tbuckley/cabot-search huggingface dataset:
Interaction of lithium and phenytoin.
Authors: W A MacCallum
Journal: BMJ (1980)

Acetylsalicylic acid and renal functionSalicylate treatment may decrease renal function in normal persons as well as in patients with systemic lupus erythematosus and rheuma- toid arthritis.' 2 Because acetylsalicylic acid is widely used and valuable in connective tissue diseases we have prospectively examined its effect on the glomerular filtration rate in patients with temporal arteritis or polymyalgia rheumatica and in patients with mild osteoarthrosis. Patients, methods, and resultsSix patients with temporal arteritis or polymyalgia rheumatica were examined.Five were taking prednisolone.This group was compared with six persons with osteoarthrosis.In both groups there was no history of renal diseases and pretreatment serum creatinine concentrations were normal.Each patient in both groups was given 3-4 g acetylsalicylic acid daily for two weeks, and the serum salicylate concentration was measured after one and two weeks' treatment.Blood samples were taken in the morning before medicine and food were taken.The serum creatinine concentration was measured before and after one and two weeks' treatment.The mean serum salicylate concentration after one week was 1450 tLmol/l (20 mg/100 ml) (range 700-2300 jimol/I (10-32 mg/100 ml)) and after two weeks' treatment 1300,Lmol/l (18 mg/100 ml) (range 700-1800 Hmol/l (10-25 mg/100 ml)), compared with an anti-inflammatory therapeutic range of 1087-2174,Lmol/l (15-30 mg/100 ml) previously reported.The glomerular filtration rate was measured by means of "5Cr-EDTA clearance3 before and after two weeks' treatment.Plasma volume was measured with 25I-albumin, and the patients were weighed.We found no changes in serum creatinine or "Cr-EDTA clearance during acetylsalicylic acid treatment.There was a slight but insignificant increase in the patients' plasma volume and weight in both groups.'Eastwood GL, Castell DO, Higgs RH.Experimental esophagitis in cats
Early detection of rejection and assessment of cyclosporine therapy by 111In antimyosin imaging in mouse heart allografts.
Authors: M Isobe, E Haber, B A Khaw
Journal: Circulation (1991)

BACKGROUND. Mice (n = 58) with abdominal heterotopic heart transplants were studied to examine the effectiveness of 111In-labeled antimyosin scintigraphy in the detection of rejection and to determine the consequence of cyclosporine therapy on the results. METHODS AND RESULTS. Allografts from B10D2 donors were transplanted into B6AF1 recipients. Of the 49 allografted mice, 19 were treated with cyclosporine (15 mg/kg.day). Nine isografted mice served as controls. Scintigraphy was performed by injecting 100 muCi 111In antimyosin monoclonal antibody 2-15 days after transplantation. An increase in the ratio of percent dose of antimyosin injected per gram (% dose/g) of the grafted heart (G) to that of the autologous heart (A) (G/A) as well as the increasing percent dose per gram of antimyosin in the grafts reflected the severity of histopathological rejection regardless of the presence or absence of cyclosporine. Scintigraphic images demonstrated unequivocally intense accumulation of 111In in rejected allografts as confirmed by histologically demonstrable myocyte necrosis. The G/A ratio in allografted mice with mildly deteriorated mechanical activity (4.2 +/- 1.0, mean +/- SD) was greater than that in mice with normal contractility (1.8 +/- 0.7) (p less than 0.001), and the necrosis correlated with this modest decline in mechanical function could be scintigraphically identified. Of mice with normally contracting allografts, the G/A ratio was greater in animals with demonstrated myocyte necrosis (2.6 +/- 0.5) than in those without necrosis (1.5 +/- 0.5) (p less than 0.001). In contrast, isografted mice or a subset of allografted mice treated with cyclosporine and not showing evidence of rejection did not manifest any significant change in G/A ratio, nor did they have scintigrams positive for rejection as late as 15 days after transplantation. CONCLUSIONS. These findings suggest that antimyosin scintigraphy is a sensitive and early indicator of cardiac transplant rejection and that it could be useful as a noninvasive method for assessing the efficacy of cyclosporine treatment.
Argininosuccinate synthase conditions the response to acute and chronic ethanol-induced liver injury in mice
Authors: Tung Ming Leung, Yongke Lu, Wei Yan, José A. Morón-Concepción, Stephen C. Ward, Xiaodong Ge, Laura Conde de la Rosa, Natalia Nieto
Journal: Hepatology (2011)

