tbuckley/cabot-search huggingface dataset:
Bronchodilator effect of sodium cromoglycate and its clinical implications.
Authors: N C Thomson, C J Clark, G Boyd, F Moran
Journal: BMJ (1981)

recipients in the same manner as Smithells because, since the January 1980 press reports of the initial Merrell v Mekdeci trial, general practice prescrib- ing has altered dramatically.The prescribing of Debendox fell sharply in February 1980 and has remained at a low level, less than half its former rate.Drug utilisation data in the context of information from the surveillance of congenital malformations can help to estimate the extent of possible drug-associated teratogenic prob- lems and to corroborate the results of anecdotal reports and epidemiological studies.In the light of the alteration in Debendox prescribing we await with interest the congenital mal- formation surveillance findings both of England and Wales and of Northern Ireland.
End-results in Primary Sterility
Authors: S. Bender
Journal: BMJ (1952)

According to a report in the New York Times (August 14) all packages of chloramphenicol distributed in the United States must now bear a special warning label.The label will read: " Warning: blood dyscrasias may be associated with intermittent or prolonged use.It is essential that adequate blood studies be made."This ruling by the Food and Drug Administration, Washington, follows a nation- wide survey of blood-disorder cases.Out of 410 cases reviewed by a committee of the National Research Council, 177 were found to have been associated with the use of chloramphenicol.' About half of these cases were fatal.Death was attributed to failure of haemopoiesis in the bone marrow.The committee, headed by
Gene Scene: Factor VIII Gene Explains Just Half of Severe Cases of Hemophilia A
Authors: Teri Randall
Journal: JAMA (1991)

THE MOST severe form of hemophilia A, in which there is virtually no factor VIII activity in the blood, has become an enigma to molecular biologists seeking a genetic basis for the disorder. Over the years, chromosome linkage analysis has linked hemophilia A to the factor VIII gene on the X chromosome in every family studied by this technique. Yet in a study published last month, researchers found no mutations in the factor VIII gene in half of the severe cases examined (<i>Proc Natl Acad Sci USA.</i>1991;88:7405-7409). "We have found no point mutations, no deletions, no insertions, and no substitutions," says Stylianos Antonarakis, MD, associate professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, Md. "The entire coding region of the gene is normal." <h3>A First in Genetics</h3> "This is the first time in which we have had a well-mapped, well-known gene in a relatively common
THE ASSOCIATION OF LEFT VENTRICULAR REMODELING WITH RIGHT VENTRICULAR STRUCTURE AND FUNCTION: THE MESA-RIGHT VENTRICLE STUDY
Authors: Susan Matulevicius, Aditya Jain, David Bluemke, Harjit Chahal, Joao AC Lima, Mark H. Drazner, Craig Johnson, Jorge R. Kizer, Richard Kronmal, Steven M. Kawut
Journal: Journal of the American College of Cardiology (2011)
Apocynin improves the efficacy of secretory leukocyte protease inhibitor in experimental emphysema.
Authors: J Stolk, W Rossie, J H Dijkman
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Secretory leukocyte protease inhibitor (SLPI) is a potent proteinase inhibitor produced in the lung. Stimulated neutrophils at sites of inflammation can inactivate SLPI by myeloperoxidase-mediated oxidation of the methionine residue in the active site of SLPI. Apocynin is a selective inhibitor of NADPH oxidase and may therefore protect SLPI against neutrophil-mediated oxidative inactivation. The aim of the present study was to determine the effect of apocynin on the efficacy of SLPI in preventing experimental emphysema. To investigate the effect of apocynin on emphysema without SLPI treatment, three groups of eight hamsters each received drinking water containing apocynin at concentrations of 2, 20, and 200 micrograms/ml, respectively. Emphysema was induced in these hamsters by intratracheal instillations of 500 micrograms of lipopolysaccharide (LPS) twice a week for 4 wk. In hamsters that received 200 micrograms/ml apocynin, the development of emphysema was reduced by 26.2% (p = 0.01). Other apocynin concentrations had no effect. The experiment was repeated, with SLPI added to the treatment. Of a total of six groups of hamsters, four groups (three with apocynin and one with solvent) received twice-weekly doses of a mixture of 500 micrograms of LPS and 1 mg SLPI in 200 microliters saline in the trachea for 4 wk. In addition, each LPS instillation was followed 24 and 48 h later by an instillation containing 1 mg of SLPI. Apocynin (20 and 200 micrograms/ml) improved the protective effect of SLPI from 37 to 64% and 79%, respectively (p < 0.01). We conclude that oral administration of apocynin can improve the efficacy of SLPI in preventing LPS-induced emphysema.
Abstract 79: The compartmentalization of folate metabolism depends on two isoforms of folylpoly-γ-glutamate synthetase and the mitochondrial folate transporter
Authors: Scott A. Lawrence, Richard G. Moran
Journal: Cancer Research (2010)

