tbuckley/cabot-search huggingface dataset:
Sweet's syndrome and malignancy: a case associated with multiple myeloma and review of the literature
Authors: J. BERTH-JONES, P.E. HUTCHINSON
Journal: British Journal of Dermatology (1989)

A case of Sweet's syndrome developed as a presenting feature of multiple myeloma. This is the third such case reported, suggesting that myeloma is among the increasing group of neoplasms in which Sweet's syndrome may occur as a paraneoplastic phenomenon.
Handbook of Sleep-Related Breathing Disorders
Authors: N J Douglas
Journal: BMJ (1994)

J R Stradling Oxford University Press, £40, pp 296 ISBN 0-19-261834-2

The Handbook of Sleep-Related Breathing Disorders is primarily an account of the sleep apnoea/hypopnoea syndrome, also known as the obstructive sleep apnoea syndrome. Starting with an excellent review of sleep physiology - which confirms how little is known about why we sleep - and of the effect of sleep on breathing in normal subjects, it then discusses mechanisms, clinical features, diagnosis, and treatment of the sleep apnoea/hypopnoea syndrome. The balance between pharyngeal dilator muscle action …
New Strategies in Renal Cell Carcinoma: Targeting the Genetic and Metabolic Basis of Disease
Authors: Ramaprasad Srinivasan, Christopher J. Ricketts, Carole Sourbier, W. Marston Linehan
Journal: Clinical Cancer Research (2015)

Abstract The development of new forms of treatment of advanced renal cell carcinoma over the past two decades has been primarily focused on targeting the VHL/HIF pathway. The recent identification of mutations of chromatin-remodeling genes in clear-cell renal carcinoma (ccRCC), of genomic heterogeneity, and of a Warburg-like metabolic phenotype in advanced disease has had a profound effect on our understanding of the evolution of ccRCC and on potential approaches to personalized therapy. Early approaches to therapy for patients with advanced type I papillary RCC that have centered around the MET/HGF pathway will expand as more genomic information becomes available. Sporadic and familial type II papillary renal cell carcinoma are characterized by enhanced aerobic glycolysis and share an antioxidant response phenotype. In fumarate hydratase–deficient RCC, fumarate-induced succination of KEAP1 activates Nrf2 signaling. CUL3 and Nrf2 mutations as well as an Nrf2 activation phenotype are found in sporadic type II papillary RCC. Therapeutic approaches designed to target the Nrf2 pathway as well as to impair blood flow and glucose delivery in these cancers that are highly dependent on a robust tumor vasculature and on ready availability of glucose for energy production and glycolysis are in development. Clin Cancer Res; 21(1); 10–17. ©2015 AACR.
Did dinosaurs have megakaryocytes? New ideas about platelets and their progenitors
Authors: L. F. Brass
Journal: Journal of Clinical Investigation (2005)

Biological evolution has struggled to produce mechanisms that can limit blood loss following injury. In humans and other mammals, control of blood loss (hemostasis) is achieved through a combination of plasma proteins, most of which are made in the liver, and platelets, anucleate blood cells that are produced in the bone marrow by megakaryocytes. Much has been learned about the underlying mechanisms, but much remains to be determined. The articles in this series review current ideas about the production of megakaryocytes from undifferentiated hematopoietic precursors, the steps by which megakaryocytes produce platelets, and the molecular mechanisms within platelets that make hemostasis possible. The underlying theme that connects the articles is the intense investigation of a complex system that keeps humans from bleeding to death, but at the same time exposes us to increased risk of thrombosis and vascular disease.
Interruption of Homologous Desensitization in Cyclic Guanosine 3′,5′-Monophosphate Signaling Restores Colon Cancer Cytostasis by Bacterial Enterotoxins
Authors: Giovanni M. Pitari, Ronnie I. Baksh, David M. Harris, Peng Li, Shiva Kazerounian, Scott A. Waldman
Journal: Cancer Research (2005)

