tbuckley/cabot-search huggingface dataset:
17 beta-Estradiol inhibits flow- and acute hypoxia-induced prostacyclin release from perfused endocardial endothelial cells.
Authors: E M Redmond, M N Cherian, R C Wetzel
Journal: Circulation (1994)

Because of the marked difference in the incidence and severity of cardiovascular diseases between men and premenopausal women, several groups have studied the effect of sex steroids, particularly estrogen, on vascular endothelial prostacyclin (PGI2) release. No previous studies have addressed the effect of estrogen on endocardial endothelial cells (EECs), which are involved in the modulation of the myocardium and potentially in downstream pulmonary and systemic vascular tone. Furthermore, all previous studies of estrogen effects on cultured endothelial cell function have used cells grown under standard static cell culture conditions, thereby ignoring the contribution of flow, the ubiquitous environmental endothelial stimulus.The effect of 17 beta-estradiol pretreatment (100 ng/mL, 72 hours) on cultured sheep EEC PGI2 release in response to multiple physiologically relevant stimuli was studied. EECs were grown in six-well plates (static conditions) or on microcarrier beads and perfused at a constant flow with normoxic (PO2 = 150 mm Hg, PCO2 = 35 mm Hg) or hypoxic (PO2 = 35 mm Hg, PCO2 = 35 mm Hg) Krebs solution. The stable metabolite of PGI2, 6-keto-PGF1 alpha, was determined in samples from both static and perfusion experiments by direct radioimmunoassay. 17 beta-Estradiol pretreatment did not alter basal or stimulated (arachidonic acid, 1 mumol/L, 10 mumol/L; A23187, 10 mumol/L; and bradykinin, 1 mumol/L) PGI2 release in static conditions. Untreated and acutely treated (100 ng/mL added to perfusate) EECs responded to flow with a time-dependent increase in PGI2 release that plateaued between 60 and 100 minutes. In contrast, 17 beta-estradiol-pretreated, perfused EECs did not increase PGI2 release over time. During perfusion, acute hypoxia increased PGI2 release: 140 +/- 65 (normoxia) to 296 +/- 113 pg (hypoxia) 6-keto-PGF1 alpha/mg per minute. 17 beta-Estradiol inhibited hypoxia-induced PGI2 release: 296 +/- 113 pg (untreated EECs, hypoxia) versus 159 +/- 60 pg (17 beta-estradiol pretreated, hypoxia) 6-keto-PGF1 alpha/mg per minute.This study demonstrates for the first time an inhibitory effect of 17 beta-estradiol on flow- and acute hypoxia-induced increase in PGI2 release from perfused EECs in the absence of any effect on pharmacologically stimulated PGI2 release from static cultures. These effects of 17 beta-estradiol may explain in part the well-recognized gender and estrogen effects in cardiovascular diseases and highlight the importance of flow in studies of endothelial cell function.
Low to moderate cumulative doses of pegylated liposomal doxorubicin in the treatment of classic Kaposi sarcoma in elderly patients with comorbidities
Authors: I. Potouridou, C. Korfitis, D. Ioannidou, D. Polydorou, N. Zakopoulou, A.J. Stratigos, A.D. Katsambas
Journal: British Journal of Dermatology (2007)

Journal Article Low to moderate cumulative doses of pegylated liposomal doxorubicin in the treatment of classic Kaposi sarcoma in elderly patients with comorbidities Get access I. Potouridou, I. Potouridou Second Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar C. Korfitis, C. Korfitis Department of Dermatology, University of Athens, A. Sygros Hospital, 21–23 Kapetan Chrona Str., 11525 Athens, Greece C. Korfitis E‐mail: chrykor@ath.forthnet.gr Search for other works by this author on: Oxford Academic Google Scholar D. Ioannidou, D. Ioannidou Second Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar D. Polydorou, D. Polydorou Second Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar N. Zakopoulou, N. Zakopoulou Second Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar A.J. Stratigos, A.J. Stratigos Department of Dermatology, University of Athens, A. Sygros Hospital, 21–23 Kapetan Chrona Str., 11525 Athens, Greece Search for other works by this author on: Oxford Academic Google Scholar A.D. Katsambas A.D. Katsambas Department of Dermatology, University of Athens, A. Sygros Hospital, 21–23 Kapetan Chrona Str., 11525 Athens, Greece Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 2, 1 February 2008, Pages 431–432, https://doi.org/10.1111/j.1365-2133.2007.08345.x Published: 01 February 2008
Exercise oxygen desaturation and DLCO: Are they correlated?
Authors: Julia Amaranta García Fuertes, Laura Tomás López, Verónica Hernández, Vanessa Zorrilla, Francisco Javier Ribas, Mikel Azpiazu, Agustina Rivas, David Bravo, Olatz Llaguno, Laura Cancelo, Patricia Sobradillo, Marta Inchausti, Begoña Lahidalga, Jose Luis Lobo Beristain
Journal: European Respiratory Journal (2013)

