, Wei; Zheng, Ye; Wang, Weixia; Bai, Lu; Chen, Liang; Feng, Yanling; Zhang, Zhanqing

    2016-01-01

    Persistent hepatitis B virus (HBV) infection is established by the formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver. Very little is known about the intrahepatic distribution of HBV cccDNA in infected patients, particularly at the single-cell level. Here, we established a highly sensitive and specific ISH assay for the detection of HBV RNA, DNA, and cccDNA. The specificity of our cccDNA probe set was confirmed by its strict intranuclear signal and by a series of Southern blot analyses. Use of our in situ assay in conjunction with IHC or immunofluorescence uncovered a surprisingly mosaic distribution of viral antigens and nucleic acids. Most strikingly, a mutually exclusive pattern was found between HBV surface antigen–positive (HBsA-positive) and HBV DNA– and cccDNA-positive cells. A longitudinal observation of patients over a 1-year period of adeforvir therapy confirmed the persistence of a nuclear reservoir of viral DNA, although cytoplasmic DNA was effectively depleted in these individuals. In conclusion, our method for detecting viral nucleic acids, including cccDNA, with single-cell resolution provides a means for monitoring intrahepatic virological events in chronic HBV infection. More important, our observations unravel the complexity of the HBV life cycle in vivo. PMID:26901811

  4. Multiple proviral integration events after virological synapse-mediated HIV-1 spread

    SciTech Connect

    Russell, Rebecca A.; Martin, Nicola; Mitar, Ivonne; Jones, Emma; Sattentau, Quentin J.

    2013-08-15

    HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes.

  5. VIROLOGICAL AND SEROLOGICAL DIAGNOSIS OF RABIES IN BATS FROM AN URBAN AREA IN THE BRAZILIAN AMAZON

    PubMed Central

    de OLIVEIRA, Rubens Souza; da COSTA, Lanna Jamile Corrêa; de ANDRADE, Fernanda Atanaena Gonçalves; UIEDA, Wilson; MARTORELLI, Luzia Fátima Alves; KATAOKA, Ana Paula de Arruda Geraldes; da ROSA, Elizabeth Salbé Travassos; VASCONCELOS, Pedro Fernando da Costa; PEREIRA, Armando de Souza; do CARMO, Antônio Ismael Barros; FERNANDES, Marcus Emanuel Barroncas

    2015-01-01

    The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a priority area for studies on this zoonosis. Given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (RABV) among bat species in Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and dry seasons. Samples of brain tissue and blood were collected for virological and serological survey, respectively. None of the 153 brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus planirostris was the most common species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested positive for infection, the high proportion of seropositive specimens indicates that RABV may be widespread in this urban area. PMID:27049703

  6. VIPERdb2: an enhanced and web API enabled relational database for structural virology

    PubMed Central

    Carrillo-Tripp, Mauricio; Shepherd, Craig M.; Borelli, Ian A.; Venkataraman, Sangita; Lander, Gabriel; Natarajan, Padmaja; Johnson, John E.; Brooks, Charles L.; Reddy, Vijay S.

    2009-01-01

    VIPERdb (http://viperdb.scripps.edu) is a relational database and a web portal for icosahedral virus capsid structures. Our aim is to provide a comprehensive resource specific to the needs of the virology community, with an emphasis on the description and comparison of derived data from structural and computational analyses of the virus capsids. In the current release, VIPERdb2, we implemented a useful and novel method to represent capsid protein residues in the icosahedral asymmetric unit (IAU) using azimuthal polar orthographic projections, otherwise known as Φ–Ψ (Phi–Psi) diagrams. In conjunction with a new Application Programming Interface (API), these diagrams can be used as a dynamic interface to the database to map residues (categorized as surface, interface and core residues) and identify family wide conserved residues including hotspots at the interfaces. Additionally, we enhanced the interactivity with the database by interfacing with web-based tools. In particular, the applications Jmol and STRAP were implemented to visualize and interact with the virus molecular structures and provide sequence–structure alignment capabilities. Together with extended curation practices that maintain data uniformity, a relational database implementation based on a schema for macromolecular structures and the APIs provided will greatly enhance the ability to do structural bioinformatics analysis of virus capsids. PMID:18981051

  7. VIROLOGICAL AND SEROLOGICAL DIAGNOSIS OF RABIES IN BATS FROM AN URBAN AREA IN THE BRAZILIAN AMAZON.

    PubMed

    Oliveira, Rubens Souza de; Costa, Lanna Jamile Corrêa da; Andrade, Fernanda Atanaena Gonçalves de; Uieda, Wilson; Martorelli, Luzia Fátima Alves; Kataoka, Ana Paula de Arruda Geraldes; Rosa, Elizabeth Salbé Travassos da; Vasconcelos, Pedro Fernando da Costa; Pereira, Armando de Souza; Carmo, Antônio Ismael Barros do; Fernandes, Marcus Emanuel Barroncas

    2015-12-01

    The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a priority area for studies on this zoonosis. Given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (RABV) among bat species in Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and dry seasons. Samples of brain tissue and blood were collected for virological and serological survey, respectively. None of the 153 brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus planirostris was the most common species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested positive for infection, the high proportion of seropositive specimens indicates that RABV may be widespread in this urban area.

