tbuckley/cabot-search huggingface dataset:
Hospital referrals for low back pain: More coherence needed
Authors: Alan J Silman, Malcolm I V Jayson, Ann C Papageorgiou, Peter R Croft
Journal: Journal of the Royal Society of Medicine (2000)

Low back pain is a common reason for hospital referral but little is known of the resulting workload in different specialties. All new outpatient attendances for conditions with low back pain were recorded over one month in a teaching hospital and a district general hospital. The patients were seen in at least ten specialties and two-fifths of them had been seen previously with the same symptom in another department. In the two hospitals, low back pain accounted for 15% and 12% of all new outpatient attendances. A more coherent referral policy is needed.
Improving drug delivery to pancreatic cancer: breaching the stromal fortress by targeting hyaluronic acid
Authors: Patrick Michl, Thomas M Gress
Journal: Gut (2012)

The dismal prognosis of pancreatic cancer has not significantly changed over the last few decades. The incidence and mortality of this tumour entity are still almost identical, associated with a 5-year survival of <5%. Given the appalling outcome of the disease and the numerous regimens tested in clinical trials over recent years that have proved futile, there is an urgent need for novel therapeutic approaches to improve the situation.

Pancreatic cancer is characterised by an extensive desmoplastic reaction consisting of a variety of stromal cells such as pancreatic stellate cells, activated fibroblasts and inflammatory cells embedded in a dense extracellular matrix comprising numerous components such as collagens and glycosaminoglycans. During the last few decades, the role of this stromal reaction has been largely neglected by the majority of research efforts, which have instead focused directly on the tumour cells as the main determinant of drug resistance. The role of the stroma as a ‘fortress’ fencing off the tumour cells from drugs applied in the circulation has only very recently1 been recognised and addressed systematically after the advent of appropriate mouse models that faithfully recapitulate human disease, in particular its intense stromal reaction.2

In 2009, Olive et al examined in a landmark paper the impact of targeting sonic hedgehog signalling as one major pathway known to stimulate stromal reaction.3 After systemic administration of the hedgehog inhibitor, IPI926, the authors observed a significant depletion of tumour-associated stroma associated with an increase in intratumoral vascular density and concentration of the coadministered cytotoxic agent, gemcitabine. On the basis of these data, the authors proposed that inefficient drug delivery due to the intense stromal reaction may be an important contributor to chemoresistance in pancreatic cancer.3

In this issue of the journal, the …
Accumulation of inflammatory cells in response to intracutaneous platelet activating factor (Paf-acether) in mang
Authors: C.B. ARCHER, C.P. PAGE, J. MORLEY, D.M. MACDONALD
Journal: British Journal of Dermatology (1985)

Platelet activating factor (Paf‐acether, AGEPC) is a family of ether‐linked phospholipids known to be released from a range of inflammatory cell types. In vitro and in experimental animals, it seems to be a mediator of inflammation, and intradermal injection of Paf‐acether in man elicits a biphasic inflammatory response, reminiscent of the dual response to allergen in sensitized individuals. In the present study, cutaneous histology was assessed in sequential skin biopsies from six normal volunteers after intradermal injection of 200 or 800 pmol Paf‐acether. Paf‐acether (200 pmol) induced intravascular accumulation of neutrophils, accompanied by a p erivascular mixed cellular infiltrate which was composed predominantly of neutrophils at 4 and 12 hours, and lymphocytes and histiocytes at 24 hours. Control injections of lyso‐Paf and normal saline induced no noteworthy histological changes. Paf‐acether (800 pmol) resulted in vessel destruction, gross endothelial swelling and a perivascular infiltrate of mononuclear cells and neutrophils, accompanied by occasional evidence of leucocytoclasis. By virtue of its ability to induce inflammatory cell accumulation in human skin, Paf‐acether should be considered as a potential mediator of inflammatory disorders such as psoriasis.
Alcohol consumption and lung cancer risk in never smokers: a meta-analysis
Authors: V. Bagnardi, M. Rota, E. Botteri, L. Scotti, M. Jenab, R. Bellocco, I. Tramacere, C. Pelucchi, E. Negri, C. La Vecchia, G. Corrao, P. Boffetta
Journal: Annals of Oncology (2011)
Reproductive outcome after bariatric surgery: a critical review
Authors: I. Guelinckx, R. Devlieger, G. Vansant
Journal: Human Reproduction Update (2008)

