tbuckley/cabot-search huggingface dataset:
PMO-141 Flagellin-induced IL-6 production is selectively impaired in patients with cirrhosis
Authors: W Alazawi, A Spyrou, R Lahiri, J Waters, G R Foster
Journal: Gut (2012)

<h3>Introduction</h3> The innate immune response is an important determinant of progression in chronic inflammatory liver diseases such as alcoholic (ALD) and non-alcoholic fatty liver disease (NAFLD). Sepsis is a frequent cause of hepatic decompensation and some authors suggest a role for toll-like receptor (TLR) sensing of gut-derived pathogens (motile and gram-negative organisms) in disease progression. Paresis of the innate immune system has been described in patients with decompensated liver disease, but the function of TLRs in compensated disease has received scant attention. Our aim was to assess TLR responsiveness in patients with compensated ALD and NAFLD using a combinatorial experimental design, measuring LPS- and flagellin-induced TNFα and IL-6 production. <h3>Methods</h3> Consenting adult outpatients with compensated ALD or NAFLD were recruited. Diagnoses were confirmed by casenote review. Exclusion criteria included alternative aetiologies, decompensated disease, other systemic immune-related illnesses, and immunosuppression (including steroids). Normal healthy volunteers without liver disease were also recruited. Monocytes isolated from peripheral blood mononuclear cells were stimulated with low dose LPS and flagellin. The production of TNF-α and IL-6 was assayed in supernatants and in patient sera by ELISA. <h3>Results</h3> We included 28 patients and six normal controls. Patients with compensated cirrhosis have a selective defect in flagellin-induced IL-6 production (330±117 pg/ml) compared to patients with non-cirrhotic ALD or NAFLD (896±146 pg/ml; p=0.01) or healthy controls (764±96 pg/ml). There were no differences in flagellin-induced TNFα nor in LPS-induced cytokine production. There were no differences between the three groups in serum concentrations of TNF, IL-6 and RANTES. <h3>Conclusion</h3> Paresis of the innate immune response is not universal; there is selective impairment of TLR5-mediated IL-6 production in patients with compensated cirrhosis compared to non-cirrhotic patients. These data identify potential signalling pathways that may be involved in the progression of liver disease or in the susceptibility of patients with cirrhosis to bacterial infections. <h3>Competing interests</h3> None declared.
Survival after liver transplantation in the United Kingdom and Ireland compared with the United States
Authors: M F Dawwas, A E Gimson, J D Lewsey, L P Copley, J H P van der Meulen
Journal: Gut (2007)

<h3>Background and objective:</h3> Surgical mortality in the US is widely perceived to be superior to that in the UK. However, previous comparisons of surgical outcome in the two countries have often failed to take sufficient account of case-mix or examine long-term outcome. The standardised nature of liver transplantation practice makes it uniquely placed for undertaking reliable international comparisons of surgical outcome. The objective of this study is to undertake a risk-adjusted disease-specific comparison of both short- and long-term survival of liver transplant recipients in the UK and Ireland with that in the US. <h3>Methods:</h3> A multicentre cohort study using two high quality national databases including all adults who underwent a first single organ liver transplant in the UK and Ireland (n = 5925) and the US (n = 41 866) between March 1994 and March 2005. The main outcome measures were post-transplant mortality during the first 90 days, 90 days to 1 year and beyond the first year, adjusted for recipient and donor characteristics. <h3>Results:</h3> Risk-adjusted mortality in the UK and Ireland was generally higher than in the US during the first 90 days (HR 1.17; 95% CI 1.07 to 1.29), both for patients transplanted for acute liver failure (HR 1.27; 95% CI 1.01 to 1.60) and those transplanted for chronic liver disease (HR 1.18; 95% CI 1.07 to 1.31). Between 90 days and 1 year post-transplantation, no statistically significant differences in overall risk-adjusted mortality were noted between the two cohorts. Survivors of the first post-transplant year in the UK and Ireland had lower overall risk-adjusted mortality than those transplanted in the US (HR 0.88; 95% CI 0.81 to 0.96). This difference was observed among patients transplanted for chronic liver disease (HR 0.88; 95% CI 0.81 to 0.96), but not those transplanted for acute liver failure (HR 1.02; 95% CI 0.70 to 1.50). <h3>Conclusions:</h3> Whilst risk-adjusted mortality is higher in the UK and Ireland during the first 90 days following liver transplantation, it is higher in the US among those liver transplant recipients who survived the first post-transplant year. Our results are consistent with the notion that the US has superior acute perioperative care whereas the UK appears to provide better quality chronic care following liver transplantation surgery.
Validity of International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Acute Renal Failure
Authors: Sushrut S. Waikar, Ron Wald, Glenn M. Chertow, Gary C. Curhan, Wolfgang C. Winkelmayer, Orfeas Liangos, Marie-Anne Sosa, Bertrand L. Jaber
Journal: Journal of the American Society of Nephrology (2006)

