tbuckley/cabot-search huggingface dataset:
Catharsis: On the Art of Medicine
Authors: Kevin Barraclough
Journal: BMJ (2006)

T his is a book about the soul of medicine—and about the relationship of medicine to science. When I incoherently fret about what is happening to doctoring, I realise that I am grieving about the loss of something that this book has captured and closely examined. It is medicine not as audited technical expertise but as an art as old as human suffering—and therefore as old as humanity itself. Andrzej Szczeklik University of Chicago Press, $20/£13, pp 161 ISBN 0 226 78869 5 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> I know nothing about the author, a Polish physician, but I suspect he was a Renaissance polymath in another life. And whoever translated him into English is clearly the Seamus Heaney of Eastern Europe, because every sentence resonates. I don't really know who would read this book, because it is overtly pointless. It drifts around among musical harmonics, leucotrienes, and Nietzsche. Yet if the psalmists had written … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
The High Cost of Lost Opportunities for Prevention
Authors: Stephen Havas
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The article by Dr Hoffman and colleagues<sup>1</sup>details the enormous cost our nation pays for chronic health conditions. It would be easy to bemoan the huge burden of these conditions in terms of higher taxes and health insurance costs, but there is a far larger tragedy that the authors failed to mention: a large proportion of the morbidity, mortality, and costs from chronic conditions is preventable. The major risk factors that cause most chronic diseases have been identified. For example, heart disease is largely attributable to unhealthy diet, elevated blood cholesterol, elevated blood pressure, smoking, and physical inactivity.<sup>2</sup>Cancer is caused largely by unhealthy diet and smoking.<sup>3</sup>Stroke is caused largely by elevated blood pressure.<sup>4</sup>Modifiable risk factors have been delineated for most of the other leading chronic conditions, and research also has identified effective techniques for controlling these risk factors and preventing
Animal rights activist is removed from government committee
Authors: S. Kumar
Journal: BMJ (2003)

India's high profile animal rights activist and former minister for welfare Ms Maneka Gandhi has been removed from her position as chairwoman of the government's Committee for the Purpose of Control and Supervision of Experiments on Animals.

The committee had earned the wrath of Indian scientific researchers over recent years for its approach to animals in scientific research and for its “raids” on both government and private laboratories ( BMJ 2002;325:1192).

The committee—which gives permission to registered institutions to carry out animal …
Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants
Authors: Raquel Moreno-Loshuertos, Rebeca Acín-Pérez, Patricio Fernández-Silva, Nieves Movilla, Acisclo Pérez-Martos, Santiago Rodriguez de Cordoba, M Esther Gallardo, José Antonio Enríquez
Journal: Nature Genetics (2006)
Aspirin induced adverse skin reactions: new pathophysiological aspects
Authors: B. Wedi
Journal: Thorax (2000)

Clinically, aspirin induced adverse skin reactions resemble true immunologically mediated allergic reactions. However, it is well accepted that aspirin intolerance is not mediated by specific IgE antibodies. The exact mechanisms involved are far from clear1 2 and therefore no reliable diagnostic in vitro tests exist, and risky and time consuming provocation tests are regarded as the diagnostic gold standard. Most studies of pathophysiological mechanisms deal with nasal polyps or asthma. However, compared with asthma and nasal polyps, aspirin intolerance is very common in chronic urticaria.3-7 The reason for the preferred organ manifestation is unknown.

Several lines of evidence point to a potent disturbance in the eicosanoid balance (cyclo-oxygenase theory) resulting in a shift towards increased production of leukotrienes.8-12 

