tbuckley/cabot-search huggingface dataset:
Role of renal nerves in the potentiation of atriopeptin-induced natriuresis by vasopressin.
Authors: D A Hartupee, A J Trapani, J P Koepke, E H Blaine
Journal: Circulation Research (1989)

Previous studies have shown that vasopressin potentiates the natriuresis produced by atriopeptin. In five anesthetized dogs of this study, we found that the potentiation was proportional to the dose of vasopressin infused. Sodium excretion was 46 +/- 16 mueq/min with atriopeptin (103-126) (AP24) alone (0.36 nmol/kg.min), was increased to 127 +/- 29 by concomitant intravenous infusion of 0.4 mU/kg.min vasopressin, was further increased to 301 +/- 75 by 1.2 mU/kg.min vasopressin and leveled off at 328 +/- 37 with 3.6 mU/kg.min vasopressin. To investigate whether the potentiation by vasopressin was due to an intrarenal action, we infused three doses of vasopressin (0.04, 0.12, and 0.36 mU/kg.min) into the renal artery during intravenous AP24 infusion in a second group of five dogs. The natriuresis, 128 +/- 18 mueq/min, was unaffected by any intrarenal dose of vasopressin. In a third group, we determined whether the potentiation produced by vasopressin was mediated by a mechanism involving the renal nerves by denervating the left kidney before AP24 infusion. In the denervated kidneys, sodium excretion was increased from a control value of 33 +/- 5 mueq/min to 303 +/- 38 with AP24 alone and was unresponsive to subsequent intravenous vasopressin administration. The exaggerated natriuresis with AP24 alone was of the same magnitude as that produced by AP24 plus the highest doses of intravenous vasopressin in the innervated kidneys of the first group. From these results we conclude that the potentiation of AP-induced natriuresis by vasopressin is mediated by a mechanism involving the renal nerves and probably results from the known effect of vasopressin to inhibit renal nerve activity.
Islet1 Deletion Causes Kidney Agenesis and Hydroureter Resembling CAKUT
Authors: Yusuke Kaku, Tomoko Ohmori, Kuniko Kudo, Sayoko Fujimura, Kentaro Suzuki, Sylvia M. Evans, Yasuhiko Kawakami, Ryuichi Nishinakamura
Journal: Journal of the American Society of Nephrology (2013)

Islet1 (Isl1) is a transcription factor transiently expressed in a subset of heart and limb progenitors. During studies of limb development, conditional Isl1 deletion produced unexpected kidney abnormalities. Here, we studied the renal expression of Isl1 and whether it has a role in kidney development. In situ hybridization revealed Isl1 expression in the mesenchymal cells surrounding the base of the ureteric bud in mice. Conditional deletion of Isl1 caused kidney agenesis or hypoplasia and hydroureter, a phenotype resembling human congenital anomalies of the kidney and urinary tract (CAKUT). The absence of Isl1 led to ectopic branching of the ureteric bud out from the nephric duct or to the formation of accessory buds, both of which could lead to obstruction of the ureter-bladder junction and consequent hydroureter. The abnormal elongation and poor branching of the ureteric buds were the likely causes of the kidney agenesis or hypoplasia. Furthermore, the lack of Isl1 reduced the expression of Bmp4, a gene implicated in the CAKUT-like phenotype, in the metanephric region before ureteric budding. In conclusion, Isl1 is essential for proper development of the kidney and ureter by repressing the aberrant formation of the ureteric bud. These observations call for further studies to investigate whether Isl1 may be a causative gene for human CAKUT.
Lymphocyte phenotype and function in chronically transfused children with sickle cell disease
Authors: Winfred Wang, Henry Herrod, Gerald Presbury, Judith Wilimas
Journal: American Journal of Hematology (1985)

