tbuckley/cabot-search huggingface dataset:
Clinical and in vivo antiarrhythmic potential of sodium-hydrogen exchange inhibitors
Authors: H. J Duff
Journal: Cardiovascular Research (1995)

Intracellular acidification may be the initial stimulus for a cascade of events contributing to intracellular calcium overload. Ischaemia results in the accumulation of lactate and other proton donors causing intracellular acidification. During reperfusion the activity of the Na+/H+ exchanger recovers, allowing extrusion of protons at the expense of increases in intracellular sodium. The rise in intracellular sodium decreases the gradient required for sodium calcium exchange, resulting in accumulation of intracellular calcium. These data are in keeping with the pathophysiological model that the Na+/H+ exchanger is an important part of a cascade leading from intracellular acidosis to intracellular sodium loading followed by calcium overload. From this model we predicted that amiloride would be antiarrhythmic. In 1988, we reported that low concentration of amiloride (0.1-0.3 microM) suppresses the induction of sustained ventricular tachyarrhythmias in dogs late following infarction. Amiloride suppressed inducible ventricular tachycardia in approximately 50% of the animals. In an extension of this work we assessed the efficacy of amiloride in suppressing inducible ventricular tachycardia in humans who presented with symptomatic ventricular tachycardia. In that study, amiloride manifested antiarrhythmic activity, but not to the degree that was observed in our dog model. Six of 31 patients (19%) had complete suppression of induced ventricular tachycardia. In an extension of this work, we assessed in our in vivo dog model which of the pharmacological effects of amiloride were associated with antiarrhythmic efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 4460: Mechanism of action of small molecule CXCR4 antagonists in human B-lymphoma cell lines
Authors: Yanping Hu, Tri-Hung Nguyen, Mark Swistak, Matt Gale, Scott Lonning, Johanne Kaplan, William Siders
Journal: Cancer Research (2010)

Abstract CXCR4 is a chemokine receptor frequently over-expressed on hematological cancers and solid tumors. CXCR4 and its ligand SDF1α (stromal derived factor-1α or CXCL12) play an important role in cancer metastasis, regulation of stem cell trafficking and neovascularization. We have observed previously that treatment with the small molecule CXCR4 antagonists Plerixafor (AMD3100, Mozobil) and AMD3465 in combination with Campath or Rituxan had a synergistic effect resulting in a prolongation of survival greater than that obtained with either agent alone in disseminated human B-lymphoma tumor models. We next explored the mechanism of action of CXCR4 antagonists in vitro using the human B-lymphoma cell lines Ramos, Raji, B104, BL31, IM9 or Wien133 which display similarly strong levels of cell surface CXCR4 expression. All cell lines responded to SDF1α but, in spite of comparable levels of CXCR4 expression, showed varying degrees of calcium influx and cell migration when stimulated. There was a good correlation between calcium influx and migratory responses for a given cell line. Addition of the CXCR4 antagonists Plerixafor or AMD3465 inhibited both responses. The compounds did not show any direct cytotoxicity and failed to inhibit spontaneous proliferation of Ramos, Raji and B104 human B-lymphoma cell lines. However, they did inhibit SDF1α-induced proliferation of these cell lines in agreement with their ability to block CXCR4. Moreover, CXCR4 antagonists inhibited SDF1α-induced phosphorylation of multiple proteins involved in cell migration, proliferation and survival signal pathways as well as some transcription factors, including Akt, ERK1/2, JNK, p70S6, p90RSK, GSK-3a/b, Tyk2, p38, MEK1, c-Jun, STAT3 and CREB. These results suggest that the CXCR4/SDF1α axis plays an important role in the migration, proliferation and survival of human B-lymphoma cells and that disruption of these functions with CXCR4 antagonists may contribute to their observed ability to enhance the anti-tumor activity of Campath and Rituxan in human B-lymphoma models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4460.
RELATION OF B-TYPE NATRIURETIC PEPTIDE LEVELS WITH DIASTOLIC STRAIN RATE IN PATIENTS WITH HYPERTENSIVE HEART DISEASE
Authors: Imran Uraizee, Susan Cheng, Chung-Lieh Hung, Anil Verma, James Thomas, Michael Zile, Gerard Aurigemma, Scott Solomon
Journal: Journal of the American College of Cardiology (2012)
Statins and Physical Activity in Older Men
Authors: David S. H. Lee, Sheila Markwardt, Leah Goeres, Christine G. Lee, Elizabeth Eckstrom, Craig Williams, Rongwei Fu, Eric Orwoll, Peggy M. Cawthon, Marcia L. Stefanick, Dawn Mackey, Douglas C. Bauer, Carrie M. Nielson
Journal: JAMA Internal Medicine (2014)

