tbuckley/cabot-search huggingface dataset:
Postnatal ultrastructural changes in the cat myocardium: a morphometric study
Authors: D. J. SHERIDAN, M. J. CULLEN, M. J. TYNAN
Journal: Cardiovascular Research (1977)

In order to understand more clearly the basis for our previously observed postnatal age related changes in the mechanical performance of the cat myocardium we have carried out a quantitative ultrastructural analysis of right ventricular papillary muscles obtained from adult cats (1.8 to 2.3 kg), infant cats (16 days of age), and neonatal kittens (less than 72 hours old). Volume fractions were calculated for myofibrils, sarcoplasm, mitochondria, lipid, sarcoplasmic reticulum (SR), golgi, and nuclei. The myofibril content of neonatal fibres was significantly less than that of the infant or adult groups (P less than 0.05 and 0.005 respectively). In addition the infant fibres contained a smaller volume of myofibrils than the adult ones (P less than 0.001). The mitochondrial content of the neonatal fibres was also significantly less than that of either the infants' (P less than 0.005) or adults' (P less than 0.001). These data provide an anatomical basis for the progressive age related increase in mechanical performance of the cat myocardium, in postnatal life.
Activation of the MEF2 transcription factor in skeletal muscles from myotonic mice
Authors: Hai Wu, Eric N. Olson
Journal: Journal of Clinical Investigation (2002)

Becker syndrome, a recessive nondystrophic myotonia caused by mutations in the chloride channel 1 gene (CLCN1), is characterized by delayed muscle relaxation after contraction. The ADR (arrested development of righting response) mouse is an animal model for Becker syndrome. Skeletal muscles from ADR myotonic animals show an increased number of oxidative fibers with a lack of glycolytic fibers as well as signs of muscle hypertrophy. Through breeding ADR myotonic mice with mice harboring a MEF2-dependent reporter gene, we found that the transcriptional activity of MEF2 was dramatically enhanced in myotonic muscles. Post-translational induction of MEF2 transcriptional activity correlated with the activation of p38 MAPK and did not affect MEF2 DNA-binding affinity. Expression of class II histone deacetylases (HDACs), which repress MEF2-dependent gene expression, was significantly reduced in skeletal muscles from myotonic mice. These findings suggest that the combined effects of class II HDAC deficiency and p38 MAPK activation lead to potent upregulation of MEF2 transcriptional activity, which contributes to the long-term changes in gene expression and fiber-type transformation observed in myotonic skeletal muscles. These findings provide new molecular targets for potential treatment of congenital myotonia.
1001-25 Primary results of the rapid emergency department heart failure outpatient trial (REDHOT): A multicenter trial examining B-type natriuretic peptide levels, emergency physician decision making and outcomes in patients presenting with shortness of breath
Authors: Alan S Maisel, Judd Hollander, David Guss, Peter McCullough, Richard Nowak, Gary Green, Mitchell Saltzberg, Radmilia Kazanegra, Paul Clopton, Robert Jesse
Journal: Journal of the American College of Cardiology (2004)
Initial and Maintenance Digitalization
Authors: Earl N. Silber
Journal: JAMA (1963)

<h3>To the Editor:</h3> —In the Oct 13, 1962, issue ofThe Journal(<b>182</b>:192), an article by Rosenblum appeared, titled, "Maintenance of Digitalis Effects After Rapid Parenteral Digitalization." Twenty patients (Group A) received 1.6 mg of deslanoside intravenously and were redigitalized 24 hr later with an oral dose of 1.6 mg of acetyldigitoxin. In the remaining 19 patients (Group B), initial digitalization with deslanoside was followed 24 hr later by the daily administration of 0.15 mg of acetyl-digitoxin. Several objections can be raised to this study. Firstly, the number of patients studied was small and the two groups were not entirely comparable: the average age in Group A was 61.6 yr as compared to 66.0 yr in Group B. Although this is not a striking difference, only 55% of the patients in Group A were 60 yr of age or over, compared to 69% in Group B. Consistent with the
Incidence and impact of abnormal liver function in patients receiving adjuvant chemotherapy for early breast cancer.
Authors: IR Macpherson, J Laskey, S Harden, P Canney
Journal: Cancer Research (2009)

