tbuckley/cabot-search huggingface dataset:
Unlicensed and off-label prescription of respiratory drugs to children
Authors: G.W. 't Jong, I.A. Eland, M.C.J.M. Sturkenboom, J.N. van den Anker, B.H.C. Stricker
Journal: European Respiratory Journal (2004)

Many respiratory drugs are not available in formulations suitable for infants and toddlers. Efficacy and safety research is mostly restricted to older children. However, respiratory drugs are frequently used in children for common diseases like asthma, upper and lower respiratory tract infections, rhinitis and sinusitis. The unlicensed and off-label use of respiratory drugs in children were studied. A population-based cohort study was conducted by using the computerised medical records in the Integrated Primary Care Information project. The study population comprised a random sample from all children aged 0–16 yrs who were registered with a general practitioner in 1998. All prescriptions for respiratory drugs during the study period were classified according to their licensing and off-label status. The study population comprised 13,426 patients (51.7% male, median age 8.7 yrs), of whom 2,502 (19%) received 5,253 prescriptions for respiratory drugs in 1998. A total of 3,306 (62.9%) prescriptions concerned licensed drugs. Of the remaining 1,947 prescriptions (37.1%), 882 (16.8%) were unlicensed for use in children, and 1,065 (20.3%) were prescribed off-label. The 1‐yr cumulative risk of receiving an unlicensed or off-label prescription was 45% among children with at least one prescription for a respiratory drug. This population-based study showed that a large proportion of respiratory drugs prescribed by the general practitioner are unlicensed for use in children, or licensed but prescribed in an off-label manner. Results have to be interpreted with caution because they may unjustly suggest inaccurate prescribing, whereas it may be difficult to treat children with respiratory symptoms and diseases, because for many respiratory drugs paediatric data on safety and efficacy are insufficient. These findings underline the importance of research on suitable formulations, dosages and efficacy of respiratory drugs in children.
USE OF NEUTRON ACTIVATION ANALYSIS FOR STUDYING STABLE IODIDE UPTAKE BY THE THYROID*
Authors: Henry N. Wagner, Wil B. Nelp, James H. Dowling
Journal: Journal of Clinical Investigation (1961)

A technique of neutron activation analysis was used to measure trace quantities of inorganic iodide in urine. Anion exchange resins and selective elution permitted removal of interfering sodium and chloride from urine prior to the activation procedure. The uptake of stable iodide by the thyroid was determined by measuring the radioiodine uptake and specific activity (I131/I127) of simultaneously excreted urine. ln 34 fasting euthyroid subjects the mean iodide uptake by the thyroid was 3 plus or minus 2 mu g per hour. Plasma concentration of inorganic iodide averaged 0.005 mu g per ml. Day to day variations in iodide intake resulted in corresponding variations in the amount of stable iodide accumulated by the thyroid, since iodide accumulation approximated a first-order reaction. Prolonged administration of exogenous iodide resulted in a gradual decrease in radioiodine accumulation. This resulted in a decreased accumulation of stable iodide only after several weeks of greatly increased iodide uptake by the thyroid. A mechanism postulated to explain the dynamics of iodide accumulation by the thyroid is presented.
Treatment of Pressure Ulcers: A Clinical Practice Guideline From the American College of Physicians
Authors: Amir Qaseem, Linda L. Humphrey, Mary Ann Forciea, Melissa Starkey, Thomas D. Denberg
Journal: Annals of Internal Medicine (2015)

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations based on the comparative effectiveness of treatments of pressure ulcers. Methods: This guideline is based on published literature on this topic that was identified by using MEDLINE, EMBASE, CINAHL, EBM Reviews, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and the Health Technology Assessment database through February 2014. Searches were limited to English-language publications. The outcomes evaluated for this guideline include complete wound healing, wound size (surface area, volume, and depth) reduction, pain, prevention of sepsis, prevention of osteomyelitis, recurrence rate, and harms of treatment (including but not limited to pain, dermatologic complications, bleeding, and infection). This guideline grades the quality of evidence and strength of recommendations by using ACP's clinical practice guidelines grading system. The target audience for this guideline includes all clinicians, and the target patient population is patients with pressure ulcers. Recommendation 1: ACP recommends that clinicians use protein or amino acid supplementation in patients with pressure ulcers to reduce wound size. (Grade: weak recommendation, low-quality evidence) Recommendation 2: ACP recommends that clinicians use hydrocolloid or foam dressings in patients with pressure ulcers to reduce wound size. (Grade: weak recommendation, low-quality evidence) Recommendation 3: ACP recommends that clinicians use electrical stimulation as adjunctive therapy in patients with pressure ulcers to accelerate wound healing. (Grade: weak recommendation, moderate-quality evidence)
Asthma and irreversible airflow obstruction.
Authors: P J Brown, H W Greville, K E Finucane
Journal: Thorax (1984)

