tbuckley/cabot-search huggingface dataset:
The “New Normal”
Authors: Jeanne M. Farnan, Vineet M. Arora
Journal: JAMA Internal Medicine (2013)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Coil embolization of congenital thoracic vascular anomalies in infants and children.
Authors: B P Fuhrman, J L Bass, W Castaneda-Zuniga, K Amplatz, J E Lock
Journal: Circulation (1984)

When significant thoracic vascular anomalies occur in children, they may present surgical difficulties making operative management undesirable. The recent development of a new, accurate coil-delivery system has enabled us to embolize 17 vessels in five children by passing Gianturco steel coils coated with thrombogenic Dacron strands through No. 5 or 6F end-hole catheters suitable for infants. Coils of 0.038 inch packed diameter were fed through the catheter lumen by a flexible guidewire emerging as 3, 5, or 8 mm diameter loose coils. Fifteen of 17 vessels were successfully occluded. No complications or errors in placement of coils occurred. Four of five children clearly benefitted from the procedure. One died in spite of partial occlusion. Coil embolization can be performed accurately and safely even in small infants with a high rate of successful occlusion and may prove to be a valuable adjunct to operative management.
Peter John James Wren
Authors: D. R. Wren
Journal: BMJ (2012)

Peter John James Wren did not have a distinguished academic career at St Francis Xavier College, Liverpool, spending much of his time in the headmaster’s study. Aged 16 years he followed his brother Richard into the Jesuit novitiate. At the outbreak of war, after it became clear to both parties that his vocation lay elsewhere, he joined the Royal Navy as a rating on Russian convoys. He trained as an officer at the Royal Naval College in Greenwich and served in coastal forces at home and in the Mediterranean, commanding motor torpedo boats. He was wounded in joint operations with US …
Mechanisms and management of functional abdominal pain
Authors: Adam D Farmer, Qasim Aziz
Journal: Journal of the Royal Society of Medicine (2014)

Summary Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory systems may have an important role. The management of patients with functional abdominal pain requires a tailored multidisciplinary approach in a supportive and empathetic environment in order to develop an effective therapeutic relationship. Patient education directed towards an explanation of the pathophysiology of functional abdominal pain is in our opinion a prerequisite step and provides the rationale for the introduction of interventions. Interventions can usefully be categorised into general measures, pharmacotherapy, psychological interventions and ‘step-up’ treatments. Pharmacotherapeutic/step-up options include tricyclic antidepressants, serotonin noradrenergic reuptake inhibitors and the gabapentinoids. Psychological treatments include cognitive behavioural therapy and hypnotherapy. However, the objective evidence base for these interventions is largely derived from other chronic pain syndrome, and further research is warranted in adult patients with functional abdominal pain.
Inhaled nitric oxide. A bronchodilator in mild asthmatics with methacholine-induced bronchospasm.
Authors: R M Kacmarek, R Ripple, B A Cockrill, K J Bloch, W M Zapol, D C Johnson
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Nitric oxide (NO) reduces airway tone in the methacholine-treated guinea pig. We examined whether low levels of inhaled NO gas would relax airway smooth muscle tone in patients with mild asthma subjected to methacholine-induced bronchospasm. Thirteen adult volunteers with mild asthma inspired increasing concentrations of methacholine until their baseline forced expiratory volume in one second (FEV1, 3.29 +/- 0.17 L, mean +/- SEM) decreased by > or = 20% (2.33 +/- 0.18 L, p < 0.01). Thereafter, they sequentially inhaled 100 parts per million (ppm) NO, 40% O2; 40% O2; and 100 ppm NO, 40% O2 while spirometry was performed. Subsequent inhalation of isoproterenol returned the FEV1 levels to baseline. Inhaling 100 ppm NO increased FEV1 to 2.66 +/- 0.18 L (p < 0.01), and this increase was maintained after NO was discontinued. FEV1 did not change during the second period of NO inhalation. Similar results were observed for vital capacity, but no significant effect was noted on forced expiratory flow at 25% of vital capacity or peak expiratory flow. Subjects were then divided into a responder subgroup, which showed a mean increase in FEV1 after initial NO inhalation of 560 +/- 150 ml, and a nonresponder subgroup, which showed a mean increase in FEV1 of 129 +/- 29 ml. Our data suggest that inhalation of nitric oxide by patients with mild asthma with methacholine-induced bronchospasm results in a minor but significant relaxation of airway tone.
Lack of investment in regulatory science is part of "innovation gap," believes FDA commissioner
Authors: E. Sukkar
Journal: BMJ (2011)