Our previous studies have shown that aspirin induced adverse skin reactions proved by positive oral provocation tests are common in chronic urticaria13 and can be characterised by enhanced sulfidoleukotriene production in IL-3 primed leucocyte suspensions after stimulation with C5a.14 15 This study was undertaken to define the rate of positive oral challenge tests in patients with chronic urticaria and a history of adverse skin reactions to aspirin. We also wanted to investigate the sensitivity and specificity of enhanced sulfidoleukotriene production induced by different basophil agonists …
SAT0432 Development of Positive Antinuclear Antibodies and Rheumatoid Factor in Systemic Juvenile Idiopathic Arthritis Points toward an Autoimmune Phenotype Later in the Disease Course
Authors: B. Hugle, C. Hinze, N. Fischer, J.-P. Haas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic onset Juvenile Idiopathic Arthritis (JIA) is now commonly considered part of the group of autoinflammatory diseases. However, systemic inflammation tends to decrease over time, leading to a phenotype of aggressive arthritis similar to other subtypes of JIA. <h3>Objectives</h3> To determine the frequencies of autoantibodies in patients with systemic onset JIA with no active systemic inflammation. <h3>Methods</h3> Patient sera and clinical data were acquired from the AIDnet database, a German database and biobank where samples from patients with inflammatory syndromes including periodic fevers syndromes and systemic onset JIA are collected prospectively. A single center sample of all patients diagnosed with systemic JIA was obtained, and patients with a follow-up of more than one year were included. A retrospective chart survey was used to extract demographic data, clinical course including total joint count and treatment as well as presence and titers of antinuclear antibodies (ANA) and rheumatoid factor (RF) at beginning and during follow-up. Analysis was performed using descriptive statistics, Student's T-Test/Fischer's Exact test, and Spearman's correlation to compare titers of ANA and total active joint count. <h3>Results</h3> 32 patients were included in the study (20/32 female), with a median age of 4.2 years (range 0.5 – 11.4 years). Median follow-up was 6.0 years (range 1.1 - 17.3 years). 96.8% were treated with DMARDs, 65.6% with any TNF antagonist and 71.9% with any other interleukin antagonist during follow-up. 8/32 patients had antinuclear antibody titers ≥ 1:80 at diagnosis, with 22/32 patients showing rising antibody titers with titers ≥ 1:80 at last follow-up (p =0.001). Using measures at 463 time points, there was no correlation between autoantibody titers and total active joint count (r=0.180, p = 0.703). However, 10/32 patients had a positive rheumatoid factor at least once during follow-up, compared to 0/32 at diagnosis (p = 0.001). In five of these patients, positive rheumatoid factors were documented at least twice, more than twelve weeks apart. Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p=0.425) or positive rheumatoid factor (p=0.703). <h3>Conclusions</h3> In this cohort, patients with systemic onset JIA developed increased titers of antinuclear antibodies or positive rheumatoid factor over the course of the disease, independent of treatment with anti-TNF medications. This might point towards an autoimmune, rather than an autoinflammatory phenotype later in the course of systemic onset JIA, possibly caused by B-cell activation as part of the inflammatory process. <h3>Disclosure of Interest</h3> None Declared
X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms
Authors: Robert S. Molday, Ulrich Kellner, Bernhard H.F. Weber
Journal: Progress in Retinal and Eye Research (2012)

X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long-term retinoschisin expression and rescue of retinal structure and function providing a 'proof of concept' that gene therapy may be an effective treatment for XLRS.
Changing Perspectives in the Preexcitation Syndromes
Authors: Agustin Castellanos, Robert J. Myerburg
Journal: New England Journal of Medicine (1987)

After the Wolff–Parkinson–White syndrome was originally described,1 Scherf suggested that the association of a short P-R interval, wide QRS complexes, and a susceptibility to paroxysmal arrhythmias was due to the presence of an accessory pathway capable of conduction in parallel with the normal atrioventricular junctional system.2 During episodes of "circus-movement" tachycardia, the accessory pathways were part of a reentry circuit involving the atria, the normal atrioventricular junctional pathways, the ventricular muscle, and the accessory pathway (Kent bundle) itself, which returned the impulse to atrial tissue. During sinus rhythm, however, the only recognizable manifestation of an accessory pathway was the electrocardiographic . . .
The heart failure revascularisation trial (HEART): rationale, design and methodology
Authors: J.G.F. Cleland, N. Freemantle, S.G. Ball, R.S. Bonser, P. Camici, S. Chattopadhyay, D. Dutka, J. Eastaugh, J. Hampton, S. Large, M.S. Norell, D.J. Pennell, J. Pepper, S. Sanda, R. Senior, D. Smith
Journal: European Journal of Heart Failure (2003)
Pseudotumor cerebri. A complication of parenteral hyperalimentation
Authors: V. K. Saxena
Journal: JAMA (1976)

SINCE THE advent of intravenous hyperalimentation through the subclavian vein, a number of complications have come to light. Pseudotumor cerebri developed in a 19-year-old woman as a result of thrombosis of the internal jugular vein and left transverse sinus. This was treated successfully with steroids and anticoagulants. <h3>Report of a Case</h3> A 19-year-old woman was admitted with complaints of lower-abdominal cramping pain and intermittent, nonbloody diarrhea for one year. Six weeks prior to admission, she had noticed an enlarging mass in the right lower quadrant, and during this period she lost 11.4 kg. She was pale, slightly emaciated, and dehydrated, and in moderate distress. Her pulse rate was 100 beats per minute and regular, and her temperature was 38.6 C. A 6×5-cm, ill-defined, nonfluctuant, tender mass was palpable in the right lower quadrant. The liver and spleen were not palpable and there were no other intra-abdominal masses. There was tenderness
The Chronotropic Action of Glucagon Studied by Direct Perfusion of the Sinus Node.
Authors: Fred W. Whitehouse
Journal: Annals of Internal Medicine (1965)

