tbuckley/cabot-search huggingface dataset:
Phase III study: AES-14 in patients at risk for mucositis secondary to anthracycline-based chemotherapy
Authors: D. E. Peterson, R. G. Petit
Journal: Journal of Clinical Oncology (2004)

8008 Background: Oral mucositis (OM) limits chemotherapy dosing and increases health care costs. AES-14 (Saforis) enhances direct oral mucosal cell uptake of L-glutamine by the Aesgen UpTec system. Prior AES-14 studies in chemotherapy patients suggested safe, effective reduction (20%) of clinically significant OM. Methods: A randomized, double-blind, placebo-controlled crossover multicenter trial was conducted in breast carcinoma patients receiving at least 3 cycles of an anthracycline regimen (AC, CAF or FAC). Patients developing WHO Grade (Gr) 2–4 OM during screening cycle were randomized for crossover in 2 subsequent cycles. Study drug began 1st day of chemotherapy and continued 14 days after last chemotherapy dose or 5 days after OM resolved. Safety was assessed by Adverse Event (AE)/Serious AE evaluations. Primary endpoint analysis compared proportion of patients with ≥ Gr 2 OM while on AES-14 versus placebo. Secondary endpoints included OM duration and OM Assessment Scale outcomes. Results: 2,064 female patients were screened for OM ≥ WHO Gr 2. 326 patients (mean age 51 years) were randomized (15.7% OM rate). Peak OM was primarily WHO Gr 2. No significant randomization imbalances occurred. Comparison of treatment versus placebo outcomes in crossover design requires that no significant drug treatment carryover effect exists. AES-14 administered during 1st treatment cycle reduced ≥ Gr 2 OM incidence in the placebo 2nd treatment cycle (p=0.0269). This carryover effect invalidated crossover efficacy comparison. Primary endpoint analysis thus compared parallel group treatment during 1st cycle only. Incidence of clinically significant OM (WHO Gr 2–4) was 22% less with AES-14 versus placebo (p=0.0261). No AES-14-related SAEs and 2 placebo-associated SAEs were reported. Conclusions: AES-14 reduced incidence of 1st cycle Gr 2–4 OM by 22% in these chemotherapy patients. The significant AES-14 carryover effect suggests that optimizing mucosal repair during one cycle may protect patients from OM during subsequent chemotherapy. Supported by Aesgen Inc. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aesgen Inc. Aesgen Inc.
Dust from carpeted and smooth floors
Authors: T. DYBENDAL, H. VIK, S. ELSAYED
Journal: Allergy (1989)

Dust samples were collected twice from smooth and carpeted floors in 10 Norwegian schools. The content of antigens and allergens of alder (Alnus incana) , birch (Betula verrucosa) , timothy (Phleum pratense) , cat and dog dander, house dust mite (Dermatophagoides farinae) , mould (Cladosporium herbarum) , hen egg white and codfish (DIII) were investigated by crossed immunoelectrophoresis (CIE), crossed radio immunoelectrophoresis (CRIE), radio allergosorbent test (RAST) inhibition and quantitative precipitation inhibition analysis by laser nephelometry. Antigens and allergens of cat and dog dander and hen egg white were most prevalent in the dust samples investigated. With the exception of hen egg white and codfish allergens, no statistically significant differences in mean allergen content were shown in identical quantities of freeze‐dried dust extracts from carpeted and smooth floors. RAST‐inhibition analyses of identical amounts of dust from either floors showed higher content of allergens of cat, dog, hen egg white, codfish, mould and timothy pollen in classrooms with carpets.
Epithelial ciliary beating analysis in chronic airway diseases
Authors: Mustapha-Kamel Khellouffi, José Geraldo, Marius Socol, Jules Dupire, Céline Garulli, Annie Viallat, Pascal Chanez, Delphine Gras
Journal: European Respiratory Journal (2012)