After many cycles of weight loss and weight gain, more and more morbidly obese patients undergo bariatric surgery, like gastric banding or gastric bypass, as the ultimate treatment for their obesity-problem. Since women of reproductive age are candidates for bariatric surgery, concerns arise regarding the potential impact on future pregnancy. English-language articles were identified in a PUBMED search from 1982 to January 2008 using the keywords for pregnancy and bariatric surgery or gastric bypass or gastric banding. The few reported case–control and cohort studies clearly show improved fertility and a reduced risk in obstetrical complications, including gestational diabetes, macrosomia and hypertensive disorders of pregnancy, in women after operatively induced weight loss when compared with morbidly obesity women. The incidence of intrauterine growth restriction (IUGR) appears to be increased, however. No conclusions can be drawn concerning the risk for preterm labour and miscarriage, although these risks are probably increased compared with controls matched for body mass index. Operative complications are not uncommon with bariatric surgery and several cases have pointed to the increased risk for intestinal hernias and nutritional deficiencies in subsequent pregnancy. Deficiencies in iron, vitamin A, vitamin B12, vitamin K, folate and calcium can result in both maternal complications, such as severe anaemia, and fetal complications, such as congenital abnormalities, IUGR and failure to thrive. Close supervision before, during and after pregnancy following bariatric surgery and nutrient supplementation adapted to the patient's individual requirements can help to prevent nutrition-related complications and improve maternal and fetal health, in this high-risk obstetric population.
Tissue factor pathway inhibitor expression by human pleural mesothelial and mesothelioma cells
Authors: M.S. Bajaj, U. Pendurthi, K. Koenig, S Pueblitz, S Idell
Journal: European Respiratory Journal (2000)

The mesothelial lining of the pleura and malignant mesothelioma promote fibrin deposition in pleural injury or neoplasia via expression of tissue factor (TF). It was hypothesized that these cells might also regulate intrapleural coagulation by elaborating TF pathway inhibitor (TFPI). TFPI activity and antigen in pleural fluids were assayed from patients with congestive heart failure (CHF), pneumonia, empyema, metastatic pleural cancer and malignant mesothelioma. The authors also assessed expression of TF and TFPI messenger ribonucleic acid (mRNA) as well as TFPI activity and antigen by human pleural mesothelial cells, malignant mesothelioma cells (MS-1 cell line) and human lung fibroblasts. Immunohistochemical analyses of normal, fibrotic, and neoplastic pleura were performed to determine whether TFPI antigen was expressed in vivo. The study revealed that TFPI was present in transudates from patients with CHF and exudative pleural effusions from patients with pneumonia, empyema or pleural carcinoma. TFPI mRNA, activity and antigen were expressed by pleural mesothelial cells, MS-1 cells and lung fibroblasts. Cytokines and serum stimulated a significant early increase in TF mRNA levels with minimal enhancement of TFPI mRNA, activity and antigen levels. TFPI antigen was found in normal, fibrotic and neoplastic pleural tissues. The current observations indicate that tissue factor pathway inhibitor is locally expressed in pleural disease, but that it does not prevent the development of a prothrombotic environment favouring local fibrin deposition in pleural inflammation or cancer.
Coeliac disease and unfavourable outcome of pregnancy
Authors: P Martinelli
Journal: Gut (2000)

<h3>BACKGROUND</h3> Up to 50% of women with untreated coeliac disease experience miscarriage or an unfavourable outcome of pregnancy. In most cases, after 6–12 months of a gluten free diet, no excess of unfavourable outcome of pregnancy is observed. The prevalence of undiagnosed coeliac disease among pregnant women is not known. <h3>AIM</h3> To determine the prevalence of untreated coeliac disease among women attending the obstetrics-gynaecological department. <h3>METHODS</h3> Endomysial antibodies, which are specific and sensitive for coeliac disease, were evaluated in all women attending the obstetrics-gynaecology department of a large city hospital over a 90 day period. <h3>RESULTS</h3> Of 845 pregnant women screened, 12 were identified as having coeliac disease. Three had previously been diagnosed but were not following a gluten free diet. The remaining nine underwent a small intestinal biopsy, which confirmed the diagnosis. The outcome of pregnancy was unfavourable in seven of these 12 women. Six healthy babies were born with no problems after the women had been on a gluten free diet for one year. <h3>CONCLUSIONS</h3> Overall, 1 in 70 women was affected by coeliac disease, either not diagnosed (nine cases) or not treated (three cases). Their history of miscarriages, anaemia, low birth weight babies, and unfavourable outcome of pregnancy suggests that testing for coeliac disease should be included in the battery of tests prescribed for pregnant women. Coeliac disease is considerably more common than most of the diseases for which pregnant women are routinely screened. Unfavourable events associated with coeliac disease may be prevented by a gluten free diet.
1004 SHORT-TERM PROGNOSTIC FACTORS OF ALCOHOLIC LIVER DISEASE PRESENTED WITH SIGNIFICANT JAUNDICE: COMPARISIONS OF SERIAL MELD, DELTA-MELD, CHILD-TURCOTTE-PUGH SCORES, AND DISCRIMINANT FUNCTION
Authors: J.D. Kim, J.M. Yang, U.I. Chang, J.Y. Choi, S.H. Bae, S.K. Yoon, J.W. Jang, C.W. Kim, S.H. Cho, J.-Y. Han, Y.S. Lee
Journal: Journal of Hepatology (2009)
Dose-response for inhaled fluticasone on airway and systemic inflammation in COPD
Authors: P.A. Williamson, D. Menzies, K.L. Clearie, S. Vaidyanathan, B.J. Lipworth
Journal: European Respiratory Journal (2010)

