tbuckley/cabot-search huggingface dataset:
Comparison of upper gastrointestinal bleeding in UK and in Treviso area (Italy): similarities and differences: Table 1
Authors: Silvano Loperfido, Luca Fabris, Luisa Maifreni, Francesco Di Mario
Journal: Gut (2012)

We have read with great interest the papers of Hearnshaw and colleagues1 ,2 reporting a prospective nationwide survey on acute upper gastrointestinal bleeding carried out in the UK in 2007. We would like to draw the attention to similarities and dissimilarities of this unique study compared with the results of a prospective population-based single-centre study we carried out in 2002–4 in the Treviso area (north-east Italy).3 Both surveys have taken a similar approach including data records on epidemiological and clinical features, variceal and non-variceal bleeding, emergency admissions and inhospital patients.

In table 1 common recorded findings of this English study have …
CD56-positive cutaneous lymphoma: a poorly recognized entity in the spectrum of primary cutaneous disease
Authors: P. SAVOIA, M.T. FIERRO, M. NOVELLI, P. QUAGLINO, A. VERRONE, M. GEUNA, M.G. BERNENGO
Journal: British Journal of Dermatology (1997)

CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas; the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis; azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR beta-chain gene.
Screening for Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) among Endometrial Cancer Patients
Authors: Heather Hampel, Wendy Frankel, Jenny Panescu, Janet Lockman, Kaisa Sotamaa, Daniel Fix, Ilene Comeras, Jennifer La Jeunesse, Hidewaki Nakagawa, Judith A. Westman, Thomas W. Prior, Mark Clendenning, Pamela Penzone, Janet Lombardi, Patti Dunn, David E. Cohn, Larry Copeland, Lynne Eaton, Jeffrey Fowler, George Lewandowski, Luis Vaccarello, Jeffrey Bell, Gary Reid, Albert de la Chapelle
Journal: Cancer Research (2006)

Abstract Endometrial cancer is the most common cancer in women with Lynch syndrome. The identification of individuals with Lynch syndrome is desirable because they can benefit from increased cancer surveillance. The purpose of this study was to determine the feasibility and desirability of molecular screening for Lynch syndrome in all endometrial cancer patients. Unselected endometrial cancer patients (N = 543) were studied. All tumors underwent microsatellite instability (MSI) testing. Patients with MSI-positive tumors underwent testing for germ line mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21.7%) were MSI positive (98 of 118 MSI high and 20 of 118 MSI low). All 118 patients with MSI-positive tumors had mutation testing, and nine of them had deleterious germ line mutations (one MLH1, three MSH2, and five MSH6). In addition, one case with an MSI-negative tumor had abnormal MSH6 immunohistochemical staining and was subsequently found to have a mutation in MSH6. Immunohistochemical staining was consistent with the mutation result in all seven truncating mutation–positive cases but was not consistent in two of the three missense mutation cases. We conclude that in central Ohio, at least 1.8% (95% confidence interval, 0.9-3.5%) of newly diagnosed endometrial cancer patients had Lynch syndrome. Seven of the 10 Lynch syndrome patients did not meet any published criteria for hereditary nonpolyposis colorectal cancer, and six of them were diagnosed at age &amp;gt;50. Studying all endometrial cancer patients for Lynch syndrome using a combination of MSI and immunohistochemistry for molecular prescreening followed by gene sequencing and deletion analysis is feasible and may be desirable. (Cancer Res 2006; 66(15): 7810-7)
Biological basis of hypoalbuminemia in ESRD.
Authors: G A Kaysen
Journal: Journal of the American Society of Nephrology (1998)

Hypoalbuminemia is associated with mortality in patients with end-stage renal disease (ESRD) maintained either on peritoneal dialysis (PD) or hemodialysis (HD). Serum albumin concentration is determined by its rate of synthesis, by the catabolic rate constant (the fraction of the vascular pool catabolized per unit time), by external losses, and by redistribution from the vascular to the extravascular space. Hypoalbuminemia in dialysis patients is primarily a consequence of reduced albumin synthesis rate in both HD and PD patients, and in the case of PD patents, of transperitoneal albumin losses as well. Continuous ambulatory peritoneal dialysis patients are able to increase albumin synthesis to replace losses. Thus, ESRD does not directly suppress albumin synthesis. The rate of albumin synthesis is inversely proportional to the serum concentration of one potential acute phase protein (alpha2 macroglobulin), and albumin concentration is inversely proportional to that of either C-reactive protein or serum amyloid A in both HD and PD patients. The cause of decreased albumin synthesis is primarily a response to inflammation (the acute phase response), although it is possible that inadequate nutrition may also contribute. The cause of the inflammatory response is not immediately evident. There is no evidence that shifts of albumin to the extravascular space or that dilution of the plasma by volume expansion plays any role in causing hypoalbuminemia in ESRD patients.
Central versus peripheral substrates of persistent pain: Which contributes more?
Authors: Marshall Devor
Journal: Behavioral and Brain Sciences (1997)

