tbuckley/cabot-search huggingface dataset:
The long-term effect of ambulatory oxygen (AO) in normoxaemic COPD patients who participate in pulmonary rehabilitation (PR) and desaturate during exercise. A randomised study
Authors: Thomas Ringbaek, Gerd Martinez, Peter Lange
Journal: European Respiratory Journal (2012)

Introduction:  The long-term benefits of AO in combination with PR in COPD patients experiencing exertional desaturation have not been studied.   Patients and methods:  Normoxaemic COPD who participated in PR and desaturate >4% and below 90% during endurance shuttle walk test (ESWT) were randomised to control (n=23) or AO 2 L/min. from a portable oxygen concentrator (n=22) to be used during physical activity.  PR consisted of supervised training 20 wks + unsupervised daily training at home and then 13 wks without supervised training.   Results:  Only 45 of 165 eligible patients wanted to participate. Mean FEV 1 =32% and MRC=4.5 (3-5).  Supplemental oxygen improved satO 2  during ESWT by 2.3% (p   Conclusions:  AO provided no additional beneficial effects in patients with COPD participating in pulmonary rehabilitation and experiencing exertional desaturation without severe resting hypoxaemia.
LSC 2013 abstract - Roles of polarized neutrophils on lung tumour cells engraftment in an orthotopic lung tumour mouse model
Authors: Natacha Rocks, Sandrine Bekaert, Geoff Warnock, Christelle Sepult, Jean-Michel Foidart, Agnes Noel, Didier Cataldo
Journal: European Respiratory Journal (2013)

Lung cancer is a deadly disease and results of current treatments are deceiving. Many research groups are focusing on development of new treatment schemes which might be associated to unpredictable side effects. Working with a non invasive, reproducible and rapidly successful animal model has therefore become a priority. It has become evident that inflammation can contribute to enhance progression of a benign tumour to a malignant phenotype. Neutrophils represent an essential part of the innate immune system, suggesting their important functions in tumour biology. The aim of this study was to develop a non invasive orthotopic mouse model of lung tumours. LLC tumour cells were intratracheally injected with or without a pro-inflammatory agent to enhance tumour development. We found that neutrophils induced by an agarose-induced inflammation, but not by LPS, are able to enhance lung tumour take. Neutrophils isolated from lungs of mice stimulated by agarose display more often a N2-protumoral phenotype when compared to neutrophils isolated from LPS-challenged lungs. Higher levels of β2-integrin are measured in agarose-induced lungs and therefore an increased number of interactions of neutrophils expressing β2-integrin with ICAM-1 molecules present on epithelial pulmonary cells might be hypothesised. We propose that N2-neutrophils induced by agarose stimulation enhance lung tumour cells anchorage on the airway epithelium by bridging the tumour cells with the epithelium.  We provide in this study the evidence that inflammation triggers lung tumor anchorage and development. However, inflammatory agents inducing N2-type neutrophils seem mandatory for a protumoral effect.
Annual direct-cost of asthma and COPD in Turkey
Authors: Sadik Ardic, Erdogan Cetinkaya, Pinar Cirkin, Ozlem Salman Sever, Hilal Onaran
Journal: European Respiratory Journal (2012)

Introduction  Asthma and COPD are considered among the top 10 leading chronic conditions with increasing prevalence that translates into increased direct and indirect medical expenditures (1).  Aims and objectives  The ONDINE study aimed to calculate annual direct medical cost of asthma and COPD in Turkey  Methods  Patients with asthma or COPD were included in this national, multicenter, cross-sectional, non-interventional study. Direct costs including treatment, tests and healthcare resources utilization were calculated.  Results  A total of 596 patients with asthma (n=301) or COPD (n=295) were included in the study. Disease control was evident in 38% of COPD and in 51% of asthma patients. COPD was severe in 31% of the patients while asthma was intermittent in 51%. Main drugs administered were long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in asthma (68%) and in COPD (71%) patients. The most commonly performed tests in asthma and COPD patients were chest XR (98% and 99%) and spirometry (98% and 98%). Average annual direct cost (including drug, non-drug application, hospital and personnel costs) was 8386 TL (3595 Euro) for asthma and 10798 TL (4629 Euro) for COPD. LABA+ICS combination (1132 TL, 485 Euro) was the highest drug-related cost. Poor control and increased severity of both asthma and COPD caused higher hospital cost and higher total direct cost (for all P  Conclusions  The study revealed that based on the significant relation to direct costs, strategies to enable better disease control and to reduce severity of the disease in asthma and COPD must be considered in healthcare policies to limit economic burden.  1. Shaya FT et al. Burden of concomitant asthma and COPD in a Medicaid population. Chest. 2008;134(1):14-9.
An Audit of Audits: Are we Completing the Cycle?
Authors: Janaki Gnanalingham, Muhuntha G Gnanalingham, Kanna K Gnanalingham
Journal: Journal of the Royal Society of Medicine (2001)

