tbuckley/cabot-search huggingface dataset:
Association of Incident Gout and Mortality in Dialysis Patients
Authors: Scott D. Cohen, Paul L. Kimmel, Robert Neff, Lawrence Agodoa, Kevin C. Abbott
Journal: Journal of the American Society of Nephrology (2008)

Previous studies have shown that gout is associated with an increased risk for cardiovascular mortality in the general population, but this has not been well studied in patients with ESRD. In this study, the incidence of gout and its association with mortality was evaluated in 259,209 patients in the United States Renal Data System. Overall, the incidence of gout in the first year of dialysis was 5% and in the first 5 yr was 15.4%. Independent risk factors for gout in adjusted analyses included black race, older age, female gender, hypertension, ischemic heart disease, congestive heart failure, and alcohol use. Factors associated with a lower risk for gout included a history of diabetes, smoking, and peripheral vascular disease. Time-dependent Cox regression analysis suggested that an episode of gout was independently associated with a 1.5-fold increase in mortality risk (adjusted hazard ratio 1.49; 95% confidence interval 1.43 to 1.55). The mechanisms underlying this association require further study.
Comparison of Levofloxacin versus Moxifloxacin for Multidrug-Resistant Tuberculosis
Authors: Won-Jung Koh, Seung Heon Lee, Young Ae Kang, Chang-Hoon Lee, Jae Chol Choi, Jae Ho Lee, Seung Hun Jang, Kwang Ha Yoo, Ki Hwan Jung, Ki Uk Kim, Sang Bong Choi, Yon Ju Ryu, Kyung Chan Kim, Soojung Um, Yong Soo Kwon, Yee Hyung Kim, Won-Il Choi, Kyeongman Jeon, Yong Il Hwang, Se Joong Kim, Young Seok Lee, Eun Young Heo, Juhee Lee, Yeo Woon Ki, Tae Sun Shim, Jae-Joon Yim
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Levofloxacin (LFX) and moxifloxacin (MXF) are the two most frequently recommended fluoroquinolones for treatment of patients with multidrug-resistant tuberculosis (MDR-TB). However, studies comparing the effectiveness of LFX and MXF among patients with MDR-TB are lacking.Objectives: To compare the effectiveness of LFX and MXF in terms of culture conversion after 3 months of treatment for MDR-TB.Methods: In this prospective multicenter randomized open label trial, we randomly assigned 182 patients with MDR-TB (sensitive to LFX and MXF) to receive either LFX (750 mg/day; 90 patients) or MXF (400 mg/day; 92 patients) with a background drug regimen. The primary outcome was the proportion of patients who achieved sputum culture conversion at 3 months of treatment. Secondary outcomes were time to culture conversion and time to smear conversion, with data censored at 3 months, and the proportions of adverse drug reactions.Measurements and Main Results: At 3 months of treatment, 68 (88.3%) of the 77 patients in the LFX group and 67 (90.5%) of the 74 in the MXF group showed conversion to negative sputum cultures (odds ratio for LFX compared with MXF, 0.78; 95% confidence interval, 0.27–2.20). Adverse drug reactions were reported in six patients (7.7%) in the LFX group and four (5.2%) in the MXF group (P = 0.75).Conclusions: The choice of LFX or MXF for treatment of patients with MDR-TB may not affect sputum culture conversion at 3 months of treatment.Clinical trial registered with www.clinicaltrials.gov (NCT 01055145).
Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation
Authors: José Barros, Joana Damásio, Assunção Tuna, Ivânia Alves, Isabel Silveira, José Pereira-Monteiro, Jorge Sequeiros, Isabel Alonso, Alda Sousa, Paula Coutinho
Journal: JAMA Neurology (2012)