Abstract Abstract #4112 Background: Abnormalities in liver function tests (LFTs) which complicate adjuvant polychemotherapy may prompt prescribers to institute a dose reduction or delay due to fears of altered pharmacokinetics and increased toxicity. However, inappropriate reduction in dose intensity is associated with reduced efficacy of adjuvant therapy. We wished to identify the incidence of abnormal liver function and its influence on decision-making and toxicity in patients (pts) receiving adjuvant chemotherapy for early breast cancer in the west of Scotland.&amp;#x2028; Methods: Data including baseline characteristics, LFTs (bilirubin, AST, ALT) on day 1 of each chemotherapy cycle, hematologic and grade 3/4 non-hematologic toxicity, dose delay or dose reduction were prospectively collected for 160 female pts commencing adjuvant chemotherapy at the Beatson West of Scotland Cancer Centre between August 2005 and February 2006. Association between LFT abnormality on day 1 of each chemotherapy cycle and toxicity occurring within that cycle was determined.&amp;#x2028; Results: The most common regimen administered was Epirubicin-CMF (n=128; epirubicin 100mg/m2 q3/52 x4; cyclophosphamide 600mg / m2, methotrexate 40mg/m2, 5-FU 600mg/m2 d1+8 q4/52 x 4) followed by AC (n=25; Doxorubicin 60mg/m2, Cyclophosphamide 600mg/m2 q3/52 x4), FEC (n=5) and CMF (n=3). Median age was 55 yrs. Febrile neutropenia or grade 3 /4 non-hematologic toxicity were recorded in 1.9% and 3.2% of cycles respectively. 8.5% of all cycles were delayed and 14% of pts (n=23) had a dose reduction. In only 1 patient was dose reduction due to abnormal LFTs. Grade 1, 2 or 3 hyperbilirubinemia occurred in 3%, 2% and 0% of pts respectively. Grade 1, 2 or 3 elevated ALT occurred in 39%, 9% and 3% of pts. Grade 1, 2 or 3 elevated AST occurred in 38%, 4%, and 1% of pts respectively. No episodes of grade 4 hyperbilirubinemia or elevated transaminases occurred. Despite receiving chemotherapy at full dose no patient with grade 2/3 elevated AST or ALT on day 1 of a chemotherapy cycle experienced either grade 3/4 non-hematologic toxicity or febrile neutropenia in that cycle.&amp;#x2028; Discussion: Although grade 1 elevation in transaminases was common, particularly in the context of the Epirubicin-CMF regimen, grade 2 or 3 abnormalities were infrequent. The absence of grade 3/4 chemotherapy-related toxicity in pts with grade 2/3 LFT abnormality supports maintenance of full dose anthracycline-based polychemotherapy in this population. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4112.
Lack of ecto-5′-nucleotidase (CD73) promotes arteriogenesis
Authors: Yang Chul Böring, Ulrich Flögel, Christoph Jacoby, Matthias Heil, Wolfgang Schaper, Jürgen Schrader
Journal: Cardiovascular Research (2012)

Adenosine can stimulate angiogenesis, but its role in the distinct process of arteriogenesis is unknown. We have previously reported that mice lacking ecto-5′-nucleotidase (CD73−/−) show enhanced monocyte adhesion to the endothelium after ischaemia, which is considered to be an important trigger for arteriogenesis. Hindlimb ischaemia was induced in wild-type (WT) and CD73−/− mice to study the role of extracellularly formed adenosine in arteriogenesis. Magnetic resonance angiography (MRA) was performed for serial visualization of newly developed vessels at a spatial resolution of 1 nL, and high-energy phosphates (HEP) were quantified by 31P MR spectroscopy (MRS). MRA of CD73−/− mice revealed substantially enhanced collateral artery conductance at day 7 [CD73−/−: 0.73 ± 0.11 a.u. (arbitrary units); WT: 0.44 ± 0.13 a.u.; P < 0.01, n = 6], and MRS of the affected hindlimb showed a faster restoration of HEP in correlation with enhanced functional recovery in the mutant. Additionally, histology showed no differences in capillary density between the groups but showed an increased monocyte infiltration in hindlimbs of CD73−/− mice. Serial assessment of dynamic changes of vessel growth and metabolism in the process of arteriogenesis demonstrate that the lack of CD73-derived adenosine importantly promotes arteriogenesis but does not alter angiogenesis in our model of hindlimb ischaemia.
Immunologic and hematopoietic effects of CD40 stimulation after syngeneic bone marrow transplantation in mice.
Authors: S Funakoshi, D D Taub, M R Anver, A Raziuddin, O Asai, V Reddy, H Rager, W C Fanslow, D L Longo, W J Murphy
Journal: Journal of Clinical Investigation (1997)

