Sample records for lymphocytes virologic worsening

  1. Mucosal immunology and virology

    National Research Council Canada - National Science Library

    Tyring, Stephen


    .... A third chapter focuses on the proximal end of the gastrointestinal tract (i.e. the oral cavity). The mucosal immunology and virology of the distal end of the gastrointestinal tract is covered in the chapter on the anogenital mucosa. Mucosa-associated lymphoid tissue (MALT) plays a role in protection against all viral (and other) infections except those that enter the body via a bite (e.g. yellow fever or dengue from a mosquito or rabies from a dog) or an injection or transfusion (e.g. HIV, Hepatitis B). ...

  2. [A cross-sectional study on the effect of virological response after HAART on subsets of T lymphocytes and expression of CD127 in pediatric AIDS patients with different viral loads]. (United States)

    Wu, Li-juan; Wu, Li-xiang; Bai, Shi


    To study the effect of HAART on subsets of T lymphocytes and expression of CD127 on memory and naїve CD4(+) and CD8(+)T cells in pediatric AIDS patients with different viral loads receiving HAART. A cross- sectional study on 194 pediatric AIDS patients receiving HAART was carried out and 52 age matched healthy children were recruited as controls. The percentage of CD4(+), CD8(+), CD8(+)CD45RA(+)CD127(+/-), CD8(+)CD45RO(+)CD127(+/-), CD4(+)CD45RA(+)CD127(+/-) and CD4(+)CD45RO(+)CD127(+/-)T cells was tested using flow cytometry, and HIV-RNA in plasma was detected by quantitative RT-PCR. The percentage of memory (CD45RO(+)) CD4(+)T cells decreased to (45.73 ± 8.85)%, and that of naїve (CD45RA(+)) CD4(+) and memory CD8(+)T increased to (60.44 ± 5.01)% and (54.69 ± 7.71) % respectively in the pediatric AIDS patients vs. controls (P memory CD4(+)CD127(+)T cells was (82.35 ± 2.31)%, which was higher than that of patients with VL ≥ 400 copies/ml, but lower than that of controls (P memory and naїve CD8(+)CD127(+)T cells was lower than that of controls (P AIDS patients is associated with viral load. Effective HAART can increase the percentage of naїve CD4(+)T cells and the life of memory CD4(+)T cells.

  3. Virological Mechanisms in the Coinfection between HIV and HCV

    Directory of Open Access Journals (Sweden)

    Maria Carla Liberto


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

  4. Detecting virological failure in HIVinfected Tanzanian children ...

    African Journals Online (AJOL)

    Background. The performance of clinical and immunological criteria to predict virological failure in HIV-infected children receiving antiretroviral therapy (ART) is not well documented. Objective. To determine the validity of clinical and immunological monitoring in detecting virological failure in children on ART. Methods.

  5. Neutrophil-to-Lymphocyte Ratio as a Predictor of Response to Peginterferon plus Ribavirin Therapy for Chronic Hepatitis C


    Kuo, Ming-Te; Hu, Tsung-Hui; Lu, Sheng-Nan; Hung, Chao Hung; Wang, Jing-Houng; Chen, Chien-Hung; Chiu, Yi-Chun; Lee, Chuan-Mo


    We aimed to determine whether neutrophil-to-lymphocyte ratio (NLR) could be a predictor of antiviral response in chronic hepatitis C patients. A total of 602 consecutive patients (genotype 1, n = 263; genotype 2, n = 297; others/unknown, n = 42) receiving response-guided therapy with peginterferon plus ribavirin were recruited. NLR was related to clinical and virological features and to treatment outcome. Rapid virological response (RVR) and sustained virological response (SVR) were achieved ...

  6. Acute Worsening of Tics on Varenicline. (United States)

    Mittal, Shivam Om; Klassen, Bryan T; Hassan, Anhar; Bower, James H; Coon, Elizabeth A

    The aim of this study was to report worsening of Tourette syndrome (TS) in 2 patients treated with varenicline. Abnormal dopaminergic signaling is likely involved in the pathophysiology of TS. Varenicline is a partial α4β2 nicotinic acetylcholine agonist that enhances dopamine release. Therefore, the use of varenicline may influence tics in patients with TS. We analyzed and described 2 case studies on patients with significant worsening of tics after treatment with varenicline. Patient 1 had motor tics in childhood, which completely resolved by the age of 20 years. At the age of 25 years, he started varenicline and stopped smoking. Within 2 weeks, he developed motor followed by vocal tics that persisted despite stopping varenicline and restarting smoking. The tics were complex, medically refractory, and caused severe disability at work and school (Yale Global Tic Severity Scale score, 86). Patient 2 developed motor and vocal tics in adolescence that persisted into her 20s and caused significant disability in association with psychiatric comorbidities. At the age of 31 years, she started varenicline to quit smoking, which led to a marked increase in tic frequency and severity. Varenicline was discontinued after 3 weeks with improvement to baseline tic severity (Yale Global Tic Severity Scale score, 94). Ultimately, both patients successfully underwent deep brain stimulation to bilateral centromedian/parafascicular complex thalamic nuclei for medically refractory TS. We report 2 patients with motor and/or vocal tics that had severe worsening of tics after varenicline use. This may be due to varenicline-induced increased striatal dopamine in conjunction with nicotine cessation, influencing dopamine receptor sensitivity in TS. Providers should be cautious in prescribing varenicline to patients with TS.

  7. Advanced Maternal Age Worsens Postpartum Vascular Function

    Directory of Open Access Journals (Sweden)

    Jude S. Morton


    Full Text Available The age at which women experience their first pregnancy has increased throughout the decades. Pregnancy has an important influence on maternal short- and long-term cardiovascular outcomes. Pregnancy at an advanced maternal age increases maternal risk of gestational diabetes, preeclampsia, placenta previa and caesarian delivery; complications which predict worsened cardiovascular health in later years. Aging also independently increases the risk of cardiovascular disease; therefore, combined risk in women of advanced maternal age may lead to detrimental cardiovascular outcomes later in life. We hypothesized that pregnancy at an advanced maternal age would lead to postpartum vascular dysfunction. We used a reproductively aged rat model to investigate vascular function in never pregnant (virgin, previously pregnant (postpartum and previously mated but never delivered (nulliparous rats at approximately 13.5 months of age (3 months postpartum or equivalent. Nulliparous rats, in which pregnancy was spontaneously lost, demonstrated significantly reduced aortic relaxation responses (methylcholine [MCh] Emax: 54.2 ± 12.6% vs. virgin and postpartum rats (MCh Emax: 84.8 ± 3.5% and 84.7 ± 3.2% respectively; suggesting pregnancy loss causes a worsened vascular pathology. Oxidized LDL reduced relaxation to MCh in aorta from virgin and postpartum, but not nulliparous rats, with an increased contribution of the LOX-1 receptor in the postpartum group. Further, in mesenteric arteries from postpartum rats, endothelium-derived hyperpolarization (EDH-mediated vasodilation was reduced and a constrictive prostaglandin effect was apparent. In conclusion, aged postpartum rats exhibited vascular dysfunction, while rats which had pregnancy loss demonstrated a distinct vascular pathology. These data demonstrate mechanisms which may lead to worsened outcomes at an advanced maternal age; including early pregnancy loss and later life cardiovascular dysfunction.


    Directory of Open Access Journals (Sweden)

    Ekaterina Vladimirovna Isaeva


    Full Text Available This work is performed as part of the cognitive-discursive paradigm of modern linguistics. The object of the investigation is the concept “computer virus” and its linguistic representation in a computer virology discourse. The research is based on the texts from the Corpus of Contemporary American English.The first stage of the linguistic and conceptual investigation of “computer virus” is based on Metaphor Investigation Process (MIPVU developed by the Metaphor Lab at VU University Amsterdam. The identification procedure includes the following main steps: reading the text/discourse, acquiring a general understanding of its meaning, selecting lexical units from the text/discourse, and establishing their contextual and contemporary meanings. If the contextual meaning contrasts with the basic meaning but can be understood in comparison with it, the lexical unit is marked as metaphorical (Pragglejaz Group 2007.The second stage of the investigation is based on the method of metaphorical modeling, which implies taxonomic categorization, developed by S. Mishlanova (Mishlanova 2002. On the basis of corpus analysis a metaphorical model “computer virus” was constructed.  The model represents a taxonomic structure, which includes the basic taxons “man as a social subject,” “man as a biological creature,” and “animal.” The most representative areas of source domains included, “military operation” (represented by such linguistic metaphors as attack, strike, defeat, “diseases” (crippling, succumb, infected, and “interpersonal relations” (be angry at, enter into, want.At the current stage of computer virology development, metaphor plays a very important role as a universal tool for conceptualization and categorization of new knowledge that relies on the preceding experience of the person participating in the cognitive process. The structure of the concept "computer virus" is a hierarchical system, fixing the unscientific

  9. Finding our roots and celebrating our shoots: Plant virology in Virology, 1955-1964. (United States)

    Scholthof, Karen-Beth G


    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice

    Directory of Open Access Journals (Sweden)

    Jones Jessica E


    Full Text Available Abstract Background Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active and passive cigarette smoke exposure are linked to an increased incidence and severity of respiratory virus infections, but underlying mechanisms are not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation of pro-inflammatory mediators by short term smoke exposure would be protective against a subsequent influenza infection. Methods BALB/c mice were subjected to whole body smoke exposure with 9 cigarettes/day for 4 days. Mice were then infected with influenza A (H3N1, Mem71 strain, and analyzed 3 and 10 days later (d3, d10. These time points are the peak and resolution (respectively of influenza infection. Results Inflammatory cell influx into the bronchoalveolar lavage (BALF, inflammatory mediators, proteases, histopathology, viral titres and T lymphocyte profiles were analyzed. Compared to smoke or influenza alone, mice exposed to smoke and then influenza had more macrophages, neutrophils and total lymphocytes in BALF at d3, more macrophages in BALF at d10, lower net gelatinase activity and increased activity of tissue inhibitor of metalloprotease-1 in BALF at d3, altered profiles of key cytokines and CD4+ and CD8+ T lymphocytes, worse lung pathology and more virus-specific, activated CD8+ T lymphocytes in BALF. Mice smoke exposed before influenza infection had close to 10-fold higher lung virus titres at d3 than influenza alone mice, although all mice had cleared virus by d10, regardless of smoke exposure. Smoke exposure caused temporary weight loss and when smoking ceased after viral infection, smoke and influenza mice regained significantly less weight than smoke alone mice. Conclusion Smoke induced inflammation does not protect against influenza infection. In most respects, smoke exposure worsened the host response to influenza. This animal model may be useful in studying how smoke worsens

  11. Diagnostic virology laboratory within a microbiology setting. (United States)

    Rubin, S J


    The virology section at St. Francis Hospital and Medical Center, Connecticut, is not a separate laboratory division but is a part of the microbiology division and is supervised by the same personnel who supervise bacteriology, mycology, mycobacteriology, and serology. Current volume is over 1,000 cultures yearly with 12 to 24 percent positive. Isolates are confirmed and typed by the Connecticut State Health Department Laboratory. Specimen distribution, percentage positive specimens, and distribution of viral isolates are similar to those reported from microbiology laboratories with separate virology laboratories directed by a full-time doctoral-level virologist. Our seven years' experience demonstrates that a microbiology laboratory without a full-time doctoral-level virologist can provide clinically useful virologic information.

  12. Artificial Intelligence and Virology - quo vadis. (United States)

    Shapshak, Paul; Somboonwit, Charurut; Sinnott, John T


    Artificial Intelligence (AI), robotics, co-robotics (cobots), quantum computers (QC), include surges of scientific endeavor to produce machines (mechanical and software) among numerous types and constructions that are accelerating progress to defeat infectious diseases. There is a plethora of additional applications and uses of these methodologies and technologies for the understanding of biomedicine through bioinformation discovery. Therefore, we briefly outline the use of such techniques in virology.

  13. Diagnostic virology laboratory within a microbiology setting.


    Rubin, S. J.


    The virology section at St. Francis Hospital and Medical Center, Connecticut, is not a separate laboratory division but is a part of the microbiology division and is supervised by the same personnel who supervise bacteriology, mycology, mycobacteriology, and serology. Current volume is over 1,000 cultures yearly with 12 to 24 percent positive. Isolates are confirmed and typed by the Connecticut State Health Department Laboratory. Specimen distribution, percentage positive specimens, and distr...

  14. Artificial Intelligence and Virology - quo vadis (United States)

    Shapshak, Paul; Somboonwit, Charurut; Sinnott, John T.


    Artificial Intelligence (AI), robotics, co-robotics (cobots), quantum computers (QC), include surges of scientific endeavor to produce machines (mechanical and software) among numerous types and constructions that are accelerating progress to defeat infectious diseases. There is a plethora of additional applications and uses of these methodologies and technologies for the understanding of biomedicine through bioinformation discovery. Therefore, we briefly outline the use of such techniques in virology. PMID:29379259

  15. Lymphocyte activation receptors:new structural paradigms in group V of C-type animal lectins

    Czech Academy of Sciences Publication Activity Database

    Pavlíček, J.; Kavan, Daniel; Pompach, Petr; Novák, Petr; Lukšan, Ondřej; Bezouška, Karel


    Roč. 32, č. 6 (2004), s. 1124-1126 ISSN 0300-5127 R&D Projects: GA AV ČR IAA5020403 Institutional research plan: CEZ:AV0Z5020903 Keywords : lectin-type receptor * ligand identification * lymphocyte Subject RIV: EE - Microbiology, Virology Impact factor: 2.267, year: 2004

  16. Predictors of disability worsening in clinically isolated syndrome (United States)

    Jokubaitis, Vilija G; Spelman, Tim; Kalincik, Tomas; Izquierdo, Guillermo; Grand'Maison, François; Duquette, Pierre; Girard, Marc; Lugaresi, Alessandra; Grammond, Pierre; Hupperts, Raymond; Cabrera-Gomez, José; Oreja-Guevara, Celia; Boz, Cavit; Giuliani, Giorgio; Fernández-Bolaños, Ricardo; Iuliano, Gerardo; Lechner-Scott, Jeannette; Verheul, Freek; van Pesch, Vincent; Petkovska-Boskova, Tatjana; Fiol, Marcela; Moore, Fraser; Cristiano, Edgardo; Alroughani, Raed; Bergamaschi, Roberto; Barnett, Michael; Slee, Mark; Vella, Norbert; Herbert, Joseph; Shaw, Cameron; Saladino, Maria Laura; Amato, Maria Pia; Liew, Danny; Paolicelli, Damiano; Butzkueven, Helmut; Trojano, Maria


    Objective To assess demographic, clinical, magnetic resonance imaging, and treatment exposure predictors of time to 3 or 12-month confirmed disability worsening in clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods We utilized the MSBase Incident Study (MSBasis), a prospective cohort study of outcome after CIS. Predictors of time to first 3 and 12-month confirmed expanded disability status scale worsening were analyzed using Cox proportional hazards regression. Results About 1989 patients were analyzed, the largest seen-from-onset cohort reported to-date. A total of 391 patients had a first 3-month confirmed disability worsening event, of which 307 were sustained for 12 months. Older age at CIS onset (adjusted hazard ratio: aHR 1.17, 95% 1.06, 1.30), pyramidal (aHR 1.45, 95% CI 1.13, 1.89) and ambulation (HR 1.60, 95% CI 1.09, 2.34) system dysfunction, annualized relapse rate (aHR 1.20, 95% CI 1.18, 1.22), and lower proportion of observation time on treatment were associated with 3-month confirmed worsening. Predictors of time to 12-month sustained worsening included pyramidal system dysfunction (Hazard ratio: aHR 1.38, 95% CI 1.05, 1.83), and older age at CIS onset (aHR 1.17, 95% CI 1.04, 1.31). Greater proportion of follow-up time exposed to treatment was associated with greater reductions in the rate of worsening. Interpretation This study provides class IV evidence for a strong protective effect of disease-modifying treatment to reduce disability worsening events in patients with CIS and early MS, and confirms age and pyramidal dysfunction at onset as risk factors. PMID:26000321

  17. Virological and Immunological Aspects of AIDS Pathogenesis

    Directory of Open Access Journals (Sweden)

    Brian Conway


    Full Text Available The most common and serious problem associated with long term antiretroviral therapy is waning efficacy over time. To date. a number of studies has suggested an association between drug resistance and clinical deterioration. However. a precise causal relationship has yet to be demonstrated. In a large American clinical trial. resistance to zidovudine (ZDV was predictive of subsequent disease progression if this therapy was continued. Surprisingly. this was also predictive of deterioration if therapy was changed to didanosine (ddl. This suggests that other factors (perhaps virological and immunological which may be present in addition to resistance. were as important (if not more so in predicting clinical outcomes. It is likely that viral load. resistance. viral phenotype and alterations in immune function interact in this regard. Proper· studies may allow us to determine a “threshold” for a composite virological and immunological parameter beyond which disease progression will occur. As more antiretroviral agents become available. we will be in a position to intervene to “improve” laboratory markers and monitor them prospectively. potentially to maintain clinical latency for an indefinite period of time. In the authors' laboratories, a quantitative polymerase chain reaction assay for the evaluation of circulating proviral load has been developed. In an initial study of 70 patients. proviral load/ 106 CD4 cells was clearly associated with the severity of immune disease. with up to 9.6% of cells being infected in subjects with CD4 cell counts below 200/µL. However. large variability in proviral load among individuals with comparable or dissimilar CD4 cell counts precludes the use of this measurement as an individual marker of the severity of immune disease. More recent work evaluated the combined use of proviral load (expressed as a dichotomous variable based on values above or below one copy/a03 CD4 cells and resistance in a prospective

  18. Synthetic virology: engineering viruses for gene delivery. (United States)

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


    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. © 2014 Wiley Periodicals, Inc.

  19. Paediatric Virology in the Hippocratic Corpus (United States)

    Mammas, Ioannis N.; Spandidos, Demetrios A.


    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. Odors as triggering and worsening factors for migraine in men

    Directory of Open Access Journals (Sweden)

    A M Lima


    Full Text Available OBJECTIVE: To assess the role of odors in triggering or worsening migraine in men. METHOD: Ninety-eight male migraineurs from the general population were assessed individually through questionnaires. Environmental factors relating to their migraine were reported, with special focus on the role of odors. RESULTS: Odors were the second most frequent triggering factor for migraine attacks (48%, behind stressful situations (59%. Likewise, odors were the second most frequent worsening factor (73%, just behind excessive light (74%. Thirty-three individuals (33.4% stated that odors were both triggering and worsening factors for their migraine attacks. Perfume, cigarette smoke and cleaning products were the most frequent migraine-related odors reported by these male migraineurs. CONCLUSION: This was the first study to assess the role of odors in migraine exclusively in men. There was a high degree of odor-related migraine among these men, thus suggesting that patient education could alert such individuals to gender-related factors, since different triggering and worsening factors have been reported by males and females.

  1. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy (United States)

    Villeneuve, Nathalie; Pinton, Florence; Bahi-Buisson, Nadia; Dulac, Olivier; Chiron, Catherine; Nabbout, Rima


    Aim: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method: From the 70 patients who received the ketogenic diet during a 3-year period at…

  2. Short Report: Worsening and unmasking of tuberculosis in HIV-1 ...

    African Journals Online (AJOL)

    Objectives: To determine the proportion of patients developing active tuberculosis (TB) versus that of patients who experience worsening of TB, after initiating highly active anti retroviral therapy (HAART). Methods: Charts of HAART naïve patients with or without clinically active TB who consecutively commenced HAART at ...

  3. Radiation effects on lymphocytes

    International Nuclear Information System (INIS)

    Roser, B.


    This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

  4. Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia.

    LENUS (Irish Health Repository)

    Houlihan, Diarmaid D


    X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

  5. Modifying Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients. (United States)

    Collins, Sean E; Grant, Philip M; Shafer, Robert W


    HIV-1-infected patients with suppressed plasma viral loads often require changes to their antiretroviral (ARV) therapy to manage drug toxicity and intolerance, to improve adherence, and to avoid drug interactions. In patients who have never experienced virologic failure while receiving ARV therapy and who have no evidence of drug resistance, switching to any of the acceptable US Department of Health and Human Services first-line therapies is expected to maintain virologic suppression. However, in virologically suppressed patients with a history of virologic failure or drug resistance, it can be more challenging to change therapy while still maintaining virologic suppression. In these patients, it may be difficult to know whether the discontinuation of one of the ARVs in a suppressive regimen constitutes the removal of a key regimen component that will not be adequately supplanted by one or more substituted ARVs. In this article, we review many of the clinical scenarios requiring ARV therapy modification in patients with stable virologic suppression and outline the strategies for modifying therapy while maintaining long-term virologic suppression.

  6. [Herpetic keratitis: clinical-virological correlation]. (United States)

    Martínez, M J; Vogel, M; Stoppel, J; Charlin, R; Squella, O; Srur, M; Traipe, L; Verdaguer, J; Suárez, M


    Herpetic keratitis is the main infectious cause of corneal opacity. The existence of effective antiviral agents underscores the need of an early diagnosis. To correlate clinical features of herpetic keratitis with virological studies. Forty one patients with a clinical diagnosis of herpetic keratitis were studied. Viral isolation, polymerase chain reaction (PCR) and typification were done in a sample taken by swabbing the ocular lesion. Twenty six patients (31% female) had epithelial keratitis, that was mild or moderate in 88% of cases and acute in 77% of them. In 20 patients (77%), viral isolation and PCR were positive (HSV-2 in one case). Fifteen patients (67% female) had stromal keratitis, 93% of cases were moderate or severe and 53% were acute. Viral isolation was negative in all cases and in 20% PCR was positive. Viral isolation and PCR were equally sensitive in epithelial keratitis, but in stromal keratitis only PCR could detect the virus. Moderate acute dendrite was the predominant clinical manifestation. The higher proportion of women with stromal keratitis supports its possibly autoimmune etiology. HSV-2 is seldomly isolated and possibly associated to vertical transmission.

  7. Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. (United States)

    Hofstra, Laura Marije; Nijhuis, Monique; Mudrikova, Tania; Fun, Axel; Schipper, Pauline; Schneider, Margriet; Wensing, Annemarie


    Dolutegravir is a second generation integrase inhibitor with a proposed high genetic barrier to resistance. However, in clinical trials, decreased virological response was seen in a subset of patients with prior exposure to raltegravir and multiple integrase resistance mutations. We describe two cases of HIV subtype B-infected patients starting dolutegravir after previous failure on a raltegravir-containing regimen with extensive resistance. Genotypic analysis was performed using population sequencing and 454 ultradeep sequencing of integrase at time of raltegravir exposure. Both patients were diagnosed in early 1990s and received mono- and dual therapy, followed by several cART-regimens. Due to presence of extensive resistance, the genotypic susceptibility score of these regimens never reached a score >2 and never resulted in sustained virological suppression despite good adherence. Early 2012, the clinical condition of patient 1 worsened during persistent failure of a mega-cART regimen despite excellent drug levels. Six major PI, six minor PI, seven NRTI, six NNRTI and two INI mutations plus DM-virus were detected (Table 1). Ultra-deep sequencing of integrase showed the selection of Q148R, E138K+Q148K, and N155H variants and phenotypic raltegravir resistance was demonstrated. After addition of dolutegravir and enfuvirtide to the failing regimen (zidovudine, lamivudine, tenofovir, etravirine, darunavir/ritonavir, maraviroc), viral load (VL) decreased from 244,000 to <20 cps/mL within five months, CD4-count increased (33 to 272 mm(3)) and the clinical condition improved substantially. In patient 2, similar worsening of the clinical condition was observed late 2012 during persistent failure on mega-cART. Five major PI, six minor PI, nine NRTI, seven NNRTI and one INI mutation plus DM-virus were detected. Ultra-deep sequencing showed selection of N155H, followed by Q95K and V151I variants and phenotypic raltegravir resistance was demonstrated. Dolutegravir was added

  8. Paediatric Virology as a new educational initiative: An interview with Nobelist Professor of Virology Harald zur Hausen. (United States)

    Mammas, Ioannis N; Spandidos, Demetrios A


    Born in Gelsenkirchen-Buer in Germany on March 11th, 1936, Professor Harald zur Hausen, Emeritus Professor of Virology at the University of Freiburg and 2008 Nobel Prize Laureate in Physiology or Medicine for his discovery of human papillomavirus (HPV), which causes cervical cancer, believes that good knowledge of virological methods and diagnostic possibilities are an asset for all young paediatricians. Professor zur Hausen considers that the creation of an educational platform on Paediatric Virology is definitely very beneficial for young paediatricians, as this will greatly enhance their knowledge in the field of Virology. He very actively advocates the vaccination of boys for the eradication of HPV infection and emphasises that male HPV vaccination should be included into the current vaccination programmes. He would have certainly considered Dr George N. Papanicolaou (Kyme, Island of Euboea, Greece, 1883 - Miami, Florida, USA, 1962) as an excellent candidate for the Nobel Prize, stating that the contribution of Dr Papanicolaou did not find sufficient recognition in the past. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens, Greece, on October 7th, 2017, Professor zur Hausen will give his plenary lecture on 'Paediatric Virology and Oncology: Virus persistence and the important first years of life'.

  9. Predictors of Oswestry Disability Index worsening after lumbar fusion. (United States)

    Gum, Jeffrey L; Carreon, Leah Y; Stimac, Jeffrey D; Glassman, Steven D


    The authors identified patients with an increase in their Oswestry Disability Index (ODI) score after lumbar spine fusion to evaluate whether this is a plausible definition of deterioration and to determine whether any common patient characteristics exist.A total of 1054 patients who underwent lumbar spinal fusion and had 2-year follow-up data, including the Short Form 36, the ODI, and numeric rating scales for back and leg pain, were identified. Patients with worsening ODI were compared with the remaining cohort. Twenty-eight patients had an absolute increase (worse) in ODI at 1 year postoperatively. Participants with worsening ODI scores included 13 men and 15 women with an average age of 43.3 years; 15 (54%) were smokers. Common medical comorbidities included obesity and hypertension. Complications occurred in 5 (18%) patients and included wound infection, dural tear, and nerve root injury. Pseudarthrosis was common (n=8; 28%). Twenty-one patients required an additional intervention, including epidural injections, fusion revision, and cervical spine surgery.It is important to have a clear definition of deterioration to better provide informed consent or choice of treatment. Only 28 (2.6%) patients were identified as having an increase in ODI score at 2-year follow-up. Copyright 2013, SLACK Incorporated.

  10. Declining sustained virological response in hepatitis c

    International Nuclear Information System (INIS)

    Batool, U.; Qureshi, S.


    Objective: To determine the response of treatment with standard interferon and Ribazole in treatment naive hepatitis C infected patients, with different grades of activity. Design: A quasi-experimental study. Place and Duration of Study: This study was carried out at the Department of Medicine, KRL General Hospital, Islamabad, from January 2001 to September 2004. Patients and Methods: A total of 300 patients were enrolled. All patients were anti-HCV positive confirmed by device method, PCR positive and had 3a genotype. A specially-designed proforma containing the patient profile, family transmission, and baseline laboratory values was filled. All patients were treated according to a set protocol of Interferon plus ribavirin therapy (IFN alpha 2a, 3MU t.i.w 24 weeks plus ribavirin 1000 to 1200 mg/day) for six months. Chi-square tests were used to analyze the data. Primary end point was a sustained virological response (SVR) that is response assessed after six months of completion of treatment. Results: Over a period of four years response rates to standard Interferon plus Ribazole therapy were studied. Out of the total 300 patients data was available for 161 patients as 60 patients were excluded and 79 patients are currently under treatment. Treatment was stopped in 3 patients due to serious side effects. In the 161 patients, 135 (83.8%), achieved response at the end of treatment at six months; End of Treatment Complete Response (EOTCR); and 26 (16.14%) were non-responders (NR). Out of the complete responders, 68 patients had been followed completely up to six months after the treatment to asses Sustained Viral Response (SVR) defined as undetectable HCV RNA in serum at the end of six months post treatment follow-up. Sustained viral response was seen in 46 patients Le. 68% ( CI: 57-79%) and 22(32.3%) were relapsers (those who developed recurrence of viremia after having achieved eradication at the end of six months treatment). Response rates are co-related with

  11. Declining sustained virological response in hepatitis C. (United States)

    Batool, Uzma; Qureshi, Saleem


    To determine the response of treatment with standard interferon and Ribazole in treatment naïve hepatitis C infected patients, with different grades of activity. A quasi-experimental study. This study was carried out at the Department of Medicine, KRL General Hospital, Islamabad, from January 2001 to September 2004. A total of 300 patients were enrolled. All patients were anti-HCV positive confirmed by device method, PCR positive and had 3a genotype. A specially-designed proforma containing the patient profile, family transmission, and baseline laboratory values was filled. All patients were treated according to a set protocol of Interferon plus ribavirin therapy (IFN alpha 2a, 3MU t.i.w 24 weeks plus ribavirin 1000 to 1200 mg/day) for six months. Chi-square tests were used to analyze the data. Primary end point was a sustained virological response (SVR) that is response assessed after six months of completion of treatment. Over a period of four years response rates to standard Interferon plus Ribazole therapy were studied. Out of the total 300 patients data was available for 161 patients as 60 patients were excluded and 79 patients are currently under treatment. Treatment was stopped in 3 patients due to serious side effects. In the 161 patients, 135 (83.8%), achieved response at the end of treatment at six months; End of Treatment Complete Response (EOTCR); and 26 (16.14%) were non-responders (NR). Out of the complete responders, 68 patients had been followed completely upto six months after the treatment to asses Sustained Viral Response (SVR) defined as undetectable HCV RNA in serum at the end of six months posttreatment follow-up. Sustained viral response was seen in 46 patients i.e. 68% ( CI: 57-79%) and 22(32.3%) were relapsers (those who developed recurrence of viremia after having achieved eradication at the end of six months treatment). Response rates are co-related with gender, baseline ALT and necroinflammatory stage assessed by liver biopsy, probable

  12. Antiseptic mouthwashes could worsen xerostomia in patients taking polypharmacy. (United States)

    Chevalier, Marlene; Sakarovitch, Charlotte; Precheur, Isabelle; Lamure, Julie; Pouyssegur-Rougier, Valerie


    Polypharmacy is a common cause of xerostomia. This study aimed to investigate whether xerostomia could be an adverse drug event of mouthwashes, when they are used for longer than 2 weeks by patients taking polypharmacy. This cross-sectional observational study included 120 hospitalized patients (60 middle-aged and 60 elderly patients), taking polypharmacy (≥4 drugs daily) and at risk of drug-induced xerostomia. Xerostomia was assessed by questioning participants. A total of 62.5% of patients complained of xerostomia. In the middle-aged group (mean age=44.0 (8.7) years; 35.0% women) xerostomia seemed independently associated to mouthwashes, at the limit of significance (OR=5.00, 95% CI=0.99-25.3, p=0.052). Active principles in mouthwashes were mainly quaternary ammonium compounds (91.9%). Mouthwashes may disturb the healthy balance of the biofilm moisturizing the oral mucosa. The biofilm contains mucins, salivary glycoproteins with oligosaccharides side chains able to sequester water and endogenous bacteria surrounded by a glycocalyx. Oral bacteria are fully susceptible to quaternary ammonium (chlorhexidine, hexetidine, cetylpyridinium chloride) and to other antiseptics used in mouthwashes, such as betain, resorcin, triclosan, essential oils and alcohol. However, caregivers currently recommend such dental plaque control products to patients suffering from xerostomia in order to reduce the risk of caries and periodontitis. This study is the first report that use of antiseptic mouthwashes for more than 2 weeks could worsen xerostomia in patients taking polypharmacy. Oral care protocols should avoid this iatrogenic practice, particularly when xerostomia alters the quality-of-life and worsens malnutrition.

  13. Quantification of Lymphocyte Dynamics

    NARCIS (Netherlands)

    Westera, L.


    The different lymphocyte populations of the immune system are maintained at fairly constant numbers throughout life. The importance of this lifelong maintenance is illustrated by clinical conditions of lymphopenia, such as human immunodeficiency virus infection, severe combined immune deficiency, or

  14. The potential advantages of digital PCR for clinical virology diagnostics. (United States)

    Hall Sedlak, Ruth; Jerome, Keith R


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

  15. Subjective worsening of memory predicts dementia after three years

    Directory of Open Access Journals (Sweden)

    Anne Brækhus


    Full Text Available  ABSTRACTStudy Objective:  Design:  Setting:  Paricipants:  Measurements:  Results:  Conclusions:  Key words:  aged, 75 years and over; subjective memory impairment; prospective study; dementiaElderly persons expressing a worsening of memory function are at increased risk ofdeveloping dementia.When adjusting for potential confounding by depressive symptoms, two of the GMSquestions scored at baseline, 'Is it more difficult to remember things than it used to be?' and 'Do youwrite reminders to yourself more often now than before?', were significant predictors of dementiawithin three years, OR = 3.3, 95% CI = 1.2–8.6 and OR = 2.8, 95% CI = 1.0–7.6, respectively.Dementia (DSM-III and DSM-III-R criteria.285 non-demented persons aged 75 years and above at start of study, 77.5% women.Persons living at home.Prospective study of a random sample of older people with follow-ups after three, six, nineand twelve years.To assess whether complaining of memory impairment, as measured by the subjectivepart of the Geriatric Mental State examination (GMS, the Canberra community version, predictslater development of dementia.

  16. Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201.

    Directory of Open Access Journals (Sweden)

    John E McKinnon

    Full Text Available Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI for future use and decreased toxicity. We hypothesized that the level of immune activation (IA and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8, natural killer (NK (CD3+CD56+CD16+ cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279.Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL >50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL >50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023, with an odds ratio of 10.3 (95% CI: 1.92-55.3. Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels.Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical NCT00084019.

  17. Serological and Virological Study of Newcastle Disease and Avian ...

    African Journals Online (AJOL)

    Serological survey on the prevalence of Newcastle disease (NCD) virus antibodies using haemagglutination inhibition test (HI) and virological detection by RT-PCR of highly pathogenic avian influenza (HPAI) H5N1, were carried out in 6 regions of Senegal from June to November 2008. Rural chickens were raised in free ...

  18. Immunological and Virological Response to HAART in HIV-1 ...

    African Journals Online (AJOL)

    Background: Among the countries highly endemic for viral hepatitis, Nigeria is found. Information on how triple infected persons (HIV, HBV, and HCV) fare on HAART in the country is lacking. Laboratory based investigation was carried out to assess the virological and immunological parameters of HIV-1 infected patients ...

  19. The pattern of immunologic and virologic responses to Highly Active ...

    African Journals Online (AJOL)

    To achieve the goals of ART, national ART programmes focus on the vital patient monitoring systems including clinical, immunologic, virologic, adherence, lost to follow-up and mortality. Objectives: This review is aimed at addressing the profile of immunovirological responses to HAART and the factors associated with, with ...

  20. Virological response without CD4 recovery | Madide | Southern ...

    African Journals Online (AJOL)

    The objective of antiretroviral therapy (ART) is to suppress viral replication so that immune restoration can occur. Failure of immune restoration is usually associated with poor virological suppression. In children a good immunological and clinical response to ART is often achieved despite incomplete viral suppression.

  1. A Biosafety Level 2 Virology Lab for Biotechnology Undergraduates (United States)

    Matza-Porges, Sigal; Nathan, Dafna


    Medical, industrial, and basic research relies heavily on the use of viruses and vectors. Therefore, it is important that bioscience undergraduates learn the practicalities of handling viruses. Teaching practical virology in a student laboratory setup presents safety challenges, however. The aim of this article is to describe the design and…

  2. Risk of triple-class virological failure in children with HIV: a retrospective cohort study

    DEFF Research Database (Denmark)

    Castro, Hannah; Judd, Ali; Gibb, Diana M


    In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological...

  3. Lymphocytic cholecystitis/cholangitis. (United States)

    Jessurun, Jose


    To describe four cases of an uncommon type of acalculous cholecystitis/cholangitis characterized by increased intraepithelial lymphocytes within the biliary epithelium. Cases were prospectively compiled during regular surgical pathology sign-out. Clinical information was obtained from the electronic medical record and the gross appearance from the surgical pathology reports. Microscopic examination was performed with emphasis on the type, location, and distribution of the inflammatory pattern; presence of intraepithelial lymphocytes (>30 per 100 biliary cells); and presence of metaplasia and epithelial hyperplasia. Immunohistochemical stains for CD3, CD8, and IgG4 were performed in some cases. All patients were adults who had either biliary pain or obstructive symptoms. All gallbladders had a relatively normal gross appearance and did not contain gallstones or biliary sludge. Microscopic examination showed numerous intraepithelial lymphocytes in the biliary epithelium. The mucosa was frequently expanded by dense inflammatory cell infiltrates. The inflammatory process was more severe in the infundibulum and bile ducts than in the body of the gallbladder. The intraepithelial lymphocytes were CD3+, CD8+. IgG4+ plasma cells were absent. The term lymphocytic cholecystitis/cholangitis is proposed. The potential clinical implications and pathogenesis of this inflammatory pattern and the differential diagnosis with other forms of acalculous cholecystitis are discussed. Copyright© by the American Society for Clinical Pathology.

  4. Baseline resistance and virological outcome in patients with virological failure who start a regimen containing abacavir: EuroSIDA study

    NARCIS (Netherlands)

    Cabrera, Cecilia; Cozzi-Lepri, Alessandro; Phillips, Andrew N.; Loveday, Clive; Kirk, Ole; Ait-Khaled, Mounir; Reiss, Peter; Kjaer, Jesper; Ledergerber, Bruno; Lundgren, Jens D.; Clotet, Bonaventura; Ruiz, Lidia


    Objectives: To investigate the ability of several HIV-1 drug-resistance interpretation systems, as well as the number of pre-specified combinations of abacavir-related mutations, to predict virological response to abacavir-containing regimens in antiretroviral therapy-experienced, abacavir-naive

  5. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.


    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  6. Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1-infected women: maternal virologic, immunologic, and clinical response.

    Directory of Open Access Journals (Sweden)

    Vlada V Melekhin


    Full Text Available Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12, during (N = 70 or after pregnancy (N = 30.Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10 copies/mL, P = 0.03 and 183.8 vs. -70.8 cells/mm(3, P = 0.03, respectively but similar to those initiating HAART before pregnancy (-0.32 log(10 copies/mL, P = 0.96 and 155.8 cells/mm(3, P = 0.81, respectively. There were 3 (25% AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4% in those initiating HAART during pregnancy, and 5 (17% in those initiating after pregnancy (P = 0.01. There were no statistical differences in rates of HIV disease progression between groups.HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

  7. HIV virology and pathogenetic mechanisms of infection: a brief overview. (United States)

    Fanales-Belasio, Emanuele; Raimondo, Mariangela; Suligoi, Barbara; Buttò, Stefano


    Studies on HIV virology and pathogenesis address the complex mechanisms that result in the HIV infection of the cell and destruction of the immune system. These studies are focused on both the structure and the replication characteristics of HIV and on the interaction of the virus with the host. Continuous updating of knowledge on structure, variability and replication of HIV, as well as the characteristics of the host immune response, are essential to refine virological and immunological mechanisms associated with the viral infection and allow us to identify key molecules in the virus life cycle that can be important for the design of new diagnostic assays and specific antiviral drugs and vaccines. In this article we review the characteristics of molecular structure, replication and pathogenesis of HIV, with a particular focus on those aspects that are important for the design of diagnostic assays.

  8. HIV virology and pathogenetic mechanisms of infection: a brief overview

    Directory of Open Access Journals (Sweden)

    Emanuele Fanales-Belasio


    Full Text Available Studies on HIV virology and pathogenesis address the complex mechanisms that result in the HIV infection of the cell and destruction of the immune system. These studies are focused on both the structure and the replication characteristics of HIV and on the interaction of the virus with the host. Continuous updating of knowledge on structure, variability and replication of HIV, as well as the characteristics of the host immune response, are essential to refine virological and immunological mechanisms associated with the viral infection and allow us to identify key molecules in the virus life cycle that can be important for the design of new diagnostic assays and specific antiviral drugs and vaccines. In this article we review the characteristics of molecular structure, replication and pathogenesis of HIV, with a particular focus on those aspects that are important for the design of diagnostic assays.

  9. Can We Predict Those With Osteoarthritis Who Will Worsen Following a Chronic Disease Management Program? (United States)

    Eyles, Jillian P; Mills, Kathryn; Lucas, Barbara R; Williams, Matthew J; Makovey, Joanna; Teoh, Laurence; Hunter, David J


    To identify predictors of worsening symptoms and overall health of the treated hip or knee joint following 26 weeks of a nonsurgical chronic disease management program for hip and knee osteoarthritis (OA) and to examine the consistency of these predictors across 3 definitions of worsening. This prospective cohort study followed 539 participants of the program for 26 weeks. The 3 definitions of worsening included symptomatic worsening based on change in the Western Ontario and McMaster Universities Osteoarthritis Index Global score (WOMAC-G) measuring pain, stiffness, and function; a transition scale that asked about overall health of the treated hip or knee joint; and a composite outcome including both. Multivariate logistic regression models were constructed for the 3 definitions of worsening. Complete data were available for 386 participants: mean age was 66.3 years, 69% were female, 85% reported knee joint pain as primary symptom (signal joint), 46% were waitlisted for total joint arthroplasty (TJA). TJA waitlist status, signal joint, 6-Minute Walk Test (6MWT), depressive symptoms, pain, and age were independently associated with at least 1 definition of worsening. TJA waitlist status and 6MWT remained in the multivariate models for the transition and composite definitions of worsening. Participants reporting worsening on the transition scale did not consistently meet the WOMAC-G definition of worsening symptoms. TJA waitlist status was predictive of the composite definition of worsening, a trend apparent for the transition definition. However, variables that predict worsening remain largely unknown. Further research is required to direct comprehensive and targeted management of patients with hip and knee OA. © 2016, American College of Rheumatology.

  10. Therapy of chronic hepatitis C: Virologic response monitoring

    Directory of Open Access Journals (Sweden)

    Kuljić-Kapulica Nada


    Full Text Available Background/Aim. Virological testing is considered to be essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, and, most importantly, as a quide for treatment decisions and assess the virological response to antiviral therapy. The aim of this study was to determine the rate of a sustained virological response (SVR and various factors associated with response rates in chronic hepatitis C infected patients treated with pegiinterferon alpha (PEGINF and ribavirin (RBV combination therapy. Methods. A total of 34 patients, treated with PEG-IFN and RBV were studied. Serum HCV-RNA was measured before the treatment, 12 weeks following the start of the therapy and 6 weeks after the treatment cessation. SVR was defined as undetectable serum HCV-RNA 6 months of post-treatment follow-up, virologic relapse (VR as relapse of HCV-RNA during the post-treatment follow-up. Serum HCV-RNA was measured with the Cobas Amplicor test. Results. At the end of post-treatment follow-up 19 (55.8% patients demonstrated a SVR. The majority of the patients were genotype 1 (27, and the other were genotype 3 (5 patients and genotype 4 (2 patients. There was VR in 6 patients 6 months after the therapy. In 9 patients HCV-RNA was positive after 12 weeks. Conclusion. We demonstrated that patients with chronic HCV infection can be successfully treated with combination of PEG-INF and RBV. This result emphasizes also that post-treatment follow-up to identify patients with SVR or VR could be important.



    Pradip Bhaumik; Karthik Pichika Lakshmanan


    BACKGROUND Hepatitis B is a global public health problem and India is in intermediate zone of endemicity. Detailed virological evaluation will provide a better idea regarding treatment plan and regular follow up. Hepatitis B Virus (HBV) is a global public health threat affecting about 350 million people across the world. Hepatitis B Virus (HBV) infection is a common cause of liver cirrhosis and Hepatocellular Carcinoma (HCC). The natural course of HBV infection is a dynamic interp...

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

    Directory of Open Access Journals (Sweden)

    Ahmed Hadidi


    Full Text Available 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.Keywords: Next-generation sequencing, NGS, plant virology, plant viruses, viroids, resistance to plant viruses by CRISPR-Cas9

  13. Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia

    DEFF Research Database (Denmark)

    Abdissa, Alemseged; Yilma, Daniel; Fonager, Jannik


    BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub......-Saharan Africa is sparse. METHODS: HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug...... was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS...

  14. Quantitative Assessment of Intra-Patient Variation in CD4+ T Cell Counts in Stable, Virologically-Suppressed, HIV-Infected Subjects. (United States)

    Gordon, Claire L; Cheng, Allen C; Cameron, Paul U; Bailey, Michael; Crowe, Suzanne M; Mills, John


    Counts of absolute CD4+ T lymphocytes (CD4+ T cells) are known to be highly variable in untreated HIV-infected individuals, but there are no data in virologically-suppressed individuals. We investigated CD4+ T cell variability in stable, virologically-suppressed, HIV-1 infected adults on combination antiretroviral therapy (cART). From a large hospital database we selected patients with stable virological suppression on cART for >3 years with >10 CD4+ T cell measurements performed over a further >2 years; and a control group of 95 patients not on cART. We identified 161 HIV-infected patients on cART without active HCV or HBV infection, with stable virological suppression for a median of 6.4 years. Over the study period 88 patients had reached a plateau in their absolute CD4+ T cell counts, while 65 patients had increasing and 8 patients had decreasing absolute CD4+ T cell counts. In patients with plateaued CD4+ T cell counts, variability in absolute CD4+ T cell counts was greater than in percent CD4+ T cells (median coefficient of variation (CV) 16.6% [IQR 13.8-20.1%] and CV 9.6% [IQR 7.4-13.0%], respectively). Patients with increasing CD4+ T cell counts had greater variability in absolute CD4+ T cell counts than those with plateaued CD4 T cell counts (CV 19.5% [IQR 16.1-23.8%], pcounts; this variation can be of clinical relevance especially around CD4+ thresholds. However, the variation seen in individuals on cART is substantially less than in untreated subjects.

  15. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (United States)


    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  16. [Environmental virology and sanitation in Brazil: a narrative review]. (United States)

    Prado, Tatiana; Miagostovich, Marize Pereira


    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.

  17. [Lymphocyte subpopulations in alopecia areata]. (United States)

    Calandria, L; Paciel, J; Bruno, J; Martini, M; Vignale, R; Civila, E


    Subsets of peripheral blood lymphocytes were studied in 19 patients with alopecia areata. The results shows: a decreased Tm/Tg ratio, decreased number of OKT4+ cells, increased OKT8+ cells, decreased OKT4+/OKT8+ cell ratio. Total lymphocytes, T cells, Tm cells, Tg cells, T DR+ cells and B lymphocytes were normal. The results are similar to those founded in autoimmune diseases and suggest the existence of an immunopathogenic mechanism in these disease.

  18. Biochemical markers of lymphocyte maturation

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Kovářů, F.; Kovářů, H.; Fišerová, Anna; Zelníčková, P.; Landa, L.


    Roč. 71, č. 4 (2002), s. 283-286 ISSN 0001-7213 R&D Projects: GA ČR GA304/01/0850; GA AV ČR KSK6005114 Keywords : pig * ontogeny * thymus Subject RIV: EE - Microbiology, Virology Impact factor: 0.370, year: 2002

  19. The 17th Rocky Mountain Virology Association Meeting

    Directory of Open Access Journals (Sweden)

    Joel Rovnak


    Full Text Available Since 2000, scientists and students from the greater Rocky Mountain region, along with invited speakers, both national and international, have gathered at the Mountain Campus of Colorado State University to discuss their area of study, present recent findings, establish or strengthen collaborations, and mentor the next generation of virologists and prionologists through formal presentations and informal discussions concerning science, grantsmanship and network development. This year, approximately 100 people attended the 17th annual Rocky Mountain Virology Association meeting, that began with a keynote presentation, and featured 29 oral and 35 poster presentations covering RNA and DNA viruses, prions, virus-host interactions and guides to successful mentorship. Since the keynote address focused on the structure and function of Zika and related flaviviruses, a special session was held to discuss RNA control. The secluded meeting at the foot of the Colorado Rocky Mountains gave ample time for in-depth discussions amid the peak of fall colors in the aspen groves while the random bear provided excitement. On behalf of the Rocky Mountain Virology Association, this report summarizes the >50 reports.

  20. Lymphocyte Trafficking to Mucosal Tissues

    DEFF Research Database (Denmark)

    Mikhak, Zamaneh; Agace, William Winston; Luster, Andrew D.


    Lymphocytes are the key cells of the adaptive immune system that provide antigen-specific responses tailored to the context of antigen exposure. Through cytokine release and antibody production, lymphocytes orchestrate and amplify the recruitment and function of other immune cells and contribute...... with various homing molecules and respond to tightly regulated navigational cues....

  1. Applications of Next-Generation Sequencing Technologies to Diagnostic Virology

    Directory of Open Access Journals (Sweden)

    Giorgio Palù


    Full Text Available Novel DNA sequencing techniques, referred to as “next-generation” sequencing (NGS, provide high speed and throughput that can produce an enormous volume of sequences with many possible applications in research and diagnostic settings. In this article, we provide an overview of the many applications of NGS in diagnostic virology. NGS techniques have been used for high-throughput whole viral genome sequencing, such as sequencing of new influenza viruses, for detection of viral genome variability and evolution within the host, such as investigation of human immunodeficiency virus and human hepatitis C virus quasispecies, and monitoring of low-abundance antiviral drug-resistance mutations. NGS techniques have been applied to metagenomics-based strategies for the detection of unexpected disease-associated viruses and for the discovery of novel human viruses, including cancer-related viruses. Finally, the human virome in healthy and disease conditions has been described by NGS-based metagenomics.


    Directory of Open Access Journals (Sweden)

    Pradip Bhaumik


    Full Text Available BACKGROUND Hepatitis B is a global public health problem and India is in intermediate zone of endemicity. Detailed virological evaluation will provide a better idea regarding treatment plan and regular follow up. Hepatitis B Virus (HBV is a global public health threat affecting about 350 million people across the world. Hepatitis B Virus (HBV infection is a common cause of liver cirrhosis and Hepatocellular Carcinoma (HCC. The natural course of HBV infection is a dynamic interplay of complex interactions between virus replication and host immune response. MATERIALS AND METHODS 716 HBsAg positive patients who attended liver clinic during a period of 4 years were analysed for epidemiological and virological status. In total, 716 blood samples that were known to be positive for HBsAg were randomly collected for this study during 2012 to 2015. The serum was separated and preserved at -20°C in sterile plastic containers. Each patient who attended the liver clinic provided informed consent to collect blood specimens and perform various serologic and biochemical assays. RESULTS Majority of the patients were between 20 and 40 years, which states a high prevalence among young individuals. More prevalent among male as compared to female population. HBeAg positive chronic hepatitis represented 15.3% of the cases. Hepatitis B viral load was substantially elevated in 28% of the study population. 20% of the study population had a family member positive for HbsAg, which is quite a significant number. CONCLUSION High prevalence of immunologically active patients increases the burden of therapy and high probability of complications in future.

  3. Radiosensitivity of lymphocytes in vitro

    International Nuclear Information System (INIS)

    Albrecht, S.


    The radiation-induced impairment of human T-lymphocytes was studied after in vitro exposure to 25.8 - 825.6 mC/kg (100 - 3200 R) of 60 Co γ-radiation by ascertaining the change in lymphocyte response to phytohaemagglutin stimulation. Following methods were used: (1) measurement of 3 H-thymidine uptake, (2) E-rosette test, and (3) morphological examination of transformed T-cells. The results revealed a dose-dependent decline in T-cell number which was still somewhat more marked with lymphocytes purified over Ficoll-Isopaque prior to irradiation. (author)

  4. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

  5. Prognostic value of worsening renal function in outpatients with chronic heart failure. (United States)

    Pimentel, Rodrigo; Couto, Marta; Laszczyńska, Olga; Friões, Fernando; Bettencourt, Paulo; Azevedo, Ana


    Renal function impairment predicts poor survival in heart failure. Attention has recently shifted to worsening renal function, based mostly on serum creatinine and estimated glomerular filtration rate. We assessed the prognostic effect of worsening renal function in ambulatory heart failure patients. Data from 306 ambulatory patients were abstracted from medical files. Worsening renal function was based on the change in estimated glomerular filtration rate, serum creatinine and urea within 6 months of referral. Prognosis was assessed by the composite endpoint all-cause death or heart failure hospitalization, censored at 2 years. Hazard ratios were estimated for worsening renal function, adjusted for sex, age, diabetes, New York Heart Association class, left ventricular systolic dysfunction, medications and baseline renal function. The agreement among definitions was fair, with kappa coefficients generally not surpassing 0.5. Worsening renal function was associated with poor outcome with adjusted hazard ratios (95% confidence interval) of 3.2 (1.8-5.9) for an increase of serum creatinine >0.3mg/dl; 2.2 (1.3-3.7) for an increase in serum urea >20mg/dl and 1.9 (1.1-3.3) for a decrease in estimated glomerular filtration rate >20%, independent of baseline renal function. The 2-year risk of death/heart failure hospitalization was approximately 50% in patients with an increase in serum creatinine or in serum urea; this positive predictive value was higher than for decreasing estimated glomerular filtration rate. In conclusion, worsening renal function was significantly associated with a worse outcome. Different definitions identified different patients at risk and increasing creatinine/urea performed better than decreasing estimated glomerular filtration rate. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  6. Stages of Chronic Lymphocytic Leukemia (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  7. Behavioral, Virologic, and Immunologic Factors Associated With Acquisition and Severity of Primary Epstein–Barr Virus Infection in University Students (United States)

    Balfour, Henry H.; Odumade, Oludare A.; Schmeling, David O.; Mullan, Beth D.; Ed, Julie A.; Knight, Jennifer A.; Vezina, Heather E.; Thomas, William; Hogquist, Kristin A.


    Background. University students were studied prospectively to determine the incidence of and risk factors for acquisition of primary Epstein–Barr virus (EBV) infection and the virologic and immune correlates of disease severity. Methods. EBV antibody–negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by polymerase chain reaction. Lymphocyte and natural killer (NK) cell numbers and activation were measured by flow cytometry, and plasma cytokine levels were measured by a multiplex assay. Results. Of 546 students screened, 202 (37%) were antibody negative; 143 antibody-negative students were enrolled. During a median of 3 years of observation, 66 subjects experienced primary infection. Of these, 77% had infectious mononucleosis, 12% had atypical symptoms, and 11% were asymptomatic. Subjects reporting deep kissing with or without coitus had the same higher risk of infection than those reporting no kissing (P < .01). Viremia was transient, but median oral shedding was 175 days. Increases were observed in numbers of NK cells and CD8+ T-cells but not in numbers of CD4+ T-cells during acute infection. Severity of illness correlated positively with both blood EBV load (P = .015) and CD8+ lymphocytosis (P = .0003). Conclusions. Kissing was a significant risk for primary EBV infection. A total of 89% of infections were symptomatic, and blood viral load and CD8+ lymphocytosis correlated with disease severity. PMID:23100562

  8. Effectiveness of donepezil in reducing clinical worsening in patients with mild-to-moderate alzheimer's disease

    DEFF Research Database (Denmark)

    Wilkinson, David; Schindler, Rachel; Schwam, Elias


    plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures). RESULTS: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds...

  9. Psychosis or Obsessions? Clozapine Associated with Worsening Obsessive-Compulsive Symptoms

    Directory of Open Access Journals (Sweden)

    Jonathan G. Leung


    Full Text Available One underrecognized adverse event of clozapine is the emergence or worsening of obsessive-compulsive symptoms (OCS. OCS, particularly violent thoughts, can be inaccurately described as psychosis and result in a misdiagnosis. We report a case of a 42-year-old man, initially diagnosed with schizoaffective, who was placed on clozapine for the management of “violent delusions.” However, clozapine led to a worsening of these violent thoughts resulting in suicidal ideation and hospitalization. After exploration of the intrusive thoughts and noting these to be egodystonic, clearly disturbing, and time consuming, an alternative diagnosis of obsessive-compulsive disorder (OCD was made. Clozapine was inevitably discontinued resulting in a significant reduction of the intrusive thoughts without emergence of psychosis or adverse events. While an overlapping phenomenology between OCD and psychotic disorders has been described, clozapine and other antiserotonergic antipsychotics have been implicated with the emergence or worsening of OCS. Unique to our case is that the patient’s obsessions had been treated as psychosis leading to the inadequate treatment of his primary illness, OCD. This case highlights the potential for OCD to masquerade as a psychotic disorder and reminds clinicians that clozapine may worsen OCS.

  10. Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Spoelstra, JA; Stolk, RP; Cohen, D; Klungel, OH; Erkens, JA; Leufkens, HGM; Grobbee, DE

    (B)ackground: Several studies have indicated that type 2 diabetes mellitus is more common among schizophrenic patients than in the general population. In this study, we investigated whether the use of antipsychotic drugs in patients with diabetes leads to worsening of glycemic control. Method: In

  11. Prevention of lymphocyte apoptosis in septic mice with cancer increases mortality. (United States)

    Fox, Amy C; Breed, Elise R; Liang, Zhe; Clark, Andrew T; Zee-Cheng, Brendan R; Chang, Katherine C; Dominguez, Jessica A; Jung, Enjae; Dunne, W Michael; Burd, Eileen M; Farris, Alton B; Linehan, David C; Coopersmith, Craig M


    Lymphocyte apoptosis is thought to have a major role in the pathophysiology of sepsis. However, there is a disconnect between animal models of sepsis and patients with the disease, because the former use subjects that were healthy prior to the onset of infection while most patients have underlying comorbidities. The purpose of this study was to determine whether lymphocyte apoptosis prevention is effective in preventing mortality in septic mice with preexisting cancer. Mice with lymphocyte Bcl-2 overexpression (Bcl-2-Ig) and wild type (WT) mice were injected with a transplantable pancreatic adenocarcinoma cell line. Three weeks later, after development of palpable tumors, all animals received an intratracheal injection of Pseudomonas aeruginosa. Despite having decreased sepsis-induced T and B lymphocyte apoptosis, Bcl-2-Ig mice had markedly increased mortality compared with WT mice following P. aeruginosa pneumonia (85 versus 44% 7-d mortality; p = 0.004). The worsened survival in Bcl-2-Ig mice was associated with increases in Th1 cytokines TNF-α and IFN-γ in bronchoalveolar lavage fluid and decreased production of the Th2 cytokine IL-10 in stimulated splenocytes. There were no differences in tumor size or pulmonary pathology between Bcl-2-Ig and WT mice. To verify that the mortality difference was not specific to Bcl-2 overexpression, similar experiments were performed in Bim(-/-) mice. Septic Bim(-/-) mice with cancer also had increased mortality compared with septic WT mice with cancer. These data demonstrate that, despite overwhelming evidence that prevention of lymphocyte apoptosis is beneficial in septic hosts without comorbidities, the same strategy worsens survival in mice with cancer that are given pneumonia.

