tbuckley/cabot-search huggingface dataset:
Changes of active expiration respiratory muscle (RM) in men with chronic obstructive pulmonary disease (COPD)
Authors: Sviatlana Lemiasheuskaya, Mikhail Nedzvedz, Alexander Makarevich, Alexander Lemiasheuski, Alexander Pochtavcev
Journal: European Respiratory Journal (2011)

Background:  For the present moment changes occurring in RM, during COPD, have been studied insufficiently.   Aim and objectives:  to investigate the RM status and compare them with histological data of bioptic muscular material.   Material and methods:  The peak histogram of the internal oblique abdominal muscle (intOAM) was detected by ultrasonic scanner. We obtained the indices: homogeneity (H), structural density (SD) and echogenicity (E). Histological research of bioptic material of intOAM has been carried out.  Research was made in 13 pts: 1st group: 8 at the 1st COPD stage; mean age 56 yrs; BMI 24kg/m 2 ; 2nd group: 5 at the 2nd COPD stage, mean age 59 yrs; BMI 24kg/m 2 . Control group was formed of 10 healthy subjects compared according to age-, sex- and BMI.   Results:  Contractions, small sites of a fragmentation, stratification of myofibrils and proliferation of fibroblasts were observed at the 1st and 2nd COPD stage. We revealed scleroses of single muscular fibril and foci of sclerosis in intramuscular regions. The median H in the 1st and 2nd groups was 21 and 18 units respectively. Increasing severity of COPD was associated with enhancing of contractions and stratification of myofibrils. Thus, we detected the significant correlations between COPD severity and contractions (r=0,72) and with stratification of myofibrils (r=0,66). Indices H and SD were lower in pts with more scleroses manifestations (r= - 0,42 and r= - 0,59). Whereas index E was higher in these patients (r=0,59). The pack/years significantly correlated with intensity of proliferation of fibroblasts (r=0,56).   Conclusions:  Indices H, E, SD reflect the pathological processes occurring in RM in COPD patients.
Royal colleges active on their behalf
Authors: B Pentecost
Journal: BMJ (1994)

SHOs: the lost tribesTroubled SHOs should seek counselling EDITOR,-At the meeting on senior house officers reported on by Luisa Dillnerl several speakers said that junior doctors were reluctant to contact the National Counselling Service for Sick Doctors for fear that their consultants or referees would hear of their difficulties.I wish to
UTILIZATION OF MECHANICAL CIRCULATORY SUPPORT IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: INSIGHTS FROM THE NCDR
Authors: Smita I. Negi, Amneet Sandhu, Lisa McCoy, Irfan Hameed, Prashant Atri, Subhi Al’Aref, Jeptha Curtis, Edward McNulty, H. Vernon Anderson, Adhir Shroff, Mark Menegus, Rajesh Swaminathan, Hitinder Gurm, John Messenger, Tracy Wang, Steven Bradley
Journal: Journal of the American College of Cardiology (2015)
Late-breaking abstract: Impact of asthma, allergic rhinitis, COPD and rhinosinusitis on healthcare resource utilization in Asia
Authors: Shalini Bagga, Sang-Heon Cho, Aloke Gopal Ghoshal, Abdul Razak Bin Abdul Muttalif, Horng-Chyuan Lin, Sanguansak Thanaviratananich, Rab Faruqi, Alan Brnabic, Francis Dehle, Wang De Yun
Journal: European Respiratory Journal (2014)

Background:  There is a lack of healthcare resource utilization (HCRU) data on respiratory diseases in Asia.   Objectives:  Asia-Pacific Burden of Respiratory Diseases (APBORD) is a cross-sectional, observational study of burden of disease of Asthma, Allergic Rhinitis (AR), COPD, and Rhinosinusitis in adults across India, Korea, Malaysia, Singapore, Taiwan, and Thailand.   Methods:  All patients presenting to a physician with primary diagnosis of interest and who consented were enrolled. Of 13,902 participants screened, the study enrolled 5250 participants - Asthma (13.5%), AR (14.0%), COPD (4.9%) or Rhinosinusitis (5.4%). Participants completed a survey of respiratory symptoms, HCRU (office visits, ER visits, hospitalization, medication use, etc.) and Work Productivity and Activity Impairment.   Results:  HCRU in four weeks before the visit was greater for participants with cough as main reason for their current medical visit compared to those presenting with a different primary symptom. More participants with cough visited a GP (31.5% vs 19.0%), emergency department (2.4% vs 1.4%) and less visited a specialist (21.4% vs 27.5%). Patients with primary diagnosis of COPD reported highest medication use (91%), followed by Asthma (87%), AR (71%) and Rhinosinusitis (67%). For all patients during the last seven days prior to visit, mean (SD) impairment at work was 33.9% (27.28%), work time missed 5.1% (14.81%), and overall productivity loss 36.0% (28.31%).   Conclusions:  Asthma, AR, COPD, and Rhinosinusitis have a major impact on HCRU and work productivity in Asia. Timely, effective management of these diseases has the potential to reduce burden and save already scarce healthcare resources.
E-learning: Are all users in front of the computer all of the time?
Authors: Josephine Busuttil, Sarah Busuttil, Martin Balzan
Journal: European Respiratory Journal (2012)