Evidence that central sensitization needs to be maintained in an ongoing manner by nociceptive input from the periphery makes the peripheral drive, rather than the central amplification process, the highest priority target for understanding and control. To stop the peripheral drives to kill two birds with one stone. Moreover, the amplification that central sensitization does provide is selective and not necessarily striking in intensity. A “magic bullet” that neutralized central sensitization would probably be less effective in controlling persistent pain than many investigators would like to believe. [berkley; blumberg et al.; coderre &amp; katz; dickenson; mcmahon; weisenfeld-hallin et al.]
Count your blessings
Authors: L. Farrell
Journal: BMJ (2003)

“Ah, the children of the night …”

“Yeah yeah, what beautiful music they make yaddyaddyadda,” I said, sitting well away, not from concern for my personal safety (a general practitioner should never show fear), but when your diet is fresh blood your breath stinks. “I'm a busy man, Count, skip the theatrics.”

“I am in a most grave predicament,” he said, in a rich deep voice, which would be ideal for flogging complementary medicines. “This warfarin—so many of my clients are …
Cd40 Ligand (Cd154) Triggers a Short-Term Cd4+ T Cell Activation Response That Results in Secretion of Immunomodulatory Cytokines and Apoptosis
Authors: Patrick J. Blair, James L. Riley, David M. Harlan, Ryo Abe, Douglas K. Tadaki, Steven C. Hoffmann, Leonard White, Tara Francomano, Stephen J. Perfetto, Allan D. Kirk, Carl H. June
Journal: The Journal of Experimental Medicine (2000)

Signals generated through CD28–B7 and CD40 ligand (CD40L)–CD40 interactions have been shown to be crucial for the induction of long-term allograft survivability. We have recently demonstrated that humanized anti-CD40L (hu5C8) prevents rejection of mismatched renal allografts in primates. To investigate potential mechanisms of CD40L–induced allograft acceptance, we coimmobilized hu5C8 with suboptimal amounts of anti-CD3 to stimulate CD4+ T cells. We now report that anti-CD3/CD40L costimulation results in CD28-independent activation and subsequent deletion of resting T cells. Coligation of CD3 and CD40L increased expression of CD69, CD25, and CD54 on CD4+ T cells. We also found that costimulation with anti-CD3/CD40L resulted in enhanced production of interleukin (IL)-10, interferon γ, and tumor necrosis factor α but not IL-2 or IL-6. Interestingly, after several days, anti-CD3/CD40L–mediated activation was followed by apoptosis in a significant population of cells. Consistent with that observation, anti-CD3/CD40L did not enhance the antiapoptotic proteins Bcl-2 and Bcl-xL. Further, the addition of CD28 at 24 h failed to rescue those cells induced to die after costimulation with anti-CD3/CD40L. Together, these data suggest that the graft-sparing effect of hu5C8 in vivo may result in part from early and direct effects on CD4+ T cells, including a vigorous induction of immunomodulatory cytokines and/or apoptosis of allograft-specific T cells.
Combined application of class I antiarrhythmic drugs causes "additive", "reductive", or "synergistic" sodium channel block in cardiac muscles
Authors: T. Kawamura, I. Kodama, J. Toyama, H. Hayashi, H. Saito, K. Yamada
Journal: Cardiovascular Research (1990)

The aim was to study the differences in cardiac sodium channel block among combinations of class I antiarrhythmic drugs.Conventional glass microelectrode techniques were used to record transmembrane action potentials and their maximum upstroke velocity (dV/dtmax) reflecting the sodium channel availability, during treatment of the preparations with mexiletine (20, 40 microM) in combination with aprindine (5 microM), disopyramide (40 microM), and flecainide (5 microM).Guinea pig papillary muscles (n = 6.8 per experiment) were used for the study.In preparations constantly stimulated at 1 Hz, a shortening of action potential duration by aprindine was further enhanced, while prolongation by disopyramide or flecainide was reduced, after additional application of mexiletine. Trains of stimuli (0.5-2.0 Hz) were applied following a long quiescent period to evaluate "tonic" and "use dependent" decrease (block) of dV/dtmax. Additional application of mexiletine to the other three drugs resulted in an enhancement of tonic block. Use dependent block by aprindine at 0.5-1.0 Hz was reduced by 8-9% after admixture of mexiletine, reflected in net increase in dV/dtmax at steady states (reductive effect). Dual exponential components of dV/dtmax recovery from use dependent block in presence of both drugs suggest their competitive interaction on a common receptor site associated with sodium channels. Use dependent block by flecainide at 0.5-2.0 Hz was increased (p less than 0.01) after admixture of mexiletine. Steady state dV/dtmax was therefore largely inhibited by the drug combination (synergistic effect). Use dependent block in the presence of both disopyramide and mexiletine was similar to that predicted from the algebraic sum of each treatment.Combined application of class I antiarrhythmic drugs causes not only additive but also reductive or synergistic effects on dV/dtmax through modulation of use dependent block.
Adeno-Associated Virus-Mediated Transduction of VEGF165 Improves Cardiac Tissue Viability and Functional Recovery After Permanent Coronary Occlusion in Conscious Dogs
Authors: Matteo Ferrarini, Nikola Arsic, Fabio A. Recchia, Lorena Zentilin, Serena Zacchigna, Xiaobin Xu, Axel Linke, Mauro Giacca, Thomas H. Hintze
Journal: Circulation Research (2006)