Clinical audit plays an important part in the drive to improve quality of patient care and thus forms a cornerstone of clinical governance. We evaluated the standard of clinical audits conducted by all departments in a teaching hospital between 1996 and 1997. Of a total of 213 audits carried out, 102 (48%) were ‘partial’ and only 29 (14%) were ‘full’. Recommendations for improvement emerged from 134 (63%) of the audits performed. In only 51 audits (24%) was the cycle completed by re-auditing, during the subsequent 3 years. Most departments undertake clinical audits but failure to close the loop undermines their effectiveness and wastes resources.
Predictors of early response to initial therapy in patients with newly diagnosed symptomatic multiple myeloma
Authors: Moritz Binder, S. Vincent Rajkumar, Morie A. Gertz, Martha Q. Lacy, Angela Dispenzieri, Francis K. Buadi, David Dingli, Suzanne R. Hayman, John A. Lust, Prashant Kapoor, Yi Lin, Ronald S. Go, Yi L. Hwa, Robert A. Kyle, Shaji K. Kumar
Journal: American Journal of Hematology (2015)

Response to therapy in newly diagnosed symptomatic multiple myeloma (NDMM) can impact long-term outcomes. It is not clear if baseline laboratory parameters can predict an early, deep response. Totally 1,304 patients with NDMM seen between 2001 and 2013 at Mayo Clinic Rochester were studied. The association between baseline laboratory parameters and early, deep response defined as a very good partial response or better (VGPR+) within four cycles of treatment was investigated. Multivariable logistic regression was used to assess the associations between the parameters of interest and response. Multivariable proportional hazards regression was used to assess the association between response and overall survival. In the entire cohort, greater absolute free light chain (FLC) differences (OR 2.38, 95% CI 1.48-3.82), younger age (OR 2.18, 95% CI 1.28-3.71), lower hemoglobin (OR 1.68, 95% CI 1.12-2.54), and IgA myeloma (OR 1.66, 95% CI 1.10-2.51) were associated with increased odds of achieving VGPR+ after four cycles. Among patients receiving novel agents in general and immunomodulators in particular, these effects were more pronounced. In patients receiving proteasome-inhibitors, higher creatinine (OR 3.83, 95% CI 1.37-10.1), lower calcium (OR 3.37, 95% CI 1.36-8.35), and greater absolute FLC differences (OR 2.50, 95% CI 1.10-5.71) were associated with better response. In a landmark analysis at 4 months from diagnosis, achieving VGPR+ was associated with decreased risk of subsequent mortality (HR 0.69, 95% CI 0.53-0.86). In summary, several parameters were associated with an early, deep response to treatment, revealing distinct sets of predictors for immunomodulator- and proteasome-inhibitor-containing regimens. Achieving VGPR+ after four cycles translated into increased overall survival.
Metalloproteases gene expression and remodeling of lung parenchyma fibers during the progression of elastase induced emphysema
Authors: Fabiola Santos Zambon Robertoni, Clarice Rosa Olivo, Juliana Dias Lourenço, Natalia Gomes Gonçalves, Ana Paula Pereira Velosa, Walcy Rosolia Teodoro, Chin Jia Lin, Milton De Arruda Martins, Fernanda Dtq dos Santos Lopes
Journal: European Respiratory Journal (2014)

