tbuckley/cabot-search huggingface dataset:
Electrocardiographic correlates of spontaneous termination of ventricular tachycardia in patients with coronary artery disease.
Authors: H J Duff, L B Mitchell, A M Gillis, R S Sheldon, L Chudleigh, P Cassidy, N Chiamvimonvat, D G Wyse
Journal: Circulation (1993)

BACKGROUND In vitro studies have reported that beat-to-beat variance in tachycardia cycle length and in conduction and repolarization properties can result in spontaneous termination of reentrant arrhythmias. The purpose of this study was to define the ECG patterns associated with spontaneous termination of ventricular tachycardia in humans late after myocardial infarction. METHODS AND RESULTS The QRS durations, QT intervals, and cycle lengths were measured on a beat-to-beat basis during episodes of sustained and spontaneously terminating ventricular tachycardias (VT) induced at antiarrhythmic drug-free and drug-assessment electrophysiological studies. Twenty-six patients were studied. Four categories of inducible ventricular tachycardia were studied: inducible sustained ventricular tachycardia in an antiarrhythmic drug-free state, spontaneously terminating ventricular tachycardia in an antiarrhythmic drug-free state, sustained ventricular tachycardia on antiarrhythmic therapy, and spontaneously terminating ventricular tachycardia on antiarrhythmic therapy. The ECG patterns that were statistically related to spontaneous termination of ventricular tachycardia included impingement of the QTP interval on the tachycardia cycle length (P &lt; .001) both in the presence and absence of drugs, transient shortening of QRS just before termination, and paradoxical prolongation of QTP after abrupt shortening of ventricular tachycardia cycle length. In addition, greater beat-to-beat variances in tachycardia cycle lengths, QT intervals, and QRS durations were statistically associated with spontaneously terminating ventricular tachycardia. These ECG patterns did not occur during sustained episodes of ventricular tachycardia during the antiarrhythmic drug-free state or during ineffective antiarrhythmic drug therapy. CONCLUSIONS A dynamic interplay between QRS duration, QT interval, and cycle length of tachycardia and their variances are associated with spontaneous termination of ventricular tachycardia in humans late after infarction. This study of ECG changes associated with spontaneous termination of ventricular tachycardia provides insight into potential mechanisms of antiarrhythmic drug efficacy.
Functional genomic and epidemiological studies reveal novel genes regulating cholesterol metabolism
Authors: Kris Richardson, Jose M Ordovas
Journal: Genome Medicine (2009)

Elevated plasma cholesterol is a heritable trait and a risk factor for the development of cardiovascular disease. Although several major biochemical pathways regulating cholesterol metabolism have been identified, questions regarding the details of this regulation remain. In fact, common genetic polymorphisms in candidate genes explain only 5 to 7% of variation in high- and low-density lipoprotein cholesterol levels between individuals. This suggests that many of the factors influencing cholesterol metabolism, and potentially the etiology of cardiovascular disease, are unknown. Here, we review recent functional genomic research that, combined with results from genome-wide association studies, provides a powerful tool to identify novel candidate genes relevant to cholesterol metabolism.
Spleen Tyrosine Kinase Inhibition Attenuates Autoantibody Production and Reverses Experimental Autoimmune GN
Authors: Stephen P. McAdoo, John Reynolds, Gurjeet Bhangal, Jennifer Smith, John P. McDaid, Anisha Tanna, William D. Jackson, Esteban S. Masuda, H. Terence Cook, Charles D. Pusey, Frederick W.K. Tam
Journal: Journal of the American Society of Nephrology (2014)

