tbuckley/cabot-search huggingface dataset:
Multicenter prospective validation of the Baveno IV and Baveno II/III criteria in cirrhosis patients with variceal bleeding
Authors: Dominique Thabut, Marika Rudler, Nina Dib, Nicolas Carbonell, Philippe Mathurin, Faouzi Saliba, Alain Mallet, Julien Massard, Brigitte Bernard‐Chabert, Frederic Oberti, Paul Cales, Jean‐Louis Golmard, Christophe Bureau
Journal: Hepatology (2014)

The criteria for defining failure to control bleeding in cirrhosis patients were introduced at the Baveno II/III meetings and were widely used as endpoints in clinical trials. Because they lacked specificity, the Baveno IV criteria were proposed in 2005 and slightly modified in 2010 (Baveno V). These criteria included a new index for patients undergoing transfusion, called adjusted‐blood‐requirement‐index (ABRI = number of blood units/(final‐initial hematocrit + 0.01)), with a cutoff value of 0.75. In this multicenter prospective study, we sought to 1) validate the Baveno IV/V criteria; 2) compare them to the Baveno II/III criteria; 3) assess ABRI performance using a standardized calculation. The key inclusion criteria were: 1) variceal bleeding; 2) cirrhosis; 3) no need to modify the transfusion policy. The patients were classified according to the Baveno IV, V, and II/III criteria. The gold standard for failure during a 5‐day period was the clinical judgment of three independent experts, blinded to the Baveno assessments. A total of 249 patients were included. The experts' agreement in clinical judgment of the failure was 80%. Failure occurred in 20.5% of patients; the c‐statistics were 0.72 versus 0.64 and 0.65 for Baveno IV versus Baveno II/III and Baveno V criteria ( P = 0.001 for both). ABRI did not improve the diagnostic performance of the Baveno IV criteria. The Baveno IV, but not Baveno II/III, criteria independently predicted survival. Conclusion : The Baveno IV criteria demonstrated a higher accuracy than the Baveno II/III and Baveno V criteria for assessing failure to control bleeding and predicted survival independently. Together, our results show that ABRI is not a useful metric, and the Baveno IV criteria should replace the Baveno II/III criteria. (H epatology 2015;61:1024–1032)
β<sub>2</sub>-Agonist Therapy in Lung Disease
Authors: Mario Cazzola, Clive P. Page, Paola Rogliani, M. Gabriella Matera
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Section:ChooseTop of pageAbstract <<Mechanism of ActionPharmacokineticsPharmacodynamicsClinical UseDosing StrategiesCost-EffectivenessCombination TherapyMeasuring Effects and Out...Adverse EffectsSafety SystemsGuidelinesFuture DevelopmentsReferencesCITING ARTICLES
Accuracy and negative predictive value of adenosine contrast echocardiography are higher in patients with single vessel than multivessel coronary artery disease
Authors: Alvaro Moraes, Caio Medeiros, Fernando Morcerf, Marcia Carrinho, Marcia Castier, Antonio Carlos Nogueira, Flavia Salek, Hans Dohmann
Journal: Journal of the American College of Cardiology (2002)
Epidemiologic Characteristics of Intraocular Pressure in the Korean and Mongolian Populations: The Healthy Twin and the GENDISCAN Study
Authors: Mi Kyeong Lee, Sung-Il Cho, Ho Kim, Yun-Mi Song, Kayoung Lee, Jong-Il Kim, Dong-Myung Kim, Tae-Young Chung, Youn Sic Kim, Jeong-Sun Seo, Don-Il Ham, Joohon Sung
Journal: Ophthalmology (2012)
Docetaxel-induced recall dermatitis on previous laser treatment sites
Authors: C-Y. Chu, C-H. Yang
Journal: British Journal of Dermatology (2005)