OBJETIVE. To determinate if echocardiographics variables and pulmonary function tests (PFT) are related to exercise oxygen desaturation using a 6 minutes walking-test (6mWT), in three groups: Pulmonary Hypertension (HP), Interstitial Lung Disease (ILD) and Combined pulmonary fibrosis and emphysema (CPFE). METHODS. Retrospective analysis of PFT, 6mWT and echocardiographics parameters, from the moment closer to diagnosis. RESULTS. 14 patients PH: 13 under group I and 1 under group IV. 10 patients ILD: 4NINE, 4UIP, 1NCO and 1DIP. 8 patients CPFE. Functional and echocardiographics values in figure1.

![Figure][1] 



Globally, DLCO was not related to exercise oxygen desaturation in none of the groups. Separately, in PH's group exercise oxygen desaturation was correlated to RightVentricule/RightAtrium gradient (RV/RA) by echocardiograph (spearman's rho -0,630 p 0,038). In ILD's group there was an association between alveolar gas volume (VA) and exercise oxygen desaturation (correlation -0,664 p 0,026) and also between total lung capacity (TLC) (r 0,648 p 0,043). In CPFE group, there was no relation between none of the parameters studied. CONCLUSIONS: 1.DLCO was not associated to exercise oxygen desaturation in none of the three groups included under our study. 2.In patients diagnosed of PH there was a relation between exercise oxygen desaturation and RV/RA. 3.In patients with ILD, the functional parameter that could better predict exercise oxygen desaturation would be VA.

 [1]: pending:yes
High-Dose Chemotherapy With Autologous Stem-Cell Transplantation and Hyperfractionated Radiotherapy As First-Line Treatment of Primary CNS Lymphoma
Authors: Gerald Illerhaus, Reinhard Marks, Gabriele Ihorst, Roland Guttenberger, Christoph Ostertag, Günther Derigs, Norbert Frickhofen, Friedrich Feuerhake, Benedikt Volk, Jürgen Finke
Journal: Journal of Clinical Oncology (2006)