s1 November 1965The Chronotropic Action of Glucagon Studied by Direct Perfusion of the Sinus Node.Fred W. Whitehouse, M.D., F.A.C.P., Thomas N. James, M. D., F.A.C.P.Fred W. Whitehouse, M.D., F.A.C.P.Search for more papers by this author, Thomas N. James, M. D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-902_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGlucagon has certain actions that resemble those of epinephrine. This similarity led us to study the chronotropic action of glucagon in 26 dogs, utilizing perfusion of the sinus node through its own artery with the intact heart in situ. Glucagon concentrations ranging from 1 X 1O-5 to 100 µg/ml were employed.Glucagon below concentration of 10-1µg/ml had had no significant effect on heart rate. From 10-1µg/ml each successively greater concentration elicited more sinus tachycardia. Maximal acceleration appeared within 1 or 2 min after injection. Peak acceleration was 40 to 70% above control rate, and maximal duration was 45... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 902-903KeywordsArteriesAttentionEpinephrineGlucagonHeartHeart rateLongitudinal studiesTachycardia Issue Published: 1 November 1965 PDF DownloadLoading ...
Effect of Age and Magnesium Depletion on Bone Magnesium Pools in Rats
Authors: Allen C. Alfrey, Nancy L. Miller, Richard Trow
Journal: Journal of Clinical Investigation (1974)

In vivo and in vitro studies were carried out to characterize the exchangeable bone magnesium pool and determine what effect age and magnesium depletion has on bone magnesium. A highly significant correlation was found between the size of the in vitro elutable and in vivo exchangeable bone magnesium (r=0.97). To show that the exchangeable bone magnesium was the surface-limited bone magnesium, elution studies were performed 4 h after the in vivo administration of radiomagnesium. Specific activity in the eluant was 85% of that found in the serum at time of death, suggesting that the elutable and exchangeable bone magnesium pools were largely the same pool. Bone magnesium concentration fell with increasing age. The entire fall in bone magnesium was a result of a decrease in the surface-limited fraction. Since bone crystals have been shown to enlarge with aging with resulting contraction of the surface area, this would be the most apparent explanation for this finding. During magnesium depletion, magnesium concentration in both the exchangeable and nonexchangeable pools decreased. The fractional change in the exchangeable pool was much larger than the change in total or nonexchangeable bone magnesium, suggesting that the surface-limited magnesium pool is available during magnesium depletion. The change in size of the nonexchangeable bone magnesium pool appeared to be more related to the duration of magnesium depletion than the change in serum magnesium levels. The fall in magnesium concentration in this pool is probably a consequence of continuing formation of low magnesium bone during the depletion period.
Technetium 99m stannous pyrophosphate myocardial imaging in patients with and without left ventricular aneurysm.
Authors: M Ahmad, J P Dubiel, T A Verdon, R H Martin
Journal: Circulation (1976)

To further explore the usefulness of technetium 99m pyrophosphate (99mTc-PYP) myocardial imaging and test its validity in the diagnosis of acute myocardial infarction, 99mTc-PYP myocardial scintigrams were performed in 50 patients. Out of 28 patients with acute myocardial infarction, myocardial scintigrams demonstrated localized activity in the 15 patients with transmural, and diffuse activity in the 13 patients with subendocardial myocardial infarction. Twenty-two patients with significant coronary artery disease documented by coronary angiography but without acute myocardial infarction were also studied. Nine of ten patients with clinical evidence of left ventricular aneurysm from previous myocardial infarction and definite left ventricular dyskinesis had positive scintigrams with activity localized to the site of the wall motion abnormality. Two of five patients without definite aneurysm but with left ventricular akinesis also had localized uptake in the involved area of the left ventricle. Seven patients with normal left ventricular wall motion had negative scintigrams. These findings suggest caution in interpreting positive 99mTc-PYP scintigrams as being indicative of acute myocardial infarction when evidence of a left ventricular aneurysm is also present.
Samuel Thomas von Soemmerring
Authors: Phoebe Peck
Journal: New England Journal of Medicine (1960)

