tbuckley/cabot-search huggingface dataset:
Impaired growth and elevated Fas receptor expression in PIGA+ stem cells in primary paroxysmal nocturnal hemoglobinuria
Authors: Rui Chen, Shanmugam Nagarajan, Gregory M. Prince, Uma Maheshwari, Leon W.M.M. Terstappen, David R. Kaplan, Stanton L. Gerson, Jeffrey M. Albert, Daniel E. Dunn, Hillard M. Lazarus, M. Edward Medof
Journal: Journal of Clinical Investigation (2000)

The genetic defect underlying paroxysmal nocturnal hemoglobinuria (PNH) has been shown to reside in PIGA, a gene that encodes an element required for the first step in glycophosphatidylinositol anchor assembly. Why PIGA-mutated cells are able to expand in PNH marrow, however, is as yet unclear. To address this question, we compared the growth of affected CD59–CD34+ and unaffected CD59+CD34+ cells from patients with that of normal CD59+CD34+ cells in liquid culture. One hundred FACS-sorted cells were added per well into microtiter plates, and after 11 days at 37°C the progeny were counted and were analyzed for their differentiation pattern. We found that CD59–CD34+ cells from PNH patients proliferated to levels approaching those of normal cells, but that CD59+CD34+ cells from the patients gave rise to 20- to 140-fold fewer cells. Prior to sorting, the patients’ CD59– and CD59+CD34+ cells were equivalent with respect to early differentiation markers, and following culture, the CD45 differentiation patterns were identical to those of control CD34+ cells. Further analyses of the unsorted CD59+CD34+ population, however, showed elevated levels of Fas receptor. Addition of agonist anti-Fas mAb to cultures reduced the CD59+CD34+ cell yield by up to 78% but had a minimal effect on the CD59–CD34+ cells, whereas antagonist anti-Fas mAb enhanced the yield by up to 250%. These results suggest that expansion of PIGA-mutated cells in PNH marrow is due to a growth defect in nonmutated cells, and that greater susceptibility to apoptosis is one factor involved in the growth impairment.
Ductal dilatation and stenting for residual hepatolithiasis: a promising treatment strategy
Authors: S-M Sheen-Chen, Y-F Cheng, F-C Chen, F-F Chou, T-Y Lee
Journal: Gut (1998)

Background and aims —Hepatolithiasis is prevalent in south-east Asia and presents a difficult management problem. Intrahepatic strictures with or without awkward ductal angulation of the biliary tree are the main reasons for the reported high incidence of postoperative residual stones. Without proper treatment, biliary strictures and residual stones can lead to repeated episodes of cholangitis, liver abscess, secondary biliary cirrhosis, portal hypertension, and death from sepsis or hepatic failure. The purposes of our treatment strategy were to achieve complete clearance of the stones and relief of bile stasis. Methods —From January 1991 to July 1992, 90 patients with residual postoperative hepatolithiasis and intrahepatic strictures were treated. Postoperative ductal dilatation with percutaneous transhepatic cholangioscopy tube stenting through a mature T tube tract was performed. Choledochoscopic electrohydraulic lithotripsy was applied when impacted or large stones were encountered. Results —Complete clearance of stones was achieved in 78 patients (87%). Mild haemobilia occurred in five patients (5.5%) and fever developed in seven patients (7.7%), and these patients recovered after conservative treatment. The rate of stone recurrence after a mean follow up of 43 months was 8%. Intrahepatic cholangiocarcinoma developed in one patient (1.1%). Conclusion —Postoperative ductal dilatation and stenting, combined with endoscopic electrohydraulic lithotripsy when indicated, is an effective and safe treatment with a low recurrence rate for complicated residual hepatolithiasis with biliary stricture.
Cardiorespiratory Arrest in Diabetic Autonomic Neuropathy
Authors: Luis Garcia-Buñuel
Journal: JAMA (1979)