  8. Virology and epidemiology analyses of global adenovirus-associated conjunctivitis outbreaks, 1953-2013.

    PubMed

    Zhang, L; Zhao, N; Sha, J; Wang, C; Jin, X; Amer, S; Liu, S

    2016-06-01

    This study aimed to compare the virology and epidemiology of epidemic keratoconjunctivitis (EKC), pharyngoconjunctival fever (PCF) and acute haemorrhagic conjunctivitis (AHC) outbreaks worldwide caused by the human adenovirus (HAdV) from 1953 to 2013. Eighty-three hexon sequences from 76 conjunctivitis outbreaks were analysed and subtyped using Mega 5.05, Clustal X and SimPlot software. Epidemiology was performed for the area, age and seasonal distribution. A phylogenetic analysis indicated that all the isolates could be divided into three subgenetic lineages, without a common ancestor. The major causes of the outbreaks were Ad8, Ad7 and Ad2 co-infection with enterovirus 70 (EV70) in EKC, PCF and AHC, respectively. The epidemiological findings suggested that EKC and AHC were circulating predominantly in Asia during the early winter and spring, whereas PCF was circulating mainly in China, Australia and the United States during the summer. This study suggests that EKC, AHC and PCF outbreaks have different circulating patterns throughout the world and are caused by different adenovirus serotypes. A global surveillance system should be established to monitor conjunctivitis outbreaks in the future.

  9. In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection.

    PubMed

    Zhang, Xiaonan; Lu, Wei; Zheng, Ye; Wang, Weixia; Bai, Lu; Chen, Liang; Feng, Yanling; Zhang, Zhanqing; Yuan, Zhenghong

    2016-03-01

    Persistent hepatitis B virus (HBV) infection is established by the formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver. Very little is known about the intrahepatic distribution of HBV cccDNA in infected patients, particularly at the single-cell level. Here, we established a highly sensitive and specific ISH assay for the detection of HBV RNA, DNA, and cccDNA. The specificity of our cccDNA probe set was confirmed by its strict intranuclear signal and by a series of Southern blot analyses. Use of our in situ assay in conjunction with IHC or immunofluorescence uncovered a surprisingly mosaic distribution of viral antigens and nucleic acids. Most strikingly, a mutually exclusive pattern was found between HBV surface antigen-positive (HBsA-positive) and HBV DNA- and cccDNA-positive cells. A longitudinal observation of patients over a 1-year period of adeforvir therapy confirmed the persistence of a nuclear reservoir of viral DNA, although cytoplasmic DNA was effectively depleted in these individuals. In conclusion, our method for detecting viral nucleic acids, including cccDNA, with single-cell resolution provides a means for monitoring intrahepatic virological events in chronic HBV infection. More important, our observations unravel the complexity of the HBV life cycle in vivo. PMID:26901811

  10. Nurse Care Coordination and Technology Effects on Health Status of Frail Elderly via Enhanced Self-management of Medication: Randomized Clinical Trial to Test Efficacy

    PubMed Central

    Marek, Karen Dorman; Stetzer, Frank; Ryan, Polly A.; Bub, Linda Denison; Adams, Scott J.; Schlidt, Andrea; Lancaster, Rachelle; O’Brien, Anne-Marie

    2013-01-01

    Background Self-management of complex medication regimens for chronic illness is challenging for many older adults. Objectives The purpose of this study was to evaluate health status outcomes of frail older adults receiving a home-based support program that emphasized self-management of medications using both care coordination and technology. Design Randomized controlled trial with three arms and longitudinal outcome measurement. Setting Older adults having difficulty self-managing medications (N = 414) were recruited at discharge from three Medicare-certified home health care agencies in a Midwestern urban area. Methods All participants received baseline pharmacy screens. The control group received no further intervention. A team of advanced practice nurses and registered nurses coordinated care for 12 months to two intervention groups who also received either an MD.2 medication-dispensing machine or a medplanner. Health status outcomes (Geriatric Depression Scale, Mini-Mental Status Examination, Physical Performance Test, and the SF-36 Physical Component Summary and Mental Component Summary) were measured at baseline, 3, 6, 9, and 12 months. Results After covariate and baseline health status adjustment, time by group interactions for the MD.2 and medplanner groups on health status outcomes were not significant; time by group interactions were significant for medplanner and control group comparisons. Discussion Participants with care coordination had significantly better health status outcomes over time than those in the control group, but addition of the MD.2 machine to nurse care coordination did not result in better health status outcomes. PMID:23817284

