tbuckley/cabot-search huggingface dataset:
A Molecular Mechanism for Adrenergic-Induced Long QT Syndrome
Authors: Jie Wu, Nobu Naiki, Wei-Guang Ding, Seiko Ohno, Koichi Kato, Wei-Jin Zang, Brian P. Delisle, Hiroshi Matsuura, Minoru Horie
Journal: Journal of the American College of Cardiology (2013)
Principles of Pediatric Fluid Therapy
Authors: Barbara Kirschner
Journal: JAMA (1983)

This short descriptive text discusses theories of fluid and acid-base homeostasis in basic terms for students, house staff, and clinicians. Each of the first three sections ("Disorders of Hydration," "Acid-Base Disorders," and "Disorders of Potassium Metabolism") provides an ample background in physiological principles to make these topics understandable to the reader. For example, the section on hydration reviews water and electrolyte flux between the extracellular, intracellular, and interstitial compartments. This information is subsequently used to instruct the reader in assessing the severity, type (isotonic, hypertonic, or hypotonic), and management of dehydration in children. The chapter on acid-base disorders contains extensive descriptions of metabolic and respiratory acidosis and alkalosis, emphasizing the clinical situations that are associated with these disorders. The importance of renal and pulmonary compensatory and corrective mechanisms is discussed. The final two chapters are entitled "Fluid Therapy" and "Parenteral Nutrition in the Pediatric Patient." The former chapter is comprehensive
A hitch-hiker's guide to the galaxy of adrenoceptors.
Authors: G M Lees
Journal: BMJ (1981)

The characteristic effects of activity of the sympathetic nervous system result from the action of the catecholamines noradrenaline and adrenaline on specialised components of cells called adrenoceptors (less correctly adrenergic receptors).Virtually every tissue has a noradrenergic innervation and is exposed to circulating adrenaline and noradrenaline, which evoke a wide variety of responses (table I).TABLE I-Responses mediated by adrenoceptors Cell, organ, or system Adrenoceptor affected type
Diffusible Serum Calcium
Authors: Edward A. Hanna
Journal: JAMA (1970)

<h3>To the Editor.—</h3> In a patient with proven hyperparathyroidism, who demonstrated normocalcemia for a 12-month period (<b>210</b>:2063, 1969), repeated total serum calcium values were within the normal range of the reporting laboratory: 8.8 to 11.0 per 100 ml. Though hypercalcemia is considered to be the most constant finding in primary hyperparathyroidism, a few cases have been reported showing a normal serum calcium level. In 1935, McLean and Hastings suggested that ionized serum calcium value increases in hyperparathyroidism. Subsequent reports have indicated that ionized serum calcium level is elevated in cases of primary hyperparathyroidism even though the total serum calcium level may be normal. Ionized serum calcium level can be determined by biological techniques. When it is estimated from the nomogram described by McLean and Hastings, however, 14 out of 35 patients with proven primary hyperparathyroidism had ionized calcium levels within the normal range. Total serum calcium is a composite
Reduced Intravascular Infection by Antibiotic Bonding-Reply
Authors: Michael A. Pfaller
Journal: JAMA (1991)

<h3>In Reply.</h3> —Dr Baltimore brings up an issue that needs to be addressed, namely, standardized definitions for catheterrelated infectious complications. Since there is currently no consensus in the literature,<sup>1</sup>investigators are obligated to state clearly the scope and meaning of definitions used by them, as we have done. Whether it is the patient, organ(s) of a patient, or prosthetic devices that get infected is an interesting point of semantics. Our reference to "infected catheter" was in the same vein as a surgeon who takes a patient to the operating room to remove an "infected graft." Baltimore rightly points out that by our definition there was no catheter-related bloodstream infection in our study. As suggested by Maki et al,<sup>2</sup>15 or more colonies represent the precursor of catheter-related septicemia. As such, we believe that a mean colony count of 252 colony-forming units per catheter has obvious significance. Dr Solomon
Misdiagnosis of diabetic ketoacidosis as hyperventilation syndrome.
Authors: R A Treasure, P B Fowler, H T Millington, P H Wise
Journal: BMJ (1987)