Abstract Bacterial diarrheagenic heat-stable enterotoxins induce colon cancer cell cytostasis by targeting guanylyl cyclase C (GCC) signaling. Anticancer actions of these toxins are mediated by cyclic guanosine 3′,5′-monophosphate (cGMP)–dependent influx of Ca2+ through cyclic nucleotide-gated channels. However, prolonged stimulation of GCC produces resistance in tumor cells to heat-stable enterotoxin–induced cytostasis. Resistance reflects rapid (tachyphylaxis) and slow (bradyphylaxis) mechanisms of desensitization induced by cGMP. Tachyphylaxis is mediated by cGMP-dependent protein kinase, which limits the conductance of cyclic nucleotide-gated channels, reducing the influx of Ca2+ propagating the antiproliferative signal from the membrane to the nucleus. In contrast, bradyphylaxis is mediated by cGMP-dependent allosteric activation of phosphodiesterase 5, which shapes the amplitude and duration of heat-stable enterotoxin–dependent cyclic nucleotide accumulation required for cytostasis. Importantly, interruption of tachyphylaxis and bradyphylaxis restores cancer cell cytostasis induced by heat-stable enterotoxins. Thus, regimens that incorporate cytostatic bacterial enterotoxins and inhibitors of cGMP-mediated desensitization offer a previously unrecognized therapeutic paradigm for treatment and prevention of colorectal cancer.
Statin administration in patients with acute coronary syndromes: results in decreased heat release of culprit atherosclerotic lesions
Authors: Christodoulos Stefanadis, Konstantinos Toutouzas, Eleftherios Tsiamis, Ioannis Kallikazaros, Manolis Vavouranakis, Sophia Vaina, Athanasios Trikas, Christina Chrysochoou, Dimos Panagiotakos, Pavlos Toutouzas
Journal: Journal of the American College of Cardiology (2002)
A Physiologic Approach to Shock
Authors: Eugene D. Jacobson
Journal: New England Journal of Medicine (1968)

A 39-year-old man attempted suicide by swallowing arsenic trioxide. On the following day he was hospitalized, and the systolic blood pressure was 38 mm. of mercury in the supine position; diastolic pressure sounds were inaudible. This capsular description of pertinent historical and physical findings might appear sufficient for a diagnosis of shock. But was he in shock? His mentation was clear; there was no weakness, he could walk, and his skin was warm and dry. These findings indicated that blood flow to major organ systems was not impaired, a situation incompatible with current concepts of shock.This case was reported . . .
Eosinophilic airway inflammation induced by repeated exposure to cigarette smoke
Authors: K Matsumoto, H Aizawa, H Inoue, H Koto, S Takata, M Shigyo, H Nakano, N Hara
Journal: European Respiratory Journal (1998)

Acute exposure to cigarette smoke causes airway hyperresponsiveness (AHR) in guinea-pigs, which resolves within a few hours. Repeated exposure may have a different effect on the airways. To address this question, guinea-pigs were repeatedly exposed to cigarette smoke (six cigarettes for 1 h x day(-1)) for 14 consecutive days. Airway responsiveness to inhaled histamine and differential cell counts in bronchoalveolar lavage fluid (BALF) were evaluated 1 day after the last exposure. Significant neutrophilia in BALF was observed after 3 days of smoke exposure. Significant eosinophilia in BALF and AHR were observed after 14 days of smoke exposure, but not after 3 or 7 days of smoke exposure. These changes persisted until 3 days after the last exposure and resolved 7 days afterwards. Histologically, the recruited eosinophils were observed predominantly in the airways, but not in the alveoli. Treatment with E-6123, a specific platelet-activating factor receptor antagonist (1 mg x kg(-1) x day(-1) p.o. during smoke exposure) significantly inhibited the eosinophil influx and AHR. Repeated exposure to cigarette smoke may induce prolonged airway inflammation and airway hyperresponsiveness in guinea-pigs. Platelet-activating factor or platelet-activating factor-like lipids may play a key role in airway hyperresponsiveness, presumably by the induction of eosinophilic airway inflammation.
Characterization of the Frequency-Force Relationship in the Dog Atrium In Situ
Authors: T. P. GRAHAM, W. J. POWELL, R. L. CLANCY, J. P. GILMORE
Journal: Circulation Research (1967)

Isometric developed tension and rate of development of tension in the in situ atrium of the anesthetized dog have been shown to increase consistently with increasing heart rate over a wide range. This study thus definitely demonstrates that both the ascending and descending staircase effects occur in the dog atrium in situ. At high cardiac rates the velocity of force development may increase without a change in the extent of force development. These changes were independent of variations in aortic pressure, intactness of betaadrenergic receptors, level of cardiac catecholamine stores, cardiac innervation, or changes in coronary flow. The character of the frequency-force relationship was found to be markedly influenced by isolation of the heart with its concomitant depression of contractility.
Essential Surgical Practice
Authors: E. Patchen Dellinger
Journal: JAMA (1983)

