tbuckley/cabot-search huggingface dataset:
Nasal High-Flow versus Venturi Mask Oxygen Therapy after Extubation. Effects on Oxygenation, Comfort, and Clinical Outcome
Authors: Salvatore Maurizio Maggiore, Francesco Antonio Idone, Rosanna Vaschetto, Rossano Festa, Andrea Cataldo, Federica Antonicelli, Luca Montini, Andrea De Gaetano, Paolo Navalesi, Massimo Antonelli
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Oxygen is commonly administered after extubation. Although several devices are available, data about their clinical efficacy are scarce.To compare the effects of the Venturi mask and the nasal high-flow (NHF) therapy on PaO2/FiO2SET ratio after extubation. Secondary endpoints were to assess effects on patient discomfort, adverse events, and clinical outcomes.Randomized, controlled, open-label trial on 105 patients with a PaO2/FiO2 ratio less than or equal to 300 immediately before extubation. The Venturi mask (n = 52) or NHF (n = 53) were applied for 48 hours postextubation.PaO2/FiO2SET, patient discomfort caused by the interface and by symptoms of airways dryness (on a 10-point numerical rating scale), interface displacements, oxygen desaturations, need for ventilator support, and reintubation were assessed up to 48 hours after extubation. From the 24th hour, PaO2/FiO2SET was higher with the NHF (287 ± 74 vs. 247 ± 81 at 24 h; P = 0.03). Discomfort related both to the interface and to airways dryness was better with NHF (respectively, 2.6 ± 2.2 vs. 5.1 ± 3.3 at 24 h, P = 0.006; 2.2 ± 1.8 vs. 3.7 ± 2.4 at 24 h, P = 0.002). Fewer patients had interface displacements (32% vs. 56%; P = 0.01), oxygen desaturations (40% vs. 75%; P < 0.001), required reintubation (4% vs. 21%; P = 0.01), or any form of ventilator support (7% vs. 35%; P < 0.001) in the NHF group.Compared with the Venturi mask, NHF results in better oxygenation for the same set FiO2 after extubation. Use of NHF is associated with better comfort, fewer desaturations and interface displacements, and a lower reintubation rate. Clinical trial registered with www.clinicaltrials.gov (NCT 01575353).
Sirtuin 1 Is Upregulated in a Subset of Hepatocellular Carcinomas where It Is Essential for Telomere Maintenance and Tumor Cell Growth
Authors: Juan Chen, Bin Zhang, Nathalie Wong, Anthony W.I. Lo, Ka-Fai To, Anthony W.H. Chan, Margaret H.L. Ng, Cecilia Y.S. Ho, Suk-Hang Cheng, Paul B.S. Lai, Jun Yu, Ho-Keung Ng, Ming-Tat Ling, Ai-Long Huang, Xue-Fei Cai, Ben C.B. Ko
Journal: Cancer Research (2011)

Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. Treatment of HCC is complicated by the fact that the disease is often diagnosed at an advanced stage when it is no longer amenable to curative surgery, and current systemic chemotherapeutics are mostly inefficacious. Sirtuin 1 (SIRT1) is a class III histone deacetylase that is implicated in gene regulations and stress resistance. In this study, we found that SIRT1 is essential for the tumorigenesis of HCC. We showed that although SIRT1 was expressed at very low levels in normal livers, it was overexpressed in HCC cell lines and in a subset of HCC. Tissue microarray analysis of HCC and adjacent nontumoral liver tissues revealed a positive correlation between the expression levels of SIRT1 and advancement in tumor grades. Downregulation of SIRT1 consistently suppressed the proliferation of HCC cells via the induction of cellular senescence or apoptosis. SIRT1 silencing also caused telomere dysfunction-induced foci and nuclear abnormality that were clearly associated with reduced expressions of telomerase reverse transcriptase (TERT), and PTOP, which is a member of the shelter in complex. Ectopic expression of either TERT or PTOP in SIRT1-depleted cells significantly restored cell proliferation. There was also a positive correlation between the level of induction of SIRT1 and TERT [corrected] in human HCC. Finally, SIRT1-silencing sensitized HCC cells to doxorubicin treatment. Together, our findings reveal a novel function for SIRT1 in telomere maintenance of HCC, and they rationalize the clinical exploration of SIRT1 inhibitors for HCC therapy.
Reassessing benzene risks using internal doses and Monte-Carlo uncertainty analysis.
Authors: L A Cox
Journal: Environmental Health Perspectives (1996)