CD40 is a molecule present on multiple cell types including B lymphocyte lineage cells. CD40 has been shown to play an important role in B cell differentiation and activation in vitro, although little is known concerning the effects of CD40 stimulation in vivo. We therefore examined the effects of CD40 stimulation in mice using a syngeneic bone marrow transplantation (BMT) model in an effort to augment B cell recovery after high dose therapy with hematopoietic reconstitution. After the BMT, mice were treated with or without 2-6 microg of a soluble recombinant murine CD40 ligand (srmCD40L) given intraperitoneally twice a week. A significant increase in B cell progenitors (B220+/ surface IgM-) was observed in the bone marrow of mice receiving the srmCD40L. The treated recipients also demonstrated improved B-cell function with increases in total serum immunoglobulin and increased splenic mitogen responsiveness to LPS being noted. Additionally, srmCD40L treatment promoted secondary lymphoid organ repopulation, accelerating germinal center formation in the lymph nodes. Total B cell numbers in the periphery were not significantly affected even with continuous srmCD40L administration. Lymphocytes obtained from mice treated with the ligand also had increases in T cell mitogen and anti-CD3 mAb responsiveness and acquired the capability to produce IL-4. Surprisingly, treatment with srmCD40L also produced hematopoietic effects in mice, resulting in an increase of BM and splenic hematopoietic progenitor cells in the mice after BMT. Treatment with srmCD40L significantly increased granulocyte and platelet recovery in the peripheral blood. Incubation of BMC with srmCD40L in vitro also resulted in increased progenitor proliferation, demonstrating that the hematopoietic effects of the ligand may be direct. Thus, stimulation of CD40 by its ligand may be beneficial in accelerating both immune and hematopoietic recovery in the setting of bone marrow transplantation.
A monokine stimulates production of human erythroid burst-promoting activity by endothelial cells in vitro.
Authors: K S Zuckerman, G C Bagby, E McCall, B Sparks, J Wells, V Patel, D Goodrum
Journal: Journal of Clinical Investigation (1985)

Conditioned media were prepared from human peripheral blood monocytes and human umbilical vein endothelial cells. These media were assayed for erythroid burst-promoting activity (BPA) using human peripheral blood monocyte-depleted mononuclear cells as targets and assessing the stimulatory effect of the conditioned media on growth of early erythroid progenitor cells. Both monocytes and endothelial cells produced modest amounts of detectable BPA. Addition of varying concentrations of media conditioned by monocytes to plateau concentrations (5-10%) of media conditioned by endothelial cells had no additive effect. Endothelial cells incubated in the presence of 50% monocyte-conditioned medium produced 2.5- to 6.6-fold more BPA than did endothelial cells incubated only in control tissue culture medium. In contrast, endothelial cell conditioned medium did not stimulate increased BPA production by monocytes. Neither neutrophil- nor marrow fibroblastoid cell-conditioned medium stimulated BPA production by endothelial cells. Therefore, both monocytes and endothelial cells produce BPA. Moreover, monocytes produce a monokine that, in turn, stimulates the production of BPA by endothelial cells. Inasmuch as a monokine also has been shown to stimulate production of granulocyte-macrophage colony-stimulating activity, we propose that monocytes play a critical role in regulating the production of humoral regulators of the very early stages of hemopoietic cell differentiation.
More mentally ill people reported in US prisons
Authors: C. Chelala
Journal: BMJ (1999)

A growing number of people with mental illness are being held in US prisons, according to a recent report by the US Department of Justice.

The report is the first in-depth national study of mental illness in US prisons. It reported a total of 283800 prison inmates with some form of mental illness in mid-1998, which is about 16% of the total prison population. …
White Coat Pockets
Authors: Martin W. Oster
Journal: Annals of Internal Medicine (1999)

