tbuckley/cabot-search huggingface dataset:
More use of private sector could cut NHS waiting lists
Authors: Richard Woodman
Journal: BMJ (1999)

Thousands of patients on long NHS waiting lists could be treated quickly in private hospitals if the two sectors collaborated instead of viewing each other with suspicion and barely suppressed hostility, according to a report from the free market Adam Smith Institute.

The report, by Nick Bosanquet, of Imperial College, London, said: “At present, there is underoccupation in private hospitals, with occupancy rates at 50% or less. The …
Successful treatment of refractory pruritic Fox-Fordyce disease with botulinum toxin type A
Authors: J. González-Ramos, M.L. Alonso-Pacheco, B. Goiburú-Chenú, A. Mayor-Ibarguren, P. Herranz-Pinto
Journal: British Journal of Dermatology (2015)

Journal Article Successful treatment of refractory pruritic Fox–Fordyce disease with botulinum toxin type A Get access J. González‐Ramos, J. González‐Ramos Department of Dermatology La Paz University Hospital Paseo La Castellana 261 Madrid CP: 28046 Spain Search for other works by this author on: Oxford Academic Google Scholar M.L. Alonso‐Pacheco, M.L. Alonso‐Pacheco Department of Dermatology La Paz University Hospital Paseo La Castellana 261 Madrid CP: 28046 Spain Search for other works by this author on: Oxford Academic Google Scholar B. Goiburú‐Chenú, B. Goiburú‐Chenú Department of Dermatopathology La Paz University Hospital Paseo La Castellana 261 Madrid CP: 28046 Spain Search for other works by this author on: Oxford Academic Google Scholar A. Mayor‐Ibarguren, A. Mayor‐Ibarguren Department of Dermatology La Paz University Hospital Paseo La Castellana 261 Madrid CP: 28046 Spain Search for other works by this author on: Oxford Academic Google Scholar P. Herranz‐Pinto P. Herranz‐Pinto Department of Dermatology La Paz University Hospital Paseo La Castellana 261 Madrid CP: 28046 Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 2, 1 February 2016, Pages 458–459, https://doi.org/10.1111/bjd.14180 Published: 01 February 2016
A novel association between YKL-40, a marker for structural lung disease, and short telomere length in 10-year old children with BPD
Authors: Ewa Henckel, Anna James, Jon Konradsson, Björn Nordlund, Christina Ebersjö, Eva Bergren Broström, Gunilla Hedlin, Kajsa Bohlin
Journal: European Respiratory Journal (2014)

Background  There is a lack of reliable biomarkers to predict future lung morbidity following bronchopulmonary dysplasia (BPD). Relative telomere length (RTL) is a biomarker for oxidative stress and the chitinase-like protein YKL-40 is a novel biomarker associated with airway remodeling and vascular smooth muscle proliferation, all of which may contribute to impaired lung function following BPD.  Aim  To investigate the relationship between RTL, YKL-40 and lung function in school age children with a history of BPD.  Methods  A cohort study of 10 year old children born preterm with BPD (n=29, mean gestational age 27 weeks) and control children (CON) born at term (n=28) with a history of asthma. All children performed lung function testing (dynamic and static spirometry). RTL was determined in whole blood by real-time PCR. Serum levels of YKL-40 was analyzed by ELISA.  Results  Serum YKL-40 was higher in BPD compared to CON, p=0.002. RTL was similar between groups, but in children with BPD there was a correlation between shorter RTL and higher levels of serum YKL-40 (r=0,47, p=0,01). Dynamic spirometry showed significantly lower values in BPD children, but lung function did not correlate to YKL-40 or RTL.  Conclusions  Short telomeres correlated to higher levels of YKL-40 suggesting a more severe structural lung disease may be associated with genetic alterations in children growing up with BPD. High levels of YKL-40 suggests an involvement of fibrosis in BPD and the correlation to RTL indicate that oxidative stress may play a part. This study indicate that YKL-40 and telomere length could be future biomarkers to predict the long-term consequences of BPD.
Probiotics and synbiotics: Effects on chronic asthma in mice
Authors: Seil Sagar, Aletta D. Kraneveld, Niki A. Georgiou, Johan Garssen, Gert Folkerts
Journal: European Respiratory Journal (2012)