Human bronchial epithelial cells (HBEC) activation and increased mucus production are constant features of epithelium in chronic airway diseases. However, the mechanisms and involvement of mucociliary component are poorly understood in these diseases. We used an  in vitro  model of bronchial epithelial cell culture in air/liquid interface obtained from bronchial biopsies of asthmatic patients (mild and severe) or COPD patients. We questioned the regulation of mucociliary couple in this system using an original approach combining biology and physics.  Methods . HBEC obtained after processing biopsy were expanded on tissue culture-treated plastic and then, were plated on uncoated nucleopore membranes in air-liquid interface for 21 days to obtain a mucociliary phenotype. For each epithelium re-differenciated  in vitro,  we first measured thickness and ciliary beating frequency (CBF). We used fast videomicroscopy (37°C). The effect of mucus presence on cilia beating was assessed by measuring frequency before and after washes with PBS.  Results . Preliminary results are presented in table 1 and are expressed as median (min-max).  Conclusion . At present we did not find any major change in the velocity of cilia beating according to the airway diseases in our air-liquid interface system. The contribution of mucus should be better investigated.
Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release
Authors: Izabela Komarowska, David Coe, Guosu Wang, Robert Haas, Claudio Mauro, Madhav Kishore, Dianne Cooper, Suchita Nadkarni, Hongmei Fu, Daniel A. Steinbruchel, Costantino Pitzalis, Graham Anderson, Pat Bucy, Giovanna Lombardi, Ross Breckenridge, Federica M. Marelli-Berg
Journal: Immunity (2015)

Highlights•HGF-induced c-Met signals during activation induce cardiotropic memory T cells•Cardiotropic T cells express a specific molecular signature (c-Met+CCR4+CXCR3+)•By inducing an autocrine chemokine loop, c-Met also promotes T cell recruitment•Blockade of the HGF-c-Met axis prevents heart, but not skin, allograft rejectionSummaryEffector-T-cell-mediated immunity depends on the efficient localization of antigen-primed lymphocytes to antigen-rich non-lymphoid tissue, which is facilitated by the expression of a unique set of "homing" receptors acquired by memory T cells. We report that engagement of the hepatocyte growth factor (HGF) receptor c-Met by heart-produced HGF during priming in the lymph nodes instructs T cell cardiotropism, which was associated with a specialized homing "signature" (c-Met+CCR4+CXCR3+). c-Met signals facilitated T cell recruitment to the heart via the chemokine receptor CCR5 by inducing autocrine CCR5 ligand release. c-Met triggering was sufficient to support cardiotropic T cell recirculation, while CCR4 and CXCR3 sustained recruitment during heart inflammation. Transient pharmacological blockade of c-Met during T cell priming led to enhanced survival of heart, but not skin, allografts associated with impaired localization of alloreactive T cells to heart grafts. These findings suggest c-Met as a target for development of organ-selective immunosuppressive therapies.Graphical abstract
Correlation of changes of IgE with skin reactivity and clinical outcome during specific immunotherapy against home dust in asthmatic subjects
Authors: Besim Prnjavorac, Rifat Sejdinovic, Enes Hondo, Adlija CauÅ¡evic, Sabina Semiz, Maja Malenica, Tamer Bego, Tanja Dujic
Journal: European Respiratory Journal (2012)

BACKGROUND: Effectiveness of SIT was well documented in many cases and published data. Selection of patients for SIT should be very serious and must include skin test and total and specific IgE measurement. How outcome of SIT correlate with changes of IgE, skin reactivity and overall symptoms reduction is aim of this study.

MATERIAL AND METHODS: Skin testing, total and specific IgE measurements were performed before and after each year of treatment. Skin test assessment was performed according to recommendation of Manual of Laboratory immunology. IgE ws performed using ELISA method. Clinical outcome was assessed using AQLQ questionnaire.

RESULTS: During five years period 58 asthmatic subjects with home dust and dermathophagoides allergy were treated by SIT. Bseline total IgE was 488,5 IU/ml (SD 78,9), mean specific IgE against dermatophagoides pteronissimus was 36,5 IU/ml (SD 15,2). Subcutaneous tests showed 15-20 mm weal in 43, and more than 21 mm in 15 cases. After 5 years mean total IgE was 227 IU/ml (SD 9,2) and mean specific IgE was 28,2 IU/ml (SD 8,9). Skin tests showed decrease diameter of weal. In 49 out of all patients clinical outcome were very well, and in 9 satisfied (according to AQLQ questionnaire). Using test of correlation, by linear regression, better correlation was shown between of skin testing and AQLQ than in total or specific IgE. So, in vivo skin tests were better predictor for success of SIT, than measurement of IgE.