Spleen tyrosine kinase (SYK) has an important role in immunoreceptor signaling, and SYK inhibition has accordingly attenuated immune-mediated injury in several in vivo models. However, the effect of SYK inhibition on autoantibody production remains unclear, and SYK inhibition has not been studied in an autoimmune model of renal disease. We, therefore, studied the effect of SYK inhibition in experimental autoimmune GN, a rodent model of antiglomerular basement membrane disease. We show glomerular SYK expression and activation by immunohistochemistry in both experimental and clinical disease, and we show that treatment with fostamatinib, a small molecule kinase inhibitor selective for SYK, completely prevents the induction of experimental autoimmune GN. In established experimental disease, introduction of fostamatinib treatment led to cessation of autoantibody production, reversal of renal injury, preservation of biochemical renal function, and complete protection from lung hemorrhage. B cell ELISpot and flow cytometric analysis suggest that short-term fostamatinib treatment inhibits the generation and activity of antigen-specific B cells without affecting overall B-cell survival. Additionally, fostamatinib inhibited proinflammatory cytokine production by nephritic glomeruli ex vivo and cultured bone marrow-derived macrophages in vitro, suggesting additional therapeutic effects independent of effects on autoantibody production that are likely related to inhibited Fc receptor signaling within macrophages in diseased glomeruli. Given these encouraging results in an in vivo model that is highly applicable to human disease, we believe clinical studies targeting SYK in GN are now warranted.
Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: an analysis of data from the Pediatric Cardiomyopathy Registry
Authors: Steven E Lipshultz, E John Orav, James D Wilkinson, Jeffrey A Towbin, Jane E Messere, April M Lowe, Lynn A Sleeper, Gerald F Cox, Daphne T Hsu, Charles E Canter, Juanita A Hunter, Steven D Colan
Journal: The Lancet (2013)
Spontaneous Turnors of the Prostate Gland in Inbred Strains of Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: C Waymouth, D R Coman, P F Ward-Bailey
Journal: JNCI Journal of the National Cancer Institute (1983)

Spontaneous tumors of the prostate gland in the house mouse (Mus musculus) have rarely been described. In a histologic survey of prostate glands from old (greater than 700 days of age) mice, we have observed 2 primary adenocarcinomas of the prostate gland, 1 in a 1,047-day-old C57BL/6J mouse (DEH 1009) and 1 with metastases to the kidney and lungs in a 778-day-old C57BL/KsJ mouse (DEH 705C). We have also found a rhabdomyosarcoma of the prostate gland in a C57BL/6J mouse (DEH 1121C) 732 days old. The histologic characteristics of these tumors, and of the prostate glands of mice of similar ages without prostatic neoplastic involvement, including a 736-day-old CBA/CaJ mouse (DEH 849) with adenomatous hyperplasia, are described.
Maximal acid output and oesophagitis in hiatus hernia
Authors: B. H. Squire, S. Glick, A. Benn
Journal: Thorax (1968)

<b>Singh, H. M., and Baker, J. T. (1974)</b>. <i>Thorax</i>, <b>29</b>, 68-74. <b>Jaundice following open-heart surgery</b>. A study was made into the factors influencing the onset of jaundice in 102 patients undergoing valve replacement during cardiopulmonary bypass. Postoperative jaundice appeared to be correlated with double valve replacement, the co-existence of an uncorrected valvular lesion, length of perfusion and myocardial ischaemia times, and also the age of the patient. Factors appearing not to be correlated with the onset of jaundice included preoperative pulmonary artery pressure, cardiac index, parameters of preoperative renal and hepatic function, and the amount of blood used during bypass. The biochemical features of the jaundice seemed to follow a pattern not previously recognized in this context, with sometimes considerably raised bilirubin levels in association with virtually normal levels of transaminases and alkaline phosphatase.
Burundi ... an illustration of the problem
Authors: C. M De Wind
Journal: BMJ (1997)

They arrived in the night of 7 November, a lorry load of wounded from a town near the Zaire border. Twenty five people with gun shot wounds and bayonet cuts, sustained at an “incident” two weeks previously. By the time we had unloaded them (a slow process as we have only one stretcher) and put them to bed, the smell in the ward was quite unbearable. The only treatment they had received so far was dressings: clean bandages hiding filthy dressings inside and those covering a wide variety of infected, purulent, and gangrenous wounds. Patients were all dirty, malnourished, and in pain.

To simplify things for the night staff–one qualified nurse and one auxiliary–I prescribed amoxycillin and paracetamol for all, adding sleeping tablets for some. Nobody was willing to give much of a history. They said they were not sure on which side of the border they were when it happened. You do not ask too many questions anyway.

