tbuckley/cabot-search huggingface dataset:
Caring for the Patient With AIDS-Reply
Authors: David E. Rogers
Journal: JAMA (1988)

<h3>In Reply.—</h3> The elegant letter by Dr Atkins is absolutely on target; I agree with him completely. My thanks to him for picking up on a point that others may have misinterpreted as well. In no way did I wish to imply that the precautions now in practice in emergency departments are inappropriate. They represent not only medical common sense, but are of absolutely critical importance today. My sorrow was related to what I perceived as the subtle attitudinal change in the feelings of emergency department personnel about critically ill young people. I was not quarreling their use of better and safer technologies.
Extracoronary Atherosclerotic Plaque at Multiple Sites and Total Coronary Calcification Deposit in Asymptomatic Men
Authors: A. Simon, P. Giral, J. Levenson
Journal: Circulation (1995)

Background Recent studies have suggested that knowledge of the extent of subclinical atherosclerosis may improve prognostic information in subjects at risk of cardiovascular disease. Therefore, we tested the value of extracoronary plaque detected with echography at multiple sites and that of total coronary calcification deposit evaluated with ultrafast computed tomography for predicting the risk of coronary events estimated on the basis of traditional risk factors. Methods and Results We analyzed in 618 asymptomatic at-risk men the extent of extracoronary atherosclerosis, as assessed with ultrasound imaging of carotid, aortic, and femoral sites and coded as number of disease sites (none, one, two, or three) on the basis of the presence of plaque at each site, and the amount of total coronary calcification deposit, as evaluated with ultrafast computed tomography and coded as grade 0, 1, 2, or 3 on the basis of the determination of a total coronary calcium score. Concomitantly, age, systolic pressure, total and HDL cholesterol levels, current smoking, presence of diabetes, and presence of ECG left ventricular hypertrophy (ECG-LVH) were evaluated with the goal of estimating coronary risk with the use of the Framingham Study risk algorithm. The prevalence rates of at least one extracoronary disease site and coronary calcification (any grade) were high (72% and 63%). There was a strong association between the number of extracoronary disease sites and the grade of coronary calcification ( P &lt;.001). As the number of extracoronary disease sites increased, age, systolic pressure, smoking frequency, and number of risk factors increased ( P &lt;.001). As the grade of coronary calcification increased, age and systolic pressure increased ( P &lt;.001), as did the number of risk factors ( P &lt;.01). The estimated coronary risk increased with the number of extracoronary disease sites and the grade of coronary calcification ( P &lt;.001). The odds ratio of coronary risk between three and no extracoronary disease site was 2.37 (95% confidence interval [CI], 1.08 to 5.21), whereas that between grade 3 and grade 0 of coronary calcification was 1.79 (95% CI, 0.94 to 3.40). Conclusions In an apparently healthy population, the extracoronary atherosclerotic burden as measured with multiple-site echography appears to be more powerful than the ultrafast computed tomography–detected coronary calcium burden in reflecting the multifactorial coronary risk profile. However, only men were included in the present study, and the present findings cannot be extrapolated to women.
Occasional Use of Marijuana-Reply
Authors: Roland E. Herrington
Journal: JAMA (1988)

In Reply. —  I would like to rebut Dr Schwartz's statement that I am a Milwaukee psychiatrist. I am a Milwaukeebased addictionologist, certified by the American Medical Society on Alcoholism and Other Drug Dependencies, and I have practiced addictionology on a full-time basis for the past 15 years.  I share the concerns of Dr Schwartz about the use and abuse of marijuana. However, the Florida physician's question was quite specific and effectively excluded many of the concerns raised by Dr Schwartz. There are no data that would warrant the many assumptions made by Dr Schwartz.  There are hundreds of thousands of recreational drug users in this country who fall far short of the drug dependency syndrome. The same is true for problem drinkers who would not meet the diagnostic criteria for the disease of alcoholism. Our society seems to engage in black or white thinking about chemical dependency.  Dr Schwartz
Electrolytes and Cardiovascular Diseases: Physiology, Pathology, Therapy, vol 2: Clinical Aspects
Authors: Alfred Soffer
Journal: JAMA (1966)

The second volume of this symposium on the role of electrolytes in cardiovascular disease consists of clinical studies contributed by an international group of investigators. While the communications are intended to provide current reviews, the defects of multiple-authorship texts are apparent—frequent repetition of historical and basic data. There is, however, a more distressing feature of this volume. In the editorial foreword, Dr. Bajusz notes, "I often encouraged the contributors to present not merely plain facts, but also to freely express views and to formulate working hypotheses." This may be a salutary approach if utilized as a basis for a thought-provoking dialogue among research units, but it presents serious dangers if these views are presented as recommendations for wide-spread clinical application. Approximately 50% of the contributions concern potassium therapy for the treatment of a variety of cardiologic abnormalities. Many of these studies present the results obtained by the administration of a
EU tightens drug safety law before it is even implemented
Authors: R. Watson
Journal: BMJ (2012)

The European Union is taking the highly unusual step of amending new measures on drug safety before the legislation introducing them, agreed almost 18 months ago, has even come into force.