Air hunger" is a classical symptom ofdiabetic ketoacidosis and was originally described by Kussmaul in 1874.1 We report three cases in which breathlessness and panic symptoms were the main presenting complaints in ketoacidosis.In all three cases an incorrect diagnosis of hyperventilation syndrome was made initially with a consequent and serious delay in the diagnosis ofdiabetes.So far as we know this is the first report of this diagnosiic error, which may be more 'frequent than is currently appreciated. Case reportsCase I-A 52 year old woman presented to the accident and emergency department with a three day history of panic attacks, palpitations, and breathlessness.In the past she had been treated for depression.Hysterical hyperventilation was diagnosed and diazepam prescribed and she was referred to a psychiatrist.Three days later she returned.In addition to her original symptoms she complained of weight loss, polyuria, and dysuria.Laboratory investigations showed a blood glucose concentration of 32-6 mmol/l and an arterial pH of 7-2.She was treated for diabetic ketoacidosis and recovered uneventfully.She continued with insulin injections and had no further "panic attacks."Case 2-A 24 year old woman attended the accident and emergency department complaining of breathlessness, faintness, and weight loss.She' had recently been suffering from depression and had attended another hospital the previous day, where she had been referred to a psychiatrist.On this occasion hysterical hyperventilation was diagnosed.She was made to rebreathe exhaled air and given an outpatient psychiatric appointment.Two days later she returned.She was semiconscious, dehydrated, and hypo- tensive.Laboratory investigations showed a blood glucose concentration of 58 mmol/l and an arterial pH of 6-99.Diabetic ketoacidosis was diagnosed and appropriate treatment instituted.She recovered and left hospital taking insulin.She remained well.Case 3-A 34 year old woman presented complaining of an infected leg wound and breathlessness.The diagnosis was an infected catbite and hysterical hyperventilation and she was prescribed diazepam and antibiotics.Two days later she was brought to the department unconscious.An infected wound to the right thigh was noted and she was hypotensive and hypothermic.Results of laboratory investigations were: blood glucose concentration 45 mmol/l, arterial pH 6-75, serum sodium concentration 128 mmol/l, blood urea concentration 27 2 mmol/l, and potassium concentration 6-8 mmol/l.A diagnosis of diabetic ketoacidosis with possible septicaemia and a groin abscess was made.She was treated with intravenous fluids, insulin, and antibiotics and the abscess drained.Dialysis was required for three days for acute renal failure.She recovered and remained well taking insulin injections.
On Pulmonary Emphysema as a cause of Death
Authors: R. T. Hunt
Journal: BMJ (1842)

the remarks now offered, I have nlot alluded to other questions involved in the comparative merits of flap and circular amputations, such as the mortality after each, tlle chance of secondary halnorrhage, of union by the first intention, &c.These I shall consider at another time.In coniclusion, Genltlemeni, should you decid6 on giviiia preference to the flap operation, when in after years you may be called on in practice to make the decisioni, I can safely recommend to youl its per- formance in the way I lhave described.PULMONARY EMPHYSEMIA AS A CAUSE OF DEATH.
X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus.
Authors: J A Towbin, J F Hejtmancik, P Brink, B Gelb, X M Zhu, J S Chamberlain, E R McCabe, M Swift
Journal: Circulation (1993)

BACKGROUND X-linked cardiomyopathy (XLCM) is a rapidly progressive primary myocardial disorder presenting in teenage males as congestive heart failure. Manifesting female carriers have later onset (fifth decade) and slower progression. The purpose of this study was to localize the XLCM gene locus in two families using molecular genetic techniques. METHODS AND RESULTS Linkage analysis using 60 X-chromosome-specific DNA markers was performed in a previously reported large XLCM pedigree and a smaller new pedigree. Two-point and multipoint linkage was calculated using the LINKAGE computer program package. Deletion analysis included multiplex polymerase chain reaction (PCR). Dystrophin protein was evaluated by Western blotting with N-terminal and C-terminal dystrophin antibody. Linkage of XLCM to the centromeric portion of the dystrophin or Duchenne muscular dystrophy (DMD) locus at Xp21 was demonstrated with combined maximum logarithm of the scores of +4.33, theta = 0 with probe XJ1.1 (DXS206) using two-point linkage and +4.81 at XJ1.1 with multipoint linkage analysis. LOD scores calculated using other proximal DMD genomic and cDNA probes and polymerase chain reaction polymorphisms supported linkage. No deletions were observed. Abnormalities of cardiac dystrophin were shown by Western blotting with N-terminal dystrophin antibody, whereas skeletal muscle dystrophin was normal, suggesting primary involvement of the DMD gene with preferential involvement of cardiac muscle. CONCLUSIONS XLCM is due to an abnormality within the centromeric half of the dystrophin genomic region in heart. This abnormality could be due to 1) a point mutation in the 5' region of the DMD coding sequence preferentially affecting cardiac function, 2) a cardiac-specific promoter mutation that alters expression in this tissue, 3) splicing abnormalities, resulting in an abnormal cardiac protein, or 4) deletion mutations undetectable by Southern and multiplex polymerase chain reaction analysis.
Activation of Protein Kinase G Increases the Expression of p21CIP1, p27KIP1, and Histidine Triad Protein 1 through Sp1
Authors: Bo Cen, Atsuko Deguchi, I. Bernard Weinstein
Journal: Cancer Research (2008)

