308 research outputs found
Long-term safety of glycopyrrolate: A randomized study in patients with moderate-to-severe COPD (GEM3)
AbstractBackgroundChronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the United States. Long-acting muscarinic antagonists (LAMAs) are a class of medications used as maintenance therapy for COPD. The GEM3 (Glycopyrrolate Effect on syMptoms and lung function) study assessed the long-term safety and efficacy of a LAMA, glycopyrrolate (GLY) 15.6 μg twice daily (b.i.d.), compared with an approved long-acting β2-agonist (LABA), indacaterol (IND) 75 μg once daily (q.d.) in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation.MethodsThis 52-week, multicenter, double-blind, parallel-group study randomized patients (1:1) of the United States to receive GLY 15.6 μg b.i.d. or IND 75 μg q.d. both delivered via the Neohaler® device. The primary objective was to assess the safety and tolerability in terms of adverse event (AE) reporting rates over 52 weeks. Safety was also determined by evaluating multiple secondary endpoints, including vital signs, electrocardiograms (ECGs), and time to first moderate or severe exacerbation. Efficacy-related secondary endpoints included pre-dose forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).ResultsOf the 511 randomized patients (GLY, n = 254; IND, n = 257), 81.6% completed the study. The overall incidences of AEs (GLY, 77.3%; IND, 77.0%) and serious AEs (GLY, 13.1%; IND, 13.3%) were comparable between the groups. The incidence of major adverse cardiovascular events was low and comparable between the groups. No clinically relevant differences for vital signs or ECG parameters were observed between the treatment groups. The three sudden deaths reported within 30 days of the treatment (GLY, n = 2; IND, n = 1) were adjudicated as unrelated to the study medication. In terms of efficacy, GLY 15.6 μg b.i.d. showed improvements in pre-dose FEV1 and FVC from baseline, which was comparable to those with IND 75 μg q.d., with no statistically significant differences. No significant differences were observed between the treatment groups in the time to first moderate or severe COPD exacerbation.ConclusionGLY 15.6 μg b.i.d. showed a long-term safety profile comparable to that of IND 75 μg q.d. and provided rapid and sustained bronchodilation over 52 weeks in patients with COPD with moderate-to-severe airflow limitation.Clinical trial registration numberNCT01697696
Seasonal variation in agglutination of Plasmodium falciparum-infected erythrocytes
Abstract. Agglutination and rosette formation are in vitro characteristics of Plasmodium falciparum–infected erythrocytes, which have been associated with host protective immune responses and also with parasite virulence. The present study was carried out in an area of seasonal and unstable malaria transmission in eastern Sudan. Plasma samples were obtained before, during, and after the transmission season from a volunteer cohort of 64 individuals seven years of age and older. These plasmas were assayed for their ability to agglutinate cultured parasitized eryth-rocytes originally obtained from acute malaria infection samples taken from five of the cohort members. Our data show that the capacity of donor plasma samples to agglutinate parasitized cells depended largely on the time of sampling relative to the transmission season, at least within this epidemiologic setting. Thus, although less than half of the pretransmission season samples could agglutinate any of the five lines of cultured parasites, all post-transmission season samples could agglutinate at least one of the parasite lines, with 74 % agglutinating two or more lines. This increase in the agglutination capacity of individual plasma samples after the transmission season occurred essentially regardless of whether an individual had experienced a clinical malaria attack during the transmission season. The study thus confirms the acquisition of agglutinating antibodies following episodes of clinical malaria, but also dem-onstrates that such acquisition can take place in the absence of disease, presumably as a consequence of subclinica
Corrigendum: The Application of the Extended Poincaré Plot in the Analysis of Physiological Variabilities
Detection of Bk Polyomavirus Antigen in Patients with Acute Lymphoblastic Leukemia
Background: BK polyomavirus that is acquired in early childhood as BKPyV is near ubiquitous in adults with a seroprevalence of >80%, it has been found as the main cause of hemorrhagic cystitis in hematopoietic stem cell transplantation patients, due to immunosuppression regimen that lead to the activation of the virus from the latency status and lead to increased viral shedding in urine (viuria).
Objective: To investigate the frequency of BK Polyomavirus antigen excretion in urine of children with acute lymphoblastic leukemia with and without chemotherapy and compare it with normal controls.
