tbuckley/cabot-search huggingface dataset:
CXCR2 Antagonist MK-7123. A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease
Authors: Stephen I. Rennard, David C. Dale, James F. Donohue, Frank Kanniess, Helgo Magnussen, E. Rand Sutherland, Henrik Watz, Susan Lu, Paul Stryszak, Elizabeth Rosenberg, Heribert Staudinger
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

An antagonist (MK-7123) of the cytokine receptor CXCR2 reduces neutrophil chemotaxis and thus may alleviate airway inflammation in chronic obstructive pulmonary disease (COPD).To assess the efficacy, safety, and tolerability of three dose levels of MK-7123, compared with placebo, in patients with moderate to severe COPD.This 6-month, double-blind study randomized patients with moderate to severe COPD (already on standard therapy) to daily MK-7123 at 10, 30, or 50 mg or placebo. The primary endpoint was change from baseline in post-bronchodilator FEV1.A total of 616 patients (71% male; mean age, 63 yr; 45% current smokers; baseline FEV1 [SD], 1.43 L [0.45]; mean FEV1 percent predicted, 43.9%) were randomized. Only MK-7123 50 mg led to significant improvement in FEV1 over placebo (mean difference [SE], 67 ml [32]). Reduced sputum neutrophil count was observed among the 122 patients examined; P = 0.003 (3 mo) and P = 0.092 (6 mo) (MK-7123 50 mg vs. placebo). The stratum of current smokers, but not that of nonsmokers, showed significant improvement versus placebo in FEV1 (168 ml) and time-to-first exacerbation, and showed numerical improvement in St. George's Respiratory Questionnaire for COPD score. MK-7123 caused a dose-dependent decrease in absolute neutrophil count (ANC) and reduced inflammatory biomarkers matrix metallopeptidase-9 and myeloperoxidase in plasma and sputum; ANC lower than 1.5 × 10(9)/L led to discontinuations with higher doses of MK-7123 (18% in the MK-7123 50-mg group vs. 1% in placebo). Plasma C-reactive protein and fibrinogen increased with MK-7123 treatment. Rates of infections at 6 months were similar in all groups.Treatment with MK-7123 50 mg versus placebo led to significant improvement in FEV1 in patients with COPD, suggesting clinically important antiinflammatory effects with CXCR2 antagonism, although dose-related discontinuations were observed because of ANC decreases with MK-7123. Greater response was observed in smokers versus ex-smokers. Clinical trial registered with www.clinicaltrials.gov (NCT 01006616).
A METHOD FOR CULTIVATING TREPONEMA PALLIDUM IN FLUID MEDIA
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1912)

1. A method is described for obtaining pure cultures of Treponema pallidum and allied species of spirochætæ in fluid media. 2. The principle of the method is based upon the superposition of a favorable culture medium upon a less favorable one. 3. The method here described is not suited to the growth of spirochætæ when they are admixed with contaminating bacteria.
Ancient Descriptions of Hemophilia and Preconception Gender Selection
Authors: Fred Rosner
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Francis and Kasper<sup>1</sup>state that hemophilia is one of the oldest recognized inherited diseases and cite an 1803 medical journal<sup>2</sup>that discusses its pattern of transmission. A familial bleeding disorder, probably hemophilia, is described in the second-century Talmud and subsequent Codes of Jewish Law and rabbinic writings.<sup>3</sup>A boy whose two older male siblings died of bleeding following circumcision may not be circumcised. The same rule applies if two sisters each had a son who died following circumcision; the third sister is forbidden to have her son circumcised. Thus, the direct maternal transmission of the disease, as demonstrated in siblings or maternal cousins, was precisely recognized by the ancient rabbis. Francis and Kasper also suggest that preconception gender selection would be appropriate for prospective parents who wish to avoid having afflicted children but refuse selective abortion. Here, too, the Sages of the Talmud claimed
Cushing's disease presenting with avascular necrosis of the femoral heads and complicated by pituitary apoplexy.
Authors: I P Wicks, D Calligeros, W Kidson, J V Bertouch
Journal: Annals of the Rheumatic Diseases (1987)

A case of Cushing9s disease presenting with avascular necrosis of the femoral heads is described. Eighteen months after the onset of hip symptoms the patient developed pituitary apoplexy and presented to hospital as a medical emergency. Endogenous hypercortisolism is a rare and important cause of avascular necrosis of bone.
Dynamic comparison of the development of combinatory manipulations between chimpanzee and human infants
Authors: Hideko Takeshita
Journal: Behavioral and Brain Sciences (2001)

