tbuckley/cabot-search huggingface dataset:
What happens to patients with COPD with long-term oxygen treatment who receive mechanical ventilation for COPD exacerbation? A 1-year retrospective follow-up study
Authors: N. Hajizadeh, K. Goldfeld, K. Crothers
Journal: Thorax (2014)

We performed a retrospective cohort study of patients with chronic obstructive lung disease (COPD) on long-term oxygen treatment (LTOT) who received invasive mechanical ventilation for COPD exacerbation. Of the 4791 patients, 23% died in the hospital, and 45% died in the subsequent 12 months. 67% of patients were readmitted at least once in the subsequent 12 months, and 26.8% were discharged to a nursing home or skilled nursing facility within 30 days. We conclude that these patients have high mortality rates, both in-hospital and in the 12 months postdischarge. If patients survive, many will be readmitted to the hospital and discharged to nursing home. These potential outcomes may support informed critical care decision making and more preference congruent care.
Evidence in Support of Hypoxia but Against High Potassium and Hyperosmolarity as Possible Mediators of Sustained Vasodilation in Rabbit Cardiac and Skeletal Muscle
Authors: Miklos Gellai, Reed Detar
Journal: Circulation Research (1974)

The vasoactive properties of hypoxia, elevated extracellular potassium concentration ([K] o ), and hyperosmolarity were studied in helical strip preparations of small coronary and deep femoral arteries (260-700 µm, o.d.) equilibrated in a physiological salt solution with an oxygen tension (Po 2 ) of 100 mm Hg, [K] o of 3.18 mM, and an osmolarity of 304 milliosmoles/liter. Increasing [K] o (2-6 mM) or osmolarity (30-50 milliosmoles/liter) produced relaxation of resting tension in 50% of the coronary strips but had no effect on resting tension in deep femoral strips. Sustained increments in [K] o or osmolarity produced concentration-dependent, transient relaxation of aganist-induced contractile tension in both coronary and deep femoral arterial strips: a potassium increment of 4 mM produced 40% relaxation with 100% recovery within 5-6 minutes, an osmotic increment of 30 milliosmoles/liter caused 20-40% relaxation with 100% recovery within 15-60 minutes, and simultaneous potassium (4 mM) and osmotic (30 milliosmoles/liter) increments produced 85-95% relaxation with 100% recovery within 10-15 minutes. Decreasing Po 2 from 100 mm Hg to 10 mm Hg resulted in a sustained 35-40% fall in agonist-induced contractile tension. Although a nonspecific additive interaction was observed during a simultaneous change to high [K] o , hyperosmolarity, and hypoxia, for any given level of vascular tone hypoxia had little or no effect on the degree or the duration of the tension relaxation-recovery sequence produced by elevated [K] o , hyperosmolarity, or both. Therefore, it is proposed that hypoxia is the only one of these three factors that, by a direct interaction with vascular smooth muscle cells, can contribute to sustained vasodilation of small arteries in rabbit cardiac or skeletal muscle.
Development, validation, and initial results of the Angioedema Activity Score
Authors: K. Weller, A. Groffik, M. Magerl, N. Tohme, P. Martus, K. Krause, M. Metz, P. Staubach, M. Maurer
Journal: Allergy (2013)

Abstract Background Recurrent angioedema ( R ec A ) is a frequent clinical problem characterized by suddenly occurring cutaneous and/or mucosal swellings. Depending on their location, R ec A may be painful, hindering, disfiguring, or even life‐threatening. The assessment of disease activity in affected patients is important to guide treatment decisions. Currently, however, there is no standardized and validated outcome measure available to do so. Objective To develop and validate the first specific patient‐reported outcome instrument to assess disease activity in R ec A patients, the A ngioedema A ctivity S core ( AAS ). Methods After a set of potential AAS items was developed, item evaluation and reduction were performed by means of impact analysis, factor analysis, regression analysis, and by checking for face validity. In addition, the items of the final AAS questionnaire were tested for their validity and reliability during a 12‐week validation study. Results In total, data from 110 and 80 R ec A patients were used during the AAS item evaluation and validation phase, respectively. The resulting AAS consisted of five items and was found to have a one‐dimensional structure and excellent internal consistency. It correlated well with other measures of disease activity and quality‐of‐life impairment, thus demonstrating its convergent validity. In addition, the known‐groups validity and test–retest reliability of the AAS were found to be good. Conclusions The AAS is the first validated and reliable tool to determine disease activity in R ec A patients, and it may serve as a valuable instrument in future clinical studies and routine patient care.
The HapMap and Genome-Wide Association Studies in Diagnosis and Therapy
Authors: Teri A. Manolio, Francis S. Collins
Journal: Annual Review of Medicine (2009)

