tbuckley/cabot-search huggingface dataset:
Relative Roles of the Sympathetic and Parasympathetic Nervous Systems in the Reflex Control of Heart Rate
Authors: GERALD GLICK, EUGENE BRAUNWALD, Robert M. Lewis
Journal: Circulation Research (1965)

This study was designed to define the relative roles of the sympathetic and parasympathetic nervous systems in the reflex alterations of heart rate consequent to changes in arterial pressure. In 23 experiments carried out on 22 anesthetized dogs and in studies performed on four trained, unanesthetized dogs, acute changes in arterial pressure were produced by administering drugs acting on the peripheral vascular bed. The effects of acutely elevating systemic pressure were also investigated in four intact unanesthetized human subjects. Augmenting arterial pressure above control levels with graded doses of phenylephrine always slowed heart rate strikingly. Although complete sympathetic blockade with guanethidine or pronethalol did not significantly alter the degree of slowing, parasympathetic blockade with atropine or vagotomy essentially abolished this response. Conversely, lowering pressure with intravenous injections of nitroglycerin always raised heart rate in the control state, a response abolished by sympathetic blockade with guanethidine or nethalide, but not by parasympathetic blockade with vagotomy or atropine. Thus, when arterial pressure rises above control, the decrease in heart rate is mediated by the parasympathetic nervous system, withdrawal of sympathetic activity playing no detectable role; when pressure falls below control levels, the elevation of heart rate is mediated primarily by the sympathetic nervous system. These findings are not consonant with the traditional concept of control of heart rate which predicates simultaneous reciprocal changes in activity occurring in the two components of the autonomic nervous system.
Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa
Authors: Catherine J. Edwards-Smith, Julie R. Jonsson, David M. Purdie, Amolak Bansal, Claudia Shorthouse, Elizabeth E. Powell
Journal: Hepatology (1999)

Serum levels of interleukin-10 (IL-10) are elevated in a proportion of patients with untreated chronic hepatitis C, and this may compromise the host immune response to the virus. The capacity for IL-10 production varies according to the genetic composition of the IL-10 locus. We examined the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with chronic hepatitis C and their association with response to treatment with interferon alfa (IFN-α). After adjusting for potential confounding variables, a highly significant relationship was found between inheritance of the IL-10 promoter −592*A and −819*T alleles or the ATA haplotype and response to IFN-α therapy ( P = .016). Response to treatment was also associated with viral genotype 3a, a low viral load, and less fibrosis on liver biopsy. Following in vitro stimulation of peripheral blood mononuclear cells, the IL-10 promoter haplotypes, GCC, ACC, and ATA, were associated with high, intermediate, and low IL-10 production, respectively. These findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis C to IFN-α therapy. Patients who are genetically predisposed to high IL-10 production have a poor response to IFN-α and may benefit from additional treatment strategies designed to enhance a T-helper type 1 (Th1) response.
Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection
Authors: Maurizio Renna, Catherine Schaffner, Karen Brown, Shaobin Shang, Marcela Henao Tamayo, Krisztina Hegyi, Neil J. Grimsey, David Cusens, Sarah Coulter, Jason Cooper, Anne R. Bowden, Sandra M. Newton, Beate Kampmann, Jennifer Helm, Andrew Jones, Charles S. Haworth, Randall J. Basaraba, Mary Ann DeGroote, Diane J. Ordway, David C. Rubinsztein, R. Andres Floto
Journal: Journal of Clinical Investigation (2011)

Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens.
Training in anaesthesia and other specialities
Authors: R J Burden, J Handel
Journal: BMJ (1994)

EDITOR, - One of the main sources of anxiety among doctors in training is being faced with a patient presenting with an emergency for which the trainee feels insufficiently trained. We believe that the principles that are used to train anaesthetists would be advantageous to trainees in other specialties in which emergencies are a feature.