To the Editors:

Asthma is an eosinophilic condition and, as such, responds readily to inhaled corticosteroids (ICS). By contrast, chronic obstructive pulmonary disease (COPD) is a heterogeneous condition associated with neutrophilic inflammation, which is relatively steroid-insensitive. Corticosteroid/long-acting β-agonist combination inhalers improve quality of life and lung function, and reduce COPD exacerbation 1. A meta-analysis of COPD studies has reported a 25% reduction in all-cause mortality using ICS, but dose varied between 400 and 1,000 μg·day−1 of fluticasone propionate (FP) equivalent and no dose–response relationship was apparent 2. There is, however, a dose-related risk of side-effects, including dysphonia, osteoporosis, cataracts and pneumonia 3, 4. Evidence is scant for an optimal ICS dose that confers long-term benefits whilst minimising potential risks.

COPD is now considered a systemic inflammatory disease. Biomarkers, such as C-reactive protein (CRP), are elevated in COPD and are associated with cardiovascular mortality and recurrent exacerbations 5. It has been proposed that ICS may play a role in treating systemic inflammation. Proposed biomarkers of inflammation in COPD include: CRP, interleukin (IL)-6, tumour necrosis factor (TNF)-α, surfactant protein (SP)D and exhaled markers, such as nitric oxide (NO). Measurement of the exhaled NO fraction ( F eNO) at multiple flow rates can be used to derive values of NO production from conducting (bronchial flux; J ′aw,NO) and small airways (alveolar nitric oxide; C A,NO). C A,NO is elevated in COPD and is not effected by smoking 6. Although studies have assessed biomarker response to fixed doses of ICS, dose response has not been addressed.

To explore the risk/benefit of ICS in COPD, we have performed a pilot study of the corticosteroid dose–response relationship on airway and systemic inflammatory outcomes.

Current or ex-smokers, >50 yrs of age, with a forced expiratory volume in 1 s (FEV …
Use of long-acting β<sub>2</sub> agonists in arginine-16 homozygous patients with asthma
Authors: R H Green, I D Pavord
Journal: Thorax (2008)

Accuracy in suspicious lung infiltrationsWe read with interest the paper by Targowski et al. 1 Suspicious lung infiltra- tions such as malignant tumours are always difficult to diagnose in clinical practice.Transthoracic fine needle biopsy (TFNB) may be a useful procedure despite a high risk of false negative results.To improve the accuracy of the technique, telomerase activity in combination with TFNB was investigated in the study by Targowski et al.We suggest that alternative options such as positron tomography scanning (CT-PET) should be evaluated, which may provide better imaging quality and accurate guidance for performing TFNB, increasing the accuracy of lung cancer diagnosis.In the Continuing Observation of Smoking Subjects (COSMOS) study recently published by Veronesi et al 2 invol- ving 5200 current or former smokers, CT-PET had a sensitivity of 100% in the diagnosis of solid pulmonary nodules of 10 mm of more.In this study, TFNB was not part of the clinical routine.In contrast, the sensitivity of the combination of TFNB with telomerase activity used by Targowski et al was lower at 89.3% and the mean size of suspected lesions was not described.
cAMP concentrations, cAMP dependent protein kinase activity, and phospholamban in non-failing and failing myocardium
Authors: M. Bohm, B. Reiger, R. H G Schwinger, E. Erdmann
Journal: Cardiovascular Research (1994)