Human cancer risks from benzene have been estimated from epidemiological data, with supporting evidence from animal bioassay data. This article reexamines the animal-based risk assessments using physiologically based pharmacokinetic (PBPK) models of benzene metabolism in animals and humans. Internal doses (total benzene metabolites) from oral gavage experiments in mice are well predicted by the PBPK model. Both the data and the PBPK model outputs are also well described by a simple nonlinear (Michaelis-Menten) regression model, as previously used by Bailer and Hoel [Metabolite-based internal doses used in risk assessment of benzene. Environ Health Perspect 82:177-184 (1989)]. Refitting the multistage model family to internal doses changes the maximum-likelihood estimate (MLE) dose-response curve for mice from linear-quadratic to purely cubic, so that low-dose risk estimates are smaller than in previous risk assessments. In contrast to Bailer and Hoel's findings using interspecies dose conversion, the use of internal dose estimates for humans from a PBPK model reduces estimated human risks at low doses. Sensitivity analyses suggest that the finding of a nonlinear MLE dose-response curve at low doses is robust to changes in internal dose definitions and more consistent with epidemiological data than earlier risk models. A Monte-Carlo uncertainty analysis based on maximum-entropy probabilities and Bayesian conditioning is used to develop an entire probability distribution for the true but unknown dose-response function. This allows the probability of a positive low-dose slope to be quantified: It is about 10%. An upper 95% confidence limit on the low-dose slope of excess risk is also obtained directly from the posterior distribution and is similar to previous q1* values. This approach suggests that the excess risk due to benzene exposure may be nonexistent (or even negative) at sufficiently low doses. Two types of biological information about benzene effects--pharmacokinetic and hematotoxic--are examined to test the plausibility of this finding. A framework for incorporating causally relevant biological information into benzene risk assessment is introduced, and it is shown that both pharmacokinetic and hematotoxic models appear to be consistent with the hypothesis that sufficiently low concentrations of inhaled benzene do not create and excess risk.
Expression and function of c-kit in hemopoietic progenitor cells.
Authors: M Ogawa, Y Matsuzaki, S Nishikawa, S Hayashi, T Kunisada, T Sudo, T Kina, H Nakauchi, S Nishikawa
Journal: The Journal of Experimental Medicine (1991)

The expression and function of a receptor tyrosine kinase, c-kit, in the adult bone marrow of the mouse were investigated by using monoclonal antibodies (mAbs) against the extracellular domain of murine c-kit. In adult C57BL/6 mouse, 7.8% of total bone marrow cells express c-kit on their surface. Half of the c-kit+ cells do not express lineage markers including Mac-1, Gr-1, TER-119, and B220, while the remainder coexpress myeloid lineage markers such as Mac-1 and Gr-1. After c-kit+ cells were removed from the bone marrow cell preparation, hemopoietic progenitor cells reactive to IL-3, GM-CSF, or M-CSF and also those which give rise to spleen colonies in irradiated recipients disappeared almost completely. Thus, most hemopoietic progenitors in the adult bone marrow express c-kit. To investigate whether or not c-kit has any role in the hemopoiesis of adult bone marrow, we took the advantage of one of the anti-c-kit mAbs that can antagonize the function of c-kit. As early as two days after the injection of 1 milligram of an antagonistic antibody, ACK2, almost all hemopoietic progenitor cells disappeared from the bone marrow, which eventually resulted in the absence of mature myeloid and erythroid cells in the bone marrow. These results provide direct evidence that c-kit is an essential molecule for constitutive intramarrow hemopoiesis, especially for the self-renewal of hemopoietic progenitor cells at various stages of differentiation.
Liver tumorigenicity promoted by microRNA-221 in a mouse transgenic model
Authors: Elisa Callegari, Bahaeldin K. Elamin, Ferdinando Giannone, Maddalena Milazzo, Giuseppe Altavilla, Francesca Fornari, Luciano Giacomelli, Lucilla D'Abundo, Manuela Ferracin, Cristian Bassi, Barbara Zagatti, Fabio Corrà, Elena Miotto, Laura Lupini, Luigi Bolondi, Laura Gramantieri, Carlo M. Croce, Silvia Sabbioni, Massimo Negrini
Journal: Hepatology (2012)