To improve survival and reduce toxicity in primary CNS lymphoma (PCNSL) treatment, we conducted a multicenter phase II study with early high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) followed by hyperfractionated whole-brain radiotherapy (WBRT) for newly diagnosed PCNSL patients younger than 65 years of age.Chemotherapy included three steps: three cycles of methotrexate (8 g/m2); cytarabine (AraC; two doses of 3 g/m2) and thiotepa (40 mg/m2) followed by stem-cell harvest; HDT with carmustine (400 mg/m2) and thiotepa (two doses of 5 mg/kg body weight) followed by ASCT. WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation.Thirty patients with PCNSL younger than 65 years of age (median, 54 years; range, 27 years to 64 years) were enrolled (nine pilot-phase; 21 phase II). Twenty-eight patients responded to methotrexate: six patients with complete remission (CR), 15 patients with partial remission (PR), and seven patients with stable disease (SD) with clinical improvement. Of 26 patients proceeding to AraC and thiotepa, 10 patients achieved CR, 14 patients achieved PR, one patient experienced SD with clinical improvement, and one patient suffered disease progression. Twenty-three patients received HDT plus ASCT, resulting in 15 patients with CRs and eight patients with PRs. After WBRT, 21 of 21 patients had CRs. One patient died from liver failure after methotrexate. HDT was well tolerated apart from WHO grade 3/4 cytopenia. With a median follow-up of 63 months (range, 4 months to 84 months), 5-year overall survival probability is 69% for all patients and 87% for the 23 patients receiving HDT plus ASCT. The 5-year probability of relapse-related death is 21% for all patients (n = 30) and 8.7% for patients treated with HDT plus ASCT (n = 23).Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL.
Serum Inter–α-Trypsin Inhibitor and Matrix Hyaluronan Promote Angiogenesis in Fibrotic Lung Injury
Authors: Stavros Garantziotis, Enrique Zudaire, Carol S. Trempus, John W. Hollingsworth, Dianhua Jiang, Lisa H. Lancaster, Elizabeth Richardson, Lisheng Zhuo, Frank Cuttitta, Kevin K. Brown, Paul W. Noble, Koji Kimata, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-α-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury.Objectives: To determine whether IaI promotes HA-mediated angiogenesis in tissue injury.Methods: An examination was undertaken of angiogenesis in IaI-sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined.Measurements and Main Results: IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. lal deficiency Ieads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC.Conclusions: Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis.Clinical trial registered with www.clinicaltrials.gov (NCT00016627).
Clustering Algorithms in Biomedical Research: A Review
Authors: Rui Xu, Donald C. Wunsch
Journal: IEEE Reviews in Biomedical Engineering (2010)

Applications of clustering algorithms in biomedical research are ubiquitous, with typical examples including gene expression data analysis, genomic sequence analysis, biomedical document mining, and MRI image analysis. However, due to the diversity of cluster analysis, the differing terminologies, goals, and assumptions underlying different clustering algorithms can be daunting. Thus, determining the right match between clustering algorithms and biomedical applications has become particularly important. This paper is presented to provide biomedical researchers with an overview of the status quo of clustering algorithms, to illustrate examples of biomedical applications based on cluster analysis, and to help biomedical researchers select the most suitable clustering algorithms for their own applications.
Impact of finite orifice size on proximal flow convergence. Implications for Doppler quantification of valvular regurgitation.
Authors: L Rodriguez, J Anconina, F A Flachskampf, A E Weyman, R A Levine, J D Thomas
Journal: Circulation Research (1992)

Analysis of velocity acceleration proximal to a regurgitant valve has been proposed as a method to quantify the regurgitant flow rate (Qo). Previous work has assumed inviscid flow through an infinitesimal orifice, predicting hemispheric isovelocity shells, with calculated flow rate given by Qc = 2 pi rN2vN, where vN is user-selected velocity of interest and rN is the distance from that velocity to the orifice. To validate this approach more rigorously and investigate the impact of finite orifice size on the assumption of hemispheric symmetry, numerical and in vitro modeling was used. Finite-difference modeling demonstrated hemispheric shape for contours more than two orifice diameters from the orifice. More proximal than this (where the measured velocity vN exceeded 3% of the orifice velocity vo), flow was progressively underestimated, with a proportional error delta Q/Qo nearly identical to the ratio of contour velocity to orifice velocity, vN/vo. For the in vitro investigations, flow rates from 4.3 to 150 cm3/sec through 0.3 and 1.0 cm2 circular orifices were imaged with color Doppler with aliasing velocities from 19 to 36 cm/sec. Overall, the calculated flow (assuming hemispheric symmetry) correlated well with the true flow, Qc = 0.88Qo-7.82 (r = 0.945, SD = 12.2 cm3/sec, p less than 0.0001, n = 48), but progressively underestimated flow when the vN approached the orifice velocity vo. Applying a correction factor predicted by the numerical modeling, delta Q was improved from -13.81 +/- 13.01 cm3/sec (mean +/- SD) to +1.54 +/- 5.67 cm3/sec.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacterial Inhibition of Phosphatidylcholine Synthesis Triggers Apoptosis in the Brain
Authors: Janine Zweigner, Suzanne Jackowski, Shannon H. Smith, Marie van der Merwe, Joerg R. Weber, Elaine I. Tuomanen
Journal: The Journal of Experimental Medicine (2004)