CONCLUSION: Results of skin tests in diagnostic assessment of allergy in asthmatic patients were better predictor of successful outcome of SIT than laboratory measurement of total and specific IgE.
Lung structure and function in a rat model of emphysema: A longitudinal study
Authors: Margit Szabari, Jó zsef Tolnai, Balázs Maár, Harikrishnan Parameswaran, Erzsébet Bartolák-Suki, Béla Suki, Zoltán Hantos
Journal: European Respiratory Journal (2012)

Our aim was to evaluate the long term structure-function relations in a rat model of emphysema. Rats were treated with porcine pancreatic elastase (50 UI, PPE, n=21) or saline (controls, C, n=19) intratracheally. Before the treatment (day 0) and 3, 10, 21 and 105 days thereafter, respiratory impedance was measured with forced oscillation technique and tissue elastance (H) was calculated. At 3, 21 and 105 day the lungs were fixed, sections were obtained and stained with hematoxylin and eosin, modified Movat9s, Masson9s and Alcian blue method to visualize elastin, collagen and proteoglycans. Randomly selected regions were photographed. The images were automatically segmented and the equivalent diameter of alveolar airspaces (D), mean elastin (Me), mean collagen content (Mc) and mean proteoglycan ratio (Mp) were measured. H decreased through the time-course in the treated animals (p
The prevalence of thyroid disease in patients with vitiligo: a systematic review
Authors: C. Vrijman, M.W. Kroon, J. Limpens, M.M.G. Leeflang, R.M. Luiten, J.P.W. van der Veen, A. Wolkerstorfer, P.I. Spuls
Journal: British Journal of Dermatology (2012)

Thyroid disease has been suggested to be associated with vitiligo. However, the outcomes of prevalence studies on thyroid disease in vitiligo vary widely.To summarize and critically appraise current evidence of the prevalence of thyroid diseases in vitiligo.A systematic review was performed searching the electronic databases OVID MEDLINE, OVID EMBASE and PubMed. Guidelines for the critical appraisal of studies on prevalence of a health problem were adapted to evaluate the methodological quality of the included studies. Results were analysed in a meta-analysis with a risk ratio (RR).Forty-eight studies published between 1968 and 2012 met the inclusion criteria. Most of the studies (50%) were of fair methodological quality, whereas 18 studies (38%) were of poor quality and six studies (12%) were of good quality. Thyroid disease, autoimmune thyroid disease and presence of thyroid-specific autoantibodies showed a mean prevalence of, respectively, 15·1%, 14·3% and 20·8% in patients with vitiligo and an RR of, respectively, 1·9, 2·5 and 5·2 (all statistically significant). This review shows an increased prevalence and an increased risk of (autoimmune) thyroid disease in patients with vitiligo compared with nonvitiligo. This risk seems to increase with age.Clinicians should be aware of this increased risk in patients with vitiligo and should be attentive for symptoms of thyroid disease. To make recommendations on screening for thyroid disease in patients with vitiligo future research of good methodological quality, including differentiation of vitiligo types and the use of standardized outcome measures, is needed.
Tumor Immunity to Murine Plasma Cell Tumors. III. Detection of Common and Unique Tumor-Associated Antigens on BALB/c, C3H, and NZB Plasmacytomas by In Vivo and In Vitro Induction of Tumor-Immune Responses 2 3
Authors: Robert C. Burton, Noel L. Warner
Journal: JNCI Journal of the National Cancer Institute (1977)

Tumor-associated antigens (TAA) were demonstrated on plasmacytomas derived from BALB/c, NZB, and C3H mouse strains, by in vivo and in vitro techniques. By immunizing the appropriate F1 hybrid mice with these tumors, it was possible to show that all the plasmacytomas expressed cross-reactive tumor-associated transplantation antigens. When cytotoxic lymphocytes (CL) were induced in vitro by the coculturing of syngeneic or F1 hybrid spleen cells with irradiated plasmacytoma cells, “shared” and “unique” plasmacytoma TAA were demonstrable. This was accomplished by inducing CL in vitro against one syngeneic plasmacytoma and assaying for lytic activity on a range of 51Cr-labeled BAlB/c, NZB, and C3H plasmacytoma cells in vitro. In a second in vitro assay, unlabeled plasmacytoma cells were tested for their ability to inhibit the lysis of a particular 51Cr-labeled plasmacytoma, with the use of Cl induced in vitro against it. The possibility that these TAA were “self” antigens was excluded by demonstrating in the inhibition assay that they were not present on T lymphomas and spleen cells of the same strain, and that CL “autosensitized” in vitro could not significantly lyse 51Cr-labeled plasmacytoma cells in vitro. From both in vivo and in vitro studies of immunity to these tumors, it was concluded that anyone plasmacytoma line possesses multiple TAA of both shared and unique types.
Bradykinin-induced contractions in guinea pig trachea after incubation and culture
Authors: Martijn Manson, Jesper Säfholm, Sven-Erik Dahlén, Mikael Adner
Journal: European Respiratory Journal (2011)

