tbuckley/cabot-search huggingface dataset:
Prone positioning for 16 h/d reduced mortality more than supine positioning in early severe ARDS
Authors: B. Taylor Thompson
Journal: Annals of Internal Medicine (2013)

ACP Journal ClubSeptember 17, 2013Prone positioning for 16 h/d reduced mortality more than supine positioning in early severe ARDSB. Taylor Thompson, MDB. Taylor Thompson, MDMassachusetts General Hospital, Boston, Massachusetts, USA (B.T.T.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-159-6-201309170-02002 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationGuérin C, Reignier J, Richard JC, et al; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368:2159-68 https://pubmed.ncbi.nlm.nih.gov/23688302Clinical Impact RatingsCritical Care: Pulmonology: References1 Abroug F, Ouanes-Besbes L, Elatrous S, Brochard L. The effect of prone positioning in acute respiratory distress syndrome or acute lung injury: a meta-analysis. Areas of uncertainty and recommendations for research. Intensive Care Med. 2008;34:1002-11. [PMID: 18350271] Google Scholar2 Gattinoni L, Carlesso E, Taccone P, et al. Prone positioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis. Minerva Anestesiol. 2010;76:448-54. [PMID: 20473258] Google Scholar3 Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303:865-73. [PMID: 20197533] Google Scholar Author, Article, and Disclosure InformationAffiliations: Massachusetts General Hospital, Boston, Massachusetts, USA (B.T.T.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics September 17, 2013Volume 159, Issue 6Page: JC2KeywordsAcute respiratory distress syndromeAdverse eventsBurnsCritical careHeartIntensive care unitsLung transplantationLungsNitric oxideNoninvasive ventilationOxygenPositive end expiratory pressurePulmonary medicineRespiratorsRespiratory failureRespiratory system proceduresSafetyTidal volumeVentilators Issue Published: September 17, 2013 CopyrightCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Identification of P450 Oxidoreductase as a Major Determinant of Sensitivity to Hypoxia-Activated Prodrugs
Authors: Francis W. Hunter, Richard J. Young, Zvi Shalev, Ravi N. Vellanki, Jingli Wang, Yongchuan Gu, Naveen Joshi, Sreevalsan Sreebhavan, Ilan Weinreb, David P. Goldstein, Jason Moffat, Troy Ketela, Kevin R. Brown, Marianne Koritzinsky, Benjamin Solomon, Danny Rischin, William R. Wilson, Bradly G. Wouters
Journal: Cancer Research (2015)

Hypoxia is a prevalent feature of many tumors contributing to disease progression and treatment resistance, and therefore constitutes an attractive therapeutic target. Several hypoxia-activated prodrugs (HAP) have been developed, including the phase III candidate TH-302 (evofosfamide) and the preclinical agent SN30000, which is an optimized analogue of the well-studied HAP tirapazamine. Experience with this therapeutic class highlights an urgent need to identify biomarkers of HAP sensitivity, including enzymes responsible for prodrug activation during hypoxia. Using genome-scale shRNA screens and a high-representation library enriched for oxidoreductases, we identified the flavoprotein P450 (cytochrome) oxidoreductase (POR) as the predominant determinant of sensitivity to SN30000 in three different genetic backgrounds. No other genes consistently modified SN30000 sensitivity, even within a POR-negative background. Knockdown or genetic knockout of POR reduced SN30000 reductive metabolism and clonogenic cell death and similarly reduced sensitivity to TH-302 under hypoxia. A retrospective evaluation of head and neck squamous cell carcinomas showed heterogeneous POR expression and suggested a possible relationship between human papillomavirus status and HAP sensitivity. Taken together, our study identifies POR as a potential predictive biomarker of HAP sensitivity that should be explored during the clinical development of SN30000, TH-302, and other hypoxia-directed agents.
Measurement of nasal potential difference in adult cystic fibrosis, Young's syndrome, and bronchiectasis.
Authors: E W Alton, J G Hay, C Munro, D M Geddes
Journal: Thorax (1987)

