bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhaled steroid/long-acting β2 agonist combination products provide 24 hours improvement in lung function in adult asthmatic patients
Authors: Lötvall Jan , Langley Stephen , Woodcock Ashley 
Published: August 2006

Abstract
Background
The combination of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide™ GSK, UK) and formoterol/budesonide (FBC, Symbicort™, AstraZeneca, UK) are commercially available.

Objectives
The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose.

Methods
Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400–1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800–1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide™ followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment.

Results
In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2–24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively

Conclusion
Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.
Rhinosinusitis derived Staphylococcal enterotoxin B plays a possible role in pathogenesis of food allergy
Authors: Liu Tao , Wang Bin-Quan , Zheng Peng-Yuan , He Shao-Heng , Yang Ping-Chang 
Published: August 2006

Abstract

Background
Staphylococcal enterotoxin B (SEB) is a potent immunomodulator and implicated with pathogenesis of inflammatory diseases mediated by Th1 or Th2 dominant immune responses. The objective of this study is to determine a possible association between rhinosinusitis derived SEB and pathogenesis of food allergy (FA).

Methods
The study included chronic rhinosinusitis (CRS) patients with FA (N = 46) or without FA (N = 33). Controls included FA patients without CRS (N = 26) and healthy volunteers (N = 25). In CRS patients, we assessed the parameters associated with FA including prick skin test (PST) reactivity to food allergens, serum levels of allergen-specific IgE and cytokines (IL-4, IL-13, IFN-Î3), and the number/reactivity of food-allergen specific Th1/Th2 cells in the peripheral blood before and 2 months after sinus surgery. Changes of these parameters were evaluated in comparison with changes in SEB concentration in the sinus lavage and stool samples and also in vitro reactivity to SEB. In CRS patients with FA, we also assessed changes in reactivity to oral challenge of offending food before and after sinus surgery.

Results
Two months following sinus surgery, we observed statistically significant reduction in PST and oral challenge reactivity in CRS patients with FA in parallel to decrease in serum levels of Th2 cytokines (IL-4 and IL-13) and allergen specific IgE. Improvement of reactivity to food allergens was positively associated with decline in SEB concentrations in the sinus lavage and stool samples. In vitro study results also indicated a role of SEB in aggravation of Th2 skewed responses to food allergens. Such changes were not observed in CRS-non FA patients or control FA patients.

Conclusion
The rhinosinusitis derived SEB plays a certain role in the pathogenesis of FA by augmenting and/or maintaining polarized Th2 responses. Removal of SEB-producing pathogens from the rhinosinuses may be beneficial for attenuating the FA symptoms in patients with CRS-FA.
Transactivation and signaling functions of Tat are not correlated: biological and immunological characterization of HIV-1 subtype-C Tat protein
Authors: Siddappa Nagadenahalli Byrareddy , Venkatramanan Mohanram , Venkatesh Prasanna , Janki Mohanbabu Vijayamma , Jayasuryan Narayana , Desai Anita , Ravi Vasanthapuram , Ranga Udaykumar 
Published: August 2006

AbstractBackgroundOf the diverse subtypes of Human Immunodeficiency Virus Type-1 (HIV-1), subtype-C strains cause a large majority of infections worldwide. The reasons for the global dominance of HIV-1 subtype-C infections are not completely understood. Tat, being critical for viral infectivity and pathogenesis, may differentially modulate pathogenic properties of the viral subtypes. Biochemical studies on Tat are hampered by the limitations of the current purification protocols. Tat purified using standard protocols often is competent for transactivation activity but defective for a variety of other biological functions. Keeping this limitation in view, we developed an efficient protein purification strategy for Tat.ResultsTat proteins obtained using the novel strategy described here were free of contaminants and retained biological functions as evaluated in a range of assays including the induction of cytokines, upregulation of chemokine coreceptor, transactivation of the viral promoter and rescue of a Tat-defective virus. Given the highly unstable nature of Tat, we evaluated the effect of the storage conditions on the biological function of Tat following purification. Tat stored in a lyophilized form retained complete biological activity regardless of the storage temperature. To understand if variations in the primary structure of Tat could influence the secondary structure of the protein and consequently its biological functions, we determined the CD spectra of subtype-C and -B Tat proteins. We demonstrate that subtype-C Tat may have a relatively higher ordered structure and be less flexible than subtype-B Tat. We show that subtype-C Tat as a protein, but not as a DNA expression vector, was consistently inferior to subtype-B Tat in a variety of biological assays. Furthermore, using ELISA, we evaluated the anti-Tat antibody titers in a large number of primary clinical samples (n = 200) collected from all four southern Indian states. Our analysis of the Indian populations demonstrated that Tat is non-immunodominant and that a large variation exists in the antigen-specific antibody titers.ConclusionOur report not only describes a simple protein purification strategy for Tat but also demonstrates important structural and functional differences between subtype-B and -C Tat proteins. Furthermore, this is the first report of protein purification and characterization of subtype-C Tat.
Identification and classification of human cytomegalovirus capsids in textured electron micrographs using deformed template matching
Authors: Ryner Martin , Strömberg Jan-Olov , Söderberg-Nauclér Cecilia , Homman-Loudiyi Mohammed 
Published: August 2006

