tbuckley/cabot-search huggingface dataset:
Second-line chemotherapy in advanced biliary cancer: a systematic review
Authors: A. Lamarca, R.A. Hubner, W. David Ryder, J.W. Valle
Journal: Annals of Oncology (2014)

The randomized NCRN phase III ABC-02 trial provided level-A evidence for first-line chemotherapy with cisplatin and gemcitabine combination in advanced biliary cancer (ABC). This systematic literature review aims to evaluate the level of evidence for the use of second-line chemotherapy for patients with ABC in terms of overall survival (OS), response, toxicity and quality of life. Eligible studies were identified using Medline, ASCO, ESMO and the World Gastrointestinal Congress databases. Searches were last updated on 15 December 2013. Eligible studies reported survival and/or response data for patients with ABC receiving second-line systemic chemotherapy. This systematic review was registered in the PROSPERO database (No. CRD42013004205). Five hundred and fifty-eight studies were identified from the searches in Medline (n = 342), ASCO (n = 160), ESMO (n = 27) and World Gastrointestinal Congress (n = 29). Twenty-five studies were eligible: 14 phase II clinical trials, 9 retrospective analyses and 2 case reports. In total, data from 761 patients were reported with median number of patients included in each study of 22 (range 9–96). The mean OS was 7.2 months [95% confidence interval (CI) 6.2–8.2] [phase II: 6.6 (95% CI 5.1–8.1); retrospective analysis: 7.7 (95% CI 6.5–8.9)]. The mean progression-free survival (PFS), response rate (RR) and disease control rate were 3.2 months (95% CI 2.7–3.7), 7.7% (95% CI 4.6–10.9) and 49.5% (95% CI 41.4–57.7), respectively. The best correlations were between OS and PFS for all studies (r = 0.54; P = 0.01) and between OS and PFS (r = 0.61; P = 0.04) and OS and RR (r = 0.62; P = 0.03) for phase II studies, respectively. Biliary tract cancer is known to be a chemo-responsive disease. There is insufficient evidence (level C) to recommend a second-line chemotherapy schedule in ABC, although the available data suggest that a cohort of patients may benefit. Further prospective and randomized studies are needed to clarify the relative value of second-line chemotherapy in this setting.
Evaluation of the hereditary Syrian hamster cardiomyopathy by 31P nuclear magnetic resonance spectroscopy: improvement after acute verapamil therapy.
Authors: W Markiewicz, S S Wu, W W Parmley, C B Higgins, R Sievers, T L James, J Wikman-Coffelt, G Jasmin
Journal: Circulation Research (1986)

The relation between metabolic and functional derangement in various cardiomyopathies has not been well characterized. This information was specifically sought in a spontaneous cardiomyopathic model. Metabolic and hemodynamic parameters were obtained in glucose-perfused beating hearts of 180-200-day-old cardiomyopathic Syrian hamsters and age-matched healthy animals. This period in the cardiomyopathic hamster lifetime is intermediary between the necrotic phase and the appearance of heart failure. We used 31P nuclear magnetic resonance spectroscopy to analyze energy metabolites and intracellular pH. Cardiomyopathic hamsters had significantly higher mole fraction values for inorganic phosphate, lower phosphocreatine mole fraction as well as lower phosphocreatine/inorganic phosphate and adenosine triphosphate/inorganic phosphate ratios. Analysis of pH indicated the presence of regions of increased acidity within the heart of myopathic hamsters. Cardiomyopathic hamsters also had significantly lower left ventricular pressure, coronary flow, and myocardial oxygen consumption. Separate groups of normal and myopathic hamsters were given verapamil for 24 hours (one injection of 4 mg/kg s.c. followed by 1.2 g/l in drinking water). Verapamil-treated myopathic hamsters had evidence of markedly improved mitochondrial function when compared with untreated animals. Left ventricular pressure and coronary flow rose to normal levels. Replacing glucose by pyruvate in the perfusate of myopathic hamsters results in a marked increase in left ventricular pressure, coronary flow, and oxygen consumption with a moderate rise in phosphocreatine. Thus, 180-200-day-old cardiomyopathic hamster heart is characterized by evidence of decreased mitochondrial function, by areas of increased acidity within the heart, and by reduced left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
microRNA-145 in Barrett's oesophagus: regulating BMP4 signalling via GATA6
Authors: Jantine W P M van Baal, Romy E Verbeek, Pauline Bus, Matteo Fassan, Rhonda F Souza, Massimo Rugge, Fiebo J W ten Kate, Frank P Vleggaar, Peter D Siersema
Journal: Gut (2012)