To document and discuss the broad phenotypic variability in a Portuguese family with cerebellar ataxia, hemiplegic migraine, and related syndromes caused by missense mutation c.1748 (p.R583Q) in the CACNA1A gene.Observational 12-year follow-up study.Community and hospital care.Sixteen patients in a 4-generation family were identified in 1998 in a population-based survey. The follow-up revealed 28 patients (25 of whom were observed) and 32 unaffected relatives with an a priori risk of 50%.Four major phenotypes (migraine with multiple auras, transient focal neurological deficits without headache, coma triggered by minor head trauma, and slowly progressive cerebellar ataxia) were present in various combinations. The initial manifestation was ataxia in 16 patients and a transient episode in 12 patients. Eighteen patients did not have migraine, and 11 showed only ataxia. The c.1748 (p.R583Q) mutation in CACNA1A was confirmed in all 23 of the patients who were tested but was not found in any of the 27 adult relatives. The CACNA1A CAG repeat expansion was excluded.A unique missense mutation in the CACNA1A gene, which exhibits a very high penetrance and expressivity, may present a phenotypic spectrum that is broader than current descriptions. Single-gene disorders can behave as complex traits, which reinforces the importance of genetic modifiers in the tightly regulated function of P/Q-type calcium channels. The clinical spectrum of missense mutation CACNA1A -related disorders is much broader than strictly familial hemiplegic migraine.
Physiological measurements of luminal stirring in the dog and human small bowel.
Authors: M D Levitt, J K Furne, A Strocchi, B W Anderson, D G Levitt
Journal: Journal of Clinical Investigation (1990)

The resistance to absorption resulting from poor stirring of luminal contents (RLum) is considered to be equivalent to an unstirred layer of greater than 600 microns in the human small intestine. We measured RLum in the jejunum of conscious dogs by assessing the absorption rate of two rapidly absorbed probes, glucose, and [14C]warfarin. When RLum was expressed as an unstirred layer, the maximal thickness of the unstirred layer (assuming negligible epithelial cell resistance) was only approximately 35 and 50 microns for perfusion rates of 26 and 5 ml/min, respectively. Maximal unstirred layer thickness for the human jejunum, calculated from previous studies of glucose absorption, yielded a mean value of only 40 microns (range: 23 to 65 microns). Since epithelial resistance appears to be negligible during absorption of low concentrations of glucose, the maximal unstirred layer of 40 microns should be close to the true value for glucose in the human small intestine. We conclude that the unstirred layer for rapidly absorbed compounds in dogs and man are less than one-tenth of previously reported values, but this layer still may remain the rate limiting step in absorption of rapidly transported compounds.
A Myosin Missense Mutation, Not A Null Allele, Causes Familial Hypertrophic Cardiomyopathy
Authors: Hirofumi Nishi, Akinori Kimura, Haruhito Harada, Yoshinori Koga, Kyo Adachi, Kohmei Matsuyama, Takeshi Koyanagi, Seikoh Yasunaga, Tsutomu Imaizumi, Hironori Toshima, Takehiko Sasazuki
Journal: Circulation (1995)

Hypertrophic cardiomyopathy (HCM) is characterized by myocardial hypertrophy of unknown etiology. Missense mutations of the cardiac beta-myosin-heavy-chain (beta-MHC) gene that may be responsible for cardiac hypertrophy have been detected in patients with HCM. On the other hand, gross structural abnormalities in the cardiac beta-MHC gene, ie, an alpha/beta hybrid gene and partial deletion of the gene, have also been reported. The direct correlation between gross abnormalities and development of HCM is not well understood.We analyzed the structure of the cardiac beta-MHC gene from patients with HCM by using polymerase chain reaction-DNA conformation polymorphism analysis and found two sequence variations in exons 3 and 22 in one patient. These sequence variations at codon 54 (exon 3; nonsense mutation) and codon 870 (exon 22; Arg-to-His mutation) were identified by direct sequencing and dot-blot hybridization with allele-specific oligonucleotide probes. Relatives of this patient were examined for the mutations. It was revealed that the missense mutation was inherited from the affected father and the nonsense mutation from the unaffected grandmother through the unaffected mother. In addition, the missense mutation was also found in seven other patients from two other unrelated multiplex HCM families.The Arg870His mutation was suggested to cause HCM. In contrast, the gene with the nonsense mutation would encode for a cardiac beta-MHC protein of only 53 amino acid residues, which may be too short to be incorporated into the thick filament assembly of cardiac myosin chains and showed no dominant phenotype of heart disease. This is the first report of a nonsense mutation in the human cardiac beta-MHC gene.
B lymphocyte alloantigens in the study of the genetic basis of rheumatoid arthritis.
Authors: G S Panayi, P H Wooley
Journal: Annals of the Rheumatic Diseases (1977)