Abstract Immunologic studies were performed on mononuclear cells from ten chronically transfused children with sickle cell disease, and the results were compared with those from five other groups: 21 sickle cell patients who were not receiving regular transfusions, 6 chronically transfused children with other forms of refractory anemia, 10 previously splenectomized children, 5 boys with hemophilia A, and 27 normal adult controls. The helper:suppressor T cell ratios (T4:T8) in all groups except hemophiliacs were normal, were unrelated to the number of units transfused, and were not suggestive of findings reported for patients with the acquired immune deficiency syndrome (AIDS) or groups at risk for the syndrome. Percentages of T3, T4, and T8 cells were low in sickle cell and splenectomized patients, but not in chronically transfused patients with other anemias. Serum IgG was frequently elevated, and IgG synthesis in vitro was increased relative to IgM synthesis in sickle cell patients. Coculture experiments indicated that such findings may stem from a selective increase in IgG synthesis by B cells. Thus, transfused sickle cell patients have a particular pattern of immunologic abnormalities that is distinct from that seen in AIDS.
Influence of Prostaglandin Synthesis Inhibitors on Pulmonary Vasodilatory Effects of Hydralazine in Dogs with Hypoxic Pulmonary Vasoconstriction
Authors: Lewis J. Rubin, Jeffrey D. Lazar
Journal: Journal of Clinical Investigation (1981)

To determine whether hydralazine, a systemic vasodilator, exerted a similar effect on the pulmonary circulation, we studied the circulatory changes in dogs during three interventions: (a) the control state during room air ventilation; (b) during continuous hypoxic ventilation with 10% oxygen, and maintaining continuous hypoxic ventilation; and (c) after 1 mg/kg hydralazine intravenously.
Effect of age, Helicobacter pylori infection, and gastritis with atrophy on serum gastrin and gastric acid secretion in healthy men.
Authors: P H Katelaris, F Seow, B P Lin, J Napoli, M C Ngu, D B Jones
Journal: Gut (1993)

Gastric acid secretion has been considered to decline with increasing age but this view is being re-evaluated as the importance of Helicobacter pylori infection emerges. This study aimed to determine the effect of age, H pylori, and gastritis with atrophy on the serum gastrin concentration, gastric secretory volumes, and acid output in healthy, asymptomatic men. Young men (mean (SD) age 22.9 (0.6) years; n = 22) were compared with old men (72.9 (1.2) years; n = 28) in respect of basal serum gastrin and basal, sham fed, pentagastrin stimulated maximal and peak acid secretion. Antral, corpus, and fundal biopsy specimens were taken for histology and H pylori status (histology, culture, and rapid urease test). H pylori associated gastritis was present in three of 22 young (13.6%) and 16 of 28 old (57.1%) men. Gastritis with atrophy was present in 11 old subjects, 10 of whom were H pylori positive. These subjects had higher mean (SD) serum gastrin concentrations than old subjects without atrophy and young subjects (61.8 (9.2); 40.0 (2.9); 36.8 (2.3) pmol/l respectively; p &lt; 0.001). H pylori infected subjects had higher gastrin values than uninfected subjects, overall (55.3 (5.9); 36.0 (1.8) pmol/l; p &lt; 0.001) and in subjects without atrophy (45.3 (4.2); 36.0 (1.8) pmol/l; p &lt; 0.03). In subjects without H pylori infection, gastrin values did not differ with age (old 37.1 (1.7); young 35.4 (2.1) pmol/l). The maximal gastric secretory volume was lower in old subjects with atrophy. Acid output (mmol/h) in subjects with atrophy was lower than in subjects with no atrophy (basal: 3.0(1.1); 5.1(0.7); p=NS; sham led: 5.4 (1.4); 9.3 (0.8); p&lt;0.02; maximal: 18.9 (4.0); 31.4(1.8); p&lt;0.002; peak: 25.1(5.3); 43.4(2.7); p&lt;0.003). However, acid secretion in old subjects without atrophy was not different to that in young subjects, irrespective of H pylori status. These results did not differ when acid output was expressed as mmol/h/kg lean body mass or mmol/h/kg fat free body weight. Using multiple linear regression analysis, gastritis with atrophy was the only factor that had an independent negative effect on acid secretion. In healthy men without atrophy, gastric acid secretion is preserved with ageing and is independent of H pylori status. Atrophy, which is closely related to H pylori infection, is associated with a decline in acid secretion. Increased basal serum gastrin is related to both atrophy and H pylori infection but not to ageing per se.
The Role of the Halfway House in Community Mental Health Programs in the United Kingdom and America
Authors: ELLY JANSEN
Journal: American Journal of Psychiatry (1970)