Patients and Methods: A case-control study conducted from December 2021 to May 2022 in Baghdad, Iraq on leukemia patients of Central Pediatrics Hospital (Al-Eskan ). Urine samples and urine sediment smears were collected from 60 acute lymphoblastic leukemia patients. And compared with 60 apparently healthy age and sex-matched children, BK polyomavirus antigen in urine was detected using Enzyme-linked Immunosorbent Assay and urine cytology were Pap stained for the detection of decoy cells (DCs).
Results: Positive BKPyV antigen in urine was seen in 55 (91.7%) of Acute lymphoblastic leukemia patients and 39 (65.0%) in controls (p=<0.001) and all the patients were decoy negative. There was no significant effect of the positivity of antigenuria on neither leukocytes level nor on the occurance of relapse in leukemia patients.
Conclusion: The very high frequency of BKPyV in the urine signifies the importance of reactivation of this virus in ALL patients with and without chemotherapy
Intracranial Vertebrobasilar Artery Dissection Associated with Postpartum Angiopathy
Background. Cervicocephalic arterial dissection (CCAD) is rare in the postpartum period. To our knowledge this is the first reported case of postpartum angiopathy (PPA) presenting with ischemic stroke due to intracranial arterial dissection. Case. A 41-year-old woman presented with blurred vision, headache, and generalized seizures 5 days after delivering twins. She was treated with magnesium for eclampsia. MRI identified multiple posterior circulation infarcts. Angiography identified a complex dissection extending from both intradural vertebral arteries, through the basilar artery, and into both posterior cerebral arteries. Multiple segments of arterial dilatation and narrowing consistent with PPA were present. Xenon enhanced CT (Xe-CT) showed reduced regional cerebral blood flow that is improved with elevation in blood pressure. Conclusion. Intracranial vertebrobasilar dissection causing stroke is a rare complication of pregnancy. Eclampsia and PPA may play a role in its pathogenesis. Blood pressure management may be tailored using quantitative blood flow studies, such as Xe-CT
Intracellular cytokine staining and flow cytometry: Considerations for application in clinical trials of novel tuberculosis vaccines
Intracellular cytokine staining combined with flow cytometry is one of a number of assays designed to assess T-cell immune responses. It has the specific advantage of enabling the simultaneous assessment of multiple phenotypic, differentiation and functional parameters pertaining to responding T-cells, most notably, the expression of multiple effector cytokines. These attributes make the technique particularly suitable for the assessment of T-cell immune responses induced by novel tuberculosis vaccines in clinical trials. However, depending upon the particular nature of a given vaccine and trial setting, there are approaches that may be taken at different stages of the assay that are more suitable than other alternatives. In this paper, the Tuberculosis Vaccine Initiative (TBVI) TB Biomarker Working group reports on efforts to assess the conditions that will determine when particular assay approaches should be employed. We have found that choices relating to the use of fresh whole blood or peripheral blood mononuclear cells (PBMC) and frozen PBMC; use of serum-containing or serum-free medium; length of stimulation period and use of co-stimulatory antibodies can all affect the sensitivity of intracellular cytokine assays. In the case of sample material, frozen PBMC, despite some loss of sensitivity, may be more advantageous for batch analysis. We also recommend that for multi-site studies, common antibody panels, gating strategies and analysis approaches should be employed for better comparability
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Changes in IgE- and antigen-dependent histamine-release in peripheral blood of Schistosoma mansoni-infected Ugandan fishermen after treatment with praziquantel.