Previous work confirmed the abnormal potential difference between the undersurface of the inferior nasal turbinate and a reference electrode in cystic fibrosis, but the technique is difficult and the results show overlap between the cystic fibrosis and the control populations. In the present study the potential difference from the floor of the nose has therefore been assessed in normal subjects, as well as in adult patients with cystic fibrosis, bronchiectasis and Young's syndrome. Voltages existing along the floor of the nasal cavity were recorded. The mean potential difference was similar in controls (-18 (SD 5) mv) and in patients with bronchiectasis (-17 (6) mv) and Young's syndrome (-20 (6) mv). The potential difference in cystic fibrosis (-45 (8) mv) was significantly different from controls (p less than 0.002) and there was no overlap between the cystic fibrosis values and values obtained in normal and diseased controls. This simple technique therefore discriminates well between patients with cystic fibrosis and other populations, raising the possibility of its use to assist in diagnosis.
Prolonged release oxycodone–naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension
Authors: Claudia Trenkwalder, Heike Beneš, Ludger Grote, Diego García-Borreguero, Birgit Högl, Michael Hopp, Björn Bosse, Alexander Oksche, Karen Reimer, Juliane Winkelmann, Richard P Allen, Ralf Kohnen
Journal: The Lancet Neurology (2013)
Regional Lung Deposition and Bronchodilator Response as a Function of β<sub>2</sub>-Agonist Particle Size
Authors: Omar S. Usmani, Martyn F. Biddiscombe, Peter J. Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Aerosol particle size influences the extent, distribution, and site of inhaled drug deposition within the airways.We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery.In a randomized, double-blind, placebo-controlled study, 12 subjects with asthma (FEV1, 76.8 +/- 11.4% predicted) inhaled technetium-99m-labeled monodisperse albuterol aerosols (30-microg dose) of 1.5-, 3-, and 6-microm mass median aerodynamic diameter, at slow (30-60 L/min) and fast (> 60 L/min) inspiratory flows. Lung and extrathoracic radioaerosol deposition were quantified using planar gamma-scintigraphy. Pulmonary function and tolerability measurements were simultaneously assessed. Clinical efficacy was also compared with unlabeled monodisperse albuterol (15-microg dose) and 200 microg metered-dose inhaler (MDI) albuterol.Smaller particles achieved greater total lung deposition (1.5 microm [56%], 3 microm [50%], and 6 microm [46%]), farther distal airways penetration (0.79, 0.60, and 0.36, respective penetration index), and more peripheral lung deposition (25, 17, and 10%, respectively). However, larger particles (30-microg dose) were more efficacious and achieved greater bronchodilation than 200 microg MDI albuterol (deltaFEV1 [ml]: 6 microm [551], 3 microm [457], 1.5 microm [347], MDI [494]). Small particles were exhaled more (1.5 microm [22%], 3 microm [8%], 6 microm [2%]), whereas greater oropharyngeal deposition occurred with large particles (15, 31, and 43%, respectively). Faster inspiratory flows decreased total lung deposition and increased oropharyngeal deposition for the larger particles, with less bronchodilation. A shift in aerosol distribution to the proximal airways was observed for all particles.Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation. Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.
Abstract A34: Splenectomy inhibits tumor development and metastases in murine lung cancer models.
Authors: Liran Levy, Inbal Mishalian, Lida Zolotarov, Rachel Bayuh, Zvi Gregorio Fridlender
Journal: Cancer Research (2013)