In order to carry out tissue typing studies in patients with rheumatoid arthritis (RA), 116 sera from pregnant multiparous women were screened for cytotoxicity specific for B lymphocytes. It was possible to identify three sera (M55, M58, M87) which reacted specifically with B cells after absorption with platelets. Each appeared to have a different specificity which was presumed to correspond to an alloantigen marker on the lymphocyte surface. The frequency of these alloantigen markers on B lymphocytes was investigated in patients with classical or definite RA and in controls. One of these, M58, occurred in 32 out of 43 RA patients (74 - 4%) compared with 10 out of 37 controls (27%). This difference was highly significant (P less than 0 - 0005). The relative risk of developing RA is 7 - 85 times greater in those possessing alloantigen M58. The other two B cell alloantigens failed to show any association with RA. The association with M58 may indicate a significant genetic contribution to disease susceptibility in RA.
Multiple False-positive Serologic Tests for HIV, HTLV-1, and Hepatitis C Following Influenza Vaccination, 1991
Authors: William R. Mac Kenzie
Journal: JAMA (1992)

<h3>Objective.</h3> —(1) To assess factors associated with the occurrence of multiple false-positive viral enzyme-linked immunosorbent assays (ELISAs) for human immunodeficiency virus (HIV), human T-cell lymphotrophic virus type 1 (HTLV-1), and hepatitis C virus (HCV) among individual blood donors and (2) to determine the frequency and time course of this phenomenon. <h3>Design.</h3> —Case-control study. <h3>Setting.</h3> —A regional blood center. <h3>Participants.</h3> —Blood donors found to have multiple false-positive viral ELISAs (case donors) and randomly selected seronegative controls (control donors) who donated between October 31, 1991, and December 15, 1991. An additional random sample of 262 donation records was reviewed to calculate the proportion of donors who received influenza vaccine. <h3>Main Outcome Measures.</h3> —Multiple false-positive viral ELISAs, receipt of influenza vaccination formulated for the 1991-1992 influenza season, and follow-up ELISA results on serum samples obtained from case donors. <h3>Results.</h3> —Among 17 941 donors, 10 case donors were identified. Nine of the 10 case donors received influenza vaccine, compared with three of 30 control donors (odds ratio [OR]=81; 95% confidence interval [CI], 6 to 3670;<i>P</i>&lt;.001 ). Among nine case donors, the mean time between vaccination and blood donation was 26 days (range, 9 to 68 days). Follow-up ELISAs of serum samples from seven case donors obtained 52 to 130 days (mean, 75 days) after vaccination demonstrated reversion to HIV and HTLV-1 seronegativity in all but one specimen, with persistence of positive HCV ELISAs in four specimens. We estimate between 0.6% and 1.7% of blood donors who received influenza vaccine this season had multiple false-positive viral ELISAs. <h3>Conclusions.</h3> —The occurrence of multiple false-positive viral ELISAs among blood donors was associated with influenza vaccination, but was infrequent among vaccinees. This phenomenon is of short duration for HIV and HTLV-1, but may persist longer for HCV. We recommend influenza vaccinees not be deferred from blood donation. Blood donors with multiple false-positive viral ELISAs should be considered for future reentry as blood donors. (<i>JAMA</i>. 1992;268:1015-1017)
Psychiatric morbidity and the menopause; screening of general population sample.
Authors: C B Ballinger
Journal: BMJ (1975)

