tbuckley/cabot-search huggingface dataset:
Medical Research Council leukaemia trial--UKALL V: an attempt to reduce the immunosuppressive effects of therapy in childhood acute lymphoblastic leukemia. Report to the Council by the Working Party on Leukaemia in Childhood.
Authors: J M Chessells, J Durrant, R M Hardy, S Richards
Journal: Journal of Clinical Oncology (1986)

The Medical Research Council UKALL V trial for children with standard-risk acute lymphoblastic leukemia (ALL) (aged 1 to 14 years, leucocyte count less than 20 X 10(9)/L) was designed to determine whether the immunosuppressive effects of treatment could be reduced without sacrifice of antileukemic effect by alterations in the type of continuing therapy or in fractionation of cranial irradiation. Remission was achieved in 496 children on standard induction therapy, and 309 children received 24 Gy of cranial irradiation in ten to 16 fractions over 21 days, and 174 received 21 Gy in five to nine fractions over 21 days. The type of radiotherapy administered had no influence on relapse at any site or rate of death in remission. All 496 children were randomized to receive chemotherapy for 2 or 3 years with 6-mercaptopurine and methotrexate either as a continuous (group C) or a semicontinuous (group G) regimen or as a five-day pulse every 3 weeks (group I). All groups also received vincristine and prednisolone every 6 weeks. With a minimum follow-up of almost 7 years, patients in group I had significantly fewer remission deaths (P = .025) but a much higher rate of bone marrow relapse than those in group C or G (P = .002). There was an overall benefit for 3 years of chemotherapy compared with 2 years, which in contrast to previous studies, was more apparent in girls and in patients in groups C and G. Testicular relapse occurred in 37 boys, including 19 patients off therapy, with a previously negative biopsy. The overall results confirmed the prognostic significance of initial leucocyte count, even among these standard-risk patients, while girls had a superior rate of disease-free survival, but not of hematologic remission. It is concluded that, even among standard-risk patients, the prognosis is influenced by the height of the initial leukocyte count. While alterations in the fractionation of cranial irradiation do not appear to have influenced disease-free survival, intermittent continuing chemotherapy, although less immunosuppressive, is less effective than conventional continuous therapy in the treatment of ALL. In this study, 3 years of chemotherapy appeared superior to 2 years.
Exploratory Phase Ii Trial Assessing Relevance of in Vitro Chemosensitivity Test As a Predictor of Survival in Gastric Cancer Undergoing Adjuvant Chemotherapy (Jaccro-Gc04)
Authors: H. Yamaue, T. Kubota, N. Tanigawa, S. Ohyama, S. Sakuramoto, T. Inada, Y. Kitagawa, T. Ochiai, M. Terashima, M. Gotoh, Y. Yasuda, A. Hara, H. Kato, J. Matsuyama, Y. Kodera, A. Nashimoto, T. Yamaguchi, M. Takeuchi, M. Fujii, T. Nakajima
Journal: Annals of Oncology (2014)
Asthma and atopy: How much is it really attributable? About a representative population of Tunis
Authors: Ines Saada, Jouda Cherif, Sonia Toujani, Hafedh Zakhama, Yacine Ouahchi, Nozha Ben Salah, Bechir Louzir, Jalloul Daghfous, Nedia Mehiri, Majed Beji
Journal: European Respiratory Journal (2012)

Introduction: In recent decades it has become routine to describe asthma as an atopic disease. We carried out this study to evaluate the prevalence of asthma and assess the association of atopy with asthma in individuals and in population.

Method: A cross-sectional survey, single pass, representative of the general population was carried out in subjects aged from 2 to 50 years. Informed consent was obtained. Prevalence was determinate through questionnaires, validated and used in international surveys, corresponding to the asthma screening and lung function test. Definition of atopy was based on clinical symptoms of rhinitis and allergy skin. Statistical analysis was performed using SPSS 18.0.

Results: The study included 4470 subjects. There was 40.2% male and 59.8% female. Current asthma prevalence was 6.8% in adults and 5.9% in children. Lung function test showed reversibility in 20%. The proportion of asthma cases that are “attributable” to atopy (defined as rhinitis and allergy skin) was estimated by the “population attributable risk”. About 53.5% of children and 43.8% of adults with asthma have suffered from rhinitis (OR=3.8, p<0,001). Positive correlation was also found between asthma and skin allergy: (15.8% versus 5.8% OR=3.5, p<0.001). There was no significant difference between adult and children in neither between male nor female.