Streptococcus pneumoniae is the most common cause of bacterial meningitis of high mortality and morbidity. Neurological sequelae include paralysis, mental retardation, and learning disorders. In humans, neurons of the hippocampus undergo apoptosis as a result of meningitis. Phosphatidylcholine (PtdCho) is an essential component of mammalian cell membranes and PtdCho deficiency, either due to chemicals or altered nutrition, leads to apoptosis, especially in hippocampal neurons. We show that apoptosis of a variety of brain cells after pneumococcal infection arises from inhibition of PtdCho biosynthesis, the first such activity described for a bacterium. Apoptosis inhibitors did not prevent the bacterial-dependent inhibition of PtdCho biosynthesis. Supplementation with exogenous lyso-phosphatidylcholine prevents cell death and treatment of mice with cytidine diphosphocholine attenuates hippocampal damage during meningitis, even after the onset of infection. We conclude that bacterial inhibition of PtdCho biosynthesis activates an apoptotic cascade that is a causative event in pathogenesis and amenable to therapeutic intervention.
GENERAL HOSPITALS AND THE PROVIDENT SYSTEM
Authors: E. C. Beale
Journal: BMJ (1908)

n " a Government subsidy to a reformed provident dispensary system would appear to form a sound basis for further developments.However this may be, a necessary feature in any perfect scheme is the provision for some means of securing consultative advice and specialized treatment in exceptional cases.The out-patient department of the voluntary hospital as an existing agency would appear to be well fitted for such work.A little* consideration will, however, show that the out-patient department cannot properly fulfil the two-fold part of competition and co-operation with the publicly-provlded service.In the interests of a satisfactory development of both systems, It is urgently!to be desired that the charitable public Ehould cease to compete with general practitioners and with the State in providing ordinary treatment for ordinary illnesses, and should restrict Its activity to providing special services for difficult and complicated cases.The public can hardly be expected to see the advantage of this proposal unless it is clearly pointed out to them by the profession, and I therefore venture to submit these few points in favour of it for the consideration of my medical eolleagues.
The Site of Plaque Rupture in Native Coronary Arteries
Authors: Myeong-Ki Hong, Gary S. Mintz, Cheol Whan Lee, Bong-Ki Lee, Tae-Hyun Yang, Young-Hak Kim, Jong-Min Song, Ki-Hoon Han, Duk-Hyun Kang, Sang-Sig Cheong, Jae-Kwan Song, Jae-Joong Kim, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2005)
Gastrin-releasing Peptide Receptor Antagonist Effects on an Animal Model of Sepsis
Authors: Felipe Dal-Pizzol, Luciane Pons Di Leone, Cristiane Ritter, Márcio Rodrigo Martins, Adalisa Reinke, Daniel Pens Gelain, Alfeu Zanotto-Filho, Luiz Fernando de Souza, Michael Andrades, Denise Frediani Barbeiro, Elena Aida Bernard, Martin Cammarota, Lia R. M. Bevilaqua, Francisco Garcia Soriano, José Cláudio, Fonseca Moreira, Rafael Roesler, Gilberto Schwartsmann
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Several new therapeutic strategies have been described for the treatment of sepsis, but to date none are related to alterations in the bombesin/gastrin-releasing peptide (GRP) receptor pathways.To determine the effects of a selective GRP receptor antagonist, RC-3095, on cytokine release from macrophages and its in vivo effects in the cecal ligation and puncture (CLP) model of sepsis and in acute lung injury induced by intratracheal instillation of LPS.We determined the effects of RC-3095 in the CLP model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. In addition, we determined the effects of RC-3095 on tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, and nitric oxide release from activated macrophages.The GRP antagonist attenuated LPS- or CLP-induced TNF-alpha, IL-1beta, and nitric oxide release in cultured macrophages and decreased the mRNA levels of inducible nitric oxide synthase. The administration of RC-3095 (0.3 mg/kg) 6 h after sepsis induction improved survival in the CLP model, and diminished lung damage after intratracheal instillation of LPS. These effects were associated with attenuation on the circulating TNF-alpha and IL-1beta levels and decreased myeloperoxidase activity in several organs.We report that a selective GRP receptor antagonist attenuates the release of proinflammatory cytokines in vitro and in vivo and improves survival in "established" sepsis. These are consistent with the involvement of a new inflammatory pathway relevant to the development of sepsis.
Prices of 18 new drug formulations are capped in India
Authors: C. Travasso
Journal: BMJ (2015)

The National Pharmaceutical Pricing Authority of India has capped the prices of 18 new drug formulations, including an intrauterine contraceptive device, antibiotics, painkillers, and drugs for diabetes and hypertension.