In paediatrics and general medicine in which we trained to registrar level, we gleaned the principles of managing patients as an …
Gentility and Professionalism
Authors: Charles D. Aring
Journal: JAMA (1974)

IN HIS interesting study entitled<i>The Decline of American Gentility</i>,<sup>1</sup>Stow Persons, Professor of History at the University of Iowa, has traced the virtual dissolution of the influence of the gentry in the United States. At the turn of the century Charles Eliot Norton characterized democracy as a "huge mass of standardized mediocrity," noting that the society was "hedonistically absorbed in the pursuit of happiness and the full-blown commercial insolence." Perhaps the steady decline of scholarly influence on the course of American affairs was a result of a rapidly burgeoning population. As Persons notes, there developed concomitantly the new illiteracy to replace the old, where most of the population became able to read but lacked the skill or will to read the things that ought to be read. A natural result was the displacement of knowledge by public opinion, often tyrannical, a democratic counterpoint of the older forms of
Mechanisms of Diesel-Induced Endothelial Nitric Oxide Synthase Dysfunction in Coronary Arterioles
Authors: Tom W. Cherng, Michael L. Paffett, Olan Jackson-Weaver, Matthew J. Campen, Benjimen R. Walker, Nancy L. Kanagy
Journal: Environmental Health Perspectives (2010)

Increased air pollutants correlate with increased incidence of cardiovascular disease potentially due to vascular dysfunction. We have reported that acute diesel engine exhaust (DE) exposure enhances vasoconstriction and diminishes acetylcholine (ACh)-induced dilation in coronary arteries in a nitric oxide synthase (NOS)-dependent manner. We hypothesize that acute DE inhalation leads to endothelial dysfunction by uncoupling NOS.Rats inhaled fresh DE (300 µg particulate matter/m3) or filtered air for 5 hr. After off-gassing, intraseptal coronary arteries were isolated and dilation to ACh recorded using videomicroscopy.Arteries from DE-exposed animals dilated less to ACh than arteries from air-exposed animals. NOS inhibition did not affect ACh dilation in control arteries but increased dilation in the DE group, suggesting NOS does not normally contribute to ACh-induced dilation in coronary arteries but does contribute to endothelial dysfunction after DE inhalation. Cyclooxygenase (COX) inhibition did not affect ACh dilation in the DE group, but combined inhibition of NOS and COX diminished dilation in both groups and eliminated intergroup differences, suggesting that the two pathways interact. Superoxide scavenging increased ACh dilation in DE arteries, eliminating differences between groups. Tetrahydrobiopterin (BH4) supplementation with sepiapterin restored ACh-mediated dilation in the DE group in a NOS-dependent manner. Superoxide generation (dihydroethidium staining) was greater in DE arteries, and superoxide scavenging, BH4 supplementation, or NOS inhibition reduced the signal in DE but not air arteries.Acute DE exposure appears to uncouple NOS, increasing reactive oxygen species generation and causing endothelial dysfunction, potentially because of depletion of BH4 limiting its bioavailability.
Abstract 3261: GRP78 regulates clusterin stability, retrotranslocation, and mitochondrial localization under ER stress in prostate cancer
Authors: Na Li, Amina Zoubeidi, Eliana Beraldi, Martin E Gleave
Journal: Cancer Research (2012)