Abstract The reactions of folate metabolism are distributed between the cytosolic and mitochondrial compartments of mammalian cells and both components are essential for mammalian cell survival. The enzyme folylpoly-γ-glutamate synthetase (FPGS) has been shown to be essential for the intracellular retention of folates as polyglutamate derivatives. The fpgs gene produces two transcripts, one for an isoform with a leader peptide targeting it to the mitochondrial matrix, and the other is transcribed without this sequence, so that the encoded isoform remains in the cytosol. Transfer of folates into the mitochondrial matrix is mediated by an inner mitochondrial membrane transport protein, the mitochondrial folate transporter (MFT). Either deletion of the MFT or of mitochondrial FPGS is cytotoxic and renders the cell auxotrophic for glycine; the mechanism of this effect is far from apparent. To better understand this compartmentalization, we generated cell lines that express only the cytosolic or mitochondrial isoform of FPGS under tetracycline-inducible control in FPGS-null AuxB1 cells. Western blot analysis of the FPGS protein in these cell lines indicate that both FPGS isoforms are expressed near endogenous levels in the presence of doxycycline and that each cell line solely expresses the FPGS isoform in the respective compartment. Clonogenic survival of each doxycycline-induced cell line demonstrates a cellular requirement for each FPGS isoform. Additional studies showed that cells complemented with cytosolic FPGS only accumulated and retained folates in the cytosol but not mitochondria, leading us to conclude that folate polyglutamates are not substrates for the MFT. In addition, expression of only the mitochondrial form of FPGS resulted in cells that progressively trapped folates in the mitochondria, leading us to the concept that folate polyglutamates do not escape the mitochondria. However, cytosolic folates were observed in cells expressing only mitochondrial FPGS. We are currently using these cell lines to study the transfer of folates across the mitochondrial membrane and polyglutamation in each compartment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 79.
Rheumatic Syndromes of Hypothyroidism and Myxedema.
Authors: John H. Bland
Journal: Annals of Internal Medicine (1969)

s1 May 1969Rheumatic Syndromes of Hypothyroidism and Myxedema.John H. Bland, M.D., F.A.C.P., John W. Frymoyer, M.D.John H. Bland, M.D., F.A.C.P.Search for more papers by this author, John W. Frymoyer, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1060_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptConnective tissue endocrinology is relatively unexplored, although rheumatic syndromes may characterize certain endocrine diseases. From 1954 to 1967, 74 undiagnosed rheumatic disease patients were clinically diagnosed as having hypothyroidism and myxedema in rheumatic disease clinics and private practices; laboratory confirmation followed in 38 patients; 5 patients had no objective supporting system signs; and 22 patients were excluded due to other accompanying causes for rheumatic symptoms and signs. Eleven myxedema patients are reported, all referred by internists for "arthritis." All recovered completely on thyroid replacement therapy.The clinical, radiologic, and biochemical characteristics of rheumatic syndromes of hypothyroidism and myxedema are presented,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Burlington, Vermont PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1060-1060KeywordsArthritisConnective tissueConnective tissue diseasesEndocrinologyHypothyroidismResearch laboratoriesSigns and symptomsThyroid Issue Published: 1 May 1969 PDF downloadLoading ...
Disruption of the guanylyl cyclase-C gene leads to a paradoxical phenotype of viable but heat-stable enterotoxin-resistant mice.
Authors: S Schulz, M J Lopez, M Kuhn, D L Garbers
Journal: Journal of Clinical Investigation (1997)