MicroRNA-221 (miR-221) is one of the most frequently and consistently up-regulated microRNAs (miRNAs) in human cancer. It has been hypothesized that miR-221 may act as a tumor promoter. To demonstrate this, we developed a transgenic (TG) mouse model that exhibits an inappropriate overexpression of miR-221 in the liver. Immunoblotting and immunostaining confirmed a concomitant down-regulation of miR-221 target proteins. This TG model is characterized by the emergence of spontaneous nodular liver lesions in approximately 50% of male mice and by a strong acceleration of tumor development in 100% of mice treated with diethylnitrosamine. Similarly to human hepatocellular carcinoma, tumors are characterized by a further increase in miR-221 expression and a concomitant inhibition of its target protein-coding genes (i.e., cyclin-dependent kinase inhibitor [Cdkn]1b/p27, Cdkn1c/p57, and B-cell lymphoma 2-modifying factor). To validate the tumor-promoting effect of miR-221, we showed that in vivo delivery of anti-miR-221 oligonucleotides leads to a significant reduction of the number and size of tumor nodules. This study not only establishes that miR-221 can promote liver tumorigenicity, but it also establishes a valuable animal model to perform preclinical investigations for the use of anti-miRNA approaches aimed at liver cancer therapy.
Sports and exercise medicine in Finland
Authors: Pekka Kannus, Jari Parkkari
Journal: British Journal of Sports Medicine (2000)

Sports and exercise medicine has a long tradition in Finland. Organised medical care of athletes has been available since the 1930s. The Finnish Society of Sports Medicine was founded in 1939 and is probably the oldest nationwide sports medicine society in the world. Today, the society has about 500 physician members (5.2 million population) and publishes, along with the Finnish Society of Sports Physical Therapists, its own journal (three or four issues a year) and, together with the other Scandinavian societies, the international peer reviewed journal Scandinavian Journal of Medicine and Science in Sports (six issues a year). Organisation of instructional courses, seminars, and symposia on sports and exercise medicine is also an important part of the work of the Finnish Society. Every other year, one of the Scandinavian societies organises the international Scandinavian Congress on Medicine and Science in Sports (300–600 participants). In 1998, this congress was held in Finland.

In 1946, the first sports medical centre was opened at the Olympic Stadium of Helsinki. In 1956, a similar unit was founded in Turku. Today, Finland has six sports and exercise medicine research centres funded by the Ministy of Education (Helsinki, Turku, Tampere, Jyvaskyla, Oulu, and Kuopio). Each has a staff of between five and …
Physiological pathway of differentiation of hematopoietic stem cell population into mural cells
Authors: Yoshihiro Yamada, Nobuyuki Takakura
Journal: The Journal of Experimental Medicine (2006)