Margaret Hamburg, the commissioner of the US Food and Drug Administration, believes that a failure to invest “adequately” in regulatory science has been one of the reasons why fewer new drugs have been making it to the market.

She told a drug and biotechnology industry conference organised by the Financial Times and held in London on 5-6 December that regulatory science was the “bridge” between a “good idea” and getting a new product to the public. The FDA defines regulatory science as the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of products.

Better regulatory science could make it easier to determine when a drug may fail, she said. She added that the FDA had developed centres of …
Innate Immune Interleukin-1 Receptor–Associated Kinase 4 Exacerbates Viral Myocarditis by Reducing CCR5 <sup>+</sup> CD11b <sup>+</sup> Monocyte Migration and Impairing Interferon Production
Authors: Alan Valaperti, Mototsugu Nishii, Youan Liu, Kotaro Naito, Megan Chan, Liyong Zhang, Carsten Skurk, Heinz-Peter Schultheiss, George A. Wells, Urs Eriksson, Peter P. Liu
Journal: Circulation (2013)

Viral myocarditis follows a fatal course in ≈30% of patients. Interleukin-1 receptor-associated kinase 4 (IRAK4), a major nodal signal transducer in innate immunity, can play a pivotal role in host inflammatory response. We sought to determine how IRAK4 modulates inflammation and outcome in a mouse model of viral myocarditis.Myocarditis was induced after intraperitoneal inoculation of coxsackievirus B3 into C57Bl/6 IRAK4-deficient mice and their littermate controls. Mortality and viral proliferation were markedly reduced in IRAK4(-/-) mice compared with their IRAK4(+/+) littermates. Disease resistance of IRAK4(-/-) mice paralleled increased amounts of protective heart-infiltrating CCR5(+) monocytes/macrophages and enhanced interferon-α and interferon-γ production 2 days after infection. Competitive bone marrow chimera demonstrated that intact IRAK4 function inhibited heart-specific migration of bone marrow-derived CCR5(+) cells. Mechanistically, lack of IRAK4 resulted in interferon regulatory factor 5 homodimerization via reduced melanoma differentiation-associated protein 5 degradation and enhanced Stat1 and Stat5 phosphorylation. Consequently, antiviral interferon-α and interferon-γ production, as well as CCR5(+) cell recruitment, increased, whereas the overall proinflammatory response was drastically reduced in the absence of IRAK4.Innate immunity signal transducer IRAK4 exacerbates viral myocarditis through inhibition of interferon production and reduced mobilization of protective CCR5(+) monocytes/macrophages to the heart. The combination of IRAK4 inhibitors and antiviral adjuvants may become an attractive therapeutic approach against viral myocarditis in the future.
mRECIST and EASL responses at early time point by contrast-enhanced dynamic MRI predict survival in patients with unresectable hepatocellular carcinoma (HCC) treated by doxorubicin drug-eluting beads transarterial chemoembolization (DEB TACE)
Authors: H.J. Prajapati, J.R. Spivey, S.I. Hanish, B.F. El-Rayes, J.S. Kauh, Z. Chen, H.S. Kim
Journal: Annals of Oncology (2012)
Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice
Authors: Alexander Froese, Stephanie S. Breher, Christoph Waldeyer, Roland F.R. Schindler, Viacheslav O. Nikolaev, Susanne Rinné, Erhard Wischmeyer, Jan Schlueter, Jan Becher, Subreena Simrick, Franz Vauti, Juliane Kuhtz, Patrick Meister, Sonja Kreissl, Angela Torlopp, Sonja K. Liebig, Sandra Laakmann, Thomas D. Müller, Joachim Neumann, Juliane Stieber, Andreas Ludwig, Sebastian K. Maier, Niels Decher, Hans-Henning Arnold, Paulus Kirchhof, Larissa Fabritz, Thomas Brand
Journal: Journal of Clinical Investigation (2012)