Heat-stable enterotoxins (STa), which cause an acute secretory diarrhea, have been suggested to mediate their actions through the guanylyl cyclase-C (GC-C) receptor. The GC-C gene was disrupted by insertion of neo into exon 1 and subsequent homologous recombination. GC-C null mice contained no detectable GC-C protein. Intestine mucosal guanylyl cyclase activity was approximately 16-fold higher in wild-type mice than in the GC-C null mice, and STa-stimulable guanylyl cyclase activity was absent in the null animals. Thus, GC-C is the major cyclase activity present in the intestine, and also completely accounts for the STa-induced elevations of cGMP. Gavage with STa resulted in marked fluid accumulation within the intestine of wild-type and heterozygous suckling mice, but GC-C null animals were resistant. In addition, infection with enterotoxigenic bacteria that produce STa led to diarrhea and death in wild-type and heterozygous mice, while the null mice were protected. Cholera toxin, in contrast, continued to cause diarrhea in GC-C null mice, demonstrating that the cAMP signaling pathway remained intact. Markedly different diets (high carbohydrate, fat, or protein) or the inclusion of high salt (K+, Na+) in the drinking water or diet also did not severely affect the null animals. Given that GC-C is a major intestinal receptor in all mammals, the pressure to retain a functional GC-C in the face of diarrhea-inflicted mortality remains unexplained. Therefore, GC-C likely provides a protective effect against stressors not yet tested, possibly pathogens other than noninvasive enterotoxigenic bacteria.
Effects of corticosteroids and immunosuppressors on idiopathic inflammatory myopathy related myocarditis evaluated by magnetic resonance imaging
Authors: Y Allanore
Journal: Annals of the Rheumatic Diseases (2006)

Cardiac involvement in idiopathic inflammatory myopathy has been recognised as an important prognostic factor, but treatment remains empirical.To investigate the effects of corticosteroids and immunosuppressors on myocarditis in patients with inflammatory myopathies.Patients with inflammatory myositis of recent onset who had not received treatment were evaluated for associated myocarditis by magnetic resonance imaging (MRI) and reinvestigated after treatment with high dose corticosteroids and immunosuppressors.Four patients with histologically proven myositis were included. Two patients with polymyositis had cardiac clinical symptoms. Two other patients with dermatomyositis and diffuse cutaneous systemic sclerosis-polymyositis overlap syndrome were asymptomatic. In three cases the usual conventional screening tests were normal. For all patients an area of contrast enhancement and hypokinesia detected by cardiac MRI was markedly reduced after treatment with corticosteroids and immunosuppressors for 6 months.Treatment with intravenous methylprednisolone followed by prednisone and immunosuppressive therapy seems to be effective for treating myocardial involvement in patients with idiopathic inflammatory myopathies, either alone or presenting as overlap syndromes. Cardiovascular MRI is a non-invasive technique that may be a powerful tool for diagnosis and monitoring of myocardial inflammation in this setting.
Anomalous Muscle Bundle of the Right Ventricle
Authors: RUSSELL V. LUCAS, RICHARD L. VARCO, C. WALTON LILLEHEI, PAUL ADAMS, RAY C. ANDERSON, JESSE E. EDWARDS
Journal: Circulation (1962)

Seven examples of anomalous muscle bundles of the right ventricle have been presented. In one patient having an associated ventricular septal defect, spaces between the anomalous muscle were confused surgically with the ventricular septal defect. In the remaining six cases, the anomalous muscle bundle caused obstruction within the right ventricular cavity. Five of these patients had associated ventricular septal defect, with a clinical picture resembling that of the cyanotic or acyanotic tetralogy of Fallot. The cases served to demonstrate that the surgeon who exposes the right ventricle to relieve an obstructive lesion in the right ventricular infundibulum or in the pulmonary valve, may find no such lesions in these locations but instead may be dealing with an obstruction more proximal than these areas. Relief of the obstruction within the right ventricle may be attained by resecting the anomalous muscle mass. In one patient having intact ventricular septum and pulmonary valvular stenosis, an anomalous muscle bundle within the right ventricle which lay proximal to the infundibulum was responsible for persistent right ventricular obstruction after pulmonary valvotomy. Anomalous muscle bundles in the right ventricle may be suspected when, in the angiocardiogram, they cause filling defects within the right ventricle.
Clinicians' contributions to district management teams
Authors: R T Marcus
Journal: BMJ (1982)

developed in parallel with peripheral services but should also be subject to the same limit of available resources.Since the publication of the Dawson report in the 1920s there has been ample evidence that general practitioners in the UK should have inpatient facilities.It has been suggested that 40% of patients in district general hospital medical beds do not require the investigative facilities of these beds and could equally be managed by their family doctors provided they had inpatient facilities.In many rural
The Carcinoid Syndrome: Chronic Treatment with Para-Chlorophenylalanine
Authors: WINSTON G. SATTERLEE
Journal: Annals of Internal Medicine (1970)