The International HapMap Project produced a genome-wide database of human genetic variation for use in genetic association studies of common diseases. The initial output of these studies has been overwhelming, with over 150 risk loci identified in studies of more than 60 common diseases and traits. These associations have suggested previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. Here we examine the development and application of the HapMap to genome-wide association (GWA) studies; present and future technologies for GWA research; current major efforts in GWA studies; successes and limitations of the GWA approach in identifying polymorphisms related to complex diseases; data release and privacy polices; use of these findings by clinicians, the public, and academic physicians; and sources of ongoing authoritative information on this rapidly evolving field.
TCR-transgenic lymphocytes specific for HMMR/Rhamm limit tumor outgrowth in vivo
Authors: Stefani Spranger, Irmela Jeremias, Susanne Wilde, Matthias Leisegang, Lilian Stärck, Barbara Mosetter, Wolfgang Uckert, Mirjam H. M. Heemskerk, Dolores J. Schendel, Bernhard Frankenberger
Journal: Blood (2012)
The global public health burden of sex work: a call for research
Authors: Brian Willis
Journal: The Lancet Global Health (2013)

An understanding of the global health burden of sex work, including sex trafficking and transactional sex, is urgently needed to direct resources to very large and vulnerable populations. Estimation of this burden will be a challenge, but similar efforts have been undertaken in other populations and for other complex issues that are difficult to measure, such as female genital mutilation. Although thousands of studies on sex work have been undertaken and substantial data collected on the health problems of sex workers, including HIV and other sexually transmitted infections, alcohol and drug use, mental health problems, and violence, we do not know the global health burden of sex work. By contrast, the health burden of other issues that profoundly affect millions of people globally, such as HIV and violence against women, have been estimated. Estimations of the health burden of sex work should consider morbidity, long-term disabilities, and mortality in male, female, and transgender sex workers. Data are needed not only for acute and present health problems of sex workers, but also for permanent and chronic disabilities and mortality..... Language: en
Role of Cytokines in the Pathogenesis of Inflammatory Bowel Disease
Authors: Konstantinos A. Papadakis, Stephan R. Targan
Journal: Annual Review of Medicine (2000)

Recent advances in the drug treatment of inflammatory bowel disease (IBD) have paralleled our understanding of the pathophysiology of ulcerative colitis and Crohn’s disease. Several proinflammatory and immune-regulatory cytokines are upregulated in the mucosa of patients with IBD, and differences and similarities in the cytokine profiles of ulcerative colitis and Crohn’s disease have been elucidated. Several clinical trials involving a chimeric anti-TNF-α (tumor necrosis factor-α) antibody have shown marked clinical benefit in the majority of patients with Crohn’s disease, verifying the importance of TNF-α in the pathogenesis of Crohn’s disease. In preliminary studies, treatment with recombinant human interleukin-10 has been beneficial in Crohn’s disease but not in ulcerative colitis. Future treatment of IBD may include combination or sequential cytokine and anticytokine administration in defined groups of patients based on their mucosal cytokine profiles.
Chimeric del20q in a case of chronic neutrophilic leukemia
Authors: Michele B. Frank, Thomas H. Norwood, Dennis M. Willerford
Journal: American Journal of Hematology (2000)