Abstract Expression of clusterin (CLU) closely correlates with regulation of apoptosis in cancer. While endoplasmic reticulum (ER) stress-induced up-regulation and retro-translocation of cytoplasmic CLU (cCLU)(also termed as presecretory and secreted forms, psCLU and sCLU) has been linked to its anti-apoptotic properties, the mechanism mediating these processes remain undefined. Here, we show that GRP78 (Bip) associates with cCLU to facilitate its retro-translocation and redistribution to the mitochondria in human prostate cancer cells. We found that ER stress inducers, such as TG or MG132, increased expression levels of both cCLU and GRP78 proteins and led to the association of these two proteins. Furthermore, GRP78 overexpression resulted in increased cCLU but reduced sCLU levels secreted into the culture media. GRP78 stabilized cCLU protein and its hypo-glycosylated forms, in particular after paclitaxel treatment. Moreover, subcellular fractionation studies indicated GRP78 increased stress-induced cCLU retro-translocation from the ER with redistribution to the mitochondria. Live cell imaging revealed that a CLUGFP localized directly to highly mobile mitochondria. Co-expression of both GRP78 and CLU in LNCaP cells led to increased CLUGFP -mitochondria co-localization and reduced apoptosis by cooperatively stabilizing mitochondrial membrane integrity. Transient depletion of GRP78 reduced cCLU protein but not mRNA transcript levels, accompanied by cell cycle arrest at G0/G1 with down-regulation of both phospho-Rb and cyclin D1, and synergistic increases in paclitaxel-induced cell apoptosis. Taken together, our findings reveal a novel role of GRP78 in the regulation of CLU retro-translocation and its redistribution to the mitochondria, suggesting that GRP78 and CLU cooperatively promote survival during ER stress in prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3261. doi:1538-7445.AM2012-3261
AN EXPERIMENTAL STUDY OF INTESTINAL OBSTRUCTION.
Authors: R. D. McCLURE
Journal: JAMA (1907)

The problems in connection with intestinal obstruction,<sup>1</sup>aside from the investigation of the causes and best methods of treatment, are concerned chiefly with the explanation of the fulminant symptoms which follow an acute occlusion and which lead rapidly to death, unless the obstruction be promptly relieved. Such symptoms, in their intensity and sudden onset, seem almost out of proportion to the mere retention of intestinal contents, especially since fecal impaction, with an equally complete retention, may persist for a long time without such a violent reaction. Various hypotheses have been offered, and particularly in recent years a number of investigators have endeavored to find an explanation of these remarkable symptoms. As is well known to every surgeon, vomiting, collapse, disturbances of blood pressure, sweating, etc., together with distension and more or less pain, follow quickly on an intestinal occlusion, and if this be not relieved a later train of
Are elderly people living alone an at risk group?
Authors: S. Iliffe, S. S. Tai, A. Haines, S. Gallivan, E. Goldenberg, A. Booroff, P. Morgan
Journal: BMJ (1992)

OBJECTIVE--To test the hypothesis that elderly people living alone are an at risk group with a high level of morbidity that makes high demands on health and social services. DESIGN--Secondary analysis of data from a community survey of 239 people aged 75 and over, identified from general practitioners9 age-sex registers. SETTING--Nine practices in the London boroughs of Brent and Islington. MAIN OUTCOME MEASURES--Scores on the mini-mental state examination; stated satisfaction with life; assessment of mobility; numbers of diagnoses of major physical problems; numbers of prescribed drugs taken; urinary incontinence; alcohol consumption; contacts with general practitioners and hospital outpatient and inpatient services; contact with community health and social services. RESULTS--There were significantly more women among those living alone (93/120 (78%) v 63/119 (53%); p &lt; 0.0005) and the median age of elderly people living alone was higher (81 v 80; p &lt; 0.04). Those living alone and those living with others showed no significant differences in measures of cognitive impairment, numbers of major physical diagnoses, impaired mobility, or use of general practitioner or hospital services. Stated satisfaction with life was somewhat higher in those living alone. Elderly people living alone were significantly more likely to have contact with chiropody, home help, and meals on wheels services and less likely to have someone they could contact in an emergency or at night. Living alone increased the likelihood of contact with one or more community health professionals (district nurses, health visitors, or chiropodists) considered as a group and also increased the likelihood of contact with social services as a whole. There was a tendency for more of those living alone than those living with others to have home visits from their general practitioners, but there were no significant differences in contact with hospital services between the two groups. CONCLUSIONS--Elderly people living alone do not have an excess of morbidity compared with those living with others and do not seem to be an at risk group requiring specifically targeted assessments. More help is needed to provide elderly people living alone with a point of contact in case of emergency.
Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study
Authors: Maarten LJ Smits, Johannes FW Nijsen, Maurice AAJ van den Bosch, Marnix GEH Lam, Maarten AD Vente, Willem PTM Mali, Alfred D van het Schip, Bernard A Zonnenberg
Journal: The Lancet Oncology (2012)
New Insights on the Simultaneous Assessment of Insulin Sensitivity and β-Cell Function With the HOMA2 Method
Authors: Shoichiro Nagasaka, Naoko Sato, Nirei Takahashi, Ikuyo Kusaka, Shun Ishibashi
Journal: Diabetes Care (2007)