We have previously shown that VEGF165 gene delivery into ischemic skeletal muscle exerts not only proangiogenic, but also remarkable antiapoptotic and proregenerative activity. The aim of this study was to determine whether recombinant adeno-associated virus (rAAV)-mediated gene delivery of VEGF165 into cardiac muscle, during acute myocardial infarction, exerts a protective effect to promote long-term functional recovery. Acute infarction of the anterior LV wall was induced in 12 chronically instrumented dogs by permanent occlusion of the LAD coronary artery. Four hours after occlusion, rAAV-VEGF165 or rAAV-LacZ (n=6 each; 5x10(12) viral particles per animal) was directly injected with an echo-guided needle into the dysfunctional cardiac wall. LV and arterial pressure, dP/dtmax, and ejection fraction were not significantly different between the two groups over time. In contrast, in the infarcted region, at four weeks after infarction, fractional shortening was 75+/-18% and -3+/-15% of baseline and length-pressure area was 54+/-15% and 0.8+/-15% of baseline in VEGF165 versus LacZ, respectively (P<0.05). Histological analysis of the border regions showed a marked increase in the number of alpha-SMA-positive arterioles (68+/-2.8 versus 100+/-3.8 vessels per microscopic field in LacZ and VEGF165 group, respectively; P<0.05). In both groups, the receptor VEGFR-2 was diffusely expressed on the surviving cardiomyocytes and, consistently, myocardial viability was significantly improved in the VEGF165-treated group, with several troponin T-expressing cardiomyocytes displaying nuclear positivity for the proliferation marker PCNA. Altogether, our results indicate that VEGF165 gene delivery exerts a marked beneficial action by enhancing both arteriologenesis and cardiomyocyte viability in infarcted myocardium.
Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial
Authors: Christopher Ritchlin, Proton Rahman, Arthur Kavanaugh, Iain B McInnes, Lluis Puig, Shu Li, Yuhua Wang, Yaung-Kaung Shen, Mittie K Doyle, Alan M Mendelsohn, Alice B Gottlieb
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. <h3>Methods</h3> In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/&gt;100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with &lt;5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. <h3>Results</h3> More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p&lt;0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p&lt;0.001), ACR50 (p≤0.05) and PASI75 (p&lt;0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. <h3>Conclusions</h3> The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.
Where Do Rodents Fit? Evidence from the Complete Mitochondrial Genome of Sciurus vulgaris
Authors: Aurelio Reyes, Carmela Gissi, Graziano Pesole, François M. Catzeflis, Cecilia Saccone
Journal: Molecular Biology and Evolution (2000)

*Centro Studio Mitocondri e Metabolismo Energetico, Consiglio Nazionale delle Ricerche, Bari, Italy; †Dipartimento di Biochimica e Biologia Molecolare, Universita di Bari, Bari, Italy; ‡Dipartimento di Fisiologia e Biochimica Generali, Universita di Milano, Milano, Italy; §Laboratoire de Paleontologie, Paleobiologie et Phylogenie, Institut des Sciences de l’Evolution, Centre National de la Recherche Scientifique, Universite Montpellier II, Montpellier, France
Substance P immunoreactive nerves in airways from asthmatics and nonasthmatics
Authors: SL Ollerenshaw, D Jarvis, CE Sullivan, AJ Woolcock
Journal: European Respiratory Journal (1991)

