tbuckley/cabot-search huggingface dataset:
Gall stone disease without gall stones--bile acid and bile lipid metabolism after complete gall stone dissolution.
Authors: D C Ruppin, G M Murphy, R H Dowling
Journal: Gut (1986)

Although bile acid and bile lipid metabolism have been studied in established cholelithiasis, little is known about them in patients destined to develop gall stones, but in whom the stones have not yet appeared (prestone gall stone disease). After confirmed complete gall stone dissolution and withdrawal of treatment, gall stones recur frequently. Before the stones reappear, these patients have 9poststone gall stone disease9. In 13 such patients we confirmed complete gall stone dissolution with two normal cholecystograms and in 11 of the 13 by normal ultrasonography, measured bile acid and bile lipid composition in fasting duodenal bile, bile acid synthesis from marker corrected three day faecal bile acid excretion, bile acid pool size using an abbreviated isotope dilution technique, 9steady-state9 bile lipid secretion using a duodenal amino acid perfusion system and then calculated the enterohepatic cycling frequency of the bile acid pool and the relationship between pool size and body weight. The results confirm that after withdrawal of treatment the biliary cholesterol saturation index reverts to levels (1.6 +/- SEM 0.4) comparable with those before dissolution therapy first began (1.6 +/- 0.2; NS). The mean bile acid pool size in the 13 patients of 4.4 +/- 0.5 mmol was comparable with that in untreated gall stone patients. Pool size was significantly smaller in the nine non-obese patients (3.5 +/- 0.3), than in the four obese (6.0 +/- 0.8; p less than 0.05). It also correlated significantly with body weight (r = 0.72) and with %IBW (r = 0.79). The coefficients of variation for biliary bile acid, phospholipid and cholesterol secretion were high, but the mean hourly secretion rates were of the same order as those seen in untreated gall stone patients studied with the amino acid duodenal perfusion stimulus. These results provide a baseline for assessing the response to postdissolution treatment and may indicate metabolic events leading to gall stone formation.
Gastroenterology Trainees Can Easily Learn Histologic Characterization of Diminutive Colorectal Polyps With Narrow Band Imaging
Authors: Swati G. Patel, Amit Rastogi, Gregory Austin, Matthew Hall, Brittany A. Siller, Kenneth Berman, Roy Yen, Ajay Bansal, Dennis J. Ahnen, Sachin Wani
Journal: Clinical Gastroenterology and Hepatology (2013)
Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge
Authors: Dominik Sturm, Sebastian Bender, David T. W. Jones, Peter Lichter, Jacques Grill, Oren Becher, Cynthia Hawkins, Jacek Majewski, Chris Jones, Joseph F. Costello, Antonio Iavarone, Kenneth Aldape, Cameron W. Brennan, Nada Jabado, Stefan M. Pfister
Journal: Nature reviews. Cancer (2014)
Eccentric/concentric ratios at selected velocities for the invertor and evertor muscles of the chronically unstable ankle.
Authors: H D Hartsell, S J Spaulding
Journal: British Journal of Sports Medicine (1999)

The use of muscle balancing by the clinician to determine return to activity or discharge of a patient is not a well understood measure. Because of the lack of information on the poorly understood concept of eccentric/concentric (E/C) ratios at the ankle, the purpose was to determine the E/C ratios for the invertor and evertor muscles at various velocities in healthy and chronically unstable ankles.Ten subjects with healthy ankles and 14 with chronically unstable ankles performed five maximal effort reciprocal eccentric/contraction contractions on an isokinetic dynamometer at four velocities (60, 120, 180, and 240 degrees/s) and for each physiological movement of inversion and eversion. Data were analysed using a two way mixed model analysis of variance with repeated measures, with Tukey's test used for post hoc analysis.Although the chronically unstable ankle was significantly weaker (p < 0.05) eccentrically and concentrically for inversion and eversion, the main effect of the E/C ratios for the ankle was not significant for either joint motion. The main effect of velocity was significant (p < 0.05) for each joint motion, but no significant interaction effects were observed. As velocity increased, the E/C ratio increased, except at 180 and 240 degrees/s for either ankle group.Chronic ankle instability and muscle weakness co-exist. Adequate E/C ratios in the chronically unstable ankle may exist in the absence of normal strength values.
Therapeutics in Respiratory Disease
Authors: D R Taylor
Journal: BMJ (1994)