Abstract Introduction &amp; Aims: It has been shown that inhibitors of the immune system (e.g. myeloid derived suppressor cells, MDSC) reside in the spleen and inhibit the endogenous anti-tumor effects of the immune system. We hypothesized that excision of the spleen (splenectomy) can inhibit growth of relatively big tumors, and reduce metastases by modulating systemic inhibition of the immune system. Our long-term goal is to implement mechanisms elucidated in these studies into future clinical trials. Methods: The clinical effect of splenectomy was evaluated in several murine lung cancer models - flank and metastatic. We compared immunological properties of blood and tumor after splenectomy or sham operation in tumor-bearing mice, using FACS analysis, RT-PCR and specific depletion studies. Results: We found that splenectomy reduces tumor growth, can induce their regression, and decreases metastases. These effects disappeared in NOD/SCID mice. No significant changes in cell types were found in the blood. Splenectomy increased the percentage out of total tumor cells of neutrophils (2.4% vs. 4.9%, p=0.012), and macrophages (10.9% vs. 14.4%, p=0.014). The tumor macrophages tended to be less immune-inhibitory (non-M2/M2 macrophages ratio increased from 3.4 to 12.1, p=0.04). We further noted a tendency to increased activation of CD8+ CTL (19.2% vs. 30%, p=0.09). Tumor microenvironment was found to be more pro-inflammatory following splenectomy (e.g. upregulation of MIG, TNF-alpha, and IFN-gamma. Using specific depletion of cells we evaluated the role of each cell in the effect described. These experiments demonstrated the importance of myeloid derived suppressor cells (MDSC) in the effect of splenectomy. Conclusions: Splenectomy inhibits the development of tumors and metastases in murine models of lung cancer, by changing the amount and characteristics of myeloid cells, and reducing activation of CD8+ T-cells. Citation Format: Liran Levy, Inbal Mishalian, Lida Zolotarov, Rachel Bayuh, Zvi Gregorio Fridlender. Splenectomy inhibits tumor development and metastases in murine lung cancer models. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A34.
Bullous pemphigoid and psoriasis: does subclinical bullous pemphigoid exist?
Authors: JOHN R. PERSON, ROY S. ROGERS
Journal: British Journal of Dermatology (1976)

Four cases are presented in which probable bullous pemphigoid and probable psoriasis co-existed. One case represents a simple coincidence of the two diseases. In the other three cases, the bullous lesions were transient and seemed to be induced by elements of the Goeckerman regimen. The hypothesis is presented that these three cases represent a subclinical form of bullous pemphigoid induced by the irritant effects of coal tar, ultraviolet light, the reduced barrier function of a pre-existing dermatosis, or a combination of these factors.
Cyclooxygenase-2 and Platelet-Derived Growth Factor Receptors as Potential Targets in Treating Aggressive Fibromatosis
Authors: Stefano Signoroni, Milo Frattini, Tiziana Negri, Elisa Pastore, Elena Tamborini, Paola Casieri, Marta Orsenigo, Luca Da Riva, Paolo Radice, Paola Sala, Alessandro Gronchi, Lucio Bertario, Marco A. Pierotti, Silvana Pilotti
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To explore the molecular bases of potential new pharmacologic targets in aggressive fibromatosis (desmoid tumor). Experimental Design: Tumor specimens from 14 patients surgically treated for aggressive fibromatosis (6 familial adenomatous polyposis and 8 sporadic cases), analyzed for adenomatous polyposis coli (APC) and CTNNB1 (β-catenin) mutations, were further investigated for β-catenin, cyclooxygenase-2 (COX-2), platelet-derived growth factor (PDGF) receptor α (PDGFRA)/PDGF receptor β (PDGFRB), their cognate ligands (PDGFA and PDGFB), and KIT using a comprehensive immunohistochemical, biochemical, molecular, and cytogenetic approach. Results: No CTNNB1 (β-catenin) mutations were found in the familial adenomatous polyposis patients, but previously reported activating mutations were found in six of the eight sporadic patients. All of the cases carrying an altered WNT pathway showed nuclear and cytoplasmic immunoreactivity for β-catenin, whereas β-catenin expression was restricted to the cytoplasm in the sporadic patients lacking CTNNB1 mutations. COX-2 protein and mRNA overexpression was detected in all 14 cases, together with the expression and phosphorylation of PDGFRA and PDGFRB, which in turn paralleled the presence of their cognate ligands. No PDGFRB mutations were found. The results are consistent with PDGFRA and PDGFRB activation sustained by an autocrine/paracrine loop. Conclusions: Aggressive fibromatosis is characterized by WNT/oncogene pathway alterations triggering COX-2–mediated constitutive coactivation of PDGFRA and PDGFRB, and may therefore benefit from combined nonsteroidal anti-inflammatory drug + tyrosine kinase inhibitor treatment.
Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study
Authors: Stella Douma, Konstantinos Petidis, Michael Doumas, Panagiota Papaefthimiou, Areti Triantafyllou, Niki Kartali, Nikolaos Papadopoulos, Konstantinos Vogiatzis, Chrysanthos Zamboulis
Journal: The Lancet (2008)
A novel mouse model of in situ stenting
Authors: Janet Chamberlain, Mark Wheatcroft, Nadine Arnold, Henry Lupton, David C. Crossman, Julian Gunn, Sheila Francis
Journal: Cardiovascular Research (2009)