The author discusses various approaches to halfway house operations, including the emergence of a philosophy arising from an experimental project in England and the subsequent establishment of a halfway house organization. She reviews problems encountered in setting up adequate halfway house facilities and government attitudes in the U. K. and the U. S. and makes suggestions for initiating a flexible yet consistent halfway house program.
Transcatheter Aortic Valve Replacement for Degenerative Bioprosthetic Surgical Valves
Authors: Danny Dvir, John Webb, Stephen Brecker, Sabine Bleiziffer, David Hildick-Smith, Antonio Colombo, Fleur Descoutures, Christian Hengstenberg, Neil E. Moat, Raffi Bekeredjian, Massimo Napodano, Luca Testa, Thierry Lefevre, Victor Guetta, Henrik Nissen, José-María Hernández, David Roy, Rui C. Teles, Amit Segev, Nicolas Dumonteil, Claudia Fiorina, Michael Gotzmann, Didier Tchetche, Mohamed Abdel-Wahab, Federico De Marco, Andreas Baumbach, Jean-Claude Laborde, Ran Kornowski
Journal: Circulation (2012)

Background— Transcatheter aortic valve-in-valve implantation is an emerging therapeutic alternative for patients with a failed surgical bioprosthesis and may obviate the need for reoperation. We evaluated the clinical results of this technique using a large, worldwide registry. Methods and Results— The Global Valve-in-Valve Registry included 202 patients with degenerated bioprosthetic valves (aged 77.7±10.4 years; 52.5% men) from 38 cardiac centers. Bioprosthesis mode of failure was stenosis (n=85; 42%), regurgitation (n=68; 34%), or combined stenosis and regurgitation (n=49; 24%). Implanted devices included CoreValve (n=124) and Edwards SAPIEN (n=78). Procedural success was achieved in 93.1% of cases. Adverse procedural outcomes included initial device malposition in 15.3% of cases and ostial coronary obstruction in 3.5%. After the procedure, valve maximum/mean gradients were 28.4±14.1/15.9±8.6 mm Hg, and 95% of patients had ≤+1 degree of aortic regurgitation. At 30-day follow-up, all-cause mortality was 8.4%, and 84.1% of patients were at New York Heart Association functional class I/II. One-year follow-up was obtained in 87 patients, with 85.8% survival of treated patients. Conclusions— The valve-in-valve procedure is clinically effective in the vast majority of patients with degenerated bioprosthetic valves. Safety and efficacy concerns include device malposition, ostial coronary obstruction, and high gradients after the procedure.
<i>NFKBIA</i>Deletion in Glioblastomas
Authors: Markus Bredel, Denise M. Scholtens, Ajay K. Yadav, Angel A. Alvarez, Jaclyn J. Renfrow, James P. Chandler, Irene L.Y. Yu, Maria S. Carro, Fangping Dai, Michael J. Tagge, Roberto Ferrarese, Claudia Bredel, Heidi S. Phillips, Paul J. Lukac, Pierre A. Robe, Astrid Weyerbrock, Hannes Vogel, Steven Dubner, Bret Mobley, Xiaolin He, Adrienne C. Scheck, Branimir I. Sikic, Kenneth D. Aldape, Arnab Chakravarti, Griffith R. Harsh
Journal: New England Journal of Medicine (2010)