Sir, Chemotherapy‐induced ‘recall’ is a phenomenon whereby the administration of a chemotherapeutic agent induces an inflammatory reaction in a previous injury site.1–3 The most well‐known recall phenomenon is radiation recall, and there is no previous report of a chemotherapy‐induced recall reaction on a laser‐induced wound.1–3 A 45‐year‐old female presented in August 2002 with intermittent headache, ataxia, vertigo and vomiting, followed by sudden loss of consciousness. Brain magnetic resonance imaging revealed multiple brain tumours at the right cerebellum, right occipital and left parietal lobes. The patient underwent excision of the right cerebellar tumour and was found to have a metastatic adenocarcinoma. Chest computed tomography (CT) study disclosed multiple nodules in the right lung field and the patient was diagnosed as having nonsmall‐cell lung cancer with multiple brain metastases. Whole brain radiotherapy with the dosage of 3000 cGy in 15 fractions was administered during September and October 2002, and all the neurological symptoms subsided. The patient was also treated with four courses of gemcitabine 1000 mg m−2 (on days 1, 8 and 15) plus cisplatin 90 mg m−2 (on day 15) from November 2002 to March 2003. In November 2003, the chest CT study revealed progression of the disease, and the patient was then treated with docetaxel 40 mg m−2 on days 1, 8 and 15. No obvious skin side‐effect was ever noted until the first infusion of the third cycle. The patient found two well‐defined, erythematous, slightly scaling, infiltrative plaques with tingling and pruritic sensations, which had developed on both cheeks 2 days after that infusion. The skin lesions were worse after the second and third infusions of that cycle (Fig. 1). An incision skin biopsy was performed on the left cheek lesion; this revealed epidermal dysmaturation with frequent dyskeratotic keratinocytes, basal vacuolar changes and pigment incontinence, which were compatible with the effects of chemotherapeutic agents (Fig. 2).
Endothelin-1 receptor blockade prevents renal injury in experimental hypercholesterolemia
Authors: Alejandro R. Chade, Patricia J. Best, Martin Rodriguez-Porcel, Joerg Herrmann, Xiangyang Zhu, Tatsuya Sawamura, Claudio Napoli, Amir Lerman, Lilach O. Lerman
Journal: Kidney International (2003)
A patient's journey: whooping cough
Authors: Ros Levenson
Journal: BMJ (2007)

Recently I had whooping cough. This has now been confirmed by the results of a blood test. I was in little doubt about the diagnosis from the beginning. However, my experience suggests that, despite considerable literature on the prevalence of whooping cough in adults, the diagnosis is still not one that doctors readily think of when they are faced with an adult rather than an infant or child.

I can well understand why the general practitioners I saw in the first couple of weeks did not diagnose whooping cough at once. I am aware that the duration of the symptoms, as well as the nature of the symptoms themselves, is important, and there were more obvious diagnoses that sprang to mind. However, when I experienced the first two or three terrifying paroxysmal coughing sessions, I knew it was a cough unlike anything I had had previously and said so. It also reminded me of my daughter's whooping cough when she was a toddler, many years ago. I was also very struck by the information on the website of Dr Doug Jenkinson (www.whoopingcough.net), which gave descriptions that matched my symptoms exactly. As a result, I spoke to the general practitioner who had first seen me and asked if he thought it could possibly be whooping cough. I also asked another general practitioner whom I saw a week or so later. In both cases their answer was similar: it was unlikely to be whooping cough as it is rare in adults.

On a visit to a chest clinic soon after this, I again raised the possibility of whooping cough. Once more this was thought to be highly unlikely. It was only on my return visit, when I felt just about well enough to be …
Mixed Chimerism and Immunologic Tolerance
Authors: Robert A. Good
Journal: New England Journal of Medicine (1993)

Type IV glycogen storage disease results in progressive destruction of the liver and other vital organs, including the heart. This disease, caused by a deficiency of the branching enzyme α-1,4-glucan-1,4-glucan 6-transferase, results in the accumulation of a damaging amylopectin-like polysaccharide in these organs. In this issue of the Journal, Starzl et al.1 extend a previous report2 that liver transplantation in patients with type IV glycogen storage disease reduced the deposition of amylopectin in the heart. Furthermore, liver transplantation in a patient with Gaucher's disease resulted in the disappearance of the toxic glucocerebroside from involved tissue1.The authors show that . . .
The Bone Morphogenetic Protein System In Mammalian Reproduction
Authors: Shunichi Shimasaki, R. Kelly Moore, Fumio Otsuka, Gregory F. Erickson
Journal: Endocrine Reviews (2004)