Animal models of stenting are mostly limited to larger animals or involve substantial abdominal surgery in rodents. We aimed to develop a simple, direct model of murine stenting. We designed a miniature, self-expanding, nitinol wire coil stent that was pre-loaded into a metal stent sheath. This was advanced into the abdominal aorta of the mouse, via femoral access, and the stent deployed. In-stent restenosis was investigated at 1, 3, 7, and 28 days post-stenting. The model was validated by investigation of neointima formation in mice deficient in signalling via the interleukin-1 receptor (IL-1R1), compared with other injury models. Ninety-two per cent of mice undergoing the procedure were successfully stented. All stented vessels were patent. Inflammatory cells were seen in the adventitia and around the stent strut up to 3 days post-stenting. At 3 days, an early neointima was present, building to a mature neointima at 28 days. In mice lacking IL-1R1, the neointima was 64% smaller than that in wild-type controls at the 28-day timepoint, in agreement with other models. This is the first description of a successful model of murine in situ stenting, using a stent specifically tailored for use in small thin-walled arteries. The procedure can be undertaken by a single operator without the need for an advanced level of microsurgical skill and is reliable and reproducible. The utility of this model is demonstrated by a reduction in in-stent restenosis in IL-1R1-deficient mice.
Pericytes in Development and Pathology of Skeletal Muscle
Authors: Ornella Cappellari, Giulio Cossu
Journal: Circulation Research (2013)

Increasing attention is currently devoted to the multiple roles that pericytes (also defined as mural, Rouget, or perivascular cells) may play during angiogenesis, vascular homeostasis, and pathology. Many recent excellent reviews thoroughly address these topics (see below); hence, we will not discuss them in detail here. However, not much is known about origin, heterogeneity, gene expression, and developmental potential of pericytes during fetal and postnatal development. This is likely because of the paucity of markers expressed by pericytes and the absence of truly unique ones. Thus, in vivo identification and ex perspective isolation are challenging and explain the relative little data available in comparison with neighbor but far more characterized cells such as the endothelium. Despite this preliminary knowledge, we will propose that contribution to growing mesoderm tissues may be an important role for pericytes. Thus, their ability to contribute to tissue regeneration may be a consequence of their role in tissue growth. However, in a severely damaged or diseased tissue, acute or chronic inflammation likely results in the production of signaling molecules that are different from those present in developing tissues, thus explaining why pericytes are easily diverted from a regenerative to a fibrotic fate.
Malignant mesothelioma of the pleura: relation between histological type and clinical behaviour.
Authors: M R Law, M E Hodson, B E Heard
Journal: Thorax (1982)

The differing clinical behaviour of malignant mesothelioma of different cell types was studied in 115 cases of pleural mesothelioma, classified histologically into epithelial (60), sarcomatous (25), and mixed (30). Epithelial mesotheliomas were associated with clinical features characteristic of carcinomas rather than sarcomas, including spread of tumour by direct extension, large pleural effusions, contralateral pleural effusions, ascites, metastases in regional lymph nodes, and occasional response to radiotherapy. Sarcomatous mesotheliomas were associated with clinical features more characteristic of sarcomas, with more frequent distant metastases, little or no effusion, and shorter survival. Mixed tumours had features of both, large pleural effusions occurring as frequently as with epithelial tumours, but survival being almost as poor as in sarcomatous cases. Despite these differences there is evidence from published reports that epithelial, sarcomatous, and mixed mesotheliomas have a common origin from mesothelial cells or their precursor cells.
Blood loss using the modified two-layer Kiil dialyser.
Authors: D B Evans, E M Clarkson, J R Curtis
Journal: BMJ (1967)