Conclusions: There is evidence of an association of the prevalence of atopy with the prevalence of asthma. Higher estimation can be obtained by using skin allergy tests and total serum IgE witch will be the purpose of the phase 2 of our study.
End-Inspiratory Airway Occlusion
Authors: GIUSEPPE FOTI, MAURIZIO CEREDA, GIULIANA BANFI, PAOLO PELOSI, ROBERTO FUMAGALLI, ANTONIO PESENTI
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We evaluated the end-inspiratory occlusion maneuver as a means to estimate the inspiratory effort during pressure support ventilation (PS). In nine nonobstructed acute lung injury (ALI) patients, we applied four levels of PS (0, 5, 10, 15 cm H2O) to modify the inspiratory effort. End inspiratory occlusions (2 to 3 s) were performed at the end of each experimental period by pushing the inspiratory hold button of the ventilator (Servo 900 C; Siemens, Berlin, Germany). We took the difference between the end-inspiratory occlusion plateau pressure and the airway pressure before the occlusion (PEEP + PS) as an estimate of the inspiratory effort and called it PMI (Pmusc,index). From the esophageal pressure tracing we obtained a reference measurement of the pressure developed by the inspiratory muscles at end inspiration (Pmusc,ei) and of the pressure-time product per breath (PTP/b) and per minute (PTP/min). In each patient, PMI was correlated with Pmusc,ei (p < 0.01) and PTP/b (p < 0.01). A PMI threshold of 6 cm H2O detected PTP/min < 125 cm H2O s/min with a sensitivity of 0.89 and a specificity of 0.89. We conclude that PMI is a good estimate of the pressure developed by the inspiratory muscles in ALI patients and may be used to titrate PS level. The major advantage of PMI is that it can be obtained from the ventilator display without any additional equipment.
γ-Globulin Metabolism in Chronic Lymphocytic Leukemia&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: R L GOLDEN, D G MILLER, H D DIAMOND
Journal: JNCI Journal of the National Cancer Institute (1962)

The half-life of γ-globulin, with use of I131-labeled protein, was determined in a group of 15 patients with chronic lymphocytic leukemia and in a comparative group of 6 patients with breast cancer. A markedly prolonged γ-globulin half-life (mean value 13.9 days) was observed in the leukemic patients as opposed to a mean value of 6.6 days in the comparative group. This difference was statistically significant. The patients with chronic lymphocytic leukemia manifested progressive hypogammaglobulinemia as a group, a feature of the evolution of the disease. This is interpreted as evidence of decreased anabolism as well as catabolism of the serum γ-globulin fraction in these patients. Speculation as to the etiology of these phenomena is presented. The relationship of the abnormal lymphocyte, with its increased survival time, to the impaired formation of γ-globulin is suggested. The variations in the γ-globulin half-life and serum concentrations may be a function of the proportion existing between the normal and pathologic lymphocyte populations at a given stage of the disease. It is postulated that the prolonged γ-globulin half-life may represent a compensatory slowdown in degradation secondary to the diminished formation of the protein.
A prospective study of the 6 min walk test as a surrogate marker for haemodynamics in two independent cohorts of treatment-naïve systemic sclerosis-associated pulmonary arterial hypertension
Authors: Sébastien Sanges, David Launay, Rennie L Rhee, Olivier Sitbon, Éric Hachulla, Luc Mouthon, Loïc Guillevin, Laurence Rottat, David Montani, Pascal De Groote, Vincent Cottin, Pascal Magro, Grégoire Prévot, Fabrice Bauer, Emmanuel Bergot, Céline Chabanne, Martine Reynaud-Gaubert, Sylvie Leroy, Matthieu Canuet, Olivier Sanchez, Christophe Gut-Gobert, Claire Dauphin, Christophe Pison, Clément Boissin, Gilbert Habib, Pierre Clerson, François Conesa, Jean-François Cordier, Steven M Kawut, Gerald Simonneau, Marc Humbert
Journal: Annals of the Rheumatic Diseases (2015)

