tbuckley/cabot-search huggingface dataset:
The effect of an inhaled corticosteroid (budesonide) on exercise-induced asthma in children. Dutch CNSLD Study Group
Authors: HJ Waalkens, EE van Essen-Zandvliet, J Gerritsen, EJ Duiverman, KF Kerrebijn, K Knol
Journal: European Respiratory Journal (1993)

The effect of long-term treatment with inhaled corticosteroid on exercise-induced asthma (EIA) was studied in 55 children, aged 7-18 yrs (mean 12 yrs). We also compared the time course of stabilization of EIA to that of other indicators of airway responsiveness, such as peak expiratory flow (PEF) variation and the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1). All children participated in an ongoing multicentre study to compare the effects of long-term treatment either with the beta 2-agonist salbutamol (600 micrograms.day-1) plus the inhaled corticosteroid budesonide (600 micrograms.day-1) (BA+CS), or salbutamol plus placebo (BA+PL), on airway calibre, airway responsiveness and symptoms. After a median follow-up of 22 months, the study design had to be changed, because of the high number of drop-outs on BA+PL. At that time, the treatment regimen of all children who had not withdrawn was changed into BA+CS. At the moment of change, and after 2 and 8 months of treatment, a treadmill exercise test was performed in two centres. Eighteen of the 22 children (82%) who were treated with BA+PL from the beginning had EIA, compared to 18 of the 33 children (55%) who were treated with BA-CS (p < 0.05). After 2 and 8 months of treatment with BA+CS in the patients previously on BA+PL this percentage decreased to 59 and 55%, respectively, and was not significantly different between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Computer bronchophonography is a new lung function diagnostic method in children
Authors: Svetlana Shatalina, Geppe Natalya, Starostina Lada, Malishev Vladimir, Borovkova Anastasiya
Journal: European Respiratory Journal (2014)

Background: Spirometry is frequently used to evaluate lung function in children older 7 years with obstructive or restrictive lung diseases such as asthma or cystic fibrosis. The development of methods of the assessment of respiratory function in younger children is necessary.

Aim: To introduce the method CBPhG for assessment of respiratory function.

Materials and methods: 200 healthy patients (age 1-18 years) without lung diseases. Lung function was examined by CBPhG. Registration of respiratory sounds is recorded by high sensitivity transducer in wide range of frequencies during quiet breathing: low 0,2-1,2, middle 1,2-5,0 and high frequency >5,0 kHz. The registration is performed for 10 seconds. The CBPhG has a high overall reliability (88.7%), sensitivity (proportion of true positive cases) (86.4%), specificity (proportion of true negative cases) (90.9%).

Results: Data were 0,12±0,96mcJ in high frequency range, 3,04±0,13mcJ in middle, 71,7±29,8mcJ in low in children without lung diseases, regardless of age.

Conclusions: CBPhG is a high sensitive method which may be used for assessment of respiratory function in even ages, especially in the childhood. This method allows to monitor efficiency of therapy of bronchial asthma.
Pharmacodynamic comparison of linezolid, teicoplanin and vancomycin against clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci collected from hospitals in Brazil
Authors: J.L. Kuti, C.R.V. Kiffer, C.M.F. Mendes, D.P. Nicolau
Journal: Clinical Microbiology and Infection (2008)
Restless Legs Syndrome
Authors: Suzanne Bertisch
Journal: Annals of Internal Medicine (2015)

This issue provides a clinical overview of restless legs syndrome, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
An ensemble approach to accurately detect somatic mutations using SomaticSeq
Authors: Li Tai Fang, Pegah Tootoonchi Afshar, Aparna Chhibber, Marghoob Mohiyuddin, Yu Fan, John C. Mu, Greg Gibeling, Sharon Barr, Narges Bani Asadi, Mark B. Gerstein, Daniel C. Koboldt, Wenyi Wang, Wing H. Wong, Hugo Y.K. Lam
Journal: Genome biology (2015)