Amplification and activating mutations of the epidermal growth factor receptor (EGFR) oncogene are molecular hallmarks of glioblastomas. We hypothesized that deletion of NFKBIA (encoding nuclear factor of κ-light polypeptide gene enhancer in B-cells inhibitor-α), an inhibitor of the EGFR-signaling pathway, promotes tumorigenesis in glioblastomas that do not have alterations of EGFR.We analyzed 790 human glioblastomas for deletions, mutations, or expression of NFKBIA and EGFR. We studied the tumor-suppressor activity of NFKBIA in tumor-cell culture. We compared the molecular results with the outcome of glioblastoma in 570 affected persons.NFKBIA is often deleted but not mutated in glioblastomas; most deletions occur in nonclassical subtypes of the disease. Deletion of NFKBIA and amplification of EGFR show a pattern of mutual exclusivity. Restoration of the expression of NFKBIA attenuated the malignant phenotype and increased the vulnerability to chemotherapy of cells cultured from tumors with NFKBIA deletion; it also reduced the viability of cells with EGFR amplification but not of cells with normal gene dosages of both NFKBIA and EGFR. Deletion and low expression of NFKBIA were associated with unfavorable outcomes. Patients who had tumors with NFKBIA deletion had outcomes that were similar to those in patients with tumors harboring EGFR amplification. These outcomes were poor as compared with the outcomes in patients with tumors that had normal gene dosages of NFKBIA and EGFR. A two-gene model that was based on expression of NFKBIA and O(6)-methylguanine DNA methyltransferase was strongly associated with the clinical course of the disease.Deletion of NFKBIA has an effect that is similar to the effect of EGFR amplification in the pathogenesis of glioblastoma and is associated with comparatively short survival.
Assessment of diaphragm paralysis with oesophageal electromyography and unilateral magnetic phrenic nerve stimulation
Authors: Y.M. Luo, M.L. Harris, R.a Lyall, A Watson, M.i Polkey, J Moxham
Journal: European Respiratory Journal (2000)

The purpose of this study was to establish a sensitive and reliable method of diagnosing diaphragm paralysis by recording the diaphragm compound muscle action potential (CMAP) using a multipair oesophageal electrode and unilateral magnetic phrenic nerve stimulation. An oesophageal electrode catheter was designed containing six coils (1 cm wide and 3 cm apart), creating an array of four sequential electrode pairs. The oesophageal catheter was taped at the nose with the proximal electrode pair 40 cm from the nares. Eight patients with unilateral (n=5) or bilateral (n=3) diaphragm paralysis were studied. Five to seven phrenic nerve stimulations were performed at 80% of maximum magnetic stimulator output and the CMAPs were recorded simultaneously from the four pairs of electrodes. In the five patients with unilateral diaphragm paralysis, the CMAP amplitudes and latencies were 1.16+/-0.29 mV and 7.6+/-1.5 ms for functioning sides. No diaphragm CMAP could be detected when stimulating nonfunctioning phrenic nerves. This study shows that diaphragm paralysis can be reliably diagnosed by unilateral magnetic stimulation combined with a multipaired oesophageal electrode.
Functional Mitral Regurgitation and Transcatheter Mitral Annuloplasty
Authors: David S. Bach
Journal: Circulation (2009)