Substance P has been localized to nerves supplying smooth muscle, blood vessels and glands in the human lung and may play a major role in the pathophysiology of asthma. We performed a morphological study, using the avidin biotin peroxidase immunostaining technique, to examine sections of airway wall from subjects with and without asthma for the presence of substance P immunoreactive nerve fibres. Airways of 200 microns-12 mm were obtained from autopsy, lobectomy and bronchoscopy. Quantitative morphological analysis was performed on 3 mm diameter airways from three asthmatic and three nonasthmatic subjects collected at autopsy, and on biopsies of 10 mm diameter airways from eight asthmatic and thirteen nonasthematic subjects. There was an increase in both the number and the length of substance P immunoreactive nerve fibres, in airways from subjects with asthma when compared with airways from subjects without asthma. Fibres were found in the lamina propria and surrounding vessels and glands. The fibres were commonly seen as bundles rather than as single fibres. There was no difference in the number of substance P nerves between normal subjects and subjects with chronic airflow limitation (CAL). The difference in the number, length and morphological characteristics of the substance P immunoreactive nerves between asthmatic and nonasthmatic subjects were striking.
CHROMATOGRAPHIC RESOLUTION OF THE FIRST COMPONENT OF HUMAN COMPLEMENT INTO THREE ACTIVITIES
Authors: I. H. Lepow, G. B. Naff, E. W. Todd, J. Pensky, C. F. Hinz
Journal: The Journal of Experimental Medicine (1963)

A euglobulin fraction of human C'1 has been chromatographically resolved into three distinct activities, designated C'1q, C'1r, and C'1s, in the order of their elution from DEAE cellulose. All three of these activities have been shown to participate in various hemolytic reactions requiring C'1, including the cold phase of the Donath-Landsteiner reaction, and to be necessary for generation of C'1 esterase. C'1q was identical with a previously described serum protein implicated in a very early step of complement action and designated the 11S component on the basis of its sedimentation constant. C'1r could not be related to a known complement activity and has been presented as a new component. C'1s, on the basis of chromatographic evidence, was identified with C'1 proesterase. Methods of assay of these components of C'1 have been presented. The significance of C'1q, C'1r, and C'1s in generation of C'1 esterase and the central role of this enzyme in reactions involving C'1, C'4, and C'2 have been discussed.
Prognostic Impact of Isocitrate Dehydrogenase Enzyme Isoforms 1 and 2 Mutations in Acute Myeloid Leukemia: A Study by the Acute Leukemia French Association Group
Authors: Nicolas Boissel, Olivier Nibourel, Aline Renneville, Claude Gardin, Oumedaly Reman, Nathalie Contentin, Dominique Bordessoule, Cécile Pautas, Thierry de Revel, Bruno Quesnel, Pascal Huchette, Nathalie Philippe, Sandrine Geffroy, Christine Terre, Xavier Thomas, Sylvie Castaigne, Hervé Dombret, Claude Preudhomme
Journal: Journal of Clinical Oncology (2010)

Recently, whole-genome sequencing in acute myeloid leukemia (AML) identified recurrent isocitrate dehydrogenase enzyme isoform (IDH1) mutations (IDH1m), previously reported to be involved in gliomas as well as IDH2 mutations (IDH2m). The prognosis of both IDH1m and IDH2m in AML remains unclear.The prevalence and the prognostic impact of R132 IDH1 and R172 IDH2 mutations were evaluated in a cohort of 520 adults with AML homogeneously treated in the French Acute Leukemia French Association (ALFA) -9801 and -9802 trials.The prevalence of IDH1m and IDH2m was 9.6% and 3.0%, respectively, mostly associated with normal cytogenetics (CN). In patients with CN-AML, IDH1m were associated with NPM1m (P = .008), but exclusive of CEBPAm (P = .03). In contrary, no other mutations were detected in IDH2m patients. In CN-AML patients, IDH1m were found in 19% of favorable genotype ([NPM1m or CEBPAm] without fms-related tyrosine kinase 3 [FLT3] internal tandem duplication [ITD]) and were associated with a higher risk of relapse (RR) and a shorter overall survival (OS). Favorable genotype in CN-AML could thus be defined by the association of NPM1m or CEBPAm with neither FLT3-ITD nor IDH1m. In IDH2m CN-AML patients, we observed a higher risk of induction failure, a higher RR and a shorter OS. In multivariate analysis, age, WBC count, the four-gene favorable genotype and IDH2m were independently associated with a higher RR and a shorter OS.Contrarily to what is reported in gliomas, IDH1m and IDH2m in AML are associated with a poor prognosis. Screening of IDH1m could help to identify high-risk patients within the subset of CN-AML with a favorable genotype.
Call for an international survey on therapeutic lavage for pulmonary alveolar proteinosis
Authors: M. Luisetti
Journal: European Respiratory Journal (2012)

To the Editors:

Pulmonary alveolar proteinosis (PAP) is a syndrome characterised by accumulation of proteinaceous, periodic acid-Schiff positive material within airspaces due to disruption of surfactant homeostasis [1]. In 95% of cases, PAP is associated with increased serum levels of auto-antibodies neutralising granulocyte-macrophage colony-stimulating factor and, therefore, this form is referred to as “auto-immune PAP” [2].

Irrespective of the underlying cause, the current standard of care for PAP is represented by whole lung lavage (WLL) and, to a lesser extent, bronchoscopic lobar/segmental lavage [3]. WLL has played such a critical role in …