<h3>To the Editor.—</h3> InThe Journal'seditorial (240:1755, 1978) on cardiorespiratory arrest in diabetic autonomic neuropathy, Samuel Vaisrub, MD, reviews recent reports that postulate a primarily respiratory, rather than cardiac, mechanism to account for these episodes. This conclusion was based on the fact that most of the arrests occurred in association with factors that interfere with normal respiration. A majority of the patients whose cases were reported, however, were pulseless as well as apneic. This and the suddenness of the failure bespeak against a purely respiratory mechanism. An alternative explanation has been subsequently proposed, based on an additional case that displayed marked vagal hyperexcitability in response to tracheal suction.<sup>1</sup>In diabetic autonomic neuropathy, the loss of restraining influences from the sympathetic system may cause an exaggerated vagal reaction to impulses arising from the tracheobronchial tree (ie, suction, severe cough) and result in an idioventricular cardiac rhythm. On cessation of
Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau
Authors: May-Lill Garly, Carlitos Balé, Cesário Lourenco Martins, Hilton C Whittle, Jens Nielsen, Ida M Lisse, Peter Aaby
Journal: BMJ (2006)

<b>Objective</b> To investigate whether prophylactic antibiotics can prevent complications of measles. <b>Design</b> Community based, randomised, double blind, placebo controlled trial. <b>Setting</b> Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa. <b>Participants</b> 84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war). <b>Interventions</b> Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days. <b>Main outcome measures</b> Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media. <b>Results</b> The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups. <b>Conclusions</b> The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries. <b>Trial registration</b> Clinical trials NCT001168532.
Patients Diagnosed With Diabetes Are at Increased Risk for Asthma, Chronic Obstructive Pulmonary Disease, Pulmonary Fibrosis, and Pneumonia but Not Lung Cancer
Authors: Samantha F. Ehrlich, Charles P. Quesenberry, Stephen K. Van Den Eeden, Jun Shan, Assiamira Ferrara
Journal: Diabetes Care (2009)

OBJECTIVE There are limited data on the risk of pulmonary disease in patients with diabetes. The aim of this study was to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia, and lung cancer in patients with and without a diagnosis of diabetes. RESEARCH DESIGN AND METHODS We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in northern California. Age and sex data were available for all cohort members (n = 1,811,228). Data on confounders were available for a subcohort that responded to surveys (n = 121,886), among whom Cox proportional hazards regression models were fit. RESULTS Age- and sex-adjusted incidence rates and 95% CIs were calculated for members with and without diabetes in the full cohort and the subcohort. No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes. These differences remained significant in regression models adjusted for age, sex, race/ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits (asthma hazard ratio [HR] 1.08 [95% CI 1.03–1.12], COPD HR 1.22 [1.15–1.28], pulmonary fibrosis HR 1.54 [1.31–1.81], and pneumonia HR 1.92 [1.84–1.99]). The risk of pneumonia and COPD increased significantly with increasing A1C. CONCLUSIONS Individuals with diabetes are at increased risk of several pulmonary conditions (asthma, COPD, fibrosis, and pneumonia) but not lung cancer. This increased risk may be a consequence of declining lung function in patients with diabetes.
Comparison of Transendocardial and Intracoronary CD34 <sup>+</sup> Cell Transplantation in Patients With Nonischemic Dilated Cardiomyopathy
Authors: Bojan Vrtovec, Gregor Poglajen, Luka Lezaic, Matjaz Sever, Aljaz Socan, Dragoslav Domanovic, Peter Cernelc, Guillermo Torre-Amione, François Haddad, Joseph C. Wu
Journal: Circulation (2013)