Using molecular, cellular, and genetic approaches, recent studies examining the role of the bone morphogenetic protein (BMP) family of growth factors in the reproductive system have led to significant breakthroughs in our understanding of mammalian reproduction and fertility. Gene expression studies have revealed that key components of the BMP system (ligands, receptors, signaling molecules, and binding proteins) exhibit coordinated spatial and temporal expression patterns in fundamental cell types throughout the reproductive system. Availability of recombinant BMPs has enabled functional studies that have demonstrated important biological activities of BMPs in controlling cellular proliferation, differentiation, and apoptosis in reproductive tissues. The physiological importance of the BMP system for mammalian reproduction has been further highlighted by the elucidation of the aberrant reproductive phenotypes of animals with naturally occurring mutations or targeted deletions of certain BMP family genes. Collectively, these studies have established the concept that the BMP system plays a crucial role in fertility in female and male mammals. The purpose of this article is to review the evidence underpinning the importance of the BMP system in mammalian reproduction.
Edmund Neville Hey
Authors: A. Craft
Journal: BMJ (2011)

Edmund Neville Hey (“Ed”) was a pioneer in the care of newborn babies. He made major contributions to understanding babies’ physiology, the evidence base for their clinical care, and perinatal epidemiology. Babies, especially those born prematurely, need to be kept warm; they need to be looked after by highly skilled nurses; and their care is best organised in tiers so that those needing the greatest medical and nursing expertise can be referred to centres with the necessary skills. Ed provided evidence on the physiology of thermal regulation and the organisation of neonatal care that continues to be central to clinical care and policy decisions today.

Ed’s work on thermoregulation in babies was as a DPhil student in Oxford working with Kenneth Cross. After birth from a very warm environment babies very quickly lose heat especially if they are born too early. His early clinical training was in Oxford, but he was appointed consultant in respiratory paediatrics at Great Ormond Street Hospital before he moved to Newcastle as senior lecturer in child health in 1970. Here he came under the influence of Gerald Neligan, who was one of the first paediatricians to specialise in the care of newborn babies. Along with Mike Parkin, they developed a system of care which was comparatively non-interventionist at a time when others were developing much more intrusive care. They believed in doing simple things well and assisting nature’s normal processes.

Hey recognised at an early stage the importance of data collection to evaluate …
Abstract 2666: Receptor protein tyrosine phosphatase type kappa is a prognostic marker, essential for regulating malignant behavior of glioma cells
Authors: Supreet Agarwal, Zita Sibenaller, Timothy C. Ryken, Mahfoud Assem
Journal: Cancer Research (2012)

Abstract Malignant gliomas have a poor survival resulting from rapid growth of the tumor and extensive dispersion throughout the brain parenchyma. Discovery of tumor-specific biomarkers hold great promise in improving survival and thus call for better understanding of regulatory signals driving glioma cell migration and dispersal. Using genome-wide exploration, we have identified frequent genetic alterations at the Receptor protein tyrosine phosphatase type kappa (PTPRK) locus. These PTPRK alterations were among the top significant and very relevant to glioma biology since PTPRK is a dephosphorylation regulator of tyrosine phosphorylation (TP) signaling, a frequently altered signaling cascade in glioma as reported previously. Understanding PTPRK function will provide relevant novel insights into the molecular mechanisms underlying glioma cell growth and migration. PTPRK expression was analyzed by quantitative-RT-PCR and western blot. Mutations of PTPRK were identified by sequencing full length PTPRK transcripts from a subset of patients’ samples showing PTPRK loss of heterozygosity. Two major PTPRK variants were cloned and expressed in cells harboring altered PTPRK (U87MG cell line) to study their effect on PTPRK phosphatase activity and functionality. PTPRK locus undergoes allelic loss in glioma and contributes to cancer phenotype. It is an independent prognostic marker in glioma. Patients with altered PTPRK (23%) have shorter survival compared to those with normal PTPRK molecular status (p=0.001, Log-rank test, 14 vs. 30 months). PTPRK mRNA as well as protein levels were lower in tumor biopsies compared to non-tumor specimens. Mutational analysis revealed missense mutations in the phosphatase domain, resulting in altered PTPRK phosphatase activity, possibly due to changes in active site conformation. Further, PTPRK alterations changed expression profiles of the PTPRK protein as a result of altered post-translational processing. Reconstitution of PTPRK expression in glioma cells (U87MG cell line) harboring PTPRK deletions suppressed cell growth and migration which was alleviated by the PTPRK variants to differing extent. PTPRK knockdown via shRNA down-regulated its onco-suppressive function compared to PTPRK expressing cells. Our findings provide the first evidence of the key role of PTPRK expression in glioma and shed light on the biological consequences of mutations in the PTPRK gene which significantly alter PTPRK functionality. Biological relevance of PTPRK variants will be determined and validated on a large scale. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2666. doi:1538-7445.AM2012-2666
Press: Raising awareness or spreading fear?
Authors: A. Kent
Journal: BMJ (2000)

Cancer charities, radio shows, medical journals—they are all in the business of getting messages across to the public. If you can't capture the reader's or listener's interest, there is no way he or she will take in the important messages that you want to deliver. One way to grab that interest is to scare the audience rigid, but can it be justified?