Cardiac pacemaker cells create rhythmic pulses that control heart rate; pacemaker dysfunction is a prevalent disorder in the elderly, but little is known about the underlying molecular causes. Popeye domain containing (Popdc) genes encode membrane proteins with high expression levels in cardiac myocytes and specifically in the cardiac pacemaking and conduction system. Here, we report the phenotypic analysis of mice deficient in Popdc1 or Popdc2. ECG analysis revealed severe sinus node dysfunction when freely roaming mutant animals were subjected to physical or mental stress. In both mutants, bradyarrhythmia developed in an age-dependent manner. Furthermore, we found that the conserved Popeye domain functioned as a high-affinity cAMP-binding site. Popdc proteins interacted with the potassium channel TREK-1, which led to increased cell surface expression and enhanced current density, both of which were negatively modulated by cAMP. These data indicate that Popdc proteins have an important regulatory function in heart rate dynamics that is mediated, at least in part, through cAMP binding. Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention.
Obstetrics: Normal and Problem Pregnancies
Authors: Warren C. Plauché
Journal: JAMA (1987)

The editors have produced an exciting obstetrics text, a large hardbound book by an impressive panel of authorities. The theme is the "new obstetrics" of the maternal-fetal medicine genre, where as much attention is devoted to myasthenia gravis as to mid-forceps, as much to Rh sensitization as to all obstetric surgery, as much to lactation physiology as to obstetric hemorrhage. The "how-to" approach of obstetric texts of the past is replaced with scientific monographs relating to the physiology of the pregnant woman and issues and problems surrounding her pregnancy. The editors intend this book to be a reference source for general practitioners of obstetrics and gynecology and a base of information for fellows in maternal-fetal medicine, with each chapter designed to be read in an evening. The book accomplishes most of these goals, but some long evenings are in store for obstetric generalists of the old school. The extensive bibliographic
Marked Malapposition and Aneurysm Formation After Sirolimus-Eluting Coronary Stent Implantation
Authors: Eugenio Stabile, Esteban Escolar, Guy Weigold, Neil J. Weissman, Lowell F. Satler, Augusto D. Pichard, William O. Suddath, Kenneth M. Kent, Ron Waksman
Journal: Circulation (2004)
THE INTERACTION OF MYCOPLASMAS WITH MAMMALIAN CELLS
Authors: Dorothea Zucker-Franklin, Morton Davidson, Lewis Thomas
Journal: The Journal of Experimental Medicine (1966)

The ultrastructure of three mycoplasma species, Mycoplasma pneumoniae, Mycoplasma gallisepticum, and Mycoplasma neurolyticum, has been studied in isolated form as well as in HeLa cell cultures and following incubation with human peripheral blood leukocytes. During log growth phase, the organisms could be distinguished from each other on the basis of their fine structure. In mammalian cell cultures, PPLO's appeared to proliferate on the plasma membranes which had markedly increased their surface area by means of long cytoplasmic processes which extended toward and surrounded them. Some of the microorganisms affected in this way may well have lain, not in vacuoles, but at the bottom of crypts. It is suggested that the cytopathogenic effect exerted by PPLO's on some tissue cultures may be attributable to membrane damage. Mycoplasmas adhered to leukocyte plasma membranes in a similar manner. They were avidly phagocytosed by neutrophils and eosinophils with accompanying degranulation of the white cells. It is thus likely that the local inflammatory reaction induced by PPLO's does not differ in essence from that caused by bacteria.
Diagnosing Genocide — The Case of Darfur
Authors: Jennifer Leaning
Journal: New England Journal of Medicine (2004)