Peter J Barnes, Kian Fan Chung, Timothy W Evans, Steven G Spiro Churchill Livingstone, pounds sterling 40, pp 174 ISBN 0-443-04134-2

Should I have referred to a dictionary definition of therapeutics before embarking on a review of this particular text? After several chapters, I was tempted. Instead, I conceitedly decided that my own working definition would suffice. And so, laden with clumsy subordinate clauses, my definition became “the therapy of disease with particular regard to background pathophysiological and pharmacological principles, and to its natural history and clinical variability.”

Such a definition may or may not be adequate. However, as a starting point, it ought to help distinguish a text which bears the title Therapeutics in Respiratory Disease …
Phase II study of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma: CALGB 90207
Authors: J.E. Rosenberg, S. Halabi, B.L. Sanford, A.L. Himelstein, J.N. Atkins, R.J. Hohl, F. Millard, D.F. Bajorin, E.J. Small
Journal: Annals of Oncology (2008)
Systems-level regulation of microRNA networks by miR-130/301 promotes pulmonary hypertension
Authors: Thomas Bertero, Yu Lu, Sofia Annis, Andrew Hale, Balkrishen Bhat, Rajan Saggar, Rajeev Saggar, W. Dean Wallace, David J. Ross, Sara O. Vargas, Brian B. Graham, Rahul Kumar, Stephen M. Black, Sohrab Fratz, Jeffrey R. Fineman, James D. West, Kathleen J. Haley, Aaron B. Waxman, B. Nelson Chau, Katherine A. Cottrill, Stephen Y. Chan
Journal: Journal of Clinical Investigation (2014)

Development of the vascular disease pulmonary hypertension (PH) involves disparate molecular pathways that span multiple cell types. MicroRNAs (miRNAs) may coordinately regulate PH progression, but the integrative functions of miRNAs in this process have been challenging to define with conventional approaches. Here, analysis of the molecular network architecture specific to PH predicted that the miR-130/301 family is a master regulator of cellular proliferation in PH via regulation of subordinate miRNA pathways with unexpected connections to one another. In validation of this model, diseased pulmonary vessels and plasma from mammalian models and human PH subjects exhibited upregulation of miR-130/301 expression. Evaluation of pulmonary arterial endothelial cells and smooth muscle cells revealed that miR-130/301 targeted PPARγ with distinct consequences. In endothelial cells, miR-130/301 modulated apelin-miR-424/503-FGF2 signaling, while in smooth muscle cells, miR-130/301 modulated STAT3-miR-204 signaling to promote PH-associated phenotypes. In murine models, induction of miR-130/301 promoted pathogenic PH-associated effects, while miR-130/301 inhibition prevented PH pathogenesis. Together, these results provide insight into the systems-level regulation of miRNA-disease gene networks in PH with broad implications for miRNA-based therapeutics in this disease. Furthermore, these findings provide critical validation for the evolving application of network theory to the discovery of the miRNA-based origins of PH and other diseases.
A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Authors: David S. Hong, Daniel W. Bowles, Gerald S. Falchook, Wells A. Messersmith, Goldy C. George, Cindy L. O'Bryant, Alex C. H. Vo, Kevin Klucher, Roy S. Herbst, S. Gail Eckhardt, Scott Peterson, Diana F. Hausman, Razelle Kurzrock, Antonio Jimeno
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The objectives of the study were to evaluate the maximum tolerated dose (MTD), safety, pharmacodynamics, pharmacokinetics, and antitumor activity of PX-866 in patients with incurable cancers. Experimental Design: This was a phase I, open-label, dose-escalation study. Drug was administered orally once per day either on an intermittent (arm 1; days 1–5 and 8–12 of a 28-day cycle) or continuous (arm 2; days 1–28 of a 28-day cycle) schedule. Additional patients were treated at the arm 2 MTD in a food effects substudy. Results: Eighty-four patients were treated in the arm 1 (n = 51), arm 2 (n = 20), and food effects (n = 13) cohorts. The most frequent study drug–related adverse events were gastrointestinal disorders (69.0%), with diarrhea being the most common (48.8%). The MTD was 12 and 8 mg for arm 1 and 2, respectively. The dose-limiting toxicities (DLT) consisted of grade III diarrhea (n = 3) and grade III elevated aspartate aminotransferase (AST; n = 1). The pharmacokinetics profile was dose proportional, with no evidence of drug accumulation. PX-866–associated inhibition of platelet pAKTSER473 was observed at the arm 2 MTD. The best response per Response Evaluation Criteria in Solid Tumors (RECIST) was stable disease in 22% of evaluable patients in arm 1, 53% in arm 2, and 11% in the food effects cohort. Eight patients were on study for 4 or more months. Conclusions: This first-in-human study shows that PX-866, an irreversible small-molecule inhibitor of phosphatidylinositol 3-kinase (PI3K), was well tolerated and was associated with prolonged stable disease, particularly when using a continuous dosing schedule. Clin Cancer Res; 18(15); 4173–82. ©2012 AACR.
Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays
Authors: Johan Staaf, David Lindgren, Johan Vallon-Christersson, Anders Isaksson, Hanna Göransson, Gunnar Juliusson, Richard Rosenquist, Mattias Höglund, Åke Borg, Markus Ringnér
Journal: Genome biology (2008)