Iron deficiency anaemia (IDA) is a major cause of morbidity and burden of disease worldwide. It can generally be diagnosed by blood testing and remedied by iron replacement therapy (IRT) using the oral or intravenous route. The many causes of iron deficiency include poor dietary intake and malabsorption of dietary iron, as well as a number of significant gastrointestinal (GI) pathologies. Because blood is iron-rich it can result from chronic blood loss, and this is a common mechanism underlying the development of IDA—for example, as a consequence of menstrual or GI blood loss. Approximately a third of men and postmenopausal women presenting with IDA have an underlying pathological abnormality, most commonly in the GI tract. Therefore optimal management of IDA requires IRT in combination with appropriate investigation to establish the underlying cause. Unexplained IDA in all at-risk individuals is an accepted indication for fast-track secondary care referral in the UK because GI malignancies can present in this way, often in the absence of specific symptoms. Bidirectional GI endoscopy is the standard diagnostic approach to examination of the upper and lower GI tract, though radiological scanning is an alternative in some situations for assessing the large bowel. In recurrent or refractory IDA, wireless capsule endoscopy plays an important role in assessment of the small bowel. IDA may present in primary care or across a range of specialties in secondary care, and because of this and the insidious nature of the condition it has not always been optimally managed despite the considerable burden of disease— with investigation sometimes being inappropriate, incorrectly timed or incomplete, and the role of IRT for symptom relief neglected. It is therefore important that contemporary guidelines for the management of IDA are available to all clinicians. This document is a revision of previous British Society of Gastroenterology guidelines, updated in the light of subsequent evidence and developments.
Virulence factors of Treponema denticola
Authors: Kazuyuki Ishihara
Journal: Periodontology 2000 (2010)

Spirochetes were first observed in the oral cavity in humans by van Leeuwenhoek (34, 101, 102, 182).Spirochetes are gram-negative microorganisms with long spiral-shaped cells which achieve motility by means of periplasmic flagella (Fig. 1).Members of the phylum "Spirochaetes" include the etiologic agents of syphilis, Lyme disease and other borrelial relapsing fevers.The phylum consists of Spirochaetaceae, Serpulinaceae and Leptospiraceae (3, 39).The first group consists of Spirochaeta, Borrelia, Clevelandina, Cristispira, Diplocalyx, Hollandina, Pillotina and Treponema.Among these, only the genus Treponema has been isolated from the oral cavity.Treponemes have been detected from a variety of environments such as the human oral cavity, the digestive tracts of cattle and termite guts (48,53, 133, 177).Treponema share many characteristics with gram-positive bacteria, and recent phylogenetic studies have shown that spirochaetes form a single cluster distinct from both gram-positive and
Respiratory insufficiency and limb muscle weakness in adults with Pompe's disease
Authors: N. Pellegrini, P. Laforet, D. Orlikowski, M. Pellegrini, C. Caillaud, B. Eymard, J-C. Raphael, F. Lofaso
Journal: European Respiratory Journal (2005)

The objective of the present study was to prospectively evaluate relationships linking age, respiratory function and locomotor function in 29 outpatients with late-onset Pompe’s disease and to retrospectively determine clinical outcomes. Using univariate regression analysis, vital capacity (VC) was weakly, but significantly, correlated to shoulder motility, Walton score and lower-limb Modified Medical Research Council score. Six patients were able to walk without a walking aid and with only the help of a handrail on the stairs (Walton score = 3), although VC was &lt;50%. No parameters were significantly correlated with age. As assessed retrospectively, VC and locomotion deteriorated over time in most patients. In contrast, among the 16 patients started on invasive or noninvasive ventilation with VC monitoring, eight had a VC increase at the first measurement time-point. The absence of correlation with age and the presence, in some patients, of severe respiratory insufficiency without severe limb girdle muscle weakness indicate that respiratory function should be monitored independently from the degree of peripheral muscle weakness. Mechanical ventilation and tracheostomy may improve vital capacity and should, therefore, be taken into account when evaluating treatments for the adult form of Pompe’s disease.
EXPERIMENTAL GLOMERULONEPHRITIS INDUCED IN RABBITS WITH THE ENDOTOXIC PRINCIPLE OF STREPTOCOCCUS SCARLATINÆ
Authors: Charles W. Duval, R. J. Hibbard
Journal: The Journal of Experimental Medicine (1926)