  12. News and views from the 8th annual meeting of the Italian Society of Virology. (United States)

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


    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.

  13. Characterization of HIV-1 from patients with virological failure to a boosted protease inhibitor regimen

    DEFF Research Database (Denmark)

    Lillemark, Marie Rathcke; Gerstoft, Jan; Obel, Niels


    The use of highly active antiretroviral treatment (HAART) regimens with unboosted protease inhibitors (PIs) has resulted in a high level of virological failure primarily due to the development of resistant virus. Current boosted PI regimens combine successfully low-dose ritonavir (r) with a second...... PI. The aim of the study was to estimate the proportion of patients, in a population based setting, who develop virological failure on a PI/r regimen. Through The Danish HIV Cohort Study 1,007 patients who received PI/r based treatment between 1995 and 2008 were identified. Twenty-three (2.......3%) experienced virological failure, of whom 19 (83%) started PI/r treatment before 2001. Patients from Copenhagen (n=19) were selected to study the development of protease (PR) and gag cleavage site (CS) mutations during PI/r treatment and PI plasma levels at the time of virological failure. Three patients (16...

  14. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis

    DEFF Research Database (Denmark)

    Martinez-Lapiscina, Elena H; Arnow, Sam; Wilson, James A


    BACKGROUND: Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker...... of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. METHODS: In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis......, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale...

  15. Evaluation of treatment outcomes for patients on first-line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses. (United States)

    Crawford, K W; Wakabi, S; Magala, F; Kibuuka, H; Liu, M; Hamm, T E


    Viral load (VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief (PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here. In this cross-sectional, observational study, patients on first-line antiretroviral therapy (ART) (efavirenz or nevirapine+zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or >24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART. We found that 85.2% of 325 subjects were virologically suppressed (viral loadclinic visits (OR 0.815; 95% CI 0.66-1.00; P=0.05), improvement in CD4 percentage (OR 1.06; 95% CI 1.014-1.107; P=0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23-0.92; P=0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy (ART) (Pclinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age. © 2014 British HIV Association.

  16. Worsening renal function in heart failure: the need for a consensus definition. (United States)

    Sheerin, Noella J; Newton, Phillip J; Macdonald, Peter S; Leung, Dominic Y C; Sibbritt, David; Spicer, Stephen Timothy; Johnson, Kay; Krum, Henry; Davidson, Patricia M


    Acute decompensated heart failure is a common cause of hospitalisation. This is a period of vulnerability both in altered pathophysiology and also the potential for iatrogenesis due to therapeutic interventions. Renal dysfunction is often associated with heart failure and portends adverse outcomes. Identifying heart failure patients at risk of renal dysfunction is important in preventing progression to chronic kidney disease or worsening renal function, informing adjustment to medication management and potentially preventing adverse events. However, there is no working or consensus definition in international heart failure management guidelines for worsening renal function. In addition, there appears to be no concordance or adaptation of chronic kidney disease guidelines by heart failure guideline development groups for the monitoring of chronic kidney disease in heart failure. Our aim is to encourage the debate for an agreed definition given the prognostic impact of worsening renal function in heart failure. We present the case for the uptake of the Acute Kidney Injury Network criteria for acute kidney injury with some minor alterations. This has the potential to inform study design and meta-analysis thereby building the knowledgebase for guideline development. Definition consensus supports data element, clinical registry and electronic algorithm innovation as instruments for quality improvement and clinical research for better patient outcomes. In addition, we recommend all community managed heart failure patients have their baseline renal function classified and routinely monitored in accordance with established renal guidelines to help identify those at increased risk for worsening renal function or progression to chronic kidney disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Reversible worsening of Parkinson disease motor symptoms after oral intake of Uncaria tomentosa (cat's claw). (United States)

    Cosentino, Carlos; Torres, Luis


    Uncaria tomentosa (UT), also known as cat's claw, isa Peruvian Rubiaceae species widely used in traditional medicine for the treatment of a wide range of health problems. There is no report about the use, safety, and efficacy of UT in neurological disorders. We describe reversible worsening of motor signs in a patient with Parkinson disease after oral intake of UT, and some possible explanations are discussed.

  18. Patients with worsening chronic heart failure who present to a hospital emergency department require hospital care

    Directory of Open Access Journals (Sweden)

    Shafazand Masoud


    Full Text Available Abstract Background Chronic heart failure (CHF is a major public health problem characterised by progressive deterioration with disabling symptoms and frequent hospital admissions. To influence hospitalisation rates it is crucial to identify precipitating factors. To characterise patients with CHF who seek an emergency department (ED because of worsening symptoms and signs and to explore the reasons why they are admitted to hospital. Method Patients (n = 2,648 seeking care for dyspnoea were identified at the ED, Sahlgrenska University Hospital/Östra. Out of 2,648 patients, 1,127 had a previous diagnosis of CHF, and of these, 786 were included in the present study with at least one sign and one symptom of worsening CHF. Results Although several of the patients wanted to go home after acute treatment in the ED, only 2% could be sent home. These patients were enrolled in an interventional study, which evaluated the acute care at home compared to the conventional, in hospital care. The remaining patients were admitted to hospital because of serious condition, including pneumonia/respiratory disease, myocardial infarction, pulmonary oedema, anaemia, the need to monitor cardiac rhythm, pathological blood chemistry and difficulties to communicate. Conclusion The vast majority of patients with worsening CHF seeking the ED required hospital care, predominantly because of co-morbidities. Patients with CHF with symptomatic deterioration may be admitted to hospital without additional emergency room investigations.

  19. Worsened physical condition due to climate change contributes to the increasing hypoxia in Chesapeake Bay. (United States)

    Du, Jiabi; Shen, Jian; Park, Kyeong; Wang, Ya Ping; Yu, Xin


    There are increasing concerns about the impact of worsened physical condition on hypoxia in a variety of coastal systems, especially considering the influence of changing climate. In this study, an EOF analysis of the DO data for 1985-2012, a long-term numerical simulation of vertical exchange, and statistical analysis were applied to understand the underlying mechanisms for the variation of DO condition in Chesapeake Bay. Three types of analysis consistently demonstrated that both biological and physical conditions contribute equally to seasonal and interannual variations of the hypoxic condition in Chesapeake Bay. We found the physical condition (vertical exchange+temperature) determines the spatial and seasonal pattern of the hypoxia in Chesapeake Bay. The EOF analysis showed that the first mode, which was highly related to the physical forcings and correlated with the summer hypoxia volume, can be well explained by seasonal and interannual variations of physical variables and biological activities, while the second mode is significantly correlated with the estuarine circulation and river discharge. The weakened vertical exchange and increased water temperature since the 1980s demonstrated a worsened physical condition over the past few decades. Under changing climate (e.g., warming, accelerated sea-level rise, altered precipitation and wind patterns), Chesapeake Bay is likely to experience a worsened physical condition, which will amplify the negative impact of anthropogenic inputs on eutrophication and consequently require more efforts for nutrient reduction to improve the water quality condition in Chesapeake Bay. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. MicroRNAs relate to early worsening of renal function in patients with acute heart failure. (United States)

    Bruno, Noemi; ter Maaten, Jozine M; Ovchinnikova, Ekaterina S; Vegter, Eline L; Valente, Mattia A E; van der Meer, Peter; de Boer, Rudolf A; van der Harst, Pim; Schmitter, Daniela; Metra, Marco; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; Pinto, Yigal M; van Veldhuisen, Dirk J; Hillege, Hans L; Berezikov, Eugene; Voors, Adriaan A


    Deregulation of microRNAs (miRNAs) may be involved in the pathogenesis of heart failure (HF) and renal disease. Our aim is to describe miRNA levels related to early worsening renal function in acute HF patients. We studied the association between 12 circulating miRNAs and Worsening Renal Function (WRF; defined as an increase in the serum creatinine level of 0.3mg per deciliter or more from admission to day 3), absolute change in creatinine and Neutrophil Gelatinase Associated Lipocalin (NGAL) from admission to day 3 in 98 patients hospitalized for acute HF. At baseline, circulating levels of all miRNAs were lower in patients with WRF, with statistically significant decreased levels of miR-199a-3p, miR-423-3p, and miR-let-7i-5p (p-valueacute HF were consistently lower in patients who developed worsening of renal function. MiR-199a-3p was the best predictor of WRF in these patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Lung Adenocarcinoma Presenting as Worsening of Chronic Neck Pain—A Cautionary Tale

    Directory of Open Access Journals (Sweden)

    Neeka N Akhavan


    Full Text Available Introduction: Neck pain is a common musculoskeletal problem that up to 70% of the world population will experience at some point in their lives. Intramedullary spinal cord metastasis is an exceedingly rare complication of malignancy that affects less than 1% of all patients with cancer. Case report: We report a case of a 61-year-old man who presented to primary care clinic with 1-month history of worsening neck pain with associated neurologic deficits. Despite initial conservative management, the patient continued to have progressive worsening of sensory and motor deficits. Magnetic resonance imaging of the cervical spine showed vasogenic edema of the brain and spinal cord and nodularity at the C4-C5 level. A computed tomography of the chest showed a dense lesion in the left lower lobe of the lung; histopathology of the biopsied specimen was consistent with moderately differentiated lung adenocarcinoma. Conclusions: A high index of suspicion is necessary when chronic neck pain acutely worsens, changes in character, or is accompanied by neurologic deficits. These clinical signs warrant further investigation into a secondary cause of neck pain. Intramedullary spinal cord metastases are rare complications of systemic cancer that commonly present with neck pain and upper extremity paraesthesias; early diagnosis and management are necessary to prevent complications such as spinal cord hemisection syndrome or spinal cord transection.

  2. Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome

    NARCIS (Netherlands)

    Morici, Nuccia; Savonitto, Stefano; Ponticelli, Claudio; Schrieks, Ilse C; Nozza, Anna; Cosentino, Francesco; Stähli, Barbara E; Perrone Filardi, Pasquale; Schwartz, Gregory G.; Mellbin, Linda; Lincoff, A. Michael; Tardif, Jean-Claude; Grobbee, Diederick E

    BACKGROUND: Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. METHODS: We considered the placebo cohort

  3. Lymphocyte receptors for pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))


    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  4. Risk factors for worsened quality of life in patients on mechanical ventilation. A prospective multicenter study. (United States)

    Busico, M; Intile, D; Sívori, M; Irastorza, N; Alvarez, A L; Quintana, J; Vazquez, L; Plotnikow, G; Villarejo, F; Desmery, P


    To identify risk factors for worsened quality of life (QoL) and activities of daily living (ADL) at 3 and 12 months after discharge from the Intensive Care Unit (ICU) in patients on mechanical ventilation (MV). A prospective, multicentric observational study was made. Three ICUs in Argentina. The study included a total of 84 out of 129 mainly clinical patients admitted between 2011-2012 and requiring over 24hours of MV. No interventions were carried out. Quality of life was assessed with the EQ-5D (version for Argentina), and ADL with the Barthel index. The EQ-5D and Barthel scores were assessed upon admission to the ICU (baseline) and after three months and one year of follow-up. Comorbidities, delirium, ICU acquired weakness (ICUAW), and medication received were daily assessed during ICU stay. The baseline QoL of the global sample showed a median index of [0.831 (IQR25-75% 0.527-0.931)], versus [0.513 (IQR0.245-0.838)] after three months and [0.850 (IQR0.573-1.00)] after one year. Significant differences were observed compared with QoL in the Argentinean general population [mean 0.880 (CI 0.872-0.888), p<0.001; p<0.001; p0.002]. Individual analysis showed that 67% of the patients had worsened their QoL at three months, while 33% had recovered their QoL. In the multivariate analysis, the variables found to be independent predictors of worsened QoL were a hospital stay ≥21 days [OR 12.57 (2.75-57.47)], age ≥50 years [OR 5.61 (1.27-24.83)], previous poor QoL [OR 0.11 (0.02-0.54)] and persistent ICUAW [OR 8.32 (1.22-56.74)]. Similar results were found for the worsening of ADL. Quality of life is altered after critical illness, and its recovery is gradual over time. Age, length of hospital stay, previous QoL and persistent ICUAW seem to be risk factors for worsened QoL. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  5. Race, sex, and risk factors in radiographic worsening of knee osteoarthritis. (United States)

    Vina, Ernest R; Ran, Di; Ashbeck, Erin L; Ratzlaff, Charles; Kwoh, C Kent


    Characterize radiographic worsening in knee osteoarthritis (KOA) by race and sex over 4 years and evaluate the role of established risk factors in observed race/sex differences. Whites (WHs) (694 males and 929 females) and African-Americans (AAs) (92 males and 167 females) at risk for radiographic KOA were eligible. Cox shared frailty models were used to estimate race and sex group differences in radiographic worsening, defined by Kellgren-Lawrence (K-L) and OARSI joint space narrowing (JSN). Mixed effect models for repeated measures were used to estimate race- and sex-specific mean medial and lateral fixed joint space width (fJSW) over 4 years of follow-up, as well as annual loss of fJSW. Risk of OARSI medial JSN grade worsening was higher among AA males than WH females [HR = 2.28, (95% CI: 1.14-4.57)], though adjustment for KOA risk factors attenuated the association. Compared to WH females, WH males had lower risk of K-L grade worsening [adjusted HR = 0.75 (95% CI: 0.58-0.96)]. Mean baseline medial fJSW (mm) was 6.49 in WH and AA males, 5.42 in WH females, and 5.41 in AA females. Annual change in mean medial fJSW was greater in AA males (-0.19mm/year) than in other subgroups (-0.09 WH males, -0.07 WH females, -0.10 AA females, p WHs, AAs had less lateral fJSW at baseline and throughout follow-up. Compared to WHs and AA females, AA males experienced higher risk of medial joint space loss. Controlling for established risk factors attenuated associations between race/sex and disease worsening, suggesting that risk factors such as obesity, history of knee injury, and bony finger joint enlargements largely explain race/sex variations in rates of KOA development and progression. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Radiosensitivity of lymphocytes among Filipinos: final report

    International Nuclear Information System (INIS)

    Medina, F.I.S.; Gregorio, J.S.; Aguilar, C.P.; Poblete, E.E.


    This report is about the studies on the radiosensitivity of Filipino lymphocytes to radiation that can elucidate on the potential of blood chromosomes as biological dosimeters. The objective of this study is to determine the radiosensitivity of lymphocytes among Filipinos and to establish the radiation-induced chromosome anomaly standard curve in lymphocytes for radiological dosimetry. 47 refs., 9 figs., 1 tab

  7. A microculture technique for rat lymphocyte transformation. (United States)

    Lindsay, V J; Allardyce, R A


    We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described.

  8. Neutrophil-to-Lymphocyte Ratio as a Predictor of Response to Peginterferon plus Ribavirin Therapy for Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Ming-Te Kuo


    Full Text Available We aimed to determine whether neutrophil-to-lymphocyte ratio (NLR could be a predictor of antiviral response in chronic hepatitis C patients. A total of 602 consecutive patients (genotype 1, n=263; genotype 2, n=297; others/unknown, n=42 receiving response-guided therapy with peginterferon plus ribavirin were recruited. NLR was related to clinical and virological features and to treatment outcome. Rapid virological response (RVR and sustained virological response (SVR were achieved in 436 (73% and 458 (76% of the patients, respectively. Higher NLR (≥1.42 was found to be associated with higher prevalence of DM (P=0.039 and higher hepatitis C viral load (P=0.002 and white cell count (P<0.001. NLR was significantly lower in patients with RVR and SVR compared to those without (P=0.032 and 0.034, resp.. However, NLR was not an independent factor by multivariate analysis. In the subgroup analysis, higher NLR (≥1.42 (odds ratio, 0.494, P=0.038 was an independent poor predictor of SVR in genotype 2 patients but was not in genotype 1 patients. In conclusion, NLR is a simple and easily accessible marker to predict response to peginterferon plus ribavirin therapy for chronic hepatitis C genotype 2.

  9. Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation. (United States)

    Imamura, Teruhiko; Kinugawa, Koichiro; Doi, Kent; Hatano, Masaru; Fujino, Takeo; Kinoshita, Osamu; Nawata, Kan; Noiri, Eisei; Kyo, Shunei; Ono, Minoru


    Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immunosuppressant for heart transplant (HTx) recipients, and is expected to preserve renal function compared to conventional calcineurin inhibitors (CNIs). However, a considerable number of recipients treated with EVL were not free from worsening renal function regardless of CNI reduction. Data were collected retrospectively from 27 HTx recipients who had received EVL (trough concentration, 3.1-9.2 ng/mL) along with reduced CNIs (%decreases in trough concentration, 27.3 ± 13.0%) because of switching from mycophenolate mophetil due to digestive symptoms or neutropenia, progressive coronary artery vasculopathy, or persistent renal dysfunction, and had been followed over 1 year between August 2008 and January 2013. Estimated glomerular filtration rate (eGFR) decreased in 5 recipients (18.5%) during the study period. Univariate logistic regression analysis demonstrated that a higher plasma neutrophil gelatinase-associated lipocalin (P-NGAL) level was the only significant predictor for a decrease in eGFR over a 1-year EVL treatment period among all baseline parameters (P = 0.008). eGFR and proteinuria worsened almost exclusively in patients with baseline P-NGAL ≥ 85 ng/mL, which was the cutoff value calculated by an ROC analysis (area under the curve, 0.955; sensitivity, 1.000; specificity, 0.955). In conclusion, higher P-NGAL may be a novel predictor for the worsening of renal function after EVL treatment that is resistant to CNI reduction in HTx recipients.

  10. Rapidly worsening bulbar symptoms in a patient with spinobulbar muscular atrophy

    Directory of Open Access Journals (Sweden)

    Montserrat Diaz-Abad


    Full Text Available X-linked spinobulbar muscular atrophy (Kennedy’s disease affects muscles and motor neurons, manifesting as weakness and wasting of bulbar, facial, and proximal limb muscles due to loss of anterior horn cells in the brain and spinal cord. We present the case of a patient with X-linked spinobulbar muscular atrophy with rapidly worsening bulbar symptoms caused by laryngopharyngeal irritation associated with a viral upper respiratory tract infection, seasonal allergies and laryngopharyngeal reflux, who dramatically improved with multimodality therapy.

  11. Plasma lopinavir concentrations predict virological failure in a cohort of South African children initiating a protease-inhibitor-based regimen (United States)

    Moholisa, Retsilisitsoe R; Schomaker, Michael; Kuhn, Louise; Meredith, Sandra; Wiesner, Lubbe; Coovadia, Ashraf; Strehlau, Renate; Martens, Leigh; Abrams, Elaine J; Maartens, Gary; Mcllleron, Helen


    Background Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characteristics and viral load >400 copies/ml. Methods A total of 237 HIV-infected children aged 4–42 months on lopinavir/ritonavir oral solution were studied prospectively and followed for up to 52 weeks. Viral load and lopinavir concentration were measured at clinic visits 12, 24, 36 and 52 weeks after starting treatment. Cox multiple failure events models were used to estimate the crude and adjusted effect of lopinavir concentrations on the hazard of viral load >400 copies/ml. Results The median (IQR) pretreatment CD4+ T-lymphocyte percentage was 18.80% (12.70–25.35) and 53% of children had a pretreatment viral load >750,000 copies/ml. The median (IQR) weight-for-age and height-for-age z-scores were −2.17 (−3.35–−2.84) and −3.34 (−4.57–−3.41), respectively. Median (IQR) lopinavir concentrations were 8.00 mg/l (4.11–12.42) at median (IQR) 3.50 h (2.67–4.25) after the dose. The hazard of viral load >400 copies/ml was increased with lopinavir concentrations <1 mg/l versus ≥1 mg/l (adjusted hazard ratio 2.3 [95% CI 1.63, 3.26]) and lower height-for-age z-scores. Conclusions Low lopinavir concentrations (<1 mg/l) are associated with viraemia in children. This measure could be used as a proxy for adherence and to determine which children are more likely to fail. PMID:24518130

  12. An audit on virological efficacy of anti-retroviral therapy in a specialist infectious disease clinic.

    LENUS (Irish Health Repository)

    Reyad, A


    We have assessed the efficacy of anti retroviral therapy (ART) using undetectable viral load (VL) (<50 RNA copies\\/ml) as a marker of virological success, in patients who have Human Immunodeficiency Virus (HIV) attending the Department of Infectious Disease. A cross-sectional review of patients\\' case notes was used to obtain their demographics and treatment details. 79% (253) of the hospital case notes of clinic population was available for analysis, which represents 90% of those receiving ART in the clinic. 166\\/253 of the cohort were receiving treatment at the time of this study and 95% (157\\/166) of these were on treatment for greater than 6 months. The total virological success rate is 93%, which is comparable to other centres and are as good as those from published clinical trials. 56% of those on therapy who have virological failure were Intravenous Drug Users (IVDUs). Case by case investigation for those with treatment failure is warranted.

  13. Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Kirk, Ole; Gatell, Jose M


    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS......: Virologic response (viral load ART was analyzed in antiretroviral-naive EuroSIDA patients. Analyses were stratified by region (south, central west, north, east) or time started cART (early, 1996-1997; mid, 1998-1999; late, 2000-1904). RESULTS: Virologic...... suppression was achieved by 60% of 2102 patients: 57% south (n = 560), 61% central west (n = 466), 63% north (n = 606), 58% east (n = 470) (P = 0.091). An increase was observed over time: 52% early cART, 56% mid cART, 69% late cART (P

  14. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J


    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS......: Virologic response (viral load ART was analyzed in antiretroviral-naive EuroSIDA patients. Analyses were stratified by region (south, central west, north, east) or time started cART (early, 1996-1997; mid, 1998-1999; late, 2000-1904). RESULTS: Virologic...... suppression was achieved by 60% of 2102 patients: 57% south (n = 560), 61% central west (n = 466), 63% north (n = 606), 58% east (n = 470) (P = 0.091). An increase was observed over time: 52% early cART, 56% mid cART, 69% late cART (P

  15. Quantitative 3D video microscopy of HIV transfer across T cell virological synapses. (United States)

    Hübner, Wolfgang; McNerney, Gregory P; Chen, Ping; Dale, Benjamin M; Gordon, Ronald E; Chuang, Frank Y S; Li, Xiao-Dong; Asmuth, David M; Huser, Thomas; Chen, Benjamin K


    The spread of HIV between immune cells is greatly enhanced by cell-cell adhesions called virological synapses, although the underlying mechanisms have been unclear. With use of an infectious, fluorescent clone of HIV, we tracked the movement of Gag in live CD4 T cells and captured the direct translocation of HIV across the virological synapse. Quantitative, high-speed three-dimensional (3D) video microscopy revealed the rapid formation of micrometer-sized "buttons" containing oligomerized viral Gag protein. Electron microscopy showed that these buttons were packed with budding viral crescents. Viral transfer events were observed to form virus-laden internal compartments within target cells. Continuous time-lapse monitoring showed preferential infection through synapses. Thus, HIV dissemination may be enhanced by virological synapse-mediated cell adhesion coupled to viral endocytosis.

  16. Nodular lymphocyte predominant Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Siddiqui, Neelam; Al-Diab, Abdulrahman I.


    To describe the clinicopathological features, treatment, treatment outcome and sequelae of patients with nodular lymphocyte, predominant Hodgkin's lymphoma (NLPHL) in Saudi population. This is a retrospective review of 29 patients with lymphocyte predominant Hodgkin's lymphoma treated at two major hospitals (King Khalid University Hospital and Security Forces Hospital) in Riyadh, Kingdom of Saudi Arabia from 1985 to 2000. Histological subtypes were confirmed by review of hematoxylin and eosin paraffin sections and immunochemistry. Details of clinical presentation, stage, treatment and results of treatment were analyzed. On pathological reappraisal of the 29 cases, 3 patients had nodular sclerosis Hodgkin's lymphoma and 4 patients were reclassified as lymphocyte rich classical Hodgkin's lymphoma. Twenty-two patients were identified to have nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). These patients comprised of 18 mails and 4 female patients with a median age at presentation of 25 years. Nineteen (86%) patients had an early stage (Ann Arbor stage I and II) disease, 2 had stage III and one patient had stage IV. The majority of patients presented with peripheral lymphadenopathy and long duration of symptoms. For 16 patients, details of treatment and follow-up were available. All of these achieved a complete response to initial treatment. Four patients relapsed following the primary therapy. Our results are consistent with the previous series reported from Western countries and confirmed that the patients with NLPHL have characteristic clinical and pathological profile that distinguish it from other types of Hodgkin's lymphoma. The disease tends to run an unusual course and although most patients achieve an excellent response to therapy there is a tendency to replace. treatment remains controversial; however, recent understanding of the molecular pathogenesis of NLPHL could lead to modification of current therapeutic approach to this disease. (author)

  17. Virologic studies in a case of transfusion-associated AIDS. (United States)

    Groopman, J E; Salahuddin, S Z; Sarngadharan, M G; Mullins, J I; Sullivan, J L; Mulder, C; O'Hara, C J; Cheeseman, S H; Haverkos, H; Forgacs, P


    The authors present the case of a 60-year old woman who developed acquired immunedeficiency syndrome (AIDS) 43 months after a blood transfusion. The blood donor was identified as a sexually active homosexual man who frequently used intravenous drugs. Although he was asymptomatic, physical examination revealed generalized lymphadenopathy of cervical, axillary, and inguinal areas. 47 months after his blood donation, the donor underwent lymph node biopsy which revealed follicular hyperplasia. He was seropositive for antibodies to human T-lymphotropic virus type III (HTLV-III) and had serologic evidence of prior infection with cytomegalovirus, Epstein-Barr virus, and hepatitis B virus. On the other hand, he had a normal total lymphocyte count and normal T-cell subsets. Striking was the difference between the seropositivity of the high-risk donor and the seronegativity of the patient with transfusion-associated AIDS with respect to cytomegalovirus, Epstein-Barr virus, and hepatitis B virus. The demonstration of apparent transmission of HTLV-III by blood transfusion and the inability to detect evidence of infection with other viruses strongly indicate a primary etiologic role for this virus in the pathogenesis of AIDS. The high-risk blood donor continues to be an asymptomatic carrier of HTLV-III. The authors are currently comparing the HTLV-III isolates obtained from the blood donor with the HTLV-III-related RNA sequences detected in the spleen of the patient in order to determine whether molecular changes occurred after transmission of the virus that might be related to the development of AIDS.

  18. [Characteristics of lymphocyte phenotypes in HBV transgenic mice and the effect of interferon-α: a preliminary study]. (United States)

    Yan, Xin; Zhong, Rui-Hua; Liu, Jin-Hong; Zhou, Yang; Tang, Li-Bo; Li, Yong-Yin; Liu, Guang-Ze; Hou, Jin-Lin


    To analyze the characteristics of lymphocyte phenotypes in hepatitis B virus (HBV) transgenic mice and the effect of exogenous interferon-α on virological profiles and lymphocytes phenotypes of the mice. HBV transgenic mice and wild-type (WT) mice were examined for serum levels of HBsAg, HBcAb, IL-21, and IL-6 using ELISA. The frequencies of CD4(+)T and CD19(+)B cells separated from the liver, spleen, and peripheral blood were detected by flow cytometry. Nine HBV transgenic mice were injected subcutaneously with recombinant mouse interferon alpha (rmIFN-α) and another 9 transgenic mice were injected with PBS, and their HBsAg, HBV DNA, IL-6, and IL-21 levels and frequencies of peripheral blood CD4(+)T and CD19(+)B cells were detected. HBV transgenic mice showed a high level of HBsAg with a detectable level of HBcAb and significantly increased serum levels of IL-21 and IL-6 as compared with WT mice (Ptransgenic mice had a significantly lower frequency of CD4(+) T cells in the peripheral blood, liver and spleen (Ptransgenic mice. Administration of rmIFN-α significantly increased the frequencies of CD4(+) T and CD19(+) B cells in the peripheral blood and the serum level of IL-6 in HBV transgenic mice (Ptransgenic mice have lymphocyte subset dysregulation and exogenous interferon-α can modulate the immune function of the mice by regulating the frequencies of lymphocyte subsets.

  19. Virologic outcome among patients receiving antiretroviral therapy at five hospitals in Haiti. (United States)

    Jean Louis, Frantz; Buteau, Josiane; François, Kesner; Hulland, Erin; Domerçant, Jean Wysler; Yang, Chunfu; Boncy, Jacques; Burris, Robert; Pelletier, Valerie; Wagar, Nicholas; Deyde, Varough; Lowrance, David W; Charles, Macarthur


    Viral load (VL) assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART). We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for ≥6 months in five hospitals around Port-au-Prince, Haiti. Plasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures. Data were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6%) achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0%) of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8%) maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86), 23 to 35 months on ART (aOR:0.72[0.54-0.96]), baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively), poor adherence (aOR: 0.69 [0.59-0.81]), and TB co-infection (aOR: 0.73 [0.55-0.97]). This study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after ≥ six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes.

  20. Virologic outcome among patients receiving antiretroviral therapy at five hospitals in Haiti.

    Directory of Open Access Journals (Sweden)

    Frantz Jean Louis

    Full Text Available Viral load (VL assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART. We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for ≥6 months in five hospitals around Port-au-Prince, Haiti.Plasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures.Data were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6% achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0% of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8% maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86, 23 to 35 months on ART (aOR:0.72[0.54-0.96], baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively, poor adherence (aOR: 0.69 [0.59-0.81], and TB co-infection (aOR: 0.73 [0.55-0.97].This study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after ≥ six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes.

  1. Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Kirk, Ole; Gatell, Jose M


    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS.......026) and time (P changes were observed (south, P = 0.061; central west, P ....001; north: P = 0.070; east, P = 0.001). CONCLUSIONS: There was some evidence of regional differences in initial virologic response to cART. Improvements over time were observed, suggesting that so far, the effect of primary resistance has not been of sufficient magnitude to prevent increasing suppression...

  2. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J


    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS.......026) and time (P changes were observed (south, P = 0.061; central west, P ....001; north: P = 0.070; east, P = 0.001). CONCLUSIONS: There was some evidence of regional differences in initial virologic response to cART. Improvements over time were observed, suggesting that so far, the effect of primary resistance has not been of sufficient magnitude to prevent increasing suppression...

  3. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J


    : Virologic response (viral load west, north, east) or time started cART (early, 1996-1997; mid, 1998-1999; late, 2000-1904). RESULTS: Virologic...... suppression was achieved by 60% of 2102 patients: 57% south (n = 560), 61% central west (n = 466), 63% north (n = 606), 58% east (n = 470) (P = 0.091). An increase was observed over time: 52% early cART, 56% mid cART, 69% late cART (P ....026) and time (P west, P

  4. Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Kirk, Ole; Gatell, Jose M


    : Virologic response (viral load west, north, east) or time started cART (early, 1996-1997; mid, 1998-1999; late, 2000-1904). RESULTS: Virologic...... suppression was achieved by 60% of 2102 patients: 57% south (n = 560), 61% central west (n = 466), 63% north (n = 606), 58% east (n = 470) (P = 0.091). An increase was observed over time: 52% early cART, 56% mid cART, 69% late cART (P ....026) and time (P west, P

  5. Worsening of coronary spasm during the perioperative period: A case report (United States)

    Teragawa, Hiroki; Nishioka, Kenji; Fujii, Yuichi; Idei, Naomi; Hata, Takaki; Kurushima, Shuji; Shokawa, Tomoki; Kihara, Yasuki


    We present the case of a 65-year-old male with vasospastic angina (VSA) whose condition worsened during the perioperative period. He had been diagnosed with VSA 10 years prior. He was treated with two types of vasodilators and had not experienced any chest symptoms for 5 years. At this juncture, he underwent surgery for relapsed maxillary sublingual carcinoma. He had taken two vasodilators one day prior to surgery. Intravenous infusion of nitroglycerin (NTG) was initiated immediately before the surgery and continued the following day. Instead of stopping NTG, a dermal isosorbide dinitrate tape was applied on post-operative day 1. Two days later, a complete atrioventricular block with pulseless electrical activity appeared. After cardiopulmonary resuscitation, emergent coronary angiography showed severe coronary spasm in both the left and right coronary arteries. Intracoronary infusion of nitroglycerin and epinephrine with percutaneous cardiopulmonary support relieved the coronary spasm. During the perioperative period, several factors can trigger coronary vasospasm, including the discontinuation of vasodilators. Thus, surgeons, anesthetists, and cardiologists should watch for coronary vasospasm during this period and for worsening coronary spasm when discontinuing vasodilators in patients at risk for VSA. PMID:25068030

  6. Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive function? (United States)

    Avanzini, Giuliano; Depaulis, Antoine; Tassinari, Alberto; de Curtis, Marco


    Relevant to the definition of epileptic encephalopathy (EE) is the concept that the epileptic activity itself may contribute to bad outcomes, both in terms of epilepsy and cognition, above and beyond what might be expected from the underlying pathology alone, and that these can worsen over time. The review of the clinical and experimental evidence that seizures or interictal electroencephalography (EEG) discharges themselves can induce a progression toward more severe epilepsy and a regression of brain function leads to the following conclusions: The possibility of seizure-dependent worsening is by no means a general one but is limited to some types of epilepsy, namely mesial temporal lobe epilepsy (MTLE) and EEs. Clinical and experimental data concur in indicating that prolonged seizures/status epilepticus (SE) are a risky initial event that can set in motion an epileptogenic process leading to persistent, possibly drug-refractory epilepsies. The mechanisms for SE-related epileptogenic process are incompletely known; they seem to involve inflammation and/or glutamatergic transmission. The evidence of the role of recurrent individual seizures in sustaining epilepsy progression is ambiguous. The correlation between high seizure frequency and bad outcome does not necessarily demonstrate a cause-effect relationship, rather high seizure frequency and bad outcome can both depend on a particularly aggressive epileptogenic process. The results of EE studies challenge the idea of a common seizure-dependent mechanism for epilepsy progression/intellectual deterioration. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  7. T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

    International Nuclear Information System (INIS)

    Han, T.; Dadey, B.


    Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

  8. Varus thrust during walking and the risk of incident and worsening medial tibiofemoral MRI lesions: the Multicenter Osteoarthritis Study. (United States)

    Wink, A E; Gross, K D; Brown, C A; Guermazi, A; Roemer, F; Niu, J; Torner, J; Lewis, C E; Nevitt, M C; Tolstykh, I; Sharma, L; Felson, D T


    To determine the association of varus thrust during walking to incident and worsening medial tibiofemoral cartilage damage and bone marrow lesions (BMLs) over 2 years in older adults with or at risk for osteoarthritis (OA). Subjects from the Multicenter Osteoarthritis Study (MOST) were studied. Varus thrust was visually assessed from high-speed videos of forward walking trials. Baseline and two-year MRIs were acquired from one knee per subject and read for cartilage loss and BMLs. Logistic regression with generalized estimating equations was used to estimate the odds of incident and worsening cartilage loss and BMLs, adjusting for age, sex, race, body mass index (BMI), and clinic site. The analysis was repeated stratified by varus, neutral, and valgus alignment. 1007 participants contributed one knee each. Varus thrust was observed in 29.9% of knees. Knees with thrust had 2.17 [95% CI: 1.51, 3.11] times the odds of incident medial BML, 2.51 [1.85, 3.40] times the odds of worsening medial BML, and 1.85 [1.35, 2.55] times the odds of worsening medial cartilage loss. When stratified by alignment, varus knees also had significantly increased odds of these outcomes. Varus thrust observed during walking is associated with increased odds of incident and worsening medial BMLs and worsening medial cartilage loss. Increased odds of these outcomes persist in varus-aligned knees. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  9. Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Guo-Yan Qi


    Full Text Available Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI on alleviating transient worsening of myasthenia gravis (MG symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW were evaluated and compared with the clinical absolute scoring (AS and relative scoring (RS system. Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P<0.000 in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2 significantly smaller (P<0.05 than in the control group (24.9 ± 2.5. At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9 compared with at TW, although no significant difference compared with the control (9.7 ± 1.1. The TW lasted 1–6 days (mean 3.7 for the treatment group, significantly shorter (P<0.05 than 2–12 days (mean 7.8 for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%, significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%. Slight side effects (18.75% included maldigestion and rash in the treatment group. Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy.

  10. Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis (United States)

    Qi, Guo-Yan; Liu, Peng


    Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system. Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P < 0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P < 0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P < 0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group. Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy. PMID:24348721

  11. Role of IL-28B polymorphisms in virologic response to combined ...

    African Journals Online (AJOL)

    Amira Youssef Shaala


    Oct 17, 2014 ... Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis. Amira Youssef Shaala a. , Mona Gamal Morsi a. , Reem Abdel Hameed Harfoush a,. *,. Ehab Hassan ElKhouly b. , Mohamed ...

  12. Detection of resistance mutations and CD4 slopes in individuals experiencing sustained virological failure

    DEFF Research Database (Denmark)

    Schultze, Anna; Paredes, Roger; Sabin, Caroline


    mutations on CD4 slopes in patients undergoing episodes of viral failure. MATERIALS AND METHODS: Patients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test...

  13. New-onset ascites as a manifestation of virologic relapse in patients with hepatitis C cirrhosis

    Directory of Open Access Journals (Sweden)

    Chua DL


    Full Text Available Deborah Lim Chua, Thomas Hahambis, Samuel H SigalDivision of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, NY, USABackground: Chronic hepatitis C is the most common cause of cirrhosis in industrialized countries. Successful treatment of chronic hepatitis C in patients with advanced fibrosis or cirrhosis has significant benefits, including improvements in inflammation, fibrosis, and portal hypertension, with prevention of esophageal varices and clinical decompensation.Case: In this report, we present two patients with well-compensated hepatitis C cirrhosis who achieved an end-of-treatment response on a direct-acting antiviral therapy-based triple regimen for hepatitis C virus, but subsequently presented with new-onset ascites associated with virologic relapse.Conclusion: We propose that the development of ascites in this setting is due to the adverse impact of inflammation of the virologic relapse on portal hypertension. Our observation that ascites formation can be a manifestation of virologic relapse has potentially important clinical implications, as it highlights not only the importance of close monitoring of cirrhotic patients after achieving end-of-treatment response but also the impact of active inflammation on the severity of portal hypertension.Keywords: chronic hepatitis C, cirrhosis, virologic relapse, portal hypertension, ascites

  14. Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Shepherd, Leah; Ryom, Lene; Law, Matthew


    Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data fro...

  15. Comparison of HIV-1 genotypic resistance test interpretation systems in predicting virological outcomes over time

    NARCIS (Netherlands)

    D. Frentz (Dineke); C.A.B. Boucher (Charles); M. Assel (Matthias); A. de Luca (Andrea); M. Fabbiani (Massimiliano); F. Incardona (Francesca); P. Libin (Pieter); N. Manca (Nino); V. Müller (Viktor); B.O. Nualláin (Breanndán); R. Paredes (Roger); M. Prosperi (Mattia); E. Quiros-Roldan (Eugenia); L. Ruiz (Lidia); P.M.A. Sloot (Peter); C. Torti (Carlo); A.M. Vandamme (Anne Mieke); K. Laethem (Kristel); M. Zazzi (Maurizio); D.A.M.C. van de Vijver (David)


    textabstractBackground: Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks.

  16. Sustained virological response to antiviral therapy reduces mortality in HCV reinfection after liver transplantation. (United States)

    Picciotto, Francesco Paolo; Tritto, Giovanni; Lanza, Alfonso Galeota; Addario, Luigi; De Luca, Massimo; Di Costanzo, Giovan Giuseppe; Lampasi, Filippo; Tartaglione, Maria Teresa; Marsilia, Giuseppina Marino; Calise, Fulvio; Cuomo, Oreste; Ascione, Antonio


    HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis. Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting. Pegylated-interferon alpha-2b and ribavirin were administered at a dose of 1 microg/kg of bwt weekly and 600-800 mg/day. Planned duration of treatment was 24 or 48 weeks according to HCV genotype. Patients who failed to respond at week 24 were considered as non-responders. 61 patients were enrolled. According to intention-to-treat analysis, 44 (72%) patients were considered as treatment failure (31 non-responders, 4 relapsers, 9 dropout). Sustained virological response was achieved in 17 cases (28%). Genotype 2, higher doses of antivirals and absence of histological cirrhosis were predictors of sustained virological response. In the follow up, patients with sustained virological response had a significantly lower mortality compared to patients with treatment failure (chi2=6.9; P<0.01). Response rate to antiviral therapy in HCV reinfection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed. Sustained virological response improves patient survival.

  17. Writing the history of virology in the twentieth century: Discovery, disciplines, and conceptual change. (United States)

    Méthot, Pierre-Olivier


    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Trends of racial and ethnic disparities in virologic suppression among women in the HIV Outpatient Study, USA, 2010-2015.

    Directory of Open Access Journals (Sweden)

    Angelica Geter

    Full Text Available In the United States, women accounted for 19% of new HIV diagnoses in 2015 and were less likely to reach virologic suppression when compared to men. We assessed trends and disparities in virologic suppression among HIV-positive women to inform HIV treatment strategies. Data were from a prospective cohort of the HIV Outpatient Study and collected at nine United States HIV clinics. We included women aged ≥18 years, with ≥1 visit, who were prescribed antiretroviral therapy, and had ≥1 viral load test performed between 2010 and 2015. We defined virologic suppression as viral load <50 copies/mL and calculated adjusted prevalence ratios (aPR with 95% confidence intervals (CI for virologic suppression by race/ethnicity and year of measure. Generalized estimating equations were used for multivariable analyses to assess factors associated with virologic suppression. Among 809 women (median age = 44 years, 482 (60% were black, 177 (22% white, 150 (19% Hispanic/Latina. Virologic suppression was less prevalent among black women (73% compared with Hispanic/Latina women (83% and white women (91%. In multivariable analyses, not achieving virologic suppression was more likely among black women (aPR = 2.13; CI = 1.50-3.02 or Hispanic/Latina women (aPR = 1.66; CI = 1.08-2.56 compared with white women, and among women who attended public clinics (aPR = 1.42; CI = 1.07-1.87 compared with those who attended a private clinic. Between 2010 and 2015, virologic suppression among HIV-positive women increased from 68% to 83%, but racial/ethnic disparities persisted. Black and Hispanic/Latina women had significantly lower rates of virologic suppression than white women. Interventions targeting virologic suppression improvement among HIV-positive women of color, especially those who attend public clinics, are warranted.

  19. Adipose tissue lymphocytes: types and roles. (United States)

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C


    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  20. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M


    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  1. The cloning of T lymphocytes. (United States)

    Schwartz, R H


    A new era of cellular immunology is clearly at hand. It is now possible, with a little bit of effort, to isolate monoclonal populations of T cells specific for any given antigen. The implications o f this technological advance are enormous in terms of applications to basic research and clinical medicine. In this article the two basic approaches that have been used to clone T lymphocytes are outlined, the pros and cons of each technique discussed and examples are given of recent experiments which have exploited this technology to gain new insights into T-cell specificity. Copyright © 1982. Published by Elsevier B.V.

  2. Transient and persistent worsening renal function during hospitalization for acute heart failure. (United States)

    Krishnamoorthy, Arun; Greiner, Melissa A; Sharma, Puza P; DeVore, Adam D; Johnson, Katherine Waltman; Fonarow, Gregg C; Curtis, Lesley H; Hernandez, Adrian F


    Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF. We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Pearson marrow-pancreas syndrome with worsening cardiac function caused by pleiotropic rearrangement of mitochondrial DNA. (United States)

    Krauch, Gabriele; Wilichowski, Ekkehard; Schmidt, Klaus G; Mayatepek, Ertan


    Pearson marrow-pancreas syndrome is a usually fatal disorder that involves the hematopoietic system, exocrine pancreas, liver, kidneys, and often presents clinically with failure to thrive. We report a 5-year-old patient who developed, in addition to the typical features of Pearson syndrome, worsening cardiac function, mainly affecting the left ventricle. The latter finding is particularly interesting because cardiac involvement has not yet been regarded as a major feature of Pearson syndrome. The diagnosis was proved by the finding of so far undescribed pleioplasmatic rearrangement of mitochondrial (mt)DNA (loss of 5,630 bp, 70% deleted and duplicated mtDNA) in blood cells. Our report demonstrates that patients with Pearson syndrome may also have impaired cardiac function. Thus, Pearson syndrome should be considered in the differential diagnosis of patients with left ventricular dysfunction of unknown origin and other clinical findings suggestive of a mitochondrial disease. Copyright 2002 Wiley-Liss, Inc.

  4. Posttransplant Lymphoproliferative Disorder in a Patient with Worsening Ascites after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Harsh D. Patel


    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a spectrum of diseases that involves abnormal lymphoid and/or plasmacytic proliferation in patients with solid organ or hematopoietic cell transplantation. It is a condition with a low incidence of 3.5–4.3% in liver transplant (LT recipients. This case involves a 63-year-old male with history of LT for chronic HCV induced cirrhosis who presented with abdominal distension related to worsening ascites. Cytological ascitic fluid analysis revealed EBV (+ malignant cells without a malignant focal point on imaging. Diagnosis of monomorphic PTLD with primary effusion lymphoma-like morphology and immunophenotype was established. This case highlights the complexity in diagnosis, different diagnostic modalities, and rare clinical presentations of PTLD.

  5. Weather conditions may worsen symptoms in rheumatoid arthritis patients: the possible effect of temperature. (United States)

    Abasolo, Lydia; Tobías, Aurelio; Leon, Leticia; Carmona, Loreto; Fernandez-Rueda, Jose Luis; Rodriguez, Ana Belen; Fernandez-Gutierrez, Benjamin; Jover, Juan Angel


    Patients with rheumatoid arthritis (RA) complain that weather conditions aggravate their symptoms. We investigated the short-term effects of weather conditions on worsening of RA and determined possible seasonal fluctuations. We conducted a case-crossover study in Madrid, Spain. Daily cases of RA flares were collected from the emergency room of a tertiary level hospital between 2004 and 2007. 245 RA patients who visited the emergency room 306 times due to RA related complaints as the main diagnostic reason were included in the study. Patients from 50 to 65 years old were 16% more likely to present a flare with lower mean temperatures. Our results support the belief that weather influences rheumatic pain in middle aged patients. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  6. Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats. (United States)

    Okponyia, Obiefuna C; McGraw, Matthew D; Dysart, Marilyn M; Garlick, Rhonda B; Rioux, Jacqueline S; Murphy, Angela L; Roe, Gates B; White, Carl W; Veress, Livia A


    Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD 58-67 ) in a whole-body exposure chamber, and given oxygen (0.8 Fi O 2 ) or air (0.21 Fi O 2 ) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.

  7. The right to health in the courts of Brazil: worsening health inequities? (United States)

    Ferraz, Octavio Luiz Motta


    This article analyzes the recent and growing phenomenon of right-to-health litigation in Brazil from the perspective of health equity. It argues that the prevailing model of litigation is likely worsening the country's already pronounced health inequities. The model is characterized by a prevalence of individualized claims demanding curative medical treatment (most often drugs) and by a high success rate for the litigant. Both elements are largely a consequence of the way Brazilian judges have interpreted the scope of the right to health recognized in Article 6 and Article 196 of the Brazilian constitution, that is, as an entitlement of individuals to the satiSfaction of all their health needs with the most advanced treatment available, irrespective of its costs. Given that resources are always scarce in relation to the health needs of the population as a whole, this interpretation can only be sustained at the expense of universality, that is, so long as only a part of the population is granted this unlimited right at any given time. The individuals and (less often) groups who manage to access the judiciary and realize this right are therefore privileged over the rest of the population. This is potentially detrimental to health equity because the criterion for privileging litigants over the rest of the population is not based on any conception of need or justice but purely on their ability to access the judiciary, something that only a minority of citizens possess. This paper examines studies that are beginning to confirm that a majority of right-to-health litigants come from social groups that are already considerably advantaged in terms of all socioeconomic indicators, including health conditions. It is a plausible assumption that the model of right-to-health litigation currently prevalent in Brazil is likely worsening health inequities.

  8. Immuno-Virological Discordance and the Risk of NonAIDS and AIDS Events in a Large Observational Cohort of HIV-Patients in Europe

    DEFF Research Database (Denmark)

    Zoufaly, Alexander; Cozzi-Lepri, Alessandro; Reekie, Joanne


    The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated.......The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated....

  9. A history of plant virology. Mendelian genetics and resistance of plants to viruses. (United States)

    Pennazio, S; Roggero, P; Conti, M


    Virology was borne at the end of the nineteenth century, some years before the re-discovery of the so-called "Mendel's Laws". The rapid development of genetics was helpful to horticulturists and plant pathologists to produce hybrids of important cropping species resistant to several virus diseases. The concepts of Mendelian genetics were applied to plant virology by Francis Oliver Holmes, an American scientist who must be considered a pioneer in several fields of modern plant virology. During the Thirties, Holmes studied in particular the hypersensitive response of solanaceous plants to TMV and discovered the N dominant gene of tobacco hypersensitive to this virus. After the Second World War, the theoretic and practical support given by geneticists assisted plant virologists in better understanding the mechanism of inheritance of the character "resistance". The major problems posed by breeding for plant resistance were detected and critically discussed in several reviews published between the Fifties and the Sixties. These results, together with the discovery of the genetic functions of RNA virus raised interest on the possible relations between viral and plant genes. This fundamental subject saw the entry into the virological scene of molecular genetics, and in 1970 the Russian virologist Joseph Atabekov introduced host specificity to viruses as a central point of plant virology. From the mid 1980s, this point attracted the interest of several virologists, and many results led to several theoretic models of genetic interactions between plant and virus products. In the last fifteen years, the introduction of transgenic plants has given a remarkable contribution to the question of host specificity, which, however, still awaits a general explanation.

  10. The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory. (United States)

    Cannell, M Brad; Bouldin, Erin D; Teigen, Kari; Akhtar, Wajiha Z; Andresen, Elena M


    Research has demonstrated a clear association between cognitive decline and non-cognitive disability; however, all of these studies focus on disability as a correlate or result of some level of cognitive impairment or dysfunction. The relationship between disability and cognition is likely a complex one, that is currently incompletely described in the literature. Our objective was to estimate the prevalence of long-term, non-cognitive disability using a population-representative sample of adults aged 18 and older, and then estimate the association between long-term, non-cognitive disability and self-reported worsening memory. Using the 2009 Florida Behavioral Risk Factor Surveillance System (BRFSS), we measured the relationship between non-cognitive disability and worsening memory using multivariable logistic regression analysis weighted to account for the complex sampling design of the BRFSS. We also estimated the adjusted odds of worsening memory by disability severity, classified according to the types of assistance needed. Approximately 18% (95% confidence interval = (16%, 19%)) of Floridians were living with a long-term, non-cognitive disability in 2009. Among adults with no disability during or prior to the last year, only 5% reported worsening memory. The proportion of Floridians reporting worsening memory increases with increasing severity of disability-related limitations. In a multivariable logistic regression model, odds of worsening memory increased significantly with severity of disability-related limitations. These results highlight the association between non-cognitive disability and subsequent increased odds of worsening memory, independent of several other known risk factors, and a dose-response association with disability-related limitations. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Lymphocyte dynamics in healthy and lymphopenic conditions

    NARCIS (Netherlands)

    Hoeven, V. van


    By a balance of cell production and cell loss, B-cell and T-cell populations are generally maintained at a relatively stable size throughout life. Following lymphocyte-depleting therapies however, for example for the treatment of hematological malignancies, reconstitution of some lymphocyte subsets

  12. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth


    AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  13. Illness Representations of HIV Positive Patients Are Associated with Virologic Success. (United States)

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


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

  14. Virological outcomes of antiretroviral therapy in Zomba central prison, Malawi; a cross-sectional study. (United States)

    Mpawa, Happy; Kwekwesa, Aunex; Amberbir, Alemayehu; Garone, Daniela; Divala, Oscar H; Kawalazira, Gift; van Schoor, Vanessa; Ndindi, Henry; van Oosterhout, Joep J


    Antiretroviral therapy (ART) outcomes that include viral suppression rates are rarely reported among African prison populations. Prisoners deal with specific challenges concerning adherence to ART. We aimed to describe virological outcomes of ART in a large prison in Malawi. A cross-sectional study of ART outcomes was conducted at the Zomba Central Prison HIV clinic, Malawi, following the introduction of routine viral load monitoring. All prisoners on ART for at least 6 months were eligible for a viral load test. Patients with ≥1,000 copies/ml received adherence support for 3 months, after which a second VL sample was taken. Patients with ≥5,000 copies/ml on the second sample had virological failure and started 2nd line ART. We describe demographics and patient characteristics and report prevalence of potential- and documented virological failure. In the potential virological failure rate, those who could not be sampled after 3 months adherence support are included as virological failures. Logistic regression analysis was used to determine factors associated with potential ART failure. Viral load testing was started at the end of 2014, when 1054 patients had ever registered on ART. Of those, 501 (47.5%) had transferred out to another clinic, 96 (9.1%) had died, 11 defaulted (1.0%) and 3 (0.3%) stopped ART. Of 443 (42.0%) remaining alive in care, an estimated 322 prisoners were on ART >6 months, of whom 262 (81.4%) were sampled. Their median age was 35 years (IQR 31-40) and 257 (98.1%) were male. Self-reported adherence was good in 258 (98.5%). The rate of potential ART failure was 8.0%, documented ART failure was 4.6% and documented HIV suppression 95.0%. No patient characteristics were independently associated with potential ART failure, possibly due to low numbers with this outcome. Good virological suppression rates can be achieved among Malawian prisoners on ART, under challenging circumstances.

  15. Acute coronary syndrome and acute kidney injury: role of inflammation in worsening renal function. (United States)

    Ortega-Hernández, Jorge; Springall, Rashidi; Sánchez-Muñoz, Fausto; Arana-Martinez, Julio-C; González-Pacheco, Héctor; Bojalil, Rafael


    Acute Kidney Injury (AKI), a common complication of acute coronary syndromes (ACS), is associated with higher mortality and longer hospital stays. The role of cytokines and other mediators is unknown in AKI induced by an ACS (ACS-AKI), leading to several unanswered questions. The worsening of renal function is usually seen as a dichotomous phenomenon instead of a dynamic change, so evaluating changes of the renal function in time may provide valuable information in the ACS-AKI setting. The aim of this study was to explore inflammatory factors associated to de novo kidney injury induced by de novo cardiac injury secondary to ACS. One hundred four consecutive patients with ACS were initially included on the time of admission to the Coronary Unit of the Instituto Nacional de Cardiología in Mexico City, from February to May 2016, before any invasive procedure, imaging study, diuretic or anti-platelet therapy. White blood count, hemoglobin, NT-ProBNP, troponin I, C-reactive protein, albumin, glucose, Na + , K + , blood urea nitrogen (BUN), total cholesterol, HDL, LDL, triglycerides, creatinine (Cr), endothelin-1 (ET-1), leukotriene-B4, matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinases-1, resolvin-D1 (RvD1), lipoxin-A4 (LXA4), interleukin-1β, -6, -8, and -10 were measured. We finally enrolled 78 patients, and subsequently we identified 15 patients with ACS-AKI. Correlations were obtained by a Spearman rank test. Low-rank regression, splines regressions, and also protein-protein/chemical interactions and pathways analyses networks were performed. Positive correlations of ΔCr were found with BUN, admission Cr, GRACE score, IL-1β, IL-6, NT-ProBNP and age, and negative correlations with systolic blood pressure, mean-BP, diastolic-BP and LxA4. In the regression analyses IL-10 and RvD1 had positive non-linear associations with ΔCr. ET-1 had also a positive association. Significant non-linear associations were seen with NT-proBNP, admission Cr, BUN

  16. Effect of sow vaccination against porcine circovirus type 2 (PCV2) on virological profiles in herds with or without PCV2 systemic disease. (United States)

    Lopez-Rodriguez, Alfonso; Dewulf, Jeroen; Meyns, Tom; Del-Pozo-Sacristán, Rubén; Andreoni, Christine; Goubier, Anne; Chapat, Ludivine; Charreyre, Catherine; Joisel, François; Maes, Dominiek


    We investigated porcine circovirus type 2 (PCV2) virological profiles in herds affected (PCVAD-AH, n = 5) or non-affected (PCVAD-NAH, n = 4) by PCV2-associated diseases (PCVAD), before and after 1 y of PCV2 gilt and sow vaccination. Fresh feces from the floor (5 pens/age/farm) and 5 blood samples (1/pen) were collected at 3, 9, 15, 21 wk. Individual feces and blood samples were collected from 5 gilts and 15 sows. Sampling was repeated 1 y after vaccination. Quantitative PCR on feces, PCV2 antibodies in blood serum and cell-mediated immunity were investigated. Before vaccination, pigs of PCVAD-AH had higher viral load in feces (9 and 15 wk), lower IgG and higher IgM (3 wk) and lower lymphocyte counts (9 and 15 wk) suggesting immunosuppression. Vaccination reduced viral load in growers, increased IgG (3 wk) suggesting improved maternal immunity, reduced IgM (3 wk), increased total antibody titers in sows and increased CD79a cells in the pigs.

  17. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez


    Full Text Available Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS and tumor flare reaction (TFR, that make its management different from other hematologic malignancies.