BACKGROUND:  Asthma is a chronic inflammatory disorder of the airways characterized by structural changes of the airways which may contribute to airway obstruction and airway hyperresponsiveness. Modulation of the intestinal microbiota by probiotics and related products as a potential therapy for allergic diseases has been subject to investigation. Several murine models of asthma and clinical studies demonstrated beneficial effects of probiotics and synbiotics in asthma management. However, the effects on chronic symptoms of asthma have never been investigated in murine models.   METHODS:  mice were sensitized twice (day 1 and 12) with ovalbumin (OVA)-imject alum and challenged from day 17 till 23 daily with OVA. From day 24 till day 56, the animals were challenged with OVA 3 times a week and on the same days the animals were treated with either control solution or glucocorticoids (GCS) budesonide by oropharyngeal aspiration or probiotics (Lactobacillus or Bifidobacterium) or synbiotics by oral gavage. Pulmonary function, total and differential leukocyte counts in bronchoalveolar lavage were determined and the lung tissues were isolated to study airway remodeling.   RESULTS:  Treatment with probiotics or GCS significantly inhibited the OVA-induced increase in basal airway resistance and hyperresponsiveness. Probiotics, synbiotics and GCS significantly reduced pulmonary leukocytes infiltration by 50% especially eosinophilia. Neutrophilia in the airways was reduced by GCS and probiotics. Effects on airway remodelling are in process.   CONCLUSION:  The probiotics and synbiotic used in this study seem to be as potent as GCS in reducing cell infiltration in mice with chronic asthma.
Alpha-melanocyte stimulating hormone potentially inhibits basophil activation, indicating a novel function of this neuropeptide in airway allergy
Authors: Ulrike Raap, Manuela Gehring, Thomas Luger, Alexander Kapp, Markus Böhm
Journal: European Respiratory Journal (2011)

Background:  It is well established that basophils play an important role in the initiation and control of airway allergy with potent effector functions during allergic responses. Using a mice model we could show that the neuropeptide alpha-melanocyte stimulating hormone (a-MSH) inhibits allergic airway inflammation. Thus we wanted to assess, whether basophils functionally respond to a-MSH in patients with upper airway allergy.   Methods:  Human basophils of patients with allergic rhinitis to grass pollen only and nonatopic controls were purified with magnetic beads with a purity of 98-100%. Expression of Melanocortin-Receptor 1 (MC-1R) was analysed by FACS, RT-PCR and Western immunoblotting. Activation of basophils was studied by calcium 2+ mobilization assay and CD63 surface expression using the basophil activation test, release of cytokines was assessed with ELISA.   Results:  Human peripheral blood basophils expressed MC-1Rs at protein and mRNA level. The MC-1R was functionally active in isolated basophils as shown by α-MSH-mediated intracellular increase of calcium 2+ . α-MSH significantly inhibited anti-IgE, fMLP or PMA induced release of IL-4 and IL-6 (p   Conclusion:  Our data show that a-MSH inhibits the allergic immune response in human basophils, presenting a novel and promising anti-inflammatory function of this peptide in allergic airway diseases.
Abstract 1886: Highly sensitive detection of circulating tumor DNA in plasma as a biomarker of colorectal cancer
Authors: Matthew Wiggin, Jaryn Perkins, Laura Mai, Valentina Vysotskaia, Andre Marziali
Journal: Cancer Research (2014)

Abstract Circulating tumor DNA (ctDNA) from the blood of cancer patients is a promising biomarker of certain types of colorectal cancer, with potential use in screening, treatment selection, therapy response monitoring, minimal residual disease detection, and surveillance. We present results demonstrating that the OnTarget ctDNA detection assay can be used as an indicator of the presence of genomic variants associated with colorectal cancer in patients prior to treatment. The study includes three cohorts of individuals: young normal controls, age-matched normal controls, and colorectal cancer patients whose blood was drawn prior to treatment or surgery, and whose diagnosis confirms the presence of a colorectal tumor. Tissue from the primary tumor biopsy was also collected and analyzed with the OnTarget assay. Using Boreal Genomics' OnTarget 46-mutation panel, we find high correlation between the tumor mutational profile and the plasma mutation profile even for early stage patients demonstrating high sensitivity (88% plasma-tissue concordance to date) of the assay. By applying the same assay in the normal population we demonstrate extremely low false positive rates, highlighting the potential of the assay as a tool for therapy monitoring, surveillance, or screening. The OnTarget assay is capable of single molecule sensitivity, specificity to ≤0.01% mutation abundance versus wild-type, and multiplexing of over 100 mutations in a single test from a single plasma sample. The OnTarget technology employs a combination of Next Generation DNA Sequencing and a proprietary target selection process that removes wild-type DNA prior to amplification to greatly improve signal to noise and reduce the error rate of sequencing. We present an overview of the technology and results from an ongoing study to demonstrate the potential clinical utility of ctDNA as an effective biomarker to guide management of colorectal cancer. Citation Format: Matthew Wiggin, Jaryn Perkins, Laura Mai, Valentina Vysotskaia, Andre Marziali. Highly sensitive detection of circulating tumor DNA in plasma as a biomarker of colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1886. doi:10.1158/1538-7445.AM2014-1886
Interstitial lung diseases in children in a tertiary hospital in North Italy
Authors: Deborah Snijders, Serena Calgaro, Ilaria Bertozzi, Silvia Quartesan, Ivana Kozuh, Francesca Lunardi, Angelo Barbato
Journal: European Respiratory Journal (2013)