We had just opened our clinic one week before, a small Christian hospital in downtown Bujumbura, set up by a local non-governmental organisation (NGO) together with World Vision and sponsored with American money. Everything was still new: staff, equipment, and management. Only the building was old, and renovations had not yet been completed. The …
Exercising with reserve: exercise regulation by perceived exertion in relation to duration of exercise and knowledge of endpoint
Authors: J Swart, R P Lamberts, M I Lambert, E V Lambert, R W Woolrich, S Johnston, T D Noakes
Journal: British Journal of Sports Medicine (2009)

Objective: The purpose of this study was to examine ratings of perceived exertion (RPE) and performance during repetitive maximal effort 40 km time trials as well as after an intervention that aimed to decrease certainty about the remaining distance of the exercise bout. In addition, we examined the RPE during exercise bouts of markedly different duration. Methods: Part 1: 12 well-trained, competitive-level cyclists completed five 40 km time trials. During the final time trial all feedback was withheld until the final kilometre. In addition, to cause confusion about the remaining distance, they were asked to report their RPE at random intervals from 18 km to 38 km. Part 2: 6 well-trained, recreation-level cyclists randomly completed a 5 km, 10 km, 40 km and 100 km time trial. Results: Part 1: Mean RPE increased during the first four trials and decreased during the final trial. The rate of RPE progression increased in linearity during the first four trials and became more conservative in the final trial. These changes were directly related to performance. Part 2: Mean RPE for longer duration trials (40 km, 100 km) were lower during the first half of trial duration but matched those of shorter trials in the final 20%. Conclusions: Increased familiarity of the exercise bout and certainty about its endpoint are associated with a more aggressive RPE strategy that produces a superior exercise performance. Certainty about the endpoint and the duration of exercise affect both the RPE strategy and performance.
Molecular Serological Detection of DNA Alterations in Transitional Cell Carcinoma Is Highly Sensitive and Stage Independent
Authors: Rolf von Knobloch, Heidrun Brandt, Andres J. Schrader, Axel Heidenreich, Rainer Hofmann
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To evaluate the efficacy of fluorescent microsatellite analysis (MSA) for the serological diagnosis of transitional cell carcinoma (TCC) of the urinary tract analyzing free tumor DNA in the serum of cancer patients. Experimental Design: We applied fluorescent MSA to detect serum–DNA alterations in patients suffering from bladder and upper urinary tract TCC and prospectively collected fresh tumor, peripheral blood, and serum specimens from 61 consecutive patients to obtain the corresponding DNA. Fluorescent MSA was performed with a total of 17 polymorphic markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q, and 20q in the 61 cancer patients, as well as in 20 healthy controls. Results: Molecular serological analysis led to tumor-specific diagnosis of TCC in 80.3% (49 of 61) of cases. Four healthy controls displayed serum–DNA artifacts rendering a specificity of 80%. The highest frequency of serum–DNA alterations was detected for chromosomal region 8p with 36%. Chromosomes 5q, 9p, and 20q showed serum–DNA alterations in 18 to 21%. The identification of serum–DNA alterations was not statistically associated with underlying local tumor stage (P = 0.29) but was more frequent in high-grade tumors (P = 0.08). Conclusions: MSA offers a highly sensitive method for serological diagnosis of TCC. To optimize specificity, simultaneous analysis of tumor DNA is advised to rule out artifacts resembling allelic imbalance in MSA of serum DNA.
Serum Levels of the Adipokine Progranulin Depend on Renal Function
Authors: Judit Richter, Denise Focke, Thomas Ebert, Peter Kovacs, Anette Bachmann, Ulrike Lössner, Susan Kralisch, Jürgen Kratzsch, Joachim Beige, Matthias Anders, Ingolf Bast, Matthias Blüher, Michael Stumvoll, Mathias Fasshauer
Journal: Diabetes Care (2012)