Abstract

Background
Characterization of the structural morphology of virus particles in electron micrographs is a complex task, but desirable in connection with investigation of the maturation process and detection of changes in viral particle morphology in response to the effect of a mutation or antiviral drugs being applied. Therefore, we have here developed a procedure for describing and classifying virus particle forms in electron micrographs, based on determination of the invariant characteristics of the projection of a given virus structure. The template for the virus particle is created on the basis of information obtained from a small training set of electron micrographs and is then employed to classify and quantify similar structures of interest in an unlimited number of electron micrographs by a process of correlation.

Results
Practical application of the method is demonstrated by the ability to locate three diverse classes of virus particles in transmission electron micrographs of fibroblasts infected with human cytomegalovirus. These results show that fast screening of the total number of viral structures at different stages of maturation in a large set of electron micrographs, a task that is otherwise both time-consuming and tedious for the expert, can be accomplished rapidly and reliably with our automated procedure. Using linear deformation analysis, this novel algorithm described here can handle capsid variations such as ellipticity and furthermore allows evaluation of properties such as the size and orientation of a virus particle.

Conclusion
Our methodological procedure represents a promising objective tool for comparative studies of the intracellular assembly processes of virus particles using electron microscopy in combination with our digitized image analysis tool. An automated method for sorting and classifying virus particles at different stages of maturation will enable us to quantify virus production in all stages of the virus maturation process, not only count the number of infectious particles released from un infected cell.
Local tumor control and toxicity in HIV-associated anal carcinoma treated with radiotherapy in the era of antiretroviral therapy
Authors: Oehler-Jänne Christoph , Seifert Burkhardt , Lütolf Urs M , Ciernik I Frank 
Published: August 2006

AbstractPurposeTo investigate the outcome of HIV-seropositive patients under highly active antiretroviral treatment (HAART) with anal cancer treated with radiotherapy (RT) alone or in combination with standard chemotherapy (CT).Patients and methodsClinical outcome of 81 HIV-seronegative patients (1988 – 2003) and 10 consecutive HIV-seropositive patients under HAART (1997 – 2003) that were treated with 3-D conformal RT of 59.4 Gy and standard 5-fluorouracil and mitomycin-C were retrospectively analysed. 10 TNM-stage and age matched HIV-seronegative patients (1992 – 2003) were compared with the 10 HIV-seropositive patients. Pattern of care, local disease control (LC), overall survival (OS), cancer-specific survival (CSS), and toxicity were assessed.ResultsRT with or without CT resulted in complete response in 100 % of HIV-seropositive patients. LC was impaired compared to matched HIV-seronegative patients after a median follow-up of 44 months (p= 0.03). OS at 5 years was 70 % in HIV-seropositive patients receiving HAART and 69 % in the matched controls. Colostomy-free survival was 70 % (HIV+) and 100 % (matched HIV-) and 78 % (all HIV-). No HIV-seropositive patient received an interstitial brachytherapy boost compared to 42 % of all HIV-seronegative patients and adherence to chemotherapy seemed to be difficult in HIV-seropositive patients. Acute hematological toxicity reaching 50 % was high in HIV-seropositive patients receiving MMC compared with 0 % in matched HIV-seronegative patients (p= 0.05) or 12 % in all HIV-seronegative patients. The rate of long-term side effects was low in HIV-seropositive patients.ConclusionDespite high response rates to organ preserving treatment with RT with or without CT, local tumor failure seems to be high in HIV-positive patients receiving HAART. HIV-seropositive patients are subject to treatment bias, being less likely treated with interstitial brachytherapy boost probably due to HIV-infection, and they are at risk to receive less chemotherapy.
Type I interferon production in HIV-infected patients
Authors: Hosmalin Anne , Lebon Pierre 
Published: August 2006

