tbuckley/cabot-search huggingface dataset:
Impairment of skeletal muscle adenosine triphosphate–sensitive K+ channels in patients with hypokalemic periodic paralysis
Authors: Domenico Tricarico, Serenella Servidei, Pietro Tonali, Karin Jurkat-Rott, Diana Conte Camerino
Journal: Journal of Clinical Investigation (1999)

The adenosine triphosphate (ATP)–sensitive K+ (KATP) channel is the most abundant K+ channel active in the skeletal muscle fibers of humans and animals. In the present work, we demonstrate the involvement of the muscular KATP channel in a skeletal muscle disorder known as hypokalemic periodic paralysis (HOPP), which is caused by mutations of the dihydropyridine receptor of the Ca2+ channel. Muscle biopsies excised from three patients with HOPP carrying the R528H mutation of the dihydropyridine receptor showed a reduced sarcolemma KATP current that was not stimulated by magnesium adenosine diphosphate (MgADP; 50–100 μM) and was partially restored by cromakalim. In contrast, large KATP currents stimulated by MgADP were recorded in the healthy subjects. At channel level, an abnormal KATP channel showing several subconductance states was detected in the patients with HOPP. None of these were surveyed in the healthy subjects. Transitions of the KATP channel between subconductance states were also observed after in vitro incubation of the rat muscle with low-K+ solution. The lack of the sarcolemma KATP current observed in these patients explains the symptoms of the disease, i.e., hypokalemia, depolarization of the fibers, and possibly the paralysis following insulin administration.
Selective infection of lower respiratory tract by respiratory viruses in children with recurrent respiratory tract infections.
Authors: D Isaacs, J R Clarke, D A Tyrrell, H B Valman
Journal: BMJ (1982)

Thirty preschool children presenting with recurrent respiratory infections and their unaffected siblings were observed prospectively for a year. The index children experienced more episodes of acute respiratory infection than their siblings. Respiratory viruses were the major cause of respiratory infections. The index children had lower respiratory tract disease, predominantly wheeze, during 34% of proved respiratory virus infections compared with 11% of such infections experienced by the control children (p less than 0.02). Atopic children had an increased tendency to wheeze that did not reach significance, but atopy was not associated with increased susceptibility to respiratory infections.
Directed Engineering of a High-expression Chimeric Transgene as a Strategy for Gene Therapy of Hemophilia A
Authors: Christopher B Doering, Gabriela Denning, Kerry Dooriss, Bagirath Gangadharan, Jennifer M Johnston, Keith W Kerstann, David A McCarty, H Trent Spencer
Journal: Molecular Therapy (2009)

Human coagulation factor VIII (fVIII) is inefficiently biosynthesized in vitro and has proven difficult to express at therapeutic levels using available clinical gene-transfer technologies. Recently, we showed that a porcine and certain hybrid human/porcine fVIII transgenes demonstrate up to 100-fold greater expression than human fVIII. In this study, we extend these results to describe the use of a humanized, high-expression, hybrid human/porcine fVIII transgene that is 89% identical to human fVIII and was delivered by lentiviral vectors (LVs) to hematopoietic stem cells for gene therapy of hemophilia A. Recombinant human immunodeficiency virus-based vectors encoding the fVIII chimera efficiently transduced human embryonic kidney (HEK)-293T cells. Cells transduced with hybrid human/porcine fVIII encoding vectors expressed fVIII at levels 6- to 100-fold greater than cells transduced with vectors encoding human fVIII. Transplantation of transduced hematopoietic stem and progenitor cells into hemophilia A mice resulted in long-term fVIII expression at therapeutic levels despite <5% genetically modified blood mononuclear cells. Furthermore, the simian immunodeficiency virus (SIV) -derived vector effectively transduced the human hematopoietic cell lines K562, EU1, U.937, and Jurkat as well as the nonhematopoietic cell lines, HEK-293T and HeLa. All cell lines expressed hybrid human/porcine fVIII, albeit at varying levels with the K562 cells expressing the highest level of the hematopoietic cell lines. From these studies, we conclude that humanized high-expression hybrid fVIII transgenes can be utilized in gene therapy applications for hemophilia A to significantly increase fVIII expression levels compared to what has been previously achieved.
Abstract 2649: Cost-Effectiveness Analysis Of Implantable Loop Recorder In The Diagnostic Management Of Patients With Unexplained Palpitations
Authors: Franco Giada, Michele Gulizia, Maura Francese, Francesco Croci, Lucio Santangelo, Maurizio Santomauro, Eraldo Occhetta, Carlo Menozzi, Antonio Raviele
Journal: Circulation (2007)
Corrigendum to “Inadvertent Germline Transmission of AAV2 Vector: Findings in a Rabbit Model Correlate with Those in a Human Clinical Trial”
Authors: Joerg Schuettrumpf, Jian-Hua Liu, Linda B. Couto, Kathakaly Addya, Debra G.B. Leonard, Zhu Zhen, Jürg Sommer, Valder R. Arruda
Journal: Molecular Therapy (2006)