Abstract The anticancer role of cyclic guanosine 3′,5′-monophosphate (cGMP)–dependent protein kinase G (PKG) has become of considerable interest, but the underlying mechanisms are not fully established. In this study, we examined the effects of activation of PKG on the expression of three tumor suppressor proteins in human SW480 colon cancer cells. Our results revealed that treatment with cell permeable cGMP derivatives, or the cGMP phosphodiesterase inhibitor sulindac sulfone (exisulind, aptosyn, hereafter called exisulind) led to increased expression of the tumor suppressor proteins p21CIP1, p27KIP1, and Histidine triad protein 1 (HINT1), and their corresponding mRNAs. Overexpression of PKG Iβ also caused increased expression of the p21CIP1, p27KIP1, and HINT1 proteins. Both the p21CIP1 and p27KIP1 promoters contain Sp1 binding sites and they were activated by PKG in luciferase reporter assays. Specific Sp1 sites in the p21 and p27 promoters were sufficient to mediate PKG-induced luciferase reporter activity, suggesting an interaction between Sp1 and PKG. Indeed, we found that PKG can phosphorylate Sp1 on serine residue(s) and this resulted in transcriptional activation of Sp1. Knockdown of Sp1 expression with siRNA inhibited the increased expression of p21CIP1, p27KIP1, and HINT1 induced by the cGMP derivative 8-pCPT-cGMP in SW480 cells. These novel effects of PKG activation on the expression of three tumor suppressor genes may explain, at least in part, the anticancer effects of activation of PKG. They also provide a rationale for further developing activators of PKG for the prevention and treatment of cancer. [Cancer Res 2008;68(13):5355–62]
Low-Dose Inhaled Nitric Oxide in Patients With Acute Lung Injury&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Robert W. Taylor
Journal: JAMA (2004)

Inhaled nitric oxide has been shown to improve oxygenation in acute lung injury.To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric oxide in patients with acute lung injury.Multicenter, randomized, placebo-controlled study, with blinding of patients, caregivers, data collectors, assessors of outcomes, and data analysts (triple blind), conducted in the intensive care units of 46 hospitals in the United States. Patients were enrolled between March 1996 and September 1999.Patients (n = 385) with moderately severe acute lung injury, a modification of the American-European Consensus Conference definition of acute respiratory distress syndrome (ARDS) using a ratio of PaO2 to FiO2 of < or =250, were enrolled if the onset was within 72 hours of randomization, sepsis was not the cause of the lung injury, and the patient had no significant nonpulmonary organ system dysfunction at randomization.Patients were randomly assigned to placebo (nitrogen gas) or inhaled nitric oxide at 5 ppm until 28 days, discontinuation of assisted breathing, or death.The primary end point was days alive and off assisted breathing. Secondary outcomes included mortality, days alive and meeting oxygenation criteria for extubation, and days patients were alive following a successful unassisted ventilation test.An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not increase the number of days patients were alive and off assisted breathing (mean [SD], 10.6 [9.8] days in the placebo group and 10.7 [9.7] days in the inhaled nitric oxide group; P =.97; difference, -0.1 day [95% confidence interval, -2.0 to 1.9 days]). This lack of effect on clinical outcomes was seen despite a statistically significant increase in PaO2 that resolved by 48 hours. Mortality was similar between groups (20% placebo vs 23% nitric oxide; P =.54). Days patients were alive following a successful 2-hour unassisted ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8) for nitric oxide patients (P =.54). Days alive and meeting criteria for extubation were also similar: 17.0 placebo vs 16.7 nitric oxide (P =.89).Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung injury not due to sepsis and without evidence of nonpulmonary organ system dysfunction results in short-term oxygenation improvements but has no substantial impact on the duration of ventilatory support or mortality.
Does This Child Have Appendicitis?
Authors: David G. Bundy, Julie S. Byerley, E. Allen Liles, Eliana M. Perrin, Jessica Katznelson, Henry E. Rice
Journal: JAMA (2007)