Administrative and claims databases may be useful for the study of acute renal failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the corresponding diagnosis and procedure codes is unknown. The performance characteristics of <i>International Classification of Diseases, Ninth Revision, Clinical Modification</i> (ICD-9-CM) codes for ARF were assessed against serum creatinine–based definitions of ARF in 97,705 adult discharges from three Boston hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical records in 150 patients with ARF-D and 150 control patients. As compared with a diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of 47.9%, and negative predictive value of 96.1%. As compared with review of medical records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and negative predictive value of 90.0%. It is concluded that administrative databases may be a powerful tool for the study of ARF, although the low sensitivity of ARF codes is an important caveat. The excellent performance characteristics of ICD-9-CM codes for ARF-D suggest that administrative data sets may be particularly well suited for research endeavors that involve patients with ARF-D.
Cx43 and Dual-Pathway Electrophysiology of the Atrioventricular Node and Atrioventricular Nodal Reentry
Authors: Vladimir P. Nikolski, Sandra A. Jones, Matthew K. Lancaster, Mark R. Boyett, Igor R. Efimov
Journal: Circulation Research (2003)

Fluorescent imaging has revealed that posterior nodal extensions provide the anatomical substrate for the dual-pathway electrophysiology of the atrioventricular (AV) node during normal conduction and reentry. The reentry can be intranodal, or as well as the posterior nodal extensions, it can involve an endocardial layer of atrial/atrial-nodal (A/AN) cells as part of the AV nodal reentry (AVNR) circuit. Using fluorescent imaging with a voltage-sensitive dye and immunolabeling of Cx43, we mapped the electrical activity and structural substrate in 3 types of AVNR induced by premature atrial stimulation in 8 rabbit hearts. In 6 cases, the AVNR pathway involved (1) a fast pathway (FP), (2) the A/AN layer, and (3) a slow pathway (SP). In 4 cases, reentry took the path (1) SP, (2) A/AN layer, and (3) FP. In 2 cases, reentry was intranodal, propagating between the 2 posterior nodal extensions. Immunolabeling revealed that the FP and SP are formed by Cx43-expressing bundles surrounded by tissue without Cx43. Cx43-expressing posterior nodal extensions are the substrate of AVNR during both intranodal and extranodal reentry.
Duration of Response to Second-Line, Platinum-Based Chemotherapy for Ovarian Cancer: Implications for Patient Management and Clinical Trial Design
Authors: Maurie Markman, Jonathan Markman, Kenneth Webster, Kristine Zanotti, Barbara Kulp, Gertrude Peterson, Jerome Belinson
Journal: Journal of Clinical Oncology (2004)

Limited information is available regarding the influence of the duration of a prior response on the length of a subsequent response to platinum chemotherapy in recurrent ovarian cancer.We retrospectively reviewed the medical records of women with ovarian cancer treated at the Cleveland Clinic from 1993 through April 2003 who received two or more platinum-based regimens for recurrence of the malignancy. Patients were considered to have responded to second-line therapy if they satisfied specific criteria, including favorable effects on both measurable or assessable disease.A total of 211 platinum-based regimens were administered to 176 women with recurrent ovarian cancer during this time period, with a response being observed in 125 treatment episodes (59%). Only four (3%) of 121 currently assessable secondary responses were of longer duration than the prior response in a specific individual. In three of these four cases, the platinum-based regimen used in the second-line approach included a drug that had not been used in that patient's primary chemotherapy program.The length of a prior response to platinum-based therapy in ovarian cancer is highly predictive of the upper limit of the duration of response to a subsequent platinum program, assuming the same or similar drugs are used. Knowledge of this clinical parameter may assist in developing optimal management for an individual patient and may potentially be exploited in clinical trial designs examining novel maintenance strategies with both cytotoxic and cytostatic agents in women who achieve a secondary response to a platinum-based regimen.
Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis
Authors: J-C Lega, Y Lacasse, L Lakhal, S Provencher
Journal: Thorax (2009)