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder in which recurrent abnormalities of chromosome 20 have been reported. We report the case of a 76-year-old woman with CNL with partial deletion of the long arm of chromosome 20 in a subset of bone marrow metaphases, suggesting coexistence of a clonal stem cell disorder and normal hematopoiesis. Review of the literature suggests that such mosaicism is common in CNL, possibly accounting for the favorable prognosis observed in many patients with this disorder. Am. J. Hematol. 64:229–231, 2000. © 2000 Wiley-Liss, Inc.
Prevention of Mother-to-Child HIV Transmission in Resource-Poor Countries
Authors: Kevin M. De Cock, Mary Glenn Fowler, Eric Mercier, Isabelle de Vincenzi, Joseph Saba, Elizabeth Hoff, David J. Alnwick, Martha Rogers, Nathan Shaffer
Journal: JAMA (2000)

Each year, an estimated 590,000 infants acquire human immunodeficiency virus type 1 (HIV) infection from their mothers, mostly in developing countries that are unable to implement interventions now standard in the industrialized world. In resource-poor settings, the HIV pandemic has eroded hard-won gains in infant and child survival. Recent clinical trial results from international settings suggest that short-course antiretroviral regimens could significantly reduce perinatal HIV transmission worldwide if research findings could be translated into practice. This article reviews current knowledge of mother-to-child HIV transmission in developing countries, summarizes key findings from the trials, outlines future research requirements, and describes public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings. Public health efforts must also emphasize primary prevention strategies to reduce incident HIV infections among adolescents and women of childbearing age. Successful implementation of available perinatal HIV interventions could substantially improve global child survival.
Streptophyte Algae and the Origin of Land Plants Revisited Using Heterogeneous Models with Three New Algal Chloroplast Genomes
Authors: Bojian Zhong, Zhenxiang Xi, Vadim V. Goremykin, Richard Fong, Patricia A. Mclenachan, Philip M. Novis, Charles C. Davis, David Penny
Journal: Molecular Biology and Evolution (2013)

The phylogenetic branching order of the green algal groups that gave rise to land plants remains uncertain despite its fundamental importance to understanding plant evolution. Previous studies have demonstrated that land plants evolved from streptophyte algae, but different lineages of streptophytes have been suggested to be the sister group of land plants. To better understand the evolutionary history of land plants and to determine the potential effects of "long-branch attraction" in phylogenetic reconstruction, we analyzed a chloroplast genome data set including three new chloroplast genomes from streptophyte algae: Coleochaetae orbicularis (Coleochaetales), Nitella hookeri (Charales), and Spirogyra communis (Zygnematales). We further applied a site pattern sorting method together with site- and time-heterogeneous models to investigate the branching order among streptophytes and land plants. Our chloroplast phylogenomic analyses support previous hypotheses based on nuclear data in placing Zygnematales alone, or a clade consisting of Coleochaetales plus Zygnematales, as the closest living relatives of land plants.
Dimethylfumarate Impairs Melanoma Growth and Metastasis
Authors: Robert Loewe, Teresa Valero, Silvia Kremling, Barbara Pratscher, Rainer Kunstfeld, Hubert Pehamberger, Peter Petzelbauer
Journal: Cancer Research (2006)

Dimethylfumarate (DMF) inhibits signals transmitted by Rel proteins and is used for the treatment of inflammatory skin diseases such as psoriasis, but potential effects of DMF on tumor progression have yet not been analyzed. We show that DMF reduced melanoma growth and metastasis in severe combined immunodeficient mouse models. To identify targets of DMF action, we analyzed mRNA expression in DMF-treated melanomas by gene chip arrays. Using BiblioSphere software for data analysis, significantly regulated genes were mapped to Gene Ontology terms cell death, cell growth, and cell cycle. Indeed, we found that DMF inhibited proliferation of human melanoma cells A375 and M24met in vitro. The cell cycle was arrested at the G(2)-M boundary. Moreover, DMF was proapoptotic, as shown by cell cycle analysis and by Annexin V and Apo2.7 staining. These results were confirmed in vivo. DMF reduced proliferation rates of tumor cells as assessed by Ki-67 immunostaining and increased apoptosis as assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining. In conclusion, DMF is antiproliferative and proapoptotic and reduces melanoma growth and metastasis in animal models.
Coadministration of Endothelial and Smooth Muscle Progenitor Cells Enhances the Efficiency of Proangiogenic Cell-Based Therapy
Authors: Philippe Foubert, Gianfranco Matrone, Boussad Souttou, Carole Leré-Déan, Véronique Barateau, Jean Plouët, Sophie Le Ricousse-Roussanne, Bernard I. Lévy, Jean-Sébastien Silvestre, Gérard Tobelem
Journal: Circulation Research (2008)