Para-chlorophenylalanine is a potent depleter of tissue serotonin (5-hydroxytryptamine). Since 5-hydroxytryptamine may contribute to the pathogenesis of several aspects of the carcinoid syndrome, for 1 year we treated a patient with this syndrome with para-chlorophenylalanine. A 59-year-old man developed chronic diarrhea, hepatomegaly, right-sided valvular heart lesion, and cutaneous flush. Exploratory abdominal examination showed ileal carcinoid tumor metastatic to liver and nodes. Urine 5-hydroxyindoleacetic acid and serum 5-hydroxytryptamine levels were abnormally high. Para-chlorophenylalanine treatment promptly reduced both levels to normal and halted the diarrhea. Chronic treatment with para-chlorophenylalanine controlled the production of 5-hydroxytryptamine and diarrhea but did not prevent tumor growth, flushing, or progression of cardiac lesions.
Eosinophilia/myalgia syndrome associated with L-tryptophan
Authors: TimothyP. Pfanner, DonaldA. Person, JeffreyL. Berenberg, EverettL. Gayle, L.John Lockett, Mori Schwartzberg, CharlesA. Weber, AshtonL. Graybiel, DianaC. Harris, RuthW. Orth
Journal: The Lancet (1990)
Inhibitory roles for SHP-1 and SOCS-3 following pituitary proopiomelanocortin induction by leukemia inhibitory factor
Authors: Corinne Bousquet, Christiane Susini, Shlomo Melmed
Journal: Journal of Clinical Investigation (1999)

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that stimulates the hypothalamo-pituitary-adrenal (HPA) axis through JAK-STAT activation. We show here that LIF-induced JAK2 and STAT3 tyrosine phosphorylation is transient, disappearing within 20 and 40 minutes, respectively. LIF activates the SH2 domain–containing tyrosine phosphatase, SHP-1, with maximal stimulation observed at 30 minutes. SHP-1 is constitutively associated with JAK2, and LIF induces recruitment of phosphorylated STAT3 to this complex. Overexpression of wild-type or dominant negative forms of SHP-1 shows decreased or increased LIF-induced proopiomelanocortin (POMC) promoter activity, respectively. LIF-induced JAK2 and STAT3 dephosphorylation is delayed until after 60 minutes in cells that overexpress the mutant SHP-1. In addition, SOCS-3, a negative regulator of LIF signaling, binds to JAK2 after 60 minutes of LIF stimulation, after which the complex is degraded by the proteasome. SOCS-3 overexpression blocks LIF-induced JAK2 tyrosine phosphorylation, confirming a role for SOCS-3 in deactivating JAK2 by direct association. Using SOCS-3 fusion proteins, we also define regions of the SOCS-3 protein that are critical for inhibition of LIF-induced POMC promoter activity. Corticotrophic signaling by LIF is thus subject to 2 forms of negative autoregulation: dephosphorylation of JAK2 and STAT3 by the SHP-1 tyrosine phosphatase, and SOCS-3–dependent inactivation of JAK2.
Subgroup Analysis of Elderly Patients in Squire: a Randomized, Multicenter, Open-Label, Phase Iii Study of Necitumumab (N) Plus Gemcitabine-Cisplatin (GC) Chemotherapy Versus Gc Alone in First-Line Treatment of Patients (PTS) with Stage Iv Squamous Non-Small Cell Lung Cancer (SQ-NSCLC)
Authors: N. Thatcher, T.-E. Ciuleanu, R. Ramlau, C. Schumann, L. Paz-Ares, H. Depenbrock, S. Nanda, N. Chouaki, M. Socinski
Journal: Annals of Oncology (2015)
* Measuring relief of dysphagia in patients with obstructing oesophageal malignancy; a pilot study using the EORTC OES-24 questionnaire in patients undergoing self-expanding metal stents (SEMS) insertion or chemotherapy
Authors: N. Fisher, C. Corbett
Journal: Gut (2011)