Interstitial lung diseases (ILDs) in children are an heterogeneous group of lung disease with very different pathophysiology. In most European countries rare orphan diseases such as pediatric interstitial lung diseases (ILDs) are still underdiagnosed.  Objective: To investigate/ describe pediatric ILDs in a tertiary university hospital in North Italy.  Methods: we included 18 children admitted to the Pediatric Department of the Padova University Hospital from 2003 until 2012 with a diagnosis of ILD. Children were identified retrospectively through clinical charts and clinical, radiological, functional, pathological, biological and genetic data were collected.  Results: Data were available for x children presenting with ILD.  Median age at diagnosis was 5.5 years [1-16 years], and the sex ratio was 0.5 male/female.  Radiologic, laboratory histology and genetics led to the following diagnosis: Bronchiolitis obliterans organizing pneumonia (BOOP), surfactant protein B mutation and viral induced interstitial lung disease were the most common diagnoses. At high resolution CT-scan, 14/18 children showed in 16 % a Honey comb pattern, in 16 %, a reticular picture, in 16% a nodular picture, and in 52% ground glass opacity.  Chronic cough and wheezing episode were the most common symptoms reported.  Conclusion: In Italy, pediatric ILD is still under estimated. A national database, such as the German, UK or France registry, and national guidelines for diagnosis and possible therapies are necessary to allow physicians and patients to have a more adequate diagnosis and follow-up.
Male gonadal function after chemotherapy for solid tumors in childhood.
Authors: F Aubier, F Flamant, R Brauner, J M Caillaud, J M Chaussain, J Lemerle
Journal: Journal of Clinical Oncology (1989)

The testicular function of 30 adolescent or adult males having undergone polychemotherapy in childhood was assessed by means of a spermogram or testicular biopsy. At the time of examination, the patients were pubertal and had completed chemotherapy between 1 and 20 years previously (mean, 9 years). All patients who were prepubertal or intrapubertal at the time of treatment achieved normal puberty with normal growth. Twenty patients presented with azoospermia and/or severe disturbances in the germinal line on biopsy. This series confirms the toxicity of alkylating agents, in particular that of the mechlorethamine, vincristine, procarbazine, and prednisone combination (MOPP) and that of cyclophosphamide (CPM). However, dactinomycin, vinblastine, and vincristine did not appear to have a toxic effect on spermatogenesis. The prepubertal state did not protect the gonads of 19 patients who were prepubertal at diagnosis: 12 are now sterile as a result of the treatment. An increase in basal follicle-stimulating hormone (FSH) levels gives a good indication of testicular damage, although normal levels do not rule out the possibility of azoospermia.
High-frequency oscillatory ventilation – A safe procedure for COPD patients?
Authors: Sven Pulletz, Ute Achtzehn, Andreas Pechmann, Ernst Schmidt, Michael Quintel, Norbert Weiler, Inéz Frerichs
Journal: European Respiratory Journal (2011)