SomaticSeq is an accurate somatic mutation detection pipeline implementing a stochastic boosting algorithm to produce highly accurate somatic mutation calls for both single nucleotide variants and small insertions and deletions. The workflow currently incorporates five state-of-the-art somatic mutation callers, and extracts over 70 individual genomic and sequencing features for each candidate site. A training set is provided to an adaptively boosted decision tree learner to create a classifier for predicting mutation statuses. We validate our results with both synthetic and real data. We report that SomaticSeq is able to achieve better overall accuracy than any individual tool incorporated.
Improved survival for patients with acute myelogenous leukemia.
Authors: A J Mitus, K B Miller, D P Schenkein, H F Ryan, S K Parsons, C Wheeler, J H Antin
Journal: Journal of Clinical Oncology (1995)

PURPOSE Despite improvement in chemotherapy and supportive care over the past two decades, overall survival for patients with acute myelogenous leukemia (AML) remains poor; only 25% to 30% of individuals with this disorder will be cured. In 1987, we initiated a prospective multiinstitution study designed to improve long-term survival in adults with AML. METHODS We modified the usual 7-day treatment scheme of daunorubicin and cytarabine with high-dose cytarabine (HiDAC) on days 8 through 10 (3 + 7 + 3). Allogeneic or autologous bone marrow transplantation (BMT) was offered to all patients who entered complete remission (CR) to decrease the rate of leukemic relapse. Data were analyzed by intention to treat. RESULTS CRs were achieved in 84 of 94 patients (89%; 95% confidence interval [CI], 83 to 95). Because of the high remission rate, factors previously thought to predict outcome, such as cytogenetics, WBC count, French-American-British (FAB) classification, sex, and age, were not useful prognostic variables. The overall survival rate for the entire cohort of patients from data of diagnosis is 55% at 5 years. Sixty percent of all patients who achieved a CR underwent marrow grafting. There was no significant difference in event-free survival (EFS) at 5 years comparing patients assigned to receive allogeneic BMT with patients assigned to receive autologous BMT (56% v 45%, P = .54). CONCLUSION The long-term disease-free survival observed in this study is excellent compared with historical data. This improvement in survival is probably due to the high rate of remission induction, as well as to the effective nature of the consolidation therapy.
Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation
Authors: BB Bjorkstrand, P Ljungman, H Svensson, J Hermans, A Alegre, J Apperley, J Blade, K Carlson, M Cavo, A Ferrant, AH Goldstone, A de Laurenzi, I Majolino, R Marcus, HG Prentice, K Remes, D Samson, A Sureda, LF Verdonck, L Volin, G Gahrton
Journal: Blood (1996)
Improving respiratory muscular strength in Pompe disease late-onset with muscles respiratory training
Authors: Mitja Jevnikar, Roberto Trevisan, Chiara Torregiani, Cinzia Longo, Rossella Cifaldi, Rossana Della Porta, Marco Confalonieri
Journal: European Respiratory Journal (2013)

BACKGROUND: Glicogenosis type II late onset or Pompe disease is a genetic disorder due to lysosomial enzyme deficiency: acid α-glucosidase. This deficiency leads to the accumulation of glycogen in muscle tissue that causes a progressive debilitation of the muscles until a severe hypoventilation. The weakness of respiratory muscles is diagnosed by functional respiratory tests (FVC in clino and orthostatism, MIP and MEP), sleep disorders study and blood gas analysis.(1) The main therapeutic option is the administration of surrogate enzyme. Despite a single report in literature, we don't know if respiratory muscle rehabilitation or training could bring any real benefits.(2)

OBJECTIVE: We want to evaluate effectiveness of respiratory muscles training using a specific appliance with adjustable resistance (Threshold). First endpoint is muscular strength of respiratory brawn by MIP and MEP measurements.

METHODS: We studied 7 patients, aged between 13 and 58 years, affected by Pompe desease late onset with respiratory muscles deficiency on functional respiratory tests. All patients were taking sostitutive enzyme therapy and underwent training with Threshold at specified pressures. During follow up they performed the measurement of MIP and MEP.

RESULTS: The values of MIP and MEP increased on average of 16.2% (p<0.05) after 3 months and of 21% (p<0.05) after 20 months of treatment in our group of patients.