  18. Worsening heart failure in 'real-world' clinical practice: predictors and prognostic impact. (United States)

    AlFaleh, Hussam; Elasfar, Abdelfatah A; Ullah, Anhar; AlHabib, Khalid F; Hersi, Ahmad; Mimish, Layth; Almasood, Ali; Al Ghamdi, Saleh; Ghabashi, Abdullah; Malik, Asif; Hussein, Gamal A; Al-Murayeh, Mushabab; Abuosa, Ahmed; Al Habeeb, Waleed; Kashour, Tarek


    The aim of this study was to compare the clinical features, predictors, and clinical outcomes of patients hospitalized with acute heart failure (AHF), with and without worsening heart failure (WHF). We used data from a multicentre prospective registry of AHF patients created in Saudi Arabia. WHF was defined as recurrence of heart failure symptoms or signs-with or without cardiogenic shock. In-hospital short- and long-term outcomes, as well as predictors of WHF are described. Of the 2609 AHF patients enrolled, 33.8% developed WHF. WHF patients were more likely to have a history of heart failure and ischaemic heart disease. Use of intravenous vasodilators, inotropic agents, furosemide infusions, and discharge beta-blockers was significantly higher in WHF patients, while use of discharge ACE inhibitors was higher in patients without WHF. Length of hospital stay was significantly longer for WHF patients than for those without WHF [median (interquartile range) 13 (14) vs. 7 (7) days, P world clinical practice, WHF during hospitalization for AHF is a strong predictor for short- and intermediate-term mortality, and a cause for longer hospital stays. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  19. Only adding stationary storage to vaccine supply chains may create and worsen transport bottlenecks. (United States)

    Haidari, Leila A; Connor, Diana L; Wateska, Angela R; Brown, Shawn T; Mueller, Leslie E; Norman, Bryan A; Schmitz, Michelle M; Paul, Proma; Rajgopal, Jayant; Welling, Joel S; Leonard, Jim; Claypool, Erin G; Weng, Yu-Ting; Chen, Sheng-I; Lee, Bruce Y


    Although vaccine supply chains in many countries require additional stationary storage and transport capacity to meet current and future needs, international donors tend to donate stationary storage devices far more often than transport equipment. To investigate the impact of only adding stationary storage equipment on the capacity requirements of transport devices and vehicles, we used HERMES (Highly Extensible Resource for Modeling Supply Chains) to construct a discrete event simulation model of the Niger vaccine supply chain. We measured the transport capacity requirement for each mode of transport used in the Niger vaccine cold chain, both before and after adding cold rooms and refrigerators to relieve all stationary storage constraints in the system. With the addition of necessary stationary storage, the average transport capacity requirement increased from 88% to 144% for cold trucks, from 101% to 197% for pickup trucks, and from 366% to 420% for vaccine carriers. Therefore, adding stationary storage alone may worsen or create new transport bottlenecks as more vaccines flow through the system, preventing many vaccines from reaching their target populations. Dynamic modeling can reveal such relationships between stationary storage capacity and transport constraints.

  20. Outcome in acute heart failure: prognostic value of acute kidney injury and worsening renal function. (United States)

    Berra, Gregory; Garin, Nicolas; Stirnemann, Jérôme; Jannot, Anne-Sophie; Martin, Pierre-Yves; Perrier, Arnaud; Carballo, Sebastian


    The prognostic value of worsening renal function (WRF) in acute heart failure is debated. Moreover, it is not clear if the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in this context is detrimental. In a retrospective cohort study of 646 patients hospitalized for acute heart failure, the risk of death or readmission associated with acute kidney injury (AKI) present at admission, WRF during the 1st 7 days, and up-titration of ACEI/ARB were analyzed in a Cox proportional hazards model. AKI, WRF, hemoglobin concentration, ACEI/ARB up-titration, and use of loop diuretics before admission were significantly associated with the primary outcome in univariate analysis. In a multivariate model, the association remained significant for AKI (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13-1.47; P = .0002), WRF (HR 1.24, 95% CI 1.06-1.45; P = .0059), and ACEI/ARB up-titration (HR 0.79, 95% CI 0.64-0.97; P = .026). There was no excess mortality in patients with ACEI/ARB up-titration despite WRF. Both AKI and WRF are strongly associated with poor outcome in patients hospitalized for acute heart failure. ACEI/ARB up-titration seems to be protective. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Hypoxia Worsens Affective Responses and Feeling of Fatigue During Prolonged Bed Rest

    Directory of Open Access Journals (Sweden)

    Nektarios A. M. Stavrou


    Full Text Available Previous research, although limited, suggests that both hypoxia and bed rest influence psychological responses by exaggerating negative psychological responses and attenuating positive emotions. The present study investigated the effect of a 21-day prolonged exposure to normobaric hypoxia and bed rest on affective responses and fatigue. Eleven healthy participants underwent three 21-day interventions using a cross-over design: (1 normobaric hypoxic ambulatory confinement (HAMB, (2 normobaric hypoxic bed rest (HBR and (3 normoxic bed rest (NBR. Affective and fatigue responses were investigated using the Activation Deactivation Adjective Check List, and the Multidimensional Fatigue Inventory, which were completed before (Pre, during (Day 7, Day 14, and Day 21 and after (Post the interventions. The most negative psychological profile appeared during the HBR intervention. Specifically, tiredness, tension, general and physical fatigue significantly increased on days 7, 14, and 21, as well as at Post. After the HBR intervention, general and physical fatigue remained higher compared to Pre values. Additionally, a deterioration of psychological responses was also noted following HAMB and NBR. In particular, both hypoxia and BR per se induced subjective fatigue and negative affective responses. BR seems to exert a moderate negative effect on the sensation of fatigue, whereas exercise attenuates the negative effects of hypoxia as noted during the HAMB condition. In conclusion, our data suggest that the addition of hypoxia to bed rest-induced inactivity significantly worsens affective responses and feeling of fatigue.

  2. Desiccating Stress-Induced MMP Production and Activity Worsens Wound Healing in Alkali-Burned Corneas (United States)

    Bian, Fang; Pelegrino, Flavia S. A.; Pflugfelder, Stephen C.; Volpe, Eugene A.; Li, De-Quan; de Paiva, Cintia S.


    Purpose To evaluate the effects of dry eye on ocular surface protease activity and sight threatening corneal complications following ocular surface chemical injury. Methods C57BL/6 mice were subjected to unilateral alkali burn (AB) with or without concomitant dry eye for 2 or 5 days. Mice were observed daily for appearance of corneal perforation. Whole corneas were harvested and lysed for RNA extraction. Quantitative real-time PCR was performed to measure expression of inflammation cytokines, matrix metalloproteinases (MMP). Matrix metalloproteinase–9 activity, gelatinase activity, and myeloperoxidase (MPO) activity were evaluated in corneal lysates. Presence of infiltrating neutrophils was evaluated by immunohistochemistry and flow cytometry. Results Eyes subjected to the combined model of AB and dry eye (CM) had 20% sterile corneal perforation rate as soon as 1 day after the initial injury, which increased to 35% by 5 days, delayed wound closure and increased corneal opacity. Increased levels of IL-1β, -6, and MMPs-1, -3, -8, -9, and -13, and chemokine (C-X-C motif) ligand 1 (CSCL1) transcripts were found after 2 days in CM compared with AB corneas. Increased MMP-1, -3, -9, and -13 immunoreactivity and gelatinolytic activity were seen in CM corneas compared with AB. Increased neutrophil infiltration and MPO activity was noted in the CM group compared with AB 2 days post injury. Conclusions Desiccating stress worsens outcome of ocular AB, creating a cytokine and protease storm with greater neutrophil infiltration, increasing the risk of corneal perforation. PMID:26225631

  3. Risk factors of virologic failure and slow response to art among HIV ...

    African Journals Online (AJOL)

    The virologic failure rates in this cohort were 43.8% after 6 months, 32.2% after 12 months, 28.8% after 18 months, and 24.0% after 24 months of first-line ART. Twelve (8.2%) of 146 children showed a slow response to ART: they initially failed ART at 12 months, but had treatment success after 18 to 24 months. The rates of ...

  4. Young adults HIV-1 infected by vertical transmission in southern Brazil - Clinical, demographic, and virological features. (United States)

    Martin, Beatris M; Santos, Jucélia S; Scapinello, Fernanda V; Ribeiro, Clea El; Gomes-da-Silva, Monica M; Raboni, Sonia M


    Combination antiretroviral therapy promotes longer life expectancy, making it possible for perinatally HIV-infected patients to achieve adulthood. Past therapy was not always optimized, suggesting that virological and host features may also play a role in survival. The aim of this study is to describe characteristics of HIV disease progression associated with virological features in adolescents perinatally that were HIV infected. A case series was conducted including 81 patients that were in follow-up at Hospital de Clínicas/Universidade Federal do Paraná, Curitiba, Brazil. Venous blood was collected to conduct tropism and viral subtype assays. The median age was 19 years old (interquartile range 18-21), and a majority of patients were female (54.3%). Viral subtype was obtained for 66 (82%) patients, and subtypes B and C were found in 34% and 59%, respectively. Tropism assay was conducted in 55 (67%) patients: 71% were R5 and 29% X4. Distribution of viral tropism and subtype shows a significant association of subtype C with R5 tropism. Subtype C is more prevalent in southern Brazil and also in the population infected with HIV by vertical transmission. Both R5 tropism and subtype C are associated with slower progression to AIDS. The survival of these patients may be related to virological features present in a benign pattern of disease progression.

  5. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052. (United States)

    Palumbo, Philip J; Wilson, Ethan A; Piwowar-Manning, Estelle; McCauley, Marybeth; Gamble, Theresa; Kumwenda, Newton; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James G; Hosseinipour, Mina C; Melo, Marineide G; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H; Fogel, Jessica M


    Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

  6. Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Ruiz, Lidia; Cozzi-Lepri, Alessandro


    ) with genotypic resistance test results available at time of initiation (baseline). Virological failure was defined as two consecutive values > 500 copies/ml after starting the regimen. Cox models were used to investigate time to virological failure (the first of two values). RESULTS: A total of 759 patients were......% NVP, 60% EFV, P = 0.011); 287 (74%) NVP and 168 (45%) EFV patients experienced virological failure after treatment initiation, P ... drug resistance (measured by Rega), the relative hazards (EFV versus NVP) of virological failure was 0.50, 95% confidence interval: 0.39-0.65, P failure, comparable levels of NNRTI resistance were detected. The K103N mutation emerged more in patients failing EFV and Y181...

  7. Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets

    NARCIS (Netherlands)

    Bienczak, A.; Denti, P.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Gibb, D.M.; Burger, D.M.; Walker, A.S.; McIlleron, H.


    BACKGROUND: Nevirapine is the only nonnucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose-combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African

  8. Gender-specific risk factors for virologic failure in KwaZulu-Natal: automobile ownership and financial insecurity. (United States)

    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


    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 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.

  9. Cryptococcal meningitis accompanying lymphocytic inflammation predominantly in cerebral deep white matter: a possible manifestation of immune reconstitution inflammatory syndrome. (United States)

    Kuwahara, Hiroya; Tsuchiya, Kuniaki; Kobayashi, Zen; Inaba, Akira; Akiyama, Haruhiko; Mizusawa, Hidehiro


    Cryptococcal meningitis is rarely complicated by immune-mediated leukoencephalopathy, but the precise pathomechanism is uncertain. A 72-year-old Japanese man treated with prednisolone for Sweet disease developed a subacute progression of meningitis, which was considered as neuro-Sweet disease. A treatment by methylprednisolone rapidly improved CSF findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the treatment. The patient developed cryptococcal meningitis and MRI showed abnormal intensities predominantly in the cerebral deep white matter along with the recovery of lymphocyte numbers in the blood, which resulted in death. A postmortem examination of the brain revealed degenerative lesions, especially at the cerebral white matter and cortex adjacent to the leptomeninges abundantly infiltrated by Cryptococcus neoformans. In the affected cerebral deep white matter, perivascular infiltration of lymphocytes was prominent in coexistence with reactive astrocytes and vascular proliferation, but these findings were not observed in the subcortical and cortical lesions. Cryptococcus neoformans was not present within the brain parenchyma. This is the first report of a case suggesting that cryptococcal meningitis can accompany lymphocytic inflammation predominantly in cerebral deep white matter as a possible manifestation of immune reconstitution inflammatory syndrome. © 2013 Japanese Society of Neuropathology.

  10. Lymphocytic Pleural Effusion in Acute Melioidosis

    Directory of Open Access Journals (Sweden)

    Kuo-Mou Chung


    Full Text Available An endemic outbreak of melioidosis developed in southern Taiwan following a flood caused by a typhoon in July 2005. A total of 27 patients were diagnosed with the acute and indigenous form of pulmonary melioidosis. Parapneumonic pleural effusions were noted on chest X-rays in six patients. Thoracentesis was done in three patients and all revealed lymphocyte predominance in differential cell count. Burkholderia pseudomallei was isolated in the pleural effusion in one of them. All three patients survived after antibiotic treatment. Lymphocytic pleural effusion is generally seen in tuberculosis or malignancy. However, our findings suggest that melioidosis should be considered in the differential diagnosis of lymphocytic pleural effusion.

  11. Trends of racial and ethnic disparities in virologic suppression among women in the HIV Outpatient Study, USA, 2010-2015 (United States)


    In the United States, women accounted for 19% of new HIV diagnoses in 2015 and were less likely to reach virologic suppression when compared to men. We assessed trends and disparities in virologic suppression among HIV-positive women to inform HIV treatment strategies. Data were from a prospective cohort of the HIV Outpatient Study and collected at nine United States HIV clinics. We included women aged ≥18 years, with ≥1 visit, who were prescribed antiretroviral therapy, and had ≥1 viral load test performed between 2010 and 2015. We defined virologic suppression as viral load women (median age = 44 years), 482 (60%) were black, 177 (22%) white, 150 (19%) Hispanic/Latina. Virologic suppression was less prevalent among black women (73%) compared with Hispanic/Latina women (83%) and white women (91%). In multivariable analyses, not achieving virologic suppression was more likely among black women (aPR = 2.13; CI = 1.50–3.02) or Hispanic/Latina women (aPR = 1.66; CI = 1.08–2.56) compared with white women, and among women who attended public clinics (aPR = 1.42; CI = 1.07–1.87) compared with those who attended a private clinic. Between 2010 and 2015, virologic suppression among HIV-positive women increased from 68% to 83%, but racial/ethnic disparities persisted. Black and Hispanic/Latina women had significantly lower rates of virologic suppression than white women. Interventions targeting virologic suppression improvement among HIV-positive women of color, especially those who attend public clinics, are warranted. PMID:29293632

  12. Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study

    DEFF Research Database (Denmark)

    Castillo-Mancilla, Jose R; Phillips, Andrew N; Neaton, James D


    Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated with heightened inflammation in cohort studies, even among people with virologic suppression. We aimed to evaluate this association among participants in the Strategies for Management of Antiretroviral Therapy (SMAR...... suboptimal vs 100% adherence, respectively. These findings confirm previous observations and support the hypothesis that suboptimal ART adherence, even in the context of virologic suppression, may have significant biological consequences. number NCT00027352....

  13. Partial meniscectomy is associated with increased risk of incident radiographic osteoarthritis and worsening cartilage damage in the following year

    Energy Technology Data Exchange (ETDEWEB)

    Roemer, Frank W. [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Kwoh, C.K. [University of Arizona Arthritis Center and University of Arizona College of Medicine, Tucson, AZ (United States); Hannon, Michael J.; Grago, Jason [University of Pittsburgh School of Medicine, Division of Rheumatology and Clinical Immunology, Pittsburgh, PA (United States); Hunter, David J. [University of Sydney, Department of Rheumatology, Royal North Shore Hospital and Kolling Institute, St Leonards (Australia); Eckstein, Felix [Paracelsus Medical University, Institute of Anatomy, Salzburg (Austria); Boudreau, Robert M. [University of Pittsburgh Graduate School of Public Health, Department of Epidemiology, Pittsburgh, PA (United States); Englund, Martin [Lund University, Clinical Epidemiology Unit, Orthopaedics, Department of Clinical Sciences Lund, Lund (Sweden); Guermazi, Ali [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States)


    To assess whether partial meniscectomy is associated with increased risk of radiographic osteoarthritis (ROA) and worsening cartilage damage in the following year. We studied 355 knees from the Osteoarthritis Initiative that developed ROA (Kellgren-Lawrence grade ≥ 2), which were matched with control knees. The MR images were assessed using the semi-quantitative MOAKS system. Conditional logistic regression was applied to estimate risk of incident ROA. Logistic regression was used to assess the risk of worsening cartilage damage in knees with partial meniscectomy that developed ROA. In the group with incident ROA, 4.4 % underwent partial meniscectomy during the year prior to the case-defining visit, compared with none of the knees that did not develop ROA. All (n = 31) knees that had partial meniscectomy and 58.9 % (n = 165) of the knees with prevalent meniscal damage developed ROA (OR = 2.51, 95 % CI [1.73, 3.64]). In knees that developed ROA, partial meniscectomy was associated with an increased risk of worsening cartilage damage (OR = 4.51, 95 % CI [1.53, 13.33]). The probability of having had partial meniscectomy was higher in knees that developed ROA. When looking only at knees that developed ROA, partial meniscectomy was associated with greater risk of worsening cartilage damage. (orig.)

  14. Ophthalmic and clinical factors that predict four-year development and worsening of diabetic retinopathy in type 1 diabetes. (United States)

    Srinivasan, Sangeetha; Dehghani, Cirous; Pritchard, Nicola; Edwards, Katie; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan


    To investigate the role of ophthalmic imaging markers - namely retinal thickness measures and corneal nerve morphology - in predicting four-year development and worsening of diabetic retinopathy (DR) in type 1 diabetes (T1DM). 126 eyes of 126 participants with T1DM were examined at baseline and after four years. Diabetic retinopathy (DR) was graded using the Early Treatment Diabetic Retinopathy Study scale. HbA 1c , nephropathy, neuropathy, cardiovascular factors, and retinal thickness using optical coherence tomography (OCT) and corneal nerve fiber length (CNFL) using corneal confocal microscopy at baseline were assessed by univariate and step-wise multiple logistic regression, and their diagnostic capabilities for single and combined measures. Four-year development of DR was 19% (13 of 68 without DR at baseline). Worsening of DR was seen in 43% (25 of 58 with DR at baseline). When adjusted for potential confounders, a lower CNFL (AUC=0.637, p=0.040, 64% sensitivity and 64% specificity at 14.9mm/mm 2 cut-off), higher triglycerides (AUC=0.669, p=0.012, 64% sensitivity, 62% specificity at 0.85mmol/L) and an elevated vibration threshold (AUC=0.708, p=0.002, 96% sensitivity, 40% specificity at 3.55Hz) were significant predictors for four-year worsening of DR. Reduced CNFL, elevated vibration perception threshold and higher triglycerides can predict future worsening of DR. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. IVIG Versus PLEX in the Treatment of Worsening Myasthenia Gravis: What is the Evidence?: A Critically Appraised Topic. (United States)

    Dhawan, Priya S; Goodman, Brent P; Harper, Charles M; Bosch, Peter E; Hoffman-Snyder, Charlene R; Wellik, Kay E; Wingerchuk, Dean M; Demaerschalk, Bart M


    Immune therapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are first line in the treatment of worsening myasthenia gravis. Although PLEX is favored in myasthenic crisis, IVIG is increasingly used in exacerbations due to cost and ease of administration. To review and critically assess current evidence on the effects of IVIG and PLEX on functional outcomes in patients with worsening myasthenia gravis. A structured critical appraisal was conducted on the objective topic. This included a creation of a structured question based on a clinical scenario, comprehensive literature search, selection of evidence for review, and critical appraisal of selected evidence. Evidence was summarized and commentary provided. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neuromuscular neurology. A single-blinded, randomized-controlled trial that compared IVIG and PLEX in 84 patients with worsening myasthenia gravis was selected for review. Primary outcome measure was functional status at 14 days after treatment, as assessed by the Quantitative Myasthenia Gravis Score. Change in Quantitative Myasthenia Gravis Score at day 14 for all subjects was 4.0, without statistically significant differences between IVIG and PLEX groups. IVIG and PLEX are equally effective in worsening myasthenia gravis. Treatment decisions may depend on several variables, including presence of respiratory distress, medical comorbidities, access to medication, and cost. PLEX will likely remain the treatment of choice in true myasthenic crisis.

  16. Worsening renal function definition is insufficient for evaluating acute renal failure in acute heart failure. (United States)

    Shirakabe, Akihiro; Hata, Noritake; Kobayashi, Nobuaki; Okazaki, Hirotake; Matsushita, Masato; Shibata, Yusaku; Nishigoori, Suguru; Uchiyama, Saori; Asai, Kuniya; Shimizu, Wataru


    Whether or not the definition of a worsening renal function (WRF) is adequate for the evaluation of acute renal failure in patients with acute heart failure is unclear. One thousand and eighty-three patients with acute heart failure were analysed. A WRF, indicated by a change in serum creatinine ≥0.3 mg/mL during the first 5 days, occurred in 360 patients while no-WRF, indicated by a change failure; n = 98). The patients were assigned to another set of four groups: no-WRF/no-AKI (n = 512), no-WRF/AKI (n = 211), WRF/no-AKI (n = 239), and WRF/AKI (n = 121). A multivariate logistic regression model found that no-WRF/AKI and WRF/AKI were independently associated with 365 day mortality (hazard ratio: 1.916; 95% confidence interval: 1.234-2.974 and hazard ratio: 3.622; 95% confidence interval: 2.332-5.624). Kaplan-Meier survival curves showed that the rate of any-cause death during 1 year was significantly poorer in the no-WRF/AKI and WRF/AKI groups than in the WRF/no-AKI and no-WRF/no-AKI groups and in Class I and Class F than in Class R and the no-AKI group. The presence of AKI on admission, especially Class I and Class F status, is associated with a poor prognosis despite the lack of a WRF within the first 5 days. The prognostic ability of AKI on admission may be superior to WRF within the first 5 days. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  17. Predicting fibrosis worsening in obese patients with NASH through parenchymal fibronectin, HOMA-IR, and hypertension. (United States)

    Sorrentino, Paolo; Terracciano, Luigi; D'Angelo, Salvatore; Ferbo, Umberto; Bracigliano, Alessandra; Vecchione, Raffaela


    Few published studies have examined the results obtained from repeat liver biopsies in obese patients with nonalcoholic fatty liver disease (NAFLD). The progressive form of this disease may be largely limited to a subgroup of NAFLD patients with nonalcoholic steatohepatitis (NASH). The presence of intralobular fibronectin (Fn) and other variables was investigated in relation to subsequent fibrosis progression. In this prospective study, 271 obese patients admitted to the hospital with NAFLD and abnormal liver enzymes were scheduled to undergo a repeat liver biopsy at least 5 years after the initial biopsy. After excluding cirrhotic patients, basal biopsy specimens obtained from patients who underwent a second liver biopsy were stained with antibodies against Fn. The progression of fibrosis in the follow-up sample was correlated with the amount of Fn and other clinicopathological variables. We obtained a second liver biopsy from 149 patients after a median time of 6.4 years. Of these, 132 showed suitable Fn staining for semi-quantitative assessments. In all, 44 out of 83 patients (53%) with basal NASH showed fibrosis progression by at least one stage in the second liver biopsy. The amount of Fn (odds ratio=14.1; PHOMA-IR) scores (>8, odds ratio=1.9; P=0.004) were independent predictive factors of worsening fibrosis. A semi-quantitative assessment of the amount of parenchymal Fn present at an early stage in obese patients with NASH is valuable for predicting the progression of fibrosis. Similarly, lobular Fn deposition may be a sensitive and early indicator of active fibrogenetic processes in the liver. Hypertension and higher HOMA-IR scores are other clinical independent risk factors that predict the progression of fibrosis.

  18. Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice (United States)

    Trevino, Michelle B.; Mazur-Hart, David; Machida, Yui; King, Timothy; Nadler, Joseph; Galkina, Elena V.; Poddar, Arjun; Dutta, Sucharita


    Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, compared with Ad-GFP liver. Lipids commonly associated with hepatic lipotoxicity, diacylglycerol, and ceramides, were also increased in Ad-PLIN5 liver. The expression of genes in lipid metabolism regulated by peroxisome proliferator-activated receptor-α was reduced suggestive of slower mobilization of stored lipids in Ad-PLIN5 mice. However, the increase of hepatosteatosis by PLIN5 overexpression did not worsen glucose homeostasis. Rather, serum insulin levels were decreased, indicating better insulin sensitivity in Ad-PLIN5 mice. Moreover, genes associated with liver injury were unaltered in Ad-PLIN5 steatotic liver compared with Ad-GFP control. Phosphorylation of protein kinase B was increased in Ad-PLIN5-transduced AML12 hepatocyte despite of the promotion of fatty acid incorporation to triacylglycerol as well. Collectively, our data indicates that the increase in liver PLIN5 during hepatosteatosis drives further lipid accumulation but does not adversely affect hepatic health or insulin sensitivity. PMID:26296152

  19. Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis. (United States)

    Morales-Nebreda, Luisa I; Rogel, Micah R; Eisenberg, Jessica L; Hamill, Kevin J; Soberanes, Saul; Nigdelioglu, Recep; Chi, Monica; Cho, Takugo; Radigan, Kathryn A; Ridge, Karen M; Misharin, Alexander V; Woychek, Alex; Hopkinson, Susan; Perlman, Harris; Mutlu, Gokhan M; Pardo, Annie; Selman, Moises; Jones, Jonathan C R; Budinger, G R Scott


    Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the α3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the α3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-β was worse in mice deficient in α3 laminin in the lung. Taken together, our results suggest that the loss of α3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-β. Thus, we speculate that the loss of the normal basement membrane organization of α3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression.

  20. Regional cortical thinning and cerebrospinal biomarkers predict worsening daily functioning across the Alzheimer disease spectrum (United States)

    Marshall, Gad A.; Lorius, Natacha; Locascio, Joseph J.; Hyman, Bradley T.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.


    Background Impairment in instrumental activities of daily living (IADL) heralds the transition from mild cognitive impairment (MCI) to dementia and is a major source of burden for both the patient and caregiver. Objective To investigate the relationship between IADL and regional cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers cross-sectionally and longitudinally in clinically normal (CN) elderly, MCI, and mild AD dementia subjects. Methods Two hundred and twenty nine CN, 395 MCI, and 188 AD dementia subjects participating in the Alzheimer's Disease Neuroimaging Initiative underwent baseline magnetic resonance imaging, baseline lumbar puncture, and clinical assessments, including the Functional Activities Questionnaire used to measure IADL, every 6 to 12 months up to 3 years. General linear regression and mixed effects models were employed. Results IADL impairment was associated with the interactions between lower inferior temporal cortical thickness and diagnosis (pdiagnosis (pdiagnosis (p=0.0002) at baseline (driven by AD dementia). Lower baseline supramarginal (p=0.02) and inferior temporal (p=0.05) cortical thickness, lower Aβ1-42 (p<0.0001), and greater total tau (t-tau) (p=0.02) were associated with greater rate of IADL impairment over time. Conclusions Temporal atrophy is associated with IADL impairment in mild AD dementia at baseline, while baseline parietal and temporal atrophy, lower CSF Aβ1-42, and greater t-tau predict worsening IADL impairment over time across the AD spectrum. These results emphasize the importance of assessing IADL at the stage of MCI and even at the transition from CN to MCI. PMID:24685624

  1. Trans-oral endoscopic partial adenoidectomy does not worsen the speech after cleft palate repair. (United States)

    Abdel-Aziz, Mosaad; Khalifa, Badawy; Shawky, Ahmed; Rashed, Mohammed; Naguib, Nader; Abdel-Hameed, Asmaa


    Adenoid hypertrophy may play a role in velopharyngeal closure especially in patients with palatal abnormality; adenoidectomy may lead to velopharyngeal insufficiency and hyper nasal speech. Patients with cleft palate even after repair should not undergo adenoidectomy unless absolutely needed, and in such situations, conservative or partial adenoidectomy is performed to avoid the occurrence of velopharyngeal insufficiency. Trans-oral endoscopic adenoidectomy enables the surgeon to inspect the velopharyngeal valve during the procedure. The aim of this study was to assess the effect of transoral endoscopic partial adenoidectomy on the speech of children with repaired cleft palate. Twenty children with repaired cleft palate underwent transoral endoscopic partial adenoidectomy to relieve their airway obstruction. The procedure was completely visualized with the use of a 70° 4mm nasal endoscope; the upper part of the adenoid was removed using adenoid curette and St. Claire Thompson forceps, while the lower part was retained to maintain the velopharyngeal competence. Preoperative and postoperative evaluation of speech was performed, subjectively by auditory perceptual assessment, and objectively by nasometric assessment. Speech was not adversely affected after surgery. The difference between preoperative and postoperative auditory perceptual assessment and nasalance scores for nasal and oral sentences was insignificant (p=0.231, 0.442, 0.118 respectively). Transoral endoscopic partial adenoidectomy is a safe method; it does not worsen the speech of repaired cleft palate patients. It enables the surgeon to strictly inspect the velopharyngeal valve during the procedure with better determination of the adenoidal part that may contribute in velopharyngeal closure. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  2. Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients. (United States)

    Lorenz, Georg; Steubl, Dominik; Kemmner, Stephan; Pasch, Andreas; Koch-Sembdner, Wilhelm; Pham, Dang; Haller, Bernhard; Bachmann, Quirin; Mayer, Christopher C; Wassertheurer, Siegfried; Angermann, Susanne; Lech, Maciej; Moog, Philipp; Bauer, Axel; Heemann, Uwe; Schmaderer, Christoph


    A novel in-vitro test (T 50 -test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. The association of longitudinal changes of T 50 with all-cause and cardiovascular mortality has not been investigated. We assessed T 50 in paired sera collected at baseline and at 24 months in 188 prevalent European HD patients from the ISAR cohort, most of whom were Caucasians. Patients were followed for another 19 [interquartile range: 11-37] months. Serum T 50 exhibited a significant decline between baseline and 24 months (246 ± 64 to 190 ± 68 minutes; p < 0.001). With serum Δ-phosphate showing the strongest independent association with declining T 50 (r = -0.39; p < 0.001) in multivariable linear regression. The rate of decline of T 50 over 24 months was a significant predictor of all-cause (HR = 1.51 per 1SD decline, 95% CI: 1.04 to 2.2; p = 0.03) and cardiovascular mortality (HR = 2.15; 95% CI: 1.15 to 3.97; p = 0.02) in Kaplan Meier and multivariable Cox-regression analysis, while cross-sectional T 50 at inclusion and 24 months were not. Worsening serum calcification propensity was an independent predictor of mortality in this small cohort of prevalent HD patients. Prospective larger scaled studies are needed to assess the value of calcification propensity as a longitudinal parameter for risk stratification and monitoring of therapeutic interventions.

  3. Smoking and worsening disability in multiple sclerosis: A meta-analysis. (United States)

    Heydarpour, P; Manouchehrinia, A; Beiki, O; Mousavi, S E; Abdolalizadeh, A; -Lakeh, M Moradi; Sahraian, M A


    Multiple sclerosis (MS) is a chronic demyelinating disorder affecting young adults. Environmental factors and lifestyle behaviors are pivotal in MS pathophysiology. Smoking has been considered as an important risk factor in MS. Various recent studies have been conducted to measure the role of smoking on worsening disability in patients with MS, thus we intended to systematically assess effect of smoking on evolution of disability in this study. We queried MEDLINE, EMBASE and Cochrane Library with following keywords "Multiple Sclerosis, Smoking, Tobacco Use, Disability" on December 1st 2016. Original articles were included when smoking history was mentioned, disability was measured via expanded disability status scale (EDSS) or multiple sclerosis severity score (MSSS). Studies with insufficient outcome data, non-human, or in other languages than English were excluded. Through literature review after duplicate removals, 268 articles were retrieved. A total of 56 articles were screened and 15 articles were assessed for eligibility, finally, eleven articles were included in this systematic review and meta-analysis. Ever smoking was significantly associated with increased EDSS (standardized mean difference (SMD) = 0.15, 95% CI = 0.01-0.28), but had no significant association with risk of reaching EDSS 4 (HR = 1.24, 95% CI = 0.89-1.72) or EDSS 6 (HR = 1.17, 95% CI = 0.88-1.57). Smoking had no effect on MSSS (SMD = 0.14, 95% CI = -0.04-0.32) or T2 lesion volume (SMD = 0.07, 95% CI = -0.08-0.22). This meta-analysis showed smoking increased EDSS, insignificant findings were possibly due to the small number of studies, significant differences in methodologies, and variations in reporting of disability outcomes. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease. (United States)

    Hacker, Mallory L; Tonascia, James; Turchan, Maxim; Currie, Amanda; Heusinkveld, Lauren; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Wang, Lily; Shi, Yaping; Shade, David M; Sternberg, Alice L; Drye, Lea T; Charles, David


    The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Frequency of worsening liver function in severe dengue hepatitis patients receiving paracetamol: A retrospective analysis of hospital data

    International Nuclear Information System (INIS)

    Syed, A.A.; Aslam, F.; Hakeem, H.; Siddiqui, F.; Nasir, N.


    To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. Methods: This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants' demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. Results: Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. Conclusion: The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low. (author)

  6. Lymphocytic Meningitis in Patients with Sympathetic Ophthalmia. (United States)

    Goudot, Mathilde; Groh, Matthieu; Salah, Sawsen; Monnet, Dominique; Blanche, Philippe; Brézin, Antoine P


    This study aimed at reporting lymphocytic meningitis in patients diagnosed with sympathetic ophthalmia (SO). In this single-center retrospective observational case series, we reviewed cases diagnosed with SO. We analyzed the patients' inciting injuries, the characteristics of uveitis and the cerebrospinal fluid (CSF) analyses. Nine patients were diagnosed with SO and CSF analyses were available in all cases. Four cases had lymphocytic pleocytosis, 3 of which showed marked CSF inflammation with more than 300 lymphocytes/mm 3 . The inciting event in these 3 patients was a globe perforation injury, whereas 4 patients without meningitis had SO following a surgical intervention. In this case series of patients with SO, lymphocytic meningitis was a common finding. The prevalence of meningitis in patients with SO and its value for the diagnosis of the disease needs to be further studied.

  7. Treatment Options by Stage (Chronic Lymphocytic Leukemia) (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  8. Treatment Option Overview (Chronic Lymphocytic Leukemia) (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  9. General Information about Chronic Lymphocytic Leukemia (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  10. Chronic Lymphocytic Leukemia: Current Concepts. (United States)

    Yu, Eun-Mi; Kittai, Adam; Tabbara, Imad A


    Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, and while in early, asymptomatic stages treatment is not indicated, the threat to the quality of life and increased mortality of patients posed by more advanced-stage disease necessitate therapeutic intervention. Guidelines of when and how to treat are not well-established because CLL is a disease of the elderly and it is important to balance preservation of functional status and control of the disease. Advances in molecular and genetic profiling has led to the ability to identify sub-groups of patients with CLL whose disease may respond to selected therapy. This review discusses current standard therapies in the major sub-groups of CLL based on age and functional status, in both the front-line and relapsed/refractory settings. It also provides a concise review of novel agents that have shown considerable efficacy in CLL. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Chemotaxis of large granular lymphocytes

    International Nuclear Information System (INIS)

    Pohajdak, B.; Gomez, J.; Orr, F.W.; Khalil, N.; Talgoy, M.; Greenberg, A.H.


    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-β and colony-stimulating factor. Interleukin 2, tuftsin, platelet-derived growth factor, and fibronectin were inactive. Migratory responses were greater in Percoll fractions with the highest lytic activity and HNK-1 + cells. The chemotactic response to f-MLP, casein, and C5a was always greater when the chemoattractant was present in greater concentration in the lower compartment of the Boyden chamber. Optimum chemotaxis was observed after a 1 hr incubation that made use of 12 μm nitrocellulose filters. LGL exhibited a high degree of nondirected locomotion when allowed to migrate for longer periods (> 2 hr), and when cultured in vitro for 24 to 72 hr in the presence or absence of IL 2 containing phytohemagluttinin-conditioned medium. LGL chemotaxis to f-MLP could be inhibited in a dose-dependent manner by the inactive structural analog CBZ-phe-met, and the RNK tumor line specifically bound f-ML( 3 H)P, suggesting that LGL bear receptors for the chemotactic peptide

  12. How T lymphocytes see antigen (United States)

    Chakraborty, Arup K.


    Complex organisms, like humans, have an adaptive immune system that enables us to do battle with diverse pathogens. This flexible system can also go awry, and many diseases are the direct consequence of the adaptive immune system failing to discriminate between markers of self and non-self. The orchestrators of adaptive immunity are a class of cells called T lymphocytes (T cells). T cells recognize minute numbers of molecular signatures of pathogens, and T cell recognition of these molecular markers of non-self is both specific and degenerate. The specific (yet, cross-reactive), diverse, and self-tolerant T cell repertoire is designed in the thymus. I will describe how an approach that brings together theoretical and computational studies (rooted in statistical physics) with experiments (carried out by key collaborators) has allowed us to shed light on the mechanistic principles underlying how T cells respond to pathogens in a digital fashion (``on'' or ``off''), and how this molecular machinery coupled with frustration (a la spin glasses) plays a key role in designing the special properties of the T cell repertoire during development in the thymus.


    Directory of Open Access Journals (Sweden)

    E. V. Abakushina


    Full Text Available The major medical problem in the treatment of skin melanoma is improvement methods of treatment, increasing their effectiveness and safety. In this study, adoptive immunotherapy, using lymphocytes activated in vitro, was performed in 15 patients with metastatic melanoma. Evaluated the phenotype of peripheral blood lymphocytes and activation markers (HLA-DR, CD25, CD314, CD38, CD69 before and 3-4 weeks after immunotherapy. It is shown that for these patients is characterized by increasing the number of CD25+ and Treg lymphocytes in the bloodstream, which has not changed after immunotherapy. Adoptive immunotherapy in combination with chemotherapy resulted in a decrease of absolute number of lymphocyte, B- and T-lymphocytes, T helper cells, NKT-cells, CD314+ lymphocytes, CD38+ lymphocytes and immature T-lymphocytes (CD3+CD38+ (р < 0,05. However, there was a positive dynamic to increase the percentage of NK-cells to 32% and CD69+NK-cells to 21% and significant increase in expression of HLA-DR on all lymphocytes (p < 0.05. Adoptive immunotherapy characterized by the absence of side effects and can be recommended as accompanying to basic radiation and chemotherapy.

  14. Orbital involvement in chronic lymphocytic leukemia. (United States)

    Skinnider, L F; Romanchuk, K G


    In a 68-year-old man with chronic lymphocytic leukemia diagnosed on the basis of peripheral lymphocytosis, marked bilateral exophthalmos developed owing to massive orbital involvement by the disease. At the time there was no lymphadenopathy or evidence of organ infiltration. The response to radiotherapy was excellent. Orbital involvement is rare as an early clinical feature of chronic lymphocytic leukemia but should be considered in the differential diagnosis of bilateral exophthalmos in adults.

  15. Lymphocytic hypophysitis and hypothalamitis - a case report

    International Nuclear Information System (INIS)

    Stelmachowska, M.; Bolko, P.; Wasko, R.; Sowinski, J.; Kosinski, D.; Towpik, I.


    Lymphocytic hypophysitis is an unusual disorder that nearly exclusively affects women. We present a case of 69 year-old female patient who developed the symptoms of diabetes insipidus and partial insufficiency of the anterior pituitary gland. Magnetic resonance imaging of the brain revealed a mass involving the sella and suprasellar region. After exclusion of other causes of infiltrate in this region and due to evident reaction to glucocorticoid treatment the diagnosis of lymphocytic hypophisitis and hypothalamitis was established. (author)

  16. Morphometric model of lymphocyte as applied to scanning flow cytometry (United States)

    Loiko, Valery A.; Ruban, Gennady I.; Gritsai, Olga A.; Gruzdev, Alexey D.; Kosmacheva, Svetlana M.; Goncharova, Natalia V.; Miskevich, Alexander A.


    The peripheral blood lymphocytes of normal individuals are investigated by methods of specialized light microscopy. Lymphocytes as a whole and T-cell subpopulation are considered. Lymphocyte structure is characterized with reference to polarizing scanning flow cytometry. The lymphocyte and lymphocyte nucleus shapes are analyzed. Linear correlation dependence between sizes of lymphocyte and its nucleus is indicated. A morphometric model of a lymphocyte is constructed using the obtained data. The findings can be used, for instance, as input parameters to solve the direct and inverse light-scattering problems of turbidimetry, nephelometry, and flow cytometry.

  17. Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis. (United States)

    Frost, Adaani E; Badesch, David B; Miller, Dave P; Benza, Raymond L; Meltzer, Leslie A; McGoon, Michael D


    Time to clinical worsening has been proposed as a primary end point in clinical trials of pulmonary arterial hypertension (PAH); however, neither standardized nor validated definitions of clinical worsening across PAH trials exist. This study aims to evaluate a proposed definition of clinical worsening within a large prospective, observational registry of patients with PAH with respect to its value as a predictor of proximate (within 1 year) risk for subsequent major events (ie, death, transplantation, or atrial septostomy). We assessed overall 2-year survival and survival free from major events to determine the relationship between clinical worsening and major events among adults with hemodynamically defined PAH (N = 3,001). Freedom from clinical worsening was defined as freedom from worsening functional class (FC), a ≥ 15% reduction in 6-min walk distance (6MWD), all-cause hospitalization, or the introduction of parenteral prostacyclin analog therapy. In the 2 years of follow-up, 583 patients died. Four hundred twenty-six died after a documented clinical worsening event, including FC worsening (n = 128), a ≥ 15% reduction in 6MWD (n = 118), all-cause hospitalization (n = 370), or introduction of a prostacyclin analog (n = 91). Patients who experienced clinical worsening had significantly poorer subsequent 1-year survival postworsening than patients who did not worsen (P < .001). Clinical worsening was highly predictive of subsequent proximate mortality in this analysis from an observational study. These results validate the use of clinical worsening as a meaningful prognostic tool in clinical practice and as a primary end point in clinical trial design.; No.: NCT00370214; URL:

  18. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jeroen Pouwels


    Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

  19. Inhibition of IKKß in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality (United States)

    Dominguez, Jessica A.; Samocha, Alexandr J.; Liang, Zhe; Burd, Eileen M.; Farris, Alton B.; Coopersmith, Craig M.


    -kB has a beneficial role in sepsis by partially preventing sepsis-induced increases in apoptosis and permeability, which are associated with worsening mortality. PMID:23939348

  20. Inhibition of IKKβ in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality. (United States)

    Dominguez, Jessica A; Samocha, Alexandr J; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M


    -specific NF-kB has a beneficial role in sepsis by partially preventing sepsis-induced increases in apoptosis and permeability, which are associated with worsening mortality.

  1. Deep gray matter volume loss drives disability worsening in multiple sclerosis. (United States)

    Eshaghi, Arman; Prados, Ferran; Brownlee, Wallace J; Altmann, Daniel R; Tur, Carmen; Cardoso, M Jorge; De Angelis, Floriana; van de Pavert, Steven H; Cawley, Niamh; De Stefano, Nicola; Stromillo, M Laura; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Vrenken, Hugo; Leurs, Cyra E; Killestein, Joep; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Wheeler-Kingshott, Claudia A M Gandini; Chard, Declan; Thompson, Alan J; Alexander, Daniel C; Barkhof, Frederik; Ciccarelli, Olga


    Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. We analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125 primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow-up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression. SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). This large

  2. Increased red blood cell transfusions are associated with worsening outcomes in pediatric heart transplant patients. (United States)

    Howard-Quijano, Kimberly; Schwarzenberger, Johanna C; Scovotti, Jennifer C; Alejos, Alexandra; Ngo, Jason; Gornbein, Jeffrey; Mahajan, Aman


    Red blood cell (RBC) transfusions are associated with increased morbidity. Children receiving heart transplants constitute a unique group of patients due to their risk factors. Although previous studies in nontransplant patients have focused primarily on the effects of postoperative blood transfusions, a significant exposure to blood occurs during the intraoperative period, and a larger percentage of heart transplant patients require intraoperative blood transfusions when compared with general cardiac surgery patients. We investigated the relationship between clinical outcomes and the amount of blood transfused both during and after heart transplantation. We hypothesized that larger amounts of RBC transfusions are associated with worsening clinical outcomes in pediatric heart transplant patients. A database comprising 108 pediatric patients undergoing heart transplantation from 2004 to 2010 was queried. Preoperative and postoperative clinical risk factors, including the amount of blood transfused intraoperatively and 48 hours postoperatively, were analyzed. The outcome measures were length of hospital stay, duration of tracheal intubation, inotrope score, and major adverse events. Bivariate and multivariate analyses were performed to control for simultaneous risk factors and determine outcomes in which the amount of blood transfused was an independent risk factor. Ninety-four patients with complete datasets were included in the final analysis. Eighty-eight percent received RBC transfusions, with a median transfusion amount of 38.7 mL/kg. A multivariate analysis correcting for 8 covariate risk factors, including the Index for Mortality Prediction After Cardiac Transplantation, age, weight, United Network for Organ Sharing status, warm and cold ischemia time, repeat sternotomy, and pretransplant hematocrit, showed RBC transfusions were independently associated with increased length of intensive care unit stay (means ratio = 1.34; 95% confidence interval, 1.03-1.76; P

  3. Association between matrix metalloproteinase-9 and worsening heart failure events in patients with chronic heart failure. (United States)

    Morishita, Tetsuji; Uzui, Hiroyasu; Mitsuke, Yasuhiko; Amaya, Naoki; Kaseno, Kenichi; Ishida, Kentaro; Fukuoka, Yoshitomo; Ikeda, Hiroyuki; Tama, Naoki; Yamazaki, Taketoshi; Lee, Jong-Dae; Tada, Hiroshi


    Matrix metalloproteinase (MMP) is up-regulated during heart failure (HF) and influences ventricular remodeling. We hypothesized that disparity between MMP-9 and tissue inhibitors of MMP-1 (TIMP-1) results in clinical manifestations and is related to prognostic risk in patients with chronic HF. Plasma levels of MMP-9, TIMP-1, and brain natriuretic peptide (BNP) were measured in 173 patients with chronic HF. Combined endpoints of worsening HF events were assessed during follow-up (median 109 months). MMP-9 and TIMP-1 levels and the MMP-9/TIMP-1 ratio increased with increasing severity of the New York Heart Association class (P for trend = 0.003, 0.011, and 0.005, respectively). Patients with HF events (n = 35) had significantly higher MMP-9 than those without HF events (P = 0.004). Kaplan-Meier analysis demonstrated a higher probability of HF events with high MMP-9 values (>23.2 ng/mL; P = 0.005). A multivariate Cox proportional hazard model showed that high MMP-9 values were an independent predictor of HF events (hazard ratio, 3.73; 95% confidence interval (CI), 1.03-13.46; P = 0.043). In patients with lower BNP levels (≤210 pg/mL), the adjusted hazard ratio for HF events was 3.63 (95% CI, 1.20-11.02; P = 0.023) among patients with high MMP-9 values compared with patients with low BNP and low MMP-9 values. MMP-9 and TIMP-1 levels correlate with the severity of chronic HF. MMP-9 is a strong predictor of HF events, suggesting that a disparity between MMP-9 and TIMP-1 levels and increased MMP-9 levels may help predict HF events. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  4. B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

    International Nuclear Information System (INIS)

    Reddy, M.M.; Goh, K.; Hempelmann, L.H.


    B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

  5. Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis

    NARCIS (Netherlands)

    Baert, F.; Wouters, K.; D'Haens, G.; Hoang, P.; Naegels, S.; D'Heygere, F.; Holvoet, J.; Louis, E.; Devos, M.; Geboes, K.


    It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis.

  6. Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients

    Directory of Open Access Journals (Sweden)

    Caimi Luigi


    Full Text Available Abstract Background The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs and T-cell receptor excision circles (TRECs by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.

  7. Hepatitis B virus: virology, molecular biology, life cycle and intrahepatic spread. (United States)

    Karayiannis, P


    Hepatitis B virus is a member of the Hepadnaviridae family and responsible for causing acute and chronic hepatitis in humans. The current estimates of people chronically infected with the virus are put at 250 million worldwide. Immune-mediated liver damage in these individuals may lead to the development of cirrhosis and hepatocellular carcinoma later in life. This review deals with our current understanding of the virology, molecular biology, life cycle and cell-to-cell spread of this very important pathogen, all of which are considered essential for current and future approaches to antiviral treatment.

  8. Are de novo acute heart failure and acutely worsened chronic heart failure two subgroups of the same syndrome?

    Directory of Open Access Journals (Sweden)

    Banović Marko


    Full Text Available Introduction. Acute heart failure (AHF is one of the most common diseases in emergency medicine, associated with poor prognosis and high in-hospital and long-term mortality. Objective. To investigate clinical presentation of patients with de novo AHF and acute worsening of chronic heart failure (CHF and to identify differences in blood levels of biomarkers and echocardiography findings. Methods. This prospective study comprised 64 consecutive patients being grouped according to the onset of the disease into patients with the de novo AHF (45.3%, and patients with acute worsening of CHF (54.7%. Results. Acute congestion (60% was the most common manifestation of de novo AHF, whereas pulmonary oedema (43.1% was the most common manifestation of acutely decompensated CHF. Patients with acutely decompensated CHF had significantly higher blood values of creatinine (147.10 vs 113.16 μmol/l; p<0.05, urea (12.63 vs 7.82 mmol/l; p<0.05, BNP (1440.11 vs 712.24 pg/ml; p<001 and NTproBNP (9097.00 vs 2827.70 pg/ml; p<0.01 on admission, and lower values of M-mode left ventricular ejection fraction (LVEF during hospitalization (49.44% vs 42.94%; p<0.05. The follow-up after one year revealed still significantly higher BNP (365.49 vs 164.02 pg/ ml; p<0.05 and lower average values of both LVEF in patients with acutely worsened CHF (46.62% vs 54.41% and 39.52% vs 47.88%; p<0.05. Conclusion. Considering differences in clinical severity on admission, echocardiography and natriuretic peptide values during hospitalization and after one year follow-up, de novo AHF and acutely worsened CHF are two different subgroups of the same syndrome.

  9. Barriers and facilitators to optimize function and prevent disability worsening: a content analysis of a nurse home visit intervention. (United States)

    Liebel, Dianne V; Powers, Bethel Ann; Friedman, Bruce; Watson, Nancy M


    This paper is a report of an analysis of how to better understand the results of the nurse home visit intervention in the Medicare Primary and Consumer-Directed Care Demonstration in terms of facilitators and barriers to disability improvement/maintenance as compared with disability worsening. There is a lack of literature describing how nurse home visit interventions are able to maintain/improve disability among older persons with disability. The present study is one of only six reporting beneficial disability outcomes. Cases were purposefully sampled to represent change in the disability construct leading to selection of ten cases each of disability maintenance/improvement (no change or decrease in total Activities of Daily Living score from baseline) and worsening (an increase in total Activities of Daily Living score from baseline). Data from nurses' progress notes and case studies (collected in March 1998-June 2002) were analysed using qualitative descriptive analysis (May 2009). These results remain relevant because the present study is one of the few studies to identify select nurse activities instrumental in postponing/minimizing disability worsening. Three primary themes captured the facilitators and barriers to effective disability maintenance/improvement: (1) building and maintaining patient-centred working relationships, (2) negotiating delivery of intervention components and (3) establishing balance between patients' acute and chronic care needs. Sub-themes illustrate nurse, patient and system factors associated with effective disability maintenance/improvement (e.g. nurse caring, communicating, facilitating interdisciplinary communication) and barriers associated with disability worsening (e.g. dementia, depression and recurring acute illnesses). This study provides new insights about the facilitators and barriers to effective disability maintenance/improvement experienced by patients receiving home visits. Potential opportunities exist to integrate

  10. Flow cytometric analysis of lymphocytes and lymphocyte subpopulations in induced sputum from patients with asthma

    Directory of Open Access Journals (Sweden)

    Yutaro Shiota


    Full Text Available Study objectives were to compare the numbers of lymphocytes and lymphocyte subpopulations in induced sputum from asthmatic patients and from healthy subjects, and to determine the effect of inhaled anti-asthmatic steroid therapy on these cell numbers. Hypertonic saline inhalation was used to non-invasively induce sputum samples in 34 patients with bronchial asthma and 21 healthy subjects. The sputum samples were reduced with dithioerythritol and absolute numbers of lymphocytes and lymphocyte subpopulations were assessed by direct immunofluorescence and flow cytometry. To assess the effect of beclomethasone dipropionate (BDP on induced sputum, numbers of lymphocytes and lymphocyte subpopulations in sputum also were evaluated after 4 weeks of BDP inhalation treatment in seven asthmatic patients. An adequate sample was obtained in 85.3% of patients with asthma and in 79.2% of the healthy subjects. Induced sputum from patients with asthma had increased numbers of lymphocytes (P = 0.009; CD4+ cells (P = 0.044; CD4+ cells-bearing interleukin-2 receptor (CD25; P = 0.016; and CD4+ cells bearing human histocompatibility leukocyte antigen (HLA-DR (P = 0.033. CD8+ cells were not increased in asthmatic patients. In patients treated with inhaled steroids, numbers of lymphocytes, CD4+ cells, CD25-bearing CD4+ cells and HLA-DR-bearing CD4+ cells in sputum decreased from pretreatment numbers (P = 0.016, 0.002, 0.003 and 0.002, respectively. Analysis of lymphocytes in induced sputum by flow cytometry is useful in assessing bronchial inflammation, and activated CD4+ lymphocytes may play a key role in the pathogenesis of airway inflammation in bronchial asthma.

  11. Lymphocyte fluctuation in bronchoalveolar lavage fluid in normal volunteers. (United States)

    Laviolette, M


    In an attempt to understand the widely varying bronchoalveolar lavage lymphocyte counts reported in normal subjects, we performed bronchoalveolar lavage in 42 healthy nonsmokers. The mean (SD) lymphocyte percentage in this first lavage was 9.6% (7.7%). The values did not fit a normal distribution. Five subjects had more than 20% of lymphocytes, and when they were excluded the distribution of lymphocyte counts was normal. Bronchoalveolar lavage was repeated once or twice in these five subjects 47 days or more after the previous lavage and the lymphocyte count decreased below 14% in four. Eight volunteers with an initial lymphocyte percentage less than 20% also had repeat lavages; two presented a transient increase of lymphocyte count above 20%. These data show that the percentage of lymphocytes in lavage fluid fluctuates significantly in normal subjects and suggest that lymphocyte counts counts higher than 14% should not be considered as normal. PMID:4060105

  12. The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure. (United States)

    Davies, Mary-Ann; Boulle, Andrew; Technau, Karl; Eley, Brian; Moultrie, Harry; Rabie, Helena; Garone, Daniela; Giddy, Janet; Wood, Robin; Egger, Matthias; Keiser, Olivia


    To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Analysis of data from children (CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children. © 2012 Blackwell Publishing Ltd.

  13. Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction

    DEFF Research Database (Denmark)

    Gheorghiade, Mihai; Greene, Stephen J; Butler, Javed


    IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem. OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, ...

  14. A diagnostic study in patients with sciatica establishing the importance of localization of worsening of pain during coughing, sneezing and straining to assess nerve root compression on MRI. (United States)

    Verwoerd, Annemieke J H; Mens, Jan; El Barzouhi, Abdelilah; Peul, Wilco C; Koes, Bart W; Verhagen, Arianne P


    To test whether the localization of worsening of pain during coughing, sneezing and straining matters in the assessment of lumbosacral nerve root compression or disc herniation on MRI. Recently the diagnostic accuracy of history items to assess disc herniation or nerve root compression on magnetic resonance imaging (MRI) was investigated. A total of 395 adult patients with severe sciatica of 6-12 weeks duration were included in this study. The question regarding the influence of coughing, sneezing and straining on the intensity of pain could be answered on a 4 point scale: no worsening of pain, worsening of back pain, worsening of leg pain, worsening of back and leg pain. Diagnostic odds ratio's (DORs) were calculated for the various dichotomization options. The DOR changed into significant values when the answer option was more narrowed to worsening of leg pain. The highest DOR was observed for the answer option 'worsening of leg pain' with a DOR of 2.28 (95 % CI 1.28-4.04) for the presence of nerve root compression and a DOR of 2.50 (95 % CI 1.27-4.90) for the presence of a herniated disc on MRI. Worsening of leg pain during coughing, sneezing or straining has a significant diagnostic value for the presence of nerve root compression and disc herniation on MRI in patients with sciatica. This study also highlights the importance of the formulation of answer options in history taking.

  15. Diffuse pulmonary infiltrates in an old man with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Alireza Hosseinnezhad


    Full Text Available An 82-year-old man known case of chronic lymphocytic leukemia (CLL presented with fever and weakness. He had never received any treatment for his CLL in the past. On admission he was found to be in mild respiratory distress with bilateral crackles and had markedly elevated white blood count (WBC (137 K/uL with 93% lymphocytes. His respiratory status deteriorated necessitating noninvasive ventilatory support. Chest computed tomography (CT scan revealed bilateral diffuse ground glass opacities, so broad spectrum antibiotic therapy was initiated. Despite that, he remained febrile and cultures were all negative. Chest x-rays showed progressive worsening of diffuse alveolar opacities. Bronchoalveolar lavage (BAL was negative for infectious etiologies, however flow cytometry of the fluid was consistent with CLL. Chemotherapy with chlorambucil was started. Although most of the pulmonary infiltrates in CLL patients are due to infectious causes, leukemic cells infiltration should be considered as well in CLL patients with respiratory symptoms who do not respond appropriately to standard antimicrobial regimen.

  16. Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke. (United States)

    Guo, Zhiliang; Yu, Shuhong; Xiao, Lulu; Chen, Xin; Ye, Ruidong; Zheng, Ping; Dai, Qiliang; Sun, Wen; Zhou, Changsheng; Wang, Shuiping; Zhu, Wusheng; Liu, Xinfeng


    The neutrophil to lymphocyte ratio (NLR) has been shown to predict short- and long-term outcomes in ischemic stroke patients. We sought to explore the temporal profile of the plasma NLR in stroke patients treated with intravenous thrombolysis (IVT) and its relationship with intracranial bleeding complications after thrombolysis. A total of 189 ischemic stroke patients were prospectively enrolled. Blood samples for leukocyte, neutrophil, and lymphocyte counts were obtained at admission and at 3-6, 12-18, and 36-48 h after IVT. Head CT was performed on admission and repeated after 36-48 h, and a CT scan was done immediately in case of clinical worsening. Hemorrhagic events were categorized as symptomatic intracranial hemorrhage (sICH) and parenchymal hematomas (PH) according to previously published criteria. An increasing trend in the NLR was observed after stroke, and the NLR was higher in patients who developed PH or sICH at 3-6, 12-18, and 36-48 h after IVT (P treatment was independently associated with PH (adjusted odds ratio [OR] 1.14) and sICH (adjusted OR 1.14). In addition, patients with a NLR ≥10.59 had an 8.50-fold greater risk for PH (95 % confidence interval [CI] 2.69-26.89) and a 7.93-fold greater risk for sICH (95 % CI 2.25-27.99) than patients with a NLR stroke patients.

  17. Chronic lymphocytic leukemia: concepts and observations

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    Chandra, P.; Chanana, A.D.; Chikkappa, G.; Cronkite, E.P.