A survey of 539 women from the general population indicated a high prevalence of minor psychiatric illness in women aged 40-55 years. There was evidence of an increase in psychiatric morbidity occurring before the menopause and lasting until about one year after menstrual periods had ended. Vasomotor symptoms increased dramatically when periods stopped and persisted up to five years after the menopause. Both these features seemed to have a clear relation to the menopause but not the same relation. The findings suggested that further investigation of the relation between perimenopausal hormonal changes and psychiatric morbidity should be directed towards premenopausal women. Environmental factors, particularly in relation to children, seemed to be associated with increased psychiatric morbidity at this time of life.
The relative order of mKATP channels, free radicals and p38 MAPK in preconditioning's protective pathway in rat heart
Authors: Y Yue
Journal: Cardiovascular Research (2002)

Objectives: Ischemic preconditioning (PC) reduces myocardial infarction by a mechanism that involves opening of mitochondrial ATP-dependent potassium channels (mKATP), reactive oxygen species (ROS), and possibly activation of p38 mitogen-activated protein kinase (p38 MAPK). The actual order of these steps, however, is a matter of current debate. This study examined whether protection afforded by menadione, which protects by causing mitochondria to produce ROS, requires mKATP opening. In addition, we tested whether protection from anisomycin, a p38 MAPK activator, is dependent on ROS production. Methods and Results: Isolated, buffer-perfused rat hearts were pretreated with menadione, and infarction was assessed after 30 min of regional ischemia and 120 min of reperfusion. Menadione reduced infarction in a dose-dependent manner with an EC50 of 270 nM. Menadione's infarct-limiting effect was insensitive to 200 μM 5-hydroxydecanoate (5HD), an mKATP channel blocker, whereas protection by diazoxide and PC were blocked by 5HD. Anisomycin caused hearts to resist infarction and this protective effect was abrogated by SB203580, a p38 MAPK inhibitor, and 2-mercaptopropionylglycine (MPG), a free radical scavenger. Conclusions: These results indicate that mKATP opening occurs upstream of mitochondrial ROS generation in the protective pathway. Furthermore, protection afforded by anisomycin was p38 MAPK- and ROS-dependent.
Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo
Authors: Shannon L. Macauley, Molly Stanley, Emily E. Caesar, Steven A. Yamada, Marcus E. Raichle, Ronaldo Perez, Thomas E. Mahan, Courtney L. Sutphen, David M. Holtzman
Journal: Journal of Clinical Investigation (2015)