Cell-based therapy is a promising approach designed to enhance neovascularization and function of ischemic tissues. Interaction between endothelial and smooth muscle cells regulates vessels development and remodeling and is required for the formation of a mature and functional vascular network. Therefore, we assessed whether coadministration of endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs) can increase the efficiency of cell therapy. Unilateral hindlimb ischemia was surgically induced in athymic nude mice treated with or without intravenous injection of EPCs (0.5×10 6 ), SMPCs (0.5×10 6 ) and EPCs+SMPCs (0.25×10 6 +0.25×10 6 ). Vessel density and foot perfusion were increased in mice treated with EPCs+SMPCs compared to animals receiving EPCs alone or SMPCs alone ( P &lt;0.001). In addition, capillary and arteriolar densities were enhanced in EPC+SMPC–treated mice compared to SMPC and EPC groups ( P &lt;0.01). We next examined the role of Ang-1/Tie2 signaling in the beneficial effect of EPC and SMPC coadministration. Small interfering RNA directed against Ang-1–producing SMPCs or Tie2-expressing EPCs blocked vascular network formation in Matrigel coculture assays, reduced the rate of incorporated EPCs within vascular structure, and abrogated the efficiency of cell therapy. Production of Ang-1 by SMPCs activates Tie2-expressing EPCs, resulting in increase of EPC survival and formation of a stable vascular network. Subsequently, the efficiency of EPC- and SMPC-based cotherapy is markedly increased. Therefore, coadministration of different types of vascular progenitor cells may constitute a novel therapeutic strategy for improving the treatment of ischemic diseases.
Combination TL01 ultraviolet B phototherapy and topical calcipotriol for psoriasis: a prospective randomized placebo-controlled clinical trial
Authors: W.K. Woo, K.E. Mckenna
Journal: British Journal of Dermatology (2003)

Summary Background Previous studies have demonstrated the ultraviolet (UV)-sparing effect of combining topical calcipotriol with broadband UVB in the treatment of psoriasis. Objectives To determine if the combination of narrowband TL01 UVB phototherapy and topical calcipotriol produces the same UVB-sparing effect. Methods This was a randomized, placebo-controlled, blinded clinical trial. Fifty psoriasis patients were recruited, 25 of whom were randomized into the active group who received TL01 phototherapy together with twice-daily application of calcipotriol cream 50 μg g−1. The control group received TL01 phototherapy and twice-daily application of a topical emollient as placebo. TL01 phototherapy was given three times per week starting at 70% minimal erythema dose with 20% increments as tolerated for up to approximately 20 sessions. Patients were assessed using the Psoriasis Area and Severity Index (PASI) and Psoriasis Disability Index (PDI). They were evaluated at treatment sessions 8, 14 and 20, and followed up at 5 and 10 weeks post-treatment. Statistical analysis was performed using a two-tailed t-test. Results There were no significant differences in demographic characteristics and baseline PASI and PDI scores between the two groups. The mean PASI score declined significantly (P < 0·01) for both groups after treatment. The difference in mean PASI score reduction from baseline between the two groups was only significant during the first eight sessions, with a net reduction of 3·6 (95% confidence interval 1·0–6·2, P = 0·008) in the active group relative to the control group. The mean PDI score declined significantly (P < 0·05) for both groups, but there was no statistical difference in mean PDI score reduction between the two groups (P = 0·8) at the end of treatment. The mean cumulative UVB dose for the active group was significantly lower (P < 0·02) at 16 204 mJ cm−2 compared with 21 082 mJ cm−2 for the control group. Conclusions We conclude that combining TL01 phototherapy with topical calcipotriol cream has a UVB-sparing effect.
MCI-154 Increases Ca <sup>2+</sup> Sensitivity of Reconstituted Thin Filament
Authors: Masataka Sata, Seiryo Sugiura, Hiroshi Yamashita, Hideo Fujita, Shin-ichi Momomura, Takashi Serizawa
Journal: Circulation Research (1995)

