tbuckley/cabot-search huggingface dataset:
Reproducibility of Doppler sonographic evaluation of portal hemodynamics. A long-term study
Authors: None SCHIEDERMAIER
Journal: Hepatology (1995)

Wnt3a and Wnt5a are ligands orchestrating the canonical and non-canonical pathways, respectively, with involvement in hepatocellular carcinoma (HCC). Hesperidin (HP) is a natural product found in citrus fruits and reputed for its antitumor activity. The present study aims to investigate the potential hepatoprotective effect of HP against thioacetamide (TAA)-induced HCC focusing on its potential role on Wnt3a and Wnt5a signaling pathways.Forty rats were equally divided into groups; normal control, HP control (receiving HP, 150 mg/kg/day), HCC (receiving TAA, 200 mg/kg twice weekly for 14 weeks) and HP-HCC (receiving HP and TAA). Gene expressions of Wnt3a, Wnt5a, β-catenin and Cyclin D1 were assessed by qPCR, while their protein levels, along with active caspase-3 level, were quantified by ELISA and immunohistochemistry. Liver functions, oxidative stress parameters and myeloperoxidase activity were measured. MTT assay of hepG2 cells treated with recombinant Wnt3a (10 ng/ml) in presence or absence of HP (100 μM) was performed.HCC group exhibited a significant increase in Wnt3a, β-catenin, Cyclin D1 and Wnt5a gene expressions, as well as, their protein levels. HP significantly prevented TAA-activated Wnt3a/β-catenin and Wnt5a pathways. Moreover, HP exerted hepatoprotective effect by significantly improving the oxidative imbalance, inflammation and liver function parameters, serum ALT, AST activities, and albumin level.Our study is the first to report the possible role of Wnt3a/β-catenin and Wnt5a pathways in TAA-induced early HCC model in rats. HP has a prophylactic effect against hepatocarcinogenesis via preventing the induction of both canonical and non-canonical Wnt pathways.
Digoxin Ups and Downs
Authors: George Dunea
Journal: JAMA (1979)

To be cast like Daniel into a den full of leonine toxicologists conjures up visions of fierce arguments about volumes of distribution and semilogarithmic graphs showing the slope of the decline of the offending poison and its predicted half-life. But before rushing to enroll in a summer makeup course in pharmacokinetics and trying to understand how a 70-kg, nongargantuan man can have a volume of distribution of 700 L, the potential victim might pause to remember that correlations between blood levels and clinical symptoms are at best imprecise, that what is being measured is not necessarily what is causing the symptoms, and that in no field of medicine have the tempestuous winds of therapeutic fashion been more violent than in the realm of toxicology. For digoxin, everybody agrees that some of the drug can be removed by charcoal or resin hemoperfusion and that one may expect a clearance of some
Europium-doped gadolinium sulfide nanoparticles as a dual-mode imaging agent for T1-weighted MR and photoluminescence imaging
Authors: Jongjin Jung, Mi Ae Kim, Jee-Hyun Cho, Seung Jae Lee, Ilseung Yang, Janggeun Cho, Seong Keun Kim, Chulhyun Lee, Joung Kyu Park
Journal: Biomaterials (2012)
Bronchogenic Carcinoma
Authors: Adrian Ehler, Allan Stranahan, Kenneth B. Olson
Journal: New England Journal of Medicine (1954)

VIRTUALLY all reports indicate a considerable rise in the incidence of bronchogenic carcinoma in white males.1 2 3 4 The increase is less striking in females and less conclusive for races other than Caucasian. The histologic5 and biologic characteristics of these tumors are probably more important in prognosis than early diagnosis. Many of the more malignant tumors are first discovered or made manifest through their metastasis and present hopeless problems at the time of diagnosis. Still other tumors may remain localized for long periods, producing chronic symptoms that are frequently misdiagnosed as asthma, cardiac disease, tuberculosis or chronic bronchitis. The last group of . . .
Infantile Pyloric Stenosis
Authors: D. Levi
Journal: BMJ (1938)