Letters19 October 1999White Coat PocketsMartin W. Oster, MDMartin W. Oster, MDColumbia University College of Physicians & Surgeons; New York, NY 10032 (Oster)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-8-199910190-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the article by Lynn and Bellini on white coat pockets (1). Their observation of an inverse relation between experience (knowledge) and crowding of the pockets reminded me of my internal medicine preceptor's comments some 30 years ago when I was a third-year medical student. Pointing at my bulging white coat pockets, which contained the Washington Manual as well as my own “black book” of medical pearls, he simply remarked, “the second best place.” Needless to say, this wise clinician carried only a stethoscope in his white coat pocket.Reference1. Lynn LA, Bellini LM. Portable knowledge: a look inside white coat pockets. Ann Intern Med. 1999;130:247-50. LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Martin W. Oster, MDAffiliations: Columbia University College of Physicians & Surgeons; New York, NY 10032 (Oster) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPortable Knowledge: A Look Inside White Coat Pockets Lorna A. Lynn and Lisa M. Bellini Metrics 19 October 1999Volume 131, Issue 8 Page: 632 ePublished: 15 August 2000 Issue Published: 19 October 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Agranulocytosis Secondary to Chlorthalidone Therapy
Authors: Martin Klein
Journal: JAMA (1963)

CHLORTHALIDONE (Hygroton), 3-hydroxy-3-(4-chloro-3-sulfamyl-phenyl) phthalimidine, introduced in 1958, is an oral diuretic with long duration of action, which is effective in various edematous states<sup>1-3</sup>and in hypertension.<sup>3, 4</sup>Chlorthalidone differs chemically from the thiazide diuretics in that it has a phthalimidine nucleus instead of the benzothiadiazine configuration. They are similar, in that they are both sulfonamides. The usual side effects found with thiazide diuretics such as hypokalemia, hyperuricemia, and decreased glucose tolerance, may also be found with chlorthalidone.<sup>3,5,6</sup>However, to date, there have been no instances of blood dyscrasias reported in the literature. A single case of pancytopenia is listed in the "Tabulation of the Registry of Blood Dyscrasias" of the Council on Drugs of the American Medical Association.<sup>7</sup>The purpose of this paper is to report a case of agranulocytosis which is believed to be due to chlorthalidone therapy. <h3>Report of a Case</h3> A 54-yr-old
NOTES ON ANESTHETICS.
Authors: D. H. GALLOWAY
Journal: JAMA (1901)

A man can not do two things at once so skilfully as he can do either one of them by itself. A surgeon can not do his most skilful operating while devoting half his attention to the anesthetic. A surgeon is frequently more concerned about the result of the anesthetizer's work than he is about the results of his own work. Constant anxiety about the anesthetic divides the attention of the surgeon between what he is doing and what some one else is doing and must hinder the progress of the operation. In many cases more skill is required to administer the anesthetic than is required to do the operation. An operation may be practically devoid of danger; an anesthetic is never administered without jeopardizing the life of the patient. In more than half of the cases the patient is in greater danger from the anesthetic than he is from
Senior house officers: the lost tribes.
Authors: L Dillner
Journal: BMJ (1993)

There are more senior house officers than doctors in any other training grade in Britain but nobody knows what they do in hospitals or has a clear idea what skills they should be learning. Nobody is responsible for them and they suffer from having a poor career structure and inadequate training. Now that there are government initiatives to reduce the hours that junior doctors work and to limit the time it takes to train to become a specialist, the problems that senior house officers face can no longer be ignored. A conference for senior house officers held last week talked about the problems that they face and tried to find some solutions.
Antimicrobial Use in Animal Feed — Time to Stop
Authors: Sherwood L. Gorbach
Journal: New England Journal of Medicine (2001)

Antimicrobials have been used in food animals in North America and Europe for nearly half a century. Among the most common are drugs that are either identical to or related to those administered to humans, including penicillins, tetracyclines, cephalosporins (including ceftiofur, a third-generation cephalosporin), fluoroquinolones, avoparcin (a glycopeptide that is related to vancomycin), and virginiamycin (a streptogramin that is related to quinupristin-dalfopristin). These antimicrobial agents are given to food animals as therapy for an infection or, in the absence of disease, for subtherapeutic purposes with the goals of growth promotion and enhanced feed efficiency (improved nutritional benefits of the animal . . .
Computational modeling of emotion: explorations through the anatomy and physiology of fear conditioning
Authors: Jorge L. Armony, David Servan-Schreiber, Jonathan D. Cohen, Joseph E. LeDoux
Journal: Trends in Cognitive Sciences (1997)