Background:  Inflammatory conditions can alter responsiveness to the endogenous mediator bradykinin (BK) in mouse and human airway smooth muscle. Guinea-pig and human airways generally display similar smooth muscle responsiveness. The aim of this study was to develop an  in vitro -model in guinea pig trachea (GPT) to study the regulation of BK responses by culture procedures.   Methods:  The contractile response to BK was determined in organ tissue baths. Either fresh, organ bath incubated (6-12 hours) or in DMEM/ F12 media cultured (4 days) GPT segments were used for these measurements. The contractile responses to BK were determined in the presence of 3μM indomethacin and 10μM captopril. Contractions were presented as a percentage of the maximal contraction of the GPT.   Results:  In fresh GPT, BK induced only weak contractions (E max : 8±2%). This response was not changed after 6 hours incubation, however after 12 hours incubation a strong enhancement of the BK induced contraction was observed (E max : 53±2%, pEC 50  7.4±0.2). This up-regulated response was partly regulated by prostanoids, since both E max  (28±2%) and pEC 50  (6.3±0.1) were decreased in segments incubated for 12 hours with indomethacin. In contrast to the 12-hour incubation in the tissue bath, the contractile response to BK after 4 days organ culture was only slightly enhanced (E max : 21±3%).   Conclusion:  This study shows that contractions in GPT to BK are inducible over time. The different effects of incubations in the tissue bath and the organ culture may be used to study different aspects of regulation of BK responsiveness in airway inflammation.
Atlantoaxial Instability in down Syndrome-Guidelines for Screening and Detection
Authors: M Roy, M Baxter, A Roy
Journal: Journal of the Royal Society of Medicine (1990)

A community survey was conducted in all adults with Down syndrome living in three health districts to see if there was any correlation between radiological and neurological abnormalities which could indicate the presence of atlantoaxial instability. There was no difference in the proportion of individuals with neurological abnormalities in the group with radiological abnormalities suggestive of atlantoaxial instability (6/14) compared with individuals with normal X-rays (50/123) as determined by the chi square test (0.01463: not significant). The clinical and ethical implications for screening of people with Down syndrome living in the community are discussed in view of these findings.
Results of an ongoing open-label, phase II study of carfilzomib in patients with relapsed and/or refractory multiple myeloma (R/R MM).
Authors: R. Vij, D. S. Siegel, J. L. Kaufman, A. J. Jakubowiak, A. K. Stewart, S. Jagannath, V. Kukreti, M. H. Le, M. K. Bennett, M. Wang
Journal: Journal of Clinical Oncology (2010)

8000 Background: Carfilzomib (CFZ) is a highly selective proteasome inhibitor with single-agent activity in patients (pts) with R/R MM. Methods: In this ongoing study of single-agent CFZ in R/R MM, pts were stratified based on prior exposure to BTZ and CFZ dose level (Table). CFZ IV was administered on days 1, 2, 8, 9, 15, and 16 every 28 d for up to 12 cycles. Study endpoints included overall response rate (ORR), defined as ≥ partial response (PR), duration of response (DOR), and safety. Results: The BTZ-treated cohort included 35 pts (14 refractory to most recent treatment). For BTZ-naive pts, cohort 1 included 59 pts and cohort 2 included 20 pts. Pts received a mean of 5 cycles of CFZ (range 1–12). Thirty-three BTZ-treated pts were evaluable with an ORR of 18%. For BTZ-naive pts, 54 pts in cohort 1 and 19 pts in cohort 2 were evaluable with ORRs of 46% and 53%, respectively. Median DOR (≥MR) was ≥8.8 months (mo). Treatment groups and patient responses are shown in the Table. In the combined pt population, the most common adverse events (AEs) included fatigue (66%), nausea (49%), dyspnea (40%), anemia (34%), diarrhea (32%) and were primarily ≤ Gr 2 in severity. The most common ≥ Gr 3 AEs were anemia, thrombocytopenia, and neutropenia (10% each). Febrile neutropenia and treatment-emergent peripheral neuropathy (PN) were uncommon. Of 23 pts who completed the 12 cycle protocol, 7 chose to continue CFZ therapy on an extended treatment protocol. Updated results for all cohorts will be presented. Conclusions: Single-agent CFZ is active in pts with R/R MM. AEs were generally mild and thereby durable disease control was obtained with continued dosing. Severe PN is rare and does not limit therapy. BTZ-treated N=35 BTZ-naive Cohort 1 N=54 Cohort 2 N=19 CFZ administration 20 mg/m2 20 mg/m2 20 mg/m2 cycle 1, 27 mg/m2 cycle 2+ Best response CR 1 1 0 VGPR 1 5 1 PR 4 19 9 MR 4 8 0 SD 13 12 6 Median DOR (≥MR) 9.0 mo 8.8 mo TBD Median TTP 5.3 mo 7.6 mo TBD Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Onyx Bristol-Myers Squibb, Celgene, Centocor Ortho Biotech, Exelixis, Genzyme, Millennium, Onyx Pharmaceuticals Onyx Bristol-Myers Squibb, Celgene, Centocor Ortho Biotech, Exelixis, Johnson & Johnson, Merck, Millennium, Onyx Celgene, Merck, Millennium, Novartis, Onyx
Microbiological pattern in infective episodes of bronchiectasis
Authors: Abdalla Khoury, Hassan Ismaeil, Hivin Hannan
Journal: European Respiratory Journal (2011)