Introduction:  High-frequency oscillatory ventilation (HFOV) is an alternative type of mechanical ventilation. HFOV is usually considered as not indicated in patients with obstructive lung disease because of the theoretical risk of air trapping and hyperinflation.   Aim and objectives:  Intention of this study was to establish if HFOV can safely be applied in patients with exacerbation of chronic obstructive pulmonary disease and hypercapnic respiratory failure.   Methods:  Ten patients with acutely exacerbated chronic obstructive pulmonary disease (GOLD stages II-IV) requiring intensive care treatment who failed on non-invasive ventilation were studied. After initial conventional mechanical ventilation (CMV) of less than 72 hours all patients were transferred to HFOV for 24 hours and then back to CMV.   Main results:  Regional lung aeration and ventilation were assessed by electrical impedance tomography. HFOV was tolerated well, no adverse effects were observed. Effective CO2 elimination and oxygenation were achieved. Arterial partial pressure of CO2 was 52±13 mmHg (mean ± SD) during CMV before transition to HFOV and 47±9 mmHg by the end of the 24-hour period of HFOV. Ventilation was more homogeneously distributed during HFOV than during initial CMV. No signs of hyperinflation induced by HFOV were identified. Higher respiratory system compliance and tidal volume were found during CMV after 24 hours of HFOV than before.   Conclusions:  Contrary to present recommendations on the use of HFOV in adult patients our pilot study indicates that this type of mechanical ventilation can safely be used in patients with chronic obstructive lung disease.
Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance.
Authors: G Schlimok, I Funke, B Bock, B Schweiberer, J Witte, G Riethmüller
Journal: Journal of Clinical Oncology (1990)

A monoclonal antibody (mAb) directed against the cytokeratin (CK) polypeptide no. 18 specifically expressed in cells derived from simple epithelia was used to detect epithelial tumor cells in bone marrow aspirates. Of 156 patients with colorectal carcinoma, 42 presented with cells at the time of primary surgery. The incidence of positive findings varied considerably with the size and the localization of the primary tumor, the involvement of regional lymph nodes, and the presence of clinically manifest metastases. Applying a sensitive double-staining procedure, we could demonstrate that epithelial cells in bone marrow showed a heterogeneic expression of receptors for epidermal growth factor (EGF-R) and transferrin (Tf-R) as well as of the proliferation-associated Ki67 antigen. Also human leukocyte antigen (HLA) class I antigens differed widely in their expression on the CK-positive cells. Clinical follow-up studies on 85 patients showed a significantly higher relapse rate in patients presenting with CK-positive cells in their bone marrow at the time of primary surgery. Twenty-three patients were monitored for the presence or absence of CK-positive cells in bone marrow over time. The majority of monitored patients (18 of 23) exhibited a constant pattern of immunocytochemical findings during the time of observation. Thus, the technique may be useful in identifying high-risk patients as well as in monitoring adjuvant therapeutic trials.
Neutrophil dysfunction in respiratory infection: Impaired killing efficiency after successive phagocytic stimuli?
Authors: James Macfarlane, Marie-Helene Ruchaud-Sparagano, Jonathan Scott, David Bulmer, Anjam Khan, John Simpson
Journal: European Respiratory Journal (2013)

Background  Neutrophils often fail to clear a single infection source such as pneumonia, but the effect of successive infective insults is unknown.   Aim  To investigate our hypothesis that neutrophil exposure to a single phagocytic stimulus or ‘primary meal’ impairs subsequent killing of a ‘secondary meal’ of live bacteria.   Methods  Healthy volunteer neutrophils were exposed to different primary stimuli: killed Staphylococcus aureus (SA), zymosan, live SA or Pseudomonas aeruginosa (PA), followed by a secondary stimulus of either live SA or PA. Phagocytosis and neutrophil viability were measured using flow cytometry; bacterial killing by serial dilution, plating and colony counting.   Results  Exposure to killed SA (at multiplicity of infection, MOI≥20:1) or zymosan (MOI≥4:1) impaired subsequent killing of both live SA and PA (both MOI∼10:1) in suspension (p   Conclusions  Our study supports our hypothesis that neutrophils lose killing efficiency after a single exposure to a phagocytic stimulus, in part due to neutrophil cell death. Potential additional factors, including competition for phagocytic receptors, excessive degranulation and oxidative burst, require further study.
Nonhormonal Management of Hot Flashes for Women on Risk Reduction Therapy
Authors: Kostandinos Sideras, Charles L. Loprinzi
Journal: Journal of the National Comprehensive Cancer Network (2010)