Recent discoveries about the neural system and cellular mechanisms in pathways mediating classical fear conditioning have provided a foundation for pursuing concurrent connectionist models of this form of emotional learning. The models described are constrained by the known anatomy underlying the behavior being simulated. To date, implementations capture salient features of fear learning, both at the level of behavior and at the level of single cells, and additionally make use of generic biophysical constraints to mimic fundamental excitatory and inhibitory transmission properties. Owing to the modular nature of the systems model, biophysical modeling can be carried out in a single region, in this case the amygdala. Future directions include application of the biophysical model to questions about temporal summation in the two sensory input paths to amygdala, and modeling of an attentional interrupt signal that will extend the emotional processing model to interactions with cognitive systems.
Consultants threaten strike over contract stalemate
Authors: Z. Kmietowicz
Journal: BMJ (2003)

<h3>Introduction</h3> Multimodal pain therapy (MPT) has been established accounting for biopsychosocial consideration in diagnostic and therapy. MPT seems to be effective, but comparability of studies is limited due to diversity of study designs and outcome measurements. The presented study aims to develop a <i>core outcome set</i> consisting of a minimum of outcome measures deemed necessary for medical and therapeutic decision-making, which must be measured in all clinical trials and non-randomised intervention studies. <h3>Methods and analysis</h3> The study consists of several parts. First, the development and recommendation of preliminary core outcome domains will be based on results of a systematic review and structured online surveys. Participants of the expert panel are representatives of methodological, medical, physiotherapeutic, psychotherapeutic profession and patients suffering from chronic pain (n=25). Subsequently, candidate instruments to measure preliminary core outcome domains will be recommended by these experts. Therefore, systematic reviews on measurement properties of preliminary outcome measures will be conducted and finalised in a consensus meeting. Consented instruments and lacking psychometric properties of relevant instruments will be addressed and validated in the following part, a prospective multicentre study in multimodal pain centres on approximately 300 patients with chronic pain. Based on all previous results, a core outcome set for MPT measured in effectiveness studies and daily recordkeeping will be finalised by consensus. Statistical analyses will be performed according to methodological standards (COSMIN). <h3>Ethics and dissemination</h3> The methods and procedure of the study are developed in compliance with the ethical principles of the Helsinki Declaration and Good Epidemiologic Practice. Recruitment of study participants will require approval of the study by the responsible ethics committee and signed informed consent from each participant. Pseudonymised data will be used for statistical analysis.
Low grade radiographic sacroiliitis as prognostic factor in patients with undifferentiated spondyloarthritis fulfilling diagnostic criteria for ankylosing spondylitis throughout follow up
Authors: G Huerta-Sil
Journal: Annals of the Rheumatic Diseases (2005)

To determine the rate and factors associated with ankylosing spondylitis in a cohort of patients with undifferentiated spondyloarthritides (SpA).62 consecutive patients with undifferentiated SpA seen between 1998 and 1999 underwent clinical and imaging evaluations throughout follow up. The main outcome measure was a diagnosis of ankylosing spondylitis.50 patients with peripheral arthritis (n = 35) and inflammatory back pain (n = 24) (26 male; mean (SD) age at onset, 20.4 (8.8) years; disease duration 5.4 (5.7) years) were followed up for 3-5 years. At baseline, >90% of patients had axial and peripheral disease, while 38% had radiographic sacroiliitis below the cut off level for a diagnosis of ankylosing spondylitis (BASDAI 3.9, BASFI 2.9). At the most recent evaluation, 21 patients (42%) had ankylosing spondylitis. Two factors were associated with a diagnosis of ankylosing spondylitis in multivariate analysis: radiographic sacroiliitis grade <2 bilateral, or grade <3 unilateral (odds ratio (OR) = 11.18 (95% confidence interval, 2.59 to 48.16), p = 0.001), particularly grade 1 bilateral (OR = 12.58 (1.33 to 119.09), p = 0.027), and previous uveitis (OR = 19.25 (1.72 to 214.39), p = 0.001). Acute phase reactant levels, juvenile onset, and HLA-B27 showed a trend to linkage with ankylosing spondylitis (NS).Low grade radiographic sacroiliitis is a prognostic factor for ankylosing spondylitis in patients originally classified as having undifferentiated SpA. Low grade radiographic sacroiliitis should be regarded as indicative of early ankylosing spondylitis in patients with undifferentiated SpA.
ALTERATIONS OF FLUID AND ELECTROLYTE DISTRIBUTION AND RENAL FUNCTION IN DIARRHEA OF INFANCY 1
Authors: Avrum L. Katcher, Marvin F. Levitt, Avron Y. Sweet, Horace L. Hodes, Charlotte Spanier, Herbert Haber
Journal: Journal of Clinical Investigation (1953)

ing the acute stage of dehydration and during the subsequent period of treatment and recovery.