We previously demonstrated an increase in gene expression of MMP-8 and MMP-13 since the first hours of the induction of emphysema in mice by porcine pancreatic elastase (PPE) and a posterior reduction in the volume ratio of collagen type I (3 days) that returned to similar values of control groups at the 21th day of the protocol. Such results suggested the importance of collagenases in emphysema progression.  Objectives : To describe the importance of MMP-12, as well as the repair process of elastin and fibrillin at the beginning of the emphysema development and correlated it with previous findings.  Methods : C57BL/6 mice were submitted to intranasal instillation of PPE (0,667 IU) and were euthanized at different times after that: 1 hour, 3 hours, 6 hours, 3 days and 21 days. Control groups (S) received the same treatment with saline (NaCl 0.9%). We used the Real-time RT-PCR to assess the gene expression of MMP-12 and immunohistochemistry to quantify the volume ratio of elastin and fibrillin in lungs.  Results : The MMP-12 gene expression was increased since 3 hs of emphysema induction until 6 hs. Fibrillin analyses showed no difference in its parenchyma percentage at any of the PPE groups comparing to S groups. Elastin instead, presented a decrease at 3rd day after PPE instillation and a increase at 21st day compared to respective S groups.  Conclusions : We attested the importance of the MMP-12 together with MMP-8 and MMP-13 activity since the first hours after the emphysema induction. Also we verified a repair process characterized by a prior reduction in quantified parenchymal fibers followed by an increase at 21th day.
Percutaneous transhepatic cholangioscopy for indeterminate biliary strictures using the SpyGlass system: a case series
Authors: Lillian Du, Pernilla D’Souza, Aducio Thiesen, Safwat Girgis, Richard Owen, Dermot McNally, Philippe Sarlieve, Gurpal Sandha
Journal: Endoscopy (2015)

Peroral cholangioscopy is useful in differentiating benign from malignant biliary strictures. However, when conventional biliary access via endoscopic retrograde cholangiopancreatography (ERCP) fails, percutaneous transhepatic cholangioscopy (PTCS) via the SpyGlass cholangioscopy system can be used to achieve a diagnosis. Four patients with biliary strictures in whom conventional ERCP was not possible and percutaneous brushings were either nondiagnostic or unsatisfactory were investigated with PTCS. The technique of PTCS involves insertion of the SpyGlass cholangioscope through a percutaneous transhepatic sheath, placed just prior to the procedure, to visualize the stricture and obtain biopsies with the SpyBite forceps. On the basis of our early observations, we conclude that PTCS using the SpyGlass cholangioscopy system for the assessment of biliary strictures is feasible, safe, and provides high diagnostic accuracy.
An unusual cause of subcutaneous emphysema, pneumomediastinum and pneumoperitoneum
Authors: WG Boersma, JP Teengs, PE Postmus, JC Aalders, HJ Sluiter
Journal: European Respiratory Journal (1988)

A 62 year old female with subcutaneous emphysema, pneumomediastinum and pneumoperitoneum, was observed. Pneumothorax, however, was not present. Laparotomy revealed a large infiltrate in the left lower abdomen, which had penetrated the anterior abdominal wall. Microscopically, a recurrence of previously diagnosed vulval carcinoma was demonstrated. Despite intensive treatment the patient died two months later.
Main features of cytokine profile in serum and bronchoalveolar lavage fluid in patients with recurrent sarcoidosis
Authors: Natalya Demyanenko, Vladimir Romanov, Svetlana Sheluhina, Eugene Shmelev
Journal: European Respiratory Journal (2013)

Introduction: It is well known that the leading element of the pathogenesis of sarcoidosis is a disorder of immune regulation. In this regard, it’s very important to study the lymphocyte mediated immunity in patients with recurrent sarcoidosis, depending on the activity of the inflammatory process.  Objective: Determination of cytokine profile in bronchoalveolar lavage fluid in patients with recurrent sarcoidosis.  Materials and Methods: The study involved 60 patients - 41 women and 19 men. All patients were divided into 2 groups based on the level of C-reactive protein. The group of patients with high CRP included 24 people, the other group with normal CRP level included 36. The method of study of the cytokine profile in bronchoalveolar lavage fluid and serum was an immunofluorescence analysis for multiplex detection of cytokines in biological fluids.  Results: When compared, the cytokine profile in bronchoalveolar lavage fluid in patients with high CRP showed a significant increase of TNF-beta, IL-12, IFN-gamma and especially IL-4 and IL-5. While, the cytokine profile in bronchoalveolar lavage fluid in the group with normal CPR showed the high levels of TNF-alpha and beta, IL-12, IFN-gamma, IL-2, -4 and -5. The elevation of IL-4 and -5 in the bronchoalveolar lavage fluid in the group with high CPR was much more significant, whereas the elevation of TNF-beta and IFN-gamma was lower.  Conclusion: Our study showed, that there is an activated T-helper 2 immune response in bronchoalveolar lavage fluid in in patients with high CPR.
Philadelphia chromosome in relapsed childhood acute lymphoblastic leukemia: a matched-pair analysis. Berlin-Frankfurt-Münster Study Group.
Authors: B Beyermann, H P Adams, G Henze
Journal: Journal of Clinical Oncology (1997)