Progranulin has recently been introduced as a novel adipokine inducing insulin resistance and obesity. In the current study, we investigated renal elimination, as well as association of the adipokine with markers of the metabolic syndrome.Progranulin serum levels were quantified by enzyme-linked immunosorbent assay and correlated to anthropometric and biochemical parameters of renal function and glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1-5 of chronic kidney disease (CKD).Median serum progranulin levels adjusted for age, sex, and BMI were significantly different between CKD stages with highest values detectable in stage 5 (stage 1, 58.3 µg/L; stage 2, 63.0 µg/L; stage 3, 65.4 µg/L; stage 4, 68.8 µg/L; and stage 5, 90.6 µg/L). Furthermore, CKD stage was the strongest independent predictor of circulating progranulin in our cohort. In addition, high-sensitivity interleukin-6 and adiponectin remained significantly and independently correlated with the adipokine.We demonstrate that progranulin serum levels increase with deteriorating renal function. These findings are in accordance with the hypothesis that renal clearance is a major elimination route for circulating progranulin. Furthermore, the adipokine is positively and independently associated with markers of inflammation and adiponectin.
Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections
Authors: Kerry Dobbs, Cecilia Domínguez Conde, Shen-Ying Zhang, Silvia Parolini, Magali Audry, Janet Chou, Emma Haapaniemi, Sevgi Keles, Ivan Bilic, Satoshi Okada, Michel Massaad, Samuli Rounioja, Adel Alwahadneh, Nina Serwas, Kelly Capuder, Ergin Çiftçi, Kerstin Felgentreff, Toshiro Ohsumi, Vincent Pedergnana, Bertrand Boisson, Şule Haskoloğlu, Arzu Ensari, Michael Schuster, Alessandro Moretta, Yuval Itan, Ornella Patrizi, Flore Rozenberg, Pierre Lebon, Janna Saarela, Mikael Knip, Slavé Petrovski, David Goldstein, Roberta Parrott, Berna Savas, Axel Schambach, Giovanna Tabellini, Christoph Bock, Talal Chatila, Anne Marie Comeau, Raif Geha, Laurent Abel, Rebecca Buckley, Aydan İkincioğullari, Waleed Al-Herz, Merja Helminen, Figen Doğu, Jean-Laurent Casanova, Kaan Boztuğ, Luigi Notarangelo
Journal: New England Journal of Medicine (2015)

Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that are present are quantitatively or functionally deficient. Impaired humoral immunity is also common. Patients have severe infections, autoimmunity, or both. The specific molecular, cellular, and clinical features of many types of combined immunodeficiencies remain unknown. Methods We performed genetic and cellular immunologic studies involving five unrelated children with early-onset invasive bacterial and viral infections, lymphopenia, and defective T-cell, B-cell, and natural killer (NK)-cell responses. Two patients died early in childhood; after allogeneic hematopoietic stem-cell transplantation, the other three had normalization of T-cell function and clinical improvement. Results We identified biallelic mutations in the dedicator of cytokinesis 2 gene (DOCK2) in these five patients. RAC1 activation was impaired in the T cells. Chemokine-induced migration and actin polymerization were defective in the T cells, B cells, and NK cells. NK-cell degranulation was also affected. Interferon-α and interferon-λ production by peripheral-blood mononuclear cells was diminished after viral infection. Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were normalized by treatment with interferon alfa-2b or after expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a new mendelian disorder with pleiotropic defects of hematopoietic and nonhematopoietic immunity. Children with clinical features of combined immunodeficiencies, especially with early-onset, invasive infections, may have this condition. (Supported by the National Institutes of Health and others.).
Mechanism of Syncope in Patients With Heart Disease and Negative Electrophysiologic Test
Authors: Carlo Menozzi, Michele Brignole, Roberto Garcia-Civera, Angel Moya, Gianluca Botto, Luis Tercedor, Roberta Migliorini, Xavier Navarro
Journal: Circulation (2002)

Background — In patients with syncope and structural heart disease, syncope is suspected to be attributable to a primary cardiac arrhythmia, but little is known of its mechanism when electrophysiologic study is unremarkable. Methods and Results — We applied an implantable loop recorder in 35 patients with overt heart disease at risk of ventricular arrhythmia, because these were patients with previous myocardial infarction or cardiomyopathy with depressed ejection fraction or nonsustained ventricular tachycardia in whom an electrophysiologic study was unremarkable. During a follow-up of 3 to 15 months, syncope recurred in 6 patients (17%) after a mean of 6±5 months; in 3 patients, the mechanism of syncope was bradycardia with long pauses (sudden-onset AV block in 2 cases and sinus arrest in 1 case); in 1 patient, there was stable sinus tachycardia; and in 2 patients, who had chronic atrial fibrillation, there was an increase in ventricular rate. A total of 23 episodes of presyncope were documented in 8 patients (23%): no rhythm variation or mild tachycardia in 12 cases, paroxysmal atrial fibrillation or atrial tachycardia in 10 cases, and sustained ventricular tachycardia in 1 case. No patient died during the study period nor suffered from injury attributable to syncopal relapse. Conclusions — The patients with unexplained syncope, structural heart disease, and negative electrophysiologic study had a favorable medium-term outcome with no case of death and a low recurrence rate of syncope without related injury. The mechanism of syncope was heterogeneous, and ventricular tachyarrhythmia was unlikely.
Community-Wide Isoniazid Preventive Therapy Drives Drug-Resistant Tuberculosis: A Model-Based Analysis
Authors: Harriet L. Mills, Ted Cohen, Caroline Colijn
Journal: Science Translational Medicine (2013)