Argininosuccinate synthase (ASS) is the rate-limiting enzyme in both the urea and the L-citrulline/nitric oxide (NO·) cycles regulating protein catabolism, ammonia levels, and NO· generation. Because a proteomics analysis identified ASS and nitric oxide synthase-2 (NOS2) as coinduced in rat hepatocytes by chronic ethanol consumption, which also occurred in alcoholic liver disease (ALD) and in cirrhosis patients, we hypothesized that ASS could play a role in ethanol binge and chronic ethanol-induced liver damage. To investigate the contribution of ASS to the pathophysiology of ALD, wildtype (WT) and Ass(+/-) mice (Ass(-/-) are lethal due to hyperammonemia) were exposed to an ethanol binge or to chronic ethanol drinking. Compared with WT, Ass(+/-) mice given an ethanol binge exhibited decreased steatosis, lower NOS2 induction, and less 3-nitrotyrosine (3-NT) protein residues, indicating that reducing nitrosative stress by way of the L-citrulline/NO· pathway plays a significant role in preventing liver damage. However, chronic ethanol-treated Ass(+/-) mice displayed enhanced liver injury compared with WT mice. This was due to hyperammonemia, lower phosphorylated AMP-activated protein kinase alpha (pAMPKα) to total AMPKα ratio, decreased sirtuin-1 (Sirt-1) and peroxisomal proliferator-activated receptor coactivator-1α (Pgc1α) messenger RNAs (mRNAs), lower fatty acid β-oxidation due to down-regulation of carnitine palmitoyl transferase-II (CPT-II), decreased antioxidant defense, and elevated lipid peroxidation end-products in spite of comparable nitrosative stress but likely reduced NOS3.Partial Ass ablation protects only in acute ethanol-induced liver injury by decreasing nitrosative stress but not in a more chronic scenario where oxidative stress and impaired fatty acid β-oxidation are key events.
Gas chromatography/mass spectrometry analysis of exhaled leukotrienes in asthmatic patients
Authors: P Cap
Journal: Thorax (2004)

Leukotriene-like immunoreactivity has been detected in exhaled breath condensate (EBC), but definitive evidence for the presence of leukotrienes (LTs) in this biological fluid is not available. A study was undertaken to determine whether LTC(4), LTD(4), LTE(4), and LTB(4) are measurable in EBC by gas chromatography/mass spectrometry and to quantify exhaled LTs in adults and children with asthma and in control subjects.Twenty eight adults and 33 children with mild to moderate persistent asthma treated with inhaled corticosteroids and age matched healthy controls (50 adults and 50 children) were studied. LTB(4), LTC(4), LTD(4), and LTE(4) in EBC were measured by gas chromatography/mass spectrometry.LTD(4), LTE(4), and LTB(4) were detectable in all samples. Concentrations of LTC(4) in EBC were either close to or below the detection limit of 1 pg/ml. Median exhaled LTD(4), LTE(4), and LTB(4) concentrations in asthmatic adults were increased 4.1-fold (p<0.001), 1.8-fold (p<0.01), and 2.6-fold (p<0.001), respectively, compared with values in healthy adults. Median exhaled LTD(4), LTE(4), and LTB(4) concentrations in asthmatic children were increased 2.8-fold (p<0.001), 1.3-fold (p<0.001), and 1.6-fold (p<0.001), respectively, compared with those in healthy children. In patients with asthma there was a correlation between exhaled LTD(4) and LTE(4) in both adults (r = 0.87, p<0.0001) and children (r = 0.78, p<0.0001).Gas chromatography/mass spectrometry can be used to accurately quantify exhaled LTs which are increased in asthmatic adults and children compared with controls.
What memory is for
Authors: Arthur M. Glenberg
Journal: Behavioral and Brain Sciences (1997)

