tbuckley/cabot-search huggingface dataset:
Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.
Authors: F Locatelli, C Niemeyer, E Angelucci, C Bender-Götze, S Burdach, W Ebell, W Friedrich, H Hasle, J Hermann, N Jacobsen, T Klingebiel, B Kremens, G Mann, A Pession, C Peters, H J Schmid, J Stary, M Suttorp, C Uderzo, E T van't Veer-Korthof, J Vossen, M Zecca, M Zimmermann
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P &lt; .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P &lt; .01). CONCLUSION Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.
Six vs twelve cycles for complete responders to chemotherapy in small cell lung cancer: definitive results of a randomized clinical trial. The "Petites Cellules" Group
Authors: B Lebeau, C Chastang, P Allard, J Migueres, F Boita, D Fichet
Journal: European Respiratory Journal (1992)

Of 320 patients with small cell lung cancer (SCLC) entered into a clinical trial of chemotherapy between January 1983 and September 1985, 106 patients achieved a complete response. The induction chemotherapy used was lomustine 60 mg.m-2 p.o., cyclophosphamide 1 g.m-2 i.v., doxorubicin 45 mg.m-2 i.v. and etoposide 150 mg.m-2 i.v., every four weeks. Lomustine was only given for the first three cycles. Seventy nine of the 106 patients still in complete response after six chemotherapy cycles were subsequently randomized to receive either six more cycles or no more treatment until relapse. In this group of 79 patients, a difference was shown from the time of inclusion between the 51 patients with limited disease and the 28 patients with disseminated disease, with overall median survivals of 395 and 165 days, respectively, (p = 0.0002). No difference was shown between the two treatment groups: the median survival was 332 days from the time of second randomization with a two year survival rate of 28% for the patients randomized to receive six more cycles and 246 days and 22% for those randomized to receive no more treatment (add 147 days to obtain overall median survival). Continuing chemotherapy for more than six cycles to patients in complete response did not improve survival.
Monitoring Response to Tyrosine Kinase Inhibitor Therapy, Mutational Analysis, and New Treatment Options in Chronic Myelogenous Leukemia
Authors: Jerald P. Radich
Journal: Journal of the National Comprehensive Cancer Network (2013)

Unlike in other leukemias, survival rates have climbed dramatically in early-phase chronic myelogenous leukemia (CML). This improvement in long-term prognosis is primarily the result of the tyrosine kinase inhibitor (TKI) imatinib and its second-generation cousins nilotinib and dasatinib. In his presentation at the NCCN 18th Annual Conference, Dr. Jerald P. Radich reviewed the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommendations for monitoring response to treatment with the TKIs, which center on complete cytogenetic response, and the role of mutational analysis for guiding treatment decisions in the setting of imatinib resistance. He also offered a brief mention of 2 new agents recently approved for resistant CML--ponatinib and bosutinib.
Naevus spilus-type congenital melanocytic naevus associated with a novel<i>NRAS</i>codon 61 mutation
Authors: S. Krengel, D.S. Widmer, K. Kerl, M.P. Levesque, C. Schiestl, L. Weibel
Journal: British Journal of Dermatology (2015)

We recently described 17 patients with a new subtype of congenital melanocytic naevi (CMN), designated as naevus spilus-type  (1). The affected patients present with a large cafe-au-lait (CAL) background macule and dozens of superimposed small and medium-sized CMN. Here we report an additional case with a novel NRAS mutation (Q61L). CMN are categorized by their largest diameter (projected adult size, PAS) (2). Small CMN (SCMN, <1.5 cm PAS) and medium-sized CMN (MCMN, 1.5 - 20 cm PAS) represent rather common, solitary, slightly thickened plaques with prominent terminal hairs. This article is protected by copyright. All rights reserved.
Vocal cord dysfunction in adolescents
Authors: Johannes Schulze, Sarah Weber, Martin Rosewich, Olaf Eickmeier, Markus Rose, Stefan Zielen
Journal: European Respiratory Journal (2011)