CONCLUSION: Our study suggests that the training with Threshold, used in addition to enzyme therapy, could improve respiratory muscular strength in Pompe disease.
Abstract P188: Impact of Metabolic Crisis on Fatal Outcome in Patients with Cardiogenic Shock Complicating ST-segment Elevation Myocardial Infarction
Authors: Makoto Suzuki, Hideaki Shimizu, Shinpei Fujita, Yasuhiro Sasaki, Akihito Miyoshi, Yaemi Takagi, Hirokazu Habara, Sumiko Sato, Mikio Kakishita, Youichi Nakamura
Journal: Circulation (2008)

We investigated the relation of initial metabolic acidemia to in-hospital mortality in patients treated with emergency coronary angioplasty for shock complicating first anterior ST-segment elevation myocardial infarction (STEMI). Methods A total of 23 consecutive patients (17 men, 73±12 years) with Killip class IV class due to anterior STEMI were studied. Using median levels of arterial base excess (BE, −5.8 mmol/L), the patients were divided into high and low BE groups, and both groups were compared regarding microvascular revascularization and clinical outcomes. To evaluate myocardial tissue-level reperfusion, severe microvascular injury was defined by the presence of both angiographic myocardial blush grade 0/1 and less than 30 % resolution of ST-elevation after angioplasty. Results In-hospital mortality was 92 % in the high BE group (−12.0±4.9 mmol/L) as compared with 9 % in the low BE group (−0.9±2.4mmol/L, p=0.0001 vs. high BE group). Baseline clinical and angiographic characteristics were not different between the two groups. Arterial gas analysis showed lower pH and higher levels of lactate in the high BE group than in the low BE group (7.22±0.16 vs. 7.42±0.06, p=0.006, 8.52±4.43 vs. 2.42±1.33, p=0.016). Despite successfully culprit angioplasty in all cases, the incidence of severe microvascular injury was significantly high in the high BE group as compared with the low BE group (83 vs. 36 %, p=0.018). Initial levels of BE showed a significant negative relation to ST-segment resolution (r=0.61, p=0.002). A multivariate regression analysis demonstrated a potent association of initial levels of BE with severe microvascular injury (r 2 =0.341, p=0.015). Conclusions We identified the pivotal association of initial metabolic crisis with severe microvascular reperfusion injury leading to high in-hospital mortality in patients with cardiogenic shock complicating STEMI.
Seasonal variations in asthma attacks and grass sensitisation
Authors: Cristina Canova, Peter Burney, Deborah Jarvis
Journal: European Respiratory Journal (2011)

Seasonal variation in asthma mortality and hospitalization has been reported. In this study we describe seasonal variation in asthma symptoms and assess whether this was modified by SPT sensitisation. Asthmatics aged 20-44 years (n=2573) taking part in the European Community Respiratory Health Survey I are included.

Participants identified bi-monthly periods they usually experienced attacks of asthma. Effect modification of sensitization to grass, cat, dust, birch, Alternaria on asthma attacks in each bi-monthly period was assessed within each country, using marginal logistic regressions, based on generalised estimating equations. Interaction coefficients were then combined using random effects meta-analysis.

Seasonal variation in asthma attacks was seen in most countries, although with different patterns. Seasonal variation was not modified by sensitisation to indoor allergens (cat, dust) but was modified by sensitisation to grass.

![Figure][1] 



In Southern Europe the risk of asthma in May/June compared to Jan/Feb in those with IgE to grass was six times that seen in asthmatics not sensitised to grass. Overall sensitisation to Alternaria increased the risk of attacks in Jul/Aug compared to Jan/Feb (OR 2.3).

Asthmatics sensitised to grass and Alternaria experience seasonal exacerbations likely triggered by allergen exposure. The effect of pollen on asthma severity in a sub group of susceptible asthmatics may be much greater than previously documented.