Despite the wide use of the 6 min walk distance (6MWD), no study has ever assessed its validity as a surrogate marker for haemodynamics and predictor of outcome in isolated pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH). We designed this work to address this issue.Treatment-naïve patients with SSc-PAH were prospectively included from two sources: the French PAH Network (a prospective epidemiological cohort) (n=83) and randomised clinical trials submitted for drug approval (Food and Drug Administration) (n=332). Correlations between absolute values of the 6MWD and haemodynamics at baseline, as well as between variations of 6MWD and haemodynamics during follow-up, were studied in both populations.In the French cohort, baseline cardiac output (CO) (R(2)=0.19, p=0.001) and New York Heart Association class (R(2)=0.10, p<0.001) were significantly and independently correlated with baseline 6MWD in multivariate analysis. A significant, independent, but weaker, correlation with CO was also found in the Food and Drug Administration sample (R(2)=0.04, p<0.001). During follow-up, there was no association between the changes in 6MWD and haemodynamic parameters in patients under PAH-specific treatments.In SSc-PAH, CO independently correlates with 6MWD at baseline, but accounts for a small amount of the variance of 6MWD in both study samples. This suggests that other non-haemodynamic factors could have an impact on the walk distance. Moreover, variations of 6MWD do not reflect changes in haemodynamics among treated patients. Our results suggest that 6MWD is not an accurate surrogate marker for haemodynamic severity, nor an appropriate outcome measure to assess changes in haemodynamics during follow-up in treated SSc-PAH.
Effect of high dose inhaled beclomethasone for respiratory syncytial virus bronchiolitis during infancy on lung function and asthma at age 6 - A randomised placebo-controlled trial
Authors: Kim Zomer-Kooijker, Kors van der Ent, Marieke Ermers, Maroeska Rovers, Louis Bont
Journal: European Respiratory Journal (2013)

Background:  Respiratory syncytial virus (RSV) bronchiolitis is the most common cause for hospitalization in infants, and is associated with preschool wheeze. However, the relationship between RSV bronchiolitis hospitalization and long-term airway disease is controversial.  Methods:  This is a 6-year follow-up report of a RCT, in which 185 infants, hospitalized for RSV bronchiolitis were treated with early initiated, high dose inhaled beclomethasone (n=86) or placebo (n=99) for 3 months. The primary outcome was FEV1%predicted. Secondary outcomes were bronchial hyperresponsiveness, physician diagnosed asthma, hay fever and eczema, and linear growth. Measures were compared to an unselected healthy birth cohort study (n=579).  Results:  At age 6, no significant differences were found in mean FEV1 %predicted between beclomethasone-treated and placebo-treated patients (91.4 v 93.4, mean difference 2.05 (95% CI -1.98 to 6.08). Physician diagnosed asthma, parent reported hay fever and eczema were comparable between groups, as was linear growth. Compared to healthy controls the RSV group had lower FEV1 %predicted, 92.4% v 100.1%, mean difference -7.68% (95% CI -10.21 to -5.14), more often physician diagnosed asthma, 22.7% versus 5.4%, RD 17.4% (95% CI 11.0 to 23.6) while similar proportions of atopic diseases.  Conclusion:  Treatment with high dose inhaled beclomethasone did not improve the long-term respiratory outcome of hospitalized infants with RSV, but was safe. Hospitalization for RSV infection is associated with a lower lung function and increased risk of physician diagnosed asthma at age 6.
Fatigue in COPD: A qualitative study of peoples experiences
Authors: Caroline Stridsman, Anne Lindberg, Lisa Skär
Journal: European Respiratory Journal (2012)