<h3>BACKGROUND AND PURPOSE:</h3> Computational fluid dynamics simulations of neurovascular diseases are impacted by various modeling assumptions and uncertainties, including outlet boundary conditions. Many studies of intracranial aneurysms, for example, assume zero pressure at all outlets, often the default (“do-nothing”) strategy, with no physiological basis. Others divide outflow according to the outlet diameters cubed, nominally based on the more physiological Murray9s law but still susceptible to subjective choices about the segmented model extent. Here we demonstrate the limitations and impact of these outflow strategies, against a novel “splitting” method introduced here. <h3>MATERIALS AND METHODS:</h3> With our method, the segmented lumen is split into its constituent bifurcations, where flow divisions are estimated locally using a power law. Together these provide the global outflow rate boundary conditions. The impact of outflow strategy on flow rates was tested for 70 cases of MCA aneurysm with 0D simulations. The impact on hemodynamic indices used for rupture status assessment was tested for 10 cases with 3D simulations. <h3>RESULTS:</h3> Differences in flow rates among the various strategies were up to 70%, with a non-negligible impact on average and oscillatory wall shear stresses in some cases. Murray-law and splitting methods gave flow rates closest to physiological values reported in the literature; however, only the splitting method was insensitive to arbitrary truncation of the model extent. <h3>CONCLUSIONS:</h3> Cerebrovascular simulations can depend strongly on the outflow strategy. The default zero-pressure method should be avoided in favor of Murray-law or splitting methods, the latter being released as an open-source tool to encourage the standardization of outflow strategies.
Incidence of peripheral blood eosinophilia and the threshold eosinophile count for indicating hypereosinophilia‐associated diseases
Authors: S. Kobayashi, S. Inokuma, K. Setoguchi, H. Kono, K. Abe
Journal: Allergy (2002)

A definite threshold of the peripheral blood eosinophile count that indicates the presence of hypereosinophilia-associated diseases has not yet been determined.The threshold eosinophile count at which cases of hypereosinophilia-associated diseases (n = 25) can be differentiated from those of bronchial asthma (n = 101) was determined. Then, the incidences of eosinophile counts greater than 1.0 x 10(9)/l or the threshold level, were studied by analysis of 43,805 samples sent to the laboratory, and the diseases associated with the increased counts were determined.The eosinophile count in cases of hypereosinophilia-associated diseases and in those of bronchial asthma were 10.967 +/- 1.680 x 10(9)/l and 0.574 +/- 0.045 x 10(9)/l, respectively (P < 0.001); the threshold was 2.052 x 10(9)/l. The percentages of samples with an eosinophile count of more than 1.0 x 10(9)/l and 2.052 x 10(9)/l were 0.6% and 0.1%, respectively; the latter comprised of 41 samples from 24 patients including eight with hypereosinophilia-associated diseases. The patients with hypereosinophilia-associated diseases had a significantly higher count, and a higher incidence of counts of more than 2.052 x 10(9)/l, than others, including patients with malignancies and symptoms conventionally referred as "atopic diseases".Hypereosinophilia-associated diseases are associated with a very high eosinophile count of more than 2.052 x 10(9)/l, which was observed rarely.
Pharmacologic Treatment of Congestive Heart Failure
Authors: Robert Anderson
Journal: JAMA (1995)

To the Editor.  —Dr Baker and colleagues 1 do not mention the importance of magnesium insufficiency and/or depletion in the pharmacologic treatment of heart failure. Patients with congestive heart failure have lower levels of magnesium compared with levels in those without disease, 2 and diuretics and digoxin induce magnesium depletion as well as potassium depletion. 3 In fact, repletion of magnesium is a significant contributor to the reversal of hypokalemia and digitalis toxicity. 4,5 The incidence of heart failure after suspected myocardial infarction was reduced 25% with early intravenous magnesium administration in the Leicester Magnesium Trials. 6
Relationships among msx gene structure and function in zebrafish and other vertebrates
Authors: M. Ekker, M. A. Akimenko, M. L. Allende, R. Smith, G. Drouin, R. M. Langille, E. S. Weinberg, M. Westerfield
Journal: Molecular Biology and Evolution (1997)

The zebrafish genome contains at least five msx homeobox genes, msxA, msxB, msxC, msxD, and the newly isolated msxE. Although these genes share structural features common to all Msx genes, phylogenetic analyses of protein sequences indicate that the msx genes from zebrafish are not orthologous to the Msx1 and Msx2 genes of mammals, birds, and amphibians. The zebrafish msxB and msxC are more closely related to each other and to the mouse Msx3. Similarly, although the combinatorial expression of the zebrafish msx genes in the embryonic dorsal neuroectoderm, visceral arches, fins, and sensory organs suggests functional similarities with the Msx genes of other vertebrates, differences in the expression patterns preclude precise assignment of orthological relationships. Distinct duplication events may have given rise to the msx genes of modern fish and other vertebrate lineages whereas many aspects of msx gene functions during embryonic development have been preserved.
PTH-177 A New Pancreatobiliary Telephone Clinic Service – Improved Service Delivery, Efficiency and Patient Experience
Authors: V Sehgal, B Krishnan, M Kumar, M H Chapman, S P Pereira, G J Webster, G J Johnson
Journal: Gut (2013)