 [1]: pending:yes
Molecular Aspects of Drug Photosensitivity With Special Emphasis on Psoralen Photosensitization Reaction12
Authors: Madhu A. Pathak
Journal: JNCI Journal of the National Cancer Institute (1982)

Photosensitization reactions involve phototoxic reactions and photoallergic reactions, which are less common. Common drugs and chemicals that photosensitize humans are listed. Phototoxic reactions include the following: 1) direct photosensitization (type I reactions), in which the reactions of the triplet-state sensitizer are directly attributable to a component other than oxygen (e.g., DNA, proteins, and cell membranes), and 2) indirect photosensitization (type II reactions), in which the triplet state of a sensitizer reacts first with molecular oxygen, producing an "active oxygen" intermediate that subsequently reacts with the biologic system. The active oxygen intermediates are singlet oxygen (1O2)k, superoxide radical anions (O(2), and hydroxy radicals. Psoralen-induced skin photosensitization appears to involve both type I and type II reactions. The formation of monofunctional bifunctional psoralen-DNA photoadducts (a type I reaction) is probably responsible for cell damage, cell death, mutation, and even skin carcinogenesis. The erythema response appears to be the result of a type II reaction.
Pitfalls of local HER2-testing
Authors: H. Bühler, B. Duvnjak, G. Schaller
Journal: Journal of Clinical Oncology (2004)

9692 Background: Herceptin therapy provides benefits for breast cancer patients with strong overexpression of the HER2 protein or amplification of the HER2 gene in the tumor. Still questionable remains the therapeutic value in cases with only weak HER2 overexpression (2+). For those patients a HER2-retesting program has been established in Germany to identify in central reference laboratories tumors with gene amplification among the locally assessed 2+ cases. In our reference lab we have tested more than 500 cases so far. Recently we have started to reanalyze the incoming 2+ material in order to check the reliability of this classification. Methods: The material was stained locally with the Dako HercepTest or with the Ventana HER2 Pathway system and judged as 2+ by the local pathologist. The concordance between HercepTest and HER2 Pathway system is about 90%. In our lab the submitted blocks were freshly cut into 4∈\({1}/{4}\)m (FISH) or 2.5 ∈\({1}/{4}\)m (IHC) slices and tested with the Ventana HER2 Inform kit (FISH) and with the Ventana HER2 Pathway system respectively. The tests were performed on a Ventana Benchmark system. Results: Only 32 of 157 specimens (20%) were 2+ in our hands. 106 cases (68%) were negative with a score of 0/1+, 19 (12%) stained strongly positive with a HER2 overexpression of 3+. The overall results of gene amplification and protein expression correlated very well: 68% negative and 32% positive tumors with both methods. In detail however, the results were discrepant for some cases. Conclusions: The results are sobering. However it has to be taken into account, that the FISH retesting program for 2+ cases is free of charge. Some pathologists might have declared their material falsely to get the FISH diagnosis for nothing. Even though - it seems that the local HER2 screening should be heavily improved, particularly in smaller pathological departments. There is evidence for similar problems in the U.S.A. (J Natl Cancer Inst 94:852–57). In the interest of the patients HER2 testing should be performed in central labs, optimally by means of FISH. No significant financial relationships to disclose.
Bleomycin: Mammalian Cell Lethality and Cellular Basis of Optimal Schedule 2
Authors: Y. Takabe, T. Miyamoto, M. Watanabe, T. Terasima
Journal: JNCI Journal of the National Cancer Institute (1977)

Experiments on the dose- and time-dependent changes in the survival of Ehrlich ascites tumor cells exposed to bleomycin were done to determine a useful regimen for the effective inactivation of the tumor cells. The experimental results on time-dependent changes in survival of bleomycin-treated cells indicated that two phenomena were involved in the survival increase observed after single bleomycin treatment: 1) The bleomycin-treated cells were resistant to the second injection when the interval between the two successive doses was within 2 hours (induced resistance), and 2) the survival was increased as a function of time when the interval between treatments was prolonged (repair of potentially lethal damage). The effect of the fractionated treatments was then investigated for the regimen that minimized the induced resistance and repair of potentially lethal damage. The results indicated that administration of a lower dose of bleomycin at shorter intervals was more effective than other fractionation schedules, and, on the basis of the same dose rate, the continuous infusion regimen was more effective than fractionation regimens for the sterilization of Ehrlich ascites tumor cells.
Community-acquired complicated parapneumonic effusions in adults without associated comorbidity - A study from India
Authors: B.N.B. Mahaveera Prasad, C.A. Tukaram
Journal: European Respiratory Journal (2012)