Let's start from scratch in thinking about what memory is for, and consequently, how it works. Suppose that memory and conceptualization work in the service of perception and action. In this case, conceptualization is the encoding of patterns of possible physical interaction with a three-dimensional world. These patterns are constrained by the structure of the environment, the structure of our bodies, and memory. Thus, how we perceive and conceive of the environment is determined by the types of bodies we have. Such a memory would not have associations. Instead, how concepts become related (and what it means to be related) is determined by how separate patterns of actions can be combined given the constraints of our bodies. I call this combination “mesh.” To avoid hallucination, conceptualization would normally be driven by the environment, and patterns of action from memory would play a supporting, but automatic, role. A significant human skill is learning to suppress the overriding contribution of the environment to conceptualization, thereby allowing memory to guide conceptualization. The effort used in suppressing input from the environment pays off by allowing prediction, recollective memory, and language comprehension. I review theoretical work in cognitive science and empirical work in memory and language comprehension that suggest that it may be possible to investigate connections between topics as disparate as infantile amnesia and mental-model theory.
A perspective on emerging mosquito and phlebotomine-borne diseases in Europe
Authors: G Hendrickx, R Lancelot
Journal: Eurosurveillance (2010)

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Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal adenocarcinoma
Authors: Eric Smith, Neville J De Young, Sandra J Pavey, Nicholas K Hayward, Derek J Nancarrow, David C Whiteman, B Mark Smithers, Andrew R Ruszkiewicz, Andrew D Clouston, David C Gotley, Peter G Devitt, Glyn G Jamieson, Paul A Drew
Journal: Molecular Cancer (2008)

Abstract Background Barrett's esophagus (BE) is the metaplastic replacement of squamous with columnar epithelium in the esophagus, as a result of reflux. It is the major risk factor for the development of esophageal adenocarcinoma (EAC). Methylation of CpG dinucleotides of normally unmethylated genes is associated with silencing of their expression, and is common in EAC. This study was designed to determine at what stage, in the progression from BE to EAC, methylation of key genes occurs. Results We examined nine genes (APC, CDKN2A, ID4, MGMT, RBP1, RUNX3, SFRP1, TIMP3, and TMEFF2), frequently methylated in multiple cancer types, in a panel of squamous (19 biopsies from patients without BE or EAC, 16 from patients with BE, 21 from patients with EAC), BE (40 metaplastic, seven high grade dysplastic) and 37 EAC tissues. The methylation frequency, the percentage of samples that had any extent of methylation, for each of the nine genes in the EAC (95%, 59%, 76%, 57%, 70%, 73%, 95%, 74% and 83% respectively) was significantly higher than in any of the squamous groups. The methylation frequency for each of the nine genes in the metaplastic BE (95%, 28%, 78%, 48%, 58%, 48%, 93%, 88% and 75% respectively) was significantly higher than in the squamous samples except for CDKN2A and RBP1. The methylation frequency did not differ between BE and EAC samples, except for CDKN2A and RUNX3 which were significantly higher in EAC. The methylation extent was an estimate of both the number of methylated alleles and the density of methylation on these alleles. This was significantly greater in EAC than in metaplastic BE for all genes except APC, MGMT and TIMP3. There was no significant difference in methylation extent for any gene between high grade dysplastic BE and EAC. Conclusion We found significant methylation in metaplastic BE, which for seven of the nine genes studied did not differ in frequency from that found in EAC. This is also the first report of gene silencing by methylation of ID4 in BE or EAC. This study suggests that metaplastic BE is a highly abnormal tissue, more similar to cancer tissue than to normal epithelium.
Apolipoprotein B Synthesis Inhibition With Mipomersen in Heterozygous Familial Hypercholesterolemia
Authors: Evan A. Stein, Robert Dufour, Claude Gagne, Daniel Gaudet, Cara East, Joanne M. Donovan, Wai Chin, Diane L. Tribble, Mary McGowan
Journal: Circulation (2012)