PURPOSE The translocation t(9;22)(q34;q11), known as Philadelphia chromosome (Ph1) or its molecular equivalent the expression of BCR-ABL-mRNA, is one of the most striking and well-characterized cytogenetic abnormalities in leukemia. Although investigated for more than 30 years, it remains unclear whether the Ph1 is an independent risk factor for outcome of leukemia or not. METHODS A matched-pair analysis was performed within a homogeneous group of patients, which consisted of children who presented with a first relapse of acute lymphoblastic leukemia (ALL) who were treated according to ALL relapse trials (ALL-REZ BFM) protocols. A total of 307 patients were eligible for this analysis: 30 positive and 277 negative for Ph1. Positive patients were matched exactly for time point of relapse (on [during] or off [after cessation of] front-line therapy), site, and immunophenotype, and as close as possible for duration of first remission, peripheral blast-cell count, WBC count, and year of relapse diagnosis. RESULTS The probability of event-free survival is 0.46 at 5 years for negative and 0.11 for positive patients, respectively (P = .0006). Multivariate analysis showed risk ratios of 4.229 for relapse on therapy, 3.561 for Ph1 and/or expression of BCR-ABL- mRNA, 1.691 for high peripheral blast-cell count, and 0.232 for bone marrow transplantation. CONCLUSION It was shown that the Ph1 is indeed an independent risk factor in childhood relapsed ALL. There are striking similarities between these patients and children at initial diagnosis, as well as adult patients. Therefore, it is highly suggestive that the Ph1 is also an independent risk factor under all of these circumstances.
Clinical modulation of multidrug resistance in multiple myeloma: effect of cyclosporine on resistant tumor cells.
Authors: P Sonneveld, M Schoester, K de Leeuw
Journal: Journal of Clinical Oncology (1994)

PURPOSE In multiple myeloma (MM) refractory to doxorubicin (DXR) and/or vincristine (VCR), myeloma cells frequently express the multidrug resistance (MDR) phenotype, associated with overexpression of P-glycoprotein (Pgp), which acts as a drug efflux pump. Recently, studies have shown that clinical resistance can be modulated by drug resistance modifiers. The present study was performed to investigate if MDR modulation in vivo is caused by a direct effect of cyclosporine (CSA) on resistant myeloma plasma cells (PC). PATIENTS AND METHODS Eight patients with VAD-refractory MM were treated with DXR, VCR, and dexamethasone (VAD) plus CSA. Pgp expression in PC was determined by flow cytometry/immunocytochemistry before and after clinical treatment. Functional Pgp expression was determined by the effect of CSA on the intracellular accumulation of DXR and VCR. RESULTS Five of eight patients responded to VAD/CSA. The percentage of Pgp-positive (Pgp+) PC was 30% to 100% (median, 90%) before treatment and 4 to 90% (median, 40%) after treatment. CD56+/- or CD38+/- PC had identical Pgp expression. CSA, as well as SDZ PSC 833, but not dexamethasone, increased pretreatment intracellular accumulation of DXR and VCR in Pgp+ PC in three of four and six of six patients, respectively. After clinical treatment, in vitro drug accumulation in residual Pgp-negative (Pgp-) PC of four of four responding patients was not further modulated by CSA or SDZ PSC 833. At later relapse, PC of two of four patients remained Pgp-. CONCLUSION These data indicate that Pgp overexpression is functional in refractory myeloma and that clinical modulation of MDR by CSA is mediated through an inhibition of Pgp-associated drug efflux. Pgp-expressing PC can be eliminated by clinical treatment with VAD/CSA.
Increased Susceptibility to Lethal Lipopolysaccharide in Mice with Effects of Bacterial B-Cell Leukemia&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M. J. Muirhead, E. S. Vitetta, P. C. Isakson, Keith A Krolick, J. H. Dees, J. W. Uhr
Journal: JNCI Journal of the National Cancer Institute (1981)