Endothelial cells (ECs), which are a major component of blood vessels, have been reported to develop in adulthood from hematopoietic cell populations, especially those of the monocyte lineage. Here we show that mural cells (MCs), another component of blood vessels, develop physiologically during embryogenesis from a hematopoietic stem cell (HSC) population, based on the in vitro culture of HSCs and histological examination of acute myeloid leukemia 1 mutant embryos, which lack HSCs. As in the embryo, HSCs in adult bone marrow differentiate into CD45+CD11b+ cells before differentiating into MCs. Moreover, CD45+CD11b+ cells are composed of two populations, CD11bhigh and CD11blow cells, both of which can differentiate into MCs as well as ECs. Interestingly, in a murine ischemia model, MCs and ECs derived from the CD11blow population had a long-term potential to contribute to the formation of newly developed blood vessels in vivo compared with the CD11high population, which could not. Moreover, injection of the CD11bhigh population induced leaky blood vessels, but the CD11blow population did not. With respect to the permeability of vessels, we found that angiopoietin 1, which is a ligand for Tie2 receptor tyrosine kinase expressed on ECs and is suggested to induce cell adhesion between ECs and MCs, is produced by the CD11blow population and plays a critical role in the formation of nonleaky vessels. These observations suggested that the CD11low cell population serves as a good source of cells for in vivo blood vessel regeneration.
Pegylated interferon -2a plus low-dose ribavirin for the retreatment of dialysis chronic hepatitis C patients who relapsed from prior interferon monotherapy
Authors: C-H Liu, C-C Liang, C-J Liu, H-B Tsai, P-H Hung, S-J Hsu, S-I Chen, J-W Lin, M-Y Lai, J-H Chen, P-J Chen, D-S Chen, J-H Kao
Journal: Gut (2009)

Chronic hepatitis C (CHC) remains frequent in dialysis patients.1 Currently, interferon (IFN) monotherapy is the standard of care for dialysis CHC patients.2 In a previous paper published in the journal, we demonstrated that treatment with weekly pegylated IFNα-2a had a significantly higher sustained virological response (SVR) rate than that with thrice weekly standard IFNα-2a in such patients (48% vs 20%, p = 0.02).3 Although dialysis CHC patients responded better to IFN monotherapy than those with normal renal function, the overall SVR rates are far from satisfactory.4 5

Retreatment with pegylated IFN plus ribavirin in ordinary CHC patients who relapsed from prior standard IFN had an SVR rate of 52%.6 Among these patients, the SVR rates for genotype 1 and 2/3 patients were 47% and 63%, respectively. Although ribavirin is contraindicated in dialysis CHC patients for the risk of …
Development of new-onset psoriasis while on anti-TNF treatment
Authors: C Matthews, S Rogers, O FitzGerald
Journal: Annals of the Rheumatic Diseases (2006)

Treatments directed against the proinflammatory cytokine tumour necrosis factor α (TNFα) are effective in rheumatoid arthritis and spondyloarthropathies. In patients with inflammatory arthritis secondary to psoriasis, chronic skin plaques also resolve with this treatment. We report on a series of clinical cases in which, conversely, there was a first presentation of psoriasis while on anti-TNF treatment.

The first case is that of a 49-year-old man with established ankylosing spondylitis, who was started on infliximab and showed an excellent response. After 8 months of treatment, he developed an erythematous, pustular rash over his back (fig 1). No clinical or serological evidence of infection was found and his medication, …
Abstract 17449: Left Ventricular Hypertrophy and Reduced Myocardial Function Are Associated with Aortic stiffness Measured by Cardiac MRI: the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Yoshiaki Ohyama, Bharath Ambale-Venkatesh, Atul R Chught, Gisera Teixido-Tura, Jang Young Kim, Sirisha Donekal, Kihei Yoneyama, Ola Gjesdal, Chia-Ying Liu, Alban Redheuil, Colin Wu, Gregory W Hundley, David A Bruemkie, Joao A Lima
Journal: Circulation (2014)