I present my observations of combinatory manipulations by three infant chimpanzees in a series of test tasks. Common characteristics of motor patterns were observed across the tasks between both infant chimpanzees and 1-year-old infants. Based on the results, I point out that comparative approach can illuminate Thelen et al.'s arguments.
Out of hours primary care centres: characteristics of those attending and declining to attend
Authors: D. K Cragg, S. M Campbell, M. O Roland
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objectives</b>: To study the number, demography, and clinical details of patients who agreed or refused to attend centralised primary care centres for out of hours medical care and to study the satisfaction with the service of those who attended. <b>Design</b>: Data collected by telephonists and doctors. Satisfaction questionnaires given to patients who attended. <b>Setting</b>: Five out of hours primary care centres in the United Kingdom.—All patients contacting the deputising service to request medical help out of hours who were asked to attend a primary care centre. The study terminated when 1000 patients had agreed to attend (200 from each centre). 1000 patients not agreeing to attend were also sampled. <b>Results</b>: The attendance rate varied from 8.9% to 52.3% in the five centres. The overall standardised attendance rate was 22.4%. The attendance rate was highest in children under 5 (465/2380, 19.5%) and fell with increasing age. Of the 1000 sampled nonattenders, 403 said that they had no transport and 345 said that they were too ill to attend. Those who attended were seen by the doctor more quickly. There was no significant difference between the groups in the number who received a prescription (810 attenders v 820 non-attenders, P=0.57) or who were admitted to hospital (59 v 52, P=0.5). Satisfaction with the service among those who attended was very high; 95% (694/731) said that they would be prepared to attend under similar circumstances in the future. <b>Conclusion</b>: Most patients are not able or prepared to attend a central facility for primary care out of hours. Substantial cultural change will be necessary and careful consideration given to planning if such centres are to provide a major part of out of hours care.
Addiction as vulnerabilities in the decision process
Authors: A. David Redish, Steve Jensen, Adam Johnson
Journal: Behavioral and Brain Sciences (2008)

Abstract In our target article, we proposed that addiction could be envisioned as misperformance of a decision-making machinery described by two systems (deliberative and habit systems). Several commentators have argued that Pavlovian learning also produces actions. We agree and note that Pavlovian action-selection will provide several additional vulnerabilities. Several commentators have suggested that addiction arises from sociological parameters. We note in our response how sociological effects can change decision-making variables to provide additional vulnerabilities. Commentators generally have agreed that our theory provides a framework within which to site addiction and treatment, but additional work will be needed to determine whether our taxonomy will help identify and treat subpopulations within the addicted community.
Prazosin Relieves Raynaud's Vasospasm
Authors: Rick Waldo
Journal: JAMA (1979)

EPISODIC digital vasospasm, Raynaud's phenomenon, is a poorly understood pathophysiological phenomenon involving the small arteries and arterioles in the hands, the feet, and occasionally the face. It is differentiated from Raynaud's disease, defined as digital vasospasm for lack of identifiable associated disorders. Numerous therapeutic approaches to episodic digital ischemia have been used, with inconsistent results. Prazosin, a recently released antihypertensive agent, provided clinical improvement in a patient with severe unilateral Raynaud's disease. <h3>Report of a Case</h3> A 60-year-old woman had an 18-month history of painful episodes of tingling and blue discoloration in the fingers of her right hand. These episodes were often precipitated by exposure to cold, were exacerbated by anxiety, and occurred up to ten times daily. The symptoms progressed in intensity despite abstinence from tobacco, and after five months a large ischemic ulcer appeared on the tip of her right index finger. Vasodilator therapy and a right transaxillary
P387Knock-in mouse model of PRKAG2 cardiomyopathy (R299Q) exhibits altered Ca2+-dependent cardiac contractility and reduced protein kinase A activity
Authors: C Turtle, P Robinson, A Yavari, S Ghaffari, K Pinter, H Watkins, C Redwood
Journal: Cardiovascular Research (2014)