In the desperate and urgent debate about what to do next in Darfur, Sudan (see map) — where a regional conflict has forced 1.3 million people from their homes and killed at least 30,000 people outright — the fragility of the humanitarian response and the nature of genocide are core themes. Professionals in medicine and public health have much to add to our understanding of both of these issues, most crucially because of our skills in using data to describe patterns of suffering and death in large populations.What makes this crisis different from many of the dire episodes of . . .
Cultured epidermal autografts and allografts: A study of differentiation and allograft survival
Authors: Tania J. Phillips, Jag Bhawan, Irene M. Leigh, Howard J. Baum, Barbara A. Gilchrest
Journal: Journal of the American Academy of Dermatology (1990)

Cultured epidermal sheets were examined before and at various times after grafting on skin ulcer beds. Before grafting, the sheet consisted of four to five layers of keratinocytes with incomplete differentiation. Ten days after grafting, graft recipient sites showed compact hyperkeratosis, a normal-appearing epidermis, and a flat dermoepidermal junction. At 6 months, the stratum corneum had a basket-weave appearance but the dermoepidermal junction remained flat. Monoclonal antibodies to keratins 14 and 10 showed normal basal and suprabasal localization, respectively. Electron microscopy showed a normal basement membrane with anchoring fibrils. LH7:2, a monoclonal antibody that binds to the type VII collagen molecule, stained the dermoepidermal junction in all biopsy specimens. AE-1, an antibody that stains suprabasal cells in hyperproliferative skin, was expressed suprabasally for up to 12 weeks after healing (16 weeks after grafting), but expression was confined to the basal layer at 18 weeks after healing (6 months after grafting). Anti-involucrin staining was found in the deeper layers of the epidermis up to 12 weeks after healing (16 weeks after grafting) but had receded to a normal distribution in upper spinous and granular layers at 18 weeks (6 months after grafting). Overall, the histologic patterns observed in recipient sites during the first 4 months after grafting resembled those observed for 10 to 14 days in newly healed epidermis and in hyperproliferative states such as psoriasis. In four sex-mismatched graft sites, specimens were reacted with a biotinylated probe to the Y chromosome by in situ hybridization. Lack of Y chromosome-positive cells suggested that host keratinocytes had replaced the allografts. Multilocus DNA analysis in one patient confirmed this observation. Our data suggest that an altered state of epithelial maturation persists for several months after culture grafting, with restoration of the normal pattern by 6 months. No differences were detected between autografted and allografted sites.
Identification of angiotensinogenic hypertension in man using 1-sar-8-ala-angiotensin II (Saralasin, P-113).
Authors: D H Streeten, J M Freiberg, G H Anderson, T G Dalakos
Journal: Circulation Research (1975)

Peripheral plasma renin activity (PRA) is not invariably elevated in patients whose ischemic renal lesion is causing hypertension. Infusions of an angiotensin II antagonist, 1-sar-8-ala-angiotensin II (P-113), have been used to determine whether the blood pressure responses might indicate angiotensin dependence in 221 consecutive hypertensive patients. In 32 patients P-113 infusion reversibly reduced blood pressure, and almost all of these "P-113 responders" had elevated renal vein and/or peripheral PRA levels, together with evidence of renal ischemia. Among the 189 "P-113 nonresponders," peripheral PRA was elevated in seven (3.8%), and renal vein PRA ratio was abnormal in two patients, who might represent exceptions to the otherwise successful record of the P-113 response in identifying "angiotensinoginic" hypertensives.
Abstract 406: Prevention of Heart Failure in delta-Sarcoglycan Knock-Out Mice after Intravenous Gene Transfer with Targeted Adeno-Associated Viral (AAV) Vectors
Authors: Caroline Goehringer, Desiree Rutschow, Stefanie Schinkel, Raffi Bekeredjian, Ralf Bauer, Dieter Weichenhan, Jurgen A Kleinschmidt, Hugo A Katus, Oliver J Muller
Journal: Circulation (2007)

Background: Delta-Sarcoglycan (SGCD) is a member of the dystrophin-associated glycoprotein complex. Mutations may result in isolated dilated cardiomyopathy or limb-girdle muscle dystrophy 2F with v...
Developmental Immunology and the Immunodeficiency Diseases
Authors: Max D. Cooper
Journal: JAMA (1982)