Background: Aortic pulse velocity (PWV) is generally considered an intrinsic marker of arterial stiffness. The association of central aortic PWV measured by MRI with cardiac structure and function remains poorly explored. We investigated how central aortic PWV assessed by MRI relates to LV structure and function in the population based study. Method: Multi-Ethnic Study of Atherosclerosis (MESA) participants at exam5 (2010-2012) were studied. Central aortic PWV was measured by phase contrast (PC) cine MRI at the level of the pulmonary artery bifurcation and black blood sagittal image. LV mass and volume indexed to height1.7, LV ejection fraction (LVEF), and LV mass volume ratio (M/V ratio) were determined by cine MRI. LV circumferential strain (Ecc), LV torsion, and early diastolic strain rate (SRe) were determined from tagged MRI. Linear regression models were used to evaluate the association between PWV and LV parameters after adjusting for demographics and cardiovascular risk factors. Results: A total of 2018 participants (age 70 ± 9 years, 53% women, 38% White, 10% Chinese, 28% African American, 24% Hispanic) were included in this cross-sectional study. Mean value of PWV was 8.9 ± 4.2 m/s. Distribution of PWV was skewed, so PWV was logarithmically transformed for linear regression models. In multivariable models adjusted for risk factors, higher PWV was associated with less/worse myocardial systolic and diastolic function parameters; LVEF, Ecc, torsion and SRe. Higher PWV was also associated with higher LV mass before and after adjusting multivariable models (Table). Conclusion: Our observations indicate that higher PWV is related to LV hypertrophy and subclinical myocardial systolic and diastolic dysfunction in multi-ethnic population.
Atrial Contribution to Stroke Volume in Dogs with Chronic Heart Block
Authors: JOSEPH H. SNYDER, FRANZ BENDER, ARTHUR H. KITCHIN, RALPH S. ZITNIK, DAVID E. DONALD, EARL H. WOOD
Journal: Circulation Research (1966)

In dogs studied without thoracotomy, under morphine-pentobarbital anesthesia and with an average heart rate of 71 beats/minute, atrial systole contributes to ventricular function to a small but significant degree. Stroke volume increased by 7 to 8% when atrial systole was timed to occur 0.1 second prior to closure of the atrioventricular valves, and decreased a similar magnitude when the contribution of atrial systole to ventricular filling was rendered ineffective by the use of an A-V delay of zero so that atrial emptying into the ventricles was prevented by the closed A-V valves. Increases or decreases in right atrial pressure of several centimeters of water induced by infusion of 6% dextran and by hemorrhage, respectively, were not associated with demonstrably significant alterations in these effects.
Hot off the breath: triple therapy for idiopathic pulmonary fibrosis—hear the PANTHER roar
Authors: Emmet E McGrath, Ann B Millar
Journal: Thorax (2011)

Idiopathic pulmonary fibrosis (IPF) is a disease characterised by alveolar epithelial damage followed by an aberrant repair mechanism characterised by fibroblast foci and activated myofibroblasts.1 Despite an incidence of 7.4/100 000 person years which is increasing year on year and a median survival of only 2–3 years, there is paucity of evidence for effective therapy.2 The current British Thoracic Society guidelines weakly recommend N -acetylcysteine (NAC), prednisolone and azathioprine (based on the IFIGENIA—Idiopathic Pulmonary Fibrosis International Group Exploring N -Acetylcysteine I Annual—trial) whereas the more recent guidelines of the American Thoracic Society/European Respiratory Society recommend lung transplantation or participation in a clinical trial as treatment options.3–5

 Increasing recognition of the clinical need for effective IPF therapy has finally led to a number of clinical trials evaluating potential anti-inflammatory and anti-fibrotic agents. IFIGENIA demonstrated that triple therapy with NAC, azathioprine and prednisolone was better than azathioprine and prednisolone in combination in preserving lung function in IPF patients, suggesting that NAC inclusion was strongly contributing to the benefits …
Structural, neuronal, and functional adaptive changes in atrophic rat ileum
Authors: K M Ekelund, E Ekblad
Journal: Gut (1999)