Detection of Bacteriuria-Bradley et al.B3RITISH 651 than at a temperature below this.Thus, from general practice, the inoculated plate can be sent to the laboratory for incubation and interpretation.If this is impossible the plates can be kept by the practitioner and only " positives " submitted for identifi- cation and sensitivity testing.Unfortunately organisms causing infections in other situations are much more fastidious in their growth requirements, and it is not possible, therefore, to use modifications of this method for other bacteriological investigations.MacConkey plates were used because they support the growth of virtually all organisms responsible for acute urinary tract infections, and they inhibit the swarming of Proteus species.They can be obtained pre-poured from commercial sources and do not deteriorate during 7 to 10 days at room temperature, especially if kept in plastic bags.Other commercial cotton-wool swabs could doubtless be used equally well, but would require initial calibration with more accurate methods.Serum-coated swabs, being water-repellent, are unsuitable.Though 105 organisms per ml. of urine has come to be regarded by many as the figure below which urinary infection is not present this is not always so. *As was pointed out in Kass's (1955) original paper one of the circumstances in which, with an active urinary infection, fewer organisms are found is when there is frequency of micturition.There is then insufficient incubation time in the bladder for organisms to reach 105/ml. of urine.In general practice there is often "built-in" frequency, as many patients micturate immediately before leaving home.Specimens of urine obtained in these circum- stances may therefore have fewer than 105 organisms per ml. in the'presence of infection.Diuresis also significantly reduces the number of organisms (Roberts et al., 1967).Other less well recognized factors, such as the excretion of inhibitory sub- stances from the diet, may also account for fewer than 105 organisms per ml. in the presence of infection.These factors must be considered in reading screening tests, just as they are in the interpretation of routine cultures.It is not necessarily of any disadvantage, therefore, that accurate counts between 250 and 500 colonies per inoculum are not possible.Indeed, it is questionable whether the rigid application of accurate methods is justifiable on such variable material.This can sometimes be undoubtedly misleading. SummaA cultural method for the investigation of urinary tract infections using commercially available cotton-wool swabs te inoculate MacConkey plates with freshly voided urine is described.This is simple to use, and does not necessarilT require incubation at 370 C. Cultural methods have advantage!over chemical screening tests, but some described previously require special equipment and thus are an added burden or laboratory preparation facilities.We wish to acknowledge the co-operation of Dr. Betty Bass Mt
The “Fish-Specific” Hox Cluster Duplication Is Coincident with the Origin of Teleosts
Authors: Karen D. Crow, Peter F. Stadler, Vincent J. Lynch, Chris Amemiya, Günter P. Wagner
Journal: Molecular Biology and Evolution (2005)

The Hox gene complement of zebrafish, medaka, and fugu differs from that of other gnathostome vertebrates. These fishes have seven to eight Hox clusters compared to the four Hox clusters described in sarcopterygians and shark. The clusters in different teleost lineages are orthologous, implying that a "fish-specific" Hox cluster duplication has occurred in the stem lineage leading to the most recent common ancestor of zebrafish and fugu. The timing of this event, however, is unknown. To address this question, we sequenced four Hox genes from taxa representing basal actinopterygian and teleost lineages and compared them to known sequences from shark, coelacanth, zebrafish, and other teleosts. The resulting gene genealogies suggest that the fish-specific Hox cluster duplication occurred coincident with the origin of crown group teleosts. In addition, we obtained evidence for an independent Hox cluster duplication in the sturgeon lineage (Acipenseriformes). Finally, results from HoxA11 suggest that duplicated Hox genes have experienced diversifying selection immediately after the duplication event. Taken together, these results support the notion that the duplicated Hox genes of teleosts were causally relevant to adaptive evolution during the initial teleost radiation.