Journal Article cAMP concentrations, cAMP dependent protein kinase activity, and phospholamban in non-failing and failing myocardium Get access Michael Böhm, Michael Böhm Klinik III für Innere Medizin, University of Cologne, Joseph-Stelzmann Str 9, 50924 Cologne, Germany: M Böhm, B Reiger, R H G Schwinger, E Erdmann. Correspondence to Dr Böhm. Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara Reiger, Barbara Reiger Klinik III für Innere Medizin, University of Cologne, Joseph-Stelzmann Str 9, 50924 Cologne, Germany: M Böhm, B Reiger, R H G Schwinger, E Erdmann. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert H G Schwinger, Robert H G Schwinger Klinik III für Innere Medizin, University of Cologne, Joseph-Stelzmann Str 9, 50924 Cologne, Germany: M Böhm, B Reiger, R H G Schwinger, E Erdmann. Search for other works by this author on: Oxford Academic PubMed Google Scholar Erland Erdmann Erland Erdmann Klinik III für Innere Medizin, University of Cologne, Joseph-Stelzmann Str 9, 50924 Cologne, Germany: M Böhm, B Reiger, R H G Schwinger, E Erdmann. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 11, November 1994, Pages 1713–1719, https://doi.org/10.1093/cvr/28.11.1713 Published: 01 November 1994 Article history Received: 16 March 1994 Accepted: 16 August 1994 Published: 01 November 1994
Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis
Authors: Brett Ley, Harold R. Collard, Talmadge E. King
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Section:ChooseTop of pageAbstract <<CLINICAL COURSE OF IPFCAUSES OF DEATHINDIVIDUAL PREDICTORS OF ...CLINICAL PREDICTION MODEL...CHALLENGES AND FUTURE DIR...ReferencesCITING ARTICLES
Minimal Residual Disease after Conventional Treatment Significantly Impacts on Progression-Free Survival of Patients with Follicular Lymphoma: The FIL FOLL05 Trial
Authors: Sara Galimberti, Stefano Luminari, Elena Ciabatti, Susanna Grassi, Francesca Guerrini, Alessandra Dondi, Luigi Marcheselli, Marco Ladetto, Pier Paolo Piccaluga, Anna Gazzola, Claudia Mannu, Luigia Monitillo, Barbara Mantoan, Ilaria Del Giudice, Irene Della Starza, Marzia Cavalli, Luca Arcaini, Alessandra Tucci, Giuseppe Alberto Palumbo, Luigi Rigacci, Alessandro Pulsoni, Umberto Vitolo, Carola Boccomini, Daniele Vallisa, Giovanni Bertoldero, Gianluca Gaidano, Pellegrino Musto, Mario Petrini, Massimo Federico
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The role of the minimal residual disease (MRD) in follicular lymphoma is still debated. In this study, we assessed whether the BCL2/IGH rearrangement could have a prognostic role in patients receiving R-CHOP, R-FM, or R-CVP. Experimental Design: DNAs from 415 patients among the 504 cases enrolled in the FOLL05 trial (NCT00774826) were centralized and assessed for the BCL2/IGH at diagnosis, at the end of treatment, and after 12 and 24 months. Results: At diagnosis, the molecular marker was detected in 53% of cases. Patients without molecular marker or with a low molecular tumor burden (&amp;lt;1 × 10−4 copies) showed higher complete remission (CR) rate and longer progression-free survival (PFS; 3-year PFS 80% vs. 59%; P = 0.015). PFS was significantly conditioned by the PCR status at 12 and 24 months, with 3-year PFS of 66% for MRD− cases versus 41% for those MRD+ at 12 months (P = 0.015), and 84% versus 50% at 24 months (P = 0.014). The MRD negativity at 12 and 24 months resulted in an improved PFS both in CR and in partial remission (PR) patients (3-year PFS = 72% for cases CR/PCR− vs. 32% for those CR/PCR+ vs. 62% for those PR/PCR− and 25% for patients in PR/PCR+; P = 0.001). The prognostic value of MRD at 12 and 24 months of follow-up was confirmed also in multivariate analysis. Conclusions: In this study, standardized molecular techniques have been adopted and applied on bone marrow samples from a large cohort. Data reported show that the MRD detection is a powerful independent predictor of PFS in patients with follicular lymphoma receiving conventional chemoimmunotherapy. Clin Cancer Res; 20(24); 6398–405. ©2014 AACR.
Podocyte Flattening and Disorder of Glomerular Basement Membrane Are Associated with Splitting of Dystroglycan-Matrix Interaction
Authors: Kenichiro Kojima, Agnes Davidovits, Helga Poczewski, Brigitte Langer, Shunya Uchida, Katalyn Nagy-Bojarski, Anny Hovorka, Roland Sedivy, Dontscho Kerjaschki
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The transmembrane component of the dystroglycan complex, a heterodimer of α- and β-dystroglycan, was recently localized at the basal cell membrane domain of podocytes, and it was speculated that it serves as a device of the podocyte for maintaining the complex podocyte foot process architecture, and for regulating the exact position of its ligands, the matrix proteins laminin and agrin, in the glomerular basement membrane (GBM). The redistribution of dystroglycan in two experimental rat models of foot process flattening and proteinuria—i.e., podocyte damage induced by polycationic protamine sulfate perfusion, and reactive oxygen species (ROS)-associated puromycin aminonucleoside nephrosis—was examined. In both experimental diseases, aggregation and reduced density of α-dystroglycan by endocytosis by podocytes was observed. In in vitro solid-phase binding assays, protamine and ROS competed with the binding of α-dystroglycan with purified laminin and a recombinant C-terminal fragment of agrin that contains the dystroglycan-binding domain. These changes were associated with disorder of the fibrillar components of the lamina rara externa of the GBM, as confirmed quantitatively by fractal analysis. These results indicate that both polycation and ROS induce similar changes in the distribution of podocyte α-dystroglycan that involve competitive disruption of α-dystroglycan/matrix protein complexes, endocytosis of the liberated receptor by podocytes, and disorganization of the matrix protein arrangement in the lamina rara externa. This links functional damage of the dystroglycan complex with structural changes in the GBM.
Metabolism of Fibrinogen in Cirrhosis of the Liver
Authors: G. N. Tytgat, D. Collen, M. Verstraete
Journal: Journal of Clinical Investigation (1971)