Tuberculosis (TB) control is especially difficult in settings of high HIV prevalence; HIV co-infection erodes host immunity and increases risk of progression to active TB. Studies have demonstrated that a 6-month (or longer) course of monotherapy with isoniazid [isoniazid preventive therapy (IPT)] can reduce this risk. The World Health Organization endorses IPT for symptom-free individuals with HIV/TB co-infection and has recommended expanding IPT to entire communities (community-wide IPT). Although previous reviews have not found a statistically significant elevated risk of isoniazid-resistant TB among individuals previously treated with IPT, community-wide IPT programs may nonetheless generate substantial selective pressure and increase the burden of drug-resistant TB (DRTB). We developed mathematical models to identify the conditions under which community-wide IPT interventions could increase the burden of isoniazid-resistant Mycobacterium tuberculosis, even when we assumed that IPT does not select for resistance among those treated with IPT. We found that in models that included any mechanism of interstrain competition (such as partial immunity conferred by a previous M. tuberculosis infection), community-wide IPT interventions conferred an indirect benefit to drug-resistant strains through selective suppression of drug-sensitive infections. This result suggests that the absence of an observed elevation in the risk of DRTB among those receiving IPT in small-scale studies of limited duration does not imply that the selective pressure imposed by community-wide IPT will not be substantial. Community-wide IPT may play an important role in TB control in these settings, and its rollout should be accompanied by interventions to detect and treat drug-resistant disease.
Hypertension and Unilateral Parenchymal Renal Disease
Authors: E. Darracott Vaughan
Journal: JAMA (1975)

Hypertension was not renin-dependent in the majority of 62 hypertensive patients with seemingly unilateral renal parenchymal disease, as indicated by plasma renin activity: low in 14 (23%), normal in 40 (56%), and high in only 8 (13%). By a weighted scoring system for analysis of differential renal-vein and peripheral renin levels, 70% (16 of 23) of these patients did not give scores predictive of cure by nephrectomy. Thus, occult bilateral disease reflected by attendant volume expansion and consequent reactive renin suppression may explain the well-known disappointing cure rate after uninephrectomy in this group. Since unilateral hypersecretion of renin with a completely normal contralateral kidney is rare in this group, abnormal renal-vein and peripheral renin values should be a prerequisite for advising nephrectomy, especially when the suspected kidney shows considerable excretory function. (<i>JAMA</i>233:1177-1183, 1975)
Racial differences in hepatitis C treatment eligibility
Authors: Michael T. Melia, Andrew J. Muir, Jonathan McCone, Mitchell L. Shiffman, John W. King, Steven K. Herrine, Greg W. Galler, Joseph R. Bloomer, Frederick A. Nunes, Kimberly A. Brown, Kevin D. Mullen, Natarajan Ravendhran, Reem H. Ghalib, Navdeep Boparai, Ruiyun Jiang, Stephanie Noviello, Clifford A. Brass, Janice K. Albrecht, John G. McHutchison, Mark S. Sulkowski
Journal: Hepatology (2011)

Black Americans are disproportionally infected with hepatitis C virus (HCV) and are less likely than whites to respond to treatment with peginterferon (PEG-IFN) plus ribavirin (RBV). The impact of race on HCV treatment eligibility is unknown. We therefore performed a retrospective analysis of a phase 3B multicenter clinical trial conducted at 118 United States community and academic medical centers to evaluate the rates of and reasons for HCV treatment ineligibility according to self-reported race. In all, 4,469 patients were screened, of whom 1,038 (23.2%) were treatment ineligible. Although blacks represented 19% of treated patients, they were more likely not to be treated due to ineligibility and/or failure to complete required evaluations (40.2%) than were nonblack patients (28.5%; P < 0.001). After the exclusion of persons not treated due to undetectable HCV RNA or nongenotype 1 infection, blacks were 65% less likely than nonblacks to be eligible for treatment (28.1% > 17.0%; relative risk, 1.65; 95% confidence interval, 1.46-1.87; P < 0.001). Blacks were more likely to be ineligible due to neutropenia (14% versus 3%, P < 0.001), anemia (7% versus 4%, P = 0.02), elevated glucose (8% versus 3%, P < 0.001), and elevated creatinine (5% versus 1%, P < 0.001).