Familial hypertrophic cardiomyopathy (HCM) is most commonly caused by mutations in sarcomeric proteins; however, a unifying mechanism of disease pathogenesis has yet to be identified. Beyond the sarcomere, mutations in the gene (PRKAG2) encoding the γ2 subunit of AMP-activated protein kinase (AMPK), an enzyme involved in energy balance regulation and cell signalling, cause ventricular hypertrophy and contractile dysfunction mimicking HCM. These AMPK γ2 mutations also result in glycogen accumulation and aberrant electrical conduction, obfuscating the cause of hypertrophy and dysfunction. Given our recent finding that cardiac troponin I (cTnI) is phosphorylated by AMPK at S150 and this phosphorylation enhances Ca2+ sensitivity of activation, we hypothesise that alterations at the myofilament level may contribute to disease pathogenesis in PRKAG2 cardiomyopathy as they do in HCM.
Mosaic Amplification of Multiple Receptor Tyrosine Kinase Genes in Glioblastoma
Authors: Matija Snuderl, Ladan Fazlollahi, Long P. Le, Mai Nitta, Boryana H. Zhelyazkova, Christian J. Davidson, Sara Akhavanfard, Daniel P. Cahill, Kenneth D. Aldape, Rebecca A. Betensky, David N. Louis, A. John Iafrate
Journal: Cancer Cell (2011)
A brain for all seasons
Authors: R. Allen Gardner
Journal: Behavioral and Brain Sciences (2007)

Merker's fine article opens a new view of brain function consistent with current developments in robotics, heuristics, and fuzzy logic. A reciprocal, tripartite organization of input/motivation/output in the midbrain can accomplish the practical tasks of a brain. A bold move places consciousness in the midbrain, raising profound questions about the practical nature of consciousness.
How Physicians Use Cimetidine
Authors: Robert R. Schade, Robert M. Donaldson
Journal: New England Journal of Medicine (1981)

WHEN the Food and Drug Administration released cimetidine for clinical use in 1977, only two indications were approved; short-term treatment of duodenal ulcer, and treatment of pathologic gastric acid hypersecretory conditions. Nevertheless, physicians presumably prescribe the drug for a much broader range of indications, since sales now amount to $500 million annually. Because little information is available about how cimetidine is actually used in clinical practice, we prospectively surveyed 200 consecutive patients who received cimetidine while hospitalized. We also reviewed published reports concerned with side effects of cimetidine and determined why the drug had been given to the 102 patients . . .
Value and quality of perinatal and infant postmortem examinations: cohort analysis of 400 consecutive deaths
Authors: P. H T Cartlidge, A. T Dawson, J. H Stewart, G. M Vujanic
Journal: BMJ (1995)

To evaluate the contribution that perinatal and infant necropsy makes to clinical practice and to see how this might be influenced by the quality of the investigation.Cohort analysis, with data from the all Wales perinatal survey, of perinatal and infant deaths during 1993 of babies born to mothers usually resident in Wales. The clinicopathological classification of death based on clinical details was compared with the classification after necropsy. Similarly, cases in which necropsy yielded new information were identified. The quality of the necropsy was assessed by scoring six aspects of the examination.400 consecutive deaths at 20 weeks of gestation to 1 year of age.Necropsy rate, effect of necropsy on clinicopathological classification, new information disclosed by necropsy, quality of necropsies, and the link between new information and quality of the necropsy.Necropsy was performed in 232 cases (58%). The clinicopathological classification was altered by necropsy in 29 cases (13%). New information was obtained in 60 cases (26%), and in 42 (18%) it disclosed the cause of death. The quality of necropsy was substantially higher when the main cause of death was detected than when nothing new was found.Necropsy is underused. Clinicians should be more positive about necropsies and realise how much clinically relevant information can be obtained from a good quality examination.
Papillary Muscle Dysfunction.
Authors: George E. Burch
Journal: Annals of Internal Medicine (1966)