Introduction: E-learning has been shown to be an effective useful tool in medical education.

Aim: To assess if medical students using e-learning are in front of the screen while using the E-lectures.

Method: 87 Final year medical students were encouraged to complete and online respiratory coarse (13 streamed lectures + 13 quizzes). A moodle E-learning management system, collected data regarding login and logout times, number of slides viewed, total time on module, and quiz scores. Project was part financed through EU funds ESF1.19(Malta). Articulate software was used for streaming.

Results: 6 lectures with corresponding quizzes were analysed for 43 medical students who completed all modules. 65.5% (Male – 66.7%, Female 64.1%) of the lectures were completed within expected time frame; 19% of lectures logged in for a period les than the duration of the lecture, while in 14.7% duration was longer than twice the total duration of the lecture. Data for 0.8% was not available. Only 16.3% of students completed all the lectures within the established period. 27.9%, 20.9%, 18.6%, missed on one 1,2,3 lectures respectively, while 16.3% missed more than 4 lectures. For log-in less than total duration, the percentage time of lecture completed inversely correlated with the actual total duration the lecture (R2=0.82). 71.6 % of those who completed lectures within the established time completed the quizzes within one hour of completing the lecture.

Conclusion: 83.7% found a way to skim through the slides for at least one lecture and/or were not physically available during presenation of the lecture all of the time. The e-learning management systems should be robust so as detect this kind of behaviour before certification.
A Comparison of Human and Animal Botulism: A Review
Authors: E M R Critchley
Journal: Journal of the Royal Society of Medicine (1991)

Botulism can arise from preformed toxin, wound infection or intestinal toxico-infection. All three forms can occur in humans as well as in animals. The examination of botulism in veterinary practice can alert the medical profession to the hazards which can occur with the introduction of dietary alterations and hermetic sealing of foodstuffs. There is also the possibility that the development of pica through lack of essential nutrients could lead to the ingestion of contaminated substances rendering the child (or even adult) susceptible to botulinum intoxication. A positive gain has been that research leading to the elimination of shaker foal disease has provided a comprehensive analysis of factors which may underline the risk of toxico-infection in infants 12 .
Use of Ender's Nails in Unstable Trochanteric Femoral Fractures
Authors: C H Marsh
Journal: Journal of the Royal Society of Medicine (1983)

Eighty consecutive patients with unstable trochanteric femoral fractures treated by the Ender technique have been studied. Early fixation failure was seen in 18% of patients. Leg shortening and external rotation deformities due to uncontrolled fragmentary collapse were found in almost 80% of the 57 surviving patients at 3 months, and caused severe disability. The continued use of the Ender technique in unstable fractures is questioned.
The Quality of Treatment for Drug Abuse
Authors: FREDERICK B. GLASER, FREDA ADLER, ARTHUR D. MOFFETT, JOHN C. BALL
Journal: American Journal of Psychiatry (1974)

In this preliminary study, less than one-third of the treatment programs for drug abusers and narcotic addicts in Pennsylvania were rated as satisfactory. Therapeutic community programs were rated significantly higher than other programs. The authors cite the importance of identifying specific factors that may be related to high-quality programs as a step toward improving the quality of the overall treatment effort.
INWORKS study: risk of leukaemia from protracted radiation exposure – Authors' reply
Authors: Mary K Schubauer-Berigan, Klervi Leuraud, David B Richardson, Elisabeth Cardis, Robert D Daniels, Michael Gillies, Jacqueline A O'Hagan, Ghassan B Hamra, Richard Haylock, Dominique Laurier, Monika Moissonnier, Isabelle Thierry-Chef, Ausrele Kesminiene
Journal: The Lancet Haematology (2015)
Cellular and molecular mechanisms of bacterial adhesion to respiratory mucosa
Authors: MC Plotkowski, O Bajolet-Laudinat, E Puchelle
Journal: European Respiratory Journal (1993)

