tbuckley/cabot-search huggingface dataset:
The emerging molecular pathogenesis of neuroblastoma: implications for improved risk assessment and targeted therapy
Authors: Nadine Van Roy, Katleen De Preter, Jasmien Hoebeeck, Tom Van Maerken, Filip Pattyn, Pieter Mestdagh, Joëlle Vermeulen, Jo Vandesompele, Frank Speleman
Journal: Genome Medicine (2009)

Neuroblastoma is one of the most common solid tumors of childhood, arising from immature sympathetic nervous system cells. The clinical course of patients with neuroblastoma is highly variable, ranging from spontaneous regression to widespread metastatic disease. Although the outcome for children with cancer has improved considerably during the past decades, the prognosis of children with aggressive neuroblastoma remains dismal. The clinical heterogeneity of neuroblastoma mirrors the biological and genetic heterogeneity of these tumors. Ploidy and MYCN amplification have been used as genetic markers for risk stratification and therapeutic decision making, and, more recently, gene expression profiling and genome-wide DNA copy number analysis have come into the picture as sensitive and specific tools for assessing prognosis. The applica tion of new genetic tools also led to the discovery of an important familial neuroblastoma cancer gene, ALK, which is mutated in approximately 8% of sporadic tumors, and genome-wide association studies have unveiled loci with risk alleles for neuroblastoma development. For some of the genomic regions that are deleted in some neuroblastomas, on 1p, 3p and 11q, candidate tumor suppressor genes have been identified. In addition, evidence has emerged for the contribution of epigenetic disturbances in neuroblastoma oncogenesis. As in other cancer entities, altered microRNA expression is also being recognized as an important player in neuroblastoma. The recent successes in unraveling the genetic basis of neuroblastoma are now opening opportunities for development of targeted therapies.
Multidrug-resistant tuberculosis around the world: what progress has been made?
Authors: Dennis Falzon, Fuad Mirzayev, Fraser Wares, Inés Garcia Baena, Matteo Zignol, Nguyen Linh, Karin Weyer, Ernesto Jaramillo, Katherine Floyd, Mario Raviglione
Journal: European Respiratory Journal (2014)

Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa. The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for &gt;90% of the estimated MDR-TB cases among notified TB cases worldwide. In 2012, a median of 14% (interquartile range 6–50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was &gt;50% higher than in 2011. Median treatment success was 53% (interquartile range 40–70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010. Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB.
Risk factors associated with superspreading events in SARS.
Authors: Ali A Mohammed
Journal: Thorax (2007)

▴ Yu IT, Xie ZH, Tsoi KK. Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? Clin Infect Dis2007;44:1017–25.

[OpenUrl][1][Abstract/FREE Full Text][2]



The severe acute respiratory syndrome (SARS) outbreak of 2003 originated in Hong Kong, China, and 71.1% of the subsequent infections in Hong Kong were attributable to superspreading events. Most of these superspreading events occurred in hospitals.

This case control study identified risk factors associated with outbreaks of SARS in hospital wards in Guangzhou and …

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Peak inspiratory flow rates through placebo dry powder inhaler device in various asthma and COPD patients
Authors: Rain Jõgi, Kaja Julge, Priit Samarüütel, Liisa Raatikainen, Timo Vanto
Journal: European Respiratory Journal (2012)

Dry powder inhalers (DPIs) are inspiratory flow driven. We sought to characterise inspiratory flow parameters of placebo dry powder inhaler devices in asthma patients of various age groups and in patients with chronic obstructive pulmonary disease (COPD) in an open, randomised, multicentre study (SALIF). Preliminary data of the Easyhaler® arm will be presented.  The primary variable was the peak inspiratory flow (PIF) rate through the inhaler. Three inspiratory flow curves were recorded and the best of them was analysed. To ensure consistent dose delivery of the drug peak inspiratory flow rates for this device should be 28 L/min or higher.  A total of 227 subjects with documented diagnosis of asthma and/or COPD of various severities were included in the open-label study. Asthmatic patients were divided into three different age groups: 4-11 years (n=60), 12-64 years (n=62) and ≥ 65 years (n=52). COPD patients consisted of all ages groups (n=53)  Irrespective of age or the severity of disease, most asthma and COPD patients were able to inhale through the studied DPI device with an adequate PIF.
Nedocromil sodium<i>versus</i>sodium cromoglycate in treatment of exercise-induced bronchoconstriction: a systematic review
Authors: K.D. Kelly, C.H. Spooner, B.H. Rowe
Journal: European Respiratory Journal (2001)

