tbuckley/cabot-search huggingface dataset:
Role of midkine in idiopathic pulmonary fibrosis
Authors: Kenichi Misa, Yoshinori Tanino, Xintao Wang, Naoko Fukuhara, Takefumi Nikaido, Suguru Sato, Manabu Uematsu, Kazue Saito, Atsuro Fukuhara, Hiroshi Yokouchi, Tadashi Ishida, Mitsuru Munakata
Journal: European Respiratory Journal (2013)

Background: Midkine (MK) is a multi-functional heparin-binding growth factor, and previous studies have shown that MK regulates cell growth, survival and migration. MK is reported to be up-regulated in proximal tubular epithelial cells by oxidative stress, suggesting its critical roles in the pathogenesis of kidney injury. In skin fibroblasts, MK is demonstrated to stimulate collagen expression and glycosaminoglycan synthesis. Although these facts suggest the important roles of MK in tissue injury and repair processes, the role of MK in pulmonary fibrosis has not been clarified. The goal of this study was to determine if MK plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF).  Methods: We analyzed the concentration of MK in serum of 28 patients with IPF and 10 healthy volunteers (HVs), and compared to several clinical parameters in patients with IPF.  Results: The concentration of MK in serum was significantly higher in patients with IPF than HVs (1730.7 + 140.4 vs 1009.6 + 209.0 pg/ml, p   Conclusion: These findings suggest the possible role of MK in the pathogenesis of IPF.
Interaction between interleukin 6 gene polymorphisms and second-hand smoke exposure on adult-onset asthma
Authors: Taina K. Lajunen, Jouni J.K. Jaakkola, Maritta S. Jaakkola
Journal: European Respiratory Journal (2014)

Background  We reported strong independent and joint effects of family asthma and second-hand smoke exposure (SHS) on the risk of adult-onset asthma (AJRCCM 2013). For interleukin 6 (IL6), an inflammatory cytokine, up-regulation of gene expression by tobacco smoke, and higher serum levels for smokers and for asthmatics were reported. IL6 single nucleotide polymorphisms (SNPs) were associated with changes in lung function parameters and asthma.  Objective  To assess interactions of IL6 SNPs and SHS on the risk of adult-onset asthma.  Methods  A population-based incident case-control study of clinically defined adult-onset asthma and random controls, among adults 21 to 63 years old in Finland. Six tagging SNPs were genotyped. Among non-smokers, genotyping was available for 217 cases and 316 disease-free controls.  Results  Rs2069827 genotype AA, rs1800797 genotype GA, and rs2069861 genotype AG had synergistic effect with recent SHS exposure. Carriage of any one of them had synergistic effect with SHS, so that the relative excess risk due to interaction (RERI) was 2.22, 95% confidence interval 0.67-5.27, and carriage of any two had even higher synergism (RERI 7.83, -0.02-79.68). In a haplotype analysis of the same SNPs, carriage of haplotype H4 (CAA) or H6 (AAG) (except for a protective haplotype pair H3/H6) was found to show synergism with SHS, RERI 3.05 (-0.66-15.46) and 2.19 (-0.20-8.70), respectively. For of H4 and H6 carriers combined, a synergistic effect was again seen (RERI 3.43, 0.76-10.03).  Conclusions  IL6 SNPs and SHS have synergistic effect on the risk of adult-onset asthma, carriage of several risk genotypes or a risk haplotype is associated with higher synergistic effect.
Acute effects of CPAP vs BiPAP low or high intensity in patients with severe congestive heart failure
Authors: Andréa Da Nóbrega Cirino Nogueira, Isabela Thomaz Takakura Guedes, Liégina Silveira Marinho, Renata Dos Santos Vasconcelos, Raquel Pinto Sales, Thiago Brasileiro De Vasconcelos, Soraya Mdn Rebouças Viana, Clarissa Bentes De Araujo Magalhae, Maria do Socorro Quintino Farias, Suzy Maria Montenegro Pontes, Vasco Pinheiro Diógenes Bastos, Carlos Roberto Martins Rodrigues Sobrinho, Marcelo Alcantara Holanda
Journal: European Respiratory Journal (2014)