    Thirty-five patients with chronic lymphocytic leukemia (CLL) were studied for assessment of total body leukemic mass and abnormality in T-lymphocyte function associated with clinical stages of CLL. Total body potassium (TBK), an indicator of lean body mass, was found to correlate well with increase in the clinical stage of the disease. Use of TBK for monitoring the regression and relapse of leukemic load is suggested. No correlation was found between whole cell and nuclear volumes of lymphocytes in CLL patients and clinical stages of the disease. Blast transformation and proliferation under phytohemagglutinin (PHA) stimulation appeared to be normal in purified T cells of early stages and abnormal in the late stages of disease.

  18. The educational challenge of Paediatric Virology: An interview with Professor of Neonatology Anne Greenough. (United States)

    Mammas, Ioannis N; Spandidos, Demetrios A


    According to Professor Anne Greenough, Professor of Neonatology and Clinical Respiratory Physiology at the King's College London (London, UK), Paediatric Virology is indeed a rapidly increasing educational challenge. Professor Greenough, who in 1992 wrote her book on congenital, perinatal and neonatal infections, believes that during the past 3 decades, paediatric health professionals are becoming increasingly involved in specialised care and follow-up of paediatric patients with viral diseases, who require advanced medical care and innovative technological services. Moreover, she highlights the expected role of new vaccines and antiviral agents that are currently under investigation, as well as the impact of emerging viral diseases that require novel prevention strategies and therapeutic protocols. However, she notes that the number of Paediatric Virologists in any one country is likely to be small; hence, a separate paediatric subspecialty needs to be considered carefully. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens, Greece, on October 7th, 2017, Professor Greenough will give her plenary lecture on the impact of viral infections on the long term outcomes of prematurely born infants.

  19. Diagnostic value of different adherence measures using electronic monitoring and virologic failure as reference standards. (United States)

    Deschamps, Ann E; De Geest, Sabina; Vandamme, Anne-Mieke; Bobbaers, Herman; Peetermans, Willy E; Van Wijngaerden, Eric


    Nonadherence to antiretroviral therapy is a substantial problem in HIV and jeopardizes the success of treatment. Accurate measurement of nonadherence is therefore imperative for good clinical management but no gold standard has been agreed on yet. In a single-center prospective study nonadherence was assessed by electronic monitoring: percentage of doses missed and drug holidays and by three self reports: (1) a visual analogue scale (VAS): percentage of overall doses taken; (2) the Swiss HIV Cohort Study Adherence Questionnaire (SHCS-AQ): percentage of overall doses missed and drug holidays and (3) the European HIV Treatment Questionnaire (EHTQ): percentage of doses missed and drug holidays for each antiretroviral drug separately. Virologic failure prospectively assessed during 1 year, and electronic monitoring were used as reference standards. Using virologic failure as reference standard, the best results were for (1) the SHCS-AQ after electronic monitoring (sensitivity, 87.5%; specificity, 78.6%); (2) electronic monitoring (sensitivity, 75%; specificity, 85.6%), and (3) the VAS combined with the SHCS-AQ before electronic monitoring (sensitivity, 87.5%; specificity, 58.6%). The sensitivity of the complex EHTQ was less than 50%. Asking simple questions about doses taken or missed is more sensitive than complex questioning about each drug separately. Combining the VAS with the SHCS-AQ seems a feasible nonadherence measure for daily clinical practice. Self-reports perform better after electronic monitoring: their diagnostic value could be lower when given independently.

  20. Mathematical virology: a novel approach to the structure and assembly of viruses. (United States)

    Twarock, Reidun


    Understanding the structure and life cycle of viruses is a fascinating challenge with a crucial impact on the public health sector. In the early 1960s, Caspar & Klug (Caspar & Klug 1962 Cold Spring Harbor Symp. Quant. Biol. 27, 1-24) established a theory for the prediction of the surface structures of the protein shells, called viral capsids, which encapsulate and hence provide protection for the viral genome. It is of fundamental importance in virology, with a broad spectrum of applications ranging from the image analysis and classification of experimental data to the construction of assembly models. However, experimental results have provided evidence for the fact that it is incomplete and, in particular, cannot account for the structures of Papovaviridae, which are of particular interest because they contain cancer-causing viruses. This gap has recently been closed by the viral tiling theory, which describes the locations of the protein subunits and inter-subunit bonds in viral capsids based on mathematical tools from the area of quasicrystals. The predictions and various recent applications of the new theory are presented, and it is discussed how further research along these lines may lead to new insights in virology and the design of anti-viral therapeutics.

  1. Platelet count is associated with sustained virological response rates in treatments for chronic hepatitis C. (United States)

    Jun, Baek Gyu; Park, Eui Ju; Lee, Woong Cheul; Jang, Jae Young; Jeong, Soung Won; Kim, Young Don; Cheon, Gab Jin; Cho, Young Sin; Lee, Sae Hwan; Kim, Hong Soo; Lee, Yun Nah; Kim, Sang Gyune; Kim, Young Seok; Kim, Boo Sung


    This study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection. This retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/- 2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment. SVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of 150 × 103 /µL (p 150 × 103 /µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001). Young age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.

  2. The proposal of Paediatric Virology and its perspectives: An interview with Professor of Paediatrics Maria Theodoridou. (United States)

    Mammas, Ioannis N; Spandidos, Demetrios A


    Professor Maria Theodoridou, Emeritus Professor of Paediatrics at the University of Athens, is one of the few paediatricians in Greece, who have experienced almost all the infectious diseases of the second half of the 20th century and their severe consequences, prior to the widespread adoption of immunisations. A milestone during her career was the establishment of a specialised National Reference Unit for the care of paediatric patients with acquired immune deficiency syndrome (AIDS) at the 'Aghia Sophia' Children's Hospital in Athens, Greece. According to Professor Theodoridou, training on the prevention, management and treatment of neonatal and paediatric viral infections represents a new educational challenge for both community as well as hospital-based paediatric health professionals. The debate of the potential strategically principal role of Paediatric Virology subspecialists in the primary, secondary and tertiary clinical practice is definitely necessary and needs further discussion and evaluation, she adds. She describes the difficulties that Greece, a country under a long-standing financial crisis, faces for the hospital-based management of paediatric viral infections and refers to the future advances, which are expected in the field of diagnosis and treatment of viral infections in neonates and children. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens on October 7th, 2017, Professor Theodoridou will focus on the immigration crisis and vaccination policy.

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

    Directory of Open Access Journals (Sweden)

    Jonathan H. Epstein


    Full Text Available 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.

  4. Lymphocyte subpopulations in hypertrophied adenoid in children. (United States)

    Musiatowicz, M; Wysocka, J; Kasprzycka, E; Hassmann, E


    Adenoid hypertophy is a common feature of childhood. It is currently accepted that it is caused by the antigen-stimulated increased activity of lymphocyte B (D. Bani, O. Gallo, O. Fini-Storchi, Intraepithelial lymphocyte subpopulations and dendritic accessory cells in normal and hypertrophic adenoids, Laryngoscope 10 (1994) 869-873). The adenoid decreases its size with age but the accompanying function alterations are not fully understood (L. Zawadzka-Glos, M. Chmielik, M. Wasik, Cell mediated response in hypertrophied tonsils in children, Nowa Pediatr. 4 (1997) 12-13). The understanding of the adenoid structure that undergoes some changes during the growth period is essential for evaluation of indications for adnoidectomy and assessment of its potential results. The aim of this study was to evaluate lymphocyte subpopulations in adenoid according to age. The analysed material was adenoids removed on the grounds of hypertrophy, which caused obstructive symptoms and/or otitis media with effusion onset. In the present study, we did not find any statistically significant differences among lymphocytes B, Th, and Ts subpopulations, respectively, in the adenoids of any of the age groups. We have found a statistically significant CD3(+) HLA-DR(+) cell percentage decrease in the group of children from 5 to 10 and above 10 years of age, respectively. We have also found a statistically significant increase in the percentage of NK (CD3(-) CD16(+) 56(+)) lymphocytes in relation to age. On the grounds of the current study, it may be stated that some changes in lymphocyte subpopulations in the adenoid take place with age.

  5. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance. (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E


    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  6. Primary lymphocytic lymphoma of lacrimal gland. (United States)

    Romero-Caballero, M D; Lozano-García, I; Gómez-Molina, C; Gil-Liñán, A I; Arcas, I


    We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin


    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) 2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy. PMID:25141905

  8. Evaluation of clinical and immunological markers for predicting virological failure in a HIV/AIDS treatment cohort in Busia, Kenya.

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    Cecilia Ferreyra

    Full Text Available BACKGROUND: In resource-limited settings where viral load (VL monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART. METHODS: In a HIV/AIDS program in Busia District Hospital, Kenya, a retrospective, cross-sectional cohort analysis was performed in April 2008 for all adult patients (>18 years old on ART for ≥12 months, treatment-naive at ART start, attending the clinic at least once in last 6 months, and who had given informed consent. Treatment failure was assessed per WHO clinical (disease stage 3 or 4 and immunological (CD4 cell count criteria, and compared with virological failure (VL >5,000 copies/mL. RESULTS: Of 926 patients, 123 (13.3% had clinically defined treatment failure, 53 (5.7% immunologically defined failure, and 55 (6.0% virological failure. Sensitivity, specificity, positive predictive value, and negative predictive value of both clinical and immunological criteria (combined in predicting virological failure were 36.4%, 83.5%, 12.3%, and 95.4%, respectively. CONCLUSIONS: In this analysis, clinical and immunological criteria were found to perform relatively poorly in predicting virological failure of ART. VL monitoring and new algorithms for assessing clinical or immunological treatment failure, as well as improved adherence strategies, are required in ART programs in resource-limited settings.

  9. Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease.

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    Mercè Rosinach

    Full Text Available The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned.To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS, which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology.Double-blind randomized clinical trial of gluten vs placebo rechallenge.>18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day and 7 placebo. Clinical symptoms, quality of life (GIQLI, and presence of gamma/delta+ cells and transglutaminase deposits were evaluated.91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01. Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01. The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50% patients as having probable 'coeliac lite' disease.This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free NCT02472704.

  10. Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease. (United States)

    Rosinach, Mercè; Fernández-Bañares, Fernando; Carrasco, Anna; Ibarra, Montserrat; Temiño, Rocío; Salas, Antonio; Esteve, Maria


    The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned. To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology. Double-blind randomized clinical trial of gluten vs placebo rechallenge. >18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated. 91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (pgluten-free diet allowed classifying 9 out of the 18 (50%) patients as having probable 'coeliac lite' disease. This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet. NCT02472704.

  11. History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; Ledergerber, B


    . METHODS: A total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional...... demographic variables. Baseline was defined as the date of starting new antiretrovirals. RESULTS: Four hundred and fifty-one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI) 6.7-8.0]. After adjustment...

  12. Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies

    DEFF Research Database (Denmark)

    Hofmann, B; Lindhardt, B O; Gerstoft, J


    To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper...... the transformation responses to pokeweed mitogen and cytomegalovirus and the absolute count of CD4 positive lymphocytes were the most common abnormal values. In particular, a low relative response to pokeweed mitogen on initial investigation correlated with a worsened clinical condition on reinvestigation. The risk...

  13. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)



    Mar 20, 2009 ... Key words: Lipopolysaccharide, lymphocytes, TLRs, cytokines. INTRODUCTION. Lipopolysaccharide (LPS), a predominant glycolipid in the outer membranes of Gam-negative bacteria, stimulates monocyte, macrophages, and neutrophils and increase expression of cell adhesion molecules (Trent et al., ...

  14. Peripheral lymphocyte subpopulations in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P


    Peripheral lymphocyte subsets--T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and naive/virgin T cells/natural killer cells (CD45RA)--were studied quantitatively in 30 patients with recurrent aphthous ulceration (RAU) and 29 sex- and age-matched RAU-free control donors. The CD4+ percentage was s...

  15. Genotoxic effects of borax on cultured lymphocytes. (United States)

    Pongsavee, Malinee


    The effect of borax on human chromosomes was analyzed in this study. Venous blood from 30 male students at Thammasat University, Thailand (age 18-25 years) was collected for lymphocyte cell cultures. This experiment was divided into two groups: the first group was the control group and the second group was the experimental group. The lymphocyte cells in the control group were cultured without borax. The experimental group was divided into four subgroups. The lymphocyte cells in each experimental subgroup were cultured with different concentrations of borax (0.1 mg/ml, 0.15 mg/ml, 0.2 mg/ml and 0.3 mg/ml). Human chromosomes were studied for abnormalities through Giemsa-staining and G-banding. The results show that the numbers of metaphase plates (the metaphase plate which contained 46 chromosomes; 46, XY) and metaphase chromosomes were reduced when lymphocyte cells were cultured with 0.15 mg/ml (57.2%), 0.2 mg/ml (50.8%) and 0.3 mg/ml (42.3%) concentrations of borax. There was a statistically significant difference between the control and experimental subgroups (p borax concentration experimental subgroup. This shows that borax (at 0.15, 0.2 and 0.3 mg/ml concentrations) affects the cell and human chromosomes (both numerical and structural abnormalities). Borax may cause human chromosome abnormalities and lead to genetic defects.

  16. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H


    the response to pokeweed mitogen. The response to concanavalin A and to various antigens was suppressed, especially the response to large particulate antigens. Oral intake of 300 mg of chloroquine base/week did not affect the lymphocyte proliferative responses. 600 mg of base/week decreased the response...

  17. Fungal natural products targeting chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen


    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds w...

  18. Lymphocyte adenylate cyclase activity in immunosuppressed patients

    NARCIS (Netherlands)

    Michel, M. C.; Brodde, O. E.


    In order to determine whether alterations of adenylate cyclase are involved in the immunosuppressive effect of glucocorticoid/cyclosporin treatment we measured basal, prostaglandin E1-, and forskolin-stimulated cAMP production in lymphocyte membranes from kidney transplant patients undergoing

  19. Spondylarthritis in the absence of B lymphocytes

    NARCIS (Netherlands)

    Baeten, Dominique; Kruithof, Elli; Breban, Maxime; Tak, Paul P.


    The highly effective treatment of rheumatoid arthritis by B cell depletion and the presence of B cells in the peripheral and axial lesions of patients with spondylarthritis (SpA) raise the question as to whether B lymphocytes could also be an appropriate therapeutic target in the latter disease. We

  20. [Enterobacterial antigen in human peripheral blood lymphocytes]. (United States)

    Faure-Fontenla, M A; García-Tamayo, F


    The following study has as prior history the research reports which have shown the existence of an antigenic tissue deposit in gram-negative enterobacteria. The antigens of the enterobacteria have also been found in the lymphocytic membranes and cytoplasm. Since intestinal lymphoid tissue cells can recirculate by means of the thoracic duct to the peripheral venous system, it was proposed that the circulating lymphocytes in healthy people could also contain small amounts of a common enterobacterial antigen. The study was carried out in 15 human venous blood samples, of which the lymphocytic population was separated to later be used in the preparation of 15 alcohol soluble extracts. This material was used for inhibiting the immuno-hemolysis assay in three occasions in order to show the presence of antigens shared by different enterobacterias, using as reference a fraction separated from the LPS of Escherichia coli 08. The results showed that the human lymphocytes also had antigenic determinants common to gram-negative bacteria.

  1. Lymphocyte dynamics in health and disease

    NARCIS (Netherlands)

    van Gent, R.


    Following immune depletion, it is vital that the immune system recovers rapidly to avoid severe or life-threatening infections. In adults, full recovery of CD4+ and CD8+ T-cell counts, important cell types of the immune system, may take years. Similar to other lymphocytes, T cells start their

  2. Immunohistochemical evaluation of lymphocyte populations in the ...

    African Journals Online (AJOL)

    Here we sought to quantify T and B lymphocyte populations in the lacrimal tissue of the nictitans glands of dogs with iKCS those with neurological KCS (nKCS)and also in dogs with tear production within the recognized normal levels and no ocular surface signs of KCS. Nictitans glands were obtained from 10 healthy dogs ...

  3. Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Caroline Boda

    Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

  4. Neutrophil lymphocyte ratio predicts postoperative pain after ...

    African Journals Online (AJOL)

    Background and Aim: Postoperative pain is well known and usually disturbing complication of surgery. Inflammation plays an important role in the development and progression of postoperative pain. We aimed to investigate possible relationship between preoperatively measured neutrophil‑lymphocyte ratio (NLR) – as an ...

  5. GABA, a natural immunomodulator of T lymphocytes

    DEFF Research Database (Denmark)

    Bjurstöm, Helen; Wang, Junyang; Ericsson, Ida


    gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could ......M and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory....

  6. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    Background and Aim: Postoperative pain is well known and usually disturbing complication of surgery. Inflammation plays an important role in the development and progression of postoperative pain. We aimed to investigate possible relationship between preoperatively measured neutrophil‑lymphocyte ratio (NLR) – as an ...

  7. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    Lipopolysaccharide (LPS) is a predominant glycolipid in the outer membranes of gam-negative bacteria that stimulates monocytes, macrophages, and neutrophils to produce cytokines. The aim was to study the expression profile of TLRs and cytokines and determine the role of LPS in the peripheral blood lymphocytes.

  8. Gender parity trends for invited speakers at four prominent virology conference series. (United States)

    Kalejta, Robert F; Palmenberg, Ann C


    Scientific conferences are most beneficial to participants when they showcase significant new experimental developments, accurately summarize the current state of the field, and provide strong opportunities for collaborative networking. A top-notch slate of invited speakers, assembled by conference organizers or committees, is key to achieving these goals. The perceived underrepresentation of female speakers at prominent scientific meetings is currently a popular topic for discussion, but one that often lacks supportive data. We compiled the full rosters of invited speakers over the last 35 years for four prominent international virology conferences, the American Society for Virology Annual Meeting (ASV), the International Herpesvirus Workshop (IHW), the Positive-Strand RNA Virus Symposium (PSR), and the Gordon Research Conference on Viruses & Cells (GRC). The rosters were cross-indexed by unique names, gender, year, and repeat invitations. When plotted as gender-dependent trends over time, all four conferences showed a clear proclivity for male-dominated invited speaker lists. Encouragingly, shifts toward parity are emerging within all units, but at different rates. Not surprisingly, both selection of a larger percentage of first time participants and the presence of a woman on the speaker selection committee correlated with improved parity. Session chair information was also collected for the IHW and GRC. These visible positions also displayed a strong male dominance over time that is eroding slowly. We offer our personal interpretation of these data to aid future organizers achieve improved equity among the limited number of available positions for session moderators and invited speakers. IMPORTANCE Politicians and media members have a tendency to cite anecdotes as conclusions without any supporting data. This happens so frequently now, that a name for it has emerged: fake news. Good science proceeds otherwise. The under representation of women as invited

  9. Worsening anatomic outcomes following aflibercept for neovascular age-related macular degeneration in eyes previously well controlled with ranibizumab

    Directory of Open Access Journals (Sweden)

    Nudleman E


    Full Text Available Eric Nudleman,1 Jeremy D Wolfe,2,3 Maria A Woodward,4 Yoshihiro Yonekawa,2,3 George A Williams,2,3 Tarek S Hassan2,3 1Department of Ophthalmology, Shiley Eye Center, University of California, San Diego, La Jolla, CA, 2Beaumont Eye Institute, Oakland University William Beaumont School of Medicine, 3Associated Retinal Consultants, Royal Oak, 4Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA Purpose: Antivascular endothelial growth factor injection is the mainstay of treating neovascular age-related macular degeneration (AMD. Previous studies have shown that switching treatment from ranibizumab to aflibercept led to an improvement in eyes with recalcitrant activity. Herein, we identify a unique subset of patients whose eyes with neovascular AMD were previously well controlled with ranibizumab injections were then worsened after being switched to aflibercept. Methods: This is a retrospective interventional case series. Eyes with neovascular AMD, previously well controlled with monthly injections of ranibizumab, which then developed worsening of subretinal fluid after being switched to aflibercept were included. Results: A total of 17 eyes were included. All eyes developed increased subretinal fluid when switched from ranibizumab to aflibercept. Fourteen patients were switched back to ranibizumab after a single injection of aflibercept and had subsequent rapid resolution of subretinal fluid. Three patients continued with monthly aflibercept injections for two subsequent months and demonstrated the persistence of the increased subretinal fluid until they were switched back to treatment with ranibizumab at which time the fluid resolved. No eye had persistent decline in visual acuity. Conclusion: Switching from intravitreal ranibizumab to aflibercept in eyes with well-controlled neovascular AMD may result in worsening in a subset of patients and resolves when therapy is switched back to ranibizumab. Keywords: anti

  10. Prognostic Impact of BNP Variations in Patients Admitted for Acute Decompensated Heart Failure with In-Hospital Worsening Renal Function. (United States)

    Stolfo, D; Stenner, E; Merlo, M; Porto, A G; Moras, C; Barbati, G; Aleksova, A; Buiatti, A; Sinagra, G


    The significance of worsening renal function (WRF) in patients admitted for acute decompensated heart failure (ADHF) is still controversial. We hypothesised that changes in brain natriuretic peptide (BNP) might identify patients with optimal diuretic responsiveness resulting in transient WRF, not negatively affecting the prognosis. Our aim was to verify if in-hospital trends of BNP might be helpful in the stratification of patients with WRF after treatment for ADHF. 122 consecutive patients admitted for ADHF were enrolled. Brain natriuretic peptide and eGFR were evaluated at admission and discharge. A 20% relative decrease in eGFR defined WRF, whereas a BNP reduction ≥40% was considered significant. The primary combined endpoint was death/urgent heart transplantation and re-hospitalisation for ADHF. Worsening renal function occurred in 23% of patients without differences in outcome between patients with and without WRF (43% vs. 45%, p=0.597). A significant reduction in BNP levels over the hospitalisation occurred in 59% of the overall population and in 71% of patients with WRF. At a median follow-up of 13.0 (IQR 6-36) months, WRF patients with ≥40% BNP reduction had a lower rate of death/urgent heart transplantation/re-hospitalisation compared to WRF patients without BNP reduction (30% and 75%, respectively; p=0.007). Favourable BNP trend was the strongest variable in predicting the outcome in WRF patients (HR 0.222, 95% CI 0.066-0.753, p=0.016). Worsening renal function does not affect the prognosis of ADHF and, when associated with a significant BNP reduction, identifies patients with adequate decongestion at discharge and favourable outcome. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  11. C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Bregenholt, S; Nording, J A


    cultures grown in the presence of complement-inactivated serum. Read-outs were cell proliferation, lymphokine production and development of T cell-mediated cytotoxicity. We found that addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte cultures inhibited proliferation, the development...... beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte...... of allospecific cytotoxic activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12 and IFN-gamma. These data clearly demonstrate a regulatory function of C1-inh on T cell-mediated immune functions....

  12. Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe

    DEFF Research Database (Denmark)

    Nakagawa, Fumiyo; Lodwick, Rebecca; Costagliola, Dominique


    Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF...

  13. Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe

    NARCIS (Netherlands)

    Zoufaly, A.; Cozzi-Lepri, A.; Reekie, J.; Kirk, O.; Lundgren, J.; Reiss, P.; Jevtovic, D.; Machala, L.; Zangerle, R.; Mocroft, A.; Lunzen, J. van; Burger, D.M.; et al.,


    BACKGROUND: The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. METHODS: Patients in EuroSIDA starting at least 1 new antiretroviral drug with

  14. DMPD: Developmental plasticity of lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18472258 Developmental plasticity of lymphocytes. Cobaleda C, Busslinger M. Curr Immunol. 2008 Apr;20(2):139-48. Epub 2008 May 9. (.png) (.svg) (.html) (.csml) Show Developmental plastic...ity of lymphocytes. PubmedID 18472258 Title Developmental plasticity of lymphocytes. Authors Cobaleda C, Bus

  15. Contribution of the "Stefan S. Nicolau" Institute of Virology to the electron microscopic study of viruses. (United States)

    Dumitrescu, S M


    The review reflects the concerns of researchers of the "Stefan S. Nicolau" Institute of Virology who used electron microscopy techniques with a view to visualizing morphological features of virus structure (influenza, adeno, hepatitis, herpes, cytomegalic, Aujeszky, rabies viruses, etc.) and different aspects of the virus - host cell relationships (Sendai virus/Hep2 cells, influenza and adenovirus/mouse lung, subacute sclerosing panencephalitis/human brain or cell cultures, Coxsackie and foot-and-mouth disease virus/myofibrils, Rubarth hepatitis virus/chick embryo liver cells, a.o.). Morphological aspects of normal or tumoral cells and the influence of chemical agents (actinomycin D, EDTA), viruses, bacteria or parasites have also been studied. Mention is made of several original techniques used to obtain electron microscopy preparations.

  16. Increased osteoprotegerin predicts poor virological outcome during anticytomegalovirus therapy in solid organ transplant recipients. (United States)

    Ueland, Thor; Rollag, Halvor; Hartmann, Anders; Jardine, Alan; Humar, Atul; Bignamini, Angelo A; Åsberg, Anders; Aukrust, Pål


    Cytomegalovirus (CMV) infection involves interaction between endothelial cells and leukocyte subsets that may promote vascular inflammation and lead to treatment failure in infected individuals. Osteoprotegerin is a marker of vascular and systemic inflammation but has not been investigated in relation to treatment outcome during CMV infection. We investigated whether circulating levels of osteoprotegerin are related to features of CMV disease and treatment outcomes during CMV infection in 291 solid organ transplant recipients receiving valganciclovir or ganciclovir in an international multicenter trial of CMV disease treatment (the VICTOR study). Elevated plasma osteoprotegerin was associated with (i) certain disease characteristics including presence of tissue invasive disease (Posteoprotegerin levels in solid organ transplant recipients with CMV infection may reflect vascular inflammation and is associated with late virological outcome in these patients.

  17. Porting of Bio-Informatics Tools for Plant Virology on a Computational Grid

    International Nuclear Information System (INIS)

    Lanzalone, G.; Lombardo, A.; Muoio, A.; Iacono-Manno, M.


    The goal of Tri Grid Project and PI2S2 is the creation of the first Sicilian regional computational Grid. In particular, it aims to build various software-hardware interfaces between the infrastructure and some scientific and industrial applications. In this context, we have integrated some among the most innovative computing applications in virology research inside these Grid infrastructure. Particularly, we have implemented in a complete work flow, various tools for pairwise or multiple sequence alignment and phylogeny tree construction (ClustalW-MPI), phylogenetic networks (Splits Tree), detection of recombination by phylogenetic methods (TOPALi) and prediction of DNA or RNA secondary consensus structures (KnetFold). This work will show how the ported applications decrease the execution time of the analysis programs, improve the accessibility to the data storage system and allow the use of metadata for data processing. (Author)

  18. 4th European Seminars in Virology on Oncogenic and Oncolytic Viruses, in Bertinoro (Bologna), Italy. (United States)

    Reale, Alberto; Messa, Lorenzo; Vitiello, Adriana; Loregian, Arianna; Palù, Giorgio


    The 4th European Seminars in Virology (EuSeV), which was focused on oncogenic and oncolytic viruses, was held in Bertinoro (Bologna), Italy, from June 10 to 12, 2016. This article summarizes the plenary lectures and aims to illustrate the main topics discussed at 4th EuSeV, which brought together knowledge and expertise in the field of oncogenic and oncolytic viruses from all over the world. The meeting was divided in two parts, "Mechanisms of Viral Oncogenesis" and "Viral Oncolysis and Immunotherapy," which were both focused on dissecting the complex and multi-factorial interplay between cancer and human viruses and on exploring new anti-cancer strategies. J. Cell. Physiol. 232: 2641-2648, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. So What Have Plant Viruses Ever Done for Virology and Molecular Biology? (United States)

    Lomonossoff, George P


    The discovery of a new class of pathogen, viruses, in the late 19th century, ushered in a period of study of the biochemical and structural properties of these entities in which plant viruses played a prominent role. This was, in large part, due to the relative ease with which sufficient quantities of material could be produced for such analyses. As analytical techniques became increasingly sensitive, similar studies could be performed on the viruses from other organisms. However, plant viruses continued to play an important role in the development of molecular biology, including the demonstration that RNA can be infectious, the determination of the genetic code, the mechanism by which viral RNAs are translated, and some of the early studies on gene silencing. Thus, the study of plant viruses should not be considered a "niche" subject but rather part of the mainstream of virology and molecular biology. © 2018 Elsevier Inc. All rights reserved.

  20. How Chikungunya Virus Virology Affects Its Epidemiology and Transmission: Implications for Influencing Public Health. (United States)

    Powers, Ann M


    Chikungunya virus has been causing a series of ongoing epidemics around the globe for the past 12 years. During that time, estimates indicate that >4 million cases occurred worldwide. Despite the magnitude of these outbreaks and the broad interest in understanding the virus and disease, significant gaps still exist in our knowledge base. An in-depth understanding of the basic virological elements that can affect the epidemiology of the agent is critical for future development of control and treatment products. This work describes how knowledge of various viral genetic and structural elements has begun to advance the development of vaccines and therapeutics and suggests that further knowledge is needed to provide additional options. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy. (United States)

    Saitoh, Akihiko; Singh, Kumud K; Sandall, Sharsti; Powell, Christine A; Fenton, Terrence; Fletcher, Courtney V; Hsia, Karen; Spector, Stephen A


    In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART. To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4+ T-lymphocyte counts in HIV-1-infected children receiving HAART with sustained virologic suppression. T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART. There was a positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA. To maintain adequate levels of CD4+ T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4+ T lymphocytes in the presence of persistent virus. The TREC level is a useful marker of thymic function in HIV-infected children.

  2. Elevated CD8 counts during HAART are associated with HIV virologic treatment failure. (United States)

    Krantz, Elizabeth M; Hullsiek, Katherine Huppler; Okulicz, Jason F; Weintrob, Amy C; Agan, Brian K; Crum-Cianflone, Nancy F; Ganesan, Anuradha; Ferguson, Tomas M; Hale, Braden R


    To evaluate whether elevated CD8 counts are associated with increased risk of virologic treatment failure in HIV-infected individuals. Retrospective cohort study. US Military HIV Natural History Study participants who initiated highly active antiretroviral therapy (HAART) in 1996-2008 had 6- and 12-month post-HAART HIV RNA count were eligible (n = 817). Baseline was 12 months after the start of HAART, virologic failure (VF) was defined as confirmed HIV RNA ≥ 400 copies per milliliter, and CD8 counts ≥ 1200 cells per cubic millimeter were considered elevated. Cox models were used to examine the effect of baseline and time-updated CD8 counts on VF. There were 216 failures for a rate of 5.6 per 100 person-years [95% confidence interval (CI): 4.9 to 6.4]. Among those initiating HAART in 2000-2008, the participants with elevated baseline CD8 counts had significantly greater risk of VF compared with those with baseline CD8 counts ≤ 600 cells per cubic millimeter [hazard ratio (HR) = 2.68, 95% CI: 1.13 to 6.35]. The participants with elevated CD8 counts at >20% of previous 6-month follow-up visits had a greater risk of failure at the current visit than those who did not (HR = 1.53, 95% CI: 1.14 to 2.06). Those with CD8 counts that increased after the start of HAART had a greater risk of failure than those with CD8 counts that decreased or remained the same (HR = 1.59, 95% CI: 1.19 to 2.13). Initial or serial elevated CD8 counts while on HAART or an increase in CD8 counts from HAART initiation may be early warnings for future treatment failure.

  3. Factors associated with HIV-1 virological failure in an outpatient clinic for HIV-infected people in Haiphong, Vietnam

    DEFF Research Database (Denmark)

    Huong, D T M; Bannister, W; Phong, P T


    The objective of our study was to investigate factors associated with virological failure in 100 consecutive HIV-1 infected Vietnamese adults who initiated antiretroviral therapy (ART) from June 2007 to June 2008. Data were collected from medical records, and a structured questionnaire was used i...

  4. Lower liver stiffness in patients with sustained virological response 4 years after treatment for chronic hepatitis C

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Moessner, Belinda Klemmensen; Christensen, Peer Brehm


    Transient elastography (TE) is a noninvasive and well validated method for measurement of liver stiffness. The aim of this study was to use TE to evaluate whether patients with sustained virological response (SVR) have lower liver stiffness than patients with non-SVR after treatment for chronic...

  5. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

    DEFF Research Database (Denmark)

    Chereau, Fanny; Madec, Yoann; Sabin, Caroline


    OBJECTIVE: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. MET...

  6. Defining a Cutoff for Atazanavir in Hair Samples Associated With Virological Failure Among Adolescents Failing Second-Line Antiretroviral Treatment. (United States)

    Chawana, Tariro D; Gandhi, Monica; Nathoo, Kusum; Ngara, Bernard; Louie, Alexander; Horng, Howard; Katzenstein, David; Metcalfe, John; Nhachi, Charles F B


    Adequate antiretroviral exposure is crucial to virological suppression. We assessed the relationship between atazanavir hair levels with self-reported adherence, virological outcomes, and the effect of a home-based adherence intervention in HIV-infected adolescents failing second-line antiretroviral treatment in Zimbabwe. HIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for ≥6 months with viral load (VL) >1000 copies/mL were randomized to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (intervention). Questionnaires were administered; VL and hair samples were collected at baseline and after 90 days in each group. Viral suppression was defined as hair concentration 2.35 ng/mg) hair concentrations. Participants with virological failure were more likely to have suboptimal atazanavir hair concentrations (RR = 7.2, 95% CI: 1 to 51, P = 0.049). There were no differences in atazanavir hair concentration between the arms after follow-up. A threshold of atazanavir concentrations in hair (2.35 ng/mg), above which virological suppression was likely, was defined for adolescents failing second-line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self-reported adherence were associated with adequate atazanavir hair concentrations. Antiretroviral hair concentrations may serve as a useful clinical tool among adolescents.

  7. Pretreatment HIV drug resistance results in virological failure and accumulation of additional resistance mutations in Ugandan children

    NARCIS (Netherlands)

    Kityo, Cissy; Boerma, Ragna S.; Sigaloff, Kim C. E.; Kaudha, Elizabeth; Calis, Job C. J.; Musiime, Victor; Balinda, Sheila; Nakanjako, Rita; Boender, T. Sonia; Mugyenyi, Peter N.; Rinke de Wit, Tobias F.


    Background: Pretreatment HIV drug resistance (PDR) can impair virological response to ART, jeopardizing effective treatment for children. Methods: Children aged <12 years initiated first-line ART in Uganda during 2010-11. Baseline and 6 monthly viral load (VL) and genotypic resistance testing if VL.

  8. Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, A; Phillips, AN; Ruiz, L


    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...

  9. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia


    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...

  10. Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose? (United States)

    Lagard, Camille; Chevillard, Lucie; Malissin, Isabelle; Risède, Patricia; Callebert, Jacques; Labat, Laurence; Launay, Jean-Marie; Laplanche, Jean-Louis; Mégarbane, Bruno


    Poisoning with opioid analgesics including tramadol represents a challenge. Tramadol may induce respiratory depression, seizures and serotonin syndrome, possibly worsened when in combination to benzodiazepines. Our objectives were to investigate tramadol-related neurotoxicity, consequences of diazepam/tramadol combination, and mechanisms of drug-drug interactions in rats. Median lethal-doses were determined using Dixon-Bruce's up-and-down method. Sedation, seizures, electroencephalography and plethysmography parameters were studied. Concentrations of tramadol and its metabolites were measured using liquid-chromatography-high-resolution-mass-spectrometry. Plasma, platelet and brain monoamines were measured using liquid-chromatography coupled to fluorimetry. Median lethal-doses of tramadol and diazepam/tramadol combination did not significantly differ, although time-to-death was longer with combination (P=0.04). Tramadol induced dose-dependent sedation (Pdiazepam/tramadol combination abolished seizures but significantly enhanced sedation (Pdiazepam/tramadol combination. Interestingly neither pretreatment with cyproheptadine (a serotonin-receptor antagonist) nor a benserazide/5-hydroxytryptophane combination (enhancing brain serotonin) reduced tramadol-induced seizures. Our study shows that diazepam/tramadol combination does not worsen tramadol-induced fatality risk but alters its toxicity pattern with enhanced respiratory depression but abolished seizures. Drug-drug interaction is mainly pharmacodynamic but increased plasma M1 and M5 metabolites may also contribute to enhancing respiratory depression. Tramadol-induced seizures are independent of brain serotonin. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Reduction in body weight but worsening renal function with late ultrafiltration for treatment of acute decompensated heart failure. (United States)

    Dev, Sandesh; Shirolkar, Shailesh C; Stevens, Susanna R; Shaw, Linda K; Adams, Patricia A; Felker, G Michael; Rogers, Joseph G; O'Connor, Christopher M


    The safety, effectiveness and indications for ultrafiltration (UF) are not well established. We hypothesized that UF would not worsen renal function in patients with heart failure (HF) who were not responding to medical therapy. Data was collected for patients who underwent UF between 2006 and 2010 (n = 72, median age 61 years, 54% males, 61% Caucasian, 54% left ventricular ejection fraction ≥ 40%). Baseline GFR was 38 ml/min/1.73 m2. All patients were initially treated with loop diuretics and 58% required a thiazide-like diuretic or vasoactive agent. UF resulted in total fluid removal of 11.3 liters and weight loss was 9.7 kg. The median decrease in eGFR during UF was 4.5 ml/min/m2 (IQR--13, 0; p < 0.01) and 43% of patients experienced a ≥ 20% decrease in eGFR. Ten percent of patients required dialysis and 13% died, received a ventricular assist device/cardiac transplant or were discharged to hospice. In a cohort of HF patients who did not respond to medical therapy, UF was associated not only with a significant reduction of body weight and fluid removal, but also acute worsening of renal function. Further research to identify the appropriate population for UF, long-term outcomes and the intensity of treatment is required if UF is to gain wide acceptance for HF management. Copyright © 2012 S. Karger AG, Basel.

  12. Characteristics and outcomes of initial virologic suppressors during analytic treatment interruption in a therapeutic HIV-1 gag vaccine trial.

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    Jonathan Z Li

    Full Text Available In the placebo-controlled trial ACTG A5197, a trend favoring viral suppression was seen in the HIV-1-infected subjects who received a recombinant Ad5 HIV-1 gag vaccine.To identify individuals with initial viral suppression (plasma HIV-1 RNA set point <3.0 log(10 copies/ml during the analytic treatment interruption (ATI and evaluate the durability and correlates of virologic control and characteristics of HIV sequence evolution.HIV-1 gag and pol RNA were amplified and sequenced from plasma obtained during the ATI. Immune responses were measured by flow cytometric analysis and intracellular cytokine expression assays. Characteristics of those with and without initial viral suppression were compared using the Wilcoxon rank sum and Fisher's exact tests.Eleven out of 104 participants (10.6% were classified as initial virologic suppressors, nine of whom had received the vaccine. Initial virologic suppressors had significantly less CD4+ cell decline by ATI week 16 as compared to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04. However, of the ten initial virologic suppressors with a pVL at ATI week 49, only three maintained pVL <3.0 log(10 copies/ml. HIV-1 Gag-specific CD4+ interferon-γ responses were not associated with initial virologic suppression and no evidence of vaccine-driven HIV sequence evolution was detected. Participants with initial virologic suppression were found to have a lower percentage of CD4+ CTLA-4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag-reactive CD4+ TNF-α+ cells expressing either CTLA-4 or PD-1.Among individuals participating in a rAd5 therapeutic HIV-1 gag vaccine trial, initial viral suppression was found in a subset of patients, but this response was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T cells and virologic outcome warrants further study in trials of other therapeutic vaccines in NCT

  13. Worsening diastolic function is associated with elevated fasting plasma glucose and increased left ventricular mass in a supra-additive fashion in an elderly, healthy, Swedish population

    DEFF Research Database (Denmark)

    Pareek, Manan; Nielsen, Mette Lundgren; Gerke, Oke


    AIMS: To examine whether increasing fasting plasma glucose (FPG) levels were associated with worsening left ventricular (LV) diastolic function, independently of LV mass index (LVMI) in elderly, otherwise healthy subjects. METHODS AND RESULTS: We tested cross-sectional associations between...

  14. Immunological and virological consequences of patient-directed antiretroviral therapy interruption during chronic HIV-1 infection. (United States)

    Burton, C T; Nelson, M R; Hay, P; Gazzard, B G; Gotch, F M; Imami, N


    Increasing numbers of patients are choosing to interrupt highly active antiretroviral therapy (HAART). We describe the effect of patient-directed treatment interruption (PDTI) on plasma viral loads (pVL), proviral DNA (pDNA), lymphocyte subsets and immune responses in 24 chronically HIV-1 infected individuals. Patients were divided into group A with pVL > 50 copies/ml and group B with pVL anti-HIV-1 immune responses do not favour the auto-vaccination hypothesis.

  15. Timing of pregnancy, postpartum risk of virologic failure and loss to follow-up among HIV-positive women. (United States)

    Onoya, Dorina; Sineke, Tembeka; Brennan, Alana T; Long, Lawrence; Fox, Matthew P


    We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. This is a retrospective cohort study of 6306 HIV-positive women aged 15-49 at antiretroviral therapy (ART) initiation, initiated on ART between January 2004 and December 2013 in Johannesburg, South Africa. The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling. The rate of postpartum virologic failure was higher following an incident pregnancy on ART [adjusted hazard ratio 1.8, 95% confidence interval (CI): 1.1-2.7] than among women who initiated ART during pregnancy. This difference was sustained among women with CD4 cell count less than 350 cells/μl at delivery (adjusted hazard ratio 1.8, 95% CI: 1.1-3.0). Predictors of postpartum virologic failure were being viremic, longer time on ART, being 25 or less years old and low CD4 cell count and anaemia at delivery, as well as initiating ART on stavudine-containing or abacavir-containing regimen. There was no difference postpartum loss to follow-up rates between the incident pregnancies group (hazard ratio 0.9, 95% CI: 0.7-1.1) and those who initiated ART in pregnancy. The risk of virologic failure remains high among postpartum women, particularly those who conceive on ART. The results highlight the need to provide adequate support for HIV-positive women with fertility intention after ART initiation and to strengthen monitoring and retention efforts for postpartum women to sustain the benefits of ART.

  16. Socioeconomic position and ten-year survival and virologic outcomes in a Ugandan HIV cohort receiving antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Andrew G Flynn

    Full Text Available Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004-2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1 mortality, 2 virologic failure, and 3 mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127 of participants died, 6% (n = 31 were lost-to-follow-up and 23% (107/472 experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10

  17. Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in Rwanda. (United States)

    Ndahimana, Jean d'Amour; Riedel, David J; Mwumvaneza, Mutagoma; Sebuhoro, Dieudone; Uwimbabazi, Jean Claude; Kubwimana, Marthe; Mugabo, Jules; Mulindabigwi, Augustin; Kirk, Catherine; Kanters, Steve; Forrest, Jamie I; Jagodzinski, Linda L; Peel, Sheila A; Ribakare, Muhayimpundu; Redfield, Robert R; Nsanzimana, Sabin


    To evaluate HIV drug resistance (HIVDR) and determinants of virological failure in a large cohort of patients receiving first-line tenofovir-based antiretroviral therapy (ART) regimens. A nationwide retrospective cohort from 42 health facilities was assessed for virological failure and development of HIVDR mutations. Data were collected at ART initiation and at 12 months of ART on patients with available HIV-1 viral load (VL) and ART adherence measurements. HIV resistance genotyping was performed on patients with VL ≥1000 copies/ml. Multiple logistic regression was used to determine factors associated with treatment failure. Of 828 patients, 66% were women, and the median age was 37 years. Of the 597 patients from whom blood samples were collected, 86.9% were virologically suppressed, while 11.9% were not. Virological failure was strongly associated with age CD4 counts <200 cells/μl (aOR 3.4; 95% CI: 1.9-6.2). Overall, 9.1% of all patients on ART had drug resistance mutations after 1 year of ART; 27% of the patients who failed treatment had no evidence of HIVDR mutations. HIVDR mutations were not observed in patients on the recommended second-line ART regimen in Rwanda. The last step of the UNAIDS 90-90-90 target appears within grasp, with some viral failures still due to non-adherence. Nonetheless, youth and late initiators are at higher risk of virological failure. Youth-focused programmes could help prevent further drug HIVDR development. © 2016 John Wiley & Sons Ltd.

  18. Association of baseline vitamin D level with genetic determinants and virologic response in patients with chronic hepatitis B. (United States)

    Yu, Rui; Tan, Deming; Ning, Qin; Niu, Junqi; Bai, Xuefan; Chen, Shijun; Cheng, Jun; Yu, Yanyan; Wang, Hao; Xu, Min; Shi, Guangfeng; Wan, Mobin; Chen, Xinyue; Tang, Hong; Sheng, Jifang; Dou, Xiaoguang; Shi, Junping; Ren, Hong; Wang, Maorong; Zhang, Hongfei; Gao, Zhiliang; Chen, Chengwei; Ma, Hong; Jia, Jidong; Hou, Jinlin; Xie, Qing; Sun, Jian


    The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week-104 treatment outcome in CHB patients. Baseline serum 25-hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine-based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104. The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62-0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization. Vitamin D insufficiency was highly prevalent in treatment-naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week-104 virologic response, but not HBeAg seroconversion or ALT normalization. © 2017 The Japan Society of Hepatology.

  19. Experimental hyperglycemia induces an increase of monocyte and T-lymphocyte content in adipose tissue of healthy obese women.

    Directory of Open Access Journals (Sweden)

    Michaela Tencerová

    Full Text Available Hyperglycemia represents one of possible mediators for activation of immune system and may contribute to worsening of inflammatory state associated with obesity. The aim of our study was to investigate the effect of a short-term hyperglycemia (HG on the phenotype and relative content of immune cells in circulation and subcutaneous abdominal adipose tissue (SAAT in obese women without metabolic complications.Three hour HG clamp with infusion of octreotide and control investigations with infusion of octreotide or saline were performed in three groups of obese women (Group1: HG, Group 2: Octreotide, Group 3: Saline, n=10 per group. Before and at the end of the interventions, samples of SAAT and blood were obtained. The relative content of immune cells in blood and SAAT was determined by flow cytometry. Gene expression analysis of immunity-related markers in SAAT was performed by quantitative real-time PCR.In blood, no changes in analysed immune cell population were observed in response to HG. In SAAT, HG induced an increase in the content of CD206 negative monocytes/macrophages (p<0.05 and T lymphocytes (both T helper and T cytotoxic lymphocytes, p<0.01. Further, HG promoted an increase of mRNA levels of immune response markers (CCL2, TLR4, TNFα and lymphocyte markers (CD3g, CD4, CD8a, TBX21, GATA3, FoxP3 in SAAT (p<0.05 and 0.01. Under both control infusions, none of these changes were observed.Acute HG significantly increased the content of monocytes and lymphocytes in SAAT of healthy obese women. This result suggests that the short-term HG can modulate an immune status of AT in obese subjects.

  20. Stretched cell cycle model for proliferating lymphocytes (United States)

    Dowling, Mark R.; Kan, Andrey; Heinzel, Susanne; Zhou, Jie H. S.; Marchingo, Julia M.; Wellard, Cameron J.; Markham, John F.; Hodgkin, Philip D.


    Stochastic variation in cell cycle time is a consistent feature of otherwise similar cells within a growing population. Classic studies concluded that the bulk of the variation occurs in the G1 phase, and many mathematical models assume a constant time for traversing the S/G2/M phases. By direct observation of transgenic fluorescent fusion proteins that report the onset of S phase, we establish that dividing B and T lymphocytes spend a near-fixed proportion of total division time in S/G2/M phases, and this proportion is correlated between sibling cells. This result is inconsistent with models that assume independent times for consecutive phases. Instead, we propose a stretching model for dividing lymphocytes where all parts of the cell cycle are proportional to total division time. Data fitting based on a stretched cell cycle model can significantly improve estimates of cell cycle parameters drawn from DNA labeling data used to monitor immune cell dynamics. PMID:24733943

  1. Lymphocytic subsets and low-dose exposure

    International Nuclear Information System (INIS)

    Tuschl, H.; Kovac, R.; Eybl, E.


    The present investigations proved the differential radiosensitivity of lymphocytic subpopulations: From in vivo and in vitro irradiations it may be followed that the most sensitive subset are CD8 positive suppressor T cells. CD4/CD8 ratios are increased both in peripheral blood and after mitogen stimulation of lymphocytes of exposed persons. The decrease in B cells is pronounced only at higher radiation doses. Though the rate of DNA synthesis after mitogen stimulation was reduced in some exposed persons, that was no general phenomenon. Especially after tritium exposure, the observed lymphopenia correlated with an increased stimulation by PHA and an increased rate of DNA synthesis in some probands. Thus the present investigations indicate that - despite an inhibition of some immune parameters by radioexposure - the body is able to maintain its immunological homoeostasis. (authors)

  2. Characteristics of T lymphocyte subpopulations 

    Directory of Open Access Journals (Sweden)

    Paulina Niedźwiedzka-Rystwej


    Full Text Available The paper describes the characteristics, receptor profile and functions of T lymphocyte subpopulations (helper, cytotoxic, regulatory, memory and others. Among T helper cells one can enumerate Th0, Th1, Th2, Th9, Th17, Th22, TFH and nTh2, while T cytotoxic cells include Tc, NKT, Tγδ, and T CD8αα (IEL. Among regulatory cells there are nTreg, iTreg, TR1, and iTR35, as well as T lymphocytes with CD8, such as CD8 CD122 , CD8 CD28-, and CD11c CD8 . And among memory T cells there are Tcm and Tem. Moreover, there are some so-called other T cells, such as Tn (T αβ CD4 and T αβ CD8 , T exhausted and T anergic. 

  3. Human CD56+ cytotoxic lung lymphocytes kill autologous lung cells in chronic obstructive pulmonary disease.

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    Christine M Freeman

    Full Text Available CD56+ natural killer (NK and CD56+ T cells, from sputum or bronchoalveolar lavage of subjects with chronic obstructive pulmonary disease (COPD are more cytotoxic to highly susceptible NK targets than those from control subjects. Whether the same is true in lung parenchyma, and if NK activity actually contributes to emphysema progression are unknown. To address these questions, we performed two types of experiments on lung tissue from clinically-indicated resections (n = 60. First, we used flow cytometry on fresh single-cell suspension to measure expression of cell-surface molecules (CD56, CD16, CD8, NKG2D and NKp44 on lung lymphocytes and of the 6D4 epitope common to MICA and MICB on lung epithelial (CD326+ cells. Second, we sequentially isolated CD56+, CD8+ and CD4+ lung lymphocytes, co-cultured each with autologous lung target cells, then determined apoptosis of individual target cells using Annexin-V and 7-AAD staining. Lung NK cells (CD56+ CD3- and CD56+ T cells (CD56+ CD3+ were present in a range of frequencies that did not differ significantly between smokers without COPD and subjects with COPD. Lung NK cells had a predominantly "cytotoxic" CD56+ CD16+ phenotype; their co-expression of CD8 was common, but the percentage expressing CD8 fell as FEV1 % predicted decreased. Greater expression by autologous lung epithelial cells of the NKG2D ligands, MICA/MICB, but not expression by lung CD56+ cells of the activating receptor NKG2D, correlated inversely with FEV1 % predicted. Lung CD56+ lymphocytes, but not CD4+ or CD8+ conventional lung T cells, rapidly killed autologous lung cells without additional stimulation. Such natural cytotoxicity was increased in subjects with severe COPD and was unexplained in multiple regression analysis by age or cancer as indication for surgery. These data show that as spirometry worsens in COPD, CD56+ lung lymphocytes exhibit spontaneous cytotoxicity of autologous structural lung cells, supporting their

  4. Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia

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    Tamayev Robert


    Full Text Available Abstract Background A mutation in the BRI2/ITM2b gene causes familial Danish dementia (FDD. BRI2 is an inhibitor of amyloid-β precursor protein (APP processing, which is genetically linked to Alzheimer’s disease (AD pathogenesis. The FDD mutation leads to a loss of BRI2 protein and to increased APP processing. APP haplodeficiency and inhibition of APP cleavage by β-secretase rescue synaptic/memory deficits of a genetically congruous mouse model of FDD (FDDKI. β-cleavage of APP yields the β-carboxyl-terminal (β-CTF and the amino-terminal-soluble APPβ (sAPPβ fragments. γ-secretase processing of β-CTF generates Aβ, which is considered the main cause of AD. However, inhibiting Aβ production did not rescue the deficits of FDDKI mice, suggesting that sAPPβ/β-CTF, and not Aβ, are the toxic species causing memory loss. Results Here, we have further analyzed the effect of γ-secretase inhibition. We show that treatment with a γ-secretase inhibitor (GSI results in a worsening of the memory deficits of FDDKI mice. This deleterious effect on memory correlates with increased levels of the β/α-CTFs APP fragments in synaptic fractions isolated from hippocampi of FDDKI mice, which is consistent with inhibition of γ-secretase activity. Conclusion This harmful effect of the GSI is in sharp contrast with a pathogenic role for Aβ, and suggests that the worsening of memory deficits may be due to accumulation of synaptic-toxic β/α-CTFs caused by GSI treatment. However, γ-secretase cleaves more than 40 proteins; thus, the noxious effect of GSI on memory may be dependent on inhibition of cleavage of one or more of these other γ-secretase substrates. These two possibilities do not need to be mutually exclusive. Our results are consistent with the outcome of a clinical trial with the GSI Semagacestat, which caused a worsening of cognition, and advise against targeting γ-secretase in the therapy of AD. Overall, the data also indicate that FDDKI

  5. Worsening dual-task gait costs after concussion and their association with subsequent sport-related injury. (United States)

    Howell, David Robert; Buckley, Thomas; Lynall, Robert C; Meehan, William


    Prior studies suggest that concussion may lead to an increased risk of a subsequent time-loss sport-related injury, but the mechanisms responsible are unknown. We measured the symptom and dual-task gait outcomes for athletes initially post-concussion and after clinical recovery. Participants then self-reported any additional injuries incurred in the year after their concussion. Forty-two athletes (52% female, mean age=16.8±3.2 years) completed the study. They underwent a dual-task gait evaluation and symptom inventory within 21 days post-concussion, and again after they were deemed clinically recovered. Approximately one year later, participants documented if they had sustained any subsequent sport-related injuries. Repeated measures ANOVAs were used to evaluate changes in dual-task gait and symptoms across time and between groups. A significant group*time interaction (p=0.02) indicated that the group who went on to sustain a subsequent time-loss injury after returning to sports (n=15) demonstrated significant average walking speed dual-task cost worsening across time (-17.9±9.1% vs. -25.1±12.5%; p=0.007). In contrast, the group who did not sustain an additional injury walked with consistent dual-task cost values across time (-25.2±9.2% vs. -24.6±8.4%; p=0.76). Symptoms improved for all participants (main effect of time p<0.001; PCSS= 25.0±16.9 vs. 2.8±7.5; p<0.001), but did not differ between groups (p=0.77). Significant dual-task gait cost worsening throughout concussion recovery was associated with time-loss injuries during sports in the year after a concussion. These findings indicate that worsening ability to execute a concurrent gait and cognitive task may relate to the risk of incurring an injury during sports after clinical concussion recovery.

  6. Radiosensitivity of human lymphocytes and thymocytes

    International Nuclear Information System (INIS)

    Kwan, D.K.; Norman, A.


    The in vitro survival of human peripheral blood lymphocytes and thymocytes was measured 4 days following graded doses of γ radiation. Results indicate considerable heterogeneity among lymphocyte subpopulations with respect to radiosensitivity. Total T lymphocytes were characterized by rosette formation with neuraminidase-treated sheep red blood cells (nSRBC); early T (T/sub E/) cells, by early rosettes; and B cells, by their inability to form nSRBC rosettes. Late T (T/sub L/) cells were defined as T -- T/sub E/. Survival curves of T, T/sub E/, and B cells are biphasic. The radiosensitive and radioresistant components of T, T/sub E/, and B cells all have a D 0 of about 50 and 550 rad, respectively. B cells appeared to be slightly more radiosensitive than T cells. T/sub L/ cells and thymocytes, however, appeared to be homogeneous with respect to radiosensitivity, both having D 0 values of about 135 rad. The survival of T cells in mixed T and B cell cultures resembled that of separated T cells, suggesting that ionizing radiation has no significant effect on rosette formation. It also indicates that interactions of T and B cells do not significantly affect their radiation responses

  7. Decreased lymphocyte dopamine transporter in romantic lovers. (United States)

    Marazziti, Donatella; Baroni, Stefano; Giannaccini, Gino; Piccinni, Armando; Mucci, Federico; Catena-Dell'Osso, Mario; Rutigliano, Grazia; Massimetti, Gabriele; Dell'Osso, Liliana


    The role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship. All subjects had no physical or psychiatric illness. The DAT was measured by means of the [3H]-WIN 35,428 binding and the [3H]-DA reuptake to resting lymphocytes membranes. Romantic love was assessed by a specific questionnaire developed by us. The results showed that the subjects in the early phase of romantic love had a global alteration of the lymphocyte DAT involving both a decreased number of proteins (Bmax) and a reduced functionality (Vmax). Taken together, these findings would indicate the presence of increased levels of DA in romantic love that, if paralleled by similar concentrations in the brain, would explain some peculiar features of this human feeling.

  8. Normal lymphocyte immunophenotype in an elderly population

    Directory of Open Access Journals (Sweden)

    Sâmia Macedo Queiroz Mota Castellão Tavares


    Full Text Available OBJECTIVE: The aim of this work was to evaluate the lymphocyte immunophenotype in an elderly population.METHODS: This study enrolled 35 over 60-year-old volunteers and a control group composed of 35 young adults. The study included elderly without diseases that might affect the functioning of the immune system. These individuals were consulted by doctors and after a physical examination, laboratory tests were performed using a Beckman Coulter (r flow cytometer. The GraphPad Prism computer program was employed for statistical analysis with the level of significance being set for p-values <0.05.RESULTS: There is a statistically significant reduction in the number of lymphocytes (CD8 +, CD2 + and CD3 + cells in the elderly compared to young adults. These low rates are explained by changes attributed to aging and may be partly responsible for the reduction in the cellular immune response, lower proliferative activity and the low cytotoxicity of lymphocytes.CONCLUSION: These parameters showed greater impairment of adaptive immunity in the elderly population and can therefore explain the greater fragility of the aged body to developing diseases.