The move to tighten up pharmacovigilance legislation agreed in December 2010 follows the launch last year of a major drug safety inquiry in France into the type 2 diabetes treatment benfluorex (Mediator), made by the French company Servier. 

Widely prescribed in Europe, especially France, the drug, which had been taken by some …
Latent TGF-β–binding protein 4 modifies muscular dystrophy in mice
Authors: Ahlke Heydemann, Ermelinda Ceco, Jackie E. Lim, Michele Hadhazy, Pearl Ryder, Jennifer L. Moran, David R. Beier, Abraham A. Palmer, Elizabeth M. McNally
Journal: Journal of Clinical Investigation (2009)

Most single-gene diseases, including muscular dystrophy, display a nonuniform phenotype. Phenotypic variability arises, in part, due to the presence of genetic modifiers that enhance or suppress the disease process. We employed an unbiased mapping approach to search for genes that modify muscular dystrophy in mice. In a genome-wide scan, we identified a single strong locus on chromosome 7 that influenced two pathological features of muscular dystrophy, muscle membrane permeability and muscle fibrosis. Within this genomic interval, an insertion/deletion polymorphism of 36 bp in the coding region of the latent TGF-β–binding protein 4 gene (Ltbp4) was found. Ltbp4 encodes a latent TGF-β–binding protein that sequesters TGF-β and regulates its availability for binding to the TGF-β receptor. Insertion of 12 amino acids into the proline-rich region of LTBP4 reduced proteolytic cleavage and was associated with reduced TGF-β signaling, decreased fibrosis, and improved muscle pathology in a mouse model of muscular dystrophy. In contrast, a 12-amino-acid deletion in LTBP4 was associated with increased proteolysis, SMAD signaling, and fibrosis. These data identify Ltbp4 as a target gene to regulate TGF-β signaling and modify outcomes in muscular dystrophy.
It's time to put the placebo out of our misery
Authors: R. Nunn
Journal: BMJ (2009)

IL-12 and PGE<sub>2</sub> promote and inhibit, respectively, the development of Th1 responses. Production of these mediators by APC residing in the central nervous system (CNS) may be involved in the local regulation of the T cell phenotype during infectious and autoimmune CNS diseases. In the present study we have examined IL-12 and PGE<sub>2</sub> secretion by cultured microglia and astrocytes from the mouse brain upon Ag-dependent interaction with I-A<sup>d</sup>-restricted, OVA<sub>323–339</sub> specific TCR transgenic Th1 and Th2 cell lines. We show that microglia, which restimulate efficiently both Th1 and Th2 cells, secrete IL-12 upon Ag-dependent interaction with Th1, but not with Th2 cells. Th1-driven IL-12 production depends on TCR ligation by MHC class II/peptide complexes, CD40 engagement on microglia, and IFN-γ secretion by activated Th1 cells. Th1 and, to a lesser extent, Th2 cells also stimulate the production of PGE<sub>2</sub> by microglia. T cell-mediated induction of PGE<sub>2</sub> requires MHC class II/peptide/TCR interactions but does not depend on CD40 engagement or on the presence of IFN-γ. Astrocytes, which preferentially activate Th2 cells, fail to produce IL-12 and secrete negligible amounts of PGE<sub>2</sub> upon interaction with either Th1 or Th2 cells. These results suggest that during CNS infection or immunopathology, IL-12 produced by microglia upon Ag-specific interaction with Th1 cells may further skew the immune response to Th1, whereas the T cell-dependent production of PGE<sub>2</sub> by microglia may represent a negative feedback mechanism, limiting the propagation of Th1 responses.
Bioequivalence of Levothyroxine Preparations: Industry Sponsorship and Academic Freedom
Authors: Carter H. Eckert
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Knoll Pharmaceutical Company appreciates the opportunity to comment on the study by Dr Dong and colleagues.<sup>1</sup> In 1987, Knoll's predecessor, Flint Laboratories, entered into an agreement with Dong and colleagues to study 4 levothyroxine preparations, including Flint's Synthroid (levothyroxine sodium tablets) brand. The protocol included a provision that "all data obtained by the investigator... is also considered confidential and is not to be published or otherwise released without written permission from Flint...." In April 1989, while the study was ongoing, the company communicated concerns about the study's execution to Dong and colleagues. Despite repeated requests, we were unable to reach agreement with the investigators on the resolution of these concerns. We did not withdraw funding because the study was nearly complete when the flaws were discovered and dialogue with the investigators on their resolution had just begun. As a partner in research, we have a responsibility
Hematopoietic stem-cell transplantation from unrelated donors in elderly patients (age&gt;55 years) with hematologic malignancies: older age is no longer a contraindication when using reduced intensity conditioning
Authors: A Shimoni, N Kröger, T Zabelina, F Ayuk, I Hardan, M Yeshurun, N Shem-Tov, A Avigdor, I Ben-Bassat, A R Zander, A Nagler
Journal: Leukemia (2004)
Single assessment of risk predicted which elderly patients would fall
Authors: C. Price, M. Suddes, L. Maguire, S. Harrison, D. O'Shea
Journal: BMJ (1998)