The name of Jurg Sommer was incorrectly listed as Jurg Summer in the author line. The correct author line appears above.
Information for patients: removal of lice and eggs by combing
Authors: Z. Kmietowicz
Journal: BMJ (2003)

Little research has been done into whether combing helps to get rid of head lice, so it's difficult to say whether it works. Success seems to depend on how committed you are to carrying out this treatment.

Combing wet hair with a special comb is called “bug busting” or “wet combing.” You use …
Quality of Life Research: An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation
Authors: Dawn Bick
Journal: JAMA (1994)

The editors, in their inaugural issue, state their principal objectives to be "the exchange of ideas and the rapid communication of research findings in this multi-disciplinary field of inquiry." Quality of life research measures health impairments, functional health status, and health perceptions, as opposed to objective clinical states or mere survival. The editors' objectives are well achieved in the first seven issues. Traditional research articles facilitate the exchange of ideas, an example being one on the use of patient reports to assess health-related quality of life after hip replacement. Formats for examining various issues included a review article on generic health-related quality of life measures for human immunodeficiency virus research, a conference report on quality of life after open heart surgery, book reviews, and special issue articles. The editorial board and authors are not only multidisciplinary but hold a broad range of affiliations in academia, research institutions, and clinical settings,
Spinal Cerebrospinal Fluid Leak Demonstrated by Radioisotopic Cisternography
Authors: MARIE PRIMEAU, LUCIE CARRIER, PIERRE C. MILETTE, RAYMONDE CHARTRAND, DANIEL PICARD, MICHEL PICARD
Journal: Clinical Nuclear Medicine (1988)

Many conditions are known to cause a cerebrospinal fluid (CSF) fistula; one of them is lumbar puncture for contrast myelography. Reported here is the case of a man who underwent contrast myelography at the L2-L3 level and who presented with postural headaches and lumbalgia with radiation to the legs three weeks after the procedure. Tc-99m albumin isotopic cisternography at the L5-S1 level was performed and clearly depicted a functional CSF leak through the dura at the L2-L3 level and CSF suffusion along several rachidian roots. Scinticisternography may thus be used to localize accurately a CSF leak.
P49 Can The Asthma Control Questionnaire (acq) And/or The Blood Eosinophil Count Accurately Detect Sputum Eosinophilia?
Authors: J. Anderson, D. Hodgson, E. Wilson, T. Harrison, D. Shaw
Journal: Thorax (2014)