<h3>Background:</h3> The role of biomarkers such as B-type natriuretic peptides (BNP and NT-proBNP) and troponins in risk stratification of acute pulmonary embolism (APE) is still debated. A meta-analysis was performed to assess the association between raised natriuretic peptide levels, alone or in conjunction with troponins, and all-cause and APE-related mortality, serious adverse events and echographic right ventricular dysfunction. <h3>Methods:</h3> MEDLINE and EMBASE databases were searched and conference abstracts were hand searched up to February 2008. Studies were included if a 2×2 table could be constructed based on natriuretic peptide results and at least one of the outcomes. <h3>Results:</h3> Twenty-three studies were included (1127 patients). Raised natriuretic peptide levels were significantly associated with all-cause mortality (odds ratio (OR) 6.2; 95% confidence interval (CI) 3.0 to 12.7), APE-related mortality (OR 5.0; 95% CI 2.2 to 11.5) and serious adverse events (OR 6.7; 95% CI 3.9 to 11.6), with homogeneity across studies. Among patients with raised natriuretic peptide levels, increased serum troponins were associated with a further increase in the risk of adverse outcomes. Analysis of the accuracy of natriuretic peptides in detecting right ventricular dysfunction was limited by heterogeneity across studies. BNP appeared to have better sensitivity and specificity than NT-proBNP in detecting right ventricular dysfunction. <h3>Conclusions:</h3> Raised levels of B-type natriuretic peptides identified a subset of patients with APE at higher risk of adverse outcomes. Among patients with raised natriuretic peptide levels, increased troponins were found to be an independent prognostic marker. The results of this meta-analysis may have important clinical implications in the management of APE.
Serum Immunoglobulin G Antibodies to Chlamydial Heat Shock Protein 60 but Not to Human and Bacterial Homologs Are Associated With Coronary Artery Disease
Authors: Olaimatu S. Mahdi, Benjamin D. Horne, Kelly Mullen, Joseph B. Muhlestein, Gerald I. Byrne
Journal: Circulation (2002)

Background— Evidence for an association between Chlamydia pneumoniae infection and coronary artery disease (CAD) has been reported by numerous studies, cross-reactive heat shock protein (Hsp) antibody responses have been causally linked to CAD, and the severity of chlamydial disease pathogenesis correlates with Hsp serology. Our aim was to determine if chlamydial Hsp (cHsp) antibody responses are predictive of CAD. Methods and Results— Patients were recruited in a case-control study: 250 cases had angiographically significant CAD (stenosis ≥70%), and 250 controls had normal coronary arteries (stenosis &lt;10%). Serum immunoglobulin G reactivity to Hsp10 and Hsp60 antigens (chlamydial, Escherichia coli , and human), and C pneumoniae whole organisms were measured by ELISA. Univariate analysis confirmed that classical CAD risk factors were predictors of CAD. Univariate analysis showed that cHsp60 ( P = 0.001, OR 3.9), cHsp10 ( P =0.045, OR 3.8), E coli Hsp60 ( P =0.04, OR 1.5) and C pneumoniae ( P =0.03, OR 1.8) ELISA optical density (OD) values were significantly different between cases and controls. Multivariate analysis found that only upper-quintile cHsp60 seroreactivity remained a significant predictor of CAD after controlling for classical CAD risk factors and seroreactivity to the other antigens (cHsp60 OD, P =0.005, OR 3.9 per OD unit; cHsp60 quintile, 5 versus 1 to 4; P =0.01, OR 2.1). Conclusions— The presence of elevated anti-cHsp60 immunoglobulin G antibodies, but not anti-human or anti– E coli homologs, was independently associated with CAD. This finding argues against previous suggestions that cross-reactive or autoimmune Hsp60 responses may contribute to disease progression. High anti-cHsp60 antibody response appears to identify the subset of patients with chlamydial infection and significant CAD.
Progress in the Curative Treatment of Childhood Hematologic Malignancies
Authors: Alan S. Wayne, Gregory H. Reaman, Lee J. Helman
Journal: JNCI Journal of the National Cancer Institute (2008)