Hot flashes are very common in women in menopause and can have a detrimental effect on quality of life. Women on risk reduction therapy are particularly prone because treatments, such as tamoxifen, raloxifene, or oophorectomy, have the potential to exacerbate these symptoms. Hormonal treatments, despite the fact that they represent the most effective therapies, are not used for the treatment of hot flashes in these women because of concerns that they may increase the risk for breast cancer. As a result, several nonhormonal therapies have been tested in randomized placebo-controlled trials and shown to be effective, such as paroxetine, venlafaxine, desvenlafaxine, fluoxetine, citalopram, gabapentin, and pregabalin. In addition, several nonpharmacologic therapies have been tested with various successes. An additional consideration is how some of those drugs, especially fluoxetine and paroxetine, interact with the metabolism of tamoxifen. This article discusses these issues, and provides some recommendations regarding use of nonhormonal therapies for treating hot flashes in women on risk reduction therapy, with an emphasis on pharmacogenomic considerations.
Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities.
Authors: P W Pisters, D H Leung, J Woodruff, W Shi, M F Brennan
Journal: Journal of Clinical Oncology (1996)

PURPOSE To identify specific independent adverse clinicopathologic factors for event-free survival in a cohort of consecutively treated patients with extremity soft tissue sarcomas. PATIENTS AND METHODS Prospectively collected data from a population of 1,041 adult patients with localized (American Joint Committee on Cancer [AJCC] stage IA to IIIB) extremity soft tissue sarcomas were analyzed. Patients were treated at a single institution between 1982 and 1994. Patient, tumor, and pathologic factors were analyzed by univariate and multivariate techniques to identify independent prognostic factors for the end points of local recurrence, distant recurrence, disease-specific survival, and post-metastasis survival. RESULTS The 5-year survival rate for this cohort of patients was 76%, with a median follow-up time of 3.95 years. Significant independent adverse prognostic factors for local recurrence were age greater than 50 years, recurrent disease at presentation, microscopically positive surgical margins, and the histologic subtypes fibrosarcoma and malignant peripheral-nerve tumor. For distant recurrence, intermediate tumor size, high histologic grade, deep location, recurrent disease at presentation, leiomyosarcoma, and nonliposarcoma histology were independent adverse prognostic factors. For disease-specific survival, large tumor size, high grade, deep location, recurrent disease at presentation, the histologic subtypes leiomyosarcoma and malignant peripheral-nerve tumor, microscopically positive surgical margins, and lower extremity site were adverse factors. For post-metastasis survival, only large tumor size ( &gt; 10 cm) was an adverse prognostic factor. CONCLUSION The independent adverse prognostic factors for distant recurrence and disease specific survival differ from those identified for subsequent local recurrence. Patients with microscopically positive surgical margins or patients who present with locally recurrent disease are at increased risk for subsequent local recurrence and tumor-related mortality. Specific histopathologic subtypes are associated with increased risks for local failure and tumor-related mortality.
Is quantitative HRCT related with diagnostic yield of fiberoptic bronchoscopy in sarcoidosis
Authors: Serpil Akten, Nurdan Kokturk, Gonca Erbas, Bulent Celik, Haluk Tuktas
Journal: European Respiratory Journal (2011)

This study aimed to evaluate the diagnostic yield of fiberoptic bronchoscopic (FOB) modalities and its relation with quantitative findings with high resolution computerized tomography (HRCT). 64 patients that consists of 19 males and 45 females with the mean age of 43 diagnosed with sarcoidosis with complete records of HRCT were retrospectively recruited for a time period of Feb 2000 to Jan 2010. HRCT scans were retrospectively assessed in random order by an experienced observer without knowledge of the bronchoscopy result or lung function tests. The diagnostic yield of transbronchial biopsy (TBB) was% 43.6. Although it did not reach statistical significance, the lobar HRCT score in the sampled lobe was associated with a positive TBB result. Bronchial mucosa appearance was significantly related with positive mucosal biopsy (MB). The diagnostic yield of MB was% 24.5 in general patient population however in patients with abnormal mucosa this rate was increased up to% 84.6 (p=0.000). The diagnostic yield of transbronchial needle aspiration (TBNA) was 25.7%. Right hilar and subcarinal lymph nodes were the most diagnostic sites. The diagnostic yield was significantly higher in patients who had larger size of lymph nodes (p=0.007). Quantitavie HRCT score did not correlate with the findings of MB and TBNA.  Quantitave HRCT did not cause remarkable impact on the results of diagnostical work up of FOB.