  11. Virologic and serologic investigations of West Nile virus circulation in Belarus.

    PubMed

    Samoilova, T I; Votiakov, V I; Titov, L P

    2003-06-01

    In 1985-1994 virologic and serologic investigations were performed for the purposes of West Nile (WN) virus circulation establishment on the territory of Belarus. Blood-sucking mosquitoes, midges, wild small mammals, birds as well as blood and cerebrospinal samples from patients with nondifferentiated fevers and from healthy individuals were under studies. Four virus strains were isolated in Belarus for the first time, namely: 1--from birds (48-WN Tremlya); 2--from Aedes mosquitoes (319 and 2438); 1--from a febrile patient (Win). Their antigenic and biological properties were examined in cell cultures and laboratory animals. The isolates turned to be identical with each other and closely related to reference Egypt strain Eg 101, that is a topotype for the African virus group. One more WN virus strain (8891) was isolated from Anopheles mosquitoes in 1999. Specific antibodies to the virus in human blood sera were identified by immunological and serologic assays in 1.7% of Belarusian population. In Gomel and Brest Regions the percentage of seropositive individuals reached 5.8 and 15.4, respectively. WN virus antibodies prevailed in 0.6-5.8% of cattle, in 2.9-6.8% of wild small mammals and in 6.5-16.7% of birds. Thus, the conclusion was made on the existence of favourable conditions for the virus spread throughout the whole country and in the south in particular. Blood-sucking mosquitoes and birds are principle vectors in WN virus circulation in Belarus. 16 serologically confirmed cases of WN encephalitis were revealed in patients with fever of obscure etiology. In the view of the given data, reports on the reemergence of the pathogen in different countries and the tendency in global warming WN virus monitoring should become a subject of concern for Belarusian public medical care services.

  12. Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study

    PubMed Central

    Caini, Saverio; Huang, Q Sue; Ciblak, Meral A; Kusznierz, Gabriela; Owen, Rhonda; Wangchuk, Sonam; Henriques, Cláudio M P; Njouom, Richard; Fasce, Rodrigo A; Yu, Hongjie; Feng, Luzhao; Zambon, Maria; Clara, Alexey W; Kosasih, Herman; Puzelli, Simona; Kadjo, Herve A; Emukule, Gideon; Heraud, Jean-Michel; Ang, Li Wei; Venter, Marietjie; Mironenko, Alla; Brammer, Lynnette; Mai, Le Thi Quynh; Schellevis, François; Plotkin, Stanley; Paget, John

    2015-01-01

    Introduction Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000. Methods Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type. Results The database included 935 673 influenza cases (2000–2013). Overall median proportion of influenza B was 22·6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in ≈25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5–17 years) than patients infected with influenza A. Conclusion Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza. PMID:26256290

  13. Virologic and serologic surveillance for dengue fever in Jeddah, Saudi Arabia, 1994-1999.

    PubMed

    Fakeeh, M; Zaki, A M

    2001-12-01

    Dengue fever infection was first documented in Jeddah, Saudi Arabia, by virus isolation of dengue type 2 virus in 1994 at the virology laboratory of Dr. Soliman Fakeeh Hospital. Dengue virus surveillance was established after that time. Blood samples were collected from 985 patients (710 male patients and 275 female patients) with suspected cases of dengue from February 1994 to December 1999. Dengue virus isolates were obtained in 207 patients (21%; 162 male patients and 45 female patients). Dengue type 2 was the predominant serotype (138 of 207 isolates, 66.7%), followed by dengue type 1 with (56 of 207 isolates, 27%) and dengue type 3 (13 of 207 isolates, 6.3%). The largest number of isolates (186 of 207 isolates, 90%) was in 1994, a year during which there was a dengue epidemic. In the next 5 years, 1995-1999, only 21 isolates (10%) were isolated. Immunoglobulin M capture enzyme-linked immunosorbent assay was positive in 160 acute samples; 52 of them were from virus culture-positive cases and 108 (11%) from culture-negative cases. The total number of cases diagnosed by both methods was 315 (32%). The prevalence of dengue immunoglobulin G antibodies, as assessed on the basis of immunofluorescent assay, hemagglutination inhibition titers > or = 1/20, or both, in the acute samples was 314 (32%) of 985, indicating past Flavivirus infection. Two patients died, one man with dengue hemorrhagic fever and one woman with dengue shock syndrome. Both fatal dengue cases were due to infection with type 2 virus. All other cases were simple dengue fever. To our knowledge, this is the first report confirming the circulation of 3 dengue serotypes in Jeddah.

  14. Prediction of virological response by pretreatment hepatitis B virus reverse transcriptase quasispecies heterogeneity: the advantage of using next-generation sequencing.