OBJECTIVE:  To analyze the acute effects of noninvasive ventilation (NIV) on cardiac function and pulmonary ventilation in patients with congestive heart failure (CHF).   METHOD:  Prospective, intervention, randomized study. Seven patients (4 men and 3 women) with stable chronic CHF with left ventricular ejection fraction (EF) ≤ 35%; mean age 54±28,9 years. Interventions: CPAP (10 cmH 2 O), BiPAP (15/10 and 25/10 cmH 2 O) of inspiratory and expiratory pressures respectively, via facial mask. NIV aplication lasted 20 min each, with periods of spontaneous breathing for 30 min between them as a washout period. Myocardial performance and changes were measured using clinical and echocardiography parameters. Statistically significant (pl0,05).  RESULTS:  CPAP significantly decrease of HR (pre: 80,6±11,2, post: 78,2±11,4bpm, p=0,004) and E/E9septal (pre: 18,5±11,6, post: 17,7±13,2bpm, p=0,03) and increased TV (pre: 5,05 ± 1,61; pos: 9,36 ± 5,50 L/min, p= 0,01). BiPAP significantly decrease of HR (pre: 80±11, post: 77±10bpm, p=0,01), TV (pre: 5,05 ± 1,61; pos: 9,36 ± 5,50 L/min, p= 0,01) and EtCO 2  (pre: 35±3; post: 25±7mmHg, p=0,05); no significantly decrease of E/E9septal (pre: 17,35±13,2, post: 17,4±12,2bpm, p=0,21) and increased SpO 2  (pre: 97±1,5, post: 98±1,4%, p=0,05). High intensity BiPAP (25/10) decreased EtCO 2  (pre: 35,4±3,6, post: 27±5,1mmHg, p=0,02) and increased PCP (pre: 22,4±10, post: 28,3±13,1, p=0,01), TV (pre: 5,16 ± 1,86; pos: 15,55 ± 4,84 L/min, p= 0,002) and SpO 2  (pre: 96,7±1,2, post: 98,7±1,4%, p=0,01).  CONCLUSION:  These preliminary results show reduces ventricular preload and that high intensity increases PCP in patients with severe stable CHF.
Validation of a multiple breath inert gas washout technique using a lung phantom
Authors: Sherif Gonem, Florian Singer, Salman Siddiqui, Per Gustafsson
Journal: European Respiratory Journal (2012)

Background:  Multiple breath inert gas washout (MBW) is a technique for assessing ventilation heterogeneity by measuring the efficiency with which an inert tracer gas is washed out of the lungs.   Aims and objectives:  We aimed to use a lung phantom to validate a previously published method for MBW (Horsley AR,  et al.  Thorax . 2008;  63 (2): 135-140).   Methods:  We built a one-compartment lung model consisting of an enclosed clear acrylic glass tank, partly filled with water at 37 o C. The tank was fitted with an off-centre vertical partition that divided it into a larger and a smaller section, but did not reach the base of the tank, thus allowing the two sides to communicate. The lid of the larger section was connected to a bi-level positive airway pressure ventilator which exerted alternating high and low pressures on the water surface, thus causing the water level in the smaller section to alternately rise and fall, simulating diaphragmatic movement. FRC, tidal volume (Vt) and respiratory rate (RR) were adjusted by altering the volume of water within the phantom lung and the ventilator settings. We performed MBW on the phantom lung at a variety of values of FRC, Vt and RR. Each experiment was performed in triplicate. Measured FRC was then compared to the true FRC in each case.   Results:  Measured FRC was within 5% of true FRC in all but one experiment. The intraclass correlation coefficient for the triplicate measurements was 0.999, suggesting that the MBW technique is highly repeatable.   Conclusion:  We conclude that MBW performed using an Innocor gas analyser is highly repeatable and accurate. Simple one-compartment lung phantoms appear to be a promising method for the validation of MBW systems.
Lung function impairment following mycoplasmal and other acute pneumonias
Authors: LA Laitinen, AK Miettinen, E Kuosma, L Huhtala, K Lehtomaki
Journal: European Respiratory Journal (1992)