s1 May 1966Papillary Muscle Dysfunction.George E. Burch, M.D., F.A.C.P., N. P. DePasquale, M.D., F.A.C.P.George E. Burch, M.D., F.A.C.P.Search for more papers by this author, N. P. DePasquale, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1157_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptNormal mitral valve function depends upon the maintenance of the proper spatial relationships between the papillary muscles, the chordae tendinae, and the mitral valve leaflets throughout the cardiac cycle. Papillary muscle dysfunction may occur as a result of (1) ischemia or infarction of a papillary muscle, (2) ventricular dilatation (including aneurysm), (3) rupture of a papillary muscle, (4) inflammatory disease of a papillary muscle, and (5) interventricular conduction disturbances.Papillary muscle dysfunction results in mitral regurgitation and an apical systolic murmur. The characteristics of the murmur vary depending upon the etiology of the papillary muscle dysfunction. In the case of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: George E. Burch, M.D., F.A.C.P.; N. P. DePasquale, M.D., F.A.C.P.Affiliations: New Orleans, Louisiana PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1157-1157KeywordsAneurysmsCardiac musclesEtiologyInfarctionIschemiaMitral insufficiencyMyositisPapillary musclesSystolic ejection murmur ePublished: 1 December 2008 Issue Published: 1 May 1966 PDF downloadLoading ...
Increased suppression of intracoronary C-myc protein synthesis within the stent or balloon injury site using an intravenous microbubble delivery system containing antisense to C-myc: Comparison with direct intracoronary injection
Authors: Thomas R. Porter, Derek Knapp, Lucia Venneri, Joseph Oberdorfer, John Lof, Patrick Iversen, Feng Xie
Journal: Journal of the American College of Cardiology (2003)
Only Homosexual Haitians, not all Haitians
Authors: Reynald Altema, Leslie Bright
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 December 1983Only Homosexual Haitians, not all HaitiansREYNALD ALTEMA, M.D., LESLIE BRIGHT, M.D.REYNALD ALTEMA, M.D.Search for more papers by this author, LESLIE BRIGHT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-6-877_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Gottlieb and associates (1), citing data from the Centers for Disease Control, listed 5% of patients with the acquired immunodeficiency syndrome as Haitians and 5% as "others. " We believe this classification is misleading because it lends itself to far more interpretations or conclusions than there are data to support them. For example, it's commonly believed that this syndrome is a Haitian disease or that it originated in Haiti. However, not until the recent epidemic of the syndrome has Kaposi's sarcoma been seen there (LIAUTAUD B, LAROCHE C, DUVIVIER J, PEAN-GUIEHARD C. Le sarcome de Kaposi (maladie...References1. GOTTLIEBGROOPMANWEINSTEINFAHEYDETELS MJWJR. The acquired immunodeficiency syndrome. Ann Intern Med. 1983;99:208-20. LinkGoogle Scholar2. QUINNSTAMMGOODELL TWS. The polymicrobial origin of intestinal infections in homosexual men. N Engl J Med. 1983;309:576-82. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: East Orange Veterans Administration Hospital East Orange, NJ 07019 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1983Volume 99, Issue 6Page: 877-878KeywordsAIDSHomosexualsKaposi sarcoma Issue Published: 1 December 1983 PDF downloadLoading ...
THE SURGICAL TREATMENT OF TRAUMATIC HEMORRHAGE OF THE SPLEEN.
Authors: N. SENN
Journal: JAMA (1903)

The timely and intelligent application of the modern hemostatic resources enables the surgeon to deal successfully with external hemorrhage, but the treatment of visceral hemorrhage from the large vascular internal organs is by no means a closed chapter. Hemorrhage from wounds of the spleen, liver and kidneys is usually profuse, and is more frequently the result of injury to the parenchyma and veins than to the principal artery or its larger branches; in other words, the loss of blood is more frequently due to parenchymatous and venous than arterial hemorrhage. As a rule, the severity of traumatic hemorrhage of these organs bears a direct relation to the degree of their vascularity. The absence of muscular tissue in these organs is largely responsible for the profuseness of the hemorrhage and the difficulties encountered in attempts to arrest it. The severed vessels do not contract; their lumina remain patent, thus maintaining
Adjuvant therapy for cutaneous malignant melanoma
Authors: Marie-France Demierre, Howard K. Koh
Journal: Journal of the American Academy of Dermatology (1997)

We discuss the current status of adjuvant therapy for melanoma by first reviewing the rationale and goals of adjuvant therapy and then analyzing the results of published randomized trials. We pay particular attention to adjuvant interferon trials that raise many challenging issues in the management of patients with melanoma at high risk of recurrence. Past adjuvant trials have used immunotherapeutic approaches, chemotherapy, radiation therapy, as well as hormonal and retinoid therapy. We also summarize ongoing adjuvant trials.
Psoralen and Ultraviolet A Light Therapy for Psoriasis
Authors: Robert S. Stern
Journal: New England Journal of Medicine (2007)