<h3>Introduction</h3> There is no clear guidance on achieving relief of dysphagia for patients who have obstructing oesophageal malignancy. There are several approaches available, including endoscopic techniques, chemotherapy or radiotherapy. However there is limited comparative evidence for each technique. We have explored usage of the 20-item EORTC OES-24 questionnaire to help measure the effect of intervention on key symptoms in two patient groups treated with typical interventions. <h3>Methods</h3> Patients with obstructing malignancy were selected prior to intervention with SEMS (Boston Oesophageal II stents) or chemotherapy (epirubicin, cisplatin and 5-fluorouracil). Chemotherapy was given as neo-adjuvant therapy prior to surgery or as first-line therapy in inoperable disease, while SEMS were used in patients with inoperable malignancy. Questionnaires were completed immediately prior to and 4 weeks after intervention was started. In this questionnaire, all scores range between 1 (for ‘not at all9) and 4 (for ‘very much9). <h3>Results</h3> 15 stent patients and 13 chemotherapy patients were recruited over a 12-month period. In the stent group, mean dysphagia scores for solids improved from 1.3 to 2.1 after treatment (p&lt;0.01, Student t test). There were also significant improvements in other scores for enjoyment of food. There was no change in pain scores. However, the overall health anxiety score worsened from 2.8 to 3.5 (p&lt;0.01). In the chemotherapy group, mean dysphagia scores improved from 2.4 to 3.1 after first chemotherapy (p&lt;0.01) and there was an improvement in overall health score (3.5 to 2.9, p&lt;0.01). <h3>Conclusion</h3> For patients with obstructing oesophageal malignancy, this pilot study suggests an overall symptomatic benefit after SEMS, but with progressive anxiety, while patients undergoing neo-adjuvant therapy have an overall symptomatic benefit without anxiety. The EORTC OES-24 questionnaire may thus be a useful tool to measure benefit in patients undergoing new interventions for oesophageal malignancy.
Dose-Dense Adjuvant Chemotherapy in Early Breast Cancer Patients: Results From a Randomized Trial
Authors: Marco Venturini, Lucia Del Mastro, Enrico Aitini, Editta Baldini, Cinzia Caroti, Antonio Contu, Franco Testore, Fulvio Brema, Paolo Pronzato, Giovanna Cavazzini, Mario Roberto Sertoli, Giuseppe Canavese, Riccardo Rosso, Paolo Bruzzi
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: To determine whether a dose-dense regimen improves outcome in early breast cancer patients, we compared outcomes with the same fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapeutic regimen administered every 3 weeks (FEC 21 ) or administered every 2 weeks (FEC 14 including support with filgrastim, a granulocyte colony-stimulating factor) in a multicenter phase III randomized trial. Methods: A total of 1214 patients with early-stage breast cancer were randomly assigned to receive six cycles of FEC 14 (604 patients) or of FEC 21 (610 patients). Study endpoints were overall survival and event-free survival. Associations were assessed by multivariable analysis with adjustment for age; tumor size; grade; proliferative rate; and menopausal, lymph node, estrogen receptor, and progesterone receptor status. All statistical tests were two-sided. Results: Patients in the FEC 14 arm had fewer dose reductions or treatment delays or discontinuation (26%) than those in the FEC 21 arm (33%) (difference = 7%, 95% confidence interval [CI] = 2% to 12%; P = .008). FEC 14 therapy, compared with FEC 21 therapy, was associated with more asthenia (36% versus 29%, difference = 7%, 95% CI = 2% to 12%; P = .01), bone pain (33% versus 4%, difference = 29%, 95% CI = 25% to 33%; P <.001), anemia (38% versus 19%, difference = 19%, 95% CI = 14% to 24%; P <.001), and thrombocytopenia (8% versus 2%, difference = 6%, 95% CI = 4% to 9%; P <.001), but with less leukopenia (12% versus 45%, difference = 33%, 95% CI = 28% to 37%; P <.001). No acute myelogenous leukemia or myelodysplastic syndrome was observed. At a median follow-up of 10.4 years, no statistically significant difference in the hazard of death (hazard ratio [HR] = 0.87, 95% CI = 0.67 to 1.13) or recurrence (HR = 0.88, 95% CI = 0.71 to 1.08) was found between FEC 14 and FEC 21 groups after adjustment by multivariable analysis. Although the study was underpowered for subset analysis, we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors. Conclusion: Our results support the long-term safety of FEC 14 chemotherapy as an adjuvant treatment of breast cancer. However, this therapy was not associated with improved outcome, but because of the limited statistical power of our study, we cannot rule out a modest improvement in outcome associated with FEC 14 therapy.
Food-pollen cross-reactivity in oral allergy syndrome and rhinitis
Authors: F. Marcucci, G.W. Canonica, F. Frati, L. Sensi, A. Riccio, A. Garzi, P. Tanganelli, E. Novembre, R. Bernardini, G. Passalacqua
Journal: Journal of Allergy and Clinical Immunology (2003)