  9. Financial crisis 2007-2009. How real estate bubble and transparency and accountability issues generated and worsen the crisis

    Directory of Open Access Journals (Sweden)

    Bilal Aziz


    Full Text Available This paper seeks to explain some main factors behind the Financial Crisis 2007–2009 with a special focus on the Real Estate Bubble and Transparency and Accountability Issues in US Financial System and how these two factors generated and worsen the crisis. Financial Crisis 2007–2009, which starts from the United States sub–prime mortgage market and spread to US financial sector and later on spread to the rest of world, is said to be an even bigger crisis than the Great Depression of 1929. This crisis is unique in this way and we haven’t seen such a bigger impact world wide from any other crisis. This paper would empirically prove the main causes which are right in the heart of the crisis and least discussed

  10. Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype. (United States)

    Lang, Jason E; Holbrook, Janet T; Mougey, Edward B; Wei, Christine Y; Wise, Robert A; Teague, W Gerald; Lima, John J


    Gastric acid blockade in children with asymptomatic acid reflux has not improved asthma control in published studies. There is substantial population variability regarding metabolism of and response to proton pump inhibitors based on metabolizer phenotype. How metabolizer phenotype affects asthma responses to acid blockage is not known. To determine how metabolizer phenotype based on genetic analysis of CYP2C19 affects asthma control among children treated with a proton pump inhibitor. Asthma control as measured by the Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month clinical trial of lansoprazole in children with asthma was analyzed for associations with surrogates of lansoprazole exposure (based on treatment assignment and metabolizer phenotype). Groups included placebo-treated children; lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes. Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two wild-type alleles were extensive metabolizers (EMs). Asthma control through most of the treatment period was unaffected by lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P = 0.02) and placebo-treated children (+0.16 vs. -0.23; P lansoprazole-treated PMs. Children with the PM phenotype developed worse asthma control after 6 months of lansoprazole treatment for poorly controlled asthma. Increased exposure to proton pump inhibitor may worsen asthma control by altering responses to respiratory infections. Clinical trial registered with (NCT00604851).

  11. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. (United States)

    Maurer, Britta; Graf, Nicole; Michel, Beat A; Müller-Ladner, Ulf; Czirják, László; Denton, Christopher P; Tyndall, Alan; Metzig, Carola; Lanius, Vivian; Khanna, Dinesh; Distler, Oliver


    To identify predictive parameters for the progression of skin fibrosis within 1 year in patients with diffuse cutaneous SSc (dcSSc). An observational study using the EUSTAR database was performed. Inclusion criteria were dcSSc, American College of Rheumatology (ACR) criteria fulfilled, modified Rodnan skin score (MRSS) ≥7 at baseline visit, valid data for MRSS at 2nd visit, and available follow-up of 12±2 months. Worsening of skin fibrosis was defined as increase in MRSS >5 points and ≥25% from baseline to 2nd visit. In the univariate analysis, patients with progressive fibrosis were compared with non-progressors, and predictive markers with panalysis. The prediction models were then validated in a second cohort. A total of 637 dcSSc patients were eligible. Univariate analyses identified joint synovitis, short disease duration (≤15 months), short disease duration in females/patients without creatine kinase (CK) elevation, low baseline MRSS (≤22/51), and absence of oesophageal symptoms as potential predictors for progressive skin fibrosis. In the multivariate analysis, by employing combinations of the predictors, 17 models with varying prediction success were generated, allowing cohort enrichment from 9.7% progressive patients in the whole cohort to 44.4% in the optimised enrichment cohort. Using a second validation cohort of 188 dcSSc patients, short disease duration, low baseline MRSS and joint synovitis were confirmed as independent predictors of progressive skin fibrosis within 1 year resulting in a 4.5-fold increased prediction success rate. Our study provides novel, evidence-based criteria for the enrichment of dcSSc cohorts with patients who experience worsening of skin fibrosis which allows improved clinical trial design. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  12. Blood leukocyte and spleen lymphocyte immune response of spleen lymphocytes and whole blood leukocytes of hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Peters, B.A.; Sothmann, M.; Wehrenberg, W.B. (Univ. of Wisconsin, Milwaukee (USA))


    This study was designed to evaluate the effects of chronic physical activity on the immune response of spleen lymphocytes and whole blood leukocytes of hamsters. Animals were kept sedentary or allowed to exercise spontaneously on running wheels for eight weeks. Physically active animals averaged 12 kilometers per day. The immune response of spleen lymphocytes whole blood leukocytes was evaluated by {sup 3}H-thymidine incorporation in response to Concanavalin A or lipopolysaccharide. There was no treatment effect between physically active and sedentary hamster in response of spleen lymphocytes. The immune response of whole blood leukocytes to these mitogens was significantly greater in physically active vs. sedentary hamsters. These results demonstrate that chronic physical activity has the capacity to modulate immunoresponses.

  13. Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy. (United States)

    Kerschberger, Bernhard; Boulle, Andrew M; Kranzer, Katharina; Hilderbrand, Katherine; Schomaker, Michael; Coetzee, David; Goemaere, Eric; Van Cutsem, Gilles


    Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p<0.001). A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.

  14. Analysis of predictive factors for rapid virologic response in treating patients with chronic hepatitis C

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    ZHANG Dandan


    Full Text Available ObjectiveTo analyze the predictive factors for rapid virologic response (RVR in patients with chronic hepatitis C (CHC who received combination therapy with pegylated interferon (PEG-IFN and ribavirin. MethodsA total of 127 CHC patients who were admitted to our department from 2010 to 2012 and received PEG-IFN combined with ribavirin were enrolled in this retrospective cohort study. The patients were divided into RVR group and non-RVR (NRVR group according to their virologic responses after 4 weeks of antiviral therapy. Demographic characteristics and the clinical features prior to treatment were compared between the two groups, and the potential factors that contributed to the acquisition of RVR were analyzed. Comparison of categorical data between groups was made by chi-square test, predictive factors were analyzed by nonparametric test for two independent samples (Mann-Whitney U test, independent predictive factors were tested by univariate and multivariate logistic regression analyses, and the continuous variables of predictive factors were analyzed using receiver operating characteristic curves. ResultsOf the 127 CHC patients, 86 were males and 41 females. There were 11 confirmed cases of liver cirrhosis. There were 100 patients (78.74% who achieved an RVR, and 27 (21.26% with NRVR. Nonparametric analysis showed that eight factors, which were age, time of infection, level of pre-treatment alanine aminotransferase, level of pre-treatment hyaluronic acid, development of hypertension, type of interferon, pathway of infection, and hepatitis C virus (HCV genotype, were significantly different between the RVR and NRVR groups (P<0.05. The logistic regression analysis identified the following factors as independent predictive factors for RVR: non-genotype 1 (OR: 0.203, 95%CI: 0.051-0.802, P<0.05, time of infection (OR: 0.925, 95%CI: 0.868-0.987, P<0.05, and absence of hypertension (OR: 0.129, 95%CI: 0.032-0.521, P<0.05. Conclusion

  15. Allograft immunity in vitro. I. Cultivation conditions and mixed lymphocyte interaction of mouse peripheral lymphocytes (United States)

    Häyry, P.; Defendi, V.


    We have adapted mouse peripheral lymphocytes to culture as a preliminary step in designing a model for the study of allograft immunity in vitro. The isolation of peripheral leucocytes is facilitated by using Plasmagel® as an erythrocyte-agglutinating agent. The yield of leucocytes can be considerably increased by intravenous injection of the donor animals with supernatant fluid from Bordetella pertussis cultures and the lymphocytes thus mobilized react both to phytohaemagglutinin (PHA) and allogeneic stimulus, as do lymphocytes from untreated animals. Preparations which contain more than 25–50 RBC/WBC are refractory in the mixed lymphocyte interaction (MLI). The optimum cell density for the proliferative response is approximately 1–3 × 106 lymphocytes/ml. Various nutritive milieu were tested and found to have little influence on the MLI; both normal and suspension media behaved in a similar manner. PHA causes a vigorous proliferative response in mouse peripheral lymphocytes, the 3H–TdR incorporation values in PHA-containing cultures at peak point of stimulation (3rd day) being up to 1000 times those observed for control cultures. The allogeneic response in the MLI takes place later (6th to 7th day) and is weaker, about one-tenth the PHA response, when strains differing at the H-2 locus are used as cell donors. Because the specific proliferative response to allogeneic stimulus in mixed culture, regardless of the way it is measured, is indistinguishable from the response produced by other non-specific factors, these other factors must be critically excluded. It appears that supplementing the culture medium with low concentrations of certain lots of foetal calf or agamma-newborn-calf serum permits the study of the specific response at an optimum sensitivity. PMID:4315207

  16. Worsening atrioventricular conduction after hospital discharge in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: the HORIZONS-AMI trial. (United States)

    Kosmidou, Ioanna; Redfors, Björn; McAndrew, Thomas; Embacher, Monica; Mehran, Roxana; Dizon, José M; Ben-Yehuda, Ori; Mintz, Gary S; Stone, Gregg W


    The chronic effects of ST-segment elevation myocardial infarction (STEMI) on the atrioventricular conduction (AVC) system have not been elucidated. This study aimed to evaluate the incidence, predictors, and outcomes of worsened AVC post-STEMI in patients treated with a primary percutaneous coronary intervention (PCI). The current analysis included patients from the HORIZONS-AMI trial who underwent primary PCI and had available ECGs. Patients with high-grade atrioventricular block or pacemaker implant at baseline were excluded. Analysis of ECGs excluding the acute hospitalization period indicated worsened AVC in 131 patients (worsened AVC group) and stable AVC in 2833 patients (stable AVC group). Patients with worsened AVC were older, had a higher frequency of hypertension, diabetes, renal insufficiency, previous coronary artery bypass grafting, and predominant left anterior descending culprit lesions. Predictors of worsened AVC included age, hypertension, and previous history of coronary artery disease. Worsened AVC was associated with an increased rate of all-cause death and major adverse cardiac events (death, myocardial infarction, ischemic target vessel revascularization, and stroke) as well as death or reinfarction at 3 years. On multivariable analysis, worsened AVC remained an independent predictor of all-cause death (hazard ratio: 2.005, confidence interval: 1.051-3.827, P=0.0348) and major adverse cardiac events (hazard ratio 1.542, confidence interval: 1.059-2.244, P=0.0238). Progression of AVC system disease in patients with STEMI treated with primary PCI is uncommon, occurs primarily in the setting of anterior myocardial infarction, and portends a high risk for death and major adverse cardiac events.

  17. Chronic Lymphocytic Leukaemia/ Small-Cell Lymphocytic Lymphoma of the Lacrimal Sac: A Case Series. (United States)

    Krishna, Yamini; Irion, Luciane D; Karim, Sozan; Dharmsena, Aruna; McCormick, Austin; Coupland, Sarah E


    Lymphomas of the lacrimal sac are rare, accounting for less than 10% of lacrimal sac malignant tumours. They may present with symptoms typical of secondary acquired nasolacrimal duct obstruction and are thus often misdiagnosed. Case series and literature review. Herein we describe 3 cases of chronic lymphocytic leukaemia (CLL)/small-cell lymphocytic lymphoma (SLL) of the lacrimal sac with immunohistochemical and in 1 case molecular confirmation. Lymphomas of the lacrimal sac should be suspected in patients with known CLL presenting with epiphora and dacryocystitis. During dacryocystorhinostomy, an incisional biopsy of the lacrimal sac is essential for confirming CLL/SLL involvement and may guide treatment.

  18. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D.; Schuresko, D.D.


    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  19. Virological and serological studies of porcine respiratory coronavirus infection on a Japanese farm. (United States)

    Usami, Yoshihide; Fukai, Katsuhiko; Ichikawa, Yutaka; Okuda, Yo; Shibata, Isao; Motoyama, Chihiro; Imai, Kunitoshi; Kirisawa, Rikio


    We detected transmissible gastroenteritis virus (TGEV) antibodies in pig farms in Tochigi prefecture, although the farms had no past record of TGEV vaccination or TGE. Among the farms, Farm A showed a high antibody incidence. We could not confirm if either TGEV or porcine respiratory coronavirus (PRCV) induced the antibodies, since conventional tests failed to discriminate PRCV from TGEV. Therefore, we conducted virological and serological examinations of this farm for 4 years to establish the etiology - TGEV or PRCV. Although no TGEV was detected, PRCVs were isolated from the nasal samples of pigs. Using a commercial ELISA kit, it was found that the antibodies detected in pigs of all the raising stages and sows were raised against PRCV but not TGEV. The phylogenetic analysis of the nucleotide sequences of the isolates showed that they were closely related to each other, and formed a separate cluster apart from the U.S.A. and European strains. In Cesarean-derived, colostrums-deprived piglets inoculated with a PRCV isolate, no clinical signs were seen, and the viruses were mainly isolated from the nasal samples. Moreover, viral genes were detected from the nasal sample of the contact pig. The result suggested that PRCV infection was located in the nasal cavity of pigs, and horizontal transmission easily occurs. From these results, PRCVs with different origins from the exotic PRCVs might be prevalent in pig farms in Japan.

  20. The serological and virological investigation of canine adenovirus infection on the dogs. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Oya Bulut


    Full Text Available 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.

  2. Epidemiological and virological studies into the poliomyelitis in Valencia (1959-1969

    Directory of Open Access Journals (Sweden)

    Báguena Cervellera, María José


    Full Text Available Studies into the polio virus began in Valencia in 1959 with the work undertaken by the microbiologist Vicente Sanchis-Bayarri Vaillant. After his education at the Rochester University and at the Pasteur Institute, Sanchis-Bayarri Vaillant established a laboratory of cell cultures at the Faculty of Medicine in Valencia, where he developed a new diagnostic technique for the poliomyelitis virus. In addition, epidemiological studies were carried out both prior to and post the 1963 vaccination campaign, which proved that Sabin’s oral vaccine was both effective and safe for use.

    Los estudios sobre el virus de la polio comenzaron en Valencia en 1959 de la mano del microbiólogo Vicente Sanchis-Bayarri Vaillant. Tras su formación en virología en la Universidad de Rochester y en el Instituto Pasteur, puso en marcha un laboratorio de cultivos celulares en la Facultad de Medicina de Valencia, en donde desarrolló una técnica diagnóstica nueva para el virus de la polio. Por otra parte, se llevaron a cabo estudios epidemiológicos antes y después de la campaña de vacunación de 1963, que demostraron la eficacia de la vacuna oral de Sabin y su inocuidad.

  3. HIV-1 DNA predicts disease progression and post-treatment virological control (United States)

    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


    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: PMID:25217531

  4. The Serological and Virological Investigation of Canine Adenovirus Infection on the Dogs (United States)

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


    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

  5. Metagenomic approaches for direct and cell culture evaluation of the virological quality of wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Aw, Tiong Gim; Howe, Adina; Rose, Joan B.


    Genomic-based molecular techniques are emerging as powerful tools that allow a comprehensive characterization of water and wastewater microbiomes. Most recently, next generation sequencing (NGS) technologies which produce large amounts of sequence data are beginning to impact the field of environmental virology. In this study, NGS and bioinformatics have been employed for the direct detection and characterization of viruses in wastewater and of viruses isolated after cell culture. Viral particles were concentrated and purified from sewage samples by polyethylene glycol precipitation. Viral nucleic acid was extracted and randomly amplified prior to sequencing using Illumina technology, yielding a total of 18 million sequence reads. Most of the viral sequences detected could not be characterized, indicating the great viral diversity that is yet to be discovered. This sewage virome was dominated by bacteriophages and contained sequences related to known human pathogenic viruses such as adenoviruses (species B, C and F), polyomaviruses JC and BK and enteroviruses (type B). An array of other animal viruses was also found, suggesting unknown zoonotic viruses. This study demonstrated the feasibility of metagenomic approaches to characterize viruses in complex environmental water samples.

  6. Respiratory Viral Infections in Infants: Causes, Clinical Symptoms, Virology, and Immunology (United States)

    Tregoning, John S.; Schwarze, Jürgen


    Summary: In global terms, respiratory viral infection is a major cause of morbidity and mortality. Infancy, in particular, is a time of increased disease susceptibility and severity. Early-life viral infection causes acute illness and can be associated with the development of wheezing and asthma in later life. The most commonly detected viruses are respiratory syncytial virus (RSV), rhinovirus (RV), and influenza virus. In this review we explore the complete picture from epidemiology and virology to clinical impact and immunology. Three striking aspects emerge. The first is the degree of similarity: although the infecting viruses are all different, the clinical outcome, viral evasion strategies, immune response, and long-term sequelae share many common features. The second is the interplay between the infant immune system and viral infection: the immaturity of the infant immune system alters the outcome of viral infection, but at the same time, viral infection shapes the development of the infant immune system and its future responses. Finally, both the virus and the immune response contribute to damage to the lungs and subsequent disease, and therefore, any prevention or treatment needs to address both of these factors. PMID:20065326

  7. Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

    Directory of Open Access Journals (Sweden)

    Glenn Wagner


    Full Text Available Background. Hepatitis C (HCV treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR. Results. Nearly half (46% the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse, and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

  8. The World of Microbes 2002: scientific advances and challenges--impressions and highlights from the 12th Congress of Virology. (United States)

    Becker, Yechiel


    Thousands of scientists participated in the World of Microbes Congress, which was organized by the International Union of the Microbiological Societies (IUMS) and took place in the Palais de Congres in Paris, France from 27 July to 1 August 2002. The attendees were members of the IUMS divisions of Bacteriology and Applied Microbiology, Mycology, and Virology. In addition to the symposia that were organized by each division, joined plenary symposia were held, which encompassed subjects of common interest to all microbiologists. The activities at the 12th Congress of Virology's plenary lectures, symposia, and poster sessions were organized to accommodate the presentation of over 1500 presentations. These brief comments are aimed to provide a sample of only a few presentations that dealt with subjects of emerging and re-emerging virus diseases, which are of general interest.

  9. Virologic Monitoring of Hepatitis B Virus Therapy in Clinical Trials and Practice: Recommendations for a Standardized Approach (United States)



    Treatment of chronic hepatitis B virus (HBV) infection is aimed at suppressing viral replication to the lowest possible level, and thereby to halt the progression of liver disease and prevent the onset of complications. Two categories of drugs are used in HBV therapy: the interferons, including standard interferon alfa or pegylated interferon alfa, and specific nucleoside or nucleotide HBV inhibitors that target the reverse-transcriptase function of HBV-DNA polymerase. The reported results of clinical trials have used varying definitions of efficacy, failure, and resistance based on different measures of virologic responses. This article discusses HBV virologic markers and tests, and their optimal use both for planning and reporting clinical trials and in clinical practice. PMID:18242209

  10. Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years

    DEFF Research Database (Denmark)

    Lodwick, Rebecca; Costagliola, Dominique; Reiss, Peter


    the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI...... ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according...... to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF. CONCLUSIONS: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over...

  11. Cell kinetic and radiosensitivity of PHA stimulated goat lymphocytes

    International Nuclear Information System (INIS)

    Debuyst, B.; Rosenthal, M.; Leonard, A.


    The harlequin-staining method has been used to study the cell kinetic of goat peripheral blood lymphocytes stimulated by phytohemagglutinin and to assess their radiosensitivity. At 48 h, the standardized culture time employed for human lymphocytes, 71% of the goat lymphocytes are in first mitosis, 23% are in second mitosis and 5% in third. Irradiation with 200 rads X-rays induces an average of 24,5 dicentric chromosomes per hundred cells in first mitosis [fr

  12. Gamma/delta T lymphocytes in Mycobacterium tuberculosis infection


    Baliko, Z.; Szereday, L.; Szekeres-Bartho, J.


    BACKGROUND: Data on the percentage of gamma/delta T lymphocytes in the peripheral blood of patients infected with Mycobacterium tuberculosis are few and contradictory. The percentage of gamma/delta T lymphocytes in the peripheral blood of tuberculin positive and tuberculin negative patients with Mycobacterium tuberculosis infection and healthy controls was compared. METHODS: Thirty six patients infected with Mycobacterium tuberculosis and 11 healthy controls were studied. Lymphocytes we...

  13. Helicobacter pylori Associated Lymphocytic Gastritis in a Child


    Kim, Min Jeong; Eom, Dae Woon; Park, Kieyoung


    Lymphocytic gastritis (LG) is a rare subtype of chronic gastritis. It is defined as dense proliferation of intraepithelial lymphocytes (IELs) more than 25 lymphocytes per 100 epithelial cells. The known major causes of LG are celiac disease and Helicobacter pylori infection. H. pylori associated LG (HpLG) has more enhanced cytotoxic and apoptotic tendencies than chronic H. pylori gastritis. A 12-year-old girl with postprandial epigastric pain was diagnosed HpLG on endoscopic biopsy. After the...

  14. Tianeptine is associated with lower risk of suicidal ideation worsening during the first weeks of treatment onset compared with other antidepressants: A naturalistic study. (United States)

    Nobile, B; Jaussent, I; Gorwood, Ph; Lopez Castroman, J; Olié, E; Guillaume, S; Courtet, Ph


    Worsening of suicidal ideation during the first weeks of antidepressant treatment is a poorly understood phenomenon that prompted regulatory bodies to issue specific warnings. To better understand the causes of this phenomenon, this study compared the risk of suicidal ideation worsening in patients taking different types of antidepressant medications. To this aim, 4017 depressed adult outpatients were followed by general practitioners and psychiatrists throughout France for 6 weeks after prescription of an antidepressant treatment. The main study outcomes were to monitor changes (worsening or improvement) in suicidal ideation between baseline (treatment onset) and the study end (week 6) and to determine the remission rates according to the treatment type. Depression severity was assessed with the patient-administered Hospital Anxiety and Depression Scale and suicidal ideation with the 9-item Montgomery-Asberg Depression Rating Scale and the Hopelessness Scale. Use of tianeptine, a mu-opioid receptor agonist was significantly associated with a lower risk of suicidal ideation worsening compared with other antidepressants in the first 6 weeks of treatment. Conversely, remission rates were not significantly affected by the treatment type. Our results highlight a potential interest of opioid agonists to reduce the risk of worsening of suicidal ideation at antidepressant initiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Janet Gare

    Full Text Available 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.

  16. 21 CFR 866.3360 - Lymphocytic choriomeningitis virus serological reagents. (United States)


    ... tests to identify antibodies to lymphocytic choriomeningitis virus in serum. The identification aids in... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents...

  17. [B lymphocyte stimulator in systemic lupus erythematosus]. (United States)

    Mercado, Ulises


    The B lymphocyte stimulator (BLyS) is an essential protein for the growth and survival of B cells. BLyS is expressed on monocytes, macrophages, and dendritic cells. BLyS binds to three receptors on B cells: BAFF-R, BCMA, and TACI. BLyS overexpression in mice leads to lupus-like syndrome, but not in all, whereas BLyS deficient mice results in a block of B cell development. High serum levels of BLyS can be detected in patients with lupus and rheumatoid arthritis. BLyS antagonists are an attractive target for treating autoimmune diseases.

  18. DNA repair in PHA stimulated human lymphocytes

    International Nuclear Information System (INIS)

    Catena, C.; Mattoni, A.


    Damage an repair of radiation induced DNA strand breaks were measured by alkaline lysis and hydroxyapatite chromatography. PHA stimulated human lymphocytes show that the rejoining process is complete within the first 50 min., afterwords secondary DNA damage and chromatid aberration. DNA repair, in synchronized culture, allows to evaluate individual repair capacity and this in turn can contribute to the discovery of individual who, although they do not demonstrate apparent clinical signs, are carriers of DNA repair deficiency. Being evident that a correlation exists between DNA repair capacity and carcinogenesis, the possibility of evaluating the existent relationship between DNA repair and survival in tumor cells comes therefore into discussion

  19. Analysis in cytokinesis-blocked human lymphocytes

    International Nuclear Information System (INIS)

    Catena, C.; Mattoni, A.


    Biological dosimetry can be considered as an additional method to physical dosimetry for estimating dose absorption after exposure to ionizing radiation. Fully validated as well as new promising approaches in this field are reviewed. Recent experiments, carried out in our laboratory, on the analysis of micronuclei in cytokinesis-blocked human lymphocytes are presented. The possible relevance of differential human individual response to ionizing radiation, in view of the occurrence of radiosensitive syndromes, for the estimation of the absorbed dose in human is also discussed

  20. Peripheral lymphocyte subpopulations in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P


    Peripheral lymphocyte subsets--T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and naive/virgin T cells/natural killer cells (CD45RA)--were studied quantitatively in 30 patients with recurrent aphthous ulceration (RAU) and 29 sex- and age-matched RAU-free control donors. The CD4+ percentage was s...... with regard to the demonstration of immunologic disturbances in RAU patients. Whether the imbalance is primary or secondary with regard to the basic etiology remains to be resolved....

  1. Fungal natural products targeting chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen


    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds......,3 This includes analysis of the spectroscopic data generated from LC-DAD-MS to reveal whether the active principles are either structurally known compounds or are likely to be novel compounds. This paper will illustrate our integrated discovery approaches and recent findings of anti-leukemia compounds....

  2. Performance and Logistical Challenges of Alternative HIV-1 Virological Monitoring Options in a Clinical Setting of Harare, Zimbabwe

    Directory of Open Access Journals (Sweden)

    Pascale Ondoa


    Full Text Available We evaluated a low-cost virological failure assay (VFA on plasma and dried blood spot (DBS specimens from HIV-1 infected patients attending an HIV clinic in Harare. The results were compared to the performance of the ultrasensitive heat-denatured p24 assay (p24. The COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0, served as the gold standard. Using a cutoff of 5,000 copies/mL, the plasma VFA had a sensitivity of 94.5% and specificity of 92.7% and was largely superior to the VFA on DBS (sensitivity = 61.9%; specificity = 99.0% or to the p24 (sensitivity = 54.3%; specificity = 82.3% when tested on 302 HIV treated and untreated patients. However, among the 202 long-term ART-exposed patients, the sensitivity of the VFA decreased to 72.7% and to 35.7% using a threshold of 5,000 and 1,000 RNA copies/mL, respectively. We show that the VFA (either on plasma or on DBS and the p24 are not reliable to monitor long-term treated, HIV-1 infected patients. Moreover, achieving acceptable assay sensitivity using DBS proved technically difficult in a less-experienced laboratory. Importantly, the high level of virological suppression (93% indicated that quality care focused on treatment adherence limits virological failure even when PCR-based viral load monitoring is not available.

  3. Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance. (United States)

    Kim, Dong Yun; Lee, Hye Won; Song, Jeong Eun; Kim, Beom Kyung; Kim, Seung Up; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub; Park, Jun Yong


    It is unclear whether chronic hepatitis B (CHB) patients with antiviral resistance, who achieve a complete virologic response (CVR) with tenofovir disoproxil fumarate (TDF) and nucleoside analogue (NUC) combination therapy, maintain CVR if switched to TDF monotherapy. We investigated the persistence of CVR after cessation of NUC in virologically suppressed antiviral resistant CHB patients using TDF+NUC combination therapy. This study recruited 76 antiviral-resistant CHB patients showing CVR on TDF+entecavir (ETV) (n = 52), TDF+lamivudine (LAM; n = 14), and TDF+telbivudine (LdT; n = 10) combination therapy, who were switched to TDF monotherapy as step-down therapy. At baseline, 47 patients were male and the median age was 53.0 years (range: 30-78 years); 72.3% cases were hepatitis B e antigen-positive (HBeAg+) and 23.7% were of liver cirrhosis. The median duration of TDF+NUC combination therapy was 20.8 months (range: 3-46 months). At a median follow-up of 24.7 months (range: 12-48 months) after switching to TDF monotherapy, all 76 patients maintained CVR, regardless of the duration of combination therapy and the type of prior NUC and antiviral resistance. Renal dysfunction was not observed during the treatment period. The step-down strategy of switching from TDF+NUC combination therapy to TDF monotherapy in virologically suppressed CHB patients with antiviral resistance should be considered. © 2017 Wiley Periodicals, Inc.

  4. Effectiveness and Risk Factors for Virological Outcome of Raltegravir-Based Therapy for Treatment-Experienced HIV-Infected Patients. (United States)

    Mata-Marín, José Antonio; Smeke, Ariane Estrella Weiser; Rodriguez, Mariana Rotzinger; Chávez-García, Marcelino; Banda-Lara, Marco Isaac; Rios, Alma Minerva Pérez; Nuñez-Rodríguez, Nohemí; Domínguez-Hermosillo, Juan Carlos; Sánchez, Alberto Chaparro; Juarez-Kasusky, Irene; Herrera, Javier Enrique Cruz; Ramírez, Jorge Luis Sandoval; Gaytán-Martínez, Jesús


    We evaluated the effectiveness of a raltegravir (RAL)-containing regimen plus an optimized background regimen in HIV-1 highly treatment-experienced patients. A retrospective cohort, multicentre study was conducted. Adult (>16 years old) HIV treatment-experience patients starting therapy with a RAL-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (treatment failure. Of the 107 patients in the cohort, 86% were men, the median age was 45 years [interquartile range (IQR) 40-52] and the median number of previous regimens was six (IQR 4-7). After 48 weeks of treatment, 73% (IQR 63-80%) of patients (n = 78) had a viral load of HIV-1 RNA of 40 years [odds ratio (OR) 5.61; 95% confidence interval (CI) 1.61-18.84; P = 0.006] and use of tenofovir in the regimen (OR 0.16; 95% CI 0.03-0.80; P = 0.026). In this Mexican cohort, RAL achieved high rates of virological suppression and an increase in CD4+ cell count in highly treatment-experienced patients infected with HIV-1. Age >40 years was associated with a good virological outcome, contrary to tenofovir use, which was associated with a poor virological outcome.

  5. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

    DEFF Research Database (Denmark)

    Gurusamy, Kurinchi S; Wilson, Edward; Koretz, Ronald L


    Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs....

  6. The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI*

    DEFF Research Database (Denmark)

    Cozzi-Lepri, A; Paredes, R; Phillips, A N


    Virological failure of first-generation nonnucleoside reverse transcriptase inhibitors (NNRTIs) can compromise the efficacy of etravirine as a result of the accumulation of NNRTI resistance mutations. How quickly NNRTI resistance accumulates in patients with a delayed switch from nevirapine...

  7. Clinical, epidemiological and virological features of dengue virus infections in vietnamese patients presenting to primary care facilities with acute undifferentiated fever

    NARCIS (Netherlands)

    Thai, Khoa T. D.; Phuong, Hoang Lan; Thanh Nga, Tran Thi; Giao, Phan Trong; Hung, Le Quoc; van Nam, Nguyen; Binh, Tran Quang; Simmons, Cameron; Farrar, Jeremy; Hien, Tran Thinh; Rogier van Doorn, H.; de Jong, Menno D.; de Vries, Peter J.


    Objectives: To explore clinical and virological characteristics and describe the epidemiology of dengue in patients who presented with acute undifferentiated fever (AUF) at primary health centers (PHC) in Binh Thuan Province, Vietnam. Methods: A prospective observational study was conducted from

  8. HLA-DP related suppression of mixed lymphocyte reaction with alloactivated lymphocytes

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jakobsen, B K


    We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and ...


    Directory of Open Access Journals (Sweden)

    Matteo eBellone


    Full Text Available The tumor is a hostile microenvironment for T lymphocytes. Indeed, irregular blood flow and endothelial cell (EC anergy that characterize most solid tumors hamper leukocyte adhesion, extravasation and infiltration. In addition, hypoxia and reprogramming of energy metabolism within cancer cells transform the tumor mass in a harsh environment that limits survival and effector functions of T cells, regardless of being induced in vivo by vaccination or adoptively transferred. In this review, we will summarize on recent advances in our understanding of the characteristics of tumor associated neoangiogenic vessels as well as of the tumor metabolism that may impact on T cell trafficking and fitness of tumor infiltrating lymphocytes. In particular, we will focus on how advances in knowledge of the characteristics of tumor ECs have enabled identifying strategies to normalize the tumor vasculature and/or overcome EC anergy, thus increasing leukocyte-vessel wall interactions and lymphocyte infiltration in tumors. We will also focus on drugs acting on cells and their released molecules to transiently render the tumor microenvironment more suitable for tumor infiltrating T lymphocytes, thus increasing the therapeutic effectiveness of both active and adoptive immunotherapies.

  10. Thymic influence on the T-lymphocyte self MHC repertoire. II. Cytotoxic T-lymphocyte precursors. (United States)

    Jenski, L J; Miller, B A


    We measured the frequency and specificity of thymic alloantigen-reactive cytotoxic T-lymphocyte precursors in spleens of allogeneic thymus-grafted nude mice tolerant to thymic alloantigens. Under our conditions of limiting dilution analysis we found no selective loss of cytotoxic T-lymphocyte precursors in allogeneic thymus-grafted mice. Upon analysis of individual cytotoxic T-lymphocyte clones, we found that lysis of specific and third party targets was mediated by distinct clones specific for H-2 antigens. Precursors from allogeneic thymus-grafted nudes stimulated at limiting dilutions with thymic alloantigens tended to lyse fewer targets than were lysed by normal cytotoxic T-lymphocytes or allogeneic thymus-grafted nude precursors stimulated with third party alloantigens, but the reduction in lytic activity was not statistically significant. Specific suppression was not demonstrated, but could not be ruled out unequivocally. We conclude that intrathymic deletion of thymic alloantigen-reactive pCTL is not necessary to achieve specific tolerance to thymic alloantigens.

  11. Failure of renal biomarkers to predict worsening renal function in high-risk patients presenting with oliguria. (United States)

    Legrand, Matthieu; Jacquemod, Aurélien; Gayat, Etienne; Collet, Corinne; Giraudeaux, Veronique; Launay, Jean-Marie; Payen, Didier


    Oliguria is a common symptom in critically ill patients and puts patients in a high risk category for further worsening renal function (WRF). We performed this study to explore the predictive value of biomarkers to predict WRF in oliguric intensive care unit (ICU) patients. Single-center prospective observational study. ICU patients were included when they presented a first episode of oliguria. Plasma and urine biomarkers were measured: plasma and urine neutrophil gelatinase-associated lipocalin (pNGAL and uNGAL), urine α1-microglobulin, urine γ-glutamyl transferase, urine indices of tubular function, cystatin C, C terminal fragment of pro-arginine vasopressin (CT-ProAVP), and proadrenomedullin (MR-ProADM). One hundred eleven patients formed the cohort, of whom 41 [corrected] had worsening renal function. Simplified Acute Physiology Score (SAPS) II was 41 (31-51). WRF was associated with increased mortality (hazard ratio 8.65 [95 % confidence interval (CI) 3.0-24.9], p = 0.0002). pNGAL, MR-ProADM, and cystatin C had the best odds ratio and area under the receiver-operating characteristic curve (AUC-ROC: 0.83 [0.75-0.9], 0.82 [0.71-0.91], and 0.83 [0.74-0.90]), but not different from serum creatinine (Screat, 0.80 [0.70-0.88]). A clinical model that included age, sepsis, SAPS II, and Screat had AUC-ROC of 0.79 [0.69-0.87]; inclusion of pNGAL increased the AUC-ROC to 0.86 (p = 0.03). The category-free net reclassification index improved with pNGAL (total net reclassification index for events to higher risk 61 % and nonevents to lower 82 %). All episodes of oliguria do not carry the same risk. No biomarker further improved prediction of WRF compared with Screat in this selected cohort of patients at increased risk defined by oliguria.

  12. Left ventricular diastolic dysfunction in pulmonary hypertension predicts functional capacity and clinical worsening: a tissue phase mapping study. (United States)

    Knight, Daniel S; Steeden, Jennifer A; Moledina, Shahin; Jones, Alexander; Coghlan, J Gerry; Muthurangu, Vivek


    wave was the only independent predictor of clinical worsening (6.3× increased risk, p = 0.009) in a model including RVEF and septal curvature. TPM metrics of LV diastolic function are significantly abnormal in PH. More importantly, abnormal LV E wave velocities are the only independent predictors of functional capacity and clinical worsening in a model that includes conventional metrics of biventricular function.

  13. Adherence to drug-refill is a useful early warning indicator of virologic and immunologic failure among HIV patients on first-line ART in South Africa.

    Directory of Open Access Journals (Sweden)

    Ziad El-Khatib


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

  14. Lymphocyte development in fetal piglets: Facts and surprises

    Czech Academy of Sciences Publication Activity Database

    Šinkora, Marek; Butler, J. E.; Holtmeier, W.; Šinkorová, J.


    Roč. 108, - (2005), s. 177-184 ISSN 0165-2427 R&D Projects: GA ČR GA524/04/0543; GA AV ČR IAA5020303 Institutional research plan: CEZ:AV0Z50200510 Keywords : development * differentiation * lymphogenesis Subject RIV: EE - Microbiology, Virology Impact factor: 1.626, year: 2005

  15. A rare case of chronic lymphocytic leukemia/small lymphocytic lymphoma presenting in the thyroid gland. (United States)

    Shin, Joyce; Chute, Deborah; Milas, Mira; Mitchell, Jamie; Siperstein, Allan; Berber, Eren


    Lymphoma involving the thyroid gland is rare. Diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma are the two most common histologic subtypes of primary thyroid lymphoma. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) presenting initially as a thyroid abnormality is extremely rare, with very few reported cases in the literature. We report a case of a patient with a long history of Hashimoto's thyroiditis and goiter who presented with a recent enlargement of her thyroid gland. The sonographic finding of a distinct thyroid nodule in the heterogeneous background of chronic lymphocytic thyroiditis led to the performance of a fine-needle aspiration biopsy and flow cytometry, with a high index of suspicion for thyroid lymphoma. Subsequent surgical removal of the thyroid gland, prompted by the patient's history of head and neck radiation, confirmed the diagnosis of CLL/SLL. The patient's systemic illness was recognized only after the management of her thyroid disease. Although thyroiditis has long been associated with lymphoma arising in the thyroid gland, CLL/SLL involving the thyroid has not been linked to chronic lymphocytic thyroiditis. Therefore, the patient also had coexisting thyroiditis. Due to the rarity of thyroid lymphomas, our experience in the detection and management of this disease is limited. Primary thyroid lymphoma should be suspected in a patient with a history of chronic lymphocytic thyroiditis presenting with a rapidly enlarging neck mass. The initial diagnostic method for thyroid lymphoma should consist of a fine-needle aspiration biopsy with the use of ancillary techniques such as flow cytometry and immunohistochemistry for improved diagnostic accuracy. Although controversial, the treatment of thyroid lymphoma is typically guided by the histologic subtype and extent of disease. CLL/SLL is one of the rarest subtypes of lymphoma that can involve the thyroid gland. Diagnosis of this entity is difficult

  16. Zinc intervention on macrophages and lymphocytes responce

    Energy Technology Data Exchange (ETDEWEB)

    Lastra, M.D.; Pastelin, R.; Camacho, A.; Monroy, B.; Aguilar, A.E. [Lab. de Investigacion en Immunologia, Univ. Nacional Autonoma de Mexico (Mexico)


    Normal zinc levels are essential for the development and maintenance of immune functions; Zn deficiency is detrimental to the embryo and offspring of experimental animals, especially concerning immune development. It is known that Zn supplementation improves immune responses. To further explore the relation between Zn administration and the metal in vitro effects, we studied zinc (500 mg/l) supplementation impact on lymphocytes and macrophages and zinc in vitro effects, in BALB/c mice supplemented from gestation to lactation. Results show a significant increase in proliferation (assessed by {sup 3}H incorporation) in lymphocytes exposed to Zn (0.1 mM) in vitro, in 3-wk-old mice; this effect is annulled when the supplementation period is lengthened, indicating saturation of the mechanisms involved in zinc induced stimulation. Macrophages functional capacity assessed by erythrophagocytosis was also improved by Zn supplementation and furthermore by the in vitro exposure to the metal, in mice 3 wk old, this was also depressed by Zn accumulation due to the supplementation period extension (9 weeks). Results show an improvement in the immune parameters analysed due to zinc supplementation and to zinc in vitro exposure. Results also suggest the accumulation of zinc as a result of prolonged supplementation periods, suppresses the cells response to zinc in vitro. (orig.)

  17. Crosstalk between T lymphocytes and dendritic cells. (United States)

    Hivroz, Claire; Chemin, Karine; Tourret, Marie; Bohineust, Armelle


    Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique property of inducing priming and differentiation of naïve CD4+ and CD8+ T cells into helper and cytotoxic effectors. Their efficiency is due to their unique ability to process antigen, express costimulatory molecules, secrete cytokines, and migrate to tissues or lymphoid organs to prime T cells. DCs also play an important role in T-cell peripheral tolerance. There is ample evidence that the DC ability to present antigens is regulated by CD4+ helper T cells. Indeed, interactions between surface receptors and ligands expressed respectively by T cells and DCs, as well as T-cell-derived cytokines modify DC functions. This T-cell-induced modification of DCs has been called "education" or "licensing." This intimate crosstalk between DCs and T lymphocytes is key in establishing appropriate adaptive immune responses. It requires cognate interactions between T lymphocytes and DCs, which are organized in time and space by structures called immunological synapses. Here we discuss the particular aspects of immunological synapses formed between T cells and DCs and the role these organized interactions have in T-cell-DC crosstalk.

  18. Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure. (United States)

    Damman, Kevin; Valente, Mattia A E; van Veldhuisen, Dirk J; Cleland, John G F; O'Connor, Christopher M; Metra, Marco; Ponikowski, Piotr; Cotter, Gad; Davison, Beth; Givertz, Michael M; Bloomfield, Daniel M; Hillege, Hans L; Voors, Adriaan A


    The aim of this study was to evaluate the ability of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to predict clinically relevant worsening renal function (WRF) in acute heart failure (AHF). Plasma NGAL and serum creatinine changes during the first 4 days of admission were investigated in 1447 patients hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of the Selective A₁Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was defined as serum creatinine rise ≥ 0.3 mg/dL through day 4. Biomarker patterns were described using linear mixed models. WRF developed in 325 patients (22%). Plasma NGAL did not rise earlier than creatinine in patients with WRF. After multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted WRF. AUCs for WRF prediction were modest (renal or cardiovascular rehospitalization by 60 days than patients with WRF and a low baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after baseline was associated with a worse outcome in patients with WRF, but not in patients without WRF ( p = 0.007). On the basis of these results, plasma NGAL does not provide additional, clinically relevant information about the occurrence of WRF in patients with AHF.

  19. Baseline albumin is associated with worsening renal function in patients with acute decompensated heart failure receiving continuous infusion loop diuretics. (United States)

    Clarke, Megan M; Dorsch, Michael P; Kim, Susie; Aaronson, Keith D; Koelling, Todd M; Bleske, Barry E


    To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics. Retrospective observational analysis. Academic tertiary medical center. A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009. The mean patient age was 61 years, 63% were male, ~45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days. Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables. Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite adjustments for other covariates. Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics. © 2013 Pharmacotherapy Publications, Inc.

  20. CO inhalation at dose corresponding to tobacco smoke worsens cardiac remodeling after experimental myocardial infarction in rats. (United States)

    Mirza, Alain; Eder, Véronique; Rochefort, Gaël Y; Hyvelin, Jean-Marc; Machet, Marie Christine; Fauchier, Laurent; Bonnet, Pierre


    We hypothesized that inhalation of carbon monoxide (CO) (500 ppm), similar to that in tobacco smoke, disturbs the cardiovascular adaptation after myocardial infarction by increasing remodeling. Four groups of rats were assessed. Two groups had myocardial infarction induced by the ligation of the left coronary artery: the first group was exposed to air (infarcted air group, n = 12), and the second was exposed to CO (infarcted CO group, n = 11). They were compared to two sham-operated groups, a control air group (n = 10), and a control CO group (n = 7) exposed (3 weeks) to CO. Aerobic endurance capacity was assessed in both the infarct CO and infarct air group (endurance capacity = 0.043 +/- 0.006 m.min(-1).g(-1) vs. 0.042 +/- 0.005 m.min(-1).g(-1), not significant). In the infarcted CO group compared to the infarcted air group, the dilatation of the left ventricle observed 3 weeks after infarction was increased, (left ventricular diastolic (LVD) diameter (D) = 9 +/- 0.4 vs. 7 +/- 0.4 mm, p infarcted CO group, the infarct size increased. Echocardiography and histology showed hypertrophy of the contralateral wall similar to that observed in the noninfarcted control CO group. In conclusion, chronic CO inhalation worsens heart failure in rats with myocardial infarction by an increase in the infarct size and hypertrophy remodeling.

  1. The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jacobsen, N


    Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR...

  2. [The virological and epidemiological aspects of human adenoviral conjunctivitis in Tunisia]. (United States)

    Fedaoui, N; Ben Ayed, N; Ben Yahia, A; Matri, L; Nacef, L; Triki, H


    Human adenoviruses (HAdV) are the main cause of viral conjunctivitis. In Tunisia and North Africa more generally, there is no regular nationwide surveillance program that monitors viruses causing conjunctivitis and keratoconjunctivitis. In this study, we report the results of HAdV screening in conjunctival samples collected for over 14 years in Tunisia. A total of 282 conjunctival samples received between 2000 and 2013 were investigated. Detection and identification of genotype were performed by PCR-sequencing at the hexon gene; 64.5% of samples (n=182) revealed positive by PCR detection without correlation noted between infection, age, sex, social class or clinical manifestations of viral conjunctivitis. HAdV-D8 was the largely predominant genotype in Tunisia, representing 81.3% of all isolates, and was detected continuously from 2000 to 2013. Minor co-circulating genotypes were also identified - HAdV-E4, HAdV-B3, B55 and HAdV-B7 - accounting for 10.7%, 4.9%, 1.9% and 0.9% of isolates, respectively. In conclusion, this work reports epidemiological data on adenoviral conjunctivitis from a region where such information is very scarce and contributes to a better knowledge of the worldwide distribution of causative genotypes. It also presents an approach for the identification of circulating HAdV in the country and demonstrates the importance of molecular tools for both detection and identification of genotypes, which allow rapid virological investigation, especially during epidemics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.


    Dudanova, O P; Shubina, M E; Belavina, I A; Elpaeva, E A; Pisareva, M M; Grudinin, M P; Kiselev, O I

    To estimate the r, virological and clinical characteristics of chronic viral hepatitis (CVH) with double B/C infection. We examined 282 patients with CVH. Genomes of hepatitis B virus (HBV) and hepatitis C virus (HCV) were studied by PCR in blood and liver (AmpliSens HBV and Amplisens HCV Russia), nuclear proteins (HBcorAg HBV and NS3 HCV) were determined by immunohistochemical method (Novocastra, UK), HBVgenome was sequenced by the Sanger method using ABI prism BigDye Terminator v3.1 kits and ABIPRISM 3100 analyzer (AppliedBiosystems, USA). Indices of histological activity (HAI), fibrosis, and portal vein (PV) congestion index (CI) were calculated by formula CI=SBB/LB V where S is P V cross section area in cm2 and LB V - linear blood flow velocity in cm/s (Vivid Pro- 7 apparatus, USA). CVH with double B/C infection was diagnosed in 85 (30.1%) patients including 44.7% with viral genomes and proteins in the live; 42.4% with HCVviremia, and 12.9% with HBJV/HCVviremia. Maximum CVH activity was documented in patients with latent HBV/HCVviremia (ALT 157.2±59.2 U/, HAI 11.6±1.3,fibrosis 2.8±0.7, C1 0.059±0.005); it was minimal inpatients.without viremia (Alt 76.25±63.0 U/I, HAI 6.7+-0.6,fibrosis 1.7±0.5, CI 0.042±0.001;p inflamation,fibrosis, and PV congestion was associated with HBV/HCV viremia and the lowest with intrahepatic localization of both viruses.

  4. Clinical and virological descriptive study in the 2011 outbreak of dengue in the Amazonas, Brazil. (United States)

    Martins, Valquiria do Carmo Alves; Bastos, Michele de Souza; Ramasawmy, Rajendranath; de Figueiredo, Regina Pinto; Gimaque, João Bosco Lima; Braga, Wornei Silva Miranda; Nogueira, Mauricio Lacerda; Nozawa, Sergio; Naveca, Felipe Gomes; Figueiredo, Luiz Tadeu Moraes; Mourão, Maria Paula Gomes


    Dengue is a vector-borne disease in the tropical and subtropical region of the world and is transmitted by the mosquito Aedes aegypti. In the state of Amazonas, Brazil during the 2011 outbreak of dengue all the four Dengue virus (DENV) serotypes circulating simultaneously were observed. The aim of the study was to describe the clinical epidemiology of dengue in Manaus, the capital city of the state of the Amazonas, where all the four DENV serotypes were co-circulating simultaneously. Patients with acute febrile illness during the 2011 outbreak of dengue, enrolled at the Fundação de Medicina Tropical Dr. Heitor Viera Dourado (FMT-HVD), a referral centre for tropical and infectious diseases in Manaus, were invited to participate in a clinical and virological descriptive study. Sera from 677 patients were analyzed by RT-nested-PCRs for flaviviruses (DENV 1-4, Saint Louis encephalitis virus-SLEV, Bussuquara virus-BSQV and Ilheus virus-ILHV), alphavirus (Mayaro virus-MAYV) and orthobunyavirus (Oropouche virus-OROV). Only dengue viruses were detected in 260 patients (38.4%). Thirteen patients were co-infected with more than one DENV serotype and six (46.1%) of them had a more severe clinical presentation of the disease. Nucleotide sequencing showed that DENV-1 belonged to genotype V, DENV-2 to the Asian/American genotype, DENV-3 to genotype III and DENV-4 to genotype II. Co-infection with more than one DENV serotype was observed. This finding should be warning signs to health authorities in situations of the large dispersal of serotypes that are occurring in the world.

  5. Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment. (United States)

    Suwantarat, Nuntra; Tice, Alan D; Khawcharoenporn, Thana; Chow, Dominic C


    To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR). A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 10(3) cells/microl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit.

  6. Mitochondrial DNA variation and virologic and immunological HIV outcomes in African Americans. (United States)

    Aissani, Brahim; Shrestha, Sadeep; Wiener, Howard W; Tang, Jianming; Kaslow, Richard A; Wilson, Craig M


    To evaluate the impact of mitochondrial DNA (mtDNA) haplogroups on virologic and immunological outcomes of HIV infection. HAART-naive African American adolescent participants to the Reaching for Excellence in Adolescent Care and Health study. The mtDNA haplogroups were inferred from sequenced mtDNA hypervariable regions HV1 and HV2 and their predictive value on HIV outcomes were evaluated in linear mixed models, controlled for human leukocyte antigen (HLA)-B27, HLA-B57 and HLA-B35-Px alleles and other covariates. We report data showing that the mtDNA L2 lineage, a group composed of L2a, L2b and L2e mtDNA haplogroups in the studied population, is significantly associated (beta  = -0.08; Bonferroni-adjusted P = 0.004) with decline of CD4 T cells (median loss of 8 ± 1 cells per month) in HAART-naive HIV-infected individuals of African American descent (n = 133). No significant association (P Trials Group study 384, implicating the L2 lineage with slower CD4 T-cell recovery after antiretroviral therapy in African Americans. Whereas the L2 lineage showed an association with unfavorable immunological outcomes of HIV infection, its phylogenetic divergence from J and U5a, two lineages associated with accelerated HIV progression in European Americans, raises the possibility that interactions with common nucleus-encoded variants drive HIV progression. Disentangling the effects of mitochondrial and nuclear gene variants on the outcomes of HIV infection is an important step to be taken toward a better understanding of HIV/AIDS pathogenesis and pharmacogenomics.

  7. Virological Quality of Irrigation Water in Leafy Green Vegetables and Berry Fruits Production Chains. (United States)

    Kokkinos, P; Kozyra, I; Lazic, S; Söderberg, K; Vasickova, P; Bouwknegt, M; Rutjes, S; Willems, K; Moloney, R; de Roda Husman, A M; Kaupke, A; Legaki, E; D'Agostino, M; Cook, N; von Bonsdorff, C-H; Rzeżutka, A; Petrovic, T; Maunula, L; Pavlik, I; Vantarakis, A


    This study condenses data acquired during investigations of the virological quality of irrigation water used in production of fresh produce. One hundred and eight samples of irrigation water were collected from five berry fruit farms in Finland (1), the Czech Republic (1), Serbia (2), and Poland (1), and sixty-one samples were collected from three leafy green vegetable farms in Poland, Serbia, and Greece. Samples were analyzed for index viruses of human or animal fecal contamination (human and porcine adenoviruses, and bovine polyoma viruses), and human pathogenic viruses (hepatitis A virus, hepatitis E virus, and noroviruses GI/GII). Both index and pathogenic viruses were found in irrigation water samples from the leafy green vegetables production chain. The data on the presence of index viruses indicated that the highest percentage of fecal contamination was of human origin (28.1 %, 18/64), followed by that of porcine (15.4 %, 6/39) and bovine (5.1 %, 2/39) origins. Hepatitis E virus (5 %, 1/20) and noroviruses GII (14.3 %, 4/28) were also detected. Samples from berry fruit production were also positive for both index and pathogenic viruses. The highest percentage of fecal contamination was of human origin (8.3 %, 9/108), followed by that of porcine, 4.5 % (4/89) and bovine, 1.1 % (1/89) origins. Norovirus GII (3.6 %, 2/56) was also detected. These data demonstrate that irrigation water used in primary production is an important vehicle of viral contamination for fresh produce, and thus is a critical control point which should be integrated into food safety management systems for viruses. The recommendations of Codex Alimentarius, as well as regulations on the use of water of appropriate quality for irrigation purposes, should be followed.

  8. Immunologic and virologic predictors of AIDS-related non-Hodgkin lymphoma in the HAART era (United States)

    Engels, Eric A.; Pfeiffer, Ruth M.; Landgren, Ola; Moore, Richard D.


    HIV-infected persons treated with highly active antiretroviral therapy (HAART) continue to have elevated risk for non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of NHL among patients at an urban HIV clinic (N=3025). Proportional hazards models identified immunologic and virologic predictors of NHL. Sixty-five NHLs arose during 1989-2006. NHL incidence declined over time. Nonetheless, 51 NHLs (78%) occurred within the HAART era (1996-2006). NHL risk increased with declining CD4 count (p-trend<0.0001) and increasing HIV viral load (p-trend=0.005). In a multivariable model, NHL risk was independently associated with both current CD4 count (hazard ratios 7.7 and 3.8, respectively, for CD4 counts 0-99 and 100-249 vs. 250+ cells/mm3; p-trend<0.0001) and prior time spent with a viral load above 5.00 log10 copies/ml (hazard ratios of 3.4, 2.6, and 6.8, respectively, for 0.1-0.4, 0.5-1.4, and 1.5+ years vs. 0 years; p-trend=0.004). Although serum globulin levels were elevated compared to the general population, NHL risk was unrelated to this B-cell activation marker (p=0.39). Among HIV-infected individuals in the HAART era, NHLs are linked to immunosuppression and extended periods of uncontrolled HIV viremia. The association with high-level viremia could reflect detrimental effects on immune function related to incompletely effective HAART or direct effects on B-cells. PMID:20418723

  9. Wastewater contamination in Antarctic melt-water streams evidenced by virological and organic molecular markers. (United States)

    Tort, L F L; Iglesias, K; Bueno, C; Lizasoain, A; Salvo, M; Cristina, J; Kandratavicius, N; Pérez, L; Figueira, R; Bícego, M C; Taniguchi, S; Venturini, N; Brugnoli, E; Colina, R; Victoria, M


    Human activities in the Antarctica including tourism and scientific research have been raised substantially in the last century with the concomitant impact on the Antarctic ecosystems through the release of wastewater mainly from different scientific stations activities. The aim of this study was to assess the wastewater contamination of surface waters and sediments of three melt-water streams (11 sites) by leaking septic tanks located in the vicinity of the Uruguayan Scientific Station in the Fildes Peninsula, King George Island, Antarctica, during summer 2015. For this purpose, we combined the analysis of fecal steroids in sediments by using gas chromatography and six enteric viruses in surface waters by quantitative and qualitative PCR. Coprostanol concentrations (from 0.03 to 3.31μgg -1 ) and fecal steroids diagnostic ratios indicated that stations C7 and C8 located in the kitchen stream presented sewage contamination. Rotavirus was the only enteric virus detected in five sites with concentration ranging from 1.2×10 5 gcL - 1 to 5.1×10 5 gcL - 1 being three of them located downstream from the leaking AINA and Kitchen septic tanks. This study shows for the first time the presence of both virological and molecular biomarkers of wastewater pollution in surface waters and sediments of three melt-water streams in the vicinity of a scientific station in the Antarctica. These results highlight the importance of the complementation of these biomarkers in two different matrices (surface waters and sediments) to assess wastewater pollution in an Antarctic environment related to anthropogenic activities in the area. Copyright © 2017. Published by Elsevier B.V.

  10. Virological investigation of hand, foot, and mouth disease in a tertiary care center in South India

    Directory of Open Access Journals (Sweden)

    Pavithra M Vijayaraghavan


    Full Text Available Context: Hand, foot, and mouth disease (HFMD remains a common problem in India, yet its etiology is largely unknown as diagnosis is based on clinical characteristics. There are very few laboratory-based molecular studies on HFMD outbreaks. Aim: The aim of this study was to characterize HFMD-related isolates by molecular techniques. Settings and Design: Between 2005 and 2008, during two documented HFMD outbreaks, 30 suspected HFMD cases presented at the Outpatient Unit of the Department of Dermatology, Christian Medical College (CMC, Vellore. Seventy-eight clinical specimens (swabs from throat, mouth, rectum, anus, buttocks, tongue, forearm, sole, and foot were received from these patients at the Department of Clinical Virology, CMC, for routine diagnosis of hand, foot, and mouth disease. Materials and Methods: Samples from these patients were cultured in Vero and rhabdomyosarcoma (RD cell lines. Isolates producing enterovirus-like cytopathogenic effect (CPE in cell culture were identified by a nested reverse transcription-based polymerase chain reaction (RT-PCR and sequenced. The nucleotide sequences were analyzed using the BioEdit sequence program. Homology searches were performed using the Basic Local Alignment Search Tool (BLAST algorithm. Statistical Analysis used: The statistical analysis was performed using Epi Info version 6.04b and Microsoft Excel 2002 (Microsoft Office XP. Results: Of the 30 suspected HFMD cases, only 17 (57% were laboratory confirmed and Coxsackievirus A16 (CVA16 was identified as the etiological agent in all these cases. Conclusions: Coxsackievirus A16 (CVA16 was identified as the virus that caused the HFMD outbreaks in Vellore between 2005 and 2008. Early confirmation of HFMD helps to initiate control measures to interrupt virus transmission. In the laboratory, classical diagnostic methods, culture and serological tests are being replaced by molecular techniques. Routine surveillance systems will help understand the

  11. Virological patterns of HCV patients with failure to interferon-free regimens. (United States)

    Starace, Mario; Minichini, Carmine; De Pascalis, Stefania; Macera, Margherita; Occhiello, Laura; Messina, Vincenzo; Sangiovanni, Vincenzo; Adinolfi, Luigi E; Claar, Ernesto; Precone, Davide; Stornaiuolo, Gianfranca; Stanzione, Maria; Ascione, Tiziana; Caroprese, Mara; Zampino, Rosa; Parrilli, Gianpaolo; Gentile, Ivan; Brancaccio, Giuseppina; Iovinella, Vincenzo; Martini, Salvatore; Masarone, Mario; Fontanella, Luca; Masiello, Addolorata; Sagnelli, Evangelista; Punzi, Rodolfo; Salomone Megna, Angelo; Santoro, Renato; Gaeta, Giovanni B; Coppola, Nicola


    The study characterized the virological patterns and the resistance-associated substitutions (RASs) in patients with failure to IFN-free regimens enrolled in the real-life setting. All 87 consecutive HCV patients with failed IFN-free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home-made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub-optimal DAA regimen, 19 with a simeprevir-based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub-optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8-57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub-optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0-25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir-based regimen group (31.6%) and sub-optimal regimen group (18.7%). In our real-life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens. © 2018 Wiley Periodicals, Inc.