Abstract
Type I IFNs display multiple biological effects. They have a strong antiviral action, not only directly but also indirectly through activation of the immune system. They may also have actions that are deleterious for the host. The cells that produce type I IFN are mostly plasmacytoid dendritic cells (pDC), but this depends on the viral stimulus. The migration and distribution of pDC into lymphoid organs, driven by chemokine interactions with their ligands, determines interaction with different cell types. In HIV infection, IFN production in vitro is impaired during primary infection and later in association with opportunistic infections. Circulating pDC numbers are decreased in parallel. These parameters may be used to help assess the prognosis of the disease and to monitor treatment.
Randomized Trial of Single Compared With Tandem High-Dose Chemotherapy Followed by Autologous Stem-Cell Transplantation in Patients With Chemotherapy-Sensitive Metastatic Breast Cancer
Authors: Kröger Nicolaus , Frick Markus , Gluz Oleg , Mohrmann Svjetlana , Metzner Bernd , Jackisch Christian , Ko Yon , Lindemann Hans-Walter , Meier Carl Richard , Lohrmann Hans Peter , Ruffert Ute , Hänel Matthias , Bodenstein Heinrich , Neubauer Andreas , Ehninger Gerhard , Wolf Hans-Heinrich , Kolbe Kathrin , Burock Karin , Zander Axel R. , Nitz Ulrike 
Published: August 2006

Purpose To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients. Patients and Methods Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation. Results One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33% in the single-dose HDT arm and 37% in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95% CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95% CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95% CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival. Conclusion Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.
Influence of Hormone Replacement Therapy on Tamoxifen-Induced Vasomotor Symptoms
Authors: Sestak Ivana , Kealy Roseann , Edwards Robert , Forbes John , Cuzick Jack 
Published: August 2006

Purpose Tamoxifen is an effective drug, but its role in prevention is limited by its adverse effect profile. Non–life-threatening adverse effects, such as vasomotor symptoms, have an important influence in its use for prevention. Vasomotor symptoms were evaluated according to follow-up time, severity, and use of hormone replacement therapy (HRT) in a retrospective analysis. Patients and Methods In the International Breast Cancer Intervention Study-I study, 7,154 women at increased risk of breast cancer were randomly assigned to either tamoxifen 20 mg/d or placebo for 5 years. Women gave detailed information on any vasomotor symptoms at each 6-month follow-up visit. Results Hot flushes were reported more often in the tamoxifen group than in the placebo group (70.6% v 57.1%, respectively; odds ratio, 1.80; 95% CI, 1.63 to 1.99). Severe hot flushes were more strongly related to tamoxifen. In the tamoxifen arm, more women taking HRT at entry experienced hot flushes in the first 6 months than those who did not take HRT (60.8% v 49.2%, respectively; P = .09). In contrast, women on placebo taking HRT at entry experienced fewer hot flushes than women who stopped HRT (22.9% v 34.3%, respectively; P = .03). Furthermore, for women who first began HRT in the first 6 months of the trial compared with women who did not begin HRT, HRT seemed to be much more effective in controlling hot flushes in months 6 to 12 in the placebo arm (47.9% v 20.4%, respectively) than in the tamoxifen arm (51.4% v 39.0%, respectively). Conclusion HRT use at entry or during the trial was not effective in alleviating hot flushes for women in the tamoxifen arm. Our retrospective study suggests that estrogen-based HRT has limited effectiveness among women receiving tamoxifen.
Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer
Authors: Heinemann Volker , Quietzsch Detlef , Gieseler Frank , Gonnermann Michael , Schönekäs Herbert , Rost Andreas , Neuhaus Horst , Haag Caroline , Clemens Michael , Heinrich Bernard , Vehling-Kaiser Ursula , Fuchs Martin , Fleckenstein Doris , Gesierich Wolfgang , Uthgenannt Dirk , Einsele Hermann , Holstege Axel , Hinke Axel , Schalhorn Andreas , Wilkowski Ralf 
Published: August 2006