THE THYMUS first appears as a proliferation of epithelial cells lining the third and fourth branchial pouches at about the sixth or seventh week of embryonic life. Lymphoid tissue first appears in the thymus at about the eighth week of gestation, presumably as a result of a thymic microenvironmental influence on pluripotential stem cells that have migrated there from the yolk sac, fetal liver, or spleen. In the thymus, these cells acquire surface differentiation antigens and function (Fig 8-1). Thymic cells forming spontaneous rosettes with sheep erythrocytes (E) have been noted as early as eight weeks. Lymphocytes with membrane markers characteristic of T cells constitute 65% to 100% of thymus cells by 18 weeks. Reactivity to phytohemagglutinin first appears in the thymus at ten weeks, in the spleen at 13 weeks, and in the peripheral blood at 14.5 weeks. Mixed lymphocyte reactivity is first detected in the thymus at 12.5
Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form
Authors: Yvon Trottier, Didier Devys, Georges Imbert, Frédéric Saudou, Isabelle An, Yves Lutz, Chantal Weber, Yves Agid, Etienne C. Hirsch, Jean-Louis Mandel
Journal: Nature Genetics (1995)
Carotid shudder as a sign of ascending aorta dissection.
Authors: R Chapman, N Conway
Journal: BMJ (1976)

By ligation of the basilar artery, the circulation of the internal carotid and vertebral arteries was separated allowing the administration of drugs to centers of the brain above or below the level of ligation. Picrotoxin, pentylenetetrazol, and nikethamide caused convulsant activity when introduced into the brain either above or below the midpontine level; however, the sensitivity of the lower centers to pentylenetetrazol was much reduced. Convulsions occurred as a result of the administration of cocaine hydrochloride by way of the internal carotid artery; whereas, this agent caused severe depression of the medullary centers when injected into the vertebral artery. Thiopental sodium produced respiratory arrest when introduced into the medullary and lower pontine portions of the central nervous system. Much higher concentrations of the drug administered into the higher centers of the brain caused no significant respiratory depression when the vagi were intact. After section of the vagi, injection of thiopental into the internal carotid artery produced respiratory depression accompanied by an apneustic pattern of respiratory activity.
Antitumor Efficacy of 34.5ENVE: A Transcriptionally Retargeted and “Vstat120”-expressing Oncolytic Virus
Authors: Ji Young Yoo, Amy Haseley, Anna Bratasz, E Antonio Chiocca, Jianying Zhang, Kimerly Powell, Balveen Kaur
Journal: Molecular Therapy (2011)

Here, we describe the construction and testing of a novel herpes simplex virus type 1 (HSV-1) derived oncolytic virus (OV): 34.5ENVE (viral ICP34.5 Expressed by Nestin promotor and Vstat120 Expressing), for the treatment of cancer. This virus showed significant glioma-specific killing and antiangiogenic effects in vitro and in vivo. Treatment of subcutaneous and intracranial glioma-bearing mice with 34.5ENVE showed a significant increase in median survival of mice in four different glioma models. Histology and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) revealed reduced microvessel density (MVD) and increased tumoral necrosis in 34.5ENVE-treated tumor tissue compared to control OV-treated tumor tissue. Collectively, these results describe the construction, efficacy, and impact on tumor microenvironment of a transcriptionally driven OV armed with Vstat120 gene expression. These preclinical results will facilitate future clinical testing of 34.5ENVE. Here, we describe the construction and testing of a novel herpes simplex virus type 1 (HSV-1) derived oncolytic virus (OV): 34.5ENVE (viral ICP34.5 Expressed by Nestin promotor and Vstat120 Expressing), for the treatment of cancer. This virus showed significant glioma-specific killing and antiangiogenic effects in vitro and in vivo. Treatment of subcutaneous and intracranial glioma-bearing mice with 34.5ENVE showed a significant increase in median survival of mice in four different glioma models. Histology and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) revealed reduced microvessel density (MVD) and increased tumoral necrosis in 34.5ENVE-treated tumor tissue compared to control OV-treated tumor tissue. Collectively, these results describe the construction, efficacy, and impact on tumor microenvironment of a transcriptionally driven OV armed with Vstat120 gene expression. These preclinical results will facilitate future clinical testing of 34.5ENVE.