The Imperial Cancer Research Fund is currently running a major advertising campaign that shows three little girls sitting on a wall. Over each head is a different label—teacher, lawyer, cancer. Meanwhile, in The Archers— Radio 4's long running soap opera of “everyday farming folk”—women's worst fears of breast cancer are exploited as an unfeasibly young character undergoes a mastectomy.

The cancer charity's campaign arose from a survey showing that the public thought an individual's lifetime risk of getting cancer was one in 10 or less. The “correct” risk is two in five. The charity then commissioned an advertising agency, Abbott Mead Vickers, to educate the public. Unfortunately, the advert creates the impression that only two of the three children will grow up to have a career. Alternatively, even if the third does grow up, her life will be defined …
Loss of MicroRNA-17∼92 in Smooth Muscle Cells Attenuates Experimental Pulmonary Hypertension via Induction of PDZ and LIM Domain 5
Authors: Tianji Chen, Guofei Zhou, Qiyuan Zhou, Haiyang Tang, Joyce Christina F. Ibe, Hongqiang Cheng, Deming Gou, Ju Chen, Jason X.-J. Yuan, J. Usha Raj
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Recent studies suggest that microRNAs (miRNAs) play important roles in regulation of pulmonary artery smooth muscle cell (PASMC) phenotype and are implicated in pulmonary arterial hypertension (PAH). However, the underlying molecular mechanisms remain elusive.Objectives: This study aims to understand the mechanisms regulating PASMC proliferation and differentiation by microRNA-17∼92 (miR-17∼92) and to elucidate its implication in PAH.Methods: We generated smooth muscle cell (SMC)-specific miR-17∼92 and PDZ and LIM domain 5 (PDLIM5) knockout mice and overexpressed miR-17∼92 and PDLIM5 by injection of miR-17∼92 mimics or PDLIM5-V5-His plasmids and measured their responses to hypoxia. We used miR-17∼92 mimics, inhibitors, overexpression vectors, small interfering RNAs against PDLIM5, Smad, and transforming growth factor (TGF)-β to determine the role of miR-17∼92 and its downstream targets in PASMC proliferation and differentiation.Measurements and Main Results: We found that human PASMC (HPASMC) from patients with PAH expressed decreased levels of the miR-17∼92 cluster, TGF-β, and SMC markers. Overexpression of miR-17∼92 increased and restored the expression of TGF-β3, Smad3, and SMC markers in HPASMC of normal subjects and patients with idiopathic PAH, respectively. Knockdown of Smad3 but not Smad2 prevented miR-17∼92-induced expression of SMC markers. SMC-specific knockout of miR-17∼92 attenuated hypoxia-induced pulmonary hypertension (PH) in mice, whereas reconstitution of miR-17∼92 restored hypoxia-induced PH in these mice. We also found that PDLIM5 is a direct target of miR-17/20a, and hypertensive HPASMC and mouse PASMC expressed elevated PDLIM5 levels. Suppression of PDLIM5 increased expression of SMC markers and enhanced TGF-β/Smad2/3 activity in vitro and enhanced hypoxia-induced PH in vivo, whereas overexpression of PDLIM5 attenuated hypoxia-induced PH.Conclusions: We provided the first evidence that miR-17∼92 inhibits PDLIM5 to induce the TGF-β3/SMAD3 pathway, contributing to the pathogenesis of PAH.
Novel Therapies Target Myasthenia Gravis
Authors: Tracy Hampton
Journal: JAMA (2007)

investigators wanted to look more carefully at the subgroup of women who reported prior hormone therapy use, said Henderson. The prior-use group included 7153 healthy women between the ages of 65 and 79 years. While this new evidence is important, Henderson cautioned that the findings are not strong enough to change clinical recommendations for hormone therapy use. “The message from the study is that the area of late cognitive outcomes [after hormone therapy] is still a viable and important area of study,” he said. But it is a message more for scientists than for clinicians.
Canalicular Bile Secretion in Man STUDIES UTILIZING THE BILIARY CLEARANCE OF [14C]MANNITOL
Authors: James L. Boyer, Joseph R. Bloomer
Journal: Journal of Clinical Investigation (1974)