We prospectively studied the lung function of 106 consecutive young patients with pneumonia. At the time of hospital admission we observed impaired spirometric function in 48% of the patients. During and following treatment, the frequency of abnormalities in pulmonary function tests decreased rapidly. However, at the 15th day of hospitalization, abnormal ventilatory function was still demonstrated in 21% of the patients. Such prolonged impairment of ventilatory function was significantly more likely to result from pneumonia caused by Mycoplasma pneumoniae than from forms caused by adenovirus or Streptococcus pneumoniae.
Epithelial Desquamation in Asthma
Authors: CLAUDIA ORDOÑEZ, RON FERRANDO, DALLAS M. HYDE, HOFER H. WONG, JOHN V. FAHY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To determine whether the denudation of the bronchial epithelium observed in endobronchial biopsies from asthmatic subjects is a true pathologic feature or an artifact of tissue sampling, we analyzed epithelial integrity in bronchial biopsies from 14 subjects with mild and moderate asthma and 12 healthy subjects. In each subject, 4 to 8 bronchial biopsies were taken from large airways during bronchoscopy, fixed in 4% paraformaldehyde, embedded in glycomethacrylate, cut into 2- μ M sections, and stained with toluidine blue. A × 4 image of each biopsy was copied to a computer file using a video camera, and lines were drawn and measured along the basement membrane underlying areas completely denuded of overlying epithelium, areas covered by a single layer of basal cells, and areas of intact epithelium. We found that the percentage of basement membrane that was denuded of epithelium was similar in the healthy and asthmatic subjects (14.8 ± 11.8 versus 11.4 ± 9.8% respectively, p = 0.38); the percentage of basement membrane that was covered by a single layer of basal cells was also similar in the two groups (46.4 ± 11.0 versus 54.5 ± 9.8%, respectively, p = 0.11). In the asthmatic subjects, we found no significant correlation between the percentage of basement membrane covered by denuded epithelium or by a single layer of basal cells and the FEV1 percentage of predicted or the PC20 methacholine. We conclude that denudation of bronchial epithelium in endobronchial biopsies from asthmatic subjects with stable mild and moderate disease is an artifact of tissue sampling and is not a true pathologic feature of the disease, and that the extent of airway epithelial denudation is not correlated with the severity of airway narrowing or the severity of bronchial hyperresponsiveness.
Fibrosis, Vascular Activation, and Immune Abnormalities Resembling Systemic Sclerosis in Bleomycin‐Treated Fli‐1–Haploinsufficient Mice
Authors: Takashi Taniguchi, Yoshihide Asano, Kaname Akamata, Shinji Noda, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Maria Trojanowska, Shinichi Sato
Journal: Arthritis & Rheumatology (2014)

Fli-1, a potential predisposing factor for systemic sclerosis (SSc), is constitutively down-regulated in the lesional skin of patients with SSc by an epigenetic mechanism. To investigate the impact of Fli-1 deficiency on the induction of an SSc phenotype in various cell types, we generated bleomycin-induced skin fibrosis in Fli-1(+/-) mice and investigated the molecular mechanisms underlying its phenotypic alterations.Messenger RNA (mRNA) levels and protein expression of target molecules were examined by quantitative reverse transcription-polymerase chain reaction and immunostaining. Transforming growth factor β (TGFβ) bioassay was used to evaluate the activation of latent TGFβ. The binding of Fli-1 to the target gene promoters was assessed with chromatin immunoprecipitation.Bleomycin induced more severe dermal fibrosis in Fli-1(+/-) mice than in wild-type mice. Fli-1 haploinsufficiency activated dermal fibroblasts via the up-regulation of αvβ3 and αvβ5 integrins and activation of latent TGFβ. Dermal fibrosis in Fli-1(+/-) mice was also attributable to endothelial-to-mesenchymal transition, which is directly induced by Fli-1 deficiency and amplified by bleomycin. Th2/Th17-skewed inflammation and increased infiltration of mast cells and macrophages were seen, partly due to the altered expression of cell adhesion molecules in endothelial cells as well as the induction of the skin chemokines. Fli-1(+/-) mouse macrophages preferentially differentiated into an M2 phenotype upon stimulation with interleukin-4 (IL-4) or IL-13.Our findings provide strong evidence for the fundamental role of Fli-1 deficiency in inducing SSc-like phenotypic alterations in dermal fibroblasts, endothelial cells, and macrophages in a manner consistent with human disease.
<i>Borrelia miyamotoi</i> Disease in the Northeastern United States
Authors: Philip J. Molloy, Sam R. Telford, Hanumara Ram Chowdri, Timothy J. Lepore, Joseph L. Gugliotta, Karen E. Weeks, Mary Ellen Hewins, Heidi K. Goethert, Victor P. Berardi
Journal: Annals of Internal Medicine (2015)