A distinguished group of British and American surgeons have collaborated to produce a major new surgical textbook addressing the needs of surgical trainees. Three editors and 66 contributors have produced a volume of 79 chapters and 1,277 pages. The editors themselves ask about the need for yet another textbook of surgery. Their stated aim is to address the care of the surgical patient with multiple problems needing both medical and surgical treatment. They have included a large section on general management and begin each of the chapters on specific organs or anatomic regions with a careful presentation of anatomic and physiological principles. They have omitted details of operative technique, referring the reader to preceptors and surgical atlases, and have kept the bibliography and references brief.  The above goals are laudable, but unfortunately the execution is inconsistent, with notable variation among chapters. Some chapters include superficial discussions of many conditions of
Should surgical outcomes be published?
Authors: Evelyn Chou, Hamid Abboudi, Mohammed Shamim Khan, Prokar Dasgupta, Kamran Ahmed
Journal: Journal of the Royal Society of Medicine (2015)

Despite publishing surgical outcomes being a positive step forwards in the progression of England’s healthcare system, it has no doubt been faced with criticism and reservations. This review article aims to discuss the pros and cons of publishing individual surgical outcomes, as well as the challenges faced. Publishing outcomes requires data from a number of sources such as national clinical audits, hospital episode statistics, patient-reported outcomes, registers and information from revalidation. As yet, eight surgical specialties have begun publishing their data, including cardiac (coronary artery bypass graft, valve and aortic surgery), endocrine (thyroidectomy, lobectomy, isthmusectomy), orthopaedic (hip and knee replacement), urological (full and partial nephrectomies, nephroureterectomy), colorectal (bowel tumour removal), upper gastrointestinal (stomach cancer and oesophageal cancer removal, bariatric surgery), ear, nose and throat surgery (larynx, oral cavity, oropharynx, hypopharynx and salivary gland cancer removal), as well as vascular surgery (abdominal aortic aneurysm, carotid endarterectomy). However, not all procedures have been addressed. Despite the controversy surrounding the topic of publishing surgical outcomes, the advantages of reporting outcomes outweigh the disadvantages, and these challenges can be overcome, to create a more reliable, trustworthy and transparent NHS. Perhaps one of the main challenges has been the difficulty in collecting large amounts of clinically significant data able to quantify the performance of surgeons.
Synthesis of hydroxyeicosatetraenoic acids and leukotrienes in rat nephrotoxic serum glomerulonephritis. Role of anti-glomerular basement membrane antibody dose, complement, and neutrophiles.
Authors: E A Lianos
Journal: Journal of Clinical Investigation (1988)

The basal and stimulated synthesis of immunoassayable 12- and 5-monohydroxyeicosatetraenoic acids (HETE) and leukotrienes (LT) B4 and C4 was studied in glomeruli isolated from rats with nephrotoxic serum glomerulonephritis (NSGN) induced by low (30 micrograms/g body weight) or high (105 micrograms/g) doses of anti-rat glomerular basement membrane (GBM) immunoglobulin (Ig). In the early heterologous phase of the disease, low doses of anti-GBM Ig enhanced the basal synthesis of 12-HETE but not that of 5-HETE or LT. High anti-GBM Ig doses enhanced the basal synthesis of 5-HETE and LTB4 as well. Under stimulated conditions, enhanced glomerular production of 5-HETE and LTB4 occurred at 15 min after infusion of anti-GBM Ig, peaked at 1 h, and returned toward control levels by 24 h. At 48 h, 72 h, and on day 12, the synthesis of these eicosanoids was impaired. Neutrophile depletion only partially reduced glomerular eicosanoid synthesis after induction of NSGN whereas complement depletion significantly reduced 5-HETE, 12-HETE, and LTB4. These observations indicate that in the heterologous phase of NSGN there is enhanced but short-lived glomerular 5-HETE and LTB4 synthesis. This phenomenon is mediated by complement activation and may be an important proinflammatory event leading to capillary wall injury in the early stages of the disease.
Respective and Combined Effects of Prone Position and Inhaled Nitric Oxide in Patients with Acute Respiratory Distress Syndrome
Authors: LAURENT PAPAZIAN, FABIENNE BREGEON, FRANÇOISE GAILLAT, XAVIER THIRION, MARC GAINNIER, RÉGINE GREGOIRE, PIERRE SAUX, FRANÇOIS GOUIN, YVES JAMMES, JEAN-PIERRE AUFFRAY
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Inhaled nitric oxide (NO) and prone position (PP) are two of the new therapeutics proposed in the setting of acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the hemodynamic and respiratory effects of NO and prone position in patients with ARDS. Fourteen patients, sedated, paralyzed, and ventilated using volume-control mode, were prospectively investigated. All patients had a radial artery catheter, a pulmonary artery catheter, and a 3-F fiberoptic thermistor catheter advanced via the femoral artery into the descending aorta. The protocol consisted of seven phases: baseline measurements in supine position, SP (T0); SP + NO (T1); baseline 2 in SP (T2); PP without NO (T3); NO + PP (T4); SP + NO (T5); and PP + NO (T6). Inhaled NO (T1) induced an increase in Po 2/Fi O2 (from 128 ± 44 to 180 ± 75 mm Hg, p < 0.004). Prone position (T3) resulted in an increase in Po 2/Fi O2 (193 ± 83 mm Hg, p < 0.003 versus T0). The association of NO with PP (T4) resulted in a significant improvement in Po 2/Fi O2 (261 ± 98 mm Hg) when compared with T0, T1, and T3. Analysis of variance showed a significant and additive effect of NO and PP on both Po 2/ Fi O2 (p < 0.000) and shunt fraction (Q˙ s/Q˙ t) (p < 0.01). Since the association of NO with PP presents additive effects on oxygenation, this association can be proposed for the treatment of ARDS.
Adeno-associated Virus–mediated Delivery of a Recombinant Single-chain Antibody Against Misfolded Superoxide Dismutase for Treatment of Amyotrophic Lateral Sclerosis
Authors: Priyanka Patel, Jasna Kriz, Mathieu Gravel, Geneviève Soucy, Christine Bareil, Claude Gravel, Jean-Pierre Julien
Journal: Molecular Therapy (2014)