Different bacterial species adhere avidly to respiratory mucus. Such adhesion, when followed by ciliary clearance, represents an important stage of the airway defense system. However, in pathological conditions, the mucociliary clearance may be severely reduced, and mucus-associated bacteria may multiply and infect the underlying epithelium. Only a few bacteria have been shown to adhere to ciliary membranes of functionally active ciliated cells. Therefore, the first way in which most of the respiratory pathogens associate with the airway epithelium is likely to be by their adhesion to mucus. Some bacteria also secrete products that may affect ciliary function and/or cause cell death and epithelial disruption. Respiratory pathogens that do not bind to normal ciliated cells may readily adhere to injured epithelial cells, or to the unmasked extracellular matrix. Furthermore, following injury, epithelial respiratory cells in the process of migration, in order to repair the wounds, may present receptors to which bacteria adhere. The adhesion to all of these epithelial receptors may contribute to the chronicity of many bacterial respiratory infections.
Relationship between risk factors for lung cancer and tumor size
Authors: Begoña Palomo Antequera, Miguel Arias-Guillen, Francisco Rodríguez Jerez, Gemma Rubinos Cuadrado, Pablo Martínez Camblor, Juan Bautista García Casas, Pere Casán Clara
Journal: European Respiratory Journal (2014)

Introduction :The probability of developing lung cancer (LC) can be predicted from mathematical models to assess risk factors. Our hypothesis is that these factors could be related with tumor size.   Objectives : Describe characteristics of a population with LC and assess the relationship between risk factors and tumor size.   Methods : Retrospective study in which were included patients diagnosed with LC in our hospital for a year. Medical history and radiology information was collected. The volume of the tumor size was calculated from the three diameters of the tumor.   Results: 212 patients patients were included, 112(80 %) men. Age 66 (10) years. BMI 27(4). Smoking history in 192 (91%), 93 (44 %) were current smokers. Smoking intensity:52(23) packs cigarettes-year. 45 (21%) had a high risk profession. COPD 80 (38%), radiology emphysema 43 (20 %). Personal history of cancer in 45 (21%) and family history of LC in 21 (10%).The most common symptoms were: pain (24%), dyspnea (20 %). Were incidental findings 22% of cases. Tumor types: non-small 83 % (46 % adeno). Tumor stage: III-IV 72%. Tumoral volume:77184(173402)mm 3 .  Tumor size was directly related to female sex (p   Conclusions:  Tumor size seems to be more related with social and health situation than risk factors. Tobacco has a relationship with the size, probably influenced by the increased monitoring of patients with other associated comorbidities.
Trial of sequential trimetrexate, fluorouracil, and high-dose leucovorin in previously treated patients with gastrointestinal carcinoma.
Authors: J A Conti, N Kemeny, K Seiter, E Goker, W Tong, M André, K Ragusa, J R Bertino
Journal: Journal of Clinical Oncology (1994)

PURPOSE Trimetrexate (TMTX) is a dihydrofolate reductase inhibitor, which, like methotrexate (MTX), has been shown to potentiate fluorouracil (FU) cytotoxicity by increasing phosphoribosylpyrophosphate (PRPP) levels. We investigated the safety and efficacy of a sequential TMTX/FU/leucovorin (LV) combination. PATIENTS AND METHODS Forty-one patients with advanced gastrointestinal carcinoma (mostly colorectal) received variable doses of TMTX followed 24 hours later by FU/LV (500 mg/m2 of each drug). Almost all patients had received previous chemotherapy. The initial 19 patients were treated on a 3-week-on/1-week-off schedule without any significant toxicity; the remaining patients were treated for 6 consecutive weeks followed by a 2-week rest period. TMTX was escalated in 30-mg/m2 increments from 20 to 110 mg/m2 in separate patient cohorts. When the 110-mg/m2 dose of TMTX was reached, the FU dose was escalated from 500 mg/m2 to 600 mg/m2. RESULTS The partial response (PR) rate in assessable patients with colorectal cancer (all previously treated) was 20% (seven of 35; 95% confidence interval, 7% to 33%), and with other gastrointestinal cancers was one of four patients. Median survival has not been reached with a median follow-up of 13.5 months. The maximum-tolerated dose (MTD) was 110 mg/m2 for TMTX, 500 mg/m2 for FU, and 500 mg/m2 for LV on a 6-weeks-on/2-weeks-off cycle. The principal toxicities were grade 3 or 4 diarrhea, which occurred in 17% of patients, and hypersensitivity reactions, which occurred in 26% of patients. CONCLUSION TMTX can be administered at maximal doses in combination with FU and LV without increasing toxicity. The PR rate of 20% in advanced colorectal carcinoma patients previously treated with chemotherapy is encouraging and merits further study.
Retinoic acid-induced CHD5 upregulation and neuronal differentiation of neuroblastoma
Authors: Mayumi Higashi, Venkatadri Kolla, Radhika Iyer, Koumudi Naraparaju, Tiangang Zhuang, Sriharsha Kolla, Garrett M. Brodeur
Journal: Molecular Cancer (2015)