JNCI | Editorials 1271 Hematologic malignancies account for approximately 40% of childhood cancer ( 1 ). Progress in the curative treatment of this group of cancers is one of the great medical success stories of the 20th century. There have been improvements in outcome for all major subtypes of pediatric leukemias and lymphomas, the most dramatic of which has been in acute lymphoblastic leukemia (ALL), the commonest childhood malignancy. At the time that the National Cancer Act of 1971 (Public Law 92-218) made the “conquest of cancer a national crusade” (President Richard M. Nixon, December 23, 1971) fewer than 10% of children with ALL survived for 10 years after diagnosis. Survival rates for children diagnosed with ALL have increased steadily over ensuing eras and now exceed 80% ( 2 , 3 ). Improvements in survival for childhood hematologic malignancies have been achieved as the result of serial clinical trials conducted by pediatric oncology cooperative groups and large single clinical research centers. Essential to these therapeutic advances has been the development of effective agents, along with combination chemotherapy and treatment phase – specific and central nervous system – directed regimens. The definition of clinical, pathological, and biologic risk groups has facilitated the critically important evolution of risk-based treatment stratification. This risk-based treatment approach occurred largely in the absence of new therapeutic agents over the past decade and represents the application of individualized cancer therapy before the introduction of molecularly targeted agents. Intensified regimens, including the judicious use of stem cell
Moderate Hypermutability of a Transgenic <b> <i>lacZ</i> </b> Reporter Gene in <b> <i>Myc</i> </b>-Dependent Inflammation-Induced Plasma Cell Tumors in Mice
Authors: Klaus Felix, Axel Polack, Walter Pretsch, Sharon H. Jackson, Lionel Feigenbaum, Georg-Wilhelm Bornkamm, Siegfried Janz
Journal: Cancer Research (2004)

Mutator phenotypes, a common and largely unexplained attribute of human cancer, might be better understood in mouse tumors containing reporter genes for accurate mutation enumeration and analysis. Previous work on peritoneal plasmacytomas (PCTs) in mice suggested that PCTs have a mutator phenotype caused by Myc-deregulating chromosomal translocations and/or phagocyte-induced mutagenesis due to chronic inflammation. To investigate this hypothesis, we generated PCTs that harbored the transgenic shuttle vector, pUR288, with a lacZ reporter gene for the assessment of mutations in vivo. PCTs exhibited a 5.5 times higher mutant frequency in lacZ (40.3 +/- 5.1 x 10(-5)) than in normal B cells (7.36 +/- 0.77 x 10(-5)), demonstrating that the tumors exhibit the phenotype of increased mutability. Studies on lacZ mutant frequency in serially transplanted PCTs and phagocyte-induced lacZ mutations in B cells in vitro indicated that mutant levels in tumors are not determined by exogenous damage inflicted by inflammatory cells. In vitro studies with a newly developed transgenic model of inducible Myc expression (Tet-off/MYC) showed that deregulated Myc sensitizes B cells to chemically induced mutations, but does not cause, on its own, mutations in lacZ. These findings suggested that the hypermutability of PCT is governed mainly by intrinsic features of tumor cells, not by deregulated Myc or chronic inflammation.
Indomethacin stimulates glucose production in adults with uncomplicated falciparum malaria
Authors: Evelien Dekker, Johannes A. Romijn, Huynh Van Thien, Mariette T. Ackermans, Erik Endert, Piet A. Kager, Le Thi Diem Thuy, Hans P. Sauerwein
Journal: Metabolism (1998)
Gestational Diabetes Mellitus
Authors: Suzie Daniells, Brin F. S. Grenyer, Warren S. Davis, Keith J. Coleman, Julie-Anne P. Burgess, Robert G. Moses
Journal: Diabetes Care (2003)

To examine anxiety levels of women diagnosed with gestational diabetes mellitus (GDM) and to compare these with glucose-tolerant (GT) women at similar stages of pregnancy.Prospective longitudinal study conducted on 50 women with GDM and 50 GT women. All women completed the Mental Health Inventory (MHI-5) forms and the Speilberger State-Trait Anxiety Inventory (STAI) at the beginning of the third trimester, antepartum, and 6 weeks postpartum. Specific questions were also assessed using a Likert scale.Women with GDM, compared with GT women, had a higher level of anxiety (state rather than trait) at the time of the first assessment. However, before delivery and in the postpartum period, there were no significant differences in anxiety scores between the two groups. Women in both groups were positive about being tested for GDM and wished to be tested during future pregnancies.There were no sustained increased levels of anxiety for women diagnosed with GDM. Concerns expressed about causing sustained maternal anxiety by testing for GDM could not be substantiated.
AINHUM-OCCURRENCE OF A CASE IN NORTHERN OHIO
Authors: Carl M. McKenna
Journal: JAMA (1960)