We read the article by Caumo et al. (1) with great interest. Using homeostasis model assessment (HOMA), they have simultaneously assessed insulin sensitivity (HOMA-S%) and β-cell function (HOMA-B%) by using the HOMA2 method (2) in a group of 76 normoglycemic subjects with or without obesity. They found the HOMA scatter plot to be reminiscent of the hyperbolic relationship previously reported using acute insulin response and insulin sensitivity index calculated by minimal model analysis of intravenous glucose tolerance testing (3). From their HOMA scatter plot, they also proposed the unique disposition index (DI), …
The error of our ways
Authors: Des Spence
Journal: BMJ (2011)

Medicine is a family. Not a nuclear family, in a framed professional photograph with a fake bookcase in the background, scrubbed school uniforms, and beaming white smiles. Medicine is a chipped tooth dysfunctional family of 15 children living in a small terraced house somewhere up north. The older ones despair of how spoilt the younger ones are, while the younger ones say the older ones never listen. There is notional parental control, but the reality is self regulated anarchy. There is perpetual feuding, kicking, scratching, hair pulling, ganging up, and name calling, but rarely punching. …
Pleural Effusion in Giant Cell Arteritis
Authors: Antonio Ramos, Pedro Laguna, Valentin Cuervas
Journal: Annals of Internal Medicine (1992)

Letters1 June 1992Pleural Effusion in Giant Cell ArteritisAntonio Ramos, MD, Pedro Laguna, MD, Valentin Cuervas, MD, PhDAntonio Ramos, MD, Pedro Laguna, MD, Valentin Cuervas, MD, PhDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-116-11-957_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: A 72-year-old woman presented with a 3-month history of muscle weakness and anorexia followed by nonproductive cough, pleural pain, fever, and progressive dyspnea. She did not have orthopnea, jaw claudication, blurred vision, scalp tenderness, proximal limb pain, tuberculosis, or symptoms of rheumatoid arthritis. Her axillary temperature was 39.1 °C. The temporal arteries were not enlarged or tender. Hypoventilation was noted in the base of the left lung.Laboratory values included a hemoglobin level of 5.84 mmol/L with normochromic, normocytic indices; and a Westergren erythrocyte sedimentation rate of 120 mm/h. A chest roentgenogram showed bilateral pleural effusion. It...References1. PrestonWarner JM. Pericardial effusion as a manifestation of giant cell arteritis. Am J Med. 1991;91:439-40. CrossrefMedlineGoogle Scholar2. GarewalUhlmannBennett HRR. Pericardial effusion in association with giant cell arteritis. West J Med. 1981;134:71-2. MedlineGoogle Scholar3. Miller J. Pericardial effusion and giant cell arteritis. Proc R Soc Lond [Biol]. 1972;65:565. Google Scholar4. Dupond J. Temporal arteritis manifested as acute febrile pericarditis. JAMA. 1982;247:2371-2. CrossrefMedlineGoogle Scholar5. KramerMelzerNesherSonnenblick MEGM. Pulmonary manifestations of temporal arteritis. European Journal of Respiratory Disease. 1987;71:430-3. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Antonio Ramos, MD; Pedro Laguna, MD; Valentin Cuervas, MD, PhDAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInterstitial Lung Disease in Giant Cell ArteritisPulmonary nodules in a patient with Giant Cell ArteritisPulmonary manifestations of large, medium, and variable vessel vasculitisPericardial effusion and giant cell arteritisSystemic Diseases and the PleuraEnfermedades sistémicas y pleuraPericardial Involvement as an Atypical Manifestation of Giant Cell Arteritis: Report of a Clinical Case and Literature ReviewPleural effusion revealing giant cell arteritisPericardial and pleural effusion in giant cell arteritisVarón de 66 años con fiebre de 5 meses de evoluciónPleural effusion as a presenting manifestation of giant cell arteritisLes manifestations respiratoires spécifiques de la maladie de Horton 1 June 1992Volume 116, Issue 11Page: 957-957KeywordsMusclesMyalgiaPainPleural effusionResearch laboratoriesRheumatic painRheumatoid arthritisTemperatureThoraxVision ePublished: 1 December 2008 Issue Published: 1 June 1992 PDF downloadLoading ...
Antibodies from patients with connective tissue diseases bind specific subsets of cellular RNA-protein particles.
Authors: J A Hardin, D R Rahn, C Shen, M R Lerner, S L Wolin, M D Rosa, J A Steitz
Journal: Journal of Clinical Investigation (1982)