Muscle pain, fatigue, and weakness are common adverse effects of statin medications and may decrease physical activity in older men.To determine whether statin use is associated with physical activity, longitudinally and cross-sectionally.Men participating in the Osteoporotic Fractures in Men Study (N = 5994), a multicenter prospective cohort study of community-living men 65 years and older, enrolled between March 2000 and April 2002. Follow-up was conducted through 2009.Statin use as determined by an inventory of medications (taken within the last 30 days). In cross-sectional analyses (n = 4137), statin use categories were users and nonusers. In longitudinal analyses (n = 3039), categories were prevalent users (baseline use and throughout the study), new users (initiated use during the study), and nonusers (never used).Self-reported physical activity at baseline and 2 follow-up visits using the Physical Activity Scale for the Elderly (PASE). At the third visit, an accelerometer measured metabolic equivalents (METs [kilocalories per kilogram per hour]) and minutes of moderate activity (METs ≥3.0), vigorous activity (METs ≥6.0), and sedentary behavior (METs ≤1.5).At baseline, 989 men (24%) were users and 3148 (76%) were nonusers. The adjusted difference in baseline PASE between users and nonusers was -5.8 points (95% CI, -10.9 to -0.7 points). A total of 3039 men met the inclusion criteria for longitudinal analysis: 727 (24%) prevalent users, 845 (28%) new users, and 1467 (48%) nonusers. PASE score declined by a mean (95% CI) of 2.5 (2.0 to 3.0) points per year for nonusers and 2.8 (2.1 to 3.5) points per year for prevalent users, a nonstatistical difference (0.3 [-0.5 to 1.0] points). For new users, annual PASE score declined at a faster rate than nonusers (difference of 0.9 [95% CI, 0.1 to 1.7] points). A total of 3071 men had adequate accelerometry data, 1542 (50%) were statin users. Statin users expended less METs (0.03 [95% CI, 0.02-0.04] METs less) and engaged in less moderate physical activity (5.4 [95% CI, 1.9-8.8] fewer minutes per day), less vigorous activity (0.6 [95% CI, 0.1-1.1] fewer minutes per day), and more sedentary behavior (7.6 [95% CI, 2.6-12.4] greater minutes per day).Statin use was associated with modestly lower physical activity among community-living men, even after accounting for medical history and other potentially confounding factors. The clinical significance of these findings deserves further investigation.
Health of the nation: personality disorder.
Authors: K. Norton
Journal: BMJ (1992)

from the area.Moreover, data from Soviet studies met, even when services are available.The reasons The Berlin nosology attempted to establish strict based on much larger samples' or the total popula-for this are not clear, and the issue merits further criteria for diagnosing Marfan's syndrome.'As tion' seem to have been arbitrarily dismissed.One attention.Young comments, skeletal characteristics may be of the most perturbing aspects of the published MARTIN BRIGYGS striking.We have studied families with no such summary is the elimination of the estimates of E S WILLIAMS skeletal features but with aortic dilatation and increased incidences of cancer and leukaemia Department of Public Health Medicine,
Targeted disruption of the Chop gene delays endoplasmic reticulum stress–mediated diabetes
Authors: Seiichi Oyadomari, Akio Koizumi, Kiyoshi Takeda, Tomomi Gotoh, Shizuo Akira, Eiichi Araki, Masataka Mori
Journal: Journal of Clinical Investigation (2002)