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder leading to premature coronary artery disease. Despite statins and additional lipid-lowering therapies, many HeFH patients fail to achieve low-density lipoprotein cholesterol (LDL-C) goals. We evaluated mipomersen, an apolipoprotein B synthesis inhibitor, to further lower LDL-C in HeFH patients with coronary artery disease.This double-blind, placebo-controlled, phase 3 trial randomized patients with HeFH and coronary artery disease on maximally tolerated statin and LDL-C ≥2.6 mmol/L (≥100 mg/dL) to weekly subcutaneous mipomersen 200 mg or placebo (2:1) for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28. Safety assessments included adverse events, laboratory tests, and magnetic resonance imaging assessment of hepatic fat. Of 124 randomized patients (41 placebo, 83 mipomersen), 114 (41 placebo, 73 mipomersen) completed treatment. Mean (95% confidence interval) LDL-C decreased significantly with mipomersen (-28.0% [-34.0% to -22.1%] compared with 5.2% [-0.5% to 10.9%] increase with placebo; P<0.001). Mipomersen significantly reduced apolipoprotein B (-26.3%), total cholesterol (-19.4%), and lipoprotein(a) (-21.1%) compared with placebo (all P<0.001). No significant change occurred in high-density lipoprotein cholesterol. Adverse events included injection site reactions and influenza-like symptoms. Five mipomersen patients (6%) had 2 consecutive alanine aminotransferase values ≥3 times the upper limit of normal at least 7 days apart; none were associated with significant bilirubin increases. Hepatic fat content increased a median of 4.9% with mipomersen versus 0.4% with placebo (P<0.001).Mipomersen is an effective therapy to further reduce apolipoprotein B-containing lipoproteins, including LDL and lipoprotein(a), in HeFH patients with coronary artery disease on statins and other lipid-lowering therapy. The significance of hepatic fat and transaminase increases remains uncertain at this time.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00706849.
Induction of T-helper cell response to hepatitis B core antigen in chronic hepatitis B: A major factor in activation of the host immune response to the hepatitis B virus
Authors: G MARINOS
Journal: Hepatology (1995)

The T helper (Th) cell response to hepatitis B core antigen (HBcAg) was analyzed in 76 chronic hepatitis B virus (HBV) carriers with varying degrees of hepatic inflammation and HBV replication. Fifty-five patients had active viral replication, 28 with minimal histological changes and normal alanine transaminase (ALT) and 27 with active hepatic inflammation and elevated ALT. The remaining 21 chronic hepatitis B surface antigen (HBsAg) carriers had undetectable HBV replication, minimal histological activity, and normal ALT. In addition, 34 chronic HBV carriers were studied prospectively during treatment with α-interferon. The HBcAg-specific Th cell response was evaluated by a proliferative assay using 3H-thymidine uptake and γ-interferon production by peripheral blood mononuclear cells. The proliferative response and γ-interferon production of patients with active hepatic inflammation were significantly higher than in patients with minimal histological changes and in controls. In the longitudinal analysis during α-interferon treatment, 22 of 34 patients sustained an ALT flare accompanied by a parallel, significant Th cell response, which preceded or coincided with the ALT flare. The elevation in the Th cell response and the ALT flare were followed by a significant rise in the serum immunoglobulin (Ig) M anti-HBc index. Ten of twenty-two patients with an enhanced Th cell response and an ALT flare seroconverted after α-interferon treatment. The Th cell activity in the 10 responders rapidly subsided after hepatitis B e antigen (HBeAg) to anti-HBe seroconversion, whereas in the 12 nonresponders it remained elevated. This study demonstrates that patients with chronic hepatitis B (CAHB) have a detectable and a significant Th cell response to HBcAg, which is likely to be involved in augmenting the immune-mediated hepatocellular damage and in the activation of HBV-specific humoral immune reaction. Thus, loss of Th cell nonresponsiveness to HBcAg is an important factor in enhancing the effector immune responses to HBV in chronic hepatitis B. (HEPATOLOGY 1995; 22:1040–1049.).
A comparison of ampicillin and amoxycillin in acute on chronic bronchitis.
Authors: G Anderson, A G Jariwalla, J Saour
Journal: Thorax (1979)

Twenty-five patients with an acute exacerbation of chronic bronchitis completed a double-blind trial of amoxycillin 1.5 g v ampicillin 4 g daily. After treatment for one week there was no difference between the treatments in the rates of achieving mucoid sputum, reduction in sputum volume, improvement in peak expiratory flow rate, or duration of hospital stay. In the doses studied ampicillin and amoxycillin are effective drugs of about equal cost.
Experimental and theoretical evidence for a similar localization of words encoded through different modalities
Authors: Sébastien Dubé, Henri Cohen
Journal: Behavioral and Brain Sciences (1999)