The first recognized cases of Borrelia miyamotoi disease (BMD) in North America were reported in the northeastern United States in 2013.To further describe the clinical spectrum and laboratory findings for BMD.Case series.Patients presenting to primary care offices, emergency departments, or urgent care clinics in 2013 and 2014.Acutely febrile patients from the northeastern United States in whom the treating health care providers suspected and ordered testing for tick-transmitted infections.Whole-blood polymerase chain reaction (PCR) testing was performed for the presence of specific DNA sequences of common tickborne infections (including BMD). Serologic testing for B. miyamotoi was performed using a recombinant glycerophosphodiester phosphodiesterase (rGlpQ) protein. Clinical records were analyzed to identify the major features of acute disease.Among 11,515 patients tested, 97 BMD cases were identified by PCR. Most of the 51 case patients on whom clinical histories were reviewed presented with high fever, chills, marked headache, and myalgia or arthralgia. Twenty-four percent were hospitalized. Elevated liver enzyme levels, neutropenia, and thrombocytopenia were common. At presentation, 16% of patients with BMD were seropositive for IgG and/or IgM antibody to B. miyamotoi rGlpQ. Most (78%) had seropositive convalescent specimens. Symptoms resolved after treatment with doxycycline, and no chronic sequelae or symptoms were observed.Findings were based on specimens submitted for testing to a reference laboratory, and medical records of only 51 of the 97 case patients with BMD were reviewed.Patients with BMD presented with nonspecific symptoms, including fever, headache, chills, myalgia, and arthralgia. Laboratory confirmation of BMD was possible by PCR on blood from acutely symptomatic patients who were seronegative at presentation. Borrelia miyamotoi disease may be an emerging tickborne infection in the northeastern United States.IMUGEN.
Acute Abdominal Pain in Children
Authors: D P Drake
Journal: Journal of the Royal Society of Medicine (1980)

During a twelve-month period, 416 children with acute abdominal pain required emergency admission to Southampton General Hospital; 46% had operations. Appendicitis was the commonest organic cause of acute abdominal pain identified (31%). Constipation (9%) can present as acute abdominal pain simulating appendicitis. All children should have a urine sample examined microscopically and the finding of significant pyuria is suggestive, but not diagnostic, of a urinary tract infection (7%). Mesenteric adenitis, which can only be diagnosed with certainty at laparotomy, was less common (4%). Despite careful clinical assessment and follow up, 45% of children in this series remained undiagnosed. Sedation but not analgesia may assist in the diagnosis of the acute abdomen in children.
Abstract 10084: Significant Improvements in Patient Reported Outcomes in Eisenmenger Syndrome with Advanced Pulmonary Hypertension Therapies and Association with Objective Improvements in Exercise Tolerance
Authors: Ian P Temple, Hoda Mirjafari, Linda Griffiths, Heiko Schneider, Vaikom S Mahadevan
Journal: Circulation (2011)