Since the first description of  (dactylolysis spontanea) by Clarke1in 1860, many case reports have appeared, primarily from the tropical areas and the southern part of the United States. Until 1945, only about 50 cases had been reported from the United States; at the time of writing somewhat more than 100 have been reported.2  Whether the condition is actually rare in the United States or simply not well recognized by the medical profession is not known. Most authors believe the latter  be true. The first case seen at the Cleveland Veterans Administration Hospital in the 13 years of its existence is reported herein. One case was previously diagnosed at the University Hospitals of Cleveland (1944), while no cases have been seen at the Metropolitan General Hospital (Cleveland City Hospital) in the past 35 years.  The term ainhum is derived from an African word meaning to saw.
Skin tight: macrophage-specific COX-2 induction links salt handling in kidney and skin
Authors: Johannes Stegbauer, Thomas M. Coffman
Journal: Journal of Clinical Investigation (2015)

The relationship between dietary salt intake and the associated risk of hypertension and cardiovascular disease is an important public health concern. In this issue of the JCI, a study by Zhang and associates shows that consumption of a high-sodium diet induces expression of cyclooxygenase-2 (COX-2) in macrophages, resulting in enhanced levels of prostaglandin E2 (PGE2), autocrine activation of the macrophage E-prostanoid 4 (EP4) receptor, and subsequent triggering of parallel pathways in the kidney and in skin that help dispose of excess sodium. The authors found that blockade or genetic elimination of the COX-2/PGE2/EP4 receptor pathway in hematopoietic cells causes salt-sensitive hypertension in mice. These studies illuminate an unexpected central role for the macrophage in coordinating homeostatic responses to dietary salt intake and suggest a complex pathophysiology for hypertension associated with NSAID use.
Rapid diagnosis of primary ciliary dyskinesia: cell culture and soft computing analysis
Authors: Massimo Pifferi, Andrew Bush, Francesca Montemurro, Giovanni Pioggia, Martina Piras, Gennaro Tartarisco, Maria Di Cicco, Iolanda Chinellato, Angela M. Cangiotti, Attilio L. Boner
Journal: European Respiratory Journal (2012)

Diagnosis of primary ciliary dyskinesia (PCD) sometimes requires repeated nasal brushing to exclude secondary ciliary alterations. Our aim was to evaluate whether the use of a new method of nasal epithelial cell culture can speed PCD diagnosis in doubtful cases and to identify which are the most informative parameters by means of a multilayer artificial neural network (ANN). A cross-sectional study was performed in patients with suspected PCD. All patients underwent nasal brushing for ciliary motion analysis, ultrastructural assessment and evaluation of ciliary function after ciliogenesis in culture by ANN. 151 subjects were studied. A diagnostic suspension cell culture was obtained in 117 nasal brushings. A diagnosis of PCD was made in 36 subjects (29 of whom were children). In nine out of the 36 patients the diagnosis was made only after a second brushing, because of equivocal results of both tests at first examination. In each of these subjects diagnosis of PCD was confirmed by cell culture results. Cell culture in suspension evaluated by means of ANN allows the separation of PCD from secondary ciliary dyskinesia patients after only 5 days of culture and allows diagnosis to be reached in doubtful cases, thus avoiding the necessity of a second sample.
Batf3-Dependent Dendritic Cells in the Renal Lymph Node Induce Tolerance against Circulating Antigens
Authors: Catherine Gottschalk, Vera Damuzzo, Janine Gotot, Richard A. Kroczek, Hideo Yagita, Kenneth M. Murphy, Percy A. Knolle, Isis Ludwig-Portugall, Christian Kurts
Journal: Journal of the American Society of Nephrology (2013)

Although the spleen is a major site where immune tolerance to circulating innocuous antigens occurs, the kidney also contributes. Circulating antigens smaller than albumin are constitutively filtered and concentrated in the kidney and reach the renal lymph node by lymphatic drainage, where resident dendritic cells (DCs) capture them and induce tolerance of specific cytotoxic T cells through unknown mechanisms. Here, we found that the coinhibitory cell surface receptor programmed death 1 (PD-1) on cytotoxic T cells mediates to their tolerance. Renal lymph node DCs of the CD8(+) XCR1(+) subset, which depend on the transcription factor Batf3, expressed the PD-1 cognate ligand PD-L1. Batf3-dependent DCs in the renal lymph node presented antigen that had been concentrated in the kidney and used PD-L1 to induce apoptosis of cytotoxic T cells. In contrast, T cell tolerance in the spleen was independent of PD-1, PD-L1, and Batf3. In summary, these results clarify how the kidney/renal lymph node system tolerizes the immune system against circulating innocuous antigens.