<h3>Introduction</h3> Following the establishment of specialist cancer centres (and other centralised services), increasing numbers of patients are referred for tertiary care. This may have implications for travel, particularly as patients now have to pay travel costs. As a tertiary referral centre for pancreaticobiliary (PB) medicine we are referred patients from across the UK for a specialist opinion on complex benign and malignant PB problems. The established system of an initial face-to-face clinic visit often then requires return visits for investigations or endoscopic intervention, with significant inconvenience and travel costs for the patient. In response to this, we developed a novel, consultant-led telephone clinic (TC) service. The aims of this service were to improve efficiency and patient satisfaction. <h3>Methods</h3> A TC service was commenced with prospective data entry into a database over a 12-week period. Data was obtained on the following: patient demographics; postcode; clinical indication; round distances patients would have otherwise travelled if visiting UCLH. The time and cost incurred for visiting UCLH was calculated using the cheapest return train fare to London Euston (nearest train station). Patients were contacted some time after their consultation by an uninvolved member of non-clinical staff to obtain feedback based on a 9-point questionnaire. <h3>Results</h3> 77 patients were listed for consultation in 10 separate TC’s. 17 (22%) were excluded (9 did not answer their original TC; 8 did not answer for feedback). Of the 60 patients analysed (35 female, median age 52.5 years), 12 (20%) were new referrals and 48 (80%) follow-ups. The average round distance if otherwise travelling to UCLH was 96 (3–606) miles. The average time and cost for a return trip to UCLH was 155 (8–593) minutes and £27.60 (£7.30–105). Clinical indications were suspected Sphincter of Oddi dysfunction 18 (30%); acute or chronic pancreatitis 12 (20%); cholangiopathy 6 (10%); choledocholithiasis 5 (8%); non-PB gastrointestinal disease 9 (15%). 14 (23%) had formal out patient clinic review following their TC consultation. In 22 (37%) a repeat TC appointment was sufficient and 7 (12%) were discharged. The remaining 17 (28%) were referred for further endoscopic or radiological imaging at UCLH with TC follow up afterwards. All 60 patients either ‘strongly agreed’ (52, 86%) or ‘agreed’ (8, 13%) that the TC service was efficient. 29 (48%) expressed concerns regarding travel costs if visiting UCLH. Only 4 (6.7%) would have preferred to have seen a doctor in person for their initial consultation. <h3>Conclusion</h3> We have demonstrated that a TC service is a useful adjunct in helping to deliver an efficient and convenient tertiary PB service, with excellent patient satisfaction. <h3>Disclosure of Interest</h3> None Declared.
SIMULTANEOUS ANALYSIS OF MULTIPLE PROTEIN BIOMARKERS IDENTIFIES INDEPENDENT MARKERS OF LONG-TERM RISK FOR DEATH OR MYOCARDIAL INFARCTION
Authors: Sharif A. Halim, Megan Neely, Karen Pieper, Svati Shah, William Kraus, Elizabeth Hauser, Robert Califf, Christopher Granger, L. Kristin Newby
Journal: Journal of the American College of Cardiology (2012)
Better surveillance is needed to halt spread of artemisinin resistant malaria
Authors: J. Zarocostas
Journal: BMJ (2010)

Countries where malaria is endemic need to improve monitoring of the effectiveness of drugs to prevent a “dramatic” rise in the cost of the treating the disease, warns the World Health Organization.

“Without regular monitoring and reporting of antimalarial drug resistance, the disease burden and the economic costs of malaria will rise dramatically,” says the agency in a report of its global review of drug effectiveness and resistance over the past decade. 

The call comes after the confirmation in February 2009 of the emergence of resistance of Plasmodium falciparum to artemisinin in the Cambodia-Thailand border region.