Chromodomain-helicase DNA binding protein 5 (CHD5) is an important tumor suppressor gene deleted from 1p36.31 in neuroblastomas (NBs). High CHD5 expression is associated with a favorable prognosis, but deletion or low expression is frequent in high-risk tumors. We explored the role of CHD5 expression in the neuronal differentiation of NB cell lines.NB cell lines SH-SY5Y (SY5Y), NGP, SK-N-DZ, IMR5, LAN5, SK-N-FI, NB69 and SH-EP were treated with 1-10 μM 13-cis-retinoic acid (13cRA) for 3-12 days. qRT-PCR and Western blot analyses were performed to measure mRNA and protein expression levels, respectively. Morphological differences were examined by both phase contrast and immunofluorescence studies.Treatment of SY5Y cells with 13cRA caused upregulation of CHD5 expression in a time- and dose-dependent manner (1, 5, or 10 μM for 7 or 12 days) and also induced neuronal differentiation. Furthermore, both NGP and SK-N-DZ cells showed CHD5 upregulation and neuronal differentiation after 13cRA treatment. In contrast, 13cRA treatment of IMR5, LAN5, or SK-N-FI induced neither CHD5 expression nor neuronal differentiation. NB69 cells showed two different morphologies (neuronal and substrate adherent) after 12 days treatment with 10 μM of 13cRA. CHD5 expression was high in the neuronal cells, but low/absent in the flat, substrate adherent cells. Finally, NGF treatment caused upregulation of CHD5 expression and neuronal differentiation in SY5Y cells transfected to express TrkA (SY5Y-TrkA) but not in TrkA-null parental SY5Y cells, and both changes were blocked by a pan-TRK inhibitor.Treatment with 13cRA induces neuronal differentiation only in NB cells that upregulate CHD5. In addition, NGF induced CHD5 upregulation and neuronal differentiation only in TrkA expressing cells. Together, these results suggest that CHD5 is downstream of TrkA, and CHD5 expression may be crucial for neuronal differentiation induced by either 13cRA or TrkA/NGF signaling.
Mouse p10, an Alternative Spliced Form of p15INK4b, Inhibits Cell Cycle Progression and Malignant Transformation
Authors: Ignacio Pérez de Castro, Marta Benet, María Jiménez, Saba Alzabin, Marcos Malumbres, Angel Pellicer
Journal: Cancer Research (2005)

Abstract The INK4 family of proteins negatively regulates cell cycle progression at the G1-S transition by inhibiting cyclin-dependent kinases. Two of these cell cycle inhibitors, p16INK4A and p15INK4B, have tumor suppressor activities and are inactivated in human cancer. Interestingly, both INK4 genes express alternative splicing variants. In addition to p16INK4A, the INK4A locus encodes a splice variant, termed p12—specifically expressed in human pancreas—and ARF, a protein encoded by an alternative reading frame that acts as a tumor suppressor through the p53 pathway. Similarly, the human INK4B locus encodes the p15INK4B tumor suppressor and one alternatively spliced form, termed as p10. We show here that p10, which arises from the use of an alternative splice donor site within intron 1, is conserved in the mouse genome and is widely expressed in mouse tissues. Similarly to mouse p15INK4B, p10 expression is also induced by oncogenic insults and transforming growth factor-β treatment and acts as a cell cycle inhibitor. Importantly, we show that mouse p10 is able to induce cell cycle arrest in a p53-dependent manner. We also show that mouse p10 is able to inhibit foci formation and anchorage-independent growth in wild-type mouse embryonic fibroblasts, and that these antitransforming properties of mouse p10 are also p53-dependent. These results indicate that the INK4B locus, similarly to INK4A-ARF, harbors two different splicing variants that can be involved in the regulation of both the p53 and retinoblastoma pathways, the two major molecular pathways in tumor suppression.
Molecular evolution of human visual pigment genes.
Authors: S Yokoyama, R Yokoyama
Journal: Molecular Biology and Evolution (1989)