  12. Epidemiological and virological characteristics of 2 subgroups of hepatitis B virus genotype C. (United States)

    Chan, Henry L Y; Tsui, Stephen K W; Tse, Chi-Hang; Ng, Eddie Y T; Au, Thomas C C; Yuen, Lilly; Bartholomeusz, Angeline; Leung, Kwong-Sak; Lee, Kin-Hong; Locarnini, Stephen; Sung, Joseph J Y


    We aimed to investigate the characteristics of hepatitis B virus (HBV) genotype C subgroups in Hong Kong and their relationship with HBV genotype C in other parts of Asia. Full-genome nucleotide sequences of 49 HBV genotype C isolates from Chinese patients with chronic hepatitis B were compared with the sequences of 69 HBV genotype C isolates and 12 non-genotype C isolates in the GenBank database. Phylogenetic analysis was performed to define the subgroups of HBV genotype C on the basis of >4% heterogeneity of the entire HBV genome. HBV in 80% of patients in Hong Kong belonged to a subgroup predominantly found in Southeast Asia (Vietnam, Thailand, Myanmar, and southern China) designated as HBV genotype "Cs," and HBV in the remaining 20% of patients belonged to another subgroup, predominantly found in the Far East (Korea, Japan, and northern China), designated as HBV genotype "Ce." Overall, the mean+/-SD nucleotide sequence difference between HBV genotype Cs and HBV genotype Ce was 4.2%+/-0.3%. When HBV genotype Cs and HBV genotype Ce were compared among patients in Hong Kong, HBV genotype Cs was associated with a higher tendency to develop basal core promoter mutations (80% vs. 50%; P=.14), a higher prevalence of C at nucleotide 1858 (95% vs. 0%; P<.001), and a lower prevalence of precore stop codon mutations (5% vs. 50%; P=.002). HBV genotype C can be differentiated into 2 subgroups--namely, genotype Ce and genotype Cs--that have different epidemiological distributions and virological characteristics.

  13. Ibrutinib treatment of a patient with relapsing chronic lymphocytic leukemia and sustained remission of Richter syndrome. (United States)

    Albi, Elisa; Baldoni, Stefano; Aureli, Patrizia; Dorillo, Erica; Del Papa, Beatrice; Ascani, Stefano; Di Ianni, Mauro; Falzetti, Franca; Sportoletti, Paolo


    Richter syndrome (RS) is a rare event in chronic lymphocytic leukemia (CLL) that is influenced by biological factors and prior CLL treatments. Ibrutinib is a Bruton tyrosine kinase inhibitor that has shown remarkable efficacy in CLL; however, little is known about its relationship to RS. We report a case of ibrutinib efficacy against CLL in a patient with prolonged remission of RS. The patient was diagnosed with CLL in 2003. Biological findings at onset included absent ZAP70 expression, mutated IGVH, and NOTCH1 mutation. He was treated with FCR with partial response. In 2013, he progressed to RS, not clonally related to the underlying CLL. The patient was treated with anthracycline- and platinum-based regimens, obtaining a complete remission. After 3 years, he presented a CLL progression with worsening lymphocytosis, anemia, thrombocytopenia, increased splenomegaly, and lymphadenopathies. Positron emission tomography-computed tomography scan excluded pathologic uptake. Thus, he was started on ibrutinib. At 12 months' follow-up, we observed white blood cell normalization, increased hemoglobin and platelet levels, disappearance of lymphadenopathy, and spleen size reduction. Therapy was well-tolerated with no evidence of RS. This case demonstrates sustained RS remission in a patient with CLL under ibrutinib therapy, thus improving our knowledge on the use of this new drug in CLL and beyond.

  14. Necrotizing Lymphocytic Vasculitis Limited to the Peripheral Nerves: Report of Six Cases and Review

    Directory of Open Access Journals (Sweden)

    José Félix Restrepo


    Full Text Available Background. The systemic vasculitides are syndromes characterized by inflammation and injury (necrosis or thrombosis of blood vessels, resulting in clinical manifestations according to the affected vascular bed, but not classically in stocking-glove neuropathy. Objective. To describe a form of primary vasculitis affecting strictly peripheral nerves manifesting as stocking-glove neuropathy. Methods. Case series of 110 patients seen in three centers in Bogotá who presented with symptoms and signs of polyneuropathy and/or were identified with vasculitis affecting only the peripheral nerves, and who underwent sural nerve biopsy. Results. Six patients had a vasculitis affecting only the peripheral nerves diagnosed on sural nerve biopsy which demonstrated a mixed infiltrate of monocytes/macrophages and lymphocytes especially in the small epineurial blood vessels. Over time, all had worsening of symptoms, with grip weakness and motor deficits in the hand and feet. Serologies and acute phase reactants were normal in all patients. Treatment response to immunosuppression was satisfactory in 5 patients; 1 patient had progressive neurologic damage. Conclusions. There is a distinct form of primary vasculitis of the peripheral nervous system characterized by distal sensory polyneuropathy with stocking-glove distribution with good prognosis, few and minor relapses and good response to treatment even after delayed diagnosis.

  15. Specific MR imaging of human-lymphocytes by monoclonal antibody-guided dextran-magnetite particles

    NARCIS (Netherlands)

    Bulte, J. W. M.; Hoekstra, Y; Kamman, R. L.; Magin, R. L.; Webb, A. G.; Briggs, R. W.; Go, K. G.; Hulstaert, C. E.; Miltenyi, S.; The, T. Hauw; de Leij, L

    Human lymphocytes were labeled with biotinylated anti-lymphocyte-directed monoclonal antibodies, to which streptavidin and subsequently biotinylated dextran-magnetite particles were coupled. This labeling resulted in a strong and selective negative contrast enhancement of lymphocyte suspensions at

  16. Apoptosis of lymphocytes in SLE: the level, correlation with ...

    African Journals Online (AJOL)

    Lymphocytes were isolated from venous blood by method of gradient centrifugation of all the blood through a Ficoll-pak solution. The quantity apoptotic cells was determined in leukocytes by flow cytometry Epics XL-2 (“Beckman Coulter”, USA). Analysis of lymphocyte subpopulations was carried by using two fluorescent ...

  17. Lymphocyte subtype dysregulation in a group of children with simple ...

    African Journals Online (AJOL)

    Background: Obesity as a global public health problem is increasing in prevalence. Reports showed that obese children are more liable to infection than lean ones; it was claimed that obese subjects have altered peripheral blood total lymphocyte counts in addition to reduced lymphocyte proliferative response to mitogen ...

  18. The behavior of pig lymphocyte populations in vivo

    International Nuclear Information System (INIS)

    Binns, R.M.; Licence, S.T.; Pabst, R.


    Lymphocyte migration provides the means of rapidly recognizing and responding to antigen and widely disseminating the resulting immune response. The porcine lymphoid system differs from that of man in structural inversion of lymph nodes and route of lymphocyte recirculation and the existence of two Peyer's patch types, one of which differs from the conventional pattern in structure, cell content and lack of lymphocyte traffic and in its regression in old age. Recirculating T and B lymphocytes enter and leave spleen and lymph nodes by the blood but Null cells do not; lymphocytes also migrate through nonlymphoid tissues. The lung is one such important site, with a small migration in and out of alveolar space and a large traffic associated with the blood vessel wall, predominantly involving T cells. Blood lymphocytes hardly traffic into the peritoneal cavity, yet major traffic of particulate material or cells is possible in this important site of abdominal defense, so often used for immunization, and follows a distinct, well defined route. Cells migrate out of subcutaneous tissue via the draining node. Lymphocytes are produced and emigrate into blood from labelled thymus. They differ in size and surface phenotype from both thymocytes and peripheral T cells. Lymphocytes also migrate from blood into most tissues. In most nonlymphoid tissues, entry relates to blood flow but in many lymphoid tissues it is an active process which differs in tempo and extent, eg, between different nodes and between the two Peyer's patch types

  19. PDCA expression by B lymphocytes reveals important functional attributes. (United States)

    Vinay, Dass S; Kim, Chang H; Chang, Kyung H; Kwon, Byoung S


    We have demonstrated in this study the existence of a PDCA-expressing functional B cell population (PDCA+ B lymphocytes), which differentiates from activated conventional B (PDCA-IgM+) lymphocytes. Stimulation with anti-micro, LPS, CpG oligodeoxynucleotide, HSV-1, or CTLA-4 Ig activates the PDCA+ B lymphocytes, leading to cell division and induction of type I IFNs and IDO. Notably, the PDCA+ B lymphocytes are capable of Ag-specific Ab production and Ig class switching, which is corroborated by transfer experiments in B- and PDCA+ B lymphocyte-deficient microMT mice. Importantly, in lupus-prone MRL-Fas(lpr) mice, PDCA+ B lymphocytes remain the principal source of autoantibodies. The PDCA+ B lymphocytes have phenotypes with plasmacytoid dendritic cells, but are a distinct cell population in that they develop from C-kit+B220+ pro-B precursors. Thus, our data suggest that not all PDCA+ cells are dendritic cell-derived plasmacytoid dendritic cells and that a significant majority is the PDCA+ B lymphocyte population having distinct phenotype and function.

  20. T-lymphocyte subsets in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P


    Peripheral T-lymphocyte subsets: T-helper (OKT4) and T-suppressor (OKT8) cells were studied quantitatively in 20 patients with recurrent aphthous ulceration (RAU) in ulcerative, as well as inactive, stages of the disease. The figures were compared with T-lymphocyte subsets from matched control do...

  1. Effect of pyrimethamine and sulphadoxine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Odum, Niels; Theander, T G


    . Sulphadoxine (SDX), added in vitro, had no effect on the lymphocytes, while SDX plus PYR had the same effect as PYR alone. Oral intake of SDX plus PYR (Fansidar) also blocked the thymidine synthesis of mitogen-stimulated lymphocytes. The possible consequences of the findings for the use of PYR in malaria...

  2. 9 CFR 113.42 - Detection of lymphocytic choriomeningitis contamination. (United States)


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Detection of lymphocytic choriomeningitis contamination. 113.42 Section 113.42 Animals and Animal Products ANIMAL AND PLANT HEALTH... contamination. The test for detection of lymphocytic choriomeningitis (LCM) virus provided in this section shall...

  3. DMPD: Calcium signaling in lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18515054 Calcium signaling in lymphocytes. Oh-hora M, Rao A. Curr Opin Immunol. 200...8 Jun;20(3):250-8. (.png) (.svg) (.html) (.csml) Show Calcium signaling in lymphocytes. PubmedID 18515054 Title Calcium sign

  4. Immunophenotypic enumeration of CD4 T-lymphocyte values in ...

    African Journals Online (AJOL)


    lymphocytes play a central role in regulation of immune response.[2] These ..... influence of sex hormones on lymphocyte subpopulations. ... Friedland GH. Early treatment for HIV-The Time. Has Come. N Engl J Med 1990;322:1000-1002. 7. Gebo KA, Gallant JE, Keruly JC, Moore RD. Absolute CD4 vs. CD4 percentage for ...

  5. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Herman, S E M; Niemann, C U; Farooqui, M


    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...

  6. Lymphocytes and liver fibrosis in HIV & HCV coinfection

    NARCIS (Netherlands)

    Feuth, M.


    Coinfection with HIV has an important impact on immunity against hepatitis C virus (HCV). In the present dissertation, phenotypes of lymphocytes derived from the peripheral blood of HCV-infected patients were studied into detail, with special attention to changes in phenotype of lymphocytes

  7. Carotenoid levels in human lymphocytes, measured by Raman microspectroscopy

    NARCIS (Netherlands)

    Ramanauskaite, R.; Ramanauskaite, Regina B.; Segers-Nolten, Gezina M.J.; de Grauw, C.J.; de Grauw, Kees J.; Sijtsema, N.M.; van der Maas, Louis; Greve, Jan; Otto, Cornelis; Figdor, Carl


    Carotenoid levels in lymphocytes obtained from peripheral blood of healthy people have been investigated by Raman microspectroscopy. We observed that carotenoids are concentrated in so-called “Gall bodies”. The level of carotenoids in living human lymphocytes was found to be age-dependent and to

  8. Carotenoid levels in human lymphocytes, measured by Raman microspectroscopy

    NARCIS (Netherlands)

    Ramanauskaite, R B; SegersNolten, IGMJ; DeGrauw, K J; Sijtsema, N M; VanderMaas, L; Greve, J; Otto, C; Figdor, C G


    Carotenoid levels in lymphocytes obtained from peripheral blood of healthy people have been investigated by Raman microspectroscopy. We observed that carotenoids are concentrated in so-called ''Gall bodies''. The level of carotenoids in living human lymphocytes was found to be age-dependent and to

  9. Tumor features and correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer with Yin deficiency

    Directory of Open Access Journals (Sweden)

    YANG Zhiyun


    Full Text Available ObjectiveTo investigate the tumor features and the correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer (PLC with yin deficiency. MethodsA total of 148 PLC patients who were treated in Beijing Ditan Hospital, Capital Medical University, from July 2013 to February 2015 were enrolled and divided into yin-deficiency PLC group (52 patients and non-yin-deficiency PLC group (96 patients. The patients′ general information and laboratory markers were collected, including oncological parameters (alpha-fetoprotein, carcinoembryonic antigen (CEA, and carbohydrate antigen 199 (CA19-9, virological parameter (HBsAg, gross type (nodular type, massive type, bulky type, and diffuse type, radiological features (main portal vein diameter, portal vein tumor thrombus, and extrahepatic metastasis, biochemical parameters (Model for End-Stage Liver Disease (MELD score, white blood cell, red blood cell, platelet (PLT, alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBil, gamma-glutamyl transpeptidase, alkaline phosphatase, albumin, cholinesterase, prothrombin time (PT, and prothrombin time activity (PTA, and lymphocyte count. The t-test was applied for comparison of normally distributed continuous data between groups, and the Pearson correlation analysis was applied for correlation analysis. The Mann-Whitney U test was applied for comparison of non-normally distributed continuous data between groups, and the Spearman correlation analysis was applied for correlation analysis. The chi-square test was applied for comparison of categorical data between groups. ResultsHBsAg showed a significant difference between the two groups (χ2=5.658, P=0.017. Compared with the non-yin-deficiency PLC group, the yin-deficiency PLC group had significantly increased CEA and CA19-9 (U=-2.200 and -2.194, both P<0.05, significantly increased MELD score, TBil, and PT (t=2.2, U=-2.0, U=-2

  10. Lymphocyte mitogen-induced proliferation in patients with allergic rhinitis

    International Nuclear Information System (INIS)

    Chorostowska-Wynimko, J.; Kleniewska, D.; Sokolnicka, I.; Rogala, E.; Skopinska-Rozewska, E.


    Lymphocytes play a central regulatory role in mechanisms contributing to impaired function of immune system in atopy. The aim of our study was evaluate the mitogen-induced proliferation of lymphocytes in a group of asymptomatic, seasonal allergic rhinitis patients. A highly significant lower mitogen-induced proliferation and, in contrast to other studies, significantly lower background proliferative activity of lymphocytes were found in the atopic persons, comparing to the controls. We concluded that the decreased mitogen-induced proliferation of lymphocytes observed in allergic patients reflects abnormal T cell function, which is due to the atopic status, and not only as it was believed to the antigen-induced lymphocyte activation. (author). 26 refs, 1 tab

  11. Lymphocyte mitogen-induced proliferation in patients with allergic rhinitis

    Energy Technology Data Exchange (ETDEWEB)

    Chorostowska-Wynimko, J.; Kleniewska, D.; Sokolnicka, I.; Rogala, E.; Skopinska-Rozewska, E. [Dept. of Immunology. Institute of Tuberculosis and Lung Diseases, Warsaw (Poland)


    Lymphocytes play a central regulatory role in mechanisms contributing to impaired function of immune system in atopy. The aim of our study was evaluate the mitogen-induced proliferation of lymphocytes in a group of asymptomatic, seasonal allergic rhinitis patients. A highly significant lower mitogen-induced proliferation and, in contrast to other studies, significantly lower background proliferative activity of lymphocytes were found in the atopic persons, comparing to the controls. We concluded that the decreased mitogen-induced proliferation of lymphocytes observed in allergic patients reflects abnormal T cell function, which is due to the atopic status, and not only as it was believed to the antigen-induced lymphocyte activation. (author). 26 refs, 1 tab.

  12. 2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio

    NARCIS (Netherlands)

    Lin, Bochao Danae; Carnero-Montoro, Elena; Bell, Jordana T; Boomsma, Dorret I; de Geus, Eco J; Jansen, Rick; Kluft, Cornelis; Mangino, Massimo; Penninx, Brenda; Spector, Tim D; Willemsen, Gonneke; Hottenga, Jouke-Jan


    Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and

  13. Lymphocyte populations and apoptosis of peripheral blood B and T lymphocytes in children with end stage renal disease. (United States)

    Saad, Khaled; Elsayh, Khalid I; Zahran, Asmaa M; Sobhy, Karema M


    End stage renal disease (ESRD) is a worldwide devastating health problem due to its increased prevalence in the population and high association with several pathologic conditions including immunodeficiency, which makes a significant contribution to morbidity and mortality. The present study aimed at analysis of T and B lymphocyte subpopulation and the detection of flowcytometric apoptosis markers on peripheral B and T lymphocytes in a cohort of children with ESRD. A case-control study was conducted on 28 children with ESRD. In addition, 30 age and sex matched healthy children were included as a control group. We used Annexin V-FITC binding assay as a sensitive probe for identifying cells undergoing apoptosis. Circulating neutrophils, T and B lymphocytes were lower in patient group. In addition, apoptotic B and T lymphocytes occurred more frequently in children with ESRD than in the control group. Our finding of low numbers of circulating neutrophils, T and B lymphocytes, and increased portion of apoptotic B and T lymphocytes in children with ESRD, may emphasize the fact that these derangements are the main mechanisms responsible for the impairment of the immune system in ESRD children, also it adds to the fact that both cellular and humoral immunity affected in ESRD children. Finally, uremia and increased peripheral lymphocyte apoptosis were the major causes of lymphocyte populations' depletion in our ESRD patients.

  14. Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I


    Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T...... T4 cells and decreased numbers of T4 cells harvested from IFN MLRs (days 5-6 of culture). In contrast, it was shown that the T8 (cytotoxic/suppressor) subset in MLRs was either not affected or slightly stimulated by the addition of IFN. The depression of the T4 cells by IFN was accompanied......4 (inducer) T-cell subset could be demonstrated as a sequence of events: decreased fluorescence intensity of the T4 inducer cells (day 2 of culture), decreased percentages of T4 cells as demonstrated by cell cytofluorometry (days 3-6 of culture), and decreased 3H-thymidine incorporation of purified...

  15. Predictive radiosensitivity tests in human lymphocytes

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Vallerga, Maria B.; Taja, Maria R.; Sardi, M.; Busto, E.; Mairal, L.; Roth, B.; Menendez, P.; Bonomi, M.


    Individual radiosensitivity is an inherent characteristic, associated with an abnormally increased reaction to ionising radiation of both the whole body and cells derived from body tissues. Human population is not uniform in its radiation sensitivity. Radiosensitive sub-groups exist, which would suffer an increased incidence of both deterministic and stochastic effects. Clinical studies have suggested that a large part of the spectrum of normal tissue reaction may be due to differences in individual radiosensitivity. The identification of such sub-groups should be relevant for radiation therapy and radiation protection purposes. It is suggested that DNA repair mechanisms are involved. Consequently, the characterization of DNA repair in lymphocytes through cytokinesis blocked micronucleus (MN) and alkaline single-cell microgel electrophoresis (comet) assays could be a suitable approache to evaluate individual radiosensitivity in vitro. The aims of this study were: 1) To assess the in vitro radiosensitivity of peripheral blood lymphocytes from two groups of cancer patients (prospectively and retrospectively studied), using MN and comet assays, in comparison with the clinical radiation reaction and 2) To test the predictive potential of both techniques for the identification of radiosensitivity sub-groups. 38 cancer patients receiving radiation therapy were enrolled in this study. 19 patients were evaluated prior, mid-way and on completion of treatment (prospective group) and 19 patients were evaluated about 6-18 month after radiotherapy (retrospective group). Cytogenetic data from the prospective group were analysed using a mathematical model to evaluate the attenuation of the cytogenetic effect as a function of the time between a single exposure and blood sampling, estimating a cytogenetic recovery factor k. In the retrospective group, blood samples were irradiated in vitro with 0 (control) or 2 Gy and evaluated using MN test. Cytogenetic data were analysed

  16. Metal ion levels and lymphocyte counts

    DEFF Research Database (Denmark)

    Penny, Jeannette Ø; Varmarken, Jens-Erik; Ovesen, Ole


    . RESULTS: The T-lymphocyte counts for both implant types declined over the 2-year period. This decline was statistically significant for CD3(+)CD8(+) in the THA group, with a regression coefficient of -0.04 × 10(9)cells/year (95% CI: -0.08 to -0.01). Regression analysis indicated a depressive effect...... of cobalt ions in particular on T-cells with 2-year whole-blood cobalt regression coefficients for CD3+ of -0.10 (95% CI: -0.16 to -0.04) × 10(9) cells/parts per billion (ppb), for CD3+CD4+ of -0.06 (-0.09 to -0.03) × 10(9) cells/ppb, and for CD3(+)CD8(+) of -0.02 (-0.03 to -0.00) × 10(9) cells...

  17. Caring for patients with chronic lymphocytic leukemia. (United States)

    Elphee, Erin E


    Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed form of leukemia in the Western world, accounting for approximately 20%-30% of all cases of leukemia. Despite recent medical and scientific advances, the literature on the subjective experience and nursing care of patients diagnosed with CLL remains scarce and sporadic. This article provides a brief overview on the pathophysiology, clinical characteristics, and treatment options of CLL with focus placed on implications for nursing care. Fatigue, the most common symptom reported by patients, and infection, the leading cause of disease-related deaths, also will be addressed. Emerging data examining quality of life and the incidence of anxiety and depression in this patient population will be reviewed, and strategies aimed at addressing the educational needs of patients and family members will be discussed.

  18. Sudden unexpected death associated with lymphocytic thyroiditis

    DEFF Research Database (Denmark)

    Vestergaard, Vibeke; Drostrup, Dorthe Høj; Thomsen, Jørgen L


    A forensic autopsy study comprising 125 cases was carried out retrospectively in order to evaluate pathological changes in the thyroid gland in different groups of death. The five groups selected consecutively were: (i) opiate addicts who died from an overdose, (ii) alcoholics who died as a result...... of their alcohol abuse, (iii) cases of fatal poisoning other than opiate addicts, (iv) unknown cause of death and (v) controls without prior disease. Tissue samples from the thyroid gland were cut and stained with haematoxylin and eosin and van Gieson. Histology examinations were subsequently performed blind...... infiltration of the thyroid parenchyma in five of the 124 cases, of which four belonged in the group of 'unknown cause of death'. This discovery leads to reflections regarding lymphocytic thyroiditis as a cause of death, either by itself or in combination with other disorders. Silent (painless) thyroiditis...

  19. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena


    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  20. Minimal residual disease in chronic lymphocytic leukaemia. (United States)

    García Vela, José Antonio; García Marco, José Antonio


    Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing. A therapeutic approach guided by the level of MRD might also determine which patients would benefit from an early stop or consolidation therapy. In this review, we discuss the different MRD methods of analysis, which source of tumour samples must be analysed, the future role of the detection of circulating tumour DNA, and the potential role of MRD negativity in clinical practice in the modern era of CLL therapy. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution. (United States)

    Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud


    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Empagliflozin Prevents Worsening of Cardiac Function in an Experimental Model of Pressure Overload-Induced Heart Failure

    Directory of Open Access Journals (Sweden)

    Nikole J. Byrne, BSc


    Full Text Available This study sought to determine whether the sodium/glucose cotransporter 2 (SGLT2 inhibitor empagliflozin improved heart failure (HF outcomes in nondiabetic mice. The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients trial demonstrated that empagliflozin markedly prevented HF and cardiovascular death in subjects with diabetes. However, despite ongoing clinical trials in HF patients without type 2 diabetes, there are no objective and translational data to support an effect of SGLT2 inhibitors on cardiac structure and function, particularly in the absence of diabetes and in the setting of established HF. Male C57Bl/6 mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Following surgery, mice that progressed to HF received either vehicle or empagliflozin for 2 weeks. Cardiac function was then assessed in vivo using echocardiography and ex vivo using isolated working hearts. Although vehicle-treated HF mice experienced a progressive worsening of cardiac function over the 2-week treatment period, this decline was blunted in empagliflozin-treated HF mice. Treatment allocation to empagliflozin resulted in an improvement in cardiac systolic function, with no significant changes in cardiac remodeling or diastolic dysfunction. Moreover, isolated hearts from HF mice treated with empagliflozin displayed significantly improved ex vivo cardiac function compared to those in vehicle-treated controls. Empagliflozin treatment of nondiabetic mice with established HF blunts the decline in cardiac function both in vivo and ex vivo, independent of diabetes. These data provide important basic and translational clues to support the evaluation of SGLT2 inhibitors as a treatment strategy in a broad range of patients with established HF.

  3. Monitoring fetal electrocortical activity during labour for predicting worsening acidemia: a prospective study in the ovine fetus near term.

    Directory of Open Access Journals (Sweden)

    Martin G Frasch

    Full Text Available Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG.Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24 ± 0.04, 52 ± 13 min prior to the pH dropping <7.00, spectral edge frequency (SEF increased to 23 ± 2 Hz from 3 ± 1 Hz during each FHR deceleration (p<0.001 and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001.The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such "adaptive brain shutdown," the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG during human labour may be a useful adjunct to FHR monitoring.

  4. Medial posterior meniscal root tears are associated with development or worsening of medial tibiofemoral cartilage damage: the multicenter osteoarthritis study. (United States)

    Guermazi, Ali; Hayashi, Daichi; Jarraya, Mohamed; Roemer, Frank W; Zhang, Yuqing; Niu, Jingbo; Crema, Michel D; Englund, Martin; Lynch, John A; Nevitt, Michael C; Torner, James C; Lewis, Cora E; Felson, David T


    To assess the association of meniscal root tear with the development or worsening of tibiofemoral cartilage damage. Institutional review board approval and written informed consent from all subjects were obtained. A total of 596 knees with radiographically depicted osteoarthritis were randomly selected from the Multicenter Osteoarthritis study cohort. Cartilage damage was semiquantitatively assessed by using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system (grades 0-6). Subjects were separated into three groups: root tear only, meniscal tear without root tear, and neither meniscal nor root tear. A log-binomial regression model was used to calculate the relative risks for knees to develop incident or progressing cartilage damage in the root tear group and the meniscal tear group, with the no tear group serving as a reference. In the medial tibiofemoral joint, there were 37 knees with isolated medial posterior root tear, 294 with meniscal tear without root tear, and 264 without meniscal or root tear. There were only two lateral posterior root tears, and no anterior root tears were found. Thus, the focus was on the medial posterior root tear. The frequency of severe cartilage damage (WORMS ≥ 5) was higher in the group with root tear than in the group without root or meniscal tear (76.7% vs 19.7%, P meniscal but no root tear (76.7% vs 65.2%, P = .055). Longitudinal analyses included 33 knees with isolated medial posterior root tear, 270 with meniscal tear, and 245 with no tear. Adjusted relative risk of cartilage loss was 2.03 (95% confidence interval [CI]: 1.18, 3.48) for the root tear group and 1.84 (95% CI: 1.32, 2.58) for the meniscal tear group. Isolated medial posterior meniscal root tear is associated with incident and progressive medial tibiofemoral cartilage loss.

  5. Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Paula Bernardo de Carvalho


    Full Text Available Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C, the pamidronate group (P, the doxorubicin group (D and the doxorubicin/pamidronate group (DP. The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP. After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP. Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy.

  6. Infrared Warming Reduced Winter Wheat Yields and Some Physiological Parameters, Which Were Mitigated by Irrigation and Worsened by Delayed Sowing (United States)

    Fang, Shibo; Su, Hua; Liu, Wei; Tan, Kaiyan; Ren, Sanxue


    Winter wheat has a central role in ensuring the food security and welfare of 1.3 billion people in China. Extensive previous studies have concluded that winter wheat yields would decrease with higher temperatures, owing to warming-induced soil drying or shortening of phenophase. Temperature in China is predicted to increase by 1–5°C by 2100, which may greatly impact plant production and cause other negative effects. We performed a manipulative field experiment, creating diverse growth regimes for wheat by infrared radiation (IR) warming day and night, including IR warming only (DW), IR warming + delayed sowing dates (DS), IR warming + increased irrigation (IW), and a control (CK). The results show that IR warming increased daily average wheat canopy and soil temperatures by 2.0°C and 2.3°C, respectively. DW was associated with an advanced maturity of 10 days and yield reduction of 8.2%. IR-warming effects on the photosynthetic apparatus of wheat varied with season as well as significant differences were found in the booting stage. DS represented a worsened situation, lowering yield per plant by 16.4%, with a significant decline in aboveground biomass and functional leaf area. Wheat under DS showed double-peak patterns of diurnal gas exchange during booting stages and, consequently, lower photosynthetic capacity with high transpiration for cooling. Significantly lower actual water use efficiency and intrinsic water use efficiency from jointing to anthesis stages were also found under DS. However, IW had no significant difference from CK, irrespective of yield and photosynthesis. Therefore, we concluded that delayed sowing date may not be a good choice for winter wheat, whereas a thoroughly-watered wheat agroecosystem should be promoted in the context of global warming. PMID:23874424

  7. Infrared warming reduced winter wheat yields and some physiological parameters, which were mitigated by irrigation and worsened by delayed sowing. (United States)

    Fang, Shibo; Su, Hua; Liu, Wei; Tan, Kaiyan; Ren, Sanxue


    Winter wheat has a central role in ensuring the food security and welfare of 1.3 billion people in China. Extensive previous studies have concluded that winter wheat yields would decrease with higher temperatures, owing to warming-induced soil drying or shortening of phenophase. Temperature in China is predicted to increase by 1-5°C by 2100, which may greatly impact plant production and cause other negative effects. We performed a manipulative field experiment, creating diverse growth regimes for wheat by infrared radiation (IR) warming day and night, including IR warming only (DW), IR warming + delayed sowing dates (DS), IR warming + increased irrigation (IW), and a control (CK). The results show that IR warming increased daily average wheat canopy and soil temperatures by 2.0°C and 2.3°C, respectively. DW was associated with an advanced maturity of 10 days and yield reduction of 8.2%. IR-warming effects on the photosynthetic apparatus of wheat varied with season as well as significant differences were found in the booting stage. DS represented a worsened situation, lowering yield per plant by 16.4%, with a significant decline in aboveground biomass and functional leaf area. Wheat under DS showed double-peak patterns of diurnal gas exchange during booting stages and, consequently, lower photosynthetic capacity with high transpiration for cooling. Significantly lower actual water use efficiency and intrinsic water use efficiency from jointing to anthesis stages were also found under DS. However, IW had no significant difference from CK, irrespective of yield and photosynthesis. Therefore, we concluded that delayed sowing date may not be a good choice for winter wheat, whereas a thoroughly-watered wheat agroecosystem should be promoted in the context of global warming.

  8. Infrared warming reduced winter wheat yields and some physiological parameters, which were mitigated by irrigation and worsened by delayed sowing.

    Directory of Open Access Journals (Sweden)

    Shibo Fang

    Full Text Available Winter wheat has a central role in ensuring the food security and welfare of 1.3 billion people in China. Extensive previous studies have concluded that winter wheat yields would decrease with higher temperatures, owing to warming-induced soil drying or shortening of phenophase. Temperature in China is predicted to increase by 1-5°C by 2100, which may greatly impact plant production and cause other negative effects. We performed a manipulative field experiment, creating diverse growth regimes for wheat by infrared radiation (IR warming day and night, including IR warming only (DW, IR warming + delayed sowing dates (DS, IR warming + increased irrigation (IW, and a control (CK. The results show that IR warming increased daily average wheat canopy and soil temperatures by 2.0°C and 2.3°C, respectively. DW was associated with an advanced maturity of 10 days and yield reduction of 8.2%. IR-warming effects on the photosynthetic apparatus of wheat varied with season as well as significant differences were found in the booting stage. DS represented a worsened situation, lowering yield per plant by 16.4%, with a significant decline in aboveground biomass and functional leaf area. Wheat under DS showed double-peak patterns of diurnal gas exchange during booting stages and, consequently, lower photosynthetic capacity with high transpiration for cooling. Significantly lower actual water use efficiency and intrinsic water use efficiency from jointing to anthesis stages were also found under DS. However, IW had no significant difference from CK, irrespective of yield and photosynthesis. Therefore, we concluded that delayed sowing date may not be a good choice for winter wheat, whereas a thoroughly-watered wheat agroecosystem should be promoted in the context of global warming.

  9. Have health trends worsened in Greece as a result of the financial crisis? A quasi-experimental approach. (United States)

    Vandoros, Sotiris; Hessel, Philipp; Leone, Tiziana; Avendano, Mauricio


    Health in Greece deteriorated after the recent financial crisis, but whether this decline was caused by the recent financial crisis has not been established. This article uses a quasi-experimental approach to examine the impact of the recent financial crisis on health in Greece. Data came from the European Union Statistics on Income and Living Conditions survey for the years 2006-09. We applied a difference-in-differences approach that compares health trends before and after the financial crisis in Greece with trends in a control population (Poland) that did not experience a recession and had health trends comparable with Greece before the crisis. We used logistic regression to model the impact of the financial crisis on poor self-rated health, controlling for demographic confounders. Results provide strong evidence of a statistically significant negative effect of the financial crisis on health trends. Relative to the control population, Greece experienced a significantly larger increase in the odds of reporting poor health after the crisis (odds ratio, 1.16; 95% confidence interval, 1.04-1.29). There was no difference in health trends between Poland and Greece before the financial crisis, supporting a causal interpretation of health declines in Greece as a result of the financial crisis. Results provide evidence that trends in self-rated health in Greece worsened as a result of the recent financial crisis. Findings stress the need for urgent health policy responses to the recent economic collapse in Greece as the full impact of austerity measures unfolds in the coming years.

  10. Comparison of virological methods applied on african swine fever diagnosis in Brazil, 1978

    Directory of Open Access Journals (Sweden)

    Tânia Rosária Pereira Freitas


    Full Text Available ABSTRACT. Freitas T.R.P., Souza A.C., Esteves E.G. & Lyra T.M.P. [Comparison of virological methods applied on african swine fever diagnosis in Brazil, 1978.] Comparação dos métodos virológicos aplicados no diagnóstico da peste suína africana no Brasil, 1978. Revista Brasileira de Medicina Veterinária, 37(3:255-263, 2015. Laboratório Nacional Agropecuário, Ministério da Agricultura, Pecuária e Abastecimento, Avenida Rômulo Joviano, s/n, Caixa postal 35/50, Pedro Leopoldo, MG 33600-000, Brasil. The techniques of leucocytes haemadsorption (HAD for the African Swine Fever (ASF virus isolation and the fluorescent antigens tissue samples (FATS for virus antigens detection were implanted in the ASF eradication campaign in the country. The complementary of techniques was studied considering the results obtained when the HAD and FATS were concomitantly applied on the same pig tissue samples. The results of 22, 56 and 30 pigs samples from of the States of Rio de Janeiro (RJ, São Paulo (SP and Paraná (PR, respectively, showed that in RJ 11 (50%; in SP, 28 (50% and in PR, 15 (50% samples were positive in the HAD, while, RJ, 18 (82%; SP, 33 (58% and PR, 17 (57% were positive in the FATS. In the universe of 108 samples submitted to both the tests, 83 (76.85% were positive in at least one of the tests, which characterized ASF positivity. Among the positive samples, 28 (34% have presented HAD negative results and 15 (18% have presented FATS negative results. The achievement of applying simultaneously the both tests was the reduction of false- negative results, conferring more ASF accurate laboratorial diagnosis, besides to show the tests complementary. This aspect is fundamentally importance concern with a disease eradiation program to must avoid false negative results. Evidences of low virulence ASFV strains in Brazilian ASF outbreaks and also the distribution of ASF outbreaks by the mesoregions of each State were discussed

  11. Does gender or mode of HIV acquisition affect virological response to modern antiretroviral therapy (ART)? (United States)

    Saunders, P; Goodman, A L; Smith, C J; Marshall, N; O'Connor, J L; Lampe, F C; Johnson, M A


    Previous UK studies have reported disparities in HIV treatment outcomes for women. We investigated whether these differences persist in the modern antiretroviral treatment (ART) era. A single-centre cohort analysis was carried out. We included in the study all previously ART-naïve individuals at our clinic starting triple ART from 1 January 2006 onwards with at least one follow-up viral load (VL). Time to viral suppression (VS; first viral load  200 copies/mL more than 6 months post-ART) and treatment modification were estimated using standard survival methods. Of 1086 individuals, 563 (52%) were men whose risk for HIV acquisition was sex with other men (MSM), 207 (19%) were men whose risk for HIV acquisition was sex with women (MSW) and 316 (29%) were women. Median pre-ART CD4 count and time since HIV diagnosis in these groups were 298, 215 and 219 cells/μL, and 2.3, 0.3 and 0.3 years, respectively. Time to VS was comparable between groups, but women [adjusted hazard ratio (aHR) 2.32; 95% confidence interval (CI) 1.28-4.22] and MSW (aHR 3.28; 95% CI 1.91-5.64) were at considerably higher risk of VF than MSM. Treatment switches and complete discontinuation were also more common among MSW [aHR 1.38 (95% CI 1.04-1.81) and aHR 1.73 (95% CI 0.97-3.16), respectively] and women [aHR 1.87 (95% CI 1.43-2.46) and aHR 3.20 (95% CI 2.03-5.03), respectively] than MSM. Although response rates were good in all groups, poorer virological outcomes for women and MSW have persisted into the modern ART era. Factors that might influence the differences include socioeconomic status and mental health disorders. Further interventions to ensure excellent response rates in women and MSW are required. © 2015 British HIV Association.

  12. Epidemiological and virological investigation of a Norovirus outbreak in a resort in Puglia, Italy

    Directory of Open Access Journals (Sweden)

    Coscia Maria


    uncommon practice of saving clinical samples for virological analysis after bacteriological testing.

  13. Baseline hepatitis B surface antigen quantitation can predict virologic response in entecavir-treated chronic hepatitis B patients. (United States)

    Wang, Chia-Chi; Tseng, Tai-Chung; Wang, Pin-Chao; Lin, Hans Hsienhong; Kao, Jia-Horng


    Several anti-viral drugs are approved for the treatment of hepatitis B virus (HBV) infection. However, whether quantitative hepatitis B surface antigen (qHBsAg) can predict the therapeutic response during long-term entecavir treatment remains unclear. Fifty-five chronic hepatitis B (CHB) patients who received entecavir for more than 2 years were enrolled. The serum qHBsAg level was measured by HBsAg II quant immunoassay. A significant decline in the qHBsAg level was defined as > 1 log reduction from baseline to 6 months of entecavir treatment. Of the 55 patients (41 males and 14 females with a mean age of 48.3 ± 11.4 years), 23 patients were positive for hepatitis B e antigen (HBeAg). The median treatment period was 34 months, and ranged from 26 months to 43 months. A total of 288 serum samples were used to determine the qHBsAg levels. At year 3 of entecavir therapy, one (1.8%) patient had HBsAg seroclearance. A high qHBsAg level was defined as greater than 10,000 IU/mL. Patients with a high baseline qHBsAg level had a lower rate of virologic response at year 1 (37.5% vs. 89.7%, p response in all patients. The baseline serum qHBsAg level can predict virologic response in entecavir-treated CHB patients. However, a significant decline in the qHBsAg level cannot predict serologic or virologic response of entecavir treatment. Copyright © 2013. Published by Elsevier B.V.

  14. Clinical and virological efficacy of etravirine plus two active Nucleos(tide analogs in an heterogeneous HIV-infected population.

    Directory of Open Access Journals (Sweden)

    Luis F López-Cortés

    Full Text Available 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(tide 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 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 NCT01437241.

  15. Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, A; Phillips, AN; Ruiz, L


    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1...

  16. Phylogenetic, Virological, and Clinical Characteristics of Genotype C Hepatitis B Virus with TCC at Codon 15 of the Precore Region


    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


    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 desig...

  17. Gammadelta lymphocyte response to porcine reproductive and respiratory syndrome virus. (United States)

    Olin, Michael R; Batista, Laura; Xiao, Zhengguo; Dee, Scott A; Murtaugh, Michael P; Pijoan, Carlos C; Molitor, Thomas W


    Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be one of the most important diseases facing swine industry today. Following PRRSV infection pigs develop both humoral and cell-mediated responses following PRRSV exposure; however, the relative importance in protection and clearance of the virus is not yet completely understood. Swine contain a large percentage of gammadelta T-lymphocytes in peripheral circulation capable of responding to various pathogens in both an innate and specific immune response. The objectives of this study were to determine whether gammadelta lymphocytes functionally respond to PRRSV upon initial exposure and re-exposure. Four month old PRRSV free gilts were intranasally inoculated with a field isolate MN-30100 then assessed at various time points post infection. On day 120, pigs were re-exposed with MN-30100 PRRSV strain and subsequently were bled on days 0, 7, and 14 post re-exposure. Lymphocyte subpopulations, antigen specific proliferation, and IFN-gamma production were evaluated throughout the study. Circulating gammadelta lymphocytes in PRRSV exposed animals expanded between days 14 to 70 (d14-d70, p = 0.016); following antigen stimulation, gammadelta lymphocyte proliferated by day 14 (d0-d14, p = 0.001) continuing through day 60. gammadelta lymphocytes produced IFN-gamma by day 14 pi continuing through day 50 (d0-d50, p = 0.004). Following re-exposure both gammadelta+ and CD4+ lymphocytes increased in IFN-gamma production. These results are not fully conclusive on the role of gammadelta lymphocytes against PRRSV; the data indicate that gammadelta lymphocytes specifically respond to PRRSV.

  18. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen. (United States)

    Piketty, C; Weiss, L; Thomas, F; Mohamed, A S; Belec, L; Kazatchkine, M D


    Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected patients who began first-line protease inhibitor therapy in 1996, the outcome of 42 patients with discrepant virologic and immunologic responses to antiretroviral treatment at 12 months was analyzed at 30 months of treatment. The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response (67%; P<.0001, log-rank test). Differences in outcome were significant (relative risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses.

  19. Determinants of virological failure among patients on highly active antiretroviral therapy in University of Gondar Referral Hospital, Northwest Ethiopia: a case-control study. (United States)

    Bayu, Belete; Tariku, Amare; Bulti, Abera Balcha; Habitu, Yohannes Ayanaw; Derso, Terefe; Teshome, Destaw Fetene


    Viral load monitoring is used as an important biomarker for diagnosing treatment failure in patients with HIV infection/AIDS. Ethiopia has started targeted viral load monitoring. However, factors leading to virological failure are not well understood and studied. Thus, the aim of this study was to identify the determinants of virological failure among HIV-infected patients on highly active antiretroviral therapy at the University of Gondar Referral Hospital, Northwest Ethiopia. A case-control study was conducted from May to June 2015. Cases were subjects who had already experienced virological failure; controls were those without virological failure. Data were extracted from 153 cases and 153 controls through chart review. A multivariate logistic regression analysis was carried out to identify factors associated with virological failure, and variables with a p -value failure was observed among patients aged failure. Therefore, evidence-based intervention should be implemented to improve adherence to ART, which in turn helps to boost immunity (CD4) and suppresses viral replication and load. Moreover, attention should be given to younger patients who have had ART for longer periods.

  20. Assessment of in vitro radiosensitivity of human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Knox, S.J.; Shifrine, M.; Rosenblatt, L.S.


    The proliferative capacity of sensitive lymphocyte progenitor cells, from thirty-one clinically normal adults, was evaluated following in vitro x-irradiation (0-400R). Radiation effects were studied using both whole blood and lymphocyte-enriched mononuclear cell fractions in the lymphocyte stimulation test and colony formation assay with 6 different mitogens and antigens. Radiation dose-response survival curves were determined for the different test groups. The sensitivity of the different assay systems is compared and normative values are presented that may be used for comparison purposes to determine the relative radiosensitivity of atypical individuals and groups of individuals

  1. Worsening Renal Function in Acute Heart Failure Patients Undergoing Aggressive Diuresis is Not Associated with Tubular Injury. (United States)

    Ahmad, Tariq; Jackson, Keyanna; Rao, Veena S; Tang, W H Wilson; Brisco-Bacik, Meredith A; Chen, Horng H; Felker, G Michael; Hernandez, Adrian F; O'Connor, Christopher M; Sabbisetti, Venkata S; Bonventre, Joseph V; Wilson, F Perry; Coca, Steven G; Testani, Jeffrey M


    Background -Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure (AHF) treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers-NAG, NGAL, and KIM-1- are now available that can quantify the degree of renal tubularinjury. The ROSE-AHF trial provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for AHF, as the ROSE-AHF protocol dictated high dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. Methods -Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed ( N =283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated using cystatin C. Results -Consistent with protocol driven aggressive dosing of loop diuretics, participants received a median 560 mg of IV furosemide equivalents (IQR 300-815 mg) which induced a urine output of 8425 mL (IQR 6341-10528 ml) over the 72-hour intervention period. Levels of NAG and KIM-1 did not change with aggressive diuresis ( P >0.59, both), whereas levels of NGAL decreased slightly [-8.7 ng/mg (-169, 35 ng/mg), P renal tubular injury: NGAL ( P =0.21), NAG ( P =0.46), or KIM-1 ( P =0.22). Increases in NGAL, NAG, and KIM-1 were paradoxically associated with improved survival (adjusted HR: 0.80 per 10 percentile increase, 95% CI: 0.69-0.91; P =0.001). Conclusions -Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of AHF patients. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

  2. Induction of hemeoxygenase-1 expression after inhibition of hemeoxygenase activity promotes inflammation and worsens ischemic brain damage in mice. (United States)

    Pérez-de-Puig, I; Martín, A; Gorina, R; de la Rosa, X; Martinez, E; Planas, A M


    Hemeoxygenase (HO) is an enzymatic system that degrades heme. HO-1 is an inducible isoform whereas HO-2 is constitutive. Stroke strongly induces HO-1 expression but the underlying mechanisms are not fully elucidated. Cytokines that are up-regulated after ischemia, like interleukin (IL)-10, can induce HO-1 gene expression, which is positively regulated by the transcriptional activator nuclear factor erythroid 2-related factor 2 (Nrf2) and negatively regulated by the transcriptional repressor breast cancer type 1 susceptibility protein (BRCA1) associated C-terminal helicase 1 (Bach-1). While Nrf2 is activated after ischemia and drugs promoting Nrf2 activation increase HO-1 and are beneficial, the involvement of Bach-1 is unknown. Here we investigated mechanisms involved in HO-1 induction and evaluated the effects of HO activity inhibition in mouse permanent middle cerebral artery occlusion (pMCAO). HO-1 was induced after ischemia in IL-10-deficient mice suggesting that post-ischemic HO-1 induction was IL-10-independent. Attenuation of Bach-1 gene repression after ischemia was associated to enhanced HO-1 induction. Administration of the HO activity inhibitor zinc proto-porphyrin IX (ZnPP) i.p. 24h before pMCAO exacerbated ischemia-induced tumor necrosis factor-α (TNF-α) and IL-1β, nitro-oxidative stress, and the presence of neutrophils at 8h, and increased infarct volume at day 4. However, ZnPP did not worsen ischemic damage when given 30min before pMCAO. ZnPP induced HO-1 expression in the cerebral vasculature at 24h, when it was still detected by high-performance liquid chromatography (HPLC) in plasma. While ZnPP was not found in brain tissue extracts of controls, it could be detected after ischemia, supporting that a small fraction of the injected drug can reach the tissue following blood-brain barrier breakdown. The deleterious effect of inhibiting HO activity in ischemia became apparent in the presence of ZnPP-induced HO-1, which is known to exert effects

  3. Beta blocker use in subjects with type 2 diabetes mellitus and systolic heart failure does not worsen glycaemic control

    Directory of Open Access Journals (Sweden)

    Wai Bryan


    Full Text Available Abstract Background The prognostic benefits of beta-blockers (BB in patients with systolic heart failure (SHF are known but despite this, in patients with diabetes they are underutilized. The aim of this study was to assess the effect of beta-blockers (BB on glycaemic control in patients with Type 2 Diabetes (T2DM and systolic heart failure (SHF stratified to beta-1 selective (Bisoprolol vs. nonselective BB (Carvedilol. Methods This observational, cohort study was conducted in patients with T2DM and SHF attending an Australian tertiary teaching hospital's heart failure services. The primary endpoint was glycaemic control measured by glycosylated haemoglobin (HbA1c at initiation and top dose of BB. Secondary endpoints included microalbuminuria, changes in lipid profile and estimated glomerular filtration rate (eGFR. Results 125 patients were assessed. Both groups were well matched for gender, NYHA class and use of guideline validated heart failure and diabetic medications. The mean treatment duration was 1.9 ± 1.1 years with carvedilol and 1.4 ± 1.0 years with bisoprolol (p = ns. The carvedilol group achieved a reduction in HbA1c (7.8 ± 0.21% to 7.3 ± 0.17%, p = 0.02 whereas the bisoprolol group showed no change in HbA1c (7.0 ± 0.20% to 6.9 ± 0.23%, p = 0.92. There was no significant difference in the change in HbA1c from baseline to peak BB dose in the carvedilol group compared to the bisoprolol group. There was a similar deterioration in eGFR, but no significant changes in lipid profile or microalbuminuria in both groups (p = ns. Conclusion BB use did not worsen glycaemic control, lipid profile or albuminuria status in subjects with SHF and T2DM. Carvedilol significantly improved glycemic control in subjects with SHF and T2DM and this improvement was non significantly better than that obtained with bisoprolol. BB's should not be withheld from patients with T2DM and SHF.

  4. Subclinical hypothyroidism might worsen the effects of aging on serum lipid profiles: a population-based case-control study. (United States)

    Zhao, Meng; Yang, Tao; Chen, Li; Tang, Xulei; Guan, Qingbo; Zhang, Bingchang; Zhang, Xu; Zhang, Haiqing; Wang, Chenggang; Xu, Jin; Hou, Xinguo; Li, Qiu; Yu, Chunxiao; Zhao, Yuanfei; Fang, Li; Yuan, Zhongshang; Xue, Fuzhong; Ning, Guang; Gao, Ling; Xu, Chao; Zhao, Jiajun


    Dyslipidemia is an important global health problem, particularly in the elderly population. Traditionally, the high prevalence of dyslipidemia in elderly people is considered a "natural condition." Notably, subclinical hypothyroidism (SCH) is one of the most important risk factors for dyslipidemia. Few studies have assessed whether SCH plays a role in the increase in age-related dyslipidemia. This study aimed to explore the association between SCH and lipid profiles in different age groups. This was a large-scale, population-based, case-control study. The population was derived from the REACTION study conducted across China. A total of 17,046 individuals (8827 cases and 8219 controls) aged 40 years or older were enrolled in the final analyses. The relationships between SCH and serum lipid parameters in each age group were evaluated after adjustment for thyroid hormones and common confounding factors. In the entire population, thyrotropin (TSH), the key indicator of SCH, was positively associated with cholesterol parameters (total cholesterol [TC] and low-density lipoprotein cholesterol [LDL-C]) through the sixth decade of life. After adjusting for common confounding factors and thyroid hormones, each 1 mIU/L increase in TSH was estimated to elevate the TC level by 0.0147 mmol/L and 0.0551 mmol/L, respectively, in individuals aged 40-49 years and 60-69 years. Similarly, with each 1 mIU/L increase in TSH, the LDL-C level tended to show gradually greater increases as age increased. In moderately old subjects (60-69 years), mild (TSH≤10 mIU/L) and significant (TSH>10 mIU/L) SCH increased the concentration of TC approximately 1.03- and 1.36-fold, and the concentration of LDL-C approximately 1.19- and 1.65-fold, respectively, when compared with younger subjects. TSH exhibited a stronger effect on the TC and LDL-C level in moderately old subjects than in younger subjects. SCH might augment and worsen the effects of aging on serum lipid profiles.

  5. Aeromedical evacuation-relevant hypobaria worsens axonal and neurologic injury in rats after underbody blast-induced hyperacceleration. (United States)

    Proctor, Julie L; Mello, Kaitlin T; Fang, Raymond; Puche, Adam C; Rosenthal, Robert E; Fourney, William L; Leiste, Ulrich H; Fiskum, Gary


    Occupants of military vehicles targeted by explosive devices often suffer from traumatic brain injury (TBI) and are typically transported by the aeromedical evacuation (AE) system to a military medical center within a few days. This study tested the hypothesis that exposure of rats to AE-relevant hypobaria worsens cerebral axonal injury and neurologic impairment caused by underbody blasts. Anesthetized adult male rats were secured within cylinders attached to a metal plate, simulating the hull of an armored vehicle. An explosive located under the plate was detonated, resulting in a peak vertical acceleration force on the plate and occupant rats of 100G. Rats remained under normobaria or were exposed to hypobaria equal to 8,000 feet in an altitude chamber for 6 hours, starting at 6 hours to 6 days after blast. At 7 days, rats were tested for vestibulomotor function using the balance beam walking task and euthanized by perfusion. The brains were then analyzed for axonal fiber injury. The number of internal capsule silver-stained axonal fibers was greater in animals exposed to 100G blast than in shams. Animals exposed to hypobaria starting at 6 hours to 6 days after blast exhibited more silver-stained fibers than those not exposed to hypobaria. Rats exposed to 100% oxygen (O2) during hypobaria at 24 hours postblast displayed greater silver staining and more balance beam foot-faults, in comparison with rats exposed to hypobaria under 21% O2. Exposure of rats to blast-induced acceleration of 100G increases cerebral axonal injury, which is significantly exacerbated by exposure to hypobaria as early as 6 hours and as late as 6 days postblast. Rats exposed to underbody blasts and then to hypobaria under 100% O2 exhibit increased axonal damage and impaired motor function compared to those subjected to blast and hypobaria under 21% O2. These findings raise concern about the effects of AE-related hypobaria on TBI victims, the timing of AE after TBI, and whether these effects

  6. Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease. (United States)

    Lurain, Nell S; Hanson, Barbara A; Martinson, Jeffrey; Leurgans, Sue E; Landay, Alan L; Bennett, David A; Schneider, Julie A


    Serum, cerebrospinal fluid (CSF), and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between cytomegalovirus (CMV) infection and clinical and pathological markers of Alzheimer disease. CMV antibody levels were associated with neurofibrillary tangles (NFTs). CSF interferon γ was only detected in seropositive subjects and was significantly associated with NFTs. The percentage of senescent T cells (CD4+ or CD8+CD28-CD57+) was significantly higher for CMV-seropositive as compared to CMV-seronegative subjects and was marginally associated with the pathologic diagnosis of Alzheimer disease (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFFs) infected with each of 3 clinical CMV strains. In the same subjects, there was no association of herpes simplex virus type 1 (HSV-1) antibody levels with CMV antibody levels or clinical or pathological markers of Alzheimer disease. HSV-1 infection of HFFs did not induce amyloid-β. These data support an association between CMV and the development of Alzheimer disease.

  7. Clinical significance of worsening versus stable preradiographic MRI lesions in a cohort study of persons at higher risk for knee osteoarthritis. (United States)

    Sharma, Leena; Nevitt, Michael; Hochberg, Marc; Guermazi, Ali; Roemer, Frank W; Crema, Michel; Eaton, Charles; Jackson, Rebecca; Kwoh, Kent; Cauley, Jane; Almagor, Orit; Chmiel, Joan S


    Whether preradiographic lesions in knees at risk for osteoarthritis are incidental versus disease is unclear. We hypothesised, in persons without but at higher risk for knee osteoarthritis, that: 12-48 month MRI lesion status worsening is associated with 12-48 month incident radiographic osteoarthritis (objective component of clinical definition of knee osteoarthritis) and 48-84 month persistent symptoms. In 849 Osteoarthritis Initiative participants Kellgren/Lawrence (KL) 0 in both knees, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci on 12 month (baseline) and 48 month MRIs. Multivariable logistic regression was used to evaluate associations between 12-48 month worsening versus stable status and outcome (12-48 month incident KL ≥1 and KL ≥2, and 48-84 month persistent symptoms defined as frequent symptoms or medication use most days of ≥1 month in past 12 month, at consecutive visits 48-84 months), adjusting for age, gender, body mass index (BMI), injury and surgery. Mean age was 59.6 (8.8), BMI 26.7 (4.2) and 55.9% were women. 12-48 month status worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs was associated with 12-48 month incident radiographic outcomes, and worsening of cartilage damage and BMLs with 48-84 month persistent symptoms. There was a dose-response association for magnitude of worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs and radiographic outcomes, and cartilage damage and BMLs and persistent symptoms. In persons at higher risk, worsening MRI lesion status was associated with concurrent incident radiographic osteoarthritis and subsequent persistent symptoms. These findings suggest that such lesions represent early osteoarthritis, and add support for a paradigm shift towards investigation of intervention effectiveness at this stage. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  8. Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

    Directory of Open Access Journals (Sweden)

    Ahoua Laurence


    Full Text Available Abstract Background Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. Methods Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/ml and subtherapeutic antiretroviral (ARV concentrations were investigated with multiple logistic regression. Results At 12 and 24 months of ART, 72% (n = 701 and 70% (n = 369 of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (1,000 copies/ml were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. Conclusion Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.