I n this issue, Schofer and colleagues present findings from the Carillon Mitral Annuloplasty Device European Union Study (AMADEUS), an uncontrolled multicenter trial in which percutaneous placement of a cinching device in the coronary sinus is used to treat functional mitral regurgitation (MR) of ischemic and nonischemic etiologies. 1 Of 48 patients enrolled, the device was successfully implanted in 30.Major adverse events occurred in 6 (13%) of 46 patients based on intent-to-treat.The severity of MR, based on 4 echocardiography/Doppler measures, decreased between 22% and 32%.There was substantial functional improvement (assessed by New York Heart Association functional class, 6-minute walk test, and the Kansas City Cardiomyopathy Questionnaire) at 1-month and 6-month follow-up.The study is at once exciting and provocative; it is the extrapolation of its results to clinical practice that may be controversial.
A double-blind placebo-controlled randomized phase III trial of 5-fluorouracil and leucovorin, plus or minus trimetrexate, in previously untreated patients with advanced colorectal cancer
Authors: C.D. Blanke, J. Shultz, J. Cox, M. Modiano, R. Isaacs, B. Kasimis, R. Schilsky, J. Fleagle, M. Moore, N. Kemeny, D. Carlin, L. Hammershaimb, D. Haller
Journal: Annals of Oncology (2002)
TNK–Tissue Plasminogen Activator Compared With Front-Loaded Alteplase in Acute Myocardial Infarction
Authors: Christopher P. Cannon, C. Michael Gibson, Carolyn H. McCabe, A. A. Jennifer Adgey, Marc J. Schweiger, Rafael F. Sequeira, Gilles Grollier, Robert P. Giugliano, Martin Frey, Hiltrud S. Mueller, Richard M. Steingart, W. Douglas Weaver, Frans Van de Werf, Eugene Braunwald
Journal: Circulation (1998)