Introduction Eisenmenger syndrome patients have a high symptomatic burden with decreased functional ability, right sided heart failure and early death. Treatment is aimed at improving symptoms and quality of life (QOL). There is limited data to advocate the prognostic benefit of treatment. CAMPHOR (Cambridge Pulmonary Hypertension Outcome Review) is a patient questionnaire specific to pulmonary artery hypertension (PAH). It assesses the impact of PAH on patients' symptoms, activity and QOL and is a validated outcome measure. Hypotheses We hypothesised that Eisenmenger syndrome patients' 6 minute walk test (6MWT) was associated with their CAMPHOR scores and that initiation of advanced therapy with bosentan resulted in improvement in their CAMPHOR scores and 6MWT. Methods All patients in a tertiary centre diagnosed with Eisenmenger syndrome on treatment with bosentan completed the CAMPHOR questionnaire provided they had capacity. This was performed prior to initiation of bosentan and repeated at each routin...
Interim Safety Results from Steam: a Randomized Phase 2 Trial of Sequential and Concurrent Folfoxiri–Bevacizumab (Bev) Vs Folfox–Bev for the First-Line (1L) Treatment (Tx) of Patients (Pts) with Metastatic Colorectal Cancer (Mcrc)
Authors: H. Hurwitz, B. Tan, J. Reeves, H. Xiong, H. Lenz, H. Hochster, R. Laeufle, N. Sommer, J. Young, M. Byrtek, J. Bendell
Journal: Annals of Oncology (2014)
Phenotypic comparison of glucose and cardiac physiology of biomass fuel induced and smoking induced COPD
Authors: Shima Rafiei, Mohan Kulkarni, S. Naik, Jyoti Londhe, Neha Iyer, Sapna Madas, Peter Barnes, Sundeep Salvi, Bill Brashier
Journal: European Respiratory Journal (2013)

There is paucity of knowledge on how physiology of systemic parameters used in predicting metabolic syndrome differs in Biomass-fuel smoke induced COPD (BF-COPD) and smoking- COPD (SM-COPD). Aim: To evaluate and compare glucose and cardiovascular (CVS) physiology of BF-COPD and SM-COPD. Methods: Physician and spirometry diagnosed, age and severity matched, 43 SM-COPD and 23 BF-COPD underwent blood pressure estimation, ECG and glucose tolerance test. Descriptive statistics were used to estimate prevalence rates and parametric test were used to compare the means (SD). Results: In glucose physiology, diabetes (DM) diagnosed in accordance to fasting glucose was 8.7% in BF-COPD versus 2.3%in SM-COPD. DM diagnosed in accordance to post-glucose test was 19.0% in BF-COPD versus 2.5% in SM-COPD. Impaired glucose tolerance (IGT) test was 14.3% in BF-COPD versus 27.5% in SM-COPD. Fasting glucose levels >100mg/dl was 34.8% in BF-COPD versus 23.3% in SM-COPD. In CVS physiology BF-COPD had higher ECG measured mean heart rate (HR) and Qtc interval versus SM-COPD [HR: 85.6(12.1) beats/min vs 78.6(13.5) beats/min, p=0.04; Qtc: 453.6(35.5) vs 418.7(25.3); p 0.05). Conclusion: In the preliminary analysis of ongoing study BF-COPD tends to have higher prevalence of DM and glucose component of metabolic syndrome, while, SM-COPD tends to have more IGT, which were greater than what has been reported from India. There were also differences in HR and Qtc interval amongst the COPD phenotypes; however, which could be due to unequal gender distribution.
Tumor Induction in &lt;italic&gt;Praomys (Mastomys) natalensis&lt;/italic&gt; by &lt;italic&gt;N,N&lt;/italic&gt;′-2,7-Fluorenylenebisacetamide
Authors: C Hoch-Ligeti, B P Wagner, M K Deringer, H L Stewart
Journal: JNCI Journal of the National Cancer Institute (1985)