Background:  Vocal cord dysfunction (VCD) often presents with dramatic and abrupt symptoms. To diagnose VCD, visualisation by direct laryngoscopy is required and usually a specific method to provoke VCD is needed.   Objectives:  Adolescents with clinical suspicion of VCD were invited to participate. The first objective was to diagnose VCD, second objectives were changes of pulmonary function test (PFT) and predictors of VCD before and after methacholine challenge test (MCT).   Methods:  After an initial PFT, a direct laryngoscopy was performed. This was followed by the MCT; the endpoint was the methacholine dose causing a 20% drop of the forced expiratory volume in one second (PD 20 FEV 1 ). After that a second laryngoscopy was conducted. PFT changes before and after MCT were compared with the data of 14 healthy controls (HC).   Results:  Thirty-five patients (8-19 years) were investigated. Three failed to have a significant reaction to methacholine and three showed anatomical alterations. Of the remaining 29 patients, 14 had VCD and 15 had bronchial hyperresponsiveness (non-VCD). PD 20 FEV 1  methacholine was significant lower in VCD compared with non-VCD (VCD 0.24 mg ± 0.4, non-VCD 0.73 mg ± 0.73, p= 0.0006). VCD patients showed significantly lower PFT parameters after MCT; FEV 1 : VCD 58.5% ± 20.1, non-VCD 77.8% ± 18.4, and HC 98.7% ± 16.6 (p   Conclusions:  The combination of MCT and laryngoscopy may be able to differentiate between VCD and non-VCD patients. VCD patients showed a positive reaction at lower methacholine doses and had a higher airway obstruction. PFT and MCT do not replace direct laryngoscopy in the diagnosis of VCD in adolescents.
India’s AIDS programmes shrink after government cuts spending
Authors: Cheryl Travasso
Journal: BMJ (2015)

Cuts in the government’s social spending are affecting India’s fight against AIDS, resulting in staff losing their jobs and several programmes being limited, Reuters has reported.

India’s AIDS programmes have been facing obstacles such as drug shortages for over a year because of government delays and funding cuts. Many staff have not received their salaries. Up to a quarter of those working on prevention programmes in some states …
Underweight as a risk factor for respiratory death in the Whitehall cohort study: exploring reverse causality using a 45-year follow-up
Authors: Mika Kivimäki, Martin J Shipley, Joshua A Bell, Eric J Brunner, G David Batty, Archana Singh-Manoux
Journal: Thorax (2015)

Underweight adults have higher rates of respiratory death than the normal weight but it is unclear whether this association is causal or reflects illness-induced weight loss (reverse causality). Evidence from a 45-year follow-up of underweight participants for respiratory mortality in the Whitehall study (N=18 823; 2139 respiratory deaths) suggests that excess risk among the underweight is attributable to reverse causality. The age-adjusted and smoking-adjusted risk was 1.55-fold (95% CI 1.32 to 1.83) higher among underweight compared with normal weight participants, but attenuated in a stepwise manner to 1.14 (95% CI 0.76 to 1.71) after serial exclusions of deaths during the first 5-35 years of follow-up (P(trend)<0.001).
Use of cannabis and primary lung cancer
Authors: Wiam El Khattabi, Loubna Qassimi, Hicham Afif, Abdelaziz Aichane
Journal: European Respiratory Journal (2014)

Bronchopulmonary cancers rank first in terms of cancer mortality. Tobacco smoke is the major risk factor. The oncological risk use of cannabis has been studied little. Epidemiological data remain fragmented. The toxicity of cannabis is greatly increased when mixed with the tobacco. This is a retrospective study of patients with primary lung cancer spread over a period of one yea from January to December 2012. 48 700 patients (7%) smoked cannabis. All were male . The average age was 52 years. Consumption of smoked tobacco or snuff and cannabis accounted for 5 %, the cannabis was only 2%. Functional signs were dominated by cough ( 70%) and chest pain ( 68%). Physical signs of altering the general condition (66%) and clubbing (26 %). Radiological opacities represented 100 %. The diagnosis was most often by bronchoscopy (65%). Bronchial carcinoma was the most common ( 34 %) followed by squamous cell carcinoma found in 10 % of cases. According to the TNM classification , 65% of patients were classified as stage III and 32% were classified stadeIV . Seventy percent of patients had obstructive ventilatory disorders.The treatment was surgical in 25% of cases, chemotherapy was indicated in 33% of cases and 35 % of patients were put under symptomatic treatment.
Implementation of BT in a centre in Barcelona: First results
Authors: Ana Mª Muñoz Fernández, Virginia Pajares Ruiz, Mª Carmen Puzo Ardanuy, Mª Angels Gil de Bernabé, Oscar Amor Carro, David Ramos-Barbón, Vicente Plaza Moral, Alfons Torrego Fernández
Journal: European Respiratory Journal (2014)