Epidemiological studies show that patients with type 2 diabetes (T2DM) and individuals with a diabetes-independent elevation in blood glucose have an increased risk for developing dementia, specifically dementia due to Alzheimer's disease (AD). These observations suggest that abnormal glucose metabolism likely plays a role in some aspects of AD pathogenesis, leading us to investigate the link between aberrant glucose metabolism, T2DM, and AD in murine models. Here, we combined two techniques – glucose clamps and in vivo microdialysis – as a means to dynamically modulate blood glucose levels in awake, freely moving mice while measuring real-time changes in amyloid-β (Aβ), glucose, and lactate within the hippocampal interstitial fluid (ISF). In a murine model of AD, induction of acute hyperglycemia in young animals increased ISF Aβ production and ISF lactate, which serves as a marker of neuronal activity. These effects were exacerbated in aged AD mice with marked Aβ plaque pathology. Inward rectifying, ATP-sensitive potassium (K(ATP)) channels mediated the response to elevated glucose levels, as pharmacological manipulation of K(ATP) channels in the hippocampus altered both ISF Aβ levels and neuronal activity. Taken together, these results suggest that K(ATP) channel activation mediates the response of hippocampal neurons to hyperglycemia by coupling metabolism with neuronal activity and ISF Aβ levels.
One year outcome of undifferentiated polyarthritis
Authors: L M A Jansen
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objective:</b> To identify variables that can predict a progressive outcome after one year of follow up in patients presenting with undifferentiated polyarthritis (UPA) at an early arthritis clinic. <b>Methods:</b> New patients with arthritis in two or more joints of less than three years9 duration were categorised at entry as UPA or as rheumatoid arthritis (RA) based on the clinical diagnosis of the rheumatologist. Outcome variables after one year were radiographic damage (Sharp/van der Heijde score) and functional status (Health Assessment Questionnaire: HAQ score). A progressive disease at one year was defined as radiographic progression ≥4, or one year radiographic damage ≥10, or HAQ score ≥1. The baseline variables of patients with UPA with a progressive or mild outcome were compared. <b>Results:</b> 280 patients (70% women; median age 56 years (range 18–90), median duration of symptoms 3.5 months) were included. 203 (72%) patients were clinically diagnosed as having RA and 77 (27%) as having UPA. The group of patients with progressive UPA (n=32 (42%)) had a significantly higher mean age, prevalence of arthritis of the hands, and disease activity (DAS28) at the first visit compared with the patients of the mild UPA group (n=45 (58%)). The RA group had significantly more frequent serum IgM-RF positivity, higher mean disease activity (DAS28) and mean C reactive protein concentration, more frequent symmetric arthritis, and arthritis in more than three joint groups than the progressive UPA group. Six (19%) of the progressive UPA group versus eight (4%) of the RA group did not receive disease modifying antirheumatic drugs during the first year. <b>Conclusions:</b> After one year of follow up, 32 (42%) of the patients with UPA had a progressive disease. A progressive outcome was associated with older age, higher disease activity, and arthritis of the hands at baseline. To avoid undertreatment of patients with UPA, treatment should be based on severity rather than on diagnosis.
A novel whole-blood miRNA signature for a rapid diagnosis of pulmonary tuberculosis
Authors: Irene Latorre, Petra Leidinger, Christina Backes, Jose Domínguez, Maria Luiza de Souza-Galvão, Jose Maldonado, Cristina Prat, Juan Ruiz-Manzano, Francisca Sánchez, Irma Casas, Andreas Keller, Hagen von Briesen, Hernando Knobel, Eckart Meese, Andreas Meyerhans
Journal: European Respiratory Journal (2015)