We characterized the RNA-containing antigens precipitated by sera from 260 patients with positive antinuclear antibodies. 49 individuals, most of whom had systemic lupus erythematosus or Sjögren's syndrome, possessed antibodies that precipitated the previously identified RNP, Sm, Ro, and La antigens either singly or in combinations. These antigens, which are located on discrete sets of small nuclear or cytoplasmic RNA-protein particles, exhibited a number of antigenic interrelationships. One patient's serum recognized a new particle containing a small RNA which we have called Th; it also precipitated the Ro complexes. Other patients with systemic lupus erythematosus, hepatitis B virus infection, juvenile rheumatoid arthritis, myositis, and rheumatoid arthritis had antibodies that precipitated specific subsets of ribosomal RNA and transfer RNA. One patient's serum contained a monoclonal immunoglobulin G that precipitated ribosomes. Most of these antibodies identified antigenic determinants constituted at least in part of protein. The specificity of the proteins bound to particular cellular RNA, probably explains the exquisite precision with which antibodies from rheumatic disease patients discriminate among RNA subsets. Such sera should be useful probes for investigating specific roles that different RNA and RNA-protein complexes play in cellular metabolism.
911 PROLONGED EFFICACY AND SAFETY OF 3 YEARS OF CONTINUOUS TELBIVUDINE TREATMENT IN POOLED DATA FROM GLOBE AND 015 STUDIES IN CHRONIC HEPATITIS B PATIENTS
Authors: C.-W. Hsu, Y.-C. Chen, Y.-F. Liaw, E. Gane, M. Manns, S. Zeuzem, Y. Wang, C.L. Lai, J. Hou, N. Leung, N. Bzowej, J. Niu, J. Jia, S.G. Hwang, Y. Cakaloglu, H. Ren, G. Papatheodoridis, Y. Chen, W. Bao, P. Lopez
Journal: Journal of Hepatology (2009)
Management of medical research. Experience confirms directors' dissatisfaction.
Authors: P J Barnard
Journal: BMJ (1993)

Council (MRC), finds himself when defending peer review is apparent in his letter' in response to my and Jenny Harrow's papers.2If he believes that our work should not have been published then he is a long way down the road to accepting the fallibility of the peer review system that allowed this, which is the very system he seeks to support.On the other hand, if he believes that peer review delivers the "right" answers then this too gives validity to our peer reviewed arguments about its shortcomings, suggesting that the MRC should give them deeper consideration than it has done.Rees is in danger of seeming to endorse peer review when its findings concur with his own while rejecting its outcomes if they are at odds with his views.