Background— In an open-label blinded study, we compared intracoronary and transendocardial CD34 + cell transplantation in patients with nonischemic dilated cardiomyopathy. Methods and Results— Of the 40 patients with dilated cardiomyopathy, 20 were randomized to receive intracoronary injection and 20 received transendocardial CD34 + cell delivery. In both groups, CD34 + cells were mobilized by filgrastim, collected via apheresis, and labeled with technetium-99m radioisotope for single-photon emission computed tomographic imaging. In the intracoronary group, cells were injected intracoronarily in the artery supplying segments of greater perfusion defect on myocardial perfusion scintigraphy. In the transendocardial group, electroanatomic mapping was used to identify viable but dysfunctional myocardium, and transendocardial cell injections were performed. Nuclear single-photon emission computed tomographic imaging for quantification of myocardial retention was performed 18 hours thereafter. At baseline, groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal pro-brain natriuretic peptide levels. The number of CD34 + cells was also comparable (105±31×10 6 in the transendocardial group versus 103±27×10 6 in the intracoronary group, P =0.62). At 18 hours after procedure, myocardial retention was higher in the transendocardial group (19.2±4.8%) than in the intracoronary group (4.4±1.2%, P &lt;0.01). At 6 months, left ventricular ejection fraction improved more in the transendocardial group (+8.1±4.3%) than in the intracoronary group (+4.2±2.3%, P =0.03). The same pattern was observed for the 6-minute walk test distance (+125±33 m in the transendocardial group versus +86±13 m in the intracoronary group, P =0.03) and N-terminal pro-brain natriuretic peptide (−628±211 versus −315±133 pg/mL, P =0.04). Conclusions— In patients with dilated cardiomyopathy, transendocardial CD34 + cell transplantation is associated with higher myocardial retention rates and greater improvement in ventricular function, N-terminal pro-brain natriuretic peptide, and exercise capacity compared with intracoronary route. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01350310.
Validation of five different questionnaires for identifying sleep apnea syndrome in a sleep clinic
Authors: Athanasia Pataka, Evdokia Sourla, Asimina Paspala, Eleni Vaitsi, Nikolaos Chavouzis, Afroditi Boutou, Sofia Akritidou, Katalin Fekete Passa, Paraskevi Argyropoulou
Journal: European Respiratory Journal (2014)

Background: Different clinical models and questionnaires have been used for the identification of patients with the highest probability for Obstructive Sleep Apnea/hypopnea Syndrome (OSAHS). Objectives: To evaluate the clinical utility of five different questionnaires: Stop, Stop Bang (S-B), Berlin (BQ), Epworth Sleepiness Scale (ESS) and 4 Variable Screening Tool (4-V) in a Sleep Clinic and to assess the best possible combination of these tools. Methods: A retrospective study of 1853 (74.4% males) patients (mean age 52 ±14 years, BMI 32.8±7 kg/m 2 ) visiting a sleep clinic who answered the 5 questionnaires and underwent polysomnography. Results: S-B had the highest sensitivity (97.6%), the highest area under the ROC curve (AUC) (0.73, 95%CI 0.7-0.76) and best OR (5.9, 95%CI 3.6-9.5), but the lowest specificity (12.7%) for AHI≥15. The 4-V≥14 had the highest specificity (74.4%) followed by ESS (67%). BQ had good sensitivity (87%), worse specificity (33%) than 4-V and ESS but better than Stop (13%) and S-B (12.7%). The combined sensitivities and specificities for the S-B and 4-V, ESS and S-B, ESS and BQ, BQ and 4-V, S-B, ESS and BQ did not improve the predictive values. Conclusions: S-B had the highest sensitivity, OR and AUC but rather low specificity and 4-V the highest specificity. The combination of different questionnaires did not improve their predictive value.
The Bayh-Dole Act Turns 30
Authors: Vicki Loise, Ashley J. Stevens
Journal: Science Translational Medicine (2010)

On 12 December 1980, in the waning days of the lame duck session of the 96th Congress, the U.S. Senate passed the University and Small Business Patent Procedures Act, now known as the Bayh-Dole Act, a seemingly obscure act that allowed universities to claim title to inventions that had been made with federal funding. It is unlikely that many present that day realized what a dramatic impact that act would have. Data clearly show that it played a critical role in rejuvenating the entire U.S. economic system, transforming it from a manufacturing base to an innovation base. Yet ironically, the act has passionate critics.
Reperfusion arrhythmias in isolated perfused pig hearts. Inhomogeneities in extracellular potassium, ST and TQ potentials, and transmembrane action potentials.
Authors: R Coronel, F J Wilms-Schopman, T Opthof, J Cinca, J W Fiolet, M J Janse
Journal: Circulation Research (1992)