<h3></h3> Induced sputum differential cell counts provide important information about airway inflammation and future risk in asthma, but are not universally available. We set out to ascertain the sensitivity and specificity of the Juniper Asthma Control Questionnaire (ACQ) and/or the peripheral blood eosinophil count to detect a sputum eosinophil count &gt;3%. <h3>Methods</h3> We performed a retrospective, cross-sectional study of 165 subjects with asthma, aged 18–80, prescribed as-required bronchodilators, long-acting β-agonists, 0–4000 mcg inhaled beclometasone diproprionate equivalent or maintenance oral steroids (0–20 mg prednisolone) from our database. Current smokers were excluded. Spirometry, FeNO at 50 ml flow, sputum induction, Asthma Control Questionnaire (ACQ) and blood eosinophils (BEos) were recorded. Induced sputum eosinophils (SEos) defined eosinophilic (EA, SEos ≥3%) and non-eosinophilic (NEA, SEos &lt;3%) groups. BEos, SEos and FeNO were log<sub>10</sub>transformed and groups were compared with t-tests or Mann-Whitney-U using STATA and GraphPad. Receiver operating characteristic (ROC) curves determined cut-points of ACQ and BEos that identified SEos ≥3%, and these were tested retrospectively in a second population of adults with asthma (n = 48, 40% EA, mean FEV<sub>1</sub> 82% predicted). <h3>Results</h3> The 31% with EA had a lower FEV<sub>1</sub>% predicted and FEV<sub>1</sub>/FVC ratio, a higher FeNO, BEos and ACQ compared to NEA (Table 1). There was a significant correlation between ACQ and sputum eosinophils (Pearson r 0.32, p &lt; 0.0001). The optimal cut-points of ACQ and BEos identifying a SEos of 3% were an ACQ &gt;1.57 (sensitivity 55%, specificity 78%) and BEos ≥0.22 × 10<sup>9</sup>/L (sensitivity 84% and specificity 68%) respectively. Individuals with both ACQ of ≥1.57 AND a BEos of ≥0.22 the sensitivity was 45% and specificity of 100% for a SEos of 3%. Testing in the second population the ACQ≥1.57 had a sensitivity 47% and specificity 86% for SEos &gt;3% while BEos ≥0.22 had sensitivity 68% and specificity 45%. The combination of ACQ ≥1.57 AND BEos ≥0.22 had a lower sensitivity of 37% but a high specificity of 93% and could be useful to exclude rather than identify the presence of sputum eosinophilia. <h3>Conclusion</h3> Combined testing using ACQ and BEos only identifies eosinophilia in 37% and can’t replace induced sputum, but may be useful to exclude sputum eosinophilia and prospective study is warranted.
Genetic resistance to the induction of experimental allergic encephalomyelitis in Lewis rats. I. Genetic analysis of an apparent mutant strain with phenotypic resistance to experimental allergic encephalomyelitis.
Authors: F J Waxman, L E Perryman, D J Hinrichs, J E Coe
Journal: The Journal of Experimental Medicine (1981)

Clinical resistance to the induction of experimental allergic encephalomyelitis was observed in a closed colony of Lewis (designated Le-R) rats. Disease susceptibility in randomly bred animals appeared to increase with increasing age. In the small group of young Le-R rats, which were susceptible, disease onset was delayed, severity of symptoms was reduced, and duration of clinical signs was abbreviated compared to conventional Lewis rats. The severity of histologic neural tissue lesions correlated with clinical observations. Breeding experiments indicated that most Le-R rats were resistant to disease induction regardless of whether their ancestors had been selected for susceptibility or resistance. The F3 generation of resistant lineage was uniformly resistant at all ages tested. Virtually all (Lewis X Le-R)F1 rats of either sex were resistant when challenged at 7-8 wk of age indicating that resistance was a dominant autosomal trait. Approximately half of (F1 X Lewis) backcross rats developed paralytic EAE whereas one-fourth were entirely resistant, suggesting that disease resistance may be mediated by one or two genes. Le-R rats shared at least some of the Lewis rat major histocompatibility antigens. Resistance apparently did not reflect a nonspecific impairment of cellular immune responsiveness. Le-R rats, which had been challenged with myelin basic protein, developed antigen-reactive cells specific for basic protein or its encephalitogenic fragment. Spleen cells obtained from basic protein-sensitized Le-R rats did not adoptively transfer disease into Lewis rats. In contrast, spleen cells obtained from basic protein-sensitized Lewis rats readily transferred disease into both Lewis and Le-R recipients. These data suggest that disease resistance may be a result of an immunologic deficit (or suppressor cell activity) expressed during the differentiation of antigen-reactive cells into disease-inducing effector cells.
Interleukin 2: Author's Reply
Authors: T J Hamblin
Journal: BMJ (1990)