The objective of this review was to compare the effects of prophylactic doses of nedocromil sodium (NCS) and sodium cromoglycate (SCG) on postexercise lung function, in persons diagnosed with exercise-induced bronchoconstriction. Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register, plus hand searching for trials in journals, bibliographies of relevant studies and review articles. Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were pooled using odds ratios (OR) for dichotomous outcomes or weighted mean differences (WMD) with 95% confidence intervals (95% CI) for continuous outcomes. No significant differences were noted between NCS and SCG with respect to the maximum per cent decrease in forced expiratory volume in one second (WMD=−0.88; 95% CI −4.50–2.74), complete protection (OR=0.95; 95% CI 0.50–1.81), clinical protection (OR=0.71; 95% CI 0.36–1.39), unpleasant taste (OR=6.85; 95% CI 0.77–60.73), or sore throat (OR=3.46; 95% CI 0.32–37.48). Subgroup analyses based on age, dosages of medications and timing of exercise postinhalation were consistent with the overall pooled analyses. No significant differences were evident between the effects of nedocromil sodium and sodium cromoglycate during the immediate postexercise period in adults and children with exercise-induced bronchoconstriction, with regards to maximum per cent decrease in forced expiratory volume in one second, complete protection, or clinical protection. Side-effect profiles were similar.
Genome-wide analysis of condensin binding in Caenorhabditis elegans
Authors: Anna-Lena Kranz, Chen-Yu Jiao, Lara Heermans Winterkorn, Sarah Elizabeth Albritton, Maxwell Kramer, Sevinç Ercan
Journal: Genome biology (2013)

Abstract Background Condensins are multi-subunit protein complexes that are essential for chromosome condensation during mitosis and meiosis, and play key roles in transcription regulation during interphase. Metazoans contain two condensins, I and II, which perform different functions and localize to different chromosomal regions. Caenorhabditis elegans contains a third condensin, I DC , that is targeted to and represses transcription of the X chromosome for dosage compensation. Results To understand condensin binding and function, we performed ChIP-seq analysis of C. elegans condensins in mixed developmental stage embryos, which contain predominantly interphase nuclei. Condensins bind to a subset of active promoters, tRNA genes and putative enhancers. Expression analysis in kle-2 -mutant larvae suggests that the primary effect of condensin II on transcription is repression. A DNA sequence motif, GCGC, is enriched at condensin II binding sites. A sequence extension of this core motif, AGGG, creates the condensin I DC motif. In addition to differences in recruitment that result in X-enrichment of condensin I DC and condensin II binding to all chromosomes, we provide evidence for a shared recruitment mechanism, as condensin I DC recruiter SDC-2 also recruits condensin II to the condensin I DC recruitment sites on the X. In addition, we found that condensin sites overlap extensively with the cohesin loader SCC-2, and that SDC-2 also recruits SCC-2 to the condensin I DC recruitment sites. Conclusions Our results provide the first genome-wide view of metazoan condensin II binding in interphase, define putative recruitment motifs, and illustrate shared loading mechanisms for condensin I DC and condensin II.
Effects of cyclosporin on collagen induced arthritis in mice.
Authors: K Takagishi, N Kaibara, T Hotokebuchi, C Arita, M Morinaga, K Arai
Journal: Annals of the Rheumatic Diseases (1986)

We have studied the effect of the immunosuppressive agent cyclosporin on collagen induced arthritis in mice. Cyclosporin, when given prophylactically, was capable of suppressing the development of collagen induced arthritis and the immunological response to native type II collagen in a dose dependent manner. Furthermore, treatment with cyclosporin, started on the same day as the booster injection with type II collagen, also resulted in inhibition of development of arthritis and of immunity to collagen. These findings suggest that the time of a booster injection, three weeks after the initial immunisation, might be still within the induction phase of arthritis since reinoculation is required to produce a high incidence of arthritis in mice. In addition, therapeutic treatment with cyclosporin did not affect the clinical course of the disease or the immune response to collagen.
National Library of Medicine: Database Gateway
Authors: Jody Zylke
Journal: JAMA (1987)

PHYSICIANS MAY USE computers to facilitate record keeping or to play computer games. Many, however, use them for access to information from remotely situated databases.  The National Library of Medicine's MEDLARS (Medical Literature Analysis and Retrieval System) probably is the best known and most widely used medical information system. It provides access to 18 databases, not restricted to medical science. For instance, the growing interaction between medicine and society is reflected in BIOETHICS, produced by the Kennedy Institute of Ethics at Georgetown University, Washington, DC, which provides references on medical ethics and public policy, and HEALTH, which deals with economic, legal, and administrative aspects of medicine.  MEDLARS also has AVLINE, providing citations to audiovisual materials, and HISTLINE, for medical history information. And some of the computer databases are the equivalent of reference books (a dictionary of chemicals, a thesaurus of biomedical terms, and a directory of organizations providing health information
Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Drugs
Authors: William Bensinger
Journal: Journal of Clinical Oncology (2007)