Overload of pancreatic β cells in conditions such as hyperglycemia, obesity, and long-term treatment with sulfonylureas leads to β cell exhaustion and type 2 diabetes. Because β cell mass declines under these conditions, apparently as a result of apoptosis, we speculated that overload kills β cells as a result of endoplasmic reticulum (ER) stress. The Akita mouse, which carries a conformation-altering missense mutation (Cys96Tyr) in Insulin 2, likewise exhibits hyperglycemia and a reduced β cell mass. In the development of diabetes in Akita mice, mRNAs for the ER chaperone Bip and the ER stress–associated apoptosis factor Chop were induced in the pancreas. Overexpression of the mutant insulin in mouse MIN6 β cells induced Chop expression and led to apoptosis. Targeted disruption of the Chop gene delayed the onset of diabetes in heterozygous Akita mice by 8–10 weeks. We conclude that ER overload in β cells causes ER stress and leads to apoptosis via Chop induction. Our findings suggest a new therapeutic approach for preventing the onset of diabetes by inhibiting Chop induction or by increasing chaperone capacity in the ER.
Dexamethasone and high dose metoclopramide: efficacy in controlling cisplatin induced nausea and vomiting.
Authors: S G Allan, M A Cornbleet, P S Warrington, I M Golland, R C Leonard, J N Smyth
Journal: BMJ (1984)

Nocturnal deaths among patients with chronic bronchitis and emphysema Patients with chronic bronchitis and emphysema may develop episodes of severe hypoxaemia with associated ventricular arrhythmias during sleep.' 2 We examined the possibility that such nocturnal abnormalities predispose such patients to sudden death.(42%) of 38 who did not), although the difference was not significant.
Evaluation of the BeTha Gene 1 Kit for the Qualitative Detection of the Eight Most Common Mediterranean β-Thalassemia Mutations
Authors: Luis A. Ugozzoli, J. D. Lowery, A. A. Reyes, C.-I. P. Lin, A. Re, F. Locati, R. Galanello, L. Macioni, A. Maggio, A. Giambona, A. Loutradi, M. Boussiou, R. Bruce Wallace
Journal: American Journal of Hematology (1998)

We describe the evaluation of the Bio-Rad BeTha Gene 1 kit (Bio-Rad Laboratories, Hercules, CA), a DNA-probe assay designed for the qualitative determination of the eight most common Mediteranean β-thalassemia mutations. The kit utilizes the principle of allele-specific oligonucleotide (ASO) hybridization. Following sample preparation and in vitro DNA amplification by the polymerase chain reaction (PCR), an allele-specific detection of the amplified products by a nonradioactive enzymatic assay is performed. Genomic DNA is prepared from an individual's whole blood with a DNA purification matrix. In a second step, the β-globin gene is amplified in a multiplex PCR reaction containing four 5′ biotinylated oligonucleotide primers. In a final step, an aliquot of the PCR reaction is first chemically denatured and then captured in two eight-well strips of a 96-well enzyme-linked immunosorbent assay (ELISA) plate by hybridization to an immobilized ASO probe. Each DNA sequence at each of the eight mutation sites is represented by one normal and one mutant ASO. During this capture/hybridization step, which is performed at 37°C, only perfectly matched PCR products will be captured by an ASO. Subsequently, the allele-specific captured biotin-labeled PCR products are detected by a colorimetric enzymatic reaction. The system permits the detection of 16 β-thalassemia alleles using a high-throughput format that can be automated easily. A clinical feasibility study was performed to evaluate the functionality (method camparison study, assay validity using samples previously collected and stored at various temperatures for different periods of time, interference on kit performance, and assay validity for prenatal diagnosis) and the usability (ease of use, sample throughput) of the kit. The analysis of 110 samples previously studied with reference methods showed 100% clinical sensitivity and specificity. We demonstrate here that the procedure not only increases the throughput of β-thalassemia allele genotyping but also provides an accurate, rapid, reliable, and nonisotopic diagnostic tool. Am. J. Hematol. 59:214–222, 1998. © 1998 Wiley-Liss, Inc.
Cardiac FDG-PET to Assess Sarcoidosis in a Cardiac Allograft
Authors: Andrew Chen, Pravien Khanna, Alexa Siddon, Raymond Russell
Journal: Clinical Nuclear Medicine (2013)

A 58-year-old man with end-stage heart failure caused by cardiac sarcoidosis underwent an orthotopic heart transplant. His immediate posttransplant course was uncomplicated, but several months later, an endomyocardial biopsy revealed likely recurrent sarcoidosis. A cardiac F-FDG PET study subsequently showed focal anteroseptal uptake that suggested the presence of inflammation. Despite steroid therapy, a study repeated 3 months later showed persistent anteroseptal FDG uptake and new hypokinesis in that region. After escalating his steroid therapy, a final FDG-PET study ultimately demonstrated resolution of the uptake and normalization of anteroseptal wall motion.
Are developmental disabilities the same in children and adults?
Authors: Paula Tallal
Journal: Behavioral and Brain Sciences (2002)