argues in his editorial that interleukin 2 has emerged as a treatment capable of inducing complete responses in patients with cancers that were previously thought to be unresponsive to treatment.'He cites as examples malignant melanoma and renal cell cancer.The assertion that malignant melanoma is unresponsive to conventional chemotherapy is unfounded and misleading.Data were presented last year on response to treatment according to the International Union against Cancer criteria and survival of patients with surgically incurable metastatic melanoma who were treated between June 1977 and June 1989 at Westminster Hospital with four consecutive chemotherapy protocols that were developed in this unit (S Retsas, second international conference on melanoma, Venice, 1989).The table summarises the updated information on 350 patients in this study.
THU0003 Fine-mapping of autoimmune susceptibility LOCI using immunochip identifies novel susceptibility LOCI for psoriatic arthritis
Authors: J. Bowes, P. Ho, E. Korendowych, N. McHugh, J. Packham, I.N. Bruce, A. Barton
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Psoriatic arthritis (PsA) is a chronic inflammatory joint disease that typically accompanies psoriasis vulagris (PsV). Both conditions are considered to be complex diseases with both genetic and environmental susceptibility factors. Genome-wide association studies (GWAS) have identified a number of genetic susceptibility loci for both diseases. Comparing GWAS results performed in many common autoimmune diseases has revealed an extensive overlap in the genetic liability between autoimmune diseases in general. <h3>Objectives</h3> Based on the observed sharing of susceptibility loci across autoimmune diseases, the aim of this project is to identify novel susceptibility loci for PsA by fine-mapping all the currently confirmed susceptibility loci for 12 autoimmune diseases. <h3>Methods</h3> Data was available for 929 PsA cases and 4537 healthy controls genotyped using the Immunochip Illumina iSelect array at the Sanger Centre (www.sanger.ac.uk). Control data was sourced from the WTCCC (www.wtccc.org.uk). This custom array was designed to comprehensively fine-map confirmed autoimmune susceptibility loci and contains 196,524 SNPs covering approximately 200 candidate regions. A strict SNP-focused quality control process was applied to the dataset followed by single point analysis using the Armitage test for trend. <h3>Results</h3> Association analysis of 182,883 high quality SNPs in 862 cases and 4306 controls robustly detected association to previously confirmed PsA risk loci; <i>HLA-C</i> (p=8.2×10<sup>-35</sup>), <i>IL23R</i> (p=8.4×10<sup>-8</sup>) and <i>TRAF3IP2</i> (p=2.8×10<sup>-7</sup>), <i>IL12B</i> (p=6.5×10<sup>-6</sup>). In addition we find convincing evidence to support association to a number of novel loci not previously reported for PsA, including; 17q21 (p<sub>trend</sub> =3.3×10<sup>-05</sup>, <i>SMARCE1)</i>, 18p11 (p<sub>trend</sub> =2.0×10<sup>-05</sup>, <i>PTPN2)</i>, 11q23 (p<sub>trend</sub> =1.4×10<sup>-05</sup>, <i>TREH)</i>, and 19p13 (p<sub>trend</sub> =9.8×10<sup>-05</sup>, <i>TYK2)</i>. Interestingly, we also find convincing evidence for association to the <i>CARD15</i> gene, supported by multiple SNPs. <h3>Conclusions</h3> The preliminary single point analysis of an autoimmune loci fine-mapping dataset identifies a number of potential novel loci for PsA susceptibility. Validation of these results is currently underway in an independent sample collection. Single-point analysis will be followed by analyses to indentify independent effects within the previously identified and newly discovered loci. <h3>Disclosure of Interest</h3> None Declared
Fetal Hemoglobin and the Glycosylated Hemoglobin Assay
Authors: David M. Grossman
Journal: Annals of Internal Medicine (1994)

Letters15 March 1994Fetal Hemoglobin and the Glycosylated Hemoglobin AssayDavid M. Grossman, MD, Gregory A. Doyle, MD, and Robert D. Hoeldtke, MD, PhDDavid M. Grossman, MDWest Virginia University School of Medicine; Morgantown, WV 26506, Gregory A. Doyle, MDWest Virginia University School of Medicine; Morgantown, WV 26506, and Robert D. Hoeldtke, MD, PhDWest Virginia University School of Medicine; Morgantown, WV 26506Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-6-199403150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We describe a 71-year-old woman with type II diabetes who had discordant indices of glycemic control. Over a 3-month period, her preprandial plasma glucose concentrations varied between 48 and 127 mg/dL, with a mean of 89 mg/dL. Her glycosylated hemoglobin values, however, were 13.9%, 15.0%, and 16.9%, respectively. Her plasma fructosamine was 267 µmol/L (normal range, 174 to 2861 µmol/L).Because of this discrepancy, we did a standard hemoglobin electrophoresis that showed a markedly elevated fetal hemoglobin level (9.5%). The patient was not anemic and had a normal mean corpuscular volume without microcytosis.Persistent elevation of fetal ...References1. Mullis P, Schuler J, Zuppinger K. Increased prevalence of fetal hemoglobin in type I (insulin-dependent) diabetes mellitus. Diabetologia. 1989; 32:227-30. Google Scholar2. Thivolet C, Goujon R, Vassy V, Revol A, Tourniaire J. Interference of elevated fetal hemoglobin on HbA1c measurements in adult type I diabetic patients (Letter). Diabetes Care. 1991; 14:1108. Google Scholar3. Allen KR, Hamilton AD, Bodansky HJ, Poon P. Prevalence of haemoglobin variants in a diabetic population and their effect on glycated haemoglobin measurement. Ann Clin Biochem. 1992; 29:426-9. Google Scholar4. Lahtela JT, Koskinen L, Koivula T. Elevated fetal hemoglobin among diabetic patients. Abstract 64. American Diabetes Association 53rd Annual Meeting; 13 June 1993. Google Scholar5. Johnson RN, Metcalf PA, Baker JR. Fructosamine: a new approach to the estimation of serum glycosylprotein. An index of diabetic control. Clin Chimica Acta. 1982; 127:87-95. Google Scholar Author, Article, and Disclosure InformationAffiliations: West Virginia University School of Medicine; Morgantown, WV 26506 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 March 1994Volume 120, Issue 6Page: 524KeywordsAttentionBlood plasmaChromatographyGlucoseHemoglobinMean corpuscular volumePlasma proteinsType 2 diabetes Issue Published: 15 March 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Computed tomography for localization and sizing of experimental acute myocardial infarcts.
Authors: W R Gray, L M Buja, H K Hagler, R W Parkey, J T Willerson
Journal: Circulation (1978)