Feeding N,N'-2,7-fluorenylenebisacetamide (CAS:304-28-9) at 0.025% to 15 male and 15 female mastomys considerably shortened their life-span. At death every treated mastomys had several primary tumors; untreated animals at comparable ages had none. Several mastomys with hepatoblastomas and 1 with giant cell hepatitis and a metastasizing pancreatic carcinoma are first reported here. The tumor load per animal averaged 4.0 for treated females, 2.6 for treated males, 1.5 for untreated females, and 0.6 for untreated males. Of 24 hepatic tumors in treated mastomys, 11 metastasized, compared to none of the incipient tumors in 8 of 26 untreated animals. Pancreatic adenomas developed in 27 treated and 1 untreated mastomys, and a metastasizing adenocarcinoma developed in 1 treated animal. All treated females, 3 treated males, and 1 untreated female developed multiple villous adenomas in the small intestine. One untreated female and 8 treated females developed mammary cancers, 4 of which metastasized. Primary tumors of other sites occurred infrequently.
Use of intravenous (IV) aminophylline in acute exacerbations of COPD with decompensated acidotic type 2 respiratory failure (T2RF) requiring non-invasive ventilation (NIV)
Authors: Edward Benison, Mithun Murthy, Rajesh Yadavilli, Hassan Burhan
Journal: European Respiratory Journal (2013)

Background  IV Aminophylline is commonly used in patients presenting with acute exacerbations of COPD (AECOPD). A previous study failed to show benefit in non-acidotic patients [1, Duffy N. et al. Thorax 2005, 60(9):713-7] albeit showing improvements in pH and pCO2. Side effects of methylxanthines are common and potentially serious.  Aim  We aimed to evaluate the use and side-effects of IV aminophylline in AECOPD presenting with acidotic T2RF who also received NIV.  Methods  Prospective data collected on 24 patients admitted to the Royal Liverpool Hospital with acidotic AECOPD.  Results  20/24 (83%) were current or ex-smokers with Mean (SD) 43 (32) pack years. Mean [SD] pH 7.22 [0.10]. 12 (50%) patients were previously on oral theophylline. IV aminophylline was commenced in the emergency department in 62.5%. Only 14 (58.3%) patients were weighed prior to maintenance dose prescription. 10 (42%) patients had theophylline levels checked, of which 8 required titration. Mean (SD) duration of infusion was 2.7 [2.2] days. In 7 patients (29.1%), infusion was stopped due to side effects. Mean (SD) duration of NIV was 1.7 (1.3) days and mean (SD) length of stay 13.4 [10.5] days. 5 (20%) patients died during admission; 1 due to acute coronary syndrome where Aminophylline may have been contributary.  Discussion  The role for IV aminophylline in AECOPD is not clear, although current guidance allows its use [2, NICE CG 101, June 2010]. IV aminophylline requires careful titration and monitoring which does not always happen and may lead to adverse effects. Further evidence of benefit, especially in acidotic AECOPD is required.
Screening of health status in patients with COPD in primary care is essential
Authors: Jeannette Peters, Leonie Daudey, Anke Lahaije, Lonneke Boer, Eveline de Geus, Johan Molema, Yvonne Heijdra, Jan Vercoulen
Journal: European Respiratory Journal (2011)

Background:  Guidelines advice to measure health status (HS) in COPD patients. In secondary care (SC) this is more common than in primary care (PC). Problems in HS in PC might be underestimated resulting in inadequate treatment.   Aim:  To investigate the proportion of COPD patients in PC with severe problems in HS.   Methods:  314 PC COPD patients were included. Eight sub-domains of HS were measured by the Nijmegen Clinical Screening Instrument (NCSI) covering Functional impairment, Symptoms and Quality of Life. Data from 303 SC COPD patients were available to compare the meaning of the incidence and severity of problems in PC patients.   Results:  Patients in PC did not differ on sex (59 vs 70% male) and age (mean 66 vs 67 years), but had less severe COPD compared to SC (stageI: 28 vs 16%; II: 59 vs 45%; III: 13 vs 32%; IV: 0 vs 8%). Lower proportions of patients with severe problems were found on the domain Functional impairment and the sub-domain Subjective symptoms in PC as compared to SC (Table 1). GOLD was not predictive for experienced problems in any of the sub-domains in PC.   Conclusion:  Severe problems in many sub-domains of HS were substantial in PC patients. In 5 of 8 sub-domains of HS similar percentages of COPD patients in PC and SC experience severe problems. This implies that screening for problems in HS is needed in PC to warrant patient tailored treatment.