Background  Fatigue is reported to be one of the most common symptoms among people with COPD. However, there is hardly any qualitative research describing how fatigue affects people living with COPD.   Aim  To study people9s experience of fatigue when living with COPD.   Method  In the years of 2008-2010, a purposive sample of 20 people with COPD stage II-IV, according to GOLD, was recruited from the OLIN COPD-study in Northern Sweden. Data was collected by semi-structured interviews and the participants were interviewed about their experience of fatigue. The interviews were subjected to a qualitative content analysis.   Results  One theme was identified: To reconcile with the dimensions of fatigue, and four categories: To understand the reason; To preserve fatigue unexpressed; To be controlled and To struggle against. In COPD, fatigue seems to appear in different dimensions. People are aware of the cause of fatigue and they seem to reconcile with the symptom believing it is a natural consequence of COPD, and therefore it remains unexpressed. Fatigue is an always present feeling that involves the whole body, raising feelings of hopelessness making life heavy and invincible. Further, by increased dyspnea, fatigue gets even heavier and more severe to manage. To cope, people have to force themselves to struggle against fatigue, regardless of dyspnea that was triggered by physical movements.   Conclusion  Fatigue affected the daily life of people living with COPD. In relation to dyspnea, fatigue was described to be overwhelming, and most important fatigue seems to be unexpressed to healthcare professionals and relatives. This knowledge is significant for nurses in order to meet the person9s needs of care.
A Learning-Disabled Woman who had been Raped: A Multi-Agency Approach
Authors: Jean O'hara, Hemmie Martin
Journal: Journal of the Royal Society of Medicine (2001)

People with learning disabilities are vulnerable to sexual exploitation and abuse1. Moreover, when incidents occur, the victims are sometimes perceived to make poor witnesses and the cases do not come to court2. Support and care may demand a multi-agency approach3,4, as illustrated by the following case.
A choice for MRC or CAT largely affects GOLD classification
Authors: Alex van 't Hul, Remco Djamin, Marlou Keim
Journal: European Respiratory Journal (2013)

Introduction:  In the recently updated GOLD guidelines, classification of disease severity is based on airway obstruction, exacerbation frequency and symptom severity. Symptom severity may be built on either the MRC dyspnoea score or the COPD assessment test (CAT). Since the CAT does not only contain questions regarding dyspnoea severity, a difference in outcome is possible. Therefore, the aim of the present study was to evaluate the effect of a choice for MRC or CAT to score symptom severity, on GOLD classification.  Methods and materials:  In patients referred to the pulmonologist between April and December 2012, measurements were performed enabling the classification of disease severity according to the new GOLD guidelines. Spirometry was performed to measure airway obstruction, annual exacerbation rate was recorded and symptom severity was assessed by MRC and CAT.  Results:  Data were collected in 125 patients enrolled in an outpatient based Care Path for patients with COPD. Table 1 gives the patient characteristics. Outcome with respect to GOLD classification based on MRC or CAT are provided in Table 2. The use of the CAT instead of MRC leads to significantly larger proportions of patients with worse disease classification, i.e. B and D in stead of A and C.  Conclusion:  Gold classification is largely affected by a choice for MRC or CAT to score symptom severity.
Genetics of Congenital Central Hypoventilation Syndrome
Authors: Debra E. Weese-Mayer, Elizabeth M. Berry-Kravis
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The initial response to a publication on a pediatric “orphan disease” is not necessarily enthusiasm, especially if the reader is an adult intensivist or pulmonologist. Although considered insignificant because of their rarity, orphan diseases can serve as models for other, more global phenomena. For example, idiopathic congenital central hypoventilation syndrome (CCHS), although first described in 1970 (1), was considered exclusively as a rare disorder of respiratory control, with nearly all publications in case report or small series format for the next 20-plus years. Although many early reports described symptoms compatible with autonomic nervous system (ANS) dysregulation, and reports on familial patterns appeared, it took another decade for the familial nature of CCHS and the associated ANS dysregulation to be identified. The American Thoracic Society increased the visibility of CCHS with the 1999 ATS statement entitled “Idiopathic Congenital Central Hypoventilation Syndrome: Diagnosis and Management” (2). The specific objectives were to (1) improve knowledge regarding CCHS to minimize delays in diagnosis; (2) state the components of a thorough diagnostic evaluation and for followup; (3) familiarize practitioners with diagnostic, treatment, and home health care options, and long-term outcomes; (4) emphasize the composite of ANS dysfunction beyond the narrow control of breathing deficit considered the hallmark of CCHS; and (5) provide evidence of a genetic component. Subsequent to the ATS statement we have documented an increase in the number of cases diagnosed, with earlier consideration of the disease. Nearly all subsequent publications have appeared in the genetics literature, leaving the readership of the American Journal of Respiratory and Critical Care Medicine potentially uninformed regarding the remarkable progress in determining the genetic basis of CCHS as well as the inheritance pattern. This Pulmonary Perspective has been prepared for three reasons: (1) to demonstrate the lesson that a seemingly straightforward orphan disease with disordered respiratory control is actually a more global phenomenon of ANS dysregulation; (2) to bring the remarkable genetic progress in CCHS, culminating with the identification of a defining gene, the paired-like homeobox gene (PHOX)2b, to the adult and pediatric pulmonologist/intensivist readership of the Journal; and (3) to demonstrate that this unique study population holds great promise for furthering our under-
Folfoxiri + Bevacizumab (Bev) in Patients (Pts) with Previously Untreated Metastatic Colorectal Cancer (Mcrc): Final Survival and Pharmacogenomic Profiling Results from the Opal Study
Authors: A. Stein, D. Atanackovic, J. Stoehlmacher, B. Hildebrandt, P. Stübs, C. Steffens, W. Brugger, G. Hapke, G. Illerhaus, E. Bluemner, C. Bokemeyer
Journal: Annals of Oncology (2014)
Specificity of Antitumor Immune Reactions Mediated by Xenogeneic Immune RNA2
Authors: David H. Kern, Carol R. Drogemuller, Nancy Chow, Deanna D. Holleman, Yosef H. Pilch
Journal: JNCI Journal of the National Cancer Institute (1977)