Thomas &amp; Karmiloff-Smith (T&amp;K-S) raise an issue of considerable theoretical importance: Are developmental disorders like cases of adult brain damage? However, a related question: Are developmental disabilities the same in children and adults? is rarely addressed. Failure to consider the cumulative and differing effects of aberrant development across the life span confounds the current literature on both developmental dyslexia and Specific Language Impairment.
Immune Aspects of Renal Diseases
Authors: Curtis B. Wilson
Journal: JAMA (1987)

ANIMAL models have long served as an introduction to understanding the possible mechanisms responsible for human immune renal injury. Exploration of these models has refined and expanded our knowledge of the ways in which nephritogenic antigen and antibody interactions can lead to phlogogenic immune deposit formation, mediator activation, and relatively nonselective damage to surrounding renal structures, thereby producing pathophysiological changes.<sup>1,2</sup>In addition, antibody reactions capable of inducing selective glomerular (or tubular) cell damage have been recently defined. Cellular immune reactions are clearly important in tubulointerstitial injury, and studies continue to define cellular immune contributions to glomerular injury. The humoral and cellular mediation pathways that magnify antibody-induced injury are increasingly defined, and the cells of the glomerulus itself are being investigated as contributors of phlogogenic mediator molecules. The elucidation of the mechanisms of human immune renal injury, unfortunately, lags behind the understanding of the experimental models of both glomerulonephritis and
A refuser's viewpoint on ‘the patient's experience of being a human subject’
Authors: Hazel Thornton
Journal: Journal of the Royal Society of Medicine (2008)

Kerrison and colleagues’ qualitative analysis of findings from focus groups, semi-structured telephone interviews and questionnaires with ‘the subjects of clinical research’ in order to ‘explore the patient's experience of clinical research with a view to improving its conduct’ produced some useful recommendations which should be noted (JRSM 2008;101:416–422).1 They also suggested that ‘opportunities should be provided for involvement in research design’. What better place than their own study to help achieve their objective of ‘improving its conduct’? Why did they not actively involve one or more of their 95 enrolled patients – out of 265 potential participants (36% response rate) – in their study and in authoring its report?

For example, had they included a patient on the writing team for this report, or invited comment from some participants, they might have begun by amending the title, so that it reflects that this is an interpretation of researchers’ findings from a small qualitative study of ‘patients’ experiences of being involved as participants in clinical research’. Plural and ‘participant’, please!

A review of active public and patient involvement would have revealed a rich seam of patients’ experiences of involvement in all stages of the research process in many disease areas. For example, one of the items on the NHS National Library for Health Patient and Public Involvement Specialist Library is an ECRI Report of 2002 that explores patients’ reasons for participating in clinical trials in some detail and provides a rich source of evidence.2 Other surveys have also been reported.3 Some patients' accounts on the DIPEx4 website include their experiences of being invited to participate in clinical research. They are developing a new module about patients' experiences of being invited to participate in clinical trials. As suggested, views of ‘refusers’ would be enlightening (and will be sought by DIPEx): not just patient refusers,5,6 but also clinicians.7
Serum complex of trypsin 2 and (alpha)(sub 1) antitrypsin as diagnostic and prognostic marker of acute pancreatitis: clinical study in consecutive patients
Authors: J. Hedstrom, V. Sainio, E. Kemppainen, R. Haapiainen, E. Kivilaakso, T. Schroder, J. Leinonen, U.-H. Stenman
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To estimate the usefulness of serum concentrations of the complex of trypsin 2 and (alpha)1 antitrypsin in diagnosing and assessing the severity of acute pancreatitis in comparison with serum C reactive protein, amylase, and trypsinogen 2 concentrations (reference markers). <b>Design</b>: Markers were measured in consecutive patients admitted with acute abdominal pain that was either due to pancreatitis or to other disease unrelated to the pancreas (controls). <b>Setting</b>: Department of surgery of a teaching hospital in Helsinki. <b>Subjects</b>: 110 patients with acute pancreatitis and 66 with acute abdominal diseases of extrapancreatic origin. On the basis of the clinical course, acute pancreatitis was classified as mild (82 patients) or severe (28 patients). <b>Main outcome measures</b>: Clinical diagnosis of acute pancreatitis and severity of the disease. <b>Results</b>: At admission all patients with acute pancreatitis had clearly raised concentrations of trypsin 2-(alpha)1 antitrypsin complex (32 μg/l), whereas only three of the controls had such values. Of the markers studied, trypsin 2-(alpha)1 antitrypsin complex had the largest area under the receiver operating curve, both in differentiating acute pancreatitis from extrapancreatic disease and in differentiating mild from severe disease. <b>Conclusions</b>: Of the markers studied, trypsin 2-(alpha)1 antitrypsin complex was the most accurate in differentiating between acute pancreatitis and extrapancreatic disease and in predicting a severe course for acute pancreatitis. <h3>Key messages</h3> This complex can be accurately measured in a sensitive immunoassay In this study the diagnostic and prognostic accuracy of serum concentrations of trypsin 2-(alpha)1 antitrypsin complex was determined in acute pancreatitis The complex was more accurate than trypsinogen 2, C reactive protein, and amylase in differentiating between acute pancreatitis and extrapancreatic disease and in predicting a severe course for the disease If the immunoassay could be automated determination of concentrations of trypsin 2-(alpha)1 antitrypsin complex could greatly improve the diagnosis of this common and potentially lethal disease
Rheumatoid Arthritis—like Deformities in an Early 16th-Century Painting of the Flemish-Dutch School
Authors: Jan Dequeker
Journal: JAMA (1992)