In his target article, Pulverm&amp;uuml;ller addresses the issue of word localization in the brain. It is not clear, however, how cell assemblies are localized in the case of sensory deprivation. Pulverm&amp;uuml;ller's claim is that words learned via other modalities (i.e., sign languages) should be localized differently. It is argued, however, based on experimental and theoretical ground, that they should be found in a similar place.
Cardiovascular Outcomes and Mortality in Patients Using Clopidogrel With Proton Pump Inhibitors After Percutaneous Coronary Intervention or Acute Coronary Syndrome
Authors: Jeremy A. Rassen, Niteesh K. Choudhry, Jerry Avorn, Sebastian Schneeweiss
Journal: Circulation (2009)

Recent studies have raised concerns about the reduced efficacy of clopidogrel when used concurrently with proton pump inhibitors (PPIs), but those studies may have overestimated the risk.We studied the potential for increased risk of adverse cardiovascular events among users of clopidogrel with versus without concurrent use of PPIs in 3 large cohorts of patients > or =65 years of age, treated between 2001 and 2005. All patients had undergone percutaneous coronary intervention or had been hospitalized for acute coronary syndrome in Pennsylvania, New Jersey, or British Columbia, and subsequently had initiated treatment with clopidogrel. We recorded myocardial infarction hospitalization, death, and revascularization among PPI users and nonusers. We assessed our primary end point of myocardial infarction hospitalization or death using cohort-specific and pooled regression analyses. We entered 18 565 clopidogrel users into our analysis. On a pooled basis, 2.6% of those who also initiated a PPI versus 2.1% of PPI nonusers had a myocardial infarction hospitalization; 1.5% versus 0.9% died; and 3.4% versus 3.1% underwent revascularization. The propensity score-adjusted rate ratio for the primary end point of myocardial infarction or death was 1.22 (95% confidence interval, 0.99 to 1.51); for death, 1.20 (95% confidence interval, 0.84 to 1.70); and for revascularization, 0.97 (95% confidence interval, 0.79 to 1.21). Matched analyses generally yielded similar results.Although point estimates indicated a slightly increased risk of myocardial infarction hospitalization or death in older patients initiating both clopidogrel and a PPI, we did not observe conclusive evidence of a clopidogrel-PPI interaction of major clinical relevance. Our data suggest that if this effect exists, it is unlikely to exceed a 20% risk increase.
Targeted Delivery of RNAi Therapeutics With Endogenous and Exogenous Ligand-Based Mechanisms
Authors: Akin Akinc, William Querbes, Soma De, June Qin, Maria Frank-Kamenetsky, K. Narayanannair Jayaprakash, Muthusamy Jayaraman, Kallanthottathil G Rajeev, William L Cantley, J Robert Dorkin, James S Butler, LiuLiang Qin, Timothy Racie, Andrew Sprague, Eugenio Fava, Anja Zeigerer, Michael J Hope, Marino Zerial, Dinah WY Sah, Kevin Fitzgerald, Mark A Tracy, Muthiah Manoharan, Victor Koteliansky, Antonin de Fougerolles, Martin A Maier
Journal: Molecular Therapy (2010)

Lipid nanoparticles (LNPs) have proven to be highly efficient carriers of short-interfering RNAs (siRNAs) to hepatocytes in vivo; however, the precise mechanism by which this efficient delivery occurs has yet to be elucidated. We found that apolipoprotein E (apoE), which plays a major role in the clearance and hepatocellular uptake of physiological lipoproteins, also acts as an endogenous targeting ligand for ionizable LNPs (iLNPs), but not cationic LNPs (cLNPs). The role of apoE was investigated using both in vitro studies employing recombinant apoE and in vivo studies in wild-type and apoE(-/-) mice. Receptor dependence was explored in vitro and in vivo using low-density lipoprotein receptor (LDLR(-/-))-deficient mice. As an alternative to endogenous apoE-based targeting, we developed a targeting approach using an exogenous ligand containing a multivalent N-acetylgalactosamine (GalNAc)-cluster, which binds with high affinity to the asialoglycoprotein receptor (ASGPR) expressed on hepatocytes. Both apoE-based endogenous and GalNAc-based exogenous targeting appear to be highly effective strategies for the delivery of iLNPs to liver.
Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study
Authors: Leonard B. Saltz, Stephen Clarke, Eduardo Díaz-Rubio, Werner Scheithauer, Arie Figer, Ralph Wong, Sheryl Koski, Mikhail Lichinitser, Tsai-Shen Yang, Fernando Rivera, Felix Couture, Florin Sirzén, Jim Cassidy
Journal: Journal of Clinical Oncology (2008)

To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).