There is emerging evidence that the misfolding of superoxide dismutase 1 (SOD1) may represent a common pathogenic event in both familial and sporadic amyotrophic lateral sclerosis (ALS). To reduce the burden of misfolded SOD1 species in the nervous system, we have tested a novel therapeutic approach based on adeno-associated virus (AAV)-mediated tonic expression of a DNA construct encoding a secretable single-chain fragment variable (scFv) antibody composed of the variable heavy and light chain regions of a monoclonal antibody (D3H5) binding specifically to misfolded SOD1. A single intrathecal injection of the AAV encoding the single-chain antibody in SOD1(G93A) mice at 45 days of age resulted in sustained expression of single-chain antibodies in the spinal cord, and it delayed disease onset and extension of life span by up to 28%, in direct correlation with scFv titers in the spinal cord. The treatment caused attenuation of neuronal stress signals and reduction in levels of misfolded SOD1 in the spinal cord of SOD1(G93A) mice. From these results, we propose that an immunotherapy based on intrathecal inoculation of AAV encoding a secretable scFv against misfolded SOD1 should be considered as potential treatment for ALS, especially for individuals carrying SOD1 mutations.
Postpartum hemorrhage: When uterotonics and sutures fail
Authors: Andra H. James, Claire McLintock, Evelyn Lockhart
Journal: American Journal of Hematology (2012)

Systemic bleeding at the time of postpartum hemorrhage (PPH) is usually the result of coagulopathy that has developed acutely as a result of massive hemorrhage after uterotonics and sutures have failed. Occasionally, the patient has a preexisting coagulopathy, but more often, coagulopathy arises acutely as the result of massive hemorrhage, which is usually related to obstetrical and less often surgical bleeding. Despite being able to identify risk factors for PPH in the antenatal and intrapartum period, the majority of women who ultimately develop PPH do not have any such factors and every pregnancy is at risk. The coagulopathy associated with massive PPH may be due to hemodilution, failure of liver synthetic function as occurs with acute liver failure of pregnancy, or disseminated intravascular coagulation (DIC). There are no data from clinical trials to help guide management of transfusion in PPH, although the management of blood component therapy in severe PPH is similar to that in other massive hemorrhage. Standard practice is to replace fibrinogen to maintain a level of ≥ 100 mg/dL, yet recent evidence suggests that the level of fibrinogen needed to prevent PPH is at least 400 mg/dL. Recombinant activated factor VIIa (rFVIIa) has been used in the management of severe PPH unresponsive to blood component therapy. Coagulation laboratory evaluation may be useful in guiding hemostatic management during massive PPH, but for the results to be useful, they must be rapidly available and provide information that would not be available from clinical assessment alone. The hematologist or hemostasis expert has the opportunity to make the difference between life and death for the patient experiencing massive PPH.
Long-Term Treatment with Neuroleptic Drugs and Eye Opacities
Authors: GEORGE E. CRANE, ALBIN W. JOHNSON, WILLIAM J. BUFFALOE
Journal: American Journal of Psychiatry (1971)