Pascal Ringwald, from WHO’s drug resistance and containment unit and lead author of …
Limited Access Trial Using Amifostine for Protection Against Cisplatin- and Three-Hour Paclitaxel–Induced Neurotoxicity: A Phase II Study of the Gynecologic Oncology Group
Authors: David H. Moore, James Donnelly, William P. McGuire, Lois Almadrones, David F. Cella, Thomas J. Herzog, Steven E. Waggoner
Journal: Journal of Clinical Oncology (2003)

The purpose of this study was to determine whether amifostine (WR-2721) prevents or ameliorates clinically significant (grade 2 to 4) neurotoxicity associated with cisplatin and 3-hour paclitaxel chemotherapy.The chemotherapy program consisted of intravenous paclitaxel 175 mg/m2 over 3 hours followed by amifostine 740 mg/m2 and cisplatin 75 mg/m2 administered over 90 minutes beginning 15 minutes after amifostine administration. At baseline, before each treatment cycle, and for 3 months after completing chemotherapy, patients were evaluated for evidence of neurotoxicity and other treatment-related adverse effects using three methods: standard clinical evaluation (National Cancer Institute common toxicity criteria [CTC] grading), a neurotoxicity questionnaire to assess symptoms and limitations imposed by peripheral neuropathy, and vibration perception threshold (VPT) testing.Four of 27 assessable patients developed grade 2 to 4 neurotoxicity based on clinical assessments and CTC grading. This number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed.Amifostine's level of activity in this trial was insufficient to warrant further study in a phase III trial. Based on the receiver operating characteristic analysis, it would appear that VPT measurements are less sensitive to the development of peripheral neuropathy than the neurotoxicity questionnaire. The questionnaire, referred to as the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, may be used instead of VPT measurements in future studies of chemotherapy-induced peripheral neuropathy.
The efficacy of activated protein C in murine endotoxemia is dependent on integrin CD11b
Authors: Chunzhang Cao, Yamei Gao, Yang Li, Toni M. Antalis, Francis J. Castellino, Li Zhang
Journal: Journal of Clinical Investigation (2010)

Activated protein C (APC), the only FDA-approved biotherapeutic drug for sepsis, possesses anticoagulant, antiinflammatory, and barrier-protective activities. However, the mechanisms underlying its anti-inflammatory functions are not well defined. Here, we report that the antiinflammatory activity of APC on macrophages is dependent on integrin CD11b/CD18, but not on endothelial protein C receptor (EPCR). We showed that CD11b/CD18 bound APC within specialized membrane microdomains/lipid rafts and facilitated APC cleavage and activation of protease-activated receptor-1 (PAR1), leading to enhanced production of sphingosine-1-phosphate (S1P) and suppression of the proinflammatory response of activated macrophages. Deletion of the gamma-carboxyglutamic acid domain of APC, a region critical for its anticoagulant activity and EPCR-dependent barrier protection, had no effect on its antiinflammatory function. Genetic inactivation of CD11b, PAR1, or sphingosine kinase-1, but not EPCR, abolished the ability of APC to suppress the macrophage inflammatory response in vitro. Using an LPS-induced mouse model of lethal endotoxemia, we showed that APC administration reduced the mortality of wild-type mice, but not CD11b-deficient mice. These data establish what we believe to be a novel mechanism underlying the antiinflammatory activity of APC in the setting of endotoxemia and provide clear evidence that the antiinflammatory function of APC is distinct from its barrier-protective function and anticoagulant activities.
The effects of beta 2-agonists and methylxanthines on neutrophil function in vitro
Authors: CG Llewellyn-Jones, RA Stockley
Journal: European Respiratory Journal (1994)

Therapeutic agents which affect polymorphonuclear neutrophil (PMN) functions have the potential to reduce or increase PMN activation and, hence, influence the progression of lung inflammation. We have assessed the effects of the beta 2-agonist, terbutaline, and the methylxanthine, aminophylline, on PMN functions in vitro at both therapeutic and higher concentrations. At therapeutic levels, both agents increased PMN chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP) in a dose-dependent manner from a control value of 22.5 +/- 3.58 cells.field-1 to 26.1 +/- 4.73 cells.field-1 with 4 mg.l-1 terbutaline, and to 26.3 +/- 4.49 cells.field-1 with 20 mg.l-1 aminophylline. When the cells were preincubated with higher doses of the agents in separate experiments there was inhibition of chemotaxis from a control value of 31.1 +/- 2.06 cells.field-1 to 18.3 +/- 0.82 cells.field-1 at 160 mg.l-1 terbutaline, and to 16.1 +/- 0.77 cells.field-1 at 400 mg.l-1 aminophylline. A similar effect was seen when the PMNs were preincubated with terbutaline and aminophylline prior to assessment of superoxide anion generation, with stimulation of superoxide release at therapeutic levels of the drugs and inhibition at higher doses (19% increase from resting control cells at terbutaline 4 mg.l-1 and 53% reduction at 160 mg.l-1; 28% increase with aminophylline 20 mg.l-1 and 22% reduction at 400 mg.l-1). Both terbutaline and aminophylline had no effect on PMN degranulation, as assessed by the degradation of fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of soybean allergens causing sensitization of occupationally exposed bakers
Authors: X. Baur, M. Pau, A. Czuppon, G. Fruhmann
Journal: Allergy (1996)