Background —Bolus thrombolytic therapy is a simplified means of administering thrombolysis that facilitates rapid time to treatment. TNK-tissue plasminogen activator (TNK-tPA) is a highly fibrin-specific single-bolus thrombolytic agent. Methods and Results —In TIMI 10B, 886 patients with acute ST-elevation myocardial infarction presenting within 12 hours were randomized to receive either a single bolus of 30 or 50 mg TNK-tPA or front-loaded tPA and underwent immediate coronary angiography. The 50-mg dose was discontinued early because of increased intracranial hemorrhage and was replaced by a 40-mg dose, and heparin doses were decreased. TNK-tPA 40 mg and tPA produced similar rates of TIMI grade 3 flow at 90 minutes (62.8% versus 62.7%, respectively, P =NS); the rate for the 30-mg dose was significantly lower (54.3%, P =0.035) and was 65.8% for the 50-mg dose ( P =NS). A prespecified analysis of weight-based TNK-tPA dosing using median TIMI frame count demonstrated a dose response ( P =0.001). Similar dose responses were observed for serious bleeding and intracranial hemorrhage, but significantly lower rates were observed for both TNK-tPA and tPA after the heparin doses were lowered and titration of the heparin was started at 6 hours. Conclusions —TNK-tPA, given as a single 40-mg bolus, achieved rates of TIMI grade 3 flow similar to those of the 90-minute bolus and infusion of tPA. Weight-adjusting TNK-tPA appears to be important in achieving optimal reperfusion; reduced heparin dosing appears to improve safety for both agents. Together with the safety results from the parallel Assessment of the Safety of a New Thrombolytic: TNK-tPA (ASSENT I) trial, an appropriate dose of this single-bolus thrombolytic agent has been identified for phase III testing.
Improvements in Patient-Reported Outcomes Associated With an Intervention to Enhance Quality of Care for Rural Patients With Type 2 Diabetes
Authors: Sheri L. Maddigan, Sumit R. Majumdar, Lisa M. Guirguis, Richard Z. Lewanczuk, T. K. Lee, Ellen L. Toth, Jeffrey A. Johnson
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to examine patient-reported outcomes in a controlled trial of a multifaceted provider-level intervention to improve quality of care for rural patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—We conducted a before/after intervention study with concurrent controls in two rural regions in Alberta, Canada. The intervention consisted of six monthly visits by a multidisciplinary health care team and was primarily directed at primary care providers. Clinical and patient-reported outcomes were assessed after 6 months. Patient-reported outcomes included changes in health-related quality of life (Health Utilities Index Mark 3 [HUI3]), satisfaction with care, lifestyle (Diabetes Lifestyle Form), and adherence to self-care activities. Analysis of covariance was used to assess differences over time between the control and intervention regions. RESULTS—A total of 200 intervention and 172 control subjects were included in this analysis. After adjusting for important clinical and demographic differences, a statistically significant and clinically important improvement in the overall HUI3 score was seen at the 6-month follow-up in the intervention region (0.06 [95% CI 0.02–0.10]) compared with the control region (0.01 [−0.04 to 0.04]) (P = 0.03 for the difference between groups). Satisfaction with general medical care (P &amp;lt; 0.001 between groups) and diabetes care (P &amp;lt; 0.001 between groups) increased among patients in the intervention region compared with the control region. Self-efficacy, attitudes, and beliefs about diabetes control all increased in the intervention region when compared with the control region, but adherence to self-care activities did not. CONCLUSIONS—A provider-level intervention directed at improving quality of clinical care for patients with type 2 diabetes also had a favorable impact on overall health-related quality of life, satisfaction with care, and other humanistic outcomes.
Skewed X chromosome inactivation in rheumatoid arthritis women
Authors: D. F. Azzouz, O. E. Onat, N. Balandraud, S. B. Kanaan, J. Roudier, T. Ozcelik, N. C. Lambert
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> It has long been recognised that women have a greater prevalence of autoimmune diseases. Rheumatoid arthritis (RA) does not escape this rule with a women:men ratio of 3:1. X chromosome inactivation (XCI) is a dosage compensation mechanism used by mammals to ensure that XX females and XY males equalise X chromosome gene expression. As a consequence, females are a mosaic of two cell lines, one expressing maternal X-linked and the other expressing paternal X-linked genes with a ratio close to 50:50 when XCI is random. However skewing, defined as a deviation from the 50:50 ratio has been described in females with autoimmune thyroid diseases, scleroderma and juvenile idiopathic arthritis (for review1). The aim of the current study is to test whether women with RA also have a skewed XCI. <h3>Methods</h3> The highly polymorphic CAG repeat on the first exon of the androgen receptor gene was genotyped, as described elsewhere2 to determine XCI bias in 84 women with RA and 100 healthy women. <h3>Results</h3> A total of 54 patients and 69 controls were informative for androgen receptor polymorphism. Among them 31.5% of women with RA (17/54) had a skewed XCI (≥80:20) compared to only 17.4% of healthy women (12/69). Only extreme skewing was statistically significant with 18.5% of patients following this pattern and 2.9% of controls (p=0.004). <h3>Conclusions</h3> Our preliminary data indicate that skewed XCI may be a risk factor for the occurrence of RA in women. Further studies need to be done to analyse whether women who have a skewed pattern have less genetic susceptibilities (shared epitope) or less specific autoantibodies (anti-CCP) as their risk factor is X chromosome linked.
The Pathobiology of Arrhythmogenic Cardiomyopathy
Authors: Jeffrey E. Saffitz
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

This review highlights current knowledge about arrhythmogenic cardiomyopathy and considers clinical, pathological, genetic, biomechanical, and pathophysiological aspects of disease pathogenesis. Although relatively uncommon, arrhythmogenic cardiomyopathy is of particular interest as a model system for study. It is caused in at least half of all cases by single-gene mutations that provide direct entry points into studies designed to elucidate mechanisms of disease. These mutations involve proteins that form desmosomes, directly implicating altered cellular biomechanical properties in disease pathogenesis and providing opportunities to investigate more broadly the ways in which abnormal cell and tissue biomechanics induce cardiac myocyte injury and alter cell biology. The highly arrhythmogenic phenotype is a cardinal feature of the disease. A more complete understanding of the pathogenesis of this aspect of arrhythmogenic cardiomyopathy may shed light onto the basic mechanisms underlying lethal ventricular arrhythmias and sudden cardiac death in more common forms of heart disease.