Abstract We present a strategy for detection of loss-of-heterozygosity and allelic imbalance in cancer cells from whole genome single nucleotide polymorphism genotyping data. Using a dilution series of a tumor cell line mixed with its paired normal cell line and data generated on Affymetrix and Illumina platforms, including paired tumor-normal samples and tumors characterized by fluorescent in situ hybridization, we demonstrate a high sensitivity and specificity of the strategy for detecting both minute and gross allelic imbalances in heterogeneous tumor samples.
Relationship of<i>EGFR</i>Mutations, Expression, Amplification, and Polymorphisms to Epidermal Growth Factor Receptor Inhibitors in the NCI60 Cell Lines
Authors: Wanqing Liu, Xiaolin Wu, Wei Zhang, Raquel C. Montenegro, Donna Lee Fackenthal, Jared A. Spitz, Lyn Mickley Huff, Federico Innocenti, Soma Das, Edwin H. Cook,, Nancy J. Cox, Susan E. Bates, Mark J. Ratain
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The mechanism of sensitivity and resistance to epidermal growth factor receptor (EGFR) inhibitors is incompletely understood, particularly in cancers other than non–small-cell lung cancer (NSCLC). To understand the variable response to this class of drugs, we used the NCI60 cancer cell lines. We aimed to determine if there are interactions between EGFR expression, mutations, polymorphisms, and gene amplification, and whether these factors are associated with variability in response to EGFR inhibitors. Experimental Design: The EGFRVIII and tyrosine kinase (TK) domain mutations were examined in the NCI60 cancer cell lines. Five polymorphisms, −216G/T, −191C/A, intron 1 (CA)n, R497K, and 2607A/G, were genotyped. EGFR amplification was also assessed with high-density single-nucleotide polymorphism chip and real-time PCR, respectively. The results were correlated with cytotoxicity data for erlotinib and other 11 EGFR inhibitors, as well as other publicly available data for these lines. Results: All 12 inhibitors behaved similarly. No EGFRVIII but putative TK mutations in two cell lines were found. Both mutant cell lines were insensitive to all inhibitors. Meanwhile, response did not correlate with EGFR amplification but with EGFR gene expression, especially in the cell lines with relatively normal gene status. In addition, EGFR expression was associated with the −216G/T polymorphism but not with the intron 1 (CA)n polymorphism. A combination of −216G/T and R497K polymorphisms was weakly associated with drug response. Conclusions: These observations suggest that in addition to TK mutations, germ-line variability may also contribute to the pharmacodynamics of EGFR inhibitors, particularly when EGFR is genetically normal.
Canonical WNT signaling components in vascular development and barrier formation
Authors: Yulian Zhou, Yanshu Wang, Max Tischfield, John Williams, Philip M. Smallwood, Amir Rattner, Makoto M. Taketo, Jeremy Nathans
Journal: Journal of Clinical Investigation (2014)