EDITOR—Oliver et al used a scientific approach to develop an evidence based risk assessment tool that predicts with high specificity which elderly inpatients will fall.1 Between July and September 1996 we examined risk factors prospectively for 154 patients admitted to two acute and rehabilitation geriatric wards in a district general hospital. Our aim was to identify factors on admission that might have predictive value for the duration of the inpatient episode. A simple risk assessment form for falls was completed once by the admitting nurse. …
A case of jaundice with a mediastinal mass
Authors: R Sinha
Journal: Gut (2005)

Background: We aimed to determine whether obese subjects experience more gastro-oesophageal reflux (GORS) symptoms than normal subjects, and further to determine if this association was explained by oesophagitis or medications that lower oesophageal sphincter pressure.Methods: In a representative Swedish population, a random sample (n = 1001, mean age 53.5 years, 51% women) had upper endoscopy.GORS was defined as any bothersome heartburn or acid regurgitation.Results: The prevalence of obesity (body mass index >30) was 16%; oesophagitis was significantly more prevalent in obesity (26.5%) than in normal subjects (9.3%).There were associations between obesity and GORS (odds ratio (OR) 2.05 (95% confidence interval (CI) 1.39, 3.01)), epigastric pain (OR 1.63 (95% CI 1.05, 2.55)), irritable bowel symptoms (OR 1.58 (95% CI 1.05, 2.38)), any abdominal pain (OR 1.59 (95% CI 1.08, 2.35)), vomiting (OR 3.11 (95% CI 1.18, 8.20)), retching (OR 1.74 (95% CI 1.1.3,2.67)), diarrhoea (OR 2.2 (95% CI 1.38, 3.46)), any stool urgency (OR 1.60 (95% CI 1.04, 2.47)), nocturnal urgency (OR 2.57 (95% CI 1.33, 4.98)), and incomplete rectal evacuation (OR 1.64 (95% CI 1.09, 2.47)), adjusting for age, sex, and education.When subjects with oesophagitis and peptic ulcer were excluded, only diarrhoea, incomplete evacuation, and vomiting were significantly associated with obesity.The association between GORS and obesity remained significant adjusting for medication use (OR 1.9 (95% CI 1.3, 3.0)).Conclusions: GORS is associated with obesity; this appears to be explained by increased upper endoscopy findings in obesity.
Repolarization abnormalities and their arrhythmogenic consequences in porcine tachycardia-induced cardiomyopathy
Authors: D Lacroix
Journal: Cardiovascular Research (2002)