The prices have been capped under the Drugs Price Control Order (DPCO) 2013, which establishes a market based pricing mechanism to control the costs of drugs in India. 

Sharmila Mary Joseph, member …
Methodologies for studying human knowledge
Authors: John R. Anderson
Journal: Behavioral and Brain Sciences (1987)

Abstract The appropriate methodology for psychological research depends on whether one is studying mental algorithms or their implementation. Mental algorithms are abstract specifications of the steps taken by procedures that run in the mind. Implementational issues concern the speed and reliability of these procedures. The algorithmic level can be explored only by studying across-task variation. This contrasts with psychology's dominant methodology of looking for within-task generalities, which is appropriate only for studying implementational issues. The implementation-algorithm distinction is related to a number of other “levels” considered in cognitive science. Its realization in Anderson's ACT theory of cognition is discussed. Research at the algorithmic level is more promising because it is hard to make further fundamental scientific progress at the implementational level with the methodologies available. Protocol data, which are appropriate only for algorithm-level theories, provide a richer source than data at the implementational level. Research at the algorithmic level will also yield more insight into fundamental properties of human knowledge because it is the level at which significant learning transitions are defined. The best way to study the algorithmic level is to look for differential learning outcomes in pedagogical experiments that manipulate instructional experience. This provides control and prediction in realistically complex learning situations. The intelligent tutoring paradigm provides a particularly fruitful way to implement such experiments. The implications of this analysis for the issue of modularity of mind, the status of language, research on human/computer interaction, and connectionist models are also examined.
Regression of Renal Vascular and Glomerular Fibrosis
Authors: Jean-Jacques Boffa, Ying Lu, Sandrine Placier, Adam Stefanski, Jean-Claude Dussaule, Christos Chatziantoniou
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Renal fibrosis is one of the major complications associated with the development of hypertension. The objective of the present study was to determine whether and by which mechanisms treatment with AT1 receptor antagonists makes possible the regression of renal vascular and glomerular fibrosis. Experiments were performed in the hypertensive model of nitric oxide (NO) deficiency in rats. After 4 wk of hypertension, mortality rates averaged 20%; the surviving animals displayed a decline of renal function (urine protein/creatinine, 1.89 ± 0.63 versus 0.24 ± 0.03 mg/mmol; creatininemia, 110 ± 14 versus 38 ± 2 mmol/L in hypertensive animals and control, respectively; P < 0.01) and an exaggerated gene and protein expression of TGF-β, collagen I, and collagen IV (P < 0.001) within the renal vasculature associated with the development of glomerulosclerosis (sclerotic index, 2.26 ± 0.29 versus 0.12 ± 0.04; P < 0.001). In addition, activities of matrix metalloproteinases 2 and 9 were increased twofold in renal vessels and glomeruli (P < 0.01). Afterwards, losartan, an antagonist of angiotensin receptor type I, or hydralazine were administered in subgroups of hypertensive animals. After 1 wk of angiotensin II antagonism, collagen I, collagen IV, and TGF-β gene and protein expressions were decreased and glomerulosclerosis was less marked (sclerotic index 1.04 ± 0.45), whereas activities of metalloproteinases remained twofold higher than controls (P < 0.01). Hydralazine failed to improve renal function despite a similar degree of systolic pressure decrease. After 4 wk of losartan, the renal functional and histologic parameters were completely normalized, whereas they remained damaged in the hypertensive animals in which the mortality rate reached 85%. These data suggest that the progression of renal vascular fibrosis is a reversible process, at least in the NO deficiency model. The mechanism of the regression appears to be dual: inhibition of collagen synthesis due to AT1 receptor antagonism and activation of metalloproteinases that is probably associated with the degree of fibrosis independently of AT1 blockade. E-mail: [email protected]