Canonical WNT signaling is required for proper vascularization of the CNS during embryonic development. Here, we used mice with targeted mutations in genes encoding canonical WNT pathway members to evaluate the exact contribution of these components in CNS vascular development and in specification of the blood-brain barrier (BBB) and blood-retina barrier (BRB). We determined that vasculature in various CNS regions is differentially sensitive to perturbations in canonical WNT signaling. The closely related WNT signaling coreceptors LDL receptor–related protein 5 (LRP5) and LRP6 had redundant functions in brain vascular development and barrier maintenance; however, loss of LRP5 alone dramatically altered development of the retinal vasculature. The BBB in the cerebellum and pons/interpeduncular nuclei was highly sensitive to decrements in canonical WNT signaling, and WNT signaling was required to maintain plasticity of barrier properties in mature CNS vasculature. Brain and retinal vascular defects resulting from ablation of Norrin/Frizzled4 signaling were ameliorated by stabilizing β-catenin, while inhibition of β-catenin–dependent transcription recapitulated the vascular development and barrier defects associated with loss of receptor, coreceptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly through β-catenin–dependent transcriptional regulation. Together, these data strongly support a model in which identical or nearly identical canonical WNT signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB.
Bronchoscopy is useful for diagnosing smear-negative tuberculosis in HIV-infected patients
Authors: W. Worodria, J.L. Davis, A. Cattamanchi, A. Andama, S. Den Boon, S.D. Yoo, P.C. Hopewell, L. Huang
Journal: European Respiratory Journal (2010)

Bronchoscopy is useful for diagnosing smear-negative tuberculosis in HIV-infected patientsTo the Editors:Tuberculosis (TB) is the leading cause of morbidity and mortality in HIV-infected patients in sub-Saharan Africa [1], in part because limited availability of diagnostic tests hinders early, directed treatment.Studies have demonstrated a substantial yield of bronchoscopy for diagnosing HIVassociated opportunistic pulmonary diseases, but few studies have explicitly considered whether bronchoscopy adds to the sensitivity of sputum culture in identifying Mycobacterium tuberculosis, or whether bronchoscopy shortens the time needed to diagnose TB.Although bronchoscopy is unavailable in many HIV and TB endemic settings, where it is available its usefulness for TB diagnosis is uncertain.Thus, we examined the performance of bronchoscopy to diagnose TB and other pulmonary diseases in HIV-infected inpatients with cough in Kampala, Uganda.We performed a prospective cross-sectional study enrolling consecutive HIV-infected patients aged o18 yrs hospitalised at Mulago Hospital with cough of o2 weeks but ,6 months duration.After providing informed consent, patients underwent a standard evaluation including chest radiography, sputum acid-fast bacillus (AFB) microscopy and bronchoscopy with bronchoalveolar lavage (BAL) if they were AFB smearnegative, according to previously described protocols [2].Trained technicians examined BAL by smear and/or culture for mycobacteria, Pneumocystis jirovecii, and other fungi.Specific pneumonia treatment was recorded.Patients were seen at a 2-month follow-up visit, after which a pulmonologist and a medical officer assigned final diagnoses based on all diagnostic information and according to a standardised protocol.A final diagnosis of pulmonary TB was based on a positive sputum mycobacterial culture (using Lowenstein-Jensen media), positive BAL AFB smear or BAL mycobacterial culture, or a clinical response to TB treatment at the 2-month follow-up visit.
Association and differential role of PRSS1 and SPINK1 mutation in early-onset and late-onset idiopathic chronic pancreatitis in Chinese subjects
Authors: Y-T Chang, S-C Wei, P-C L, Y-W Tien, I-S Jan, Y-N Su, J-M Wong, M-C Chang
Journal: Gut (2009)

Chronic pancreatitis (CP) may be associated with genetic susceptibility. We read with interest the article by Mahurkar et al ( Gut 2006; 55 :1270–5) which described the role of pancreatic secretory trypsin inhibitor (SPINK1) gene mutation and cathepsin B gene polymorphisms in tropical calcific pancreatitis. Mutations in the cationic trypsinogen gene (PRSS1) and SPINK1 gene have been reported to be associated with different types of pancreatitis.1 However, controversial data also exist.2 The discordant observations demonstrate that the role of the PRSS1/SPINK1 mutation might differ in distinct types of CP or different ethnic populations.3 4