Hand deformities resembling those of rheumatoid arthritis have been depicted in a painting by an anonymous artist of the Flemish-Dutch School, mid-15th to early 16th century. The painting is presently in the Escorial Museum near Madrid, Spain. This observation, like other earlier observations of rheumatoid deformities in paintings of the Middle Ages, suggests that rheumatoid arthritis is not a modern disease; it had, indeed, appeared several centuries before Landré-Beauvais' description in 1800. (<i>JAMA</i>. 1992;268:249-251)
CONCEPTUAL AND COGNITIVE PSYCHIATRY
Authors: SILVANO ARIETI
Journal: American Journal of Psychiatry (1965)

Conceptual (or cognitive) psychiatry—a field which has so far been relatively neglected-is described in three of its major branches. The importance of conceptual life in the psychodynamics of the human being has been reaffirmed. Man is not motivated only by physiological needs and primitive wishes. The conceptualization of one's self, his family and the world at large may become powerful psychodynamic forces. Cognitive psychiatry studies all forms of cognition, especially thinking disorders which occur in psychiatric conditions and their relation to psychodynamic factors. Finally, conceptual psychiatry is viewed as a science which may offer levels of generalization applicable to other disciplines, such as general system theory, language and creativity.
Response to Comment on Hinnouho et al. Metabolically Healthy Obesity and Risk of Mortality: Does the Definition of Metabolic Health Matter? Diabetes Care 2013;36:2294–2300
Authors: Guy-Marino Hinnouho, Sébastien Czernichow, Archana Singh-Manoux
Journal: Diabetes Care (2014)

We thank Drs. Doehner and Pfeiffer (1) for their letter in response to our article (2) on the association of metabolically healthy obese (MHO) phenotype with mortality. We used five definitions of metabolic health to show that for most definitions of metabolic health both metabolically healthy and unhealthy obese patients carry a similar, elevated risk of mortality. Doehner and Pfeiffer do not question the validity of our findings in relation to the MHO phenotype, but suggest that overweight and obesity may not be harmful at older ages and in those with a chronic disease. They suggest that “weight management should be …
Physiologic Effects of Pressor Agents.
Authors: John W. Eckstein
Journal: Annals of Internal Medicine (1964)

s1 February 1964Physiologic Effects of Pressor Agents.John W. Eckstein, M.D. (Associate)John W. Eckstein, M.D. (Associate)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-316_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe arterial pressure depends upon the rate of blood flow into the arteries and the resistance to flow from them. Pressure may fall because of reduced cardiac output or reduced peripheral resistance, or both. It is common to attribute hypotension, regardless of the disease process, to decreased peripheral resistance and loss of arterial tone. Frequently, the reduced output is regarded as a contributing, but secondary, phenomenon caused by reduced coronary perfusion that results from the fall in aortic pressure. In reality, the low output often is a primary rather than a secondary event. A fall in cardiac output could result... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Iowa City, Iowa PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1964Volume 60, Issue 2_Part_1Page: 316-317KeywordsArteriesBlood flowBlood pressureCardiac outputFallsHypotension Issue Published: 1 February 1964 PDF downloadLoading ...