A 52-year-old man with psoriasis seeks treatment for his skin condition. Treatment with psoralen and ultraviolet A (PUVA) is recommended. PUVA has been used since the 1970s for the treatment of psoriasis, although few randomized studies and clinical trials comparing this treatment with no treatment or with other forms of treatment have been conducted. PUVA therapy increases the risks of both nonmelanoma skin cancer and melanoma.
A leaner nativist solution to the origin of concepts
Authors: Jean M. Mandler
Journal: Behavioral and Brain Sciences (2011)

Abstract There must be innate conceptual machinery, but perhaps not as much as Carey proposes. A single mechanism of Perceptual Meaning Analysis that simplifies spatiotemporal information into a small number of conceptual primitives may suffice. This approach avoids the complexities and ambiguities of interactions between separate dedicated analyzers and central concepts that Carey posits, giving learning a somewhat larger role in early concept formation.
Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus.
Authors: K Matsumoto, Y Yoshikai, T Asano, K Himeno, A Iwasaki, K Nomoto
Journal: The Journal of Experimental Medicine (1991)

Transplantation of bone marrow cells of lpr/lpr mice into irradiated normal mice fails to develop massive lymphadenopathy or autoimmunity but causes severe graft-vs.-host-like syndrome. To elucidate an abnormality of lpr/lpr bone marrow-derived T cells, we transplanted bone marrow cells of Mlsb lpr/lpr mice into H-2-compatible Mlsa non-lpr mice. Although lpr/lpr T cell precursors repopulated the host thymus as well as +/+ cells, a proportion of CD4+CD8+ cells decreased, and that of both CD4- and CD8- single-positive cells increased compared with those of +/+ recipients. Notably, in MRL/lpr----AKR and C3H/lpr----AKR chimeras, CD4 single-positive thymocytes contained an increased number of V beta 6+ cells in spite of potentially deleting alleles of Mlsa, whereas V beta 6+ mature T cells were deleted in the MRL/+ ----AKR and C3H/+ ----AKR chimeras. There was no difference between MRL/+ ----AKR and MRL/lpr----AKR chimeras in their proportion of V beta 3+ cells because both host and donor strain lack the deleting alleles. Interleukin 2 receptor expression of mature T cells, in the thymus and lymph node, was obviously higher in the MRL/lpr----AKR chimeras, in particular in the "forbidden" V beta 6+ subset. Moreover, lpr donor-derived peripheral T cells showed vigorous anti-CD3 response. These results indicate that lpr-derived T cells escape not only tolerance-related clonal deletion but also some induction of unresponsiveness in the non-lpr thymus.
Application of a closely linked polymorphism of restriction fragment length to counselling and prenatal testing in families with myotonic dystrophy.
Authors: A L Meredith, S M Huson, P W Lunt, M Sarfarazi, H G Harley, J D Brook, D J Shaw, P S Harper
Journal: BMJ (1986)

The close genetic linkage between the loci for apolipoprotein CII (ApoC2) and myotonic dystrophy makes ApoC2 the closest fully validated marker for prediction of myotonic dystrophy. Application to genetic counselling and presymptomatic and prenatal prediction is reported in seven families with myotonic dystrophy, including one case in which the disorder was excluded prenatally. Only one of the families did not have members with ApoC2 genotypes that allowed prediction, but careful clinical study of older family members was found to be an important factor. ApoC2 typing of families with myotonic dystrophy should be of practical help both in prediction for asymptomatic relatives and for prenatal diagnosis in pregnancies of an affected parent.
Assessment of Real-Time Polymerase Chain Reaction Detection of Acanthamoeba and Prognosis Determinants of Acanthamoeba Keratitis
Authors: Yoshifumi Ikeda, Dai Miyazaki, Keiko Yakura, Asako Kawaguchi, Ryoko Ishikura, Yoshitsugu Inoue, Tsuyoshi Mito, Atsushi Shiraishi, Yuichi Ohashi, Shiro Higaki, Motoki Itahashi, Masahiko Fukuda, Yoshikazu Shimomura, Kenji Yagita
Journal: Ophthalmology (2012)
THE PROGNOSTIC VALUE OF LEFT VENTRICULAR DYSSYNCHRONY BY GATED SPECT MYOCARDIAL PERFUSION IMAGING IN PATIENTS WITH END STAGE RENAL DISEASE
Authors: Nilay Kumar, Himanshu Aggarwal, Shikha Mehta, Roslyn Mannon, Jaekyeong Heo, Ami Iskandrian, Fadi Hage
Journal: Journal of the American College of Cardiology (2013)