  9. Separation and properties of EA-rosette-forming lymphocytes in humans

    NARCIS (Netherlands)

    van Oers, M. H.; Zeijlemaker, W. P.; Schellekens, P. T.


    Human peripheral blood lymphocytes were separated into subpopulations enriched or depleted with respect to B lymphocytes (Ig-bearing cells), T lymphocytes, (cell forming rosettes with sheep erythrocytes: E-RFC) and Fc receptor-bearing lymphocytes (EA-RFC). From the distributions and recoveries of

  10. PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Weisser, Martin; Yeh, Ru-Fang; Duchateau-Nguyen, Guillemette


    Addition of rituximab (R) to fludarabine and cyclophosphamide (FC) has significantly improved patient outcomes in chronic lymphocytic leukemia (CLL). Whether baseline gene expression can identify patients who will benefit from immunochemotherapy over chemotherapy alone has not been determined. We...

  11. Langerhans cells and subsets of lymphocytes in the nasal mucosa

    DEFF Research Database (Denmark)

    Hellquist-Dahl, B; Olsen, K E; Irander, K


    Langerhans cells and different lymphocytes were studied in the nasal mucosa of 39 woodwork teachers and a control group of 14 healthy subjects. Ten of the woodwork teachers were sensitized as determined by skin prick test. A panel of different monoclonal antibodies was applied on the frozen nasal...... mucosal specimens. Intraepithelial CD1-positive dendritic cells were found in all specimens. However, there was no difference between the number of these Langerhans cells found in the study group and the number found in the controls. In every specimen the intraepithelial lymphocyte population...... was dominated by T lymphocytes, and there were relatively few B cells. Similarly the ratio between CD4- and CD8-positive lymphocytes in the study group and the controls was the same. In all specimens there was a dominance of T suppressor/cytotoxic cells compared with T helper/inducer cells. The study confirms...

  12. Lymphocytic Mural Folliculitis Resembling Epitheliotropic Lymphoma in Tigers ( Panthera tigris). (United States)

    Sula, Mee-Ja M; Frank, Linda A; Ramsay, Edward C


    A striking form of lymphocytic mural folliculitis is described in 6 tigers ( Panthera tigris). Clinically, all tigers exhibited regionally extensive chronic, variably waxing and waning alopecia with minimal scaling and crusting most pronounced over the head, neck, and shoulders. More severely affected tigers exhibited marked hyperpigmentation and lichenification. Pruritus was not a feature. Tigers generally lacked signs of systemic illness and clinical pathology findings were unremarkable. Histologic examination of skin biopsies revealed infiltrative lymphocytic mural folliculitis extending the length of the hair follicle. Mild epidermal lymphocytic infiltrates were frequent. The surrounding dermis was histologically unremarkable in 4 of 6 tigers or associated with mild perifollicular and periadnexal mixed inflammation in 2 of 6 tigers. The cause of the mural folliculitis was not identified, and tigers responded poorly to immunomodulatory therapy. Lymphocytic mural folliculitis might be a nonspecific hypersensitivity reaction pattern in tigers, and care should be taken to differentiate this reaction pattern from epitheliotropic T-cell lymphoma.

  13. Radiosensitivity and life span of dog peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Leonard, A.; Decat, G.; Fritz, T.E.


    Observations made after 48 h of cultivation show that 52% of dog lymphocytes are already in M 2 and 17% in M 3 at that fixation time. Evidently, the large discrepancy observed between man and dog with respect to the yield of dicentric chromosomes induced by an exposure to 200 rad of X-rays and observed after a culture time of 48 h does not correspond to a difference in chromosomal radiosensitivity. There is, indeed no statistically significant difference between the yield of dicentrics observed in M 1 human lymphocytes (32.0 per 100 cells) and that in dog lymphocytes after correction of the values obtained at 48 h (28.6 per 100 cells.) From the observations performed on whole-body irradiated dogs one can estimate that the half-time of dog lymphocytes carrying chromosome aberrations is less than 30 days. (orig.)

  14. CD3 immunohistochemical staining in diagnosis of lymphocytic colitis

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Engel, Ulla; Holck, Susanne


    Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Traditionally, MC encompasses the 2 subgroups lymphocytic colitis (LC) and collagenous colitis, but recently, an additional subgroup, MC incomplete, has been introduced. Distinguishing between the subgroups relies exclusively...

  15. The genotoxicity of sodium arsenite in human lymphocyte culture

    International Nuclear Information System (INIS)

    Elhabit, O.H.M.


    Sodium arsenite was tested for its clastogenic effect alone and in combination with x-irradiation on whole blood culture and on isolated lymphocyte culture. The results showed a significant difference in the yield of aberrations induced with respect to the culture time 48 hr whole blood culture showed significant increase in gaps and breaks whereas isolated lymphocytes culture showed significant inhibition of cell cycle and 75% of the lymphocytes were in first cell cycle at 72 hr. Arsenite showed co-mutagenicity with different doses of x-ray delivered immediately or few hours after treatment of the culture with SA. The results suggest that SA also is mutagenic at the dose level used and provide support for the indispensability of whole blood culture for evaluation of the in vivo effect any suspected mutagen. Using isolated lymphocytes appear to have problems leading to extensive cell cycle delay

  16. Orbital involvement in chronic lymphocytic leukemia: Case report

    Directory of Open Access Journals (Sweden)

    Romana Rotdajč


    Conclusions: In patients with chronic lymphocytic leukemia, progression of the disease should be suspected at impairment of the eye and the surrounding tissues. Monotherapy with rituximab can be successful, which is indicated particularly in elderly patients.

  17. Lymphocytic hypophysitis in a dog with diabetes insipidus. (United States)

    Meij, B P; Voorhout, G; Gerritsen, R J; Grinwis, G C M; Ijzer, J


    An 8-year-old male German longhaired pointer was referred for diabetes insipidus responsive to treatment with desmopressin. The dog had polyuria and polydipsia, exercise intolerance and a dull hair coat. Plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone (GH) and insulin-like growth factor-1 were decreased; plasma adrenocorticotropic hormone (ACTH) was slightly elevated and plasma α-melanocyte-stimulating hormone (MSH) was within the reference range. Computed tomography revealed a heterogeneously contrast-enhancing pituitary mass compressing the hypothalamus. Transsphenoidal hypophysectomy was performed and microscopical examination of the surgical biopsy samples revealed hypophysitis without evidence of pituitary adenoma. The hypophysitis was characterized by marked lymphocytic infiltration of the adenohypophysis that contained a mixed population of neuroendocrine cells expressing GH, ACTH or α-MSH. The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Cytogenetical analysis in blood lymphocytes of cigarette smokers in ...

    African Journals Online (AJOL)

    Cytogenetical analysis in blood lymphocytes of cigarette smokers in Tiruchirappalli district, Tamil Nadu, India. S. Christobher, M. Periyasamy, H.E. Syed Mohamed, A. Sadiq Bukhari, Alagamuthu Karthickkumar, Vellingiri Balachandar ...

  19. Genetics Home Reference: bare lymphocyte syndrome type II (United States)

    ... Immunodeficiency Disorders Health Topic: Immune System and Disorders Genetic and Rare Diseases Information Center (1 link) Bare lymphocyte syndrome 2 Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (6 ...


    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari


    Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  1. Spontaneous unscheduled DNA synthesis in human lymphocytes

    International Nuclear Information System (INIS)

    Forell, B.; Myers, L.S. Jr.; Norman, A.


    The rate of spontaneous unscheduled DNA synthesis in human lymphocytes was estimated from measurements of tritiated thymidine incorporation into double-stranded DNA (ds-DNA) during incubation of cells in vitro. The contribution of scheduled DNA synthesis to the observed incorporation was reduced by inhibiting replication with hydroxyurea and by separating freshly replicated single-stranded DNA (ss-DNA) from repaired ds-DNA by column chromatography. The residual contribution of scheduled DNA synthesis was estimated by observing effects on thymidine incorporation of: (a) increasing the rate of production of apurinic sites, and alternatively, (b) increasing the number of cells in S-phase. Corrections based on estimates of endogenous pool size were also made. The rate of spontaneous unscheduled DNA synthesis is estimated to be 490 +- 120 thymidine molecules incorporated per cell per hour. These results compare favorably with estimates made from rates of depurination and depyrimidination of DNA, measured in molecular systems if we assume thymidine is incorporated by a short patch mechanism which incorporates an average of four bases per lesion

  2. Imaging B lymphocytes in autoimmune inflammatory diseases

    International Nuclear Information System (INIS)

    Iodice, V.; Lauri, C.; Capriotti, G.; Lagana', B.; Germano, V.; D’Amelio, R.; Picchianti Diamanti, A.


    B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients

  3. Emerging immunological drugs for chronic lymphocytic leukemia. (United States)

    Robak, Pawel; Smolewski, Piotr; Robak, Tadeusz


    Over the last few years, several new immunological drugs, particularly monoclonal antibodies (mAbs), immunomodulatory drugs and B-cell receptor (BCR) pathway inhibitors have been developed and investigated in chronic lymphocytic leukemia (CLL). This article summarizes recent discoveries regarding their mechanism of action, pharmacological properties, clinical activity and toxicity, as well as the emerging role of these agents in CLL. A literature review of mAbs, BCR pathway inhibitors and immunomodulating drugs was conducted of the MEDLINE database via PubMed for articles in English. Publications from 2000 through February 2015 were scrutinized. The search terms used were alemtuzumab, BI 836826, duvelisib ibrutinib, idelalisib, lenalidomide, monoclonal antibodies, MEDI-551, MOR208, obinutuzumab, ocaratuzumab, ofatumumab, ONO-4059, otlertuzumab, spebrutinib, veltuzumab and XmAb5574 in conjunction with CLL. Conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. The use of mAbs, BCR inhibitors and immunomodulating drugs is a promising new strategy for chemotherapy-free treatment of CLL. However, definitive data from ongoing and future clinical trials will aid in better defining the status of immunological drugs in the treatment of this disease.

  4. Isochromosome 17q in Chronic Lymphocytic Leukemia (United States)

    Alhourani, Eyad; Rincic, Martina; Melo, Joana B.; Carreira, Isabel M.; Glaser, Anita; Pohle, Beate; Schlie, Cordula; Liehr, Thomas


    In chronic lymphocytic leukemia (CLL), presence of acquired cytogenetic abnormalities may help to estimate prognosis. However, deletion of TP53 gene, which is associated with an aggressive course of the disease and poor prognosis along with a lack of response to treatment, is one of the alterations which may escape cytogenetic diagnoses in CLL. Thus, other techniques have emerged such as interphase fluorescence in situ hybridization (iFISH). Deletion of TP53 may but must not go together with the formation of an isochromosome i(17q); surprisingly this subgroup of patients was not in the focus of CLL studies yet. This study was about if presence of i(17q) could be indicative for a new subgroup in CLL with more adverse prognosis. As a result, TP53 deletion was detected in 18 out of 150 (12%) here studied CLL cases. Six of those cases (~33%) had the TP53 deletion accompanied by an i(17q). Interestingly, the cases with i(17q) showed a tendency towards more associated chromosomal aberrations. These findings may be the bases for follow-up studies in CLL patients with TP53 deletion with and without i(17q); it may be suggested that the i(17q) presents an even more adverse prognostic marker than TP53 deletion alone. PMID:26697230

  5. Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura


    OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...... with detection of TDR, with virological (viral loadresponse (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression...... (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral...

  6. Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study

    DEFF Research Database (Denmark)

    Røge, B T; Barfod, T S; Kirk, O


    OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA...... collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing...... adherent patients on randomized treatment failed in the RS-arm, none in the NN-arm, and six in the ASD-arm. CONCLUSIONS: Primary virological failure was caused mainly by treatment interruption. No primary protease inhibitor (PI) mutations were found in patients failing on boosted saquinavir, whereas...

  7. A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

    DEFF Research Database (Denmark)

    Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy


    Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated...... in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI...... = .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure...

  8. Prevalence and virological profiles of hepatitis B infection in human immunodeficiency virus patients. (United States)

    Attia, Koffi Alain; Eholié, Serge; Messou, Eugène; Danel, Christine; Polneau, Sandrine; Chenal, Henri; Toni, Thomas; Mbamy, Myreille; Seyler, Catherine; Wakasugi, Naomi; N'dri-Yoman, Thérèse; Anglaret, Xavier


    To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm(3) and without antiretroviral therapy; to describe different HBV-HIV coinfection virological profiles; and to search for factors associated with HBs antigen (HBsAg) presence in these HIV positive patients. During four months (June through September 2006), 491 patients were received in four HIV positive monitoring clinical centers in Abidjan. HIV-1 or HIV-1 and 2 positive patients, age ≥ 18 years, CD4+ T-cell count HBcAb). We performed HBeAg, anti-HBe antibody (anti-HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients. Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb-positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg negative status and without anti-HBsAb. Univariate analysis (Pearson χ(2) test or Fischer exact test) and multivariate analysis (backward step-wise selection logistic regression) were performed as statistical analysis. Mean age of 491 patients was 36 ± 8.68 years and 73.3% were female. Type-1 HIV was found in 97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO) clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172 (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm(3) (interquartile range: 221-470). One hundred and twelve patients had less than 200 CD4+ T-cell/mm(3). Plasma HIV-1 RNA load was elevated (≥ 5 log(10) copies/mL) in 221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and 72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%), 21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and detectable HBV DNA) was 21.3%. Three

  9. Concanavalin A-induced activation of lymphocytic choriomeningitis virus memory lymphocytes into specifically cytotoxic T cells

    DEFF Research Database (Denmark)

    Marker, O; Thomsen, Allan Randrup; Andersen, G T


    When spleen cells, which have been primed to Lymphocytic Choriomeningitis (LCM) virus during a primary infection several months previously, are stimulated in vitro with Con A. highly specific secondary cytotoxic effector cells are generated. The degree of cytotoxicity revealed by such Con A-stimu......-stimulated cells is higher than that of non-incubated spleen cells harvested nine days following the primary infection, and the effect is totally inhibited by anti-theta serum plus complement treatment of the effector cells immediately before the cytotoxic test....

  10. Cell proliferation and radiosensitivity of cow lymphocytes in culture

    International Nuclear Information System (INIS)

    Modave, C.; Fabry, L.; Leonard, A.


    The harlequin-staining technique has been used to study, after PHA-stimulation, the cell proliferation of cow lymphocytes in culture and to assess the radiosensitivity in first mitosis cells. At the 48 h fixation time, only 34% of the cells are in first mitosis whereas 55% are already in second and 11% in third mitosis. The exposure of cow lymphocytes to 200 rad X-rays result in the production of 16% dicentric chromosomes in first mitosis cells [fr

  11. Bare lymphocyte syndrome: imaging findings in an adult

    Energy Technology Data Exchange (ETDEWEB)

    Bernaerts, A.; Vandevenne, J.E.; De Schepper, A.M. [Dept. of Radiology, Universitair Ziekenhuis Antwerpen, Edegem (Belgium); Lambert, J. [Dept. of Dermatology, Universitair Ziekenhuis Antwerpen, Edegem (Belgium); De Clerck, L.S. [Dept. of Immunology, Universitair Ziekenhuis Antwerpen, Edegem (Belgium)


    Bare lymphocyte syndrome (BLS) is a rare primary immune disorder characterized by defective expression of human leukocyte antigen (HLA) on lymphocytes, often resulting in extensive and recurrent multi-organ infections. We describe a previously undiagnosed case of an adult woman who presented with radiological findings of severe bronchiectases, near-total granulomatous destruction of facial bones, and osteomyelitis. Diagnosis of BLS should be considered when evaluating children with unexplained bronchiectases or adults with long history of chronic multi-organ infections. (orig.)

  12. Mitogenic stimulation of peripheral lymphocytes of thorium workers

    International Nuclear Information System (INIS)

    Serio, C.S.; Henning, C.B.; Lloyd, E.L.


    Mitogenic stimulation of lymphocyte cultures from 30 thorium workers was studied to determine whether their immunocompetence was affected by their occupational exposure to radiation. A decrease in lymphocyte responsiveness was seen in these workers when compared with age-matched normal control subjects. The mean decrease relative to the normal controls for three different mitogens tested was 26% with phytohemagglutinin, 40% with concanavalin A, and 30% with poke week mitogen

  13. Modeling Adenovirus Latency in Human Lymphocyte Cell Lines ▿ †


    Zhang, Yange; Huang, Wen; Ornelles, David A.; Gooding, Linda R.


    Species C adenovirus establishes a latent infection in lymphocytes of the tonsils and adenoids. To understand how this lytic virus is maintained in these cells, four human lymphocytic cell lines that support the entire virus life cycle were examined. The T-cell line Jurkat ceased proliferation and died shortly after virus infection. BJAB, Ramos (B cells), and KE37 (T cells) continued to divide at nearly normal rates while replicating the virus genome. Viral genome numbers peaked and then decl...

  14. Factors associated with clinical, immunological and virological responses in protease-inhibitor-experienced brazilian children receiving highly active antiretroviral therapy containing Lopinavir-Ritonavir

    Directory of Open Access Journals (Sweden)

    Daisy Maria Machado

    Full Text Available This study evaluates clinical, virological and immunological responses to antiretroviral (ARV therapy based on Lopinavir/ritonovir (LPV/r in previously protease -inhibitor-experienced children. The study included 29 Brazilian children (median age = 5.91 years who had failed previous ARV therapy and had begun a regimen based on LPV/r. At 12 months follow-up, a good virological response to LPV/r therapy was defined as achieving an undetectable viral load or as a decrease in plasma HIV RNA levels to > 1 log. A good immunological response was defined as an increase in CD4+ cell count from baseline sufficient to attain a better CDC immune stage classification. The number of infectious episodes 12 months before and 12 months after beginning LPV/r was assessed. Sixteen (55.2% and 19 (65.5% of 29 patients exhibited good virological and immunological responses, respectively. Baseline CD4+ values (>500 predicted both virological and immunological responses (p<0.05. Older children were less likely to develop an immunological response (p<0.001 than younger children. Nine children receiving 3 ARV drugs plus LPV/r showed an immunological response (100% compared to 10/20 (50% children receiving 2 drugs plus LPV/r (p=0.01. A lower number (n<5 of infectious episodes was noted after 12 months follow-up in children using the LPV/r regimen (p=0.006. There was a positive correlation between children whose baseline CD4+ values were greater than 500 cells/mm³ and virological responses. Although virological responses to therapy were seen in about half the children (55.2%, the use of HAART containing LPV/r provided clinical and immmunological benefits.

  15. Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis. (United States)

    Laurito, Marcela Pezzoto; Parise, Edison Roberto


    Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  16. Hypermetabolism in B–lymphocytes from malignant hyperthermia susceptible individuals (United States)

    Hoppe, Kerstin; Hack, Guido; Lehmann–Horn, Frank; Jurkat–Rott, Karin; Wearing, Scott; Zullo, Alberto; Carsana, Antonella; Klingler, Werner


    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism which is characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca2+ release in myotubes via the ryanodine receptor type 1 (RyR1). As RyR1 is also expressed in B–lymphocytes, this study investigated whether cellular metabolism of native B–lymphocytes was also altered in MH susceptible (MHS) individuals. A potent activator of RyR1, 4–chloro–m–cresol (4-CmC) was used to challenge native B-lymphocytes in a real–time, metabolic assay based on a pH–sensitive silicon biosensor chip. At the cellular level, a dose–dependent, phasic acidification occurred with 4–CmC. The acidification rate, an indicator of metabolic activation, was significantly higher in B–lymphocytes from MHS patients and required 3 to 5 fold lower concentrations of 4–CmC to evoke similar acidification rates to MHN. Native B–lymphocytes from MHS individuals are more sensitive to 4–CmC than those from MHN, reflecting a greater Ca2+ turnover. The acidification response, however, was less pronounced than in muscle cells, presumably reflecting the lower expression of RyR1 in B–lymphocytes. PMID:27646467

  17. Cell titration assay for measuring blastogenesis of bovine lymphocytes. (United States)

    Baldwin, C L; Antczak, D F; Winter, A J


    The blastogenic response of bovine peripheral blood lymphocytes to phytohemagglutinin (PHA) and to microbial antigens was measured using a lymphocyte titration assay. Culture conditions, including lymphocyte concentrations, incubation periods and medium formulation, were established which produced linear or nearly linear responses over a range of cell concentrations. These conditions were established by testing lymphocytes from unimmunized cattle and from heifers infected with Brucella abortus with PHA and a B. abortus extract. Four cell concentrations in 2-fold increments were selected for measuring responses to PHA (3.125 X 10(3) to 2.5 X 10(4) cells/well) and to antigens (5.0 X 10(4) to 4.0 X 10(5) cells/well). The strength of response varied among animals and also over time for individual animals, but the titration assay allowed exponential proliferation to be distinguished from decline, which may have been due to overcrowding of microtiter wells, exhaustion of nutrients or induction of regulatory events. This assay provided a more reliable and discriminating method of evaluating lymphocyte proliferation responses than that achieved by single point assays. The displacement of the titration curves could be used to estimate the relative frequency of lymphocytes responding to antigens or mitogens.

  18. Detection of cardiac transplant rejection with radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.


    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy

  19. Lymphocyte subset reference intervals in blood donors from northeastern Brazil

    Directory of Open Access Journals (Sweden)



    Full Text Available The reference intervals for leukocytes and lymphocytes currently used by most clinical laboratories present limitations as they are primarily derived from individuals of North American and European origin. The objective this study was to determine reference values for peripheral blood B lymphocytes, T lymphocyte subsets (CD4+, CD8+, naïve, memory, regulatory, TCRαβ and TCRγδ+ and NK cells from blood donors in Salvador-Bahia, Brazil. Results: The proportion of included male subjects was 73.7% and the median ages of males (34 and females (35 were found to be similar. Absolute counts total lymphocytes subsets to both gender was 1,956 (1,060-4,186 cells and relative values 34%. The T CD4+ and T CD8+ lymphocytes relative values was 51% (20-62 and 24% (9-28, respectively. The most statistically significant finding observed was a higher percentage of B lymphocytes (p=0.03 in females. Commonly cited subset reference intervals were found to be consistent with values in several populations from different geographic areas.

  20. Expression and in vitro upregulation of MHCII in koala lymphocytes. (United States)

    Lau, Quintin; Canfield, Paul J; Higgins, Damien P


    Understanding and measuring immune activity of the koala (Phascolarctos cinereus), is important to studies of the epidemiology and impact of the widespread chlamydial and koala retroviral (KoRV) infections that occur in this iconic but increasingly threatened species. To explore the interaction of disease and immunity, and to assess the potential for use of class II major histocompatibility complex (MHCII) upregulation as an indicator of lymphocyte activation in in vitro immune assays, we have investigated the expression of MHCII in koala lymphocytes by flow cytometry. MHCII expression was upregulated in mitogen stimulated B lymphocytes in vitro but no such increase was detected in vivo in free-living koalas with active inflammation. In assessing phenotypic baseline data of captive koalas, we have identified that MHCII is expressed predominantly on circulating B lymphocytes (85.7 ± 2.4%) but on very few T lymphocytes (3.4 ± 1.9%), even following activation, and suggest that the latter finding might be compensated by the greater absolute numbers of peripheral blood B lymphocytes in this species relative to many eutherian species. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Gamma/delta T lymphocytes in Mycobacterium tuberculosis infection. (United States)

    Balikó, Z; Szereday, L; Szekeres-Bartho, J


    Data on the percentage of gamma/delta T lymphocytes in the peripheral blood of patients infected with Mycobacterium tuberculosis are few and contradictory. The percentage of gamma/delta T lymphocytes in the peripheral blood of tuberculin positive and tuberculin negative patients with Mycobacterium tuberculosis infection and healthy controls was compared. Thirty six patients infected with Mycobacterium tuberculosis and 11 healthy controls were studied. Lymphocytes were separated, cytocentrifuged onto glass microscope slides, and reacted with anti-gamma/delta monoclonal antibody. The percentage of gamma/delta positive cells was determined by microscopic counting of 300 lymphocytes. No difference was found in the percentage of gamma/delta T lymphocytes between patients and controls. However, when the patients were divided into two groups according to reactivity or non-reactivity in the Mantoux skin reaction a higher percentage of gamma/delta T lymphocytes was found in the peripheral blood of patients with tuberculin anergy than in tuberculin positive patients or controls. Higher gamma/delta T cell counts are found in tuberculin negative patients with tuberculosis than in tuberculin positive patients or tuberculin positive controls. The high gamma/delta T cell counts in tuberculin anergic patients may reflect a shift in the immune response in a Th2 direction characterised by increased antibody production and decreased cell mediated responses.

  2. Lymphocyte subset numbers depend on the bacterial origin of sepsis. (United States)

    Holub, M; Klucková, Z; Helcl, M; Príhodov, J; Rokyta, R; Beran, O


    To determine the quantitative variances in peripheral blood lymphocyte subsets during sepsis, and their clinical significance. Peripheral blood lymphocyte subsets were enumerated in 32 non-surgical septic patients during the first 14 days of hospitalization; results from septic patients were compared with those from 34 healthy controls. Influences of the severity and the bacterial etiology of sepsis on changes in lymphocyte subsets were also assessed. Significant decreases (P or=14 days. Conversely, patients with sepsis due to Gram-negative pathogens (Neisseria meningitidis, n = 8; enterobacteria, n = 2) achieved full recovery of the subsets within 3 days. Moreover, the patients with Gram-negative sepsis demonstrated a significant increase in B-lymphocytes, and a rise in the numbers of CD3+/DR+ and CD4+ T-lymphocytes, which were more rapid than in patients with Gram-positive sepsis. Our results indicate that Gram-positive sepsis causes stronger suppression of peripheral blood lymphocyte subsets in comparison to sepsis due to Gram-negative pathogens.

  3. Mechanism of chlorphentermine-induced lymphocyte toxicity: initial investigations

    International Nuclear Information System (INIS)

    Sauers, L.J.; Wierda, D.; Reasor, M.J.


    Chlorphentermine (CP) inhibits the blastogenic response of mouse splenic and human peripheral blood lymphocytes to the T-cell mitogens, phytohemagglutinin (PHA) and concanavalin A (Con A). The purpose of these studies was to examine in vitro the mechanism mediating this immunosuppression. If mouse or human lymphocytes are pretreated with CP for 30 minutes, then stimulated with PHA, their blastogenic response is inhibited 80% and 45%, respectively. However, if CP is not added until 10 minutes or later following PHA stimulation, the inhibitory effect of the drug is essentially eliminated. The authors also determined that CP can potentiate Con A-induced agglutination of human lymphocytes. Enhanced agglutination can result from changes in the integrity of membrane phospholipids. Because changes in membrane phospholipid biochemistry characteristically occur within 10 minutes after mitogen-induced lymphocyte activation, the authors examined whether CP altered the incorporation of choline into cellular phospholipids. They found that CP decreases overall incorporation of 14 C-choline into cellular phospholipids of mouse lymphocytes by 45% during the first 4 hours of activation. These data suggest that the immunotoxicity associated with CP may be mediated by drug-induced changes at the membrane level that appear to occur early during lymphocyte activation

  4. Pathologic and Molecular Virologic Characterization of a Canine Distemper Outbreak in Farmed Civets. (United States)

    Techangamsuwan, S; Banlunara, W; Radtanakatikanon, A; Sommanustweechai, A; Siriaroonrat, B; Lombardini, E D; Rungsipipat, A


    In October 2011, a fatal disease outbreak occurred in 3 civet species farmed for their use in the coffee industry in Thailand. The disease quickly killed 20 animals in a mixed population of Asian palm civets (Paradoxurus hermaphroditus; n = 18), a masked palm civet (Paguma larvata; n = 1), and small Indian civet (Viverricula indica; n = 1). Clinical signs consisted of severe lethargy, weakness, vomiting, and diarrhea with associated dehydration, dyspnea, nasal and footpad hyperkeratosis, and seizures. All civets were positive for canine morbillivirus using the commercial canine distemper virus (CDV) antigen test kit. Consistently observed necropsy findings consisted of severe pneumonia and hemorrhagic enteritis. Microscopic examination revealed severe gastroenteritis, bronchointerstitial pneumonia, lymphadenitis, necrotizing dermatitis, nonsuppurative polioencephalitis, and characteristic intranuclear/intracytoplasmic eosinophilic viral inclusions in multiple tissues. Immunohistochemical analysis revealed immunoreactivity of varying intensity, while virus isolation demonstrated typical cytopathic effects. To confirm CDV infection, reverse transcription-polymerase chain reaction against fusion (F), phosphoprotein (P), and hemagglutinin (H) genes showed bands of expected size using conjunctival swabs (9 civets, 1 dog [Canis lupus familiaris] living on the farm). Phylogenetic analyses and restriction fragment length polymorphism results indicated that the civets were infected by the Asia-1 strain of CDV commonly found in dogs in Thailand. The deduced amino acid sequences of the signaling lymphocyte activation molecule binding region of the CDV-H proteins revealed a Y549H mutation in both CDV-infected Asian palm civets (n = 4) and a co-located dog. We report a canine distemper outbreak in a civet colony with lineage classification and a Y549H mutation in noncanid species in Thailand. © The Author(s) 2014.

  5. A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review. (United States)

    Özdin, Selçuk; Sarisoy, Gökhan; Böke, Ömer


    Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have recently been used as indicators of inflammation. Higher MLR and PLR values have been determined in the euthymic and manic periods in patients with bipolar disorder compared to a control group. High NLR values were determined in the only study investigating this ratio in schizophrenia patients. The purpose of this study was to compare NLR, PLR and MLR values and complete blood count elements in patients receiving treatment and hospitalized due to schizophrenic psychotic episode and bipolar disorder manic episode. All patients meeting the inclusion criteria among subjects receiving treatment and hospitalized due to schizophrenia-psychotic episode and bipolar affective disorder-manic episode at the Ondokuz Mayıs University Medical Faculty Psychiatry Department, Turkey, in 2012-2016 were included in our study. A total of 157 healthy donors were included as a control group. White blood cell (WBC), neutrophil, lymphocyte, platelet and monocyte numbers were noted retrospectively from complete blood counts at time of admission, and NLR, PLR and MLR were calculated from these. NLR, PLR and MLR values and platelet numbers in this study were higher and lymphocyte numbers were lower in bipolar disorder patients compared to the controls. Elevation in NLR, MLR and PLR values and neutrophil numbers and lower lymphocyte numbers were determined in schizophrenia patients compared to the controls. Higher NLR and MLR values were found in schizophrenia patients compared to bipolar disorder. Findings of our study supported the inflammation hypothesis for schizophrenia and bipolar disorder.

  6. Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study

    DEFF Research Database (Denmark)

    Roge, BT; Barfod, TS; Kirk, O


    OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA...... collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing...

  7. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    DEFF Research Database (Denmark)

    NN, NN; Mugavero, Michael J; May, Margaret


    OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between.......04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). CONCLUSION: Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because...

  8. Hot News: Impact of Low-level Viremia on Treatment Outcomes During ART - Is it Time to Revise the Definition of Virological Failure? (United States)

    Poveda, Eva; Crespo, Manuel


    The level of HIV-RNA in plasma (HIV viral load) is the main marker used to monitor the virological response to antiretroviral therapy (ART) in HIV-infected patients. The threshold used to define virological suppression has historically been dictated by the limits of detection of the commercial assays used to quantify the plasma viral load. Thus, as more sensitive assays have proliferated and become more widely available, the definition has shifted from definition of virological failure as a confirmed plasma viral load > 200 cop/mL, or even > 1000 cop/mL according to the WHO guidelines for low-income and middle-income countries. Several studies have evaluated the impact of low-level viremia as intermittent episodes (blips) or persistent detectable low-level viremia (50-1000 cop/mL) on treatment outcomes during ART. Some of these studies have suggested a potential role for low-level viremia as a predictor of virological failure, although up to now the data have been insufficient and controversial to guide clinical management. Hermans et al. have recently published the results of a large (n = 70.930 HIV-infected patients) multicenter study (57 clinical sites in South Africa) with a median follow-up for more than 2 years, to evaluate the incidence and impact of low-level viremia (defined as HIV-RNA viral load of 51-999 cop/mL) and its association with virological failure (Hermans et al., Lancet Infect Dis 2018;18:188-97). This large cohort study concludes that overall, patients with low-level viremia are predisposed to subsequent virological failure. The risk of virological failure was 5 times higher for patients with low-level viremia ranging 400-999 cop/mL, and 2 times higher for those with viremia ranging 51-199 cop/mL, compared with patients maintaining viral load suppression (definition of virological failure as a confirmed viral load of > 200 cop/mL established for most current HIV treatment guidelines. The implementation of new recommendations for the management

  9. The worsening factors of dengue hemorrhagic fever (DHF) based on cohort study with nested case-control in a tertiary hospital (United States)

    Lardo, S.; Soesatyo, M. H. N. E.; Juffrie; Umniyati, S. R.


    The clinical pathway of DHF has a broad pathophysiological and pathogenesis spectrum. Clinical and laboratory characteristics are some of the parameters to determine the factors that contribute to the worsening of the disease. The objective of this study is to determine the clinical and laboratory characteristics which contribute to the worsening of DHF. The study had been conducted from January 2012-December 2014 at the general ward of the Internal Medicine Department, Indonesia Army Central Hospital Gatot Soebroto. There were 101 male patients (64.7%) and 55 female patients (35.3 %) ages ranging from 14 - 62 years old. The diagnosis was divided into: 124 patients DHF grade I, 6 DHF grade II, 20 DHF grade III and 6 with dengue shock syndrome (DSS) patients. Clinically and statistically, there were 4 variables apparently found with the severity of DHF, as follows: decreased appetite with p = 0.007 (OR 4.87), hepatomegaly with p = 0.009 (OR 27.00), systolic blood pressure with p = 0.037 (OR 0.95), and initial thrombocyte with p = 0.000 (OR 0.97). This cohort and nested case-control study found that worsening of DHF is related with decreased appetite, hepatomegaly, systolic blood pressure and initial thrombocyte count.

  10. Do changes in subjective sleep and biological rhythms predict worsening in postpartum depressive symptoms? A prospective study across the perinatal period. (United States)

    Krawczak, Elizabeth M; Minuzzi, Luciano; Hidalgo, Maria Paz; Frey, Benicio N


    Abnormalities of sleep and biological rhythms have been widely implicated in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). However, less is known about the influence of biological rhythm disruptions across the perinatal period on postpartum depression (PPD). The objective of this study was to prospectively evaluate the relationship between subjective changes in both sleep and biological rhythms and worsening of depressive symptoms from pregnancy to the postpartum period in women with and without mood disorders. Eighty-three participants (38 euthymic women with a history of a mood disorder and 45 healthy controls) were studied. Participants completed subjective assessments of sleep (Pittsburgh Sleep Quality Index), biological rhythm disturbances (Biological Rhythms Interview of Assessment in Neuropsychiatry), and depressive symptoms (Edinburgh Postnatal Depression Scale) prospectively at two time points: third trimester of pregnancy and at 6-12 weeks postpartum. Multivariate regression analyses showed that changes in biological rhythms across the perinatal period predicted worsening of depressive symptoms in both groups. Moreover, women with a history of a mood disorder showed higher levels of sleep and biological rhythm disruption during both pregnancy and the postpartum period. These findings suggest that disruptions in biological rhythms during the perinatal period increase the risk for postpartum mood worsening in healthy pregnant as well as in pregnant women with a history of mood disorders.

  11. Long-Term Treatment of Restless Legs Syndrome (RLS): An Approach to Management of Worsening Symptoms, Loss of Efficacy, and Augmentation. (United States)

    Mackie, Susan; Winkelman, John W


    Restless legs syndrome (RLS) is a common, frequently chronic, sensorimotor neurological disorder characterized by nocturnal leg dysesthesias and an irresistible urge to move the legs, usually resulting in sleep disturbance. Dopaminergic agonists, alpha-2-delta calcium-channel ligands, and opioids have all demonstrated efficacy to relieve symptoms of RLS and improve sleep. However, long-term treatment with dopamine agonists (the most commonly prescribed agents) is often characterized by worsening symptoms and loss of efficacy. A more worrisome complication of dopaminergic agents is augmentation, an iatrogenic worsening of RLS symptoms that can produce progressively more severe symptoms resulting in around-the-clock restlessness and near sleeplessness. Recent research has yielded consensus regarding a precise definition of augmentation and has contributed to improved knowledge regarding strategies for preventing this complication. When RLS symptoms worsen during the course of treatment, the clinician must consider the myriad of environmental, medical, pharmacologic, and psychiatric factors that can exacerbate RLS. In the absence of fully developed, evidence-based guidelines there remains uncertainty regarding the optimal management strategy if augmentation develops. However, we discuss several key principles based on the available published data and the authors' clinical experience. We also explore the recent increasing interest in alternative initial treatment strategies that avoid dopamine agonists and their associated complications altogether.

  12. Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Pediatric Patients with Idiopathic Sudden Hearing Loss. (United States)

    Bulğurcu, Suphi; Dikilitaş, Bünyamin; Arslan, İlker Burak; Çukurova, İbrahim


    We investigated the significance of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, which have recently been used in adults for the prognosis of idiopathic sudden hearing loss (ISHL), in the prognosis of idiopathic sudden hearing loss in a pediatric population. A total of 13 males and 8 females younger than19 years with idiopathic sudden hearing loss were retrospectively examined between January 2008 and August 2016.The control group consisted of 12 healthy males and 12 healthy females. Patients were divided into two groups: those who recovered after treatment and those who did not. A statistical significance for the neutrophil-to-lymphocyte ratio was detected between the patient group and control group and between patients who recovered and those who did not (p0.05). The neutrophil-to-lymphocyte ratio is an important marker for the prognosis of idiopathic sudden hearing loss in pediatric patients, similar to its use in adult patients.

  13. Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting. (United States)

    Salimi, Ahmad; Motallebi, Abbasali; Ayatollahi, Maryam; Seydi, Enayatollah; Mohseni, Ali Reza; Nazemi, Melika; Pourahmad, Jalal


    Natural products isolated from marine environment are well known for their pharmacodynamic potential in diversity of disease treatments such as cancer or inflammatory conditions. Sea cucumbers are one of the marine animals of the phylum Echinoderm. Many studies have shown that the sea cucumber contains antioxidants and anti-cancer compounds. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5 + B lymphocytes. CLL is the most common leukemia in adults, about 25-30% of all leukemias. In this study B lymphocytes and their mitochondria (cancerous and non-cancerous) were obtained from peripheral blood of human subjects and B lymphocyte cytotoxicity assay, and caspase 3 activation along with mitochondrial upstream events of apoptosis signaling including reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and mitochondrial swelling were determined following the addition of Holothuria parva extract to both cancerous and non-cancerous B lymphocytes and their mitochondria. Our in vitro finding showed that mitochondrial ROS formation, MMP collapse, and mitochondrial swelling and cytochrome c release were significantly (P < 0.05) increased after addition of different concentrations of H. parva only in cancerous BUT NOT normal non-cancerous mitochondria. Consistently, different concentrations of H. parva significantly (P < 0.05) increased cytotoxicity and caspase 3 activation only in cancerous BUT NOT normal non-cancerous B lymphocytes. These results showed that H. parva methanolic extract has a selective mitochondria mediated apoptotic effect on chronic lymphocytic leukemia B lymphocytes hence may be promising in the future anticancer drug development for treatment of CLL. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1158-1169, 2017. © 2016 Wiley Periodicals, Inc.

  14. Associations between lifestyles and neutrophil-lymphocyte and platelet-lymphocyte ratios in colorectal cancer. (United States)

    Hong, Chuyuan; Wei, Yisheng; Jiang, Jianxin; Zhao, Chuxiong; Liang, Guojian; Wang, Guoqiang; Yang, Hui


    To explore the etiology of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) abnormalities in colorectal cancer. In total, 230 patients with histopathologically confirmed colorectal cancer from August 2009 to August 2011 were recruited to our study. The associations between lifestyles (smoking, alcohol and pickled food consumption) and pretreatment NLR and PLR were estimated using the Kruskal-Wallis tests and linear regression model. The Kruskal-Wallis test showed a significant association between pickled food intake and pretreatment NLR but not PLR (P = 0.002, 0.057, respectively). Pairwise comparisons showed that, compared with those with a moderately frequent (2-3 times/week) and an infrequent (≤ once a week) intake of pickled food, high frequency (≥ four times/week) consumption of pickled food had a higher pretreatment NLR (P = 0.01, 0.007, respectively). Multivariate linear regression analysis showed pretreatment NLR increased significantly in high frequency (≥ four times/week) consumption of pickled food (P frequency intake of pickled food possibly contributes to higher NLR, which may reflect a systemic inflammatory response in colorectal cancer. © 2013 Wiley Publishing Asia Pty Ltd.

  15. New Predictive Parameters of Bell's Palsy: Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio. (United States)

    Atan, Doğan; İkincioğulları, Aykut; Köseoğlu, Sabri; Özcan, Kürşat Murat; Çetin, Mehmet Ali; Ensari, Serdar; Dere, Hüseyin


    Bell's palsy is the most frequent cause of unilateral facial paralysis. Inflammation is thought to play an important role in the pathogenesis of Bell's palsy. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are simple and inexpensive tests which are indicative of inflammation and can be calculated by all physicians. The aim of this study was to reveal correlations of Bell's palsy and degree of paralysis with NLR and PLR. Case-control study. The retrospective study was performed January 2010 and December 2013. Ninety-nine patients diagnosed as Bell's palsy were included in the Bell's palsy group and ninety-nine healthy individuals with the same demographic characteristics as the Bell's palsy group were included in the control group. As a result of analyses, NLR and PLR were calculated. The mean NLR was 4.37 in the Bell's palsy group and 1.89 in the control group with a statistically significant difference (pBell's palsy group and 113.75 in the control group with a statistically significant difference (p=0.008). No statistically significant relation was detected between the degree of facial paralysis and NLR and PLR. The NLR and the PLR were significantly higher in patients with Bell's palsy. This is the first study to reveal a relation between Bell's palsy and PLR. NLR and PLR can be used as auxiliary parameters in the diagnosis of Bell's palsy.

  16. Recent therapeutic advances in chronic lymphocytic leukemia (United States)

    Bose, Prithviraj; Gandhi, Varsha


    The last several years have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL). The course of this very heterogeneous disease, traditionally treated with chemotherapeutic agents usually in combination with rituximab, typically has been characterized by remissions and relapses, and survival times vary greatly, depending on intrinsic biological attributes of the leukemia. The developments of the last few years have been transformative, ushering in an era of novel, molecularly targeted therapies, made possible by extensive efforts to elucidate the biology of the disease that predated the new targeted drugs. Thus, successful therapeutic targeting of the B-cell receptor signaling pathway and of the Bcl-2 anti-apoptotic protein with small molecules has now made chemotherapy-free approaches possible, hopefully mitigating the risk of development of therapy-related myeloid neoplasms and making eventual cure of CLL with the use of optimal drug combinations a realistic goal. Most importantly, these therapies have demonstrated unprecedented efficacy in patients with deletion 17p/TP53 mutation, a subset that historically has been very difficult to treat. However, as we gain more experience with the newer agents, unique safety concerns and resistance mechanisms have emerged, as has the issue of cost, as these expensive drugs are currently administered indefinitely. Accordingly, novel laboratory-based strategies and clinical trial designs are being explored to address these issues. The availability of whole exome/genome sequencing has given us profound insights into the mutational landscape of CLL. In this article, we highlight some of the most impactful advances since this topic was last reviewed in this journal. PMID:29152232

  17. Chronic lymphocytic leukemia: an updated review. (United States)

    Faguet, G B


    To review recent advances in the pathogenesis, biology, diagnosis, and management of chronic lymphocytic leukemia (CLL). A literature search restricted to English-language articles, abstracts, book chapters, and reports published between 1975 and 1993 was conducted both electronically using MEDLINE and CANCERLIT and manually using the bibliographies of the electronically retrieved data base. Of approximately 1,000 publications identified for analysis, 233 were selected as representative of important advances in CLL. The last 10 years have witnessed renewed interest in the biology and treatment of CLL, a disease long viewed by clinicians as following an indolent course and perceived by investigators as uninspiring. This interest, based on advances in understanding the lineage and biology of CLL and on the advent of new and more efficacious chemotherapeutic agents, has led to improvements in patient survival and, for the first time, to complete remissions (CRs) in large subsets of patients. As we learn to use these agents better, especially in combination chemotherapy, alternative therapeutic modalities, are being vigorously pursued, including high-dose ablative chemotherapy with allogeneic or autologous bone marrow transplantation (BMT) rescue and the use of powerful tumor-cell target-specific immunoreagents. These therapeutic advances, coupled with the recent availability of molecular probes to ascertain objectively minimal remnant disease posttreatment, provide a basis for developing and assessing ever more efficacious and potentially curative treatment strategies for the management of this disease. For the first time since the original 1924 monograph by Minot and Isaacs, the cure of subsets of patients with CLL appears not to be an unreasonable goal.

  18. Factors associated with HIV virologic failure among patients on HAART for one year at three sentinel surveillance sites in China. (United States)

    Wang, Xia; Yang, Liting; Li, Huiqin; Zuo, La; Liang, Shujia; Liu, Wei; Dong, Yonghui; Yang, Shaomin; Shang, Hong; Li, Jingyun; Kang, Laiyi; Zhong, Ping; Zheng, Wei; Liao, Lingjie; Xing, Hui; Chen, Ray Y; Ruan, Yuhua; Shao, Yiming


    Emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of highly active antiretroviral therapy (HAART). To understand the incidence of HIVDR and estimate the proportion of potential HIVDR and its associated risk factors among the patients on HAART for one year. Antiretroviral-naïve patients ≥ 18 years old were invited to participate in this one-year prospective study from seven clinics in Yunnan, Guangxi, and Xinjiang provinces. A questionnaire and blood draw were collected at baseline and 12 month follow-up. The protocol used was modified slightly from the WHO Protocol for Surveys of HIV Drug Resistance Emerging During Treatment and Related Program Factors in Sentinel ART Sites in Resource-limited Settings. 435 subjects were included in the final analysis, with median baseline CD4 cell count 139 cells/mm3. Of the total 417 patients who fall under WHO guidelines for 'Classification of outcomes based on endpoints' (on ART at 12 months, switch, lost to follow-up, and stop), 90 (21.6%) did not have any drug resistant mutations (potential HIVDR) and 17 (4.1%) did (HIVDR, Table 2). The remaining 310 (75.3%) had a viral load 1000 copies/ml.Patients who self-reported missing doses in the previous month were 6.2 fold (95% CI 2.5-15.7) more likely to fail than those who did not. and those from Xinjiang were 12.1 fold (95% CI 5.2-28.1) more likely to fail compared to those from Yunnan and Guangxi. Why Xinjiang was associated with virologic failure was not clear but may be related to the demographics of the participants from Xinjiang, being significantly more IDUs, poorer, and less adherent than those from Yunnan and Guangxi. Although successful virologic outcomes were seen in the vast majority (75.3%) of those treated at one year, virologic failure continues to be a problem particularly among those less adherent and from Xinjiang. Additional data are needed to understand the generalizability of these results, particularly those

  19. Predictors of sustained virological response in Greek and Egyptian patients with hepatitis C genotype 4: does ethnicity matter? (United States)

    Papastergiou, Vasilios; Dimitroulopoulos, Dimitrios; Skorda, Lamprini; Lisgos, Philippos; Ketikoglou, Ioannis; Kostas, Nikolaos; Karatapanis, Stylianos


    Hepatitis C virus genotype 4 (HCV-4) is spreading beyond Africa and the Middle East but data regarding treatment with pegylated interferon alpha and ribavirin of European populations infected with HCV-4 remains limited. Interestingly, European (vs. Egyptian) origin has been associated with lower sustained virological response rates. Hence the aim of this study was to investigate the treatment outcomes of Greek (vs. Egyptian), treatment-naïve patients infected with HCV-4 (subtype a) and to identify factors influencing response rates. One hundred seventy-seven consecutive patients (mean age: 44.6 ± 10.2, males: 143/177; 80.8%, Egyptians: 76/177; 42.9%) treated over a 7-year period at the Hepatology clinics of three tertiary care hospitals in Greece were retrospectively evaluated. Overall, sustained virological response was achieved in 75/177 (42.4%) of the cohort without a significant difference between the two ethnic groups [Greek: 44/101 (43.6%); Egyptian 31/76 (40.8%), P = 0.7598]. In multivariate analysis, it was found that ethnicity was not associated with an impaired response but age ≥45 years [odds ratio (OR): 0.4225, 95% confidence interval (CI): 0.2135-0.8133; P = 0.0134], diabetes (OR: 0.2346, 95% CI: 0.0816-0.0674; P = 0.0071), advanced liver fibrosis (OR: 0.3964, 95% CI: 0.1933-0.8133; P = 0.0116), and treatment suspension (OR: 0.1738, 95% CI: 0.0482-0.6262; P = 0.0075) showed an independent negative association with response to antiviral treatment. In contrast to previous European data suggesting Egyptian ethnicity to be a positive predictor for a sustained virological response, there was no influence of Greek versus Egyptian ethnicity on treatment outcomes. Higher age, advanced liver fibrosis, and diabetes have been shown to reduce significantly response rates in patients infected with HCV-4. Copyright © 2012 Wiley Periodicals, Inc.

  20. Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

    Directory of Open Access Journals (Sweden)

    Suzuki F


    Full Text Available Fumitaka Suzuki,1,2 Hitomi Sezaki,1 Norio Akuta,1 Yoshiyuki Suzuki,1 Yusuke Kawamura,1 Tetsuya Hosaka,1 Masahiro Kobayashi,1 Satoshi Saitoh,1 Yasuji Arase,1 Kenji Ikeda,1 Mariko Kobayashi,3 Sachiyo Watahiki,3 Rie Mineta,3 Yukiko Suzuki,3 Hiromitsu Kumada1 1Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 2Okinaka Memorial Institute for Medical Research, Tokyo, Japan; 3Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan Abstract: Tenofovir disoproxil fumarate (TDF is widely used to treat hepatitis B virus (HBV patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV, against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg, whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out. Keywords: hepatitis B virus, resistant

  1. Locomotion in Lymphocytes is Altered by Differential PKC Isoform Expression (United States)

    Sundaresan, A.; Risin, D.; Pellis, N. R.


    Lymphocyte locomotion is critical for proper elicitation of the immune response. Locomotion of immune cells via the interstitium is essential for optimal immune function during wound healing, inflammation and infection. There are conditions which alter lymphocyte locomotion and one of them is spaceflight. Lymphocyte locomotion is severely inhibited in true spaceflight (true microgravity) and in rotating wall vessel culture (modeled microgravity). When lymphocytes are activated prior to culture in modeled microgravity, locomotion is not inhibited and the levels are comparable to those of static cultured lymphocytes. When a phorbol ester (PMA) is used in modeled microgravity, lymphocyte locomotion is restored by 87%. This occurs regardless if PMA is added after culture in the rotating wall vessel or during culture. Inhibition of DNA synthesis also does not alter restoration of lymphocyte locomotion by PMA. PMA is a direct activator of (protein kinase C) PKC . When a calcium ionophore, ionomycin is used it does not possess any restorative properties towards locomotion either alone or collectively with PMA. Since PMA brings about restoration without help from calcium ionophores (ionomycin), it is infer-red that calcium independent PKC isoforms are involved. Changes were perceived in the protein levels of PKC 6 where levels of the protein were downregulated at 24,72 and 96 hours in untreated rotated cultures (modeled microgravity) compared to untreated static (1g) cultures. At 48 hours there is an increase in the levels of PKC & in the same experimental set up. Studies on transcriptional and translational patterns of calcium independent isoforms of PKC such as 8 and E are presented in this study.

  2. Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression. (United States)

    Castillo-Mancilla, Jose R; Morrow, Mary; Boum, Yap; Byakwaga, Helen; Haberer, Jessica E; Martin, Jeffrey N; Bangsberg, David; Mawhinney, Samantha; Musinguzi, Nicholas; Huang, Yong; Tracy, Russell P; Burdo, Tricia H; Williams, Kenneth; Muzzora, Conrad; Hunt, Peter W; Siedner, Mark J


    Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, and the kynurenine/tryptophan ratio, in addition to CD8 T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naive adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit. Adherence was measured through medication event monitoring system and calculated as the ratio of observed/prescribed device openings per participant. We fit adjusted linear regression models to estimate the association between ART adherence and the log-transformed plasma concentrations of inflammatory biomarkers. We evaluated 282 participants (median age, 35 years; 70% women). The median (interquartile range) adherence was 93% (84-98). In the adjusted analyses, for every 10% increase in average ART adherence, we found a 15% [P < 0.0001; 95% confidence interval (CI), -21.0 to -7.9], 11% (P = 0.017; 95% CI, -18.3 to -2.0), and 3% (P = 0.028; 95% CI, -5.0 to -0.3) decrease in IL-6, D-dimer, and sCD14, respectively. Higher ART adherence was associated with lower levels of biomarkers of inflammation, immune activation, and coagulopathy among Ugandans living with HIV who achieved viral suppression shortly after ART initiation. This suggests that ART adherence could have biological consequences beyond viral suppression. Whether ART adherence optimization in virologically suppressed individuals could reduce residual inflammation remains unknown.

  3. Structured Treatment Interruptions and Low Doses of IL-2 in Patients with Primary HIV Infection. Inflammatory, Virological and Immunological Outcomes. (United States)

    Sued, Omar; Ambrosioni, Juan; Nicolás, David; Manzardo, Christian; Agüero, Fernando; Claramonte, Xavier; Plana, Montserrat; Tuset, Montserrat; Pumarola, Tomás; Gallart, Teresa; Gatell, José María; Miró, José María


    Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of interleukin-2 (IL-2) in treated PHI patients is unknown. Twelve PHI patients with viral load (VL) 500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL 500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19). STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials. NCT02300623.

  4. Immunological and virological benefits resulted from short-course treatment during primary HIV infection: a meta-analysis. (United States)

    Chen, Jingjing; Han, Xiaoxu; An, Minghui; Liu, Jing; Xu, Junjie; Geng, Wenqing; Ji, Yangtao; Shang, Hong


    To assess the potential immunological and virological effects that result from short-course antiretroviral treatment during primary HIV infection (PHI). And to investigate whether treatment initiation time, treatment duration and follow-up time after treatment interruption would affect these post-treatment immunovirological outcomes. We systematically searched PubMed, Cochrane Library (to September 2013) and retrieved conference abstracts for studies regarding effects of early treatment during PHI on CD4 count and viral load (VL). Using the method of calculating weighted mean differences with Stata11.0, we conducted meta-analyses on the effect of early treatment on CD4 count and VL. Then we performed subgroup analyses by follow-up time after treatment interruption, treatment initiation time and treatment duration. Baseline immunovirological characteristics were also analyzed to account for potential bias. Compared to the untreated arm, treatment during PHI not only increased CD4 count by 85.92 cells/μl but also lowered viral load by 0.30 log copies/ml within one year after treatment interruption. However, the benefits declined gradually, reaching no significance 12-24 months after treatment interruption. Baseline immunovirological characteristics and sensitivity analyses of randomized controlled trials indicated that the benefits mentioned above were underestimated. Extending treatment duration beyond 12 months did not increase efficacy. Short-course treatment during PHI was associated with immunological and virological benefits which last for at least one year after treatment interruption. The conclusions from our study would help the decision-making in the clinical management of PHI.

  5. Clinical trial methodology and clinical cohorts: the importance of complete follow-up in trials evaluating the virological efficacy of anti-HIV medicines

    DEFF Research Database (Denmark)

    Kirk, Ole; Lundgren, Jens Dilling


    with virological failure assessed with and without data after the premature discontinuation of randomized therapy could be elicited. Substantial differences were seen in the comparisons of two highly active antiretroviral therapy regimens according to the choice of analytical approach. In all three studies...

  6. HIV Stigma and Depressive Symptoms are Related to Adherence and Virological Response to Antiretroviral Treatment Among Immigrant and Indigenous HIV Infected Patients

    NARCIS (Netherlands)

    Sumari-de Boer, I. Marion; Sprangers, Mirjam A. G.; Prins, Jan M.; Nieuwkerk, Pythia T.


    We compared adherence to cART and viro-logical response between indigenous and immigrant HIV-infected patients in the Netherlands, and investigated if a possible difference was related to a difference in the psychosocial variables: HIV-stigma, quality-of-life, depression and beliefs about

  7. HIV stigma and depressive symptoms are related to adherence and virological response to antiretroviral treatment among immigrant and indigenous HIV infected patients. (United States)

    Sumari-de Boer, I Marion; Sprangers, Mirjam A G; Prins, Jan M; Nieuwkerk, Pythia T


    We compared adherence to cART and virological response between indigenous and immigrant HIV-infected patients in the Netherlands, and investigated if a possible difference was related to a difference in the psychosocial variables: HIV-stigma, quality-of-life, depression and beliefs about medications. Psychosocial variables were assessed using validated questionnaires administered during a face-to-face interview. Adherence was assessed trough pharmacy-refill monitoring. We assessed associations between psychosocial variables and non-adherence and having detectable plasma viral load using logistic regression analyses. Two-hundred-two patients participated of whom 112 (55%) were immigrants. Viral load was detectable in 6% of indigenous patients and in 15% of the immigrants (P stigma and prior virological failure were associated with non-adherence, and depressive symptoms, prior virological failure and non-adherence with detectable viral load. Our findings suggest that HIV-stigma and depressive symptoms may be targets for interventions aimed at improving adherence and virological response among indigenous and immigrant HIV-infected patients.

  8. [Seventy years of research in experimental mycology at the Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine]. (United States)

    Zhdanova, N M


    The history of development of mycology at the D.K. Zabolotny Institute of Microbiology and Virology of the NAS of Ukraine and main achievements of the Department of Physiology and Taxonomy of Micromycetes during 1933-2003 were described in this publication.