We recorded direct current electrograms and local [K+]o at multiple sites and transmembrane potentials at selected sites during reperfusion after 5 minutes and 10 minutes of regional ischemia in isolated perfused pig hearts. After 10 minutes of ischemia, the incidence of ventricular fibrillation (VF) was 38%. At 80-90 seconds after reperfusion, [K+]o was 0.8 mM less than in normal tissue in half of the reperfused tissue, especially in the border zone. This was associated with TQ elevation of +4.5 mV and large peaked T waves. The latter was caused by an abrupt decrease of action potential duration in reperfused tissue, leading to a difference of up to 165 msec with normal tissue. Reperfusion VF started with a closely coupled ventricular premature beat. Activation block between reperfused and normal tissue permitted reentrant activation, leading to VF. Pretreatment with ryanodine (10(-6) M) and reperfusion with elevated [K+] (both of which prevent delayed afterdepolarizations) did not prevent closely coupled ventricular premature beats or VF. Five minutes of ischemia never caused VF. K+ depletion and TQ elevation in the reperfused zone was less frequent and smaller (-0.4 mM and 1.8 mV, respectively). Peaked T waves did not occur, and shortening of the action potential duration was less. We conclude that extracellular K+ depletion and marked action potential duration shortening in the reperfused tissue play a role in the genesis of reperfusion VF, which is caused by reentry. The closely coupled ventricular premature beat that initiates reentry is not caused by delayed afterdepolarizations but most likely by intramural reentry.
Return to work after thoracic organ transplantation in a clinically‐stable population
Authors: Lucia Petrucci, Susanna Ricotti, Ilaria Michelini, Patrizio Vitulo, Tiberio Oggionni, Alessandro Cascina, Andrea M. D'Armini, Claudio Goggi, Carlo Campana, Mario Viganò, Elena Dalla‐Toffola, Carmine Tinelli, Catherine Klersy
Journal: European Journal of Heart Failure (2007)
UDP-Glucuronosyltransferase 1A7 Genetic Polymorphisms Are Associated with Hepatocellular Carcinoma in Japanese Patients with Hepatitis C Virus Infection
Authors: Yue Wang, Naoya Kato, Yujin Hoshida, Motoyuki Otsuka, Hiroyoshi Taniguchi, Masaru Moriyama, Shuichiro Shiina, Takao Kawabe, Yoichi M. Ito, Masao Omata
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Genetic polymorphisms of UDP-glucuronosyltransferase 1A7 (UGT1A7), which detoxifies endogenous and environmental carcinogens, have been reported to be associated with hepatocellular carcinoma (HCC) in German populations. On the other hand, we reported that interleukin-1β (IL-1β) gene polymorphisms were associated with hepatitis C virus (HCV)-related HCC. In this study, we evaluated the association of both genes with the risk of HCC in Japanese HCV-infected patients. Experimental Design: Genetic polymorphisms of UGT1A7 and IL-1β were investigated in 280 Japanese patients (122 with HCC and 158 without HCC) with chronic HCV infections, by use of standard PCR-based genotyping techniques. Results: We designated the UGT1A7*1 allele (a haplotype conferring higher activity) as H and the *2, *3, and *4 alleles (haplotypes conferring lower activity) as L. The proportions of UGT1A7 L/L and H/L alleles (genotypes) in patients with HCC (25% and 45%, respectively) were higher than those in patients without HCC (15% and 39%, respectively) with odds ratios of 2.73 (95% confidence interval, 1.40–5.35) and 1.80 (95% confidence interval, 1.05–3.09), respectively, compared with the UGT1A7 H/H alleles. Multivariate analyses revealed that UGT1A7 L/L and IL-1β/−31T/T−511C/C genotypes, the presence of cirrhosis, age &amp;gt;60 years, male sex, and α-fetoprotein &amp;gt;20 μg/ml were associated with the presence of HCC (odds ratios, 2.33, 2.67, 4.20, 3.12, 3.09, and 2.90, respectively). Conclusion: The UGT1A7 polymorphisms together with IL-1β were associated with the presence of HCC in Japanese HCV-infected patients.
Prognostic value of pretransplantation host thymic function in HLA-identical sibling hematopoietic stem cell transplantation
Authors: Emmanuel Clave, Vanderson Rocha, Kimmo Talvensaari, Marc Busson, Corinne Douay, Marie-Lorraine Appert, Claire Rabian, Maryvonnick Carmagnat, Federico Garnier, Alain Filion, Gérard Socié, Eliane Gluckman, Dominique Charron, Antoine Toubert
Journal: Blood (2004)
Serum angiotensin I-converting enzyme response to exercise; no differential effect of genotype
Authors: A Yau, A D Moss, L J James, J Hynes, J J Ashworth, G H Evans
Journal: British Journal of Sports Medicine (2011)