Approximately 100 chronic schizophrenic patients were examined for drug-induced eye changes. The lens was affected in 36 patients, the cornea in 19. There was a linear relationship between eye opacities and the total intake of drugs. Corneal opacities were also related to the intake of high doses of chlorpromazine over a short period of time. In most instances the ocular changes were irreversible. Despite heavy deposits in the anterior part of the eye, vision was unimpaired and the retina appeared to be intact.
491 Peginterferon alpha-2a (40KD) (PEGASYS) reverses cirrhosis, improves fibrosis and slows progression of fibrosis in patients with HBeAg-positive or HBeAg-negative chronic hepatitis B (CHB)
Authors: G. Cooksley, G.K.K. Lau, P. Marcellin, T. Piratvisuth, E. Bonino, K.X. Luo, S. Hadziyannis, R. Jin, P. Button, N. Pluck
Journal: Journal of Hepatology (2006)
Yesterday and To-morrow in Child Health
Authors: C. McNeil
Journal: BMJ (1954)

This address gives a short review in general terms of child health in the last hundred years.Although the examples and figures used in it have been drawn mainly from Scotland, the history has been much the same in England, Wales, and Ireland, and indeed far beyond these islands: it has been similar both in the measures taken to promote child health and in the results obtained.From such a historical survey we can get a perspective view of the growth of the suLbject and of its future progress.The Infant Death Rates Child health is a phrase full of meaning.but is so wide and deep in its meaning that it is difficult and perhaps impossible to define it.As an idea in the mind and as an object of human effort it is as old as the human family; and long before human records were kept the health and well-being of children must have been deeply cherished by their natural guardians, their fathers and mothers.But as a medical concept, and especially as a medico-social problem, it emerged in Britain about the middle of the last century ; while the actual phrase-child health obtained a recognized place in the medical vocabulary only about twenty years ago.It was the publication, for England and Wales in 1840, and for Scotland in 1855, of the num- bers of births, deaths, and marriages, and of the population that drew attention to public health and to child mortality, for among these figures, called vital statistics, was included an infant death rate.This infant death rate (or infant mortality rate) is the number of babies dying in the first year of life in every thousand who survive birth.These rates do not com- pletely measure child mortality, for they omit the heavy loss of infants during birth (stillbirths), and also the
Systemic and gut O2 extraction during endotoxemia. Role of nitric oxide synthesis.
Authors: P T Schumacker, J Kazaglis, H V Connolly, R W Samsel, M F O'Connor, J G Umans
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Endotoxin administration decreases intrinsic responsiveness of arteries to contractile agonists, both in vivo and in vitro. Endotoxin also impairs systemic and intestinal ability to increase microvascular O2 extraction in response to decreases in O2 delivery. During endotoxemia, contractile responsiveness can be increased by stereospecific inhibitors of nitric oxide (NO) synthase, suggesting that the hypotension and loss of microvascular function caused by endotoxin may result from increased nitric oxide biosynthesis. This study tested whether inhibition of NO synthesis could reverse the systemic and intestinal oxygen extraction defects seen after endotoxin challenge in the dog. Oxygen extraction and hemodynamic responses to progressive decreases in O2 delivery (stagnant hypoxia) were measured systemically and in isolated autoperfused intestine segments in anesthetized dogs. Systemic and intestinal O2 extractions at the onset of O2 supply dependency were significantly impaired in endotoxin-challenged (n = 6) compared with control (n = 7) animals. Inhibition of NO synthase activity with N omega-nitro-L-arginine methyl ester (L-NAME), 50 mg/kg + 100 mg/kg/h, completely inhibited endothelium-dependent vasodilation responses evaluated in vitro, and significantly but incompletely reversed the systemic hypotension in animals previously given endotoxin (n = 9). Despite this improvement, critical O2 extraction ratios remained significantly reduced. Administration of L-NAME in the absence of endotoxin (n = 8) significantly increased systemic vascular resistance and decreased cardiac output and O2 delivery, but it did not impair critical O2 extraction ratios in whole body or isolated intestine. We conclude that inhibition of NO synthesis in this model of endotoxemia can improve arterial pressure without improving those microvascular functions that may influence tissue O2 extraction efficacy.