One essential aspect for controlling the spread of tuberculosis (TB) is to diagnose it in an early stage. However, the commonly used test systems are still insufficient. Moreover, current assays perform poorly in discriminating between active TB and latent tuberculosis infection (LTBI). Due to limited knowledge of promising TB biomarkers, global "omics" approaches bear attractive options to follow [1]. MiRNAs are important post-transcriptional regulators shown to be involved in the modulation of immune responses against intracellular pathogens [2]. These findings open the possibility of using miRNAs as TB biomarkers for diagnosis. In the present study, we have investigated their role as blood biomarkers for detecting active TB. A novel, whole-blood miRNA signature enables to rapidly diagnose TB with 91.21% sensitivity and 87.95% specificity <http://ow.ly/FVvHt> Andreas Meyerhans and Irene Latorre were supported by Ministerio de Economía y Competitividad (SAF2010–21336) and ERS/SEPAR-fellowship (LTRF 82-2012), respectively. Jose Domínguez is a researcher from the Miguel Servet programme. Irene Latorre, Jose Domínguez, Maria Luiza de Souza-Galvão, Juan Ruiz-Manzano, Jose Maldonado, Cristina Prat and Andreas Meyerhans are TB-NET members.
Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study
Authors: Benjamin F Voight, Gina M Peloso, Marju Orho-Melander, Ruth Frikke-Schmidt, Maja Barbalic, Majken K Jensen, George Hindy, Hilma Hólm, Eric L Ding, Toby Johnson, Heribert Schunkert, Nilesh J Samani, Robert Clarke, Jemma C Hopewell, John F Thompson, Mingyao Li, Gudmar Thorleifsson, Christopher Newton-Cheh, Kiran Musunuru, James P Pirruccello, Danish Saleheen, Li Chen, Alexandre FR Stewart, Arne Schillert, Unnur Thorsteinsdottir, Gudmundur Thorgeirsson, Sonia Anand, James C Engert, Thomas Morgan, John Spertus, Monika Stoll, Klaus Berger, Nicola Martinelli, Domenico Girelli, Pascal P McKeown, Christopher C Patterson, Stephen E Epstein, Joseph Devaney, Mary-Susan Burnett, Vincent Mooser, Samuli Ripatti, Ida Surakka, Markku S Nieminen, Juha Sinisalo, Marja-Liisa Lokki, Markus Perola, Aki Havulinna, Ulf de Faire, Bruna Gigante, Erik Ingelsson, Tanja Zeller, Philipp Wild, Paul I W de Bakker, Olaf H Klungel, Anke-Hilse Maitland-van der Zee, Bas J M Peters, Anthonius de Boer, Diederick E Grobbee, Pieter W Kamphuisen, Vera H M Deneer, Clara C Elbers, N Charlotte Onland-Moret, Marten H Hofker, Cisca Wijmenga, WM Monique Verschuren, Jolanda MA Boer, Yvonne T van der Schouw, Asif Rasheed, Philippe Frossard, Serkalem Demissie, Cristen Willer, Ron Do, Jose M Ordovas, Gonçalo R Abecasis, Michael Boehnke, Karen L Mohlke, Mark J Daly, Candace Guiducci, Noël P Burtt, Aarti Surti, Elena Gonzalez, Shaun Purcell, Stacey Gabriel, Jaume Marrugat, John Peden, Jeanette Erdmann, Patrick Diemert, Christina Willenborg, Inke R König, Marcus Fischer, Christian Hengstenberg, Andreas Ziegler, Ian Buysschaert, Diether Lambrechts, Frans Van de Werf, Keith A Fox, Nour Eddine El Mokhtari, Diana Rubin, Jürgen Schrezenmeir, Stefan Schreiber, Arne Schäfer, John Danesh, Stefan Blankenberg, Robert Roberts, Ruth McPherson, Hugh Watkins, Alistair S Hall, Kim Overvad, Eric Rimm, Eric Boerwinkle, Anne Tybjaerg-Hansen, L Adrienne Cupples, Muredach P Reilly, Olle Melander, Pier M Mannucci, Diego Ardissino, David Siscovick, Roberto Elosua, Kari Stefansson, Christopher J O'Donnell, Veikko Salomaa, Daniel J Rader, Leena Peltonen, Stephen M Schwartz, David Altshuler, Sekar Kathiresan
Journal: The Lancet (2012)
Selective Attenuation of Isoproterenol-Stimulated Arrhythmic Activity by a Partial Agonist of Adenosine A <sub>1</sub> Receptor
Authors: Yejia Song, Lin Wu, John C. Shryock, Luiz Belardinelli
Journal: Circulation (2002)

Background — The goal of this study was to examine the hypothesis that a partial agonist of the adenosine A 1 receptor (A 1 AdoR) may cause a greater attenuation of catecholamine-induced ventricular arrhythmic activity than of contractility. Methods and Results — The effects of CVT-2759 and adenosine, a partial and a full agonist of the A 1 AdoR, on isoproterenol-stimulated arrhythmic activity and contractility of guinea pig isolated ventricular myocytes were determined. CVT-2759 (10 μmol/L) and adenosine (10 μmol/L) significantly inhibited isoproterenol-induced arrhythmic activity (aftercontraction and transient inward current) but did not reduce the amplitudes of twitch shortening and L-type Ca 2+ current. Increasing the concentration of the full agonist adenosine from 10 to 100 μmol/L, however, caused significant attenuation of twitch shortening as well as aftercontractions, whereas increasing the concentration of the partial agonist CVT-2759 from 10 to 100 μmol/L did not. CVT-2759 also significantly inhibited isoproterenol-induced spontaneous ventricular beats in isolated hearts. In contrast to adenosine, CVT-2759 neither activated adenosine-sensitive K + current nor shortened the duration of the atrial APD. Conclusions — The present results support the hypothesis and suggest a potential role for a partial agonist of the A 1 AdoR in the treatment of cardiac arrhythmias.