1. Broth-grown cultures, cultures from blood agar slants and culture filtrates (Berkefeld N or V) of H. Streptococcus scarlatinae are without appreciable effect upon the rabbit, no matter how large the dose or by what route introduced. 2. The active toxic principle of H. Streptococcus scarlatinae for rabbits is intimately associated with the protein of the bacterial cell, and is not given off in the artificial medium during the growth activity of the organism, indicating, therefore, its endotoxic character. 3. The endotoxin is readily obtained from the viable scarlatinal cultures through the medium of the peritoneal cavity of the rabbit immunized against the homologous strain (Pfeiffer phenomenon). The toxic substance thus obtained we have termed a lysate. 4. The rabbit is highly susceptible to the in vivo prepared lysate of Streptococcus scarlatinae, at least from the cultures we have employed. The degree of the toxic effect upon the rabbit depends upon the size of the dose and the route through which it is introduced. The specific effects range from mild to severe and fatal forms of toxemia as indicated by high fever, leucocytosis, paralysis and acute hemorrhagic glomerular nephritis. 5. The experimentally induced nephritic lesions are analogous in kind and variety to those of acute scarlatinal nephritis in man, including the "epithelial crescent" formation, hyaline thrombi of glomerular capillaries, hemorrhage into capsular space and necrosis of capillary tufts.
STUDIES ON THE FORMATION OF COLLAGEN
Authors: Jerome Gross
Journal: The Journal of Experimental Medicine (1959)

The skin of severely scorbutic guinea pigs which were losing weight contained no detectible neutral salt-extractible collagen. Conditions of growth (weight gain) which actively induced the formation of neutral salt-extractible collagen in the skin of normal guinea pigs failed to do so in the animal with ascorbic acid deficiency. No excess of non-collagenous proline was found in neutral salt extracts of scorbutic skin as compared with normal. Fractionation of these extracts failed to reveal the presence of significant amounts of a soluble component containing unusual proportions of glycine and proline relative to hydroxyproline. It is concluded that deficiency of ascorbic acid either interferes with the synthesis of new collagen in intact skin or causes its destruction and removal as rapidly as it is produced.
Insulin and insulin-like growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms.
Authors: D A Fryburg, L A Jahn, S A Hill, D M Oliveras, E J Barrett
Journal: Journal of Clinical Investigation (1995)

Insulin inhibits proteolysis in human muscle thereby increasing protein anabolism. In contrast, IGF-I promotes muscle protein anabolism principally by stimulating protein synthesis. As increases or decreases of plasma amino acids may affect protein turnover in muscle and also alter the muscle's response to insulin and/or IGF-I, this study was designed to examine the effects of insulin and IGF-I on human muscle protein turnover during hyperaminoacidemia. We measured phenylalanine balance and [3H]-phenylalanine kinetics in both forearms of 22 postabsorptive adults during a continuous [3H] phenylalanine infusion. Measurements were made basally and at 3 and 6 h after beginning a systemic infusion of a balanced amino acid mixture that raised arterial phenylalanine concentration about twofold. Throughout the 6 h, 10 subjects received insulin locally (0.035 mU/min per kg) into one brachial artery while 12 other subjects were given intraaterial IGF-I (100 ng/min per kg) to raise insulin or IGF-I concentrations, respectively, in the infused arm. The contralateral arm in each study served as a simultaneous control for the effects of amino acids (aa) alone. Glucose uptake and lactate release increased in the insulin- and IGF-I-infused forearms (P < 0.01) but did not change in the contralateral (aa alone) forearm in either study. In the aa alone arm in both studies, hyperaminoacidemia reversed the postabsorptive net phenylalanine release by muscle to a net uptake (P < 0.025, for each) due to a stimulation of muscle protein synthesis. In the hormone-infused arms, the addition of either insulin or IGF-I promoted greater positive shifts in phenylalanine balance than the aa alone arm (P < 0.01). With insulin, the enhanced anabolism was due to inhibition of protein degradation (P < 0.02), whereas IGF-I augmented anabolism by a further stimulation of protein synthesis above aa alone (P < 0.02). We conclude that: (a) hyperaminoacidemia specifically stimulates muscle protein synthesis; (b) insulin, even with hyperaminoacidemia, improves muscle protein balance solely by inhibiting proteolysis; and (c) hyperaminoacidemia combined with IGF-I enhances protein synthesis more than either alone.
Admission hypoglycaemia is associated with adverse outcome in community-acquired pneumonia
Authors: A. Singanayagam, J. D. Chalmers, A. T. Hill
Journal: European Respiratory Journal (2009)