Evidence that xenogeneic immune RNA (I-RNA) mediated specific cytotoxic immune responses against human tumor-associated antigens was obtained from in vitro studies in two autologous melanoma systems. In these systems, malignant melanoma target cells, matching normal fibroblast target cells, lymphocyte effector cells, and melanoma and normal skin tissue used to immunize RNA donor animals were derived from the same autochthonous hosts. When incubated with autologous lymphocytes, I-RNA extracted from the lymphoid organs of donor animals immunized with melanoma tissue mediated immune reactions against autologous melanoma target cells in vitro. I-RNA from animals immunized with normal skin tissue from autochthonous hosts did not increase the cytotoxicity of autologous lymphocytes for autologous melanoma cells. Using autologous fibroblasts as target cells, we detected no increase in cytotoxicity when autologous lymphocytes were incubated with RNA from animals immunized either with melanoma tissue or normal skin tissue from the autochthonous host. By contrast, when allogeneic lymphocytes were used as effector cells, RNA extracted from animals immunized either with melanoma tissue or normal skin mediated cytotoxic immune reactions against melanoma target cells and normal fibroblast target cells derived from the same patient.
The impact of lung cancer subtypes, smoking status and corticosteroid treatment on exhaled nitric oxide levels in patients with lung cancer
Authors: Alica Bencova, Martina Antosova, Ivan Kocan, Eva Rozborilova
Journal: European Respiratory Journal (2014)

Long term exposure of cells to high nitric oxide (NO) concentrations during chronic inflammation coud have a role in cancer formation.  The aim of our study was to asses the importance of exhaled nitric oxide (FeNO) measurement in lung lancer patients and its relationship to type of cancer, smoking status and use of inhaled corticosteroids (ICS) in indication of chronic obstructive pulmonary disease (COPD) treatment. 33 newly diagnosed patients with lung cancer and 43 healthy individuals took part in the study. FeNO was measured by analyzer NIOX. Patients with lung cancer had significantly (p=0,004) higher levels of FeNO (13ppb, IQR 8) than controls (10,1ppb, IQR 3,05). Patients with non-small cell lung cancer (NSCLC) had significantly (p=0,005) higher levels of FeNO (15ppb, IQR 11) than controls, as well as small cell lung cancer (SCLC) patients (12,5ppb, IQR 6,25) (p=0,043). FeNO levels in 8 non-smokers with lung cancer (16,5ppb, IQR 5 ppb) were significantly higher (p=0,001) than in healthy non-smokers as well as FeNO levels in 24 smokers with lung cancer (12,5ppb, IQR 7,5) (p=0,022). FeNO in 17 patients with lung cancer, current smokers with COPD without ICS tratment (13ppb, IQR 8) was significantly higher (p=0,024) than in healthy subjects. When lung cancer smokers with COPD were treated with ICS, the FeNO levels (11ppb, IQR 4) did not differ from FeNO levels in controls.  In lung cancer patients the production of NO is increased regardless of type of cancer and smoking status. FeNO levels in lung cancer smoking patients treated with ICS are similar as in healthy controls.  Support: VEGA 1/0062/13, VEGA 1/0110/12, Projectu code: 26110230067.