Background:Bronchial thermoplasty (BT) is a novel treatment for symptomatic and uncontrolled severe asthma patients despite medical treatment (step 4-5 GINA).  Objective:Describe the clinical response of first asthma patients treated with BT in our centre.  Methods:Uncontrolled (ACT  Results:5 patients (80% W, 49±20yr) were treated with BT (3/5 step 5 GINA; 2/5 step 4). All patients suffered transitory worsening of their respiratory symptoms; 1/5 segmental collapse of the treated lobe. 4/5 improved scores in ACT and miniAQLQ.  In 2 it was reduced medical treatment. No severe adverse events attributable to BT were observed at follow-up. Clinical results are shown.  Conclusions:BT is a new treatment for severe asthma with a variable grade of response. Secondary effects after each bronchoscopic session are mild-moderate.
MADD-4/Punctin and Neurexin Organize C. elegans GABAergic Postsynapses through Neuroligin
Authors: Géraldine S. Maro, Shangbang Gao, Agnieszka M. Olechwier, Wesley L. Hung, Michael Liu, Engin Özkan, Mei Zhen, Kang Shen
Journal: Neuron (2015)
The relationships between hyperinflation during exercise and symptoms in adults with cystic fibrosis
Authors: Daniela Savi, Mattia Internullo, Gabriele Valli, Paolo Marinelli, Serenella Bertasi, Matilde Rolla, Riccardo Valerio De Biase, Salvatore Cucchiara, Paolo Palange
Journal: European Respiratory Journal (2012)

Exercise tolerance is reduced in patients with Cystic Fibrosis (CF). Ventilatory limitation, peripheral skeletal muscle weakness and poor nutritional status may contribute to exercise intolerance .  The mechanisms of exertional dyspnoea are less understood, but it seems that dynamic hyperinflation may play a role .  So we wonted to investigate the role of exercise dynamic hyperinflation on breathlessness (DYS) and leg fatigue (LEG) in CF patients. 17 stable CF patients (32±8SD yrs; FEV 1  2.66±0.7 l; 68±16% pred; IC 3.4±1.0 l), during constant load cycle ergometry at 80% V9O 2  max were studied. Intensity of breathlessness and leg fatigue, by Borg scale, and IC were recorded every 2 minutes. The individual slopes of the change in IC vs DYS and IC vs LEG were also computed.  Results.  In most patients we did not observe a correlation between changes in IC during exercise vs either DYS (r 2  =0.30±0.28) or vs LEG (r 2  =0.35±0.26). In addition, resting IC did not predict the rate of change in DYS or LEG. Conversely, we found a close relathionship between the rate of increase in DYS per unit change in IC and the rate of increase in LEG per unit change in IC (r 2 =0.85 p LIM  (r 2 =0.44 p LIM .  Conclusions.  CF patients show considerable variation in the rate at which symptoms develop during exercise, suggesting that different physiological processes underline these symptoms. Baseline IC strongly predict the duration of the endurance tolerance, while the degree of resting hyperinflation is poorly predictive of exercise induced changes in DYS and LEG.
Abstract 122: A Coordinated Pre-Hospital Initiated Thrombolytic Strategy Coupled With Urgent PCI Dramatically Reduces Time to Treatment for STEMI Patients.
Authors: James J McCarthy, David E Persse, Colin M Barker, H Anderson, Ali E Denktas, Stefano Sdringola, Troy Weirick, Mary T Vooletich, Bonnie K Richter, Richard W Smalling
Journal: Circulation (2010)
Factors predicting outcome of non-invasive ventilation (NIV) for acidotic hypercapnic respiratory failure (AHRF) from lung diseases other than COPD
Authors: Sarah Elgarf, Alice Turner, Ben Beauchamp, Rahul Mukherjee
Journal: European Respiratory Journal (2012)