  9. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    NARCIS (Netherlands)

    Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C; Niesters, Bert


    OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between

  10. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

    NARCIS (Netherlands)

    Ledergerber, B; Lundgren, JD; Walker, AS; Sabin, C; Justice, A; Reiss, P; Mussini, C; Wit, F; Monforte, AD; Weber, R; Fusco, G; Staszewski, S; Law, M; Hogg, R; Lampe, F; Gill, MJ; Castelli, F; Phillips, AN; Castelli, F; Fusco, GP; Gill, MJ; Hogg, R; Lampe, F; Law, M; Ledergerber, B; Lundgren, JD; Monforte, AD; Mussini, C; Phillips, AN; Reiss, P; Staszewski, S; Walker, AS; Rooney, P; Taylor, S; Couldwell, D; Austin, D; Block, M; Clemons, J; Finlayson, R; Law, M; Petoumenos, K; Quan, D; Smith, D; O'Connor, C; Gorton, C; Allen, D; Mulhall, B; Mutimer, K; Smith, D; Keeffe, N; Cooper, D; Carr, A; Miller, J; Pell, C; Ellis, D; Baker, D; Kidd, J; McFarlane, R; Liang, MT; Brown, K; Huffam, S; Savage, J; Morgan, S; Knibbs, P; Sowden, D; Walker, A; Orth, D; Lister, G; Chuah, J; Fankhauser, W; Dickson, B; Bradford, D; Wilson, C; Ree, H; Magon, H; Moore, R; Russell, D; McGovern, G; McNair, R; Bal, J; Fairley, K; Roth, N; Eu, B; Strecker, S; Russell, D; Wood, H; Mijch, A; Hoy, J; Pierce, A; McCormack, C; Watson, K; Medland, N; Daye, J; Mallal, S; French, M; Skett, J; Maxwel, D; Cain, A; Montroni, M; Scalise, G; Costantini, A; Giacometti, A; Tirelli, U; Nasti, G; Pastore, G; Ladisa, N; Perulli, ML; Suter, F; Arici, C; Chiodo, F; Gritti, FM; Colangeli, [No Value; Fiorini, C; Guerra, L; Carosi, G; Cadeo, GP; Castelli, F; Minardi, C; Vangi, D; Rizzardini, G; Migliorino, G; Manconi, PE; Piano, P; Ferraro, T; Scerbo, A; Pizzigallo, E; Ricci, F; Santoro, D; Pusterla, L; Carnevale, G; Galloni, D; Vigano, P; Mena, M; Ghinelli, F; Sighinolfi, L; Leoncini, F; Mazzotta, F; Pozzi, M; Lo Caputo, S; Angarano, G; Grisorio, B; Ferrara, S; Grima, P; Tundo, P; Pagano, G; Piersantelli, N; Alessandrini, A; Piscopo, R; Toti, M; Chigiotti, S; Soscia, F; Taccooni, L; Orani, A; Perini, P; Scasso, A; Vincenti, A; Scalzini, A; Fibbia, G; Moroni, M; Lazzarin, A; Cargnel, A; Vigevani, GM; Caggese, L; Monforte, AD; Tordato, F; Novati, R; Galli, A; Merli, S; Pastecchia, C; Moioli, C; Esposito, R; Mussini, C; Abrescia, N; Chirianni, A; Izzo, C; Piazza, M; De Marco, M; Montesarchio, [No Value; Manzillo, E; Nappa, S; Colomba, A; Abbadessa, [No Value; Prestileo, T; Mancuso, S; Ferrari, C; Pzzaferri, P; Filice, G; Minoli, L; Bruno, R; Maserati, R; Pauluzzi, S; Baldelli, F; Petrelli, E; Cioppi, A; Alberici, F; Ruggieri, A; Menichetti, F; Martinelli, C; De Stefano, C; La Gala, A; Zauli, T; Ballardini, G; Magnani, G; Ursitti, MA; Arlotti, M; Ortolani, P; Ortona, L; Dianzani, F; Ippolito, G; Antinori, A; Antonucci, G; D'Elia, S; Narciso, P; Petrosillo, N; Vullo, [No Value; De Luca, A; Del Forno, L; Zaccarelli, M; De Longis, P; Ciardi, M; D'Offizi, G; Noto, P; Lichtner, M; Capobianchi, MR; Girardi, E; Pezzotti, P; Rezza, G; Mura, MS; Mannazzu, M; Caramello, P; Sinicco, A; Soranzo, ML; Gennero, L; Sciandra, M; Salassa, B; Grossi, PA; Basilico, C; Poggio, A; Bottari, G; Raise, E; Pasquinucci, S; De Lalla, F; Tositti, G; Resta, F; Chimienti, A; Lepri, AC; Bachmann, S; Battegay, M; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Tarr, P; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; de Wolf, F; van Sighem, AI; van Valkengoed, [No Value; Gras, L; Bronsveld, W; Prins, JM; Bos, JC; Schattenkerk, JKME; Godfried, MH; Lange, JMA; Lowe, SH; van der Meer, JTM; Nellen, FJB; Pogany, K; van der Poll, T; Reiss, P; Ruys, TA; Sankatsing, S; van der Valk, M; van Vonderen, MGA; Wit, FWMN; ten Veen, JH; van Dam, PS; Hillebrand-Haverkort, ME; Brinkman, K; Frissen, PHJ; Weigel, HM; Mulder, JW; van Gorp, ECM; Meenhorst, PL; Mairuhu, ATA; Veenstra, J; Danner, SA; Van Agtmael, MA; Claessen, FAP; Geerlings, SE; Perenboom, RM; Richter, C; van der Berg, J; van Leusen, R; Vriesendorp, R; Jeurissen, FJF; Kauffmann, RH; Koger, ELW; Bravenboer, B; Mudrikova, T; Sprenger, HG; Miesen, WMAJ; ten Kate, RW; van Houte, DPF; Leemhuis, MP; Pole, M; Schippers, EF; Schreij, G; van de Geest, S; Verbon, A; Koopmans, PP; Telgt, M; van der Ven, AJAM; van der Ende, Marchina E.; Gyssens, IC; de Marie, S; Nouwen, JL; Juttmann, [No Value; Schneider, MME; Bonten, MJM; Borleffs, JCC; Hoepelman, IM; Jaspers, CAJJ; Schouten, [No Value; Schurink, CAM; Blok, WL; Groenveld, PHP; Jurriaans, S; Back, NKT; Cuijpers, T; Rietra, PJGM; Roozendaal, KJ; Pauw, W; van Zanten, AP; Smits, PHM; von Blomberg, BME; Savelkoul, P; Zaaijer, H; Swanink, C; Franck, PFH; Lampe, AS; Jansen, CL; Hendriks, R; Schirm, J; Benne, D; Veenendaal, D; Storm, H; van Zeijl, JH; Claas, HCJ; Bruggeman, CAMVA; Goossens, VJ; Galama, JMD; Poort, YAGM; Niesters, MG; Osterhaus, ADME; Buiting, AGM; Swaans, CAM; Boucher, CAB; Schuurman, R; Boel, E; Jansz, AF; Veldkamp, A; Beijnen, JH; Crommentuyn, KML; Huitema, ADR; Kappelhoff, B; de Maat, MMR; Burger, DM; Hugen, PWH; Dabis, F; Thiebaut, R; Chene, G; Lawson-Ayayi, S; Meyer, L; Boufassa, F; Hamouda, O; Pezzotti, P; Rezza, G; Touloumi, G; Hatzakis, A; Karafoulidou, A; Katsarou, O; Brettle, R; Del Amo, J; del Romero, J; van Asten, L; van Benthem, B; Prins, M; Coutinho, R; Kirk, O; Pedersen, C; Aguado, IH; Perez-Hoyos, S; Eskild, A; Bruun, JN; Sannes, M; Sabin, C; Lee, C; Johnson, AM; Phillips, AN; Babiker, A; Darbyshire, J; Gill, N; Porter, K; Francioli, P; Vanhems, P; Egger, M; Rickenbach, M; Cooper, D; Kaldor, J; Ashton, L; Cooper, D; Kaldor, J; Ashton, L; Cooper, D; Vizzard, J; Muga, R; Vanhems, P; Gill, J; Cayla, J; de Olalla, PG; Day, NE; De Angelis, D; Porter, K; Babiker, A; Walker, S; Darbyshire, J; Tyrer, F; Beral, [No Value; Coutinho, R; Darbyshire, J; Del Amo, J; Gill, N; Lee, C; Meyer, L; Rezza, G; Raffanti, S; Becker, S; Scarsella, A; Braun, J; Justice, A; Fusco, G; Most, B; Balu, R; Gilbert, L; Fleenor, R; Ising, T; Dieterich, D; Fusco, J; Losso, M; Duran, A; Vetter, N; Clumeck, N; De Wit, S; Kabeya, K; Poll, B; Colebunders, R; Machala, L; Rozsypal, H; Nielsen, J; Lundgren, J; Kirk, O; Olsen, CH; Gerstoft, J; Katzenstein, T; Hansen, ABE; Skinhoj, P; Pedersen, C; Zilmer, K; Rauka, M; Katlama, C; De Sa, M; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Stellbrink, HJ; Miller, [No Value; Staszewski, S; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, [No Value; Burke, M; Pollack, S; Hassoun, J; Sthoeger, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, [No Value; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Castagna, A; Monforte, AD; Viksna, L; Rozentale, B; Chaplinskas, S; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, [No Value; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Wiercinska-Drapalo, A; Boron-Kaczmarska, A; Pynka, M; Beniowski, M; Trocha, H; Smiatacz, T; Antunes, F; Mansinho, K; Maltez, F; Duiculescu, D; Streinu-Cercel, A; Mokras, M; Stanekova, D; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, [No Value; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Zamora, L; Blaxhult, A; Karlsson, A; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Hirschel, B; Schiffer, [No Value; Furrer, H; Chentsova, N; Barton, S; Johnson, AM; Mercey, D; Phillips, A; Youle, M; Johnson, MA; Mocroft, A; Murphy, M; Weber, J; Scullard, G; Fisher, M; Brettle, R; Loveday, C; Clotet, B; Ruiz, L; Staszewski, S; Helm, EB; Carlebach, A; Mosch, M; Muller, A; Haberl, A; Korn, S; Stephan, C; Bickel, M; Gute, P; Locher, L; Lutz, T; Klauke, S; Doerr, HW; Sturmer, M; Sabin, C; Dauer, B; Jennings, B; Alexander, C; Braitstein, P; Chan, K; Cote, H; Gataric, N; Harrigan, PR; Harris, M; Bonner, S; Hogg, R; Montaner, J; O'Shaughnessy, M; Wood, E; Yip, B; Lampe, F; Chaloner, C; Gumley, H; Ransom, D; Sabin, CA; Mocroft, A; Lipman, M; Phillips, AN; Youle, M; Johnson, M; Gill, J; Read, R; Carosi, G; Castelli, F; Paraninfo, G; Casari, S; Pan, A; Patroni, A; Torti, C; Quiros-Roldan, E; Tomasoni, L; Moretti, F; Nasta, P; Uccelli, MC; Cadeo, GP; Bertelli, D; Orani, A; Perini, P; Nigro, M; Rizzardini, G; Migliorino, M; Abeli, C; Mazzotta, F; Suter, F; Maggiolo, F; Arici, C; Ghinelli, F; Sighinolfi, L; Minoli, L; Maserati, R; Novati, S; Tinelli, C; Pastore, G; Ladisa, N; Carnevale, G; Poggio, A; Riccio, G; Mussini, C; Borghi, [No Value; Bedini, A; Esposito, R; ten Napel, C.H.


    Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological

  11. Clinical trial methodology and clinical cohorts: the importance of complete follow-up in trials evaluating the virological efficacy of anti-HIV medicines

    DEFF Research Database (Denmark)

    Kirk, Ole; Lundgren, Jens Dilling


    PURPOSE OF REVIEW: It has been common practice in randomized trials of HIV medicines to classify switches away from the original therapy as failures in analyses of virological effect, in line with an HIV-RNA measurement above a given level of quantification. This approach precludes the ability...

  12. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

    DEFF Research Database (Denmark)

    Ledergerber, Bruno; Lundgren, Jens D; Walker, A Sarah


    Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure....

  13. Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

    DEFF Research Database (Denmark)

    Costagliola, Dominique; Ledergerber, Bruno; Torti, Carlo


    Low CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure....

  14. Outcomes following detection of low level plasma HIV RNA in HIV-infected patients previously virologically suppressed on antiretroviral therapy: a retrospective observational study. (United States)

    Warren, Annabelle M; Cheng, Allen C; Watson, Kerrie; Lewin, Sharon R; Hoy, Jennifer F


    Progressively sensitive assays for plasma HIV RNA have led to increased detection of plasma HIV RNA between 20 and 200 copies/ml, known as low level viremia (LLV) when recurrent or persistent, in HIV-infected patients on antiretroviral therapy (ART). The aim of this study was to determine outcomes following initial detection of LLV in an Australian cohort. A retrospective study using the HIV Service Database (Alfred Hospital) included all patients on ART who recorded plasma HIV RNA 20-200 copies/mL following prior virological suppression (viral load (VL) HIV RNA 200 copies/mL. Factors associated with LLV included co-morbid type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count. Clinician management of VL 20-200 copies/mL was generally conservative, with infrequent requests for genotypic analysis (3.3% cases) or change in ART (<1% cases). LLV following virological suppression is common, and occurred as an isolated viral blip in half the patients. Those patients with persistent or recurrent LLV had higher rates of type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count.

  15. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

    DEFF Research Database (Denmark)

    Judd, A; Lodwick, R; Noguera-Julian, A


    OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS:...

  16. A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

    NARCIS (Netherlands)

    Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy; Kisic, Mónica; Cozzi-Lepri, Alessandro; Pou, Christian; Bellido, Rocío; Betancor, Gilberto; Bogner, Johannes; Gargalianos, Panagiotis; Bánhegyi, Dénes; Clotet, Bonaventura; Lundgren, Jens; Menéndez-Arias, Luis; Martinez-Picado, Javier; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Clumeck, N.; de Wit, S.; Poll, B.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Rozsypal, H.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Oestergaard, L.; Zilmer, K.; Ristola, M.; Katlama, C.; Viard, J.-P.; Girard, P.-M.; Livrozet, J. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.; Schmidt, R.; van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Staszewski, S.; Fätkenheuer, G.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Panos, G.; Filandras, A.; Karabatsaki, E.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Pollack, S.; Hassoun, G.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Chirianni, A.; Montesarchio, E.; Gargiulo, M.; Antonucci, G.; Iacomi, F.; Narciso, P.; Vlassi, C.; Zaccarelli, M.; Lazzarin, A.; Finazzi, R.; Galli, M.; Ridolfo, A.; d'Arminio, A.; Rozentale, B.; Aldins, P.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Reiss, P.; Ormaasen, V.; Maeland, A.; Brunn, J.; Knysz, B.; Gasiorowski, J.; Horban, A.; Bakowska, E.; Prokopowicz, D.; Flisiak, R.; Boron-Kaczmarska, A.; Pynka, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Valadas, E.; Mansinho, K.; Maltez, F.; Duiculescu, D.; Rakhmanova, A.; Vinogradova, E.; Buzunova, S.; Jevtovic, D.; Mokrás, M.; Staneková, D.; Tomazic, J.; González-Lahoz, J.; Soriano, V.; Martin-Carbonero, L.; Labarga, P.; Moreno, S.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miró, J. M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Karlsson, A.; Persson, P. O.; Ledergerber, B.; Weber, R.; Francioli, P.; Cavassini, M.; Hirschel, B.; Boffi, E.; Furrer, H.; Battegay, M.; Elzi, L.; Kravchenko, E.; Chentsova, N.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A. M.; Mercey, D.; Phillips, A.; Johnson, M. A.; Murphy, M.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.; Gatell, J.; Gazzard, B.; Lundgren, J.; d'Arminio Monforte, A.; Kirk, O.; Mocroft, A.; Cozzi-Lepri, A.; Grint, D.; Ellefson, M.; Podlekareva, D.; Kjaer, J.; Peters, L.; Reekie, J.; Kowalska, J.; Tverland, J.; Fischer, A. H.


    The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who

  17. Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection

    DEFF Research Database (Denmark)

    Pedersen, Court; Alsiö, A; Lagging, M


    Summary. In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin is ...

  18. Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue based regimens in ART-naïve and experienced patients

    DEFF Research Database (Denmark)

    Silberstein, F; Cozzi-Lepri, A; Ruiz, L


    BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started ...

  19. Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen: An international collaboration

    NARCIS (Netherlands)

    S.Y. Rhee (Soo Yoon); V. Varghese (Vici); Holmes, S.P. (Susan P.); Van Zyl, G.U. (Gert U.); Steegen, K. (Kim); Boyd, M.A. (Mark A.); D.A. Cooper (David); Nsanzimana, S. (Sabin); Saravanan, S. (Shanmugam); C. Charpentier (Charlotte); T. de Oliveira (Tulio); Etiebet, M.A.A. (Mary-Ann A.); F. Garcia; D. Goedhals; Gomes, P. (Perpetua); H.F. Günthard; R.L. Hamers (Raph); Hoffmann, C.J. (Christopher J); G.M. Hunt (Gillian M.); Jiamsakul, A. (Awachana); P. Kaleebu (Pontiano); P.J. Kanki; R. Kantor (Rami); B. Kerschberger; V.C. Marconi; D'amour Ndahimana, J. (Jean); N. Ndembi (Nicaise); Ngo-Giang-Huong, N. (Nicole); C. Rokx (Casper); M.M. Santoro (Maria); J.M. Schapiro (Jonathan); D. Schmidt; Seu, L. (Lillian); K.C. Sigaloff (Kim); S. Sirivichayakul (Sunee); Skhosana, L. (Lindiwe); H. Sunpath; M. Tang; Yang, C. (Chunfu); Carmona, S. (Sergio); Gupta, R.K. (Ravindra K.); R.W. Shafer (Robert)


    textabstractTenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected

  20. Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

    NARCIS (Netherlands)

    Rhee, Soo-Yon; Varghese, Vici; Holmes, Susan P.; van Zyl, Gert U.; Steegen, Kim; Boyd, Mark A.; Cooper, David A.; Nsanzimana, Sabin; Saravanan, Shanmugam; Charpentier, Charlotte; de Oliveira, Tulio; Etiebet, Mary-Ann A.; Garcia, Federico; Goedhals, Dominique; Gomes, Perpetua; Günthard, Huldrych F.; Hamers, Raph L.; Hoffmann, Christopher J.; Hunt, Gillian; Jiamsakul, Awachana; Kaleebu, Pontiano; Kanki, Phyllis; Kantor, Rami; Kerschberger, Bernhard; Marconi, Vincent C.; D'amour Ndahimana, Jean; Ndembi, Nicaise; Ngo-Giang-Huong, Nicole; Rokx, Casper; Santoro, Maria M.; Schapiro, Jonathan M.; Schmidt, Daniel; Seu, Lillian; Sigaloff, Kim C. E.; Sirivichayakul, Sunee; Skhosana, Lindiwe; Sunpath, Henry; Tang, Michele; Yang, Chunfu; Carmona, Sergio; Gupta, Ravindra K.; Shafer, Robert W.


    Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in

  1. [Occurrence of associated tumours in chronic lymphocytic leukemia]. (United States)

    Szerafin, László; Jakó, János; Varju, Lóránt


    Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

  2. The relationship between lymphocytes activated by pokeweed mitogen and by lipopolysaccharides and their radiosensitivity

    International Nuclear Information System (INIS)

    Su Liaoyuan; Liu Fenju; Liu Keliang; Xu Changshao; Xu Yingdong; Geng Yongzhi


    Human whole blood was incubated in vitro. Lymphocytes were activated by poke-weed mitogen (PWM) and by Lipopolysaccharides (LPS). The relationship between the two kinds of lymphocytes was investigated using radioactive compound incorporation. The study showed that PWM-activated lymphocytes were able to promote the stimulating effect of LPS on B lymphocytes. The stimulating effect of PWM-activated lymphocytes was obviously decreased after they were irradiated with 10 Gy gamma rays. When PWM-activated lymphocytes and LPS-activated lymphocytes were incubated together after one of the cell populations had been exposed 10 Gy 60 Co gamma rays, the incorporation of [ 3 H] TdR was much decreased and the synergistic function disappeared, especially when the PWM-activated lymphocytes were irradiated. In cells from patients treated with 60 Co gamma rays for carcinoma of nasopharynx, the incorporation in LPS-activated lymphocytes approached normal levels while that in PWM-activated lymphocytes was reduced significantly and the stimulating effect of PWM-activated lymphocytes on LPS-activated lymphocytes was also markedly reduced. These demonstrate that PWM-activated lymphocytes have a similar function to T-helper cells and seem to be more radiosensitive than LPS-activated lymphocytes

  3. Molecular Mechanisms of Particle Ration Induced Apoptosis in Lymphocyte (United States)

    Shi, Yufang

    Space radiation, composed of high-energy charged nuclei (HZE particles) and protons, has been previously shown to severely impact immune homeostasis in mice. To determine the molecular mechanisms that mediate acute lymphocyte depletion following exposure to HZE particle radiation mice were exposed to particle radiation beams at Brookhaven National Laboratory. We found that mice given whole body 5 6Fe particle irradiation (1GeV /n) had dose-dependent losses in total lymphocyte numbers in the spleen and thymus (using 200, 100 and 50 cGy), with thymocytes being more sensitive than splenocytes. All phenotypic subsets were reduced in number. In general, T cells and B cells were equally sensitive, while CD8+ T cells were more senstive than CD4+ T cells. In the thymus, immature CD4+CD8+ double-positive thymocytes were exquisitely sensitive to radiation-induced losses, single-positive CD4 or CD8 cells were less sensitive, and the least mature double negative cells were resistant. Irradiation of mice deficient in genes encoding essential apoptosis-inducing proteins revealed that the mechanism of lymphocyte depletion is independent of Fas ligand and TRAIL (TNF-ralated apoptosis-inducing ligand), in contrast to γ-radiation-induced lymphocyte losses which require the Fas-FasL pathway. Using inhibitors in vitro, lymphocyte apoptosis induced by HZE particle radiation was found to be caspase dependent, and not involve nitric oxide or oxygen free radicals.

  4. T Lymphocytes Inhibit the Vascular Response to Injury (United States)

    Hansson, Goran K.; Holm, Jan; Holm, Susanna; Fotev, Zisi; Hedrich, Hans-Jurgen; Fingerle, Jurgen


    The proliferation of vascular smooth muscle cells is controlled by specific growth factors and cytokines acting in paracrine networks. Macrophage products such as the platelet-derived growth factor and interleukin 1 promote smooth muscle proliferation and are released in the arterial wall during atherosclerosis and repair processes. T lymphocytes are also present in vascular tissue, but their role in vascular growth control in vivo has been unclear. We now demonstrate that rats in which T lymphocytes have been eliminated by a monoclonal antibody develop larger proliferative arterial lesions after balloon-catheter injury. Larger lesions also develop in athymic rnu/rnu rats that lack T lymphocytes, when compared with rnu/+ littermates with normal T-cell levels. Finally, injection of the lymphokine interferon γ inhibits smooth muscle proliferation and results in smaller lesions compared with controls injected with buffer alone. These results indicate that T lymphocytes modulate smooth muscle proliferation during vascular repair. We propose that T lymphocytes may play an important, immunologically nonspecific role in tissue repair processes.

  5. Rituximab for the treatment of patients with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    M Gentile


    Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

  6. Lymphocyte subsets and response to PHA among atomic bomb survivors

    International Nuclear Information System (INIS)

    Nakao, Susumu; Noguchi, Kyouichi; Eida, Kazuyuki; Tashiro, Kazunori; Hayashida, Ken


    In an effort to elucidate the effect of radiation exposure on immune competence in man, the number of lymphocytes, lymphocyte subsets, and the percentage of phytohemagglutinin (PHA)-induced transformation of lymphocytes were determined in 66 cancer patients, 25 of whom were exposed to atomic radiation at ≤ 2,000 m from ground zero and 41 others were not exposed. The number of lymphocytes was decreased with increasing age at exposure. The percentage of OKT3-positive cells tended to be lower in exposed patients who were in their twenties at the time of exposure than the non-exposed patients. Among patients in their teens and twenties at the time of exposure, there was a tendency toward decreased percentage of OKT4-positive cells (T4) and increased percentage of OKT8-positive cells (T8). The T4/T8 ratio was reduced. Patients who were in their first decade of life at the time of exposure tended to have decreased OKIa 1-positive cells, and increased Leulla-positive cells. Patients exposed in their twenties and thirties had slightly decreased percentage of PHA-induced transformation of lymphocytes. (Namekawa, K.)

  7. Lymphocyte Proliferation Response in Patients with Acute and Chronic Brucellosis

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    Khadijeh Khosravi


    Full Text Available Abstract Background: Brucella is an intracellular bacterium that causes chronic infection in humans and domestic animals. The underlying mechanisms that cause prolonged illness are complex and not fully understood. Immune responses may have an important role in the chronicity of infection. Here, we evaluated the lymphocyte proliferation responses in patients with chronic and acute brucellosis. Materials and Methods: This descriptive - analytical study was performed on 22 patients with acute brucellosis, 21 patients with chronic brucellosis and 21 healthy people with the similar age, sex and genetic background as control group. Peripheral lymphocytes were isolated using Ficoll and the cellular proliferation was quantified in presence of antigen and phytohemaglutinin-A by MTT method. Results: The brucella antigen-specific stimulation index in patients with chronic brucellosis was significantly lower than the acute brucellosis patients (p=0.001. Also, stimulating the lymphocytes with phytohemaglutinin-A has shown that proliferative response in patients with chronic brucellosis was lower than the other groups (p=0.04. Conclusion: The results indicated that chronic brucellosis inhibits lymphocyte proliferation. This inhibition of lymphocyte proliferation may be due to the induction of anergy.

  8. The significance of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in vestibular neuritis. (United States)

    Chung, Jae Ho; Lim, Jonghyun; Jeong, Jin Hyeok; Kim, Kyung Rae; Park, Chul Won; Lee, Seung Hwan


    To investigate the significance of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in vestibular neuritis. Retrospective, case-control study. The study subjects were patients who received treatment for vestibular neuritis between January 2009 and December 2013, and a control group composed of 70 age- and sex-matched healthy subjects who received laboratory testing as part of a routine health checkup. The subjects underwent a complete blood cell count and counts of the various cell subtypes to compare NLR and PLR in the vestibular neuritis patients and controls. The associations between laboratory test results and values of the vestibular function test and clinical information were examined. In addition, a subgroup analysis according to the duration of spontaneous nystagmus was performed. The mean NLR and PLR values of the patient group were significantly higher than those of the control group. Although caloric test outcomes and hospitalization period were not significantly correlated with blood profiles, the duration of dizziness needing antivertiginous drugs was positively correlated with NLR and PLR (P = .021, P = .020, respectively). In addition, NLR was negatively correlated with the length of time between symptom start and blood sampling (P = .005). The NLR and PLR value of patients with nystagmus for more than 5 days were significantly higher than those of patients whose nystagmus ceased within 5 days. This is the first report to evaluate the significance of NLR and PLR in vestibular neuritis. NLR and PLR should be taken into consideration as simple and reliable parameters for predicting the cause and severity of the disease. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting

    Directory of Open Access Journals (Sweden)

    Lawn Stephen D


    Full Text Available Abstract Background Viral load monitoring is not available for the vast majority of patients receiving antiretroviral therapy in resource-limited settings. However, the practical utility of CD4 cell count measurements as an alternative monitoring strategy has not been rigorously assessed. Methods In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART, VL measurements and risk of virological failure (VL > 1,000 copies/ml following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (ΔCD4 count and the difference between consecutive values (CD4 count slope using all 3-monthly CD4 count measurements during follow-up. Results During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n = 179, VL correlated significantly with absolute CD4 counts (r = - 0.08, P = 0.003, ΔCD4 counts (r = - 0.11, P P P = 0.99, P = 0.92 and P = 0.75, respectively. Moreover, in a receiver operating characteristic (ROC curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve = 0.59; sensitivity = 53.0%; specificity = 63.6%; positive predictive value = 10.9%. Conclusion CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure.

  10. Trends and Disparities in Antiretroviral Therapy Initiation and Virologic Suppression Among Newly Treatment-Eligible HIV-Infected Individuals in North America, 2001–2009 (United States)

    Hanna, David B.; Buchacz, Kate; Gebo, Kelly A.; Hessol, Nancy A.; Horberg, Michael A.; Jacobson, Lisa P.; Kirk, Gregory D.; Kitahata, Mari M.; Korthuis, P. Todd; Moore, Richard D.; Napravnik, Sonia; Patel, Pragna; Silverberg, Michael J.; Sterling, Timothy R.; Willig, James H.; Lau, Bryan; Althoff, Keri N.; Crane, Heidi M.; Collier, Ann C.; Samji, Hasina; Thorne, Jennifer E.; Gill, M. John; Klein, Marina B.; Martin, Jeffrey N.; Rodriguez, Benigno; Rourke, Sean B.; Gange, Stephen J.; Benson, A.; Bosch, Ronald J.; Collier, Ann C.; Boswell, Stephen; Grasso, Chris; Mayer, Ken; Hogg, Robert S.; Harrigan, Richard; Montaner, Julio; Cescon, Angela; Brooks, John T.; Buchacz, Kate; Gebo, Kelly A.; Moore, Richard D.; Rodriguez, Benigno; Horberg, Michael A.; Silverberg, Michael J.; Thorne, Jennifer E.; Goedert, James J.; Jacobson, Lisa P.; Klein, Marina B.; Rourke, Sean B.; Burchell, Ann; Rachlis, Anita R.; Hunter-Mellado, Robert F.; Mayor, Angel M.; Gill, M. John; Deeks, Steven G.; Martin, Jeffrey N.; Saag, Michael S.; Mugavero, Michael J.; Willig, James; Eron, Joseph J.; Napravnik, Sonia; Kitahata, Mari M.; Crane, Heidi M.; Justice, Amy C.; Dubrow, Robert; Fiellin, David; Sterling, Timothy R.; Haas, David; Bebawy, Sally; Turner, Megan; Gange, Stephen J.; Anastos, Kathryn; Moore, Richard D.; Saag, Michael S.; Gange, Stephen J.; Kitahata, Mari M.; McKaig, Rosemary G.; Justice, Amy C.; Freeman, Aimee M.; Moore, Richard D.; Freeman, Aimee M.; Lent, Carol; Platt, Aaron; Kitahata, Mari M.; Van Rompaey, Stephen E.; Crane, Heidi M.; Webster, Eric; Morton, Liz; Simon, Brenda; Gange, Stephen J.; Abraham, Alison G.; Lau, Bryan; Althoff, Keri N.; Zhang, Jinbing; Jing, Jerry; Golub, Elizabeth; Modur, Shari; Hanna, David B.; Rebeiro, Peter; Wong, Cherise; Mendes, Adell


    Background. Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes. Methods. We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count <350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non–injection drug abuse, alcohol abuse, and mental illness. Results. Among 10 692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend < .001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend < .001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P < .001). Conclusions. In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide. PMID:23315317

  11. Paradoxical Expansion of Th1 and Th17 Lymphocytes in Rheumatoid Arthritis Following Infliximab Treatment: a Possible Explanation for a Lack of Clinical Response. (United States)

    Talotta, Rossella; Berzi, Angela; Atzeni, Fabiola; Batticciotto, Alberto; Clerici, Mario; Sarzi-Puttini, Piercarlo; Trabattoni, Daria


    The immunogenicity of anti-TNF-α drugs may affect their safety and efficacy. Infliximab (IFX), a chimeric monoclonal antibody, induces antibody formation in up to 60% of cases. Some studies have suggested the involvement of a Th1 response to TNFα blockers following immunization, but the triggering of Th17 responses has never been reported. The aim of this study is to investigate whether the immunogenicity of IFX affects the Th1, Th17 and Treg compartments in rheumatoid arthritis (RA) patients failing IFX therapy, and verify whether this may be responsible for treatment failure. The study involved 55 patients with RA (15 treatment-naïve patients; 20 IFX responders; 20 IFX non-responders) and 10 healthy controls. PBMCs were cultured in the presence/absence of IFX, and the variations in the percentage of Th1, Th17 and Treg lymphocytes following IFX treatment were analysed. IFX-specific Th1 and Th17 responses and an increase in IL-21 production were observed in patients failing IFX (p Th1 and Th17 responses and IL-21 production (p Th17 or Th1 lymphocytes following sensitisation, thus worsening the patients' inflammatory status.

  12. Echo and natriuretic peptide guided therapy improves outcome and reduces worsening renal function in systolic heart failure: An observational study of 1137 outpatients. (United States)

    Simioniuc, Anca; Carluccio, Erberto; Ghio, Stefano; Rossi, Andrea; Biagioli, Paolo; Reboldi, Gianpaolo; Galeotti, Gian Giacomo; Lu, Fei; Zara, Cornelia; Whalley, Gillian; Temporelli, Pier Luigi; Dini, Frank Lloyd


    B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide management of patients with chronic heart failure (HF).Thus, the aim of this retrospective, multicenter study was to compare outcomes and renal function in outpatients with chronic HF with reduced ejection fraction (HFrEF) who underwent an echo and BNP guided or a clinically driven protocol for follow-up. In 1137 consecutive outpatients, management was guided according to echo-Doppler signs of elevated left ventricular filling pressure and BNP levels conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group in 570 (mean EF=30%), while management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department in 567 (mean EF=33%). Propensity score, matching several confounding baseline variables, was used to match pairs based on treatment strategy. The median follow-up was 37.4months. After propensity matching, a lower incidence of death (HR 0.45, 95%CI: 0.30-0.67, p<0.0001), and death or worsening renal function (HR 0.49, 95%CI 0.36-0.67, p<0.0001) was apparent in echo-BNP-guided group compared to clinically-guided group. Worsening of renal function (≥0.3mg/dl increase in serum creatinine) was observed in 9.8% of echo-BNP-guided group and in 21.4% of clinical assessed group (p<0.0001). The daily dose of loop diuretics did not change in echo-BNP-guided group, while it increased in 65% of patients in clinically-guided group (p<0.0001). Echo and BNP guided management may improve the outcome and reduce worsening of renal function in outpatients with chronic HFrEF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Whole blood microculture assay of human lymphocyte function. (United States)

    Pauly, J L; Han, T


    A whole blood microculture assay is described for measuring lymphocyte reactivity to mitogenic and antigenic stimulants. This assay employs heparinized whole blood, serum-free culture medium, microtiter plates, and a Multiple Automated Sample Harvester (MASH). When this assay is compared to other leukocyte assays, its major advantages include (1) the utilization of fewer lymphocytes per microculture, thuus reducing the amount of blood required per test while increasing the number of test agents and replicate cultures which can be employed in any given experiment; (2) the conservation of mitogens, antigens, drugs, enzymes, hormones, lymphokines, and other test agents, some of which are either expensive of difficult to prepare in large quantities; (3) the elimination of lymphocyte isolation and purification procedures which may disrupt the relative proportion of T cells, B cells and antigen-processing cells; and (4) the application of an automated harvester which simplifies and expedites procedures required for processing cells for liquid scintillation counting.

  14. Tumor-infiltrating lymphocytes. Cytologic, phenotypic and morphometric analysis. (United States)

    Oliver, G; Yannelli, J; Solomon, D


    To characterize the cytologic, phenotypic and morphometric features of tumor-infiltrating lymphocytes (TILs). Morphology and cell size parameters of 50 TILs and five normal donor peripheral blood lymphocyte (PBL) specimens were compared using light microscopy, manual ocular measurements and digital image processing. Cytologically, all TILs demonstrated similar morphologic findings regardless of the initial tumor type. Changes included large; eccentric nuclei, sometimes hyperlobated; clumped chromatin; and prominent nucleoli. The cytoplasm was abundant and basophilic. Mitotic figures were usually evident. In addition, TIL showed significant increases in cell size parameters as compared to PBLs. The activated morphology of TILs resembles the appearance of high grade lymphoma. Several cell size parameters are increased; that may help to explain differences in previously reported trafficking patterns between TILs and peripheral blood lymphocytes.

  15. Effects of pulsed electric fields on DNA of human lymphocytes. (United States)

    Delimaris, J; Tsilimigaki, S; Messini-Nicolaki, N; Ziros, E; Piperakis, S M


    The effects of pulsed electric fields of low frequency (50 Hz) on DNA of human lymphocytes were investigated. The influence of additional external factors, such as hydrogen peroxide (H2O2) and gamma-irradiation, as well as the repair efficiency in these lymphocytes, was also evaluated. The comet assay, a very sensitive and rapid method for detecting DNA damage at the single cells level was the method used. A significant amount of damage was observed after exposure to the electric fields, compared to the controls. After 2 h incubation at 37 degrees C, a proportion of damage was repaired. H2O2 and gamma-irradiation increased the damage to lymphocytes exposed to pulsed electric fields according to the dose used, while the amount of the repair was proportional to the damage.

  16. D-ribose inhibits DNA repair synthesis in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Zunica, G.; Marini, M.; Brunelli, M.A.; Chiricolo, M.; Franceschi, C.


    D-ribose is cytotoxic for quiescent human lymphocytes and severely inhibits their PHA-induced proliferation at concentrations (25-50 mM) at which other simple sugars are ineffective. In order to explain these effects, DNA repair synthesis was evaluated in PHA-stimulated human lymphocytes treated with hydroxyurea and irradiated. D-ribose, in contrast to other reducing sugars, did not induce repair synthesis and therefore did not apparently damage DNA in a direct way, although it markedly inhibited gamma ray-induced repair. Taking into account that lymphocytes must rejoin physiologically-formed DNA strand breaks in order to enter the cell cycle, we suggest that D-ribose exerts its cytotoxic activity by interfering with metabolic pathways critical for the repair of DNA breaks.

  17. Genetically enhanced T lymphocytes and the intensive care unit (United States)

    Tat, Tiberiu; Li, Huming; Constantinescu, Catalin-Sorin; Onaciu, Anca; Chira, Sergiu; Osan, Ciprian; Pasca, Sergiu; Petrushev, Bobe; Moisoiu, Vlad; Micu, Wilhelm-Thomas; Berce, Cristian; Tranca, Sebastian; Dima, Delia; Berindan-Neagoe, Ioana; Shen, Jianliang; Tomuleasa, Ciprian; Qian, Liren


    Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors. DLI represents a form of adoptive therapy used after hematopoietic stem cell transplant for its anti-tumor and anti-infectious properties. This article covers the current status of CAR-T cells and DLI research in the intensive care unit (ICU) patient, including the efficacy, toxicity, side effects and treatment. PMID:29662667

  18. The germinal center: a crucible for lymphocyte selection. (United States)

    Kelsoe, G


    Antigen first activates T and B lymphocytes in the T-cell areas of secondary lymphoid tissues where cognate- and costimulus-dependent proliferation expands the population of reactive lymphocytes. Selected T- and B-cell progeny from this population migrate into B-cell zones to form germinal centers (GC), where intense proliferation, apoptosis, and V(D)J hypermutation takes place. It is now known that each of these processes occur in both compartments of GC lymphocytes and that the GC T-cell represents an unusual Thy-1- subset of alpha beta T-helper cells that may represent a terminally differentiated cell that is lost with the end of the GC reaction.

  19. The effect of deoxyguanosine on human lymphocyte function. II. Analysis of the interference with B lymphocyte differentiation in vitro. (United States)

    Spaapen, L J; Rijkers, G T; Staal, G E; Rijksen, G; Duran, M; Stoop, J W; Zegers, B J


    The differentiation of normal human peripheral blood B lymphocytes into plasma cells in vitro, studied in mononuclear cells stimulated with PWM or in purified B cells stimulated with a T cell-replacing factor (TRF), can be inhibited by both deoxyguanosine (dGuo) and guanosine. The mechanism underlying this effect, which differs from the in vivo findings in PNP deficiency, was analyzed. dGuo toxicity can be antagonized by hypoxanthine but not by deoxycytidine. PNP-deficient and HGPRT-deficient B lymphocytes are not sensitive to the intoxicating properties of (deoxy)guanosine. Inhibition of PNP activity in normal B lymphocytes by 8-aminoguanosine decreases the sensitivity for dGuo intoxication. Incubation of purified B cells (stimulated with TRF) with dGuo leads to increased intracellular levels of guanosine di- and triphosphate (GDP and GTP), whereas deoxyguanosine triphosphate (dGTP) levels remain low. These observations lead to the conclusion that inhibition of B lymphocyte differentiation by dGuo is brought about by one of the end products of the pathway starting with degradation of dGuo by PNP, followed by guanine salvage by HGPRT, and possibly further phosphorylation of GMP into GDP and GTP. According to this mechanism, B lymphocyte differentiation in PNP deficiency is not sensitive to (deoxy)guanosine; because of the absence of PNP activity, these cells cannot accumulate GMP, GDP, and GTP, and therefore escape dGuo intoxication.


    Directory of Open Access Journals (Sweden)

    S. V. Khaidukov


    Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

  1. High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Weyer, Christian; Lindsay, Robert S


    Chronic low-grade inflammation may be involved in the pathogenesis of insulin resistance and type 2 diabetes. We examined whether a high white blood cell count (WBC), a marker of inflammation, predicts a worsening of insulin action, insulin secretory function, and the development of type 2 diabetes...... action and the development of type 2 diabetes in Pima Indians. These findings are consistent with the hypothesis that a chronic activation of the immune system may play a role in the pathogenesis of type 2 diabetes....

  2. Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers. (United States)

    Silva, Angela M Monteiro da; Speranza, Francisco A B; Ishii, Solange Kiyoko; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Milagres, Lucimar Gonçalves


    To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers.

  3. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.


    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  4. Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers (United States)

    Monteiro da Silva, Angela M; Speranza, Francisco A B; Ishii, Solange Kiyoko; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Milagres, Lucimar Gonçalves


    OBJECTIVE: To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. METHODS: Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. RESULTS: The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (ppeacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. CONCLUSION: The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers. PMID:25789525

  5. Lymphocyte glutathione levels in children with cystic fibrosis. (United States)

    Lands, L C; Grey, V; Smountas, A A; Kramer, V G; McKenna, D


    Lung disease in cystic fibrosis (CF) is characterized by a neutrophilic inflammatory response. This can lead to the production of oxidants, and to oxidative stress in the lungs. Glutathione (GSH) represents the primary intracellular antioxidant, and provides an important defense in the epithelial lining fluid. Evidence suggests that lymphocyte GSH reflects lung GSH concentrations, and so could potentially serve as a peripheral marker of lung inflammation. We assessed peripheral blood lymphocyte GSH concentrations in 20 children (13 boys) with CF who were in stable condition at the time of evaluation. Values were compared with nutritional status and lung function parameters. Patients were 11.7+/-3.03 years old (mean +/- SD). Their percentage of ideal body weight was 101.8+/-17.92%; FEV1, 79.5+/-19.22% predicted; FEV1/FVC, 75.0+/-10.08%; and residual volume (RV)/total lung capacity (TLC), 31.3+/-10.47%. For the group, the GSH concentration was 1.31+/-0.52 micromol/10(6) lymphocytes, which was not different from laboratory control values. GSH values were correlated with nutritional status (percentage of ideal body weight: r = 0.49, p 0.1). We interpret the inverse correlation between lymphocyte GSH concentration and lung function as a reflection of upregulation of GSH production by lung epithelial tissue in response to oxidative stress. We interpret the correlation between lymphocyte GSH concentration and nutritional status as a reflection of the role of cysteine in hepatic glutamine metabolism. Peripheral blood lymphocyte GSH concentration may potentially serve as a convenient marker of lung inflammation. Furthermore, the increased demand for GSH production in the face of ongoing inflammation suggests a potential role for supplementation with cysteine donors.

  6. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Wang D


    Full Text Available Dan Wang, Jia-Xin Yang, Dong-Yan Cao, Xi-Run Wan, Feng-Zhi Feng, Hui-Fang Huang, Keng Shen, Yang Xiang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and cervical stromal involvement in patients with endometrioid adenocarcinoma. Methods: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. Results: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively. Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively. At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. Conclusion: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement. Keywords: neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, endometrioid adenocarcinoma

  7. The chromosomal radiosensitivity of lymphocytes from the chimpanzee (Pan troglodytes)

    International Nuclear Information System (INIS)

    Leonard, A.; Decat, G.; Leonard, E.D.; Mortelmans, J.


    The yield of chromosomal aberrations induced by exposure to X-irradiation in vitro was studied in the lymphocytes of the chimpanzee (Pan troglodytes), a hominoid ape phylogenically and chromosomally closely related to man. In agreement with the similarity of the chromosome characteristics, no significant difference was observed between man and chimpanzee with respect to the incidence of dicentrics and fragments. It is obvious that the nuclear area, which apparently constitutes the most evident difference between the nuclei of man and chimpanzee lymphocytes, did not play an important role in the yields of aberrations

  8. Polycyclic’ Aromatic Hydrocarbon Induced Intracellular Signaling and Lymphocyte Apoptosis

    DEFF Research Database (Denmark)

    Schneider, Alexander M.

    lymphocytes. Our experiments on preB lymphocytes supported by stromal cells suggest that apoptosis is one of the mechanisms for PAH immunosuppression. It could be either due to direct effect of the PAH on the B cells, via stromal cell signaling. Ubiquitous PAH-like toxin, fluoranthene, was tested for it......’s ability to initiate apoptosis in T cell hybridomas. Our data demonstrate that PAH may induce apoptosis and innnunotoxicity in T cell branch of immune system. The mechanism of this process seems to be the AhR independent, and mediated by Ca...

  9. Acute lymphocytic leukaemia in children in the Netherlands

    International Nuclear Information System (INIS)

    Does-van den Berg, A. van der.


    Some features, present at diagnosis in children with acute lymphocytic leukaemia, investigated during the period 1973-1975, and the results of treatment according to protocol AL II of the Dutch Childhood Leukaemia Study Group (SNWLK), are described. This report concerns the results of induction treatment, elective treatment of the central nervous system, and also of the prospective comparative study on the influence of the addition of cyclophosphamide to maintenance treatment with 6-mercaptopurine and methotrextate. In the context of the investigation of long-term side effects of disease and treatment, the immunocompetence of children with acute lymphocytic leukaemia in continuous remission after cessation of therapy was studied. (Auth.)

  10. The dogma of bacteriology and other events as spearheads of virology Dogma de la bacteriología y otros eventos como puntas de lanza de la virología

    Directory of Open Access Journals (Sweden)

    Charles Volcy


    Full Text Available

    This review analyzes some of the main events during the twentieth century that led to the birth of virology. In the literature of the time, a relationship of causality was established between virus and disease, and within this pathological context, the notions of fixed virus, volatile virus, contagium vivum fluidum and contagium fixum were formed. The transformation of the virus concept as a technoscientific object took place based on the criterion of filterability and on the methodology devised for the bacteriology dogma. Studies on tobacco mosaic virus are highlighted, as well as those on viral diseases of human beings and animals, which led to the discovery of these submicroscopic agents through the appropriation of technologies and the impulse triggered by political and economic factors.

    Esta investigación analiza algunos de los eventos principales del siglo XIX que condujeron hacia la cristalización de la virología. En los documentos de esta investigación analiza algunos de los eventos principales del siglo XIX que condujeron hacia la cristalización de la virología. En los documentos de aquella época, se plasmó una relación de causalidad entre virus y enfermedad o contagio, y en este contexto patológico, se elaboraron las nociones de virus fijo, virus volátil, contagium vivum fluidum y contagium fixum. De otro lado, la transformación conceptual hacia el virus como objeto tecnocientífico tuvo lugar con base en el criterio de filtrabilidad y en la metodología trazada por la bacteriología convertida en dogma. Asimismo, se

  11. Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

    Directory of Open Access Journals (Sweden)

    Zhaodong Li


    Full Text Available Death receptor 3 (DR3, a member of the tumor necrosis factor receptor (TNFR superfamily, has been implicated in regulating T-helper type-1 (TH1, type-2 (TH2, and type-17 (TH17 responses as well as regulatory T cell (Treg and innate lymphoid cell (ILC functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn’s disease (CD. In this study, we tested a specific DR3 agonistic antibody (4C12 in SAMP1/YitFc (SAMP mice with CD-like ileitis. Interestingly, treatment with 4C12 prior to disease manifestation markedly worsened the severity of ileitis in SAMP mice despite an increase in FoxP3+ lymphocytes in mesenteric lymph node (MLN and small-intestinal lamina propria (LP cells. Disease exacerbation was dominated by overproduction of both TH1 and TH2 cytokines and associated with expansion of dysfunctional CD25−FoxP3+ and ILC group 1 (ILC1 cells. These effects were accompanied by a reduction in CD25+FoxP3+ and ILC group 3 (ILC3 cells. By comparison, genetic deletion of DR3 effectively reversed the inflammatory phenotype in SAMP mice by promoting the expansion of CD25+FoxP3+ over CD25−FoxP3+ cells and the production of IL-10 protein. Collectively, our data demonstrate that DR3 signaling modulates a multicellular network, encompassing Tregs, T effectors, and ILCs, governing disease development and progression in SAMP mice with CD-like ileitis. Manipulating DR3 signaling toward the restoration of the balance between protective and inflammatory lymphocytes may represent a novel and targeted therapeutic modality for patients with CD.

  12. Long-term real-world entecavir therapy in treatment-naïve hepatitis B patients: base-line hepatitis B virus DNA and hepatitis B surface antigen levels predict virologic response. (United States)

    Cho, Ju-Yeon; Sohn, Won; Sinn, Dong-Hyun; Gwak, Geum-Youn; Paik, Yong-Han; Choi, Moon Seok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul; Lee, Joon Hyeok


    Entecavir is a potent nucleoside analogue with high efficacy and barrier for resistance. We aimed to investigate the long-term efficacy and viral resistance rate of entecavir and explore the factors associated with virologic response, including quantitative hepatitis B surface antigen (qHBsAg) levels. One thousand and nine treatment-naïve chronic hepatitis B (CHB) patients were evaluated for cumulative rates of virologic response, biochemical response, and entecavir mutations. The role of baseline qHBsAg for virologic response was assessed in 271 patients with qHBsAg prior to entecavir treatment. The median duration of entecavir treatment was 26.5 months. The cumulative rate of virologic response at years 1, 3, and 5 were 79.0%, 95.6%, and 99.4%, respectively. The cumulative rate of entecavir resistance was 1.0% and 2.1% in years 3 and 5. Multivariate analysis identified baseline hepatitis B e antigen (HBeAg) negative status ( p response. Lower qHBsAg was an independent predictor of virologic response in patients with baseline qHBsAg. There were no serious adverse events during treatment. Long-term entecavir treatment of nucleos(t)ide-naïve CHB patients was associated with an excellent virologic response and a low rate of entecavir-resistant mutations at 5 years. Baseline HBV DNA load, qHBsAg levels, and HBeAg status were predictors of virologic response during entecavir treatment.

  13. Measures of hip morphology are related to development of worsening radiographic hip osteoarthritis over 6 to 13 year follow-up: the Johnston County Osteoarthritis Project. (United States)

    Nelson, A E; Stiller, J L; Shi, X A; Leyland, K M; Renner, J B; Schwartz, T A; Arden, N K; Jordan, J M


    We sought to describe the effect of alterations in hip morphology with respect to worsening hip OA in a community-based sample including African American (AA) and white men and women. This nested case-control study defined case hips as Kellgren Lawrence grade (KLG) Oxford, UK). Descriptive means and standard errors were obtained from generalized estimating equation (GEE) models. Sex-stratified GEE regression models (accounting for within-person correlation), adjusted for age, race, BMI, and side were then employed. A total of 120 individuals (239 hips; 71 case/168 control) were included (25% male, 26% AA, mean age 62 years, BMI 30 kg/m(2)). Case hips tended to have greater baseline AP alpha angles, smaller minimum joint space width (mJSW) and more frequent triangular index signs. Adjusted results among men revealed that higher AP alpha angle, Gosvig ratio, and acetabular index were positively associated with case hips; coxa profunda was negatively associated. Among women, greater AP alpha angle, smaller mJSW, protrusio acetabuli, and triangular index sign were associated with case hips. We confirmed an increased risk of worsening hip OA due to baseline features of cam deformity among men and women, as well as protrusio acetabuli among women, and provide the first estimates of these measures in AAs. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Plasma neutrophil gelatinase-associated lipocalin as a marker for the prediction of worsening renal function in children hospitalized for acute heart failure. (United States)

    Elsharawy, Sahar; Raslan, Lila; Morsy, Saed; Hassan, Basheir; Khalifa, Naglaa


    Acute heart failure (AHF) is frequently associated with worsening renal function in adult patients. Neutrophil gelatinase-associated lipocalin (NGAL) serves as an early marker for acute renal tubular injury. To assess the role of plasma NGAL in predicting worsening renal function (WRF) in children with AHF, we studied 30 children hospitalized for AHF; children with history of chronic renal disease or on nephrotoxic drugs were excluded. Twenty age- and sex-matched healthy children were included in the study as a control group. Echocardiographic examination was performed on admission. Blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR) and plasma NGAL levels were measured on admission and 72 h later. Seventeen (56.6%) patients developed WRF within the three-day follow-up period. At presentation, plasma NGAL level was significantly elevated in children who developed WRF. Admission plasma NGAL level correlated with renal parameters (BUN, creatinine and eGFR) as well as with left ventricular systolic parameters (ejection fraction and fractional shortening). For prediction of WRF, admission plasma, NGAL level>27.5 μg/L had sensitivity and specificity of 90% and 68%, respectively. The area under the receiver-operator curve was higher for NGAL (0.869) than for BUN (0.569) or eGFR (0.684). We conclude that admission plasma NGAL level can predict WRF in children hospitalized for AHF.

  15. Rac1 mediates collapse of microvilli on chemokine-activated T lymphocytes

    NARCIS (Netherlands)

    Nijhara, Ruchika; van Hennik, Paula B.; Gignac, Michelle L.; Kruhlak, Michael J.; Hordijk, Peter L.; Delon, Jerome; Shaw, Stephen


    Lymphocytes circulate in the blood and upon chemokine activation rapidly bind, where needed, to microvasculature to mediate immune surveillance. Resorption of microvilli is an early morphological alteration induced by chemokines that facilitates lymphocyte emigration. However, the antecedent

  16. B lymphocytes not required for progression from insulitis to diabetes in non-obese diabetic mice. (United States)

    Charlton, B; Zhang, M D; Slattery, R M


    Previous studies have implicated B lymphocytes in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse. While it is clear that B lymphocytes are necessary, it has not been clear at which stage of disease they play a role; early, late or both. To clarify when B lymphocytes are needed, T lymphocytes were transferred from 5-week-old NOD female mice to age-matched NOD/severe combined immunodeficiency (SCID) recipient mice. NOD/SCID mice, which lack functionally mature T and B lymphocytes, do not normally develop insulitis or insulin-dependent diabetes melitus (IDDM). The NOD/SCID mice that received purified T lymphocytes from 5-week-old NOD mice subsequently developed insulitis and diabetes even though they did not have detectable B lymphocytes. This suggests that while B lymphocytes may be essential for an initial priming event they are not requisite for disease progression in the NOD mouse.

  17. Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk

    NARCIS (Netherlands)

    van Attekum, Martijn H. A.; Eldering, Eric; Kater, Arnon P.


    The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander

  18. Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia (United States)

    A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

  19. Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

    Directory of Open Access Journals (Sweden)

    Borba HHL


    Full Text Available Helena HL Borba,1 Astrid Wiens,1 Laiza M Steimbach,1 Fernanda S Tonin,1 Maria LA Pedroso,2 Cláudia AP Ivantes,3 Fernando Fernandez-Llimos,4 Roberto Pontarolo1 1Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy, 2Gastroenterology Service, Hospital de Clínicas, Federal University of Paraná, 3Guidance and Counseling Center, Curitiba City Hall, Curitiba, Paraná, Brazil; 4Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines, University of Lisboa, Lisbon, Portugal Background: Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil.Materials and methods: A prospective longitudinal and multicenter study was conducted in five centers in the State of Paraná between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR. Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load on RVR achievement.Results: Data were collected from 117 patients with chronic hepatitis C virus (HCV genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6 years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (≥800,000 IU/mL and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group. Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir and the baseline viral load

  20. Coinfection with human herpesvirus 8 is associated with persistent inflammation and immune activation in virologically suppressed HIV-infected patients.

    Directory of Open Access Journals (Sweden)

    Mar Masiá

    Full Text Available Infection with co-pathogens is one of the postulated factors contributing to persistent inflammation and non-AIDS events in virologically-suppressed HIV-infected patients. We aimed to investigate the relationship of human herpesvirus-8 (HHV-8, a vasculotropic virus implicated in the pathogenesis of Kaposi's sarcoma, with inflammation and subclinical atherosclerosis in HIV-infected patients.Prospective study including virologically suppressed HIV-infected patients. Several blood biomarkers (highly-sensitive C-reactive protein [hsCRP], tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, malondialdehyde, plasminogen activator inhibitor [PAI-1], D-dimer, sCD14, sCD163, CD4/CD38/HLA-DR, and CD8/CD38/HLA-DR, serological tests for HHV-8 and the majority of herpesviruses, carotid intima-media thickness, and endothelial function through flow-mediated dilatation of the brachial artery were measured.A total of 136 patients were included, 34.6% of them infected with HHV-8. HHV-8-infected patients were more frequently co-infected with herpes simplex virus type 2 (HSV-2 (P<0.001, and less frequently with hepatitis C virus (HCV (P = 0.045, and tended to be older (P = 0.086. HHV-8-infected patients had higher levels of hsCRP (median [interquartile range], 3.63 [1.32-7.54] vs. 2.08 [0.89-4.11] mg/L, P = 0.009, CD4/CD38/HLA-DR (7.67% [4.10-11.86]% vs. 3.86% [2.51-7.42]%, P = 0.035 and CD8/CD38/HLA-DR (8.02% [4.98-14.09]% vs. 5.02% [3.66-6.96]%, P = 0.018. After adjustment for the traditional cardiovascular risk factors, HCV and HSV-2 infection, the associations remained significant: adjusted difference between HHV-8 positive and negative patients (95% confidence interval for hsCRP, 74.19% (16.65-160.13%; for CD4/CD38/HLA-DR, 89.65% (14.34-214.87%; and for CD8/CD38/HLA-DR, 58.41% (12.30-123.22%. Flow-mediated dilatation and total carotid intima