By comparing the published DNA sequences for (a) the genes encoding the human visual color pigments (red, green, and blue) with (b) the genes encoding human, bovine, and Drosophila rhodopsins, a phylogenetic tree for the mammalian pigment genes has been constructed. This evolutionary tree shows that the common ancestor of the visual color pigment genes diverged first from that of the rhodopsin genes; then the common ancestor of the red and green pigment genes and the ancestor of the blue pigment gene diverged; and finally the red and green pigment genes diverged from each other much more recently. Nucleotide substitutions in the rhodopsin genes are best explained by the neutral theory of molecular evolution. However, important functional adaptations seem to have occurred twice during the evolution of the color pigment genes in humans: first, to the common ancestor of the three color pigment genes after its divergence from the ancestor of the rhodopsin gene and, second, to the ancestor of the red pigment gene after its divergence from that of the green pigment gene.
Formoterol-induced downregulation of the beta2-adrenoceptor in asthmatics with homozygous glycine-16 polymorphism
Authors: Leonello Fuso, Alessandra Di Perna, Anna Longobardi, Andrea Trove, Michela Bisceglia, Benedetta Bibi, Carla Angelozzi, Francesco Danilo Tiziano, Raffaele Antonelli Incalzi
Journal: European Respiratory Journal (2013)

Polymorphism at codon 16 of the beta2-adrenoceptor (beta2-AR) affects the responsiveness to salmeterol in asthmatics. Data concerning formoterol are more controversial in literature. The aim of this study was to verify whether homozygous for arginine-16 (ArgArg16) and homozygous for glycine-16 (GlyGly16) genotypes differently influence the long-term responsiveness to formoterol. Twenty-nine patients with mild-to-moderate asthma, in stable clinical conditions, underwent genotyping at codon 16 of the beta2-AR by RFLP-PCR assay and performed baseline respiratory function tests. The effects of a 4-week mono-therapy with formoterol (12 mcg BID) were tested on the peak expiratory flow (PEF) variability and the forced expiratory volume in 1 sec (FEV1) slope of the dose-response curve to salbutamol. According to the genotypic analysis, 14 patients were GlyGly16, 5 were ArgArg16, and 10 were heterozygous ArgGly16. Variability in PEF significantly increased during the 4-week treatment period in GlyGly16, but not in pooled ArgArg16 and ArgGly16 patients (p=0.032). The FEV1 slope of the dose-response curve to salbutamol decreased in GlyGly16, but not in pooled ArgArg16 and ArgGly16 patients. This study provides preliminary evidence that tolerance to formoterol develops more frequently in asthmatics carrying the GlyGly16 genotype. If confirmed in a larger population, this finding might be introductory to choose formoterol or salmeterol on the basis of genetic polymorphism at codon 16 of the beta2-AR.
Evaluation of the Xpert Flu test and comparison with in-house real-time RT-PCR assays for detection of influenza virus from 2008 to 2011 in Marseille, France
Authors: N. Salez, L. Ninove, L. Thirion, C. Gazin, C. Zandotti, X. de Lamballerie, R.N. Charrel
Journal: Clinical Microbiology and Infection (2012)
Abstract 370: Modeling signaling networks in tumor immunology
Authors: Trevor Clancy, Eivind Hovig
Journal: Cancer Research (2014)

Abstract Despite decades of successful discoveries, the overwhelming molecular complexity of cells has been a significant barrier to gain a fundamental understanding of how cells work as a whole, how they are perturbed in cancer, and how they interact with signals from the immune system. To achieve a more complete understanding, will require the assistance of network modeling. By developing computational network models we can introduce cancer mutations to simulate pharmacological perturbations, or loss-of-function and gain-of-function experiments and study the dynamics of biochemical networks change under different immune signaling states. We are developing and applying rule-base (kappa) network modeling of signaling networks to study how microenvironment immune factors influence a tumor's behavior. In particular, that of immune mediated cellular senescence in tumor cells. We have built a rule-base network model of the biochemical network regulating immune mediated cell senescence in melanomas, which carry a BRAFV600 mutation in the MAPK signaling network. Using computational methods we have characterized the crosstalk with cytokine signaling networks and the crosstalk with other growth signaling networks. The development of such a computational model may help researchers understand how BRAFV600 cells in melanomas communicate with their environment by secreting various cytokines and growth factors, as it has become clear that this immune ‘secretory phenotype’ can have pro- as well as anti-tumorigenic effects. By combining rule-based descriptions of the biochemical reactions associated to this phenotype with computer simulation we can open up new avenues for exploring such complex networks linked to melanoma progression. Citation Format: Trevor Clancy, Eivind Hovig. Modeling signaling networks in tumor immunology. [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 370. doi:10.1158/1538-7445.AM2014-370