Fourteen bakers suffering from workplace-related respiratory symptoms and sensitized to soybean were studied. Twelve of them were also allergic to wheat flour, 10 to rye flour, and five to alpha-amylase of Aspergillus oryzae (Asp o 2). IgE estimation by RAST strongly indicated that the trypsin inhibitor and lipoxidase are major allergens of soybean. Various allergenic components could be characterized by immunoblotting after two-dimensional electrophoresis. Our RAST and immunoblotting results show an interindividually different allergic response to inhalative soybean constituents, and that the trypsin inhibitor (20 kDa, pI approximately 4.5) is an important inhalative soybean allergen recognized by IgE antibodies in the sera of 86% of the examined sensitized bakers.
NHS trusts lambasted for failing to tackle race inequality
Authors: Caroline White
Journal: BMJ (2007)

An initiative from the World Health Organization has been launched to make drugs as simply and safely available to children as they are to adults.Speaking last week at the launch in London, WHO's assistant director general, Howard Zucker, said that "there is a gap between the availability of children's medicines and the actual need.That gap is global and must be addressed."The problem is not new."It's a reality we've lived with for many years," Dr Zucker admitted.Most drugs are developed for and tested in adults.Less than a third come in a form appropriate for children.As a result, many children are treated using drugs that are effectively unlicensed.Medical staff may be obliged to estimate the appropriate fraction of an adult dose, and then crush tablets or extract part of the contents of a capsule.One study by WHO has shown that drug errors are three times as common in children as in adults (JAMA 2001;285:2114-20).Unicef claims that of the 10 million under 5s who will have died by the end of this year, specific products for children could have saved two thirds.Hans Hogerzeil, WHO's director of drugs policy and standards, listed areas in which more effort is needed, in which drugs do exist but were of unknown safety and efficacy.Examples include agents for dealing with tuberculosis; HIV; and several neglected conditions, such as schistosomiasis.Development is essential in areas in which adult drugs need to be adapted to make them suitable and safe for children.Illnesses in this category include malaria, neonatal infections that could be treated by antibiotics, and tuberculosis.Finally, said Dr Hogerzeil, improved access is the priority where drugs exist but are prevented from reaching the children who needed them because of cost."Make medicines child size" is at www.who.int/childmedicines/en. WHO launches� campaign to make drugs� s�afer for childrenUK NEWS GMC approves change in the standard of proof, p 1230 World NEWS �d�� �a�� a��o�� dr�g co�panies to pro�ote off��a�e� �ses, p 122� �d�� �a�� a��o�� dr�g co�panies to pro�ote off��a�e� �ses, p 122� , p 122� ��j.co�Go�iath �oves into hea�thcare records Go�iath �oves into hea�thcare records
TREATMENT OF EXPERIMENTAL ACUTE GENERAL PERITONITIS IN THE DOG WITH ILEOSTOMY AND SODIUM CHLORIDE SOLUTION
Authors: Thomas G. Orr, Russell L. Haden
Journal: The Journal of Experimental Medicine (1929)

1. In experimentally produced general peritonitis drainage of the gut by ileostomy 6 inches above the cecum has no beneficial effect. 2. Animals with experimentally produced general peritonitis treated with ileostomy plus 1 per cent sodium chloride solution live three times as long as those not given the salt solution.
K-RasG12D expression induces hyperproliferation and aberrant signaling in primary hematopoietic stem/progenitor cells
Authors: Margaret E. M. Van Meter, Ernesto Díaz-Flores, Joehleen A. Archard, Emmanuelle Passegué, Jonathan M. Irish, Nikesh Kotecha, Garry P. Nolan, Kevin Shannon, Benjamin S. Braun
Journal: Blood (2006)
A Dipeptidyl Peptidase-4 Inhibitor, Des-Fluoro-Sitagliptin, Improves Endothelial Function and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E–Deficient Mice
Authors: Junichi Matsubara, Seigo Sugiyama, Koichi Sugamura, Taishi Nakamura, Yukio Fujiwara, Eiichi Akiyama, Hirofumi Kurokawa, Toshimitsu Nozaki, Keisuke Ohba, Masaaki Konishi, Hirofumi Maeda, Yasuhiro Izumiya, Koichi Kaikita, Hitoshi Sumida, Hideaki Jinnouchi, Kunihiko Matsui, Shokei Kim-Mitsuyama, Motohiro Takeya, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2012)