SAMUEL Thomas von Soemmerring (Fig. 1), inventor of an early electric telegraph, was born in Thorn, Poland, on January 25, 1755, the son of the city physician. At the age of twenty-three, he received his degree from the University of Göttingen and wrote his thesis on the cranial nerves, using a classification that later superseded that of Willis. A year later he was appointed professor of anatomy at the Collegio Carolino in Kassel, where the only strictly scientific work he did was his classic study of the anthropology of the Negro (1784). He went to Mainz in 1784 as professor . . .
Insulin-Like Growth Factors as Intraovarian Regulators of Granulosa Cell Growth and Function*
Authors: ELI Y. ADASHI, CAROL E. RESNICK, A. JOSEPH D'ERCOLE, MARJORIE E. SVOBODA, JUDSON J. VAN WYK
Journal: Endocrine Reviews (1985)

A relatively large body of evidence now appears to support the existence of the essential ingredients for novel intraovarian IGF-driven control mechanisms. Indeed, evidence presented in this communication is in keeping with the possibility that the granulosa cell may be the site of IGF production, reception, and action. Although the relevance of IGFs to ovarian cell types other than the granulosa cell is largely unknown, one cannot at the present time exclude the possibility of nongranulosa cell contributions to intraovarian IGF production, reception, and action. Indeed, preliminary affinity cross-linking studies (Adashi, Resnick, Svoboda, Van Wyk and D'Ercole; unpublished data) suggest the existence of type-I and type-II receptors in nongranulosa cell compartments. The above notwithstanding, IGFs of granulosa (and possibly circulatory) origins may interact with granulosa cell autoreceptors either independently or in synergy with other granulosa cell agonists. According to this view, IGFs may act in the autocrine mode to stimulate granulosa cell replication on the one hand and promote granulosa cell differentiation on the other. Although proliferation and terminal differentiation may prove mutually exclusive under some circumstances, coexistence of the two processes is being increasingly recognized. In this context, some studies of porcine granulosa cells support a dual role for IGFs in granulosa cell ontogeny. As such, the IGFs can be added to a growing list of growth factors known to modulate granulosa cell growth and function, including EGF, PDGF, and FGF. Our findings indicate that Sm-C/IGF-I synergizes with FSH in the induction of rat granulosa cell aromatase activity at nanomolar concentrations compatible with its granulosa cell receptor binding affinity (thus far studied only in porcine cells. A role for Sm-C/IGF-I in the regulation of this key granulosa cell function would be in keeping with the possibility that Sm-C/IGF-I may partake in the assertion and maintenance of dominance by the selected follicle(s) or in promoting juvenile and early follicular development. Moreover, the ability of Sm-C/IGF-I to potentiate this and other FSH-driven ovarian functions may also account, at least in part, for the puberty-promoting effect of growth hormone. This permissive action of growth hormone has been initially suggested by observation in growth hormone-deficient rats, mice (dwarf mutants, and humans (sporadic, hereditary or acquired growth hormone deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
Abstract 2463: Protease nexin 1 modulates prostate adenocarcinoma by regulating the Hedgehog pathway in humans and mice
Authors: Chad McKee, Danmei Xu, Sheheryar Kabraji, Danny Allen, Veerle Kersemans, John Beech, Sean Smart, Freddy Hamdy, Wan Lam, Theodorus van der Kwast, Robert Bristow, Ruth Muschel
Journal: Cancer Research (2012)

Abstract Prostate adenocarcinoma is the most frequent cancer and is the second leading cause of cancer death of men in the Western world. Aberrant activation of the Hedgehog (Hh) pathway is implicated in the growth and progression of prostate cancer. We show that the Hh pathway is inhibited by the serine protease inhibitor, protease nexin 1 (PN1), an extracellular matrix (ECM) protein highly expressed in normal prostate. We demonstrate here that PN1 regulates Hh signalling by reduction of the Hh ligand, Sonic (SHH), and its downstream effectors in tissue culture and in vivo. Conversely, matrix metalloproteinase 9 (MMP9) enhances Hh signalling through degradation of PN1. MRI imaging was used to determine variation in tumour formation in an orthotopic prostate tumour model using PN1 and MMP9 knock-out mice. In PN1-/- animals, SHH was increased and tumor growth was stimulated. In contrast, PN1 levels were elevated in MMP9-/- mice while Hh signalling was reduced with concomitant decreased tumor growth. Finally, genetic alterations in Hh pathway genes identified by comparative genomic hybridization (CGH) from intermediate risk prostate cancer patients correlated with a worse clinical outcome (HR=2.67, p=0.00067), indicating the importance of this pathway in human cancer. Our data identify PN1 as a novel regulator of SHH and its downstream targets allowing PN1 levels to influence prostate tumor growth. Regulation of the PN1-Hh pathway could constitute a significant therapeutic advance in treating cancers that exhibit high expression of Hh markers. These data also provide a mechanism through which MMP-9 can regulate hedgehog pathway signalling in tissues rich in PN1. 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 2463. doi:1538-7445.AM2012-2463