Objectives: Action potential prolongation related to the alteration of several membrane currents is constantly reported in heart failure (HF) but reports about its role in arrhythmogenesis are sparse. Our aim was to determine, by analogy with long QT syndromes, whether prolonged repolarization is associated with increased dispersion or linked to bradycardia-dependent ventricular arrhythmias in pacing-induced cardiomyopathy. Methods: QT intervals, action potentials and transmural activation-to-recovery intervals (ARIs) along with whole-cell delayed rectifier (IK) and transient outward (Ito1) K+ currents were recorded in left ventricle from pigs with HF and controls. HF was obtained after 14 days of rapid pacing at 250 ms. Results: Repolarization was delayed as indexed by corrected QT intervals (13.7% increase, P<0.01) or ARIs (252±4 to 340±7 ms, P<0.01). ARIs were uniformly prolonged with disappearance of the transmural gradient, spatial dispersion of repolarization decreased by 50% (P<0.05). Ito1 density was reduced in HF from 1.35±0.1 to 0.57±0.04 pA/pF subepicardially, from 1.05±0.19 to 0.55±0.08 pA/pF midmyocardially and from 1.04±0.1 to 0.48±0.04 pA/pF subendocardially. IK density was significantly decreased in HF pigs vs. controls: subepicardially from 0.46±0.04 to 0.22±0.02 pA/pF; midmyocardially from 0.46±0.05 to 0.25±0.03 pA/pF; and subendocardially from 0.49±0.04 to 0.20±0.04 pA/pF following depolarization at +50 mV. Electrocardiogram (ECG) monitoring at the time of death did not disclose any polymorphic ventricular tachyarrhythmia. Conclusion: Despite a profound alteration in K+ currents, repolarization is uniformly prolonged in this model with no proclivity to develop bradycardia-dependent arrhythmias.
Genetics of fibrosing lung diseases
Authors: J. C. Grutters, R. M. du Bois
Journal: European Respiratory Journal (2005)

Genetic studies in familial lung fibrosis have demonstrated an association with surfactant protein C genes: two mutations have been found resulting in protein misfolding and causing type-II epithelial cell injury. Remarkably, different histological patterns were observed in the affected subjects, suggesting the influence of modifier genes and/or environmental factors. Surfactant protein C gene variations have not, however, been associated with sporadic cases, i.e. idiopathic pulmonary fibrosis (IPF). Susceptibility to IPF probably involves a combination of polymorphisms related to epithelial cell injury and abnormal wound healing. To date, the genetic associations with IPF that have been reported in different cohorts include the genes encoding tumour necrosis factor (TNF; −308 adenine), interleukin-1 receptor antagonist (+2018 thymidine) and association with severity and progression (interleukin-6/TNF receptor II and transforming growth factor-β1 (TGFB1; +869 cytosine)), but none of these associations have been replicated by others. Unlike in IPF, immunological inflammation seems to be more prominent in the pathogenesis of scleroderma lung fibrosis, being an autoimmune disease with specific autoantibodies, such as antitopoisomerase antibodies, in patients with diffuse lung disease, and anticentromere antibodies, in patients with pulmonary vascular disease. Antitopoisomerase antibody positivity is associated with the carriage of human leukocyte antigen DRB1*11 and DPB1*1301 alleles, suggesting the recognition of a specific amino-acid motif. Extended haplotype analysis also supports the conclusion that TNF may be the primary association with anticentromere positivity. Intriguingly, associations with TGFB1 and genes involved in extracellular matrix homeostasis have been reported in this disease. In conclusion, significant steps forward have been taken in the understanding of the genetic contribution to fibrosing lung diseases, but major challenges lay ahead. It is the present authors' opinion that only a combined approach studying large numbers of familial and sporadic cases, all clinically well phenotyped, using multiple distinct cohorts, and genotyped according to relevant gene ontologies will be successful. It will be necessary to be particularly vigilant with regard to phenotype; the absence of very strong reproducible associations may be because of the rigidity of phenotype definition, coupled with the possibility that idiopathic pulmonary fibrosis may still be a heterogeneous group of diseases, despite the more rigid definition set out by the European Respiratory Society/American Thoracic Society statement.
Characterization of the expression and activation of the epidermal growth factor receptor in squamous cell carcinoma of the skin
Authors: G.B. Fogarty, N.M. Conus, J. Chu, G. McArthur
Journal: British Journal of Dermatology (2006)