Background : NIV is the treatment of choice for AHRF in acute exacerbation of COPD, neuromuscular and thoracic cage disorders, but its indications have widened in UK hospitals, particularly in patients with AHRF of any cause whose comorbidities preclude invasive ventilation - we sought to establish the predictors of outcome in non-COPD Lung and Airway patients with AHRF.   Methods : Cohort analysis of prospectively collected data on acute NIV for non-COPD Lung and Airway diseases with AHRF in a ward-based NIV unit over 5 years recording diagnoses, demographics, response to NIV at 4 hours and in-hospital deaths (univariate analyses as total numbers too low for logistic regression).   Results : NIV was used to treat 39 episodes of pneumonia, 25 of exacerbations of non-cystic fibrosis (CF) bronchiectasis, 15 of asthma and 3 of CF (in 38, 22, 11 and 3 individuals respectively); comprising 5.67% of all acute NIV episodes. All subgroups among non-COPD Lung and Airway patients receiving NIV for AHRF had impaired lung function with mean FEV1 of 34%, 41%, 43% and 18% respectively; 2 from the pneumonia group were intubated and 12 died during the admission - significantly more than the other subgroups (p=0.049); initial pH significantly predicted death in non-CF bronchiectasis (p=0.007).   Conclusions : In conditions other than COPD exacerbations, neuromuscular and thoracic cage disorders, acute NIV is used little in our unit (5.67%); when used, the predictors of death are broadly similar to COPD in non-CF bronchiectasis, but less predictable in the other groups, pneumonias being associated with higher co-morbidity and in-hospital mortality.
Rescuing the physician-scientist workforce: the time for action is now
Authors: Dianna M. Milewicz, Robin G. Lorenz, Terence S. Dermody, Lawrence F. Brass
Journal: Journal of Clinical Investigation (2015)

The 2014 NIH Physician-Scientist Workforce (PSW) Working Group report identified distressing trends among the small proportion of physicians who consider research to be their primary occupation. If unchecked, these trends will lead to a steep decline in the size of the workforce. They include high rates of attrition among young investigators, failure to maintain a robust and diverse pipeline, and a marked increase in the average age of physician-scientists, as older investigators have chosen to continue working and too few younger investigators have entered the workforce to replace them when they eventually retire. While the policy debates continue, here we propose four actions that can be implemented now. These include applying lessons from the MD-PhD training experience to postgraduate training, shortening the time to independence by at least 5 years, achieving greater diversity and numbers in training programs, and establishing Physician-Scientist Career Development offices at medical centers and universities. Rather than waiting for the federal government to solve our problems, we urge the academic community to address these goals by partnering with the NIH and national clinical specialty and medical organizations.
Effect of increased compulsion on readmission to hospital or disengagement from community services for patients with psychosis: follow-up of a cohort from the OCTET trial
Authors: Tom Burns, Ksenija Yeeles, Constantinos Koshiaris, Maria Vazquez-Montes, Andrew Molodynski, Stephen Puntis, Francis Vergunst, Alexandra Forrest, Amy Mitchell, Kiki Burns, Jorun Rugkåsa
Journal: The Lancet Psychiatry (2015)
Clinical and Immune Responses in Resected Colon Cancer Patients Treated With Anti-Idiotype Monoclonal Antibody Vaccine That Mimics the Carcinoembryonic Antigen
Authors: Kenneth A. Foon, William J. John, Mala Chakraborty, Ruma Das, April Teitelbaum, Juanita Garrison, Oscar Kashala, Sunil K. Chatterjee, Malaya Bhattacharya-Chatterjee
Journal: Journal of Clinical Oncology (1999)