Methods:  Retrospective analysis of clinical, radiological, bacteriological, pleural fluid characteristics and treatment out come of cases managed at a multispeciality hospital in rural India.   Results:  17 cases in this study had 15 males and 2 females between 21 to 53 years of age. All presented with acute onset of fever, chest pain, pulmonary consolidation and leucocytosis. Mean duration of symptoms averaged 6 days prior to hospitalisation. 2 had mild effusion while moderate effusions was observed in the remaining with 3 among them having multiloculation. Pleural fluid grew streptococcus pneumoniae in 5 and staphylococcus aureus in 2 cases. Blood and sputum grew streptococcus pneumoniae in 2 cases. Pleural pus was present in 11 cases and in the remaining pleural fluid revealed polymorphonuclear leucocytosis with glucose below 50 mg/dl. Pleural fluid gram stain was positive in 8 cases. All cases recieved appropriate antibiotics. Pleural drainage with 24 F chest tube was instituted in 11 cases while in the remaining with 12 F pigtail catheter. 3 cases with multiloculation required instillation of intrapleural streptokinase and placement of pigtail catheters at two different sites for an effective pleural drainage. Amount of pleural fluid drained varied from 450 ml to 2400 ml with mean chest tube dwell time of 6.5 days. All patients responded well to therapy. 2 cases had residual pleural thickening without functional abnormality.   Conclusions:  ACCP category 4 effusion was the commonest with infection by streptococcus pneumoniae predominating among them. Early institution of pleural drainage along with appropriate antibiotic therapy resulted in excellent outcome.
Response criteria for phase II studies of supratentorial malignant glioma.
Authors: D R Macdonald, T L Cascino, S C Schold, J G Cairncross
Journal: Journal of Clinical Oncology (1990)

We suggest "new" response criteria for phase II studies of supratentorial malignant glioma and favor rigorous criteria similar to those in medical oncology, with important modifications. Four response categories are proposed: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Response in this scheme is based on major changes in tumor size on the enhanced computed tomographic (CT) or magnetic resonance imaging (MRI) scan. Scan changes are interpreted in light of steroid use and neurologic findings. We advocate careful patient selection, emphasize pitfalls in the assessment of response, and suggest guidelines to minimize misinterpretations of response.
Prospective randomized trial of two dose levels of interferon alfa with zidovudine for the treatment of Kaposi's sarcoma associated with human immunodeficiency virus infection: a Canadian HIV Clinical Trials Network study.
Authors: F A Shepherd, R Beaulieu, K Gelmon, C A Thuot, C Sawka, S Read, J Singer
Journal: Journal of Clinical Oncology (1998)

PURPOSE Interferon alfa alone has shown antitumor activity against Kaposi's sarcoma (KS), and phase I and II clinical trials showed that interferon and zidovudine could be administered safely to patients with human immunodeficiency virus (HIV)-associated KS. These observations led to our trial of zidovudine with two dose levels of interferon alfa. METHODS HIV-positive patients with KS were eligible if they were older than 18 years of age, had a performance status of 0 to 2, and were free of active infection. All patients received zidovudine 500 mg daily and were randomized to receive-interferon alfa 1 million U or 8 million U subcutaneously daily. RESULTS The 108 eligible and assessable patients were well balanced for known prognostic factors. Response was reported in 31% of high-dose therapy and 8% of low-dose therapy patients (P=.011). Response at both dose levels was higher for patients with CD4 counts greater than 150 x 10(9)/L. The median time to progression was longer for patients in the 8-million U arm (18 v 13 weeks; P=.002). Both hematologic and nonhematologic toxicities were higher in the high-dose arm; 50 of 54 patients who received 8 million U required dose alterations in the first 4 months compared with only 19 of 53 patients who received 1 million U (P=.0002). No significant differences were reported with respect to improvement in CD4 count, elimination of p24 antigen, or development of opportunistic infections. CONCLUSION Zidovudine and moderate-dose-interferon alfa may be combined safely for the treatment of HIV-associated KS, and both response to treatment and toxicity are dose related.