The treatment of multiple myeloma (MM) is changing rapidly. During the last 10 years, higher rates of complete response (CR) and prolonged progression-free and overall survival have been seen with high-dose chemotherapy plus autologous stem-cell transplantation (HDT-ASCT). Achievement of CR and good partial response have been shown to be key prognostic factors for prolonged survival, with eradication of minimal residual disease seeming crucial to long-term disease-free survival. Until recently, high rates of CR and other major responses were primarily seen with HDT-ASCT, but insights into the biology of MM have led to the development and approval of new drugs with significant activity, and new induction regimens based on these novel agents are offering improved responses. Thalidomide, bortezomib, and lenalidomide have been combined with corticosteroids, alkylators, and anthracyclines in front-line MM treatment. Phase II studies have indicated that high rates of response and CR may be achieved. The substantial activity seen with these new drug combinations has prompted a re-examination of the role of SCT in MM treatment. Will achievement of major responses with these new regimens translate into improved survival after consolidation with transplantation? Will these improved induction regimens reduce the need for tandem transplantation, or does achievement of CR obviate the need for front-line transplantation altogether? To help address these questions, randomized trials are needed, as well as tests with improved sensitivity to better define depth of remission.
Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine
Authors: Scott M. Hammer, Magdalena E. Sobieszczyk, Holly Janes, Shelly T. Karuna, Mark J. Mulligan, Doug Grove, Beryl A. Koblin, Susan P. Buchbinder, Michael C. Keefer, Georgia D. Tomaras, Nicole Frahm, John Hural, Chuka Anude, Barney S. Graham, Mary E. Enama, Elizabeth Adams, Edwin DeJesus, Richard M. Novak, Ian Frank, Carter Bentley, Shelly Ramirez, Rong Fu, Richard A. Koup, John R. Mascola, Gary J. Nabel, David C. Montefiori, James Kublin, M. Juliana McElrath, Lawrence Corey, Peter B. Gilbert
Journal: New England Journal of Medicine (2013)

A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States.
Familial and idiopathic colonic varices: an unusual cause of lower gastrointestinal haemorrhage.
Authors: J P Iredale, P Ridings, F P McGinn, M J Arthur
Journal: Gut (1992)

A patient is described presenting with an acute lower gastrointestinal haemorrhage as a result of extensive colonic varices. Further investigation revealed that there were no oesophageal varices or splenomegaly. Liver biopsy showed grade II fatty change only, with no other specific or significant pathological features. Transhepatic portography showed a raised portal pressure (20 mm/Hg) but the portal system was patent throughout. There was an abnormal leash of vessels in the caecum thought to represent a variceal plexus. This patient was diagnosed as having idiopathic colonic varices. This case is discussed together with nine other reports of idiopathic colonic varices from the published literature. Four of these reports describe idiopathic colonic varices in more than one member of the same family. Possible modes of inheritance, aetiology of variceal change, natural history, and prognosis are discussed.
Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages
Authors: Borja G. Cosio, Loukia Tsaprouni, Kazuhiro Ito, Elen Jazrawi, Ian M. Adcock, Peter J. Barnes
Journal: The Journal of Experimental Medicine (2004)

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lungs with little or no response to glucocorticoids and a high level of oxidative stress. Histone deacetylase (HDAC) activity is reduced in cells of cigarette smokers, and low concentrations of theophylline can increase HDAC activity. We measured the effect of theophylline on HDAC activity and inflammatory gene expression in alveolar macrophages (AM) from patients with COPD. AM from normal smokers showed a decrease in HDAC activity compared with normal control subjects, and this was further reduced in COPD patients (51% decrease, P &amp;lt; 0.01). COPD AMs also showed increased basal release of IL-8 and TNF-α, which was poorly suppressed by dexamethasone. Theophylline induced a sixfold increase in HDAC activity in COPD AM lysates and significantly enhanced dexamethasone suppression of induced IL-8 release, an effect that was blocked by the HDAC inhibitor trichostatin A. Therefore, theophylline might restore steroid responsiveness in COPD patients.
Phenotypic Heterogeneity in Multiple Myeloma Families
Authors: Henry T. Lynch, Patrice Watson, Stefano Tarantolo, Peter H. Wiernik, Brigid Quinn-Laquer, Karin Isgur Bergsagel, Laetitia Huiart, O.I. Olopade, Hagay Sobol, Warren Sanger, David Hogg, Dennis Weisenburger
Journal: Journal of Clinical Oncology (2005)