Computed tomography (CT) has been used to quantitate acute myocardial infarct size in isolated, arrested canine hearts. Acute myocardial infarcts were produced in 20 hearts by either left anterior descending (13 dogs) or circumflex coronary artery ligation (seven dogs). Each animal was given iodinated contrast media intravenously immediately before sacrifice 24--72 hours postinfarction. All infarcts greater than 1 g and one of three infarcts 0.5 g or less were detected by CT imaging. Infarct volume determined by CT correlated with gross infarct weight (r=0.83). CT imaging, however, consistently underestimated infarct volume; underestimation was largest in a group of patchy, predominantly subendocardial infarcts. As adequate equipment and techniques for in vivo studies are developed, CT imaging of the heart may become important in clinical evaluation of myocardial infarction.
Cost Containment and Quality Care-Reply
Authors: Eugene V. Boisaubin
Journal: JAMA (1988)

<h3>In Reply.</h3> —Dr Carlen raises important questions that are pertinent to the practitioner and the dilemma of cost containment. It is conceptually easier to reallocate funds for large groups than to deny care to an individual patient. Three observations, however, are germane. First, there is good evidence that American physicians can practice both excellent and cost-effective medicine. Many recent, well-done studies have shown that "routine" tests, such as the admission chest roentgenogram, may be reduced or eliminated without detriment to the patient, and yet with substantial savings. This procedure alone was performed more than 30 million times in 1980, with $1.5 billion in charges to the consumer.<sup>1</sup> Second, as these studies become aggregate and accepted by professional groups, they help modify existing or create new standards of care. The courts not only consider but welcome standards of practice that are supported by professional groups such as the American Medical
Laryngectomee Tracheostomee Communication
Authors: C. DuWayne Schmidt
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Communication with a patient who is intubated or who has a tracheostomy and is receiving ventilatory support is difficult. Even alert patients find writing cumbersome; emotions are best conveyed by speaking. We have found the artificial larynx to be helpful in restoring spoken communication to many tracheostomy patients. This device, originally designed for laryngectomy patients, has proven effective and practical except when an oral endotracheal tube exists (Figures). Successful use of the artificial larynx requires coordination with patient mouth movement as well as proper placement on the neck. Although the technique cannot be used in all patients, its further application in intensive care units can be helpful.
Insulin resistance: A metabolic pathway to chronic liver disease
Authors: Elisabetta Bugianesi, Arthur J. McCullough, Giulio Marchesini
Journal: Hepatology (2005)

Insulin resistance (IR) is the pathophysiological hallmark of nonalcoholic fatty liver disease (NAFLD), one of the most common causes of chronic liver disease in Western countries. We review the definition of IR, the methods for the quantitative assessment of insulin action, the pathophysiology of IR, and the role of IR in the pathogenesis of chronic liver disease. Increased free fatty acid flux from adipose tissue to nonadipose organs, a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and in the liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a proinflammatory state, which may be limited to the liver or more extensively expressed throughout the body. IR is the common characteristic of the metabolic syndrome and its related features. It is a systemic disease affecting the nervous system, muscles, pancreas, kidney, heart, and immune system, in addition to the liver. A complex interaction between genes and the environment favors or enhances IR and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic liver disease is associated with multiple features of the metabolic syndrome, and the risk of progressive liver disease should not be underestimated in individuals with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the liver (metformin) and in the periphery (thiazolidinediones) are discussed.