Evaluation of abdominal pain in children can be difficult. Rapid, accurate diagnosis of appendicitis in children reduces the morbidity of this common cause of pediatric abdominal pain. Clinical evaluation may help identify (1) which children with abdominal pain and a likely diagnosis of appendicitis should undergo immediate surgical consultation for potential appendectomy and (2) which children with equivocal presentations of appendicitis should undergo further diagnostic evaluation.To systematically assess the precision and accuracy of symptoms, signs, and basic laboratory test results for evaluating children with possible appendicitis.We searched English-language articles in MEDLINE (January 1966-March 2007) and the Cochrane Database, as well as physical examination textbooks and bibliographies of retrieved articles, yielding 2521 potentially relevant articles.Studies were included if they (1) provided primary data on children aged 18 years or younger in whom the diagnosis of appendicitis was considered; (2) presented medical history data, physical examination findings, or basic laboratory data; and (3) confirmed or excluded appendicitis by surgical pathologic findings, clinical observation, or follow-up. Of 256 full-text articles examined, 42 met inclusion criteria.Twenty-five of 42 studies were assigned a quality level of 3 or better. Data from these studies were independently extracted by 2 reviewers.In children with abdominal pain, fever was the single most useful sign associated with appendicitis; a fever increases the likelihood of appendicitis (likelihood ratio [LR], 3.4; 95% confidence interval [CI], 2.4-4.8) and conversely, its absence decreases the chance of appendicitis (LR, 0.32; 95% CI, 0.16-0.64). In select groups of children, in whom the diagnosis of appendicitis is suspected and evaluation undertaken, rebound tenderness triples the odds of appendicitis (summary LR, 3.0; 95% CI, 2.3-3.9), while its absence reduces the likelihood (summary LR, 0.28; 95% CI, 0.14-0.55). Midabdominal pain migrating to the right lower quadrant (LR range, 1.9-3.1) increases the risk of appendicitis more than right lower quadrant pain itself (summary LR, 1.2; 95% CI, 1.0-1.5). A white blood cell count of less than 10,000/microL decreases the likelihood of appendicitis (summary LR, 0.22; 95% CI, 0.17-0.30), as does an absolute neutrophil count of 6750/microL or lower (LR, 0.06; 95% CI, 0.03-0.16). Symptoms and signs are most useful in combination, particularly for identifying children who do not require further evaluation or intervention.Although the clinical examination does not establish a diagnosis of appendicitis with certainty, it is useful in determining which children with abdominal pain warrant immediate surgical evaluation for consideration of appendectomy and which children may warrant further diagnostic evaluation. More child-specific, age-stratified data are needed to improve the utility of the clinical examination for diagnosing appendicitis in children.
An experimental model of chronic cardiac failure using adriamycin in the rabbit: central haemodynamics and regional blood flow
Authors: R. B WANLESS, I. S ANAND, P. A POOLE-WILSON, P. HARRIS
Journal: Cardiovascular Research (1987)

Journal Article An experimental model of chronic cardiac failure using adriamycin in the rabbit: central haemodynamics and regional blood flow Get access RICHARD B WANLESS, RICHARD B WANLESS From the Department of Cardiac Medicine, Cardiothoracic Institute, London Address for correspondence and reprints: Dr R B Wanless, Department of Cardiac Medicine, Cardiothoracic Institute, 2 Beaumont Street, London W1N 2DX. Search for other works by this author on: Oxford Academic PubMed Google Scholar INDERJIT S ANAND, INDERJIT S ANAND From the Department of Cardiac Medicine, Cardiothoracic Institute, London Search for other works by this author on: Oxford Academic PubMed Google Scholar PHILIP A POOLE-WILSON, PHILIP A POOLE-WILSON From the Department of Cardiac Medicine, Cardiothoracic Institute, London Search for other works by this author on: Oxford Academic PubMed Google Scholar PETER HARRIS PETER HARRIS From the Department of Cardiac Medicine, Cardiothoracic Institute, London Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 21, Issue 1, January 1987, Pages 7–13, https://doi.org/10.1093/cvr/21.1.7 Published: 01 January 1987 Article history Received: 29 April 1986 Accepted: 07 July 1986 Published: 01 January 1987
L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy
Authors: Gavin Y Oudit, Hui Sun, Maria G Trivieri, Sheryl E Koch, Fayez Dawood, Cameron Ackerley, Mehrdad Yazdanpanah, Greg J Wilson, Arnold Schwartz, Peter P Liu, Peter H Backx
Journal: Nature Medicine (2003)
Instilling Professionalism in Medical Education
Authors: Kenneth M. Ludmerer
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Ataxia, Dementia, and Hypogonadotropism Caused by Disordered Ubiquitination
Authors: David H. Margolin, Maria Kousi, Yee-Ming Chan, Elaine T. Lim, Jeremy D. Schmahmann, Marios Hadjivassiliou, Janet E. Hall, Ibrahim Adam, Andrew Dwyer, Lacey Plummer, Stephanie V. Aldrin, Julia O'Rourke, Andrew Kirby, Kasper Lage, Aubrey Milunsky, Jeff M. Milunsky, Jennifer Chan, E. Tessa Hedley-Whyte, Mark J. Daly, Nicholas Katsanis, Stephanie B. Seminara
Journal: New England Journal of Medicine (2013)

The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive.We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model.Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis.The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).