[14C]Mannitol was administered i.v. as a bolus injection to five postcholecystectomy patients with indwelling T-tubes and re-established enterohepatic circulations to evaluate the biliary clearance of [14C]mannitol as a means of estimating canalicular bile flow in man. [14C]Mannitol appeared in collections of bile 9-22.5 min after intravenous injection, rose to a peak, and thereafter paralleled the plasma [14C]mannitol disappearance curve. Bile-plasma [14C]mannitol ratios and [14C]mannitol clearances were determined during control and choleretic periods after correction of the bile [14C]mannitol points for the transit time of a given sample. After i.v. injection of sodium dehydrocholate in five studies, bile flow and mannitol clearance increased proportionately. However, when ductular secretion was stimulated with an i.v. bolus of secretin in three other studies, [14C]mannitol clearance remained essentially unchanged, indicating that [14C]mannitol entered bile at the level of the hepatocyte and could be utilized as a marker of canalicular flow in man.
Respiratory responses to repeated prolonged exposure to 0.12 ppm ozone.
Authors: L J Folinsbee, D H Horstman, H R Kehrl, S Harder, S Abdul-Salaam, P J Ives
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Repeated exposure to high concentrations of ozone results first in augmentation (typically on the second day) and then attenuation of pulmonary response in humans. To determine the effects of repeated prolonged low-concentration ozone exposure, we exposed 17 healthy nonsmoking male subjects to 0.12 ppm ozone for 6.6 h on 5 consecutive days. Subjects were also exposed once to filtered air. Volunteers exercised at a ventilation of approximately 39 L/min for 50 min of each hour during the exposure. Spirometry, plethysmography, and symptom responses were obtained before, during, and after each exposure. Nasal lavage and aerosol bolus dispersion were obtained before and after exposure. Spirometry decreased and symptoms increased on the first day. Responses were less on the second day compared with those on the first day, and they were absent compared with control values on the subsequent 3 days of ozone exposure. Percent change in FEV1 after ozone exposure compared with that after air exposure averaged -12.79, -8.73, -2.54, -0.6, +0.18% for Days 1 to 5 of ozone exposure, respectively. FEV1 responses ranged from a zero to 34% decrease on Days 1 and 2. After each exposure, we determined the ratio of SRaw after inhaling a fixed dose of methacholine to SRaw after inhaling saline aerosol, as an index of airway responsiveness. Airway responsiveness was significantly increased after each ozone exposure. The mean ratios were 2.22, 3.67, 4.55, 3.99, 3.24, and 3.74 for filtered air and ozone Days 1 to 5, respectively. Symptoms of cough and pain on deep inspiration increased significantly on ozone Day 1 only.(ABSTRACT TRUNCATED AT 250 WORDS)
Behaviorism and altruistic acts
Authors: J. McKenzie Alexander
Journal: Behavioral and Brain Sciences (2002)

Rachlin's idea that altruism, like self-control, is a valuable, temporally extended pattern of behavior, suggests one way of addressing common problems in developing a rational choice explanation of individual altruistic behavior. However, the form of Rachlin's explicitly behaviorist account of altruistic acts suffers from two faults, one of which questions the feasibility of his particular behaviorist analysis.
Preventive effect of Curcumin on AD through increasing PS1/E-cadherin/beta-catenin complex mediated by E-cadherin
Authors: Xiong Zhang, Wenke Yin, Xiaodong Shi, Yu Li
Journal: Molecular Neurodegeneration (2012)

Background The deprivation or abnormality of the molecular function of Wnt/b-catenin triggers the genesis and development of AD, and b-catenin is an important positive mediator in the Wnt/b-catenin signaling pathway. In our previous study, we found that Curcumin could inhibit the expression of b-catenin and prevent AD, but the mechanisms were not fully understood. E-cadherin is a negative mediator in the Wnt/b-catenin signaling pathway, and interacts with b-catenin and PS1 form a trimeric complex, so, we hypothesized that Curcumin prevented AD through increasing PS1/E-cadherin/bcatenin complex by overexpression of E-cadherin.