The aim of our study was to investigate if hypoglycaemia correlates with outcome in community-acquired pneumonia (CAP). We performed a prospective, observational study of consecutive patients presenting with a primary diagnosis of CAP in Lothian (UK). Admission plasma glucose was measured and, on this basis, patients were divided into two groups, hypoglycaemic (&lt;4.4 mmol·L −1 or &lt;79.0 mg·dL −1 ) and nonhypoglycaemic (≥4.4 mmol·L −1 or ≥79.0 mg·dL −1 ). Outcomes of interest were 30-day mortality, need for mechanical ventilation and inotropic support. Multivariable logistic regression was used to compare these outcomes in hypoglycaemic patients to nonhypoglycaemic patients, adjusting for diabetes mellitus, prior statin use and Pneumonia Severity Index. In total, 1,050 patients were included in the study with 5.4% classified as hypoglycaemic. Increased rates of 30-day mortality (28.1% versus 7.5%, p&lt;0.0001), need for mechanical ventilation (29.8% versus 6.5%, p&lt;0.0001) and need for inotropic support (21.1% versus 4.8%, p&lt;0.0001) were observed in hypoglycaemic patients compared with nonhypoglycaemic patients. On multivariable analysis, hypoglycaemia was independently associated with increased 30-day mortality (OR 2.25, 95% CI 1.1–4.7; p = 0.03), need for mechanical ventilation (OR 3.8, 95% CI 1.9–7.5; p = 0.0002) and need for inotropic support (OR, 2.9, 95% CI 1.4–6.3; p = 0.0006). Admission hypoglycaemia is associated with increased 30-day mortality, need for mechanical ventilation and inotropic support in patients presenting with CAP.
Factors Affecting Use of Insulin Pens by Patients With Type 2 Diabetes
Authors: Richard R. Rubin, Mark Peyrot
Journal: Diabetes Care (2008)

To assess factors that might affect patient use of insulin pens.Patients (n = 600: 300 using vial and syringe and 300 using pen) were recruited from national panels to participate in computer-assisted telephone interviews. Measures included: demographic characteristics; diabetes treatment and self-care factors; perceptions of pen convenience, clinical efficacy, facilitation of self-care, and cost; and degree of physicians' recommending pen use.Physician recommendation of pen use powerfully discriminated pen users from nonusers (odds ratio 135.6). Other factors that discriminated pen users included physicians' presenting pens as an option (14.1) and patient perceptions that pens facilitate diabetes self-care (20.2) and are not costly (4.8).The physician's role in presenting the pen as an option and recommending pen use was a critical factor in patient pen use. Enhanced physician education regarding the potential benefits of pen use and encouraging physicians to discuss pen use with patients could improve diabetes outcomes.
AMN107, a Novel Aminopyrimidine Inhibitor of Bcr-Abl, Has <i>In vitro</i> Activity against Imatinib-Resistant Chronic Myeloid Leukemia
Authors: Mirna Golemovic, Srdan Verstovsek, Francis Giles, Jorge Cortes, Taghi Manshouri, Paul W. Manley, Jürgen Mestan, Margaret Dugan, Leila Alland, James D. Griffin, Ralph B. Arlinghaus, Tong Sun, Hagop Kantarjian, Miloslav Beran
Journal: Clinical Cancer Research (2005)

Abstract Resistance to or intolerance of imatinib in patients with Philadelphia chromosome–positive chronic myelogenous leukemia (CML) has encouraged the development of more potent Bcr-Abl inhibitors. AMN107 is a novel, orally bioavailable ATP-competitive inhibitor of Bcr-Abl. The effects of AMN107 were compared with those of imatinib on imatinib-sensitive (KBM5 and KBM7) and imatinib-resistant CML cell lines (KBM5-STI571R1.0 and KBM7-STI571R1.0). Compared with the antiproliferative activity of imatinib, AMN107 was 43 times more potent in KBM5 (IC50 of 11.3 versus 480.5 nmol/L) and 60 times more potent in KBM7 (IC50 of 4.3 versus 259.0 nmol/L) cells. IC50 for AMN107 and imatinib were 2,418.3 and 6,361.4 nmol/L, respectively, in KBM5-STI571R1.0, and 97.2 and 2,497.3 nmol/L, respectively, in KBM7-STI571R1.0 cells. AMN107 inhibited autophosphorylation of Bcr-Abl kinase more effectively than imatinib in all cell lines. They had similar effects on cell cycle progression and apoptotic response in these cell lines. Among severe combined immunodeficient mice bearing KBM5 cells, mean survival times of groups treated with 10, 20, and 30 mg/kg/d of AMN107, starting day 20 after leukemic cell grafting and continuing for 20 days, were 144%, 159%, and 182%, respectively, compared with controls. These results strongly support investigation of the clinical efficacy of AMN107 in patients with CML.
Expression of Prenylated Rab Acceptor 1 Domain Family, Member 2 (PRAF2) in Neuroblastoma: Correlation with Clinical Features, Cellular Localization, and Cerulenin-Mediated Apoptosis Regulation
Authors: Dirk Geerts, Christopher J. Wallick, Dana-Lynn T. Koomoa, Jan Koster, Rogier Versteeg, Ramon Christopher V. Go, André S. Bachmann
Journal: Clinical Cancer Research (2007)

Prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is a novel 19-kDa protein that has recently been implicated in human cancer. In the present study, we analyzed for the first time PRAF2 mRNA expression in a large set of human tumors. The high expression in neuroblastic tumors prompted us to analyze PRAF2 expression correlations with genetic and clinical features of these tumors. In addition, we determined the localization of PRAF2 protein in neuroblastoma cells and studied its regulation in apoptosis.Affymetrix microarray analysis was done with a set of 41 different tumor types (1,426 samples) in the public domain, a set of three different neuroblastic tumor types (110 samples), and a panel of 25 neuroblastoma cell lines. The subcellular localization of endogenous PRAF2 in neuroblastoma cells was identified by immunofluorescence microscopy and apoptosis detected by Annexin V staining and poly(ADP-ribose) polymerase cleavage.PRAF2 mRNA was detected in 970 of 1,426 samples in the public data set. All 110 neuroblastic tumors expressed PRAF2 at higher levels than any other tumor examined. Importantly, PRAF2 expression levels significantly correlated with the following clinical features: patient age at diagnosis (P = 6.19 x 10(-5)), survival (P = 1.32 x 10(-3)), International Neuroblastoma Staging System stage (P = 2.86 x 10(-4)), and MYCN amplification (P = 3.74 x 10(-3)). PRAF2 localized in bright cytoplasmic punctae and protein levels increased in neuroblastoma cells that underwent cerulenin-induced apoptosis.Elevated PRAF2 expression levels correlated with unfavorable genetic and clinical features, suggesting PRAF2 as a candidate prognostic marker of neuroblastoma.
Intravitreal Ranibizumab May Induce Retinal Arteriolar Vasoconstriction in Patients with Neovascular Age-related Macular Degeneration
Authors: Domniki N. Papadopoulou, Efstratios Mendrinos, Georgios Mangioris, Guy Donati, Constantin J. Pournaras
Journal: Ophthalmology (2009)
CCL2/Monocyte Chemoattractant Protein-1 Regulates Inflammatory Responses Critical to Healing Myocardial Infarcts
Authors: Oliver Dewald, Pawel Zymek, Kim Winkelmann, Anna Koerting, Guofeng Ren, Tareq Abou-Khamis, Lloyd H. Michael, Barrett J. Rollins, Mark L. Entman, Nikolaos G. Frangogiannis
Journal: Circulation Research (2005)

The CC chemokine Monocyte Chemoattractant Protein (MCP)-1/CCL2 has potent mononuclear cell chemo-attractant properties, modulates fibroblast and endothelial cell phenotype and may play an important role in wound healing. In order to examine whether MCP-1 critically regulates myocardial infarct healing, we studied the effects of MCP-1 gene disruption and antibody neutralization in a closed-chest model of reperfused murine myocardial infarction. MCP-1 −/− mice had decreased and delayed macrophage infiltration in the healing infarct and demonstrated delayed replacement of injured cardiomyocytes with granulation tissue. In contrast, the time course and density of neutrophil infiltration was similar in MCP-1 null and wild-type animals. MCP-1 −/− infarcts had decreased mRNA expression of the cytokines TNF-α, IL-1β, TGF-β 2 , -β 3 , and IL-10 and demonstrated defective macrophage differentiation evidenced by decreased Osteopontin-1 expression. MCP-1 deficiency diminished myofibroblast accumulation but did not significantly affect infarct angiogenesis. Despite showing delayed phagocytotic removal of dead cardiomyocytes, MCP-1 −/− mice had attenuated left ventricular remodeling, but similar infarct size when compared with wild-type animals. MCP-1 antibody inhibition resulted in defects comparable with the pathological findings noted in infarcted MCP-1 −/− animals without an effect on macrophage recruitment. MCP-1 has important effects on macrophage recruitment and activation, cytokine synthesis and myofibroblast accumulation in healing infarcts. Absence of MCP-1 results in attenuated post-infarction left ventricular remodeling, at the expense of a prolonged inflammatory phase and delayed replacement of injured cardiomyocytes with granulation tissue.