BACKGROUND: Parasite-specific IgE levels correlate with human resistance to reinfection with Schistosoma spp. after chemotherapy. Although the role of eosinophils in schistosomiasis has been the focus of a great deal of important research, the involvement of other Fcepsilon receptor-bearing cells, such as mast cells and basophils, has not been investigated in relation to human immunity to schistosomes. Chemotherapy with praziquantel (PZQ) kills schistosomes living in an in vivo blood environment rich in IgE, eosinophils and basophils. This releases parasite Ags that have the potential to cross-link cell-bound IgE. However, systemic hypersensitivity reactions are not induced by treatment. Here, we describe the effects of schistosomiasis, and its treatment, on human basophil function by following changes in total cellular histamine and in vitro histamine-release induced by schistosome Ags or anti-IgE, in blood samples from infected Ugandan fishermen, who are continuously exposed to S. mansoni infection, before and 1-day and 21-days after PZQ treatment. RESULTS: There was a significant increase in the total cellular histamine in blood samples at 1-day post-treatment, followed by a very significant further increase by 21-days post-treatment. In vitro histamine-release induced by S. mansoni egg (SEA) or worm (SWA) Ags or anti-IgE antibody, was significantly reduced 1-day post-treatment. The degree of this reduction correlated with pre-treatment infection intensity. Twenty-1-days post-treatment, SEA-induced histamine-release was still significantly lower than at pretreatment. Histamine-release was not correlated to plasma concentrations of total or parasite-specific IgE, nor to specific IgG4 plasma concentrations. CONCLUSION: The biology of human blood basophils is modulated by S. mansoni infection and praziquantel treatment. Infection intensity-dependent suppression of basophil histamine-release, histamine-dependent resistance to infection, and similarities with allergen desensitisation are discussed as possible explanations of these observations
Performance of the 2007 WHO Algorithm to diagnose Smear-negative Pulmonary Tuberculosis in a HIV prevalent setting
The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya
Stronger diversity effects with increased environmental stress : a study of multitrophic interactions between oak, powdery mildew and ladybirds
Recent research has suggested that increasing neighbourhood tree species diversity may mitigate the impact of pests or pathogens by supporting the activities of their natural enemies and/or reducing the density of available hosts. In this study, we attempted to assess these mechanisms in a multitrophic study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe spp.) and a mycophagous ladybird (Psyllobora vigintiduo-punctata). We assessed ladybird mycophagy on oak PM in function of different neighbourhood tree species compositions. We also evaluated whether these species interactions were modulated by environmental conditions as suggested by the Stress Gradient Hypothesis. We adopted a complementary approach of a field experiment where we monitored oak saplings subjected to a reduced rainfall gradient in a young planted forest consisting of different tree species mixtures, as well as a lab experiment where we independently evaluated the effect of different watering treatments on PM infections and ladybird mycophagy. In the field experiment, we found effects of neighbourhood tree species richness on ladybird mycophagy becoming more positive as the target trees received less water. This effect was only found as weather conditions grew drier. In the lab experiment, we found a preference of ladybirds to graze on infected leaves from trees that received less water. We discuss potential mechanisms that might explain this preference, such as emissions of volatile leaf chemicals. Our results are in line with the expectations of the Natural Enemies Hypothesis and support the hypothesis that biodiversity effects become stronger with increased environmental stress
The Application of the Extended Poincaré Plot in the Analysis of Physiological Variabilities
The Poincaré plot is a geometrical technique used to visualize and quantify the correlation between two consecutive data points in a time-series. Since the dynamics of fluctuations in physiological rhythms exhibit long-term correlation and memory, this study aimed to extend the Poincaré plot by calculating the correlation between sequential data points in a time-series, rather than between two consecutive points. By incorporating this so-called lag, we hope to integrate a temporal aspect into quantifying the correlation, to depict whether a physiological system holds prolonged association between events separated by time. In doing so, it attempts to instantaneously characterize the intrinsic behavior of a complex system. We tested this hypothesis on three different physiological time-series: heart rate variability in patients with liver cirrhosis, respiratory rhythm in asthma and body temperature fluctuation in patients with cirrhosis, to evaluate the potential application of the extended Poincaré method in clinical practice. When studying the cardiac inter-beat intervals, the extended Poincaré plot revealed a stronger autocorrelation for patients with decompensated liver cirrhosis compared to less severe cases using Pearson’s correlation coefficient. In addition, long-term variability (known as SD2 in the extended Poincaré plot) appeared as an independent prognostic variable. This holds significance by acting as a non-invasive tool to evaluate patients with chronic liver disease and potentially facilitate transplant selection as an adjuvant to traditional criteria. For asthmatics, employing the extended Poincaré plot allowed for a non-invasive tool to differentially diagnose various classifications of respiratory disease. In the respiratory inter-breath interval analysis, the receiver operating characteristic (ROC) curve provided evidence that the extension of the Poincaré plot holds a greater advantage in the classification of asthmatic patients, over the traditional Poincaré plot. Lastly, the analysis of body temperature from patients using the extended Poincaré plot helped identify inpatients from outpatients with cirrhosis. Through these analyses, the extended Poincaré plot provided unique and additional information which could potentially make a difference in clinical practice. Conclusively, the potential use of our work lies in its possible application of predicting mortality for the organ allocation procedure in patients with cirrhosis and non-invasively distinguish between atopic and non-atopic asthma
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