The genetic basis of pancreatitis of PRSS1 and SPINK1 genes in Chinese patients has rarely been explored. We undertook a study with idiopathic chronic pancreatitis (ICP) to determine whether PRSS1 and SPINK1 mutations are associated with ICP in Chinese patients and to analyse the genotype–phenotype correlation in the ICP subgroups …
The soluble form of a disintegrin and metalloprotease 33 promotes angiogenesis: Implications for airway remodeling in asthma
Authors: Ilaria Puxeddu, Yun Yun Pang, Anna Harvey, Hans Michael Haitchi, Ben Nicholas, Hajime Yoshisue, Domenico Ribatti, Geraldine Clough, Rob M. Powell, Gillian Murphy, Neil A. Hanley, David I. Wilson, Peter H. Howarth, Stephen T. Holgate, Donna E. Davies
Journal: Journal of Allergy and Clinical Immunology (2008)
Arrhythmogenic activity of cardiac muscle in pulmonary veins of the dog: implication for the genesis of atrial fibrillation
Authors: Y Chen
Journal: Cardiovascular Research (2000)

Objective: Pulmonary veins are important foci of ectopic beats to initiate paroxysmal atrial fibrillation. The purpose of this study were to investigate the electrophysiological characteristics of excitable cells in canine pulmonary veins obtained from healthy and chronic rapid atrial pacing dogs and their responses to cardioactive agents. Methods: Transmembrane action potentials (APs) were recorded from multiple sites of pulmonary veins isolated from 17 healthy dogs and 14 dogs with chronic (6–8 weeks) rapid atrial pacing (780 bpm). Results: In normal superfusate, several types of electrical activities were identified, including silent electrical activity, fast response APs driven by electrical stimulation, and spontaneous fast or slow response APs (with or without early afterdepolarizations). The incidences of AP with an early afterdepolarization (93% versus 41%) was greater in chronic pacing dogs. The spontaneous activities were depressed by beta-adrenoceptor blocker, calcium channel blocker, adenosine and acetylcholine. High frequency (<8 Hz) irregular rhythms occurred spontaneously or were induced by cardioactive agents or electrical stimuli. The incidence of spontaneously occurring tachyarrhythmias was much higher in preparations from chronic pacing dogs (93%) than from control (12%). The tachyarrhythmias were suppressed by sodium channel blocker, potassium channel blocker or magnesium. Conclusions: Pulmonary veins have arrhythmogenic ability through spontaneous activities or high-frequency irregular rhythms. The higher incidence of spontaneously occurring high-frequency irregular rhythms in chronic rapid atrial pacing dogs may account for the increased risk of atrial fibrillation in these dogs.
Negative pressure ventilation in the treatment of acute respiratory failure: an old noninvasive technique reconsidered
Authors: A. Corrado, M. Gorini, G. Villella, E. De Paola
Journal: European Respiratory Journal (1996)

Noninvasive mechanical ventilatory techniques include the use of negative and positive pressure ventilators. Negative pressure ventilators, such as the "iron lung", support ventilation by exposing the surface of the chest wall to subatmospheric pressure during inspiration; whereas, expiration occurs when the pressure around the chest wall increases and becomes atmospheric or greater than atmospheric. In this review, after a description of the more advanced models of tank ventilators and the physiological effects of negative pressure ventilation (NPV), we summarize the recent application of this old technique in the treatment of acute respiratory failure (ARF). Several uncontrolled studies suggest that NPV may have a potential therapeutic role in the treatment of acute on chronic respiratory failure in patients with chronic obstructive pulmonary disease and restrictive thoracic disorders, reducing the need for endotracheal intubation. In the paediatric field, after substantial technical improvement, NPV has been successfully reintroduced for the treatment of ARF due to neonatal distress syndrome and bronchopulmonary dysplasia, and for the weaning from positive pressure ventilation in intubated patients. The positive results of these reports need to be formally confirmed by further prospective and controlled studies before recommending the generalized use of negative pressure ventilation in acute respiratory failure as a standard of care.
Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial
Authors: Jean-Louis Bresson, Christian Perronne, Odile Launay, Catherine Gerdil, Melanie Saville, John Wood, Katja Höschler, Maria C Zambon
Journal: The Lancet (2006)