Susceptibility to the lethal effects of bacterial lipopolysaccharide (LPS) increased more than one hundredfold in BALB/c mice given syngeneic B-cell tumor transplants. The increased susceptibility to LPS that developed during the following weeks paralleled tumor growth in the liver and spleen. The tumor-bearing animals also developed an enhanced capacity to clear colloidal carbon from the blood, consistent with mcreased activity of the reticuloendothelial system. Although hypersusceptibility to LPS had been reported in a number of animal models, our experiment was the first demonstration in a tumor model that susceptibility correlates with tumor burden.
Mature T cell responses are controlled by microRNA-142
Authors: Yaping Sun, Katherine Oravecz-Wilson, Nathan Mathewson, Ying Wang, Richard McEachin, Chen Liu, Tomomi Toubai, Julia Wu, Corinne Rossi, Thomas Braun, Thomas Saunders, Pavan Reddy
Journal: Journal of Clinical Investigation (2015)

T cell proliferation is critical for immune responses; however, the molecular mechanisms that mediate the proliferative response are poorly understood. MicroRNAs (miRs) regulate various molecular processes, including development and function of the immune system. Here, utilizing multiple complementary genetic and molecular approaches, we investigated the contribution of a hematopoietic-specific miR, miR-142, in regulating T cell responses. T cell development was not affected in animals with a targeted deletion of Mir142; however, T cell proliferation was markedly reduced following stimulation both in vitro and in multiple murine models of graft-versus-host disease (GVHD). miR-142-deficient T cells demonstrated substantial cell-cycling defects, and microarray and bioinformatics analyses revealed upregulation of genes involved in cell cycling. Moreover, 2 predicted miR-142 target genes, the atypical E2F transcription factors E2f7 and E2f8, were most highly upregulated in miR-142-deficient cells. Clustered regularly interspaced short palindromic repeat interference-mediated (CRISPRi-mediated) silencing of E2F7 and E2F8 in miR-142-deficient T cells ameliorated cell-cycling defects and reduced GVHD, and overexpression of these factors in WT T cells inhibited the proliferative response. Together, these results identify a link between hematopoietic-specific miR-142 and atypical E2F transcription factors in the regulation of mature T cell cycling and suggest that targeting this interaction may be relevant for mitigating GVHD.
Bronchoscopic treatment of benign tumors of the tracheobronchial tree
Authors: Levent Dalar, Ahmet Levent Karasulu, Sinem Nedime Sokucu, Seda Onur, Aysegul Akbas, Sezin Altay, Ramazan Celik, Sedat Altin
Journal: European Respiratory Journal (2012)

Aim: To evaluate the efficacy of the bronchoscopic treatment approach and follow up results of the treatment of the benign tumors of the tracheobronchial tree.  Method: In this retrospective cross sectional cohort study, 44 consecutive patient treated in between January 2006 to June 2011 in our Interventional Pulmonology Unit were evaluated. All patients undergone rigid bronchoscopy under general anestesia. In all of the patients firstly mechanical debridement after coagulation was applied and cryotherapy to the base of the tumor for excluding residue were applied.  Recurrence and residue ratios, early and late complications were evaluated.  Results: Most commonly treated benign tumor was hamartoma (38%, n=17). Other than this, procedures were applied to other rare tumors like as adenoma, amyloidosis, etc. In eight of the patients, tumor was located at the trachea. One to six sequence of procedure were applied to cases (mean two). No major complication was observed due to the procedures. Mortality was not observed. Surgical resection was needed in two of the cases.  Conclusion: Interventional bronchoscopic approach is safe and effective in the treatment of benign tumors of the trachea. Complete cure can be optained in all of the benign tumors in which the tumor base was seen and not advanced beyond cartilage layers.
Major Vascular Injury during Lumbar Laminectomy
Authors: E Ezra, J L Richenberg, W A B Smellie
Journal: Journal of the Royal Society of Medicine (1996)

Major vascular injury during lumbar laminectomy is an extremely rare complication of one of the commonest surgical procedures performed in orthopaedic and neurosurgical units. Its occurrence may be associated with high morbidity and mortality, particularly if it is not diagnosed in the early stages. Early diagnosis and repair is associated with an improved prognosis in the long term. We illustrate these points with a description of two cases, and discuss the anatomical factors predisposing to these injuries and the importance of angiography in the management and early diagnosis of suspected cases.