BACKGROUND Inactivity of the gut leads to atrophic changes of which little is known. AIMS To investigate structural, neuronal, and functional changes occurring in bypassed rat ileum. METHODS Morphometry was used to characterise the atrophic changes. The numbers of enteric neurones, their expression of neurotransmitters, and the presence of interstitial cells of Cajal were studied using immunocytochemistry and in situ hybridisation. Motor activity was studied in vitro. RESULTS Adaptive changes in bypassed ileum include atrophy and remodelling of the gut wall. The total numbers of submucous and myenteric neurones per unit length increased one and four weeks after bypass but were identical to sham operated intestine 10 weeks after bypass. Neurones expressing vasoactive intestinal peptide, neuropeptide Y, or pituitary adenylate cyclase activating peptide decreased gradually in number in bypassed ileum. Nitric oxide synthase expressing neurones were increased, particularly in the myenteric ganglia. No change in the frequency and distribution of interstitial cells of Cajal was noted. The contractile response elicited by electrical stimulation of sham operated ileum consisted of a fast cholinergic twitch followed by a slower non-adrenergic, non-cholinergic contraction. In the bypassed ileum an identical biphasic contraction was elicited; however, the entire response was non-adrenergic, non-cholinergic. The relaxatory response to electrical stimulation in sham operated ileum was nitric oxide mediated; after bypass it was non-nitrergic. CONCLUSIONS Notable atrophic changes were seen in the rat ileum after bypass. The enteric nervous system reacted with neuronal cell death and plasticity in terms of release and expression of neurotransmitters.
Anti-Hypertensive Agents Inhibit In Vivo the Formation of Advanced Glycation End Products and Improve Renal Damage in a Type 2 Diabetic Nephropathy Rat Model
Authors: Masaomi Nangaku, Toshio Miyata, Toshio Sada, Makoto Mizuno, Reiko Inagi, Yasuhiko Ueda, Naoyoshi Ishikawa, Hiroko Yuzawa, Hiroyuki Koike, Charles van Ypersele de Strihou, Kiyoshi Kurokawa
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Prevention or retardation of diabetic nephropathy (DN) includes anti-hypertensive treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) on the premises that these drugs have an added protective effect beyond their influence on BP. The present study used a strain of spontaneously hypertensive/NIH-corpulent rats [SHR/NDmc-cp (fat/fat)] as a model of type II DN to unravel the renoprotective effects of anti-hypertensive drugs. Olmesartan (1 or 5 mg/kg per d), an ARB, and hydralazine (5mg/kg per d), an anti-hypertensive drug without effect on the renin-angiotensin system (RAS), were given for 20 wk. BP, renal function, glucose and insulin levels, and proteinuria were monitored. Glomerular lesions and kidney pentosidine content were assessed at the end of the study. Olmesartan (1 and 5 mg) significantly reduced BP and kidney pentosidine content and improved histologic renal damage and proteinuria. The changes were dose-dependent. The effect of hydralazine (5 mg) was similar to that of olmesartan (1 mg) but reached statistical significance only for kidney pentosidine content. The similarity of both drugs' effects on kidney damage and proteinuria suggest that renoprotection does not hinge on manipulation of RAS in these rats. By contrast, the inhibition of renal pentosidine formation assessed both by immunohistochemistry and HPLC suggests a critical role of advanced glycation end product (AGE) formation together with hypertension in the genesis of diabetic nephropathy. This view is supported by the correlation found between renal pentosidine content and proteinuria. The unsuspected AGE-lowering effect of hydralazine was further confirmed in vitro and elucidated; it is due to both reactive carbonyl compounds trapping and modifications of the oxidative metabolism. It is concluded that AGE inhibition should be included in the therapeutic strategy of DN. E-mail: [email protected]