We generated an anti-idiotype antibody, designated CeaVac, that is an internal image of the carcinoembryonic antigen (CEA). We previously demonstrated that the majority of patients with advanced colorectal cancer generate specific anti-CEA responses. The purpose of the current study was to treat patients with surgically resected colon cancer with CeaVac to determine the immune response and clinical outcome to treatment with vaccine. We also compared the immune responses between patients treated with fluorouracil (5-FU) chemotherapy regimens plus vaccine versus vaccine alone.Thirty-two patients with resected Dukes' B, C, and D, and incompletely resected Dukes' D disease were treated with 2 mg of CeaVac every other week for four injections and then monthly until tumor recurrence or progression. Fourteen patients were treated concurrently with 5-FU chemotherapy regimens.All 32 patients entered onto this trial generated high-titer immunoglobulin G and T-cell proliferative immune responses against CEA. The 5-FU regimens did not have a qualitative or quantitative effect on the immune response. Three of 15 patients with Dukes' B and C disease progressed at 19, 24, and 35 months. Seven of eight patients with completely resected Dukes' D disease remained on study from 12 to 33 months; one patient with resected Dukes' D disease relapsed at 9 months. One patient with incompletely resected Dukes' D disease remained on study at 14 months without evidence of progression; eight experienced disease progression at 6 to 31 months.CeaVac consistently generated a potent anti-CEA humoral and cellular immune response in all 32 patients entered onto this trial. A number of very high-risk patients continue on study. 5-FU regimens, which are the standard of care for patients with Dukes' C disease, did not affect the immune response. These data warrant a phase III trial for patients with resected colon cancer.
Influence of glutoxim and its derivatives on the growth of mycobacterium tuberculosis (Mtb)
Authors: Olga Manicheva, Natalia Solovyeva, Marine Dogonadze, Natalia Melnikova, Vyacheslav Zhuravlev, Anna Zmaznova
Journal: European Respiratory Journal (2014)

Background.  Study of the ability of immunomodulators to potentiate the effect of isoniazide (I) on Mtb isoniazid-resistant strains is a promising line of research in conditions of spreading of the of multidrug-resistant Mtb.   Aim  is to study isoniazid potentiating activity of commercial immunomodulatory drug Glutoxim (G) and  to determine the minimum inhibitory concentration (MIC) of its derivatives (GD).   Design . It were investigated H37Rv and two clinical isoniazid-resistant Mtb isolates with mutations in the genes  katG ,  ahpC  and  inhA  from our collection of clinical Mtb strains. Modified checkerboard method” and microdilution method with Middlebrook 7H9 with OADC, Thiazolyl blue visualization and photometric (630 nm) growth registration were used to evaluate MICs of I, G, their combinations and GDs .   Results . G had no effect on the Mtb growth in all tests series. I MIC for H37Rv was 0.062 μg/ml, G(50-3.1 μg/ml) had reduced it to 0.031 μg/ml. Only salt V-007-8 of ten GDs has lowered MIC in twofold, activity of the other GDs did not differ from the isoniazid. Mtb strain with complex of mutations in genes  katG  (Ser315 → Thr, IIe335 → Va),  ahpC _T10 had high level of resistance to isoniazid (23.3 μg/ml), addition of G (50-3,1 μg/ml) has lowered MIC in twofold, salt V-007-8 has decreased MIC in 1.75 time. I MIC for the strain with mutation of inhA-T15 was 0,33-0,5 μg/ml, addition of G enhanced the I activity in 1.6 times. MIC of salt V-007-8 was less than the I MIC in 2 times.   Conclusion.  G has potentiated the activity of I in 1.6-2 times, MIC of V-007-8 was less than the I MIC in 1.75-2.0 times both sensitive strain H37Rv, and clinical Mtb isolates with mutations in the genes  katG, ahpC  and  inhA.
An Affordable Care Act at Year 5
Authors: Timothy Stoltzfus Jost
Journal: JAMA (2015)

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