Locally advanced skin cancers including squamous cell carcinoma (SCC) of the skin are increasing in incidence. Patients are often elderly with significant comorbidities and therapy can be difficult. New targeted therapies, such as treatment directed at the epidermal growth factor receptor (EGFR), may be effective and less toxic in these patients. However, before designing appropriate clinical trials it is necessary to characterize the expression and activation of targets such as the EGFR to evaluate the rationale of using EGFR inhibitors (EGFRIs) in the treatment of this type of cancer.To characterize the expression and activation by phosphorylation of EGFR in SCC of the skin by quantitative Western blotting using the LiCor immunofluorescence detection system with validation by immunohistochemistry. Secondary objectives were to evaluate downstream targets of EGFR expression and activation in SCC of the skin and to examine the associations between EGFR, pathological features and clinical behaviour of these tumours.Twenty-one mainly locally advanced skin SCCs collected in our institution and stored in our tissue bank over a 4-year period were used for the study.Nine of 21 (43%) tumours expressed EGFR above background. Of those nine, five expressed phosphorylated EGFR. There was no correlation with downstream activation of canonical signalling pathways, pathological features or clinical behaviour.EGFR is expressed in a minority of tumours and then is not always activated. These results show that, before designing a trial with a targeted agent such as an EGFRI in SCC of the skin, it is important to verify the presence of the appropriate target to maximize the best outcome.
Leukemia Inhibitory Factor Inhibits T Helper 17 Cell Differentiation and Confers Treatment Effects of Neural Progenitor Cell Therapy in Autoimmune Disease
Authors: Wei Cao, Yiqing Yang, Zhengyi Wang, Ailian Liu, Lei Fang, Fenglan Wu, Jian Hong, Yufang Shi, Stewart Leung, Chen Dong, Jingwu Z. Zhang
Journal: Immunity (2011)
The Toxoplasma Apicoplast Phosphate Translocator Links Cytosolic and Apicoplast Metabolism and Is Essential for Parasite Survival
Authors: Carrie F. Brooks, Hanne Johnsen, Giel G. van Dooren, Mani Muthalagi, San San Lin, Wolfgang Bohne, Karsten Fischer, Boris Striepen
Journal: Cell Host & Microbe (2010)
Introductory Remarks Concerning Neural Factors in Essential Hypertension
Authors: EDGAR A. KAHN
Journal: Circulation (1958)

The vasoconstrictor effect of neural stimuli from frontal and hypothalamic centers to the blood vessels, including the renal arterioles, is reviewed. Such a theory of the pathogenesis of hypertension is probably deficient, since humoral or atherogenic factors also play a part. Nevertheless, splanchnicectomy may sometimes alleviate superimposed vasoconstriction and help in treatment of the patient.
Women's reasons for not participating in follow up visits before starting short course antiretroviral prophylaxis for prevention of mother to child transmission of HIV: qualitative interview study
Authors: Thomas M Painter, Kassamba L Diaby, Danielle M Matia, Lillian S Lin, Toussaint S Sibailly, Moïse K Kouassi, Ehounou R Ekpini, Thierry H Roels, Stefan Z Wiktor
Journal: BMJ (2004)

To find out why pregnant women who receive HIV-1 positive test results and are offered short course antiretroviral prophylaxis to prevent transmission of HIV from mother to child do not participate in necessary follow up visits before starting prophylaxis.Qualitative interview study.A programme aiming to prevent transmission of HIV from mother to child at a public antenatal clinic in Abidjan, Côte d'Ivoire.Purposive sample of 27 women who had received HIV-1 positive test results and were invited to return for monthly follow up visits before starting prophylaxis with zidovudine at 36 weeks' gestation, but who had either refused or discontinued the visits. None of the women started prophylaxis.Most of the women explained their non-participation in follow up visits by referring to negative experiences that they had had while interacting with programme staff or to their views about the programme. Additional reasons concerned their disbelief of HIV positive test results and personal factors.Difficulties experienced by women during their contacts with staff working on the prevention programme and negative views that they have about the programme can contribute to their non-participation in prophylaxis. Training and supervision of programme staff may increase the likelihood of positive interactions between staff and clients, thereby facilitating women's participation in preventing transmission of HIV from mother to child. Outreach and mobilisation in communities that are served by prevention programmes may complement these measures at programme level by contributing to increased social support for women's efforts to prevent transmission of HIV from mother to child.
Controversial costs of cocaine
Authors: D. Page
Journal: JAMA (1992)

To the Editor.  —In the article by Phibbs et al, 1 The Neonatal Costs of Maternal Cocaine Use, the abstract did not adequately reflect the results presented in the article. In the results section of the abstract, the authors state that the cost of neonatal care until medically cleared for discharge was significantly higher for cocaine-exposed than for non-cocaine-exposed infants. This leaves the reader to assume that cocaine exposure is the factor that explains the impressive difference.  However, the two populations compared in the study (cocaine-exposed and non-cocaine-exposed) differed in several important ways. These included use of other substances, adequacy of prenatal care, smoking, racial composition, age, and gravidity of mothers. Each of these variables could be important confounders and (as the authors rightly demonstrated) should be controlled in drawing conclusions as to the effect of the cocaine exposure itself.  In the body of the text the authors are