Abstract MCI-154 (6-[4-(4′-pyridylamino)phenyl]-4,5-dihydro-3(2 H )pyridazinone hydrochloride trihydrate) is a potent novel cardiotonic agent whose positive inotropism is shown to be mainly based on an increase in Ca 2+ sensitivity of the contractile apparatus. To elucidate the exact mechanism through which this drug acts, we investigated the movement of the reconstituted thin filament on a myosin layer in vitro. Cardiac thin filaments were reconstituted from actin and tropomyosin-troponin complex purified from rat cardiac acetone powder separately. Double staining of the filament showed that tropomyosin-troponin complex was integrated along actin filament homogeneously. Thin filaments thus prepared were fluorescently labeled and made to slide on rat cardiac myosin fixed on a glass coverslip while varying the [Ca 2+ ] of the medium (control, pH 7.2 at 25°C). When [Ca 2+ ] was low, the filaments showed only brownian motion. However, above a certain level of [Ca 2+ ] (the threshold [Ca 2+ ]), the filaments started to slide, and the velocity increased, reaching the maximum velocity within a very narrow range of [Ca 2+ ]. The regulation was completely abolished by using simple actin filaments without tropomyosin-troponin complex, demonstrating that the regulatory proteins are responsible for this Ca 2+ regulation of the movement of the reconstituted thin filament. Under the control condition, addition of MCI-154 shifted the threshold [Ca 2+ ] to a lower level (sensitization) in a concentration-related manner. And 10 −4 mol/L of MCI-154 reversed the desensitization effect induced by either acidosis (pH 6.8), low temperature (15°C), or the addition of inorganic phosphate (10 mmol/L). However, the maximum sliding velocity was not affected by the drug under any condition. In conclusion, MCI-154 directly sensitized the contractile apparatus under not only physiological but also pathophysiological conditions. This in vitro motility assay technique using reconstituted thin filaments is a useful tool for studying the mechanism of action of Ca 2+ sensitizers.
Critical care dysmotility: abnormal foregut motor function in the ICU/ITU patient
Authors: E M M Quigley
Journal: Gut (2005)

While aspiration and feeding difficulties are well known challenges in the intensive care unit, their pathophysiology has been poorly understood. New information suggests that the critically ill are subject to profound alterations in motor and sensory function of the oesophagus, lower oesophageal sphincter, stomach, and duodenum which go some way to explaining their propensity to reflux and gastroparesis, with their attendant risks

As medicine changes so should all aspects of medical care and knowledge; as more and more patients are subjected to surgical procedures of increasing complexity and risk and as survival rates from catastrophic illness rise, due to advances in surgery, anaesthesia, and intensive care, one would expect an associated growth in awareness of, and research into, the effects of critical illness on gut motor function. However, motor function and dysfunction, in this context, have received scant attention and have remained, for the most part, poorly understood. While a high prevalence of such phenomena as gastro-oesophageal reflux and gastroparesis are assumed, their true rates of occurrence have been scarcely documented. Similarly, while potential consequences of these entities, such as aspiration, oesophagitis, nosocomial pneumonia, feeding difficulties, and even gastric perforation are well known and, justifiably, feared, the effects of critical illness on oesophageal and gastric motor function have been little investigated. There are, it must be conceded, many reasons for this. Several factors, intrinsic to any intensive care (or therapy) unit (IC/TU) patient population, deter the clinician-scientist from embarking on the investigation of these subjects and confound the interpretation of any studies completed.

First and foremost, this is, by definition, a heterogeneous population. Depending on the nature of a particular unit, it may include among its patients a wide range of ages as well as a diverse catalogue of precipitating illnesses and events. Among the latter, prior surgery, raised intracranial …