Purpose To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. Patients and Methods Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. Results One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. Conclusion These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.
Symptom Improvement in Lung Cancer Patients Treated With Erlotinib: Quality of Life Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21
Authors: Bezjak Andrea , Tu Dongsheng , Seymour Lesley , Clark Gary , Trajkovic Aleksandra , Zukin Mauro , Ayoub Joseph , Lago Sergio , de Albuquerque Ribeiro Ronaldo , Gerogianni Alexandra , Cyjon Arnold , Noble Jonathan , Laberge Francis , Chan Raymond Tsz-Tong , Fenton David , von Pawel Joachim , Reck Martin , Shepherd Frances A. 
Published: August 2006

Purpose This report describes the quality of life (QOL) findings of a randomized placebo controlled study of erlotinib, an epidermal growth factor receptor inhibitor, in patients with non–small-cell lung cancer (NSCLC). Patients and Methods This double-blind phase III trial randomly assigned 731 patients with NSCLC who had progressed after prior chemotherapy to erlotinib 150 mg daily or placebo, with survival as the primary study outcome. QOL was assessed by European Organisation for Research and Treatment of Cancer QLQ-C30 and the lung cancer module QLQ-LC13. The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea, and pain. Results Survival was significantly longer (hazard ratio, 0.70; P < .0001) in the erlotinib arm. Compliance with QOL was 87% at baseline and more than 70% during treatment. Patients receiving erlotinib had significantly longer median time to deterioration for all three symptoms (4.9 v 3.7 months for cough [P = .04]; 4.7 v 2.9 months for dyspnea [P = .04], and 2.8 v 1.9 months for pain [P = .03]). QOL response analyses showed that 44%, 34%, and 42% of patients receiving erlotinib had improvement in these three symptoms, respectively. This was accompanied by a significant improvement in the physical function (31% erlotinib v 19% placebo, P = .01), and global QOL (35% v 26%, P < .0001). Patients with complete or partial response were more likely to have improvement in the QOL response than patients with stable or progressive disease (P < .01). Conclusion Erlotinib not only improves survival in previously treated patients with NSCLC, but also improves tumor-related symptoms and important aspects of QOL.
Comparison of Long-Term Neurocognitive Outcomes in Young Children With Acute Lymphoblastic Leukemia Treated With Cranial Radiation or High-Dose or Very High-Dose Intravenous Methotrexate
Authors: Spiegler Brenda J. , Kennedy Kimberly , Maze Ronnen , Greenberg Mark L. , Weitzman Sheila , Hitzler Johann K. , Nathan Paul C. 
Published: August 2006

Purpose Cranial radiation therapy (CRT) is associated with neurocognitive morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). For most patients, CRT has been replaced with intensified systemic and intrathecal chemotherapy, often including methotrexate (MTX). The impact of chemotherapy-only protocols on neurocognitive outcomes is unclear, and the importance of systemic MTX dose has not been established. Patients and Methods Seventy nine of 120 eligible children diagnosed with high-risk ALL between the ages of 1.0 and 4.9 years participated in this retrospective cohort study. All patients were treated on a uniform chemotherapy protocol with one of three modalities of CNS prophylaxis, depending on their treatment era. In addition to intrathecal therapy, CNS-directed therapy consisted of CRT (18 Gy in 10 fractions) in 25 patients, high-dose intravenous (IV) MTX (8 g/m2 × 3 doses) in 32 patients and very high-dose IV MTX (33.6 g/m2 x 3 doses) in 22 patients. Participants completed tests of intelligence, academic achievement, attention, and memory. Results Neurocognitive assessment was conducted at least 5 years after diagnosis (mean, 10.5 years, standard deviation, 2.7 years). No difference was detected on any neurocognitive measure between children treated with high-dose or very high-dose IV MTX. The combined MTX groups scored near the population mean on 17/18 measures. Children treated with CRT performed more poorly than the MTX group on most measures. Conclusion Treatment strategies for young children with ALL that avoid CRT are associated with good long-term neurocognitive outcomes. In this cohort, the dose of IV MTX did not influence these outcomes.