To describe a series of families with familial multiple myeloma (MM). Observations were used to generate hypotheses about the role of genetic factors, the mode of inheritance of these factors, and the association of other cancers with familial MM.This observational study consisted of 39 families with multiple cases of MM or related disorders from four collaborating research centers. Each center followed its usual family study method. Probands were interviewed, and, when possible, cancers were verified by medical records and pathology review. A working pedigree was compiled on each family.Seventeen families had affected members in two or more generations, and eight families had two or more affected members in a single generation. Four families had two or more members with plasma cell dyscrasias, with or without a single case of MM. In the remaining 10 families, a single MM case occurred with a family history of other cancers. Other cancers observed in family members included hematologic malignancies and solid tumors. In families with MM in multiple generations, there was a decrease in the age at MM diagnosis in successive generations.The study of familial MM may provide insights into the pathogenesis and, ultimately, the control and prevention of MM and related disorders. Population-based epidemiologic studies are crucial, but because of the rarity of familial MM, a concerted case-finding approach may also be fruitful. Therefore, we propose an international consortium to study familial MM, and we invite all interested colleagues to participate.
Nutrition and Cancer: Physiological Interrelationships
Authors: Jan van Eys
Journal: Annual Review of Nutrition (1985)

There are many tumors that have paraneoplastic syndromes. Furthermore, location of certain tumors can result in very specific effects on the host, especially tumors in the hypothalamus, the intestinal tract, or the liver. Finally, tumors of the immune system can have significant distant consequences. However, from direct experimental evidence, from model systems, and from the utilization of nutritional manipulation in the treatment of cancer, the data suggest very strongly that there is no unique cancer malnutrition. Early diagnosed cancer does not show malnutrition as a presenting symptom. Furthermore, all metabolic disturbances can be explained on the basis of the metabolic differences of tumor cells and normal cells and are very frequently proportional to the bulk of the tumor. The cachexia that is associated with malignancies is more likely cachexia in cancer patients than it is a specific cancer cachexia, unless the tumor burden is very large. This point was clearly made in a short review of the causes of cachexia in nearly 1500 cancer patients in Russia (145). Brennan also feels that most cases of malnutrition are uncomplicated starvation, and cancer cachexia has many features seen in major injury or sepsis (16). This distinction has great implications in the management of cancer patients.
Antimicrobial profile and bacterial resistance in patients wit acute exacerbation of COPD, an Upper Egypt multicenters experience
Authors: Yaser Gad, Gamal Agmy
Journal: European Respiratory Journal (2013)

PURPOSE:  To identify the causative bacteria, antibiotic sensitivity and antibiotic resistance of acute exacerbation of COPD (AECOPD) in Upper Egypt considering this an important issue to be investigated in our locality.  METHODS:  A multicentre prospective study was performed for two years in Assiut, El-Minia and Sohag universities. Sampling was done for all patients including, sputum for gram stain and culture, and serum sample for serology. The validated sputum as well as BAL samples were cultured on three bacteriological media (Nutrient, Chocolate and MaConkey,s agar plates). atypical pathogens were identified through the use of serological indirect Fluorescent Antibody method.  RESULTS:  The predominant isolates in 376 patients with acute exacerbation of COPD (AECOPD) were Heamophilus Influnza (32%), streptococcus pneumonia (30%), Moraxella catarrhalis (14%), Klebsiella pneumoniae (10%) and chlamydia pneumoniae (7%). A higher sensitivity was recorded for Moxifloxacin, Levofloxacin, Macrolides, and Cefipime. A higher rate of resistance was recorded for tetracyclines, first or second generations cephalosporins and gentamicin.  CONCLUSIONS:  Heamophilus Influnza, streptococcus pneumonia are the predominant pathogens in nearly two third of patients with AECOPD in upper Egypt, Respiratory quinolones, macrolids and cefipime showed the highest sensitivity while tetracyclines, first or second generations cephalosporins and gentamicin shoed the lowest sensitivity in dealing with such excerbation  CLINICAL IMPLICATIONS:  Respiratory quinolones, cefipime and macrolides are the most efficient antibiotics in treatment of AECOPD in upper Egypt.
Learning how to control biases in studies to identify adverse effects of drugs: a brief personal history
Authors: Hershel Jick
Journal: Journal of the Royal Society of Medicine (2009)

Prior to 1966, almost all available information on drug safety for marketed medicines was strictly qualitative. It was predominantly based on anecdotal reports and clinical opinions derived primarily from the known pharmacology of particular drugs. While the medical environment for identifying and quantifying drug toxicity was generally informal and undirected, the use of anecdotal reports to detect serious drug toxicity was sufficient for identifying the toxicity associated with thalidomide.1,2 But the mechanism of discovery was unacceptably inefficient since an estimated 9000 babies were born with thalidomide‐caused phocomelia before the toxic effect was recognized and described in 1960.