Background:  Infections usually cause inflammatory reaction and destruction of bronchial wall, this further leads to more disturbance in local defense and a vicious cycle of inflammation and bacterial colonization occurs.   Objectives:  The purpose of this paper was to studying the microbiological pattern during infective episodes of Bronchiectasis and possible relation between the invasive Bacteria and lung functions.   Materials and methods:  A retrospective analysis of 60 episodes in 50 patients. Forty patients fulfilled our protocol criteria of reliable microbiological result and reproducible lung function tests. The patients were categorized into three stages of severity. Fibroptic bronchoscopy was performed just after spirometry, and BAL sampling was achieved. Cut off point of 10000CFU was considered for positivity of culture media.   Results:  H.influenza was the causative agent in 10 episodes (17%), S.pneumoniae in 8 (14%) and P.aeroginosa in 9 (14%), Morexella catarrhalis in 7 (12%) episodes.  Lung function tests revealed an FEV1 with 50% of predicted value in 20 patients (stage 1), an FEV1 with 35-50% in 12 patients (stage 2)and FEV1 with 35% in 8 patients (stage 3).  There was a correlation between deterioration of lung function and the bacteria isolated from patients with infective exacerbations of Bronchiectasis, in acute episodes Pseudomonas Aeuroginosa and Enterobactericeae were the predominant bacteria in patients with FEV1 at 35% of predicted value.   Conclusion:  There were no correlations between the isolated bacteria and the duration of symptoms, number of previous hospitalization, or radiological findings. In contrast there was a correlation between the deterioration of lung function and the isolated bacteria.
Effects of phasic electrical stimulation during expiration in elderly patients with chronic obstructive pulmonary disease: A randomised control trial
Authors: Kenichi Ito, Tatsuo Nozoe, Miyuki Okuda, Koji Nonaka, Jun Horie, Hirobumi Kawamura
Journal: European Respiratory Journal (2013)

Background:  The objective of this study was to shed light on the effects of phasic electrical stimulation during expiration (PESE) on ventilatory function during exercise in patients with chronic obstructive pulmonary disease (COPD).   Methods:  Twenty-four patients with COPD were randomised to either a sham group or a PESE group in a double-blind controlled study. Ventilatory functions (minute ventilation, tidal volume, respiratory rate, inspiratory time and expiratory time), oxygen saturation and the rate of perceived exertion (Borg scale) were measured at rest (5 min) and during exercise (5 min) before and after the intervention of both sham and PESE groups. A total of four electrodes were placed on the abdominal muscles. The stimulation protocols of sham consisted of square pulse at 25Hz, duty cycle of 10 s on and 10 s off, pulse time of 200 µs. The stimulation protocols of PESE consisted of square pulse at 20Hz, duty cycle of during expiration on and during inspiration off, pulse time of 200 µs.   Results:  Data obtained from 23 (12 from the electrical stimulation group and 11 from the sham group) of 24 patients with COPD were analysed. PESE improved tidal volume (sham: 1085.0 → 1237.0 ml, p = 0.075 vs PESE: 1104.0 → 1403.0 ml, p = 0.015) and respiratory rate (sham: 21.6 → 19.3 n/min, p = 0.061 vs PESE: 20.2 → 16.9 n/min, p = 0.028) during exercise. Oxygen saturation and the rate of perceived exertion (Borg scale) during exercise did not significantly change with PESE.   Conclusion:  This study indicates an improvement in ventilatory function due to PESE, which may be useful for rehabilitation of elderly patients with COPD.