The metabolism of human fibrinogen labeled with radioactive iodine was studied in 50 patients with documented cirrhosis of the liver and in 35 healthy control subjects. Results in cirrhotic subjects were the following: plasma volume 47 ± 10 ml/kg; plasma fibrinogen concentration 250 ± 102 mg/100 ml; total plasma fibrinogen pool 118 ± 59 mg/kg, representing 0.73 ± 0.10 of the total body pool; fibrinogen half-life 2.99 ± 0.59 days; fractional catabolic rate 0.34 ± 0.09 of the plasma pool per day; absolute catabolic rate 39 ± 20 mg/kg per day; fractional transcapillary efflux rate 0.82 ± 0.30 of the plasma pool per day. Results in the control subjects were the following: plasma volume 42 ± 7 ml/kg; plasma fibrinogen concentration 284 ± 71 mg/100 ml; total plasma fibrinogen pool 119 ± 40 mg/kg, representing 0.72 ± 0.07 of the total body pool; fibrinogen half-life 4.14 ± 0.56 days; fractional catabolic rate 0.24 ± 0.04 of the plasma pool per day; absolute catabolic rate 28 ± 9 mg/kg per day; fractional transcapillary efflux rate 0.60 ± 0.26 of the plasma pool per day.
Expression of interleukin-1 beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1ra) on asthmatic bronchial epithelium.
Authors: A R Sousa, S J Lane, J A Nakhosteen, T H Lee, R N Poston
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Accumulating evidence suggests that the cytokine network is central to the immunopathology of bronchial asthma and recent findings have suggested that naturally occurring cytokine antagonists may also be involved. In this study we looked at the expression of interleukin-1 beta (IL-1beta) and its naturally occurring receptor antagonist, IL-1ra, in the normal and asthmatic bronchial wall. Frozen bronchial biopsies from 12 normal and 18 asthmatic individuals were double stained with EBM11 (a CD68 macrophage marker) and either a rabbit anti-IL-1beta or a rabbit anti-IL-1ra. Hue-saturation-intensity color image analysis (HSI) was used to quantify the brown immunoperoxidase reaction product present on the bronchial epithelium. There was an increased expression of both IL-1beta and IL-1ra in the asthmatic bronchial epithelium, p < 0.0002 and p < 0.0001, respectively. Additionally, the numbers of macrophages, of IL-1beta producing cells, and the percentage of macrophages producing IL-1beta were significantly increased in the asthmatic submucosa (p < 0.004, p < 0.002, and p < 0.008, respectively).