    PubMed

    Han, Y; Gong, L; Sheng, J; Liu, F; Li, X-H; Chen, L; Yu, D-M; Gong, Q-M; Hao, P; Zhang, X-X

    2015-08-01

    Prediction of antiviral efficacy prior to treatment remains largely unavailable. We have previously demonstrated the clinical value of on-treatment hepatitis B virus (HBV) reverse transcriptase (RT) quasispecies (QS) evolution patterns. In this study, we aimed to elucidate the relevance for prediction of pretreatment HBV RT QS characteristics by comparing the performance of next-generation sequencing (NGS) and clone-based Sanger sequencing (CBS). Thirty-six lamivudine-treated patients were retrospectively studied, including 18 responders and 18 non-responders. CBS and NGS data of pretreatment serum HBV were used to generate RT QS genetic complexity and diversity scores, according to our previous studies. The ability of both methods to predict responsiveness was evaluated with receiver operating characteristic (ROC) curves. A cut-off value was generated on the basis of prediction ability. Responders had significantly higher pretreatment RT QS genetic complexity and diversity (in the first two parts, which overlapped with the S gene, at both the nucleotide and amino acid levels) than non-responders by NGS-based testing. NGS-based algorithms predicted response better than CBS in the ROC curve analysis. The mean distance of the second contig had the highest area under the curve (AUC) value. When the cut-off value was set to 0.007186, the difference between survival curves was significant (p 0.0090). Pretreatment HBV RT QS heterogeneity in the overlapping region of the RT and S genes could be a predictor of antiviral efficacy. NGS improves the predictions of virological outcomes relative to CBS algorithms. This may have important implications for the clinical management of subjects chronically infected with HBV.

  15. Status epilepticus in adults.

    PubMed

    Betjemann, John P; Lowenstein, Daniel H

    2015-06-01

    Status epilepticus is a common neurological emergency with considerable associated health-care costs, morbidity, and mortality. The definition of status epilepticus as a prolonged seizure or a series of seizures with incomplete return to baseline is under reconsideration in an effort to establish a more practical definition to guide management. Clinical research has focused on early seizure termination in the prehospital setting. The approach of early escalation to anaesthetic agents for refractory generalised convulsive status epilepticus, rather than additional trials of second-line anti-epileptic drugs, to avoid neuronal injury and pharmaco-resistance associated with prolonged seizures is gaining momentum. Status epilepticus is also increasingly identified in the inpatient setting as the use of extended electroencephalography monitoring becomes more commonplace. Substantial further research to enable early identification of status epilepticus and efficacy of anti-epileptic drugs will be important to improve outcomes.

  16. The effect of purslane seeds on glycemic status and lipid profiles of persons with type 2 diabetes: A randomized controlled cross-over clinical trial

    PubMed Central

    Esmaillzadeh, Ahmad; Zakizadeh, Elahe; Faghihimani, Elham; Gohari, Mahmoodreza; Jazayeri, Shima

    2015-01-01

    Background: We are aware of limited data about the effects of purslane on diabetes. Earlier studies have mostly indicated the beneficial effects in animal models. This study aimed to evaluate the effect of purslane seeds on glycemic status and lipid profiles of persons with type 2 diabetes. Materials and Methods: This cross-over randomized controlled clinical trial was conducted on 48 persons with type 2 diabetes. Participants were randomly assigned to receive either 10 g/day purslane seeds with 240 cc low-fat yogurt (intervention group) or only 240 cc low-fat yogurt (as a control group) for 5 weeks. After a 2-week washout period, subjects were moved to the alternate arm for an additional 5 weeks. At baseline and end of each phase of the study, fasting blood samples were collected to quantify plasma glucose levels, as well as serum insulin and lipid profiles. Within-group and between-group changes in anthropometric measures, as well as biochemical indicators, were compared using a paired-samples t-test. Results: Mean age of study participants was 51.4 ± 6.0 year. We found a significant reduction in weight (−0.57 vs. 0.09 kg, P = 0.003) and body mass index (−0.23 vs. 0.02 kg/m2, P = 0.004) following purslane seeds consumption. Despite a slight reduction in fasting plasma glucose levels (−2.10 vs. −2.77 mg/dL, P = 0.90), we failed to find any significant effect on serum insulin levels and homeostatic model of assessment of insulin resistance score. Furthermore, purslane consumption decreased serum triglyceride levels (−25.5 vs. −1.8 mg/dL, P = 0.04) but could not affect serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol levels. We observed a significant reduction in systolic blood pressure (−3.33 vs. 0.5 mmHg, P = 0.01) and a borderline significant decrease in diastolic blood pressure (−3.12 vs. −0.93 mmHg, P = 0.09) after purslane seeds intake. Conclusion: In summary, consumption of purslane

  17. Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future.

    PubMed

    Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

    2016-05-12