Angiotensin I-converting enzyme (ACE) plays a pivotal role in whole body fluid balance and the degradation of bradykinin. A common allelic variant with a 287 base pair insert has been identified on the ACE gene. The homozygous insertion genotype ( II ) corresponds with lower basal serum ACE concentrations compared to the heterozygous ( WI ) and homozygous wild type genotypes ( WW ). Higher circulating levels of ACE may decrease vasodilation; affecting blood flow and sweat loss during exercise. A genotype-independent rise in ACE activity following 20 min of exercise has been reported, but the response to prolonged exercise is unknown. The aim was to examine the influence of ACE genotype on the serum ACE response to exercise in the heat. Healthy Caucasian males ( n =45, 18–45 y) completed 60 min of cycle exercise at (mean ± SD) 62 ± 5% VO 2max in 30.5 ± 0.3°C, with fluid ad libitum . Fluid intake and sweat loss were recorded. Venous blood samples were drawn pre, mid, and postexercise for the determination of serum ACE concentration and ACE genotype. Basal serum ACE concentrations were dependent on ACE genotype ( WW : 215 ± 57 ng.ml -1 ; WI : 158 ± 28 ng.ml -1 ; II : 106 ± 29 ng.ml -1 , P &lt;0.001). Serum ACE concentrations increased at 30 min of exercise to 231 ± 55 ng.ml -1 , 166 ± 29 ng.ml -1 and 115 ± 30 ng.ml -1 for WW , WI and II , respectively ( P &lt;0.001), and remained elevated post exercise. Serum ACE response was not influenced by ACE genotype ( P = 0.321). No differences were found for mean fluid intake ( WW : 613 ± 388 ml; WI : 753 ± 385 ml; II : 862 ± 421 ml, P = 0.31), or sweat loss ( WW : 1013 ± 257 ml; WI : 1048 ± 254 ml; II : 1257 ± 675 ml, P = 0.28). Serum ACE concentration increased independently of ACE genotype within 30 min exercise at 30.5°C. Coupled with the lack of genotype effect on sweat loss and fluid intake, these results suggest ACE genotype plays little role in fluid balance during exercise.
The Kidney Research Predicament
Authors: Lisa Bryan, Tod Ibrahim, Roy Zent, Michael J. Fischer
Journal: Journal of the American Society of Nephrology (2014)

Research funding from public and private sources has reached an all-time low. Economic conditions, sequestration, and a trend of low award success rates have created an imbalance between the supply of highly qualified research investigators and the availability of critically necessary research dollars. This grim environment continues to hinder the success of established investigators and deter potential investigators from joining the research workforce. Without action and support of innovative science, the future of the US health care system is in jeopardy, and its leadership role in medical research will decrease. This work discusses the effects of the decline in research funding, the plight of kidney research, and the impact of the American Society of Nephrology Grants Program on scientists. The ASN also calls on the entire nephrology community to rejuvenate the research environment, improve the lives of millions of people with kidney disease, and ultimately, find a cure.
Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients
Authors: Rafael Fonseca, Emily A. Blood, Martin M. Oken, Robert A. Kyle, Gordon W. Dewald, Richard J. Bailey, Scott A. Van Wier, Kimberly J. Henderson, James D. Hoyer, David Harrington, Neil E. Kay, Brian Van Ness, Philip R. Greipp
Journal: Blood (2002)