To determine whether asthma alone can cause irreversible airflow obstruction 42 men and 47 women with chronic asthma (mean duration 22 (SD 13) years) without evidence of other disease likely to cause irreversible airflow obstruction were treated with theophylline orally and a beta agonist both orally and by inhalation for four weeks. After two weeks of treatment the FEV1 was less than 85% of the predicted normal value (%P) in 48 patients and these individuals then received prednisolone 0.6 mg/kg/day for two weeks. Duration and severity of asthma and smoking history were quantified by questionnaire; 38 patients were current smokers or ex-smokers. FEV1 was measured at 0, 2, and 4 weeks. The mean difference between the best FEV1 during the study and the predicted normal value was 0.29 l (p less than 0.001); FEV1 %P decreased with age (r = -0.30, p less than 0.01) and with the duration (r = -0.47, p less than 0.001) and severity (r = -0.55, p less than 0.001) of asthma. Similar findings were noted when the results for non-smokers and those whose asthma started in adult life were analysed separately. We conclude that asthma alone can cause irreversible airflow obstruction and that the degree of obstruction is a function of the duration and severity of previous asthma. The results suggest the possibility that irreversible airflow obstruction in asthma may be preventable by minimising the degree of persistent asthma.
Association of Exaggerated HPA Axis Response to the Initial Injection of Interferon-Alpha With Development of Depression During Interferon-Alpha Therapy
Authors: Lucile Capuron, Charles L. Raison, Dominique L. Musselman, David H. Lawson, Charles B. Nemeroff, Andrew H. Miller
Journal: American Journal of Psychiatry (2003)

The authors assessed the relationship between the hypothalamic-pituitary-adrenal (HPA) axis response to interferon-alpha (IFN-alpha) and the development of major depression during IFN-alpha treatment.Adrenocorticotropic hormone (ACTH), cortisol, and interleukin-6 (IL-6) plasma concentrations were measured in 14 patients with malignant melanoma at regular intervals during the first 12 weeks of IFN-alpha therapy, both immediately before and 1, 2, and 3 hours after IFN-alpha administration. Symptom criteria for major depression were also evaluated at each visit.ACTH and cortisol responses but not IL-6 responses to the initial administration of IFN-alpha were significantly higher in the seven patients who subsequently developed symptom criteria for major depression than in those who did not. No differences in hormonal or cytokine responses were found between these two groups during chronic IFN-alpha administration.The HPA axis response to the acute administration of IFN-alpha reveals a vulnerability to IFN-alpha-induced depression, possibly due to sensitization of corticotropin-releasing factor pathways.
Inhibition of Na <sup>+</sup> -H <sup>+</sup> Exchange Prevents Hypertrophy, Fibrosis, and Heart Failure in β <sub>1</sub> -Adrenergic Receptor Transgenic Mice
Authors: Stefan Engelhardt, Lutz Hein, Ursula Keller, Kerstin Klämbt, Martin J. Lohse
Journal: Circulation Research (2002)

Chronic stimulation of the beta(1)-adrenergic receptor leads to hypertrophy and heart failure in beta(1)-adrenergic receptor transgenic mice and contributes to disease progression in heart failure patients. The cellular mechanisms underlying these detrimental effects are largely unknown. In this study, we have identified the cardiac Na(+)-H(+) exchanger (NHE1) as a novel mediator of adrenergically induced heart failure. beta(1)-Adrenergic receptor transgenic mice showed upregulation of both NHE1 mRNA (+140+/-6%) and protein (+42+/-19%). In order to test whether increased NHE1 is causally related to beta(1)-adrenergic-induced hypertrophy, fibrosis, and heart failure, beta(1)-adrenergic receptor transgenic (TG) and wild-type (WT) littermates were treated with a diet containing 6000 ppm of the NHE1 inhibitor cariporide or control chow for 8 months. There was significant hypertrophy of cardiac myocytes in beta(1)-adrenergic receptor transgenic mice (2.3-fold increase in myocyte cross-sectional area), which was virtually absent in cariporide-fed animals. Interstitial fibrosis was prominent throughout the left ventricular wall in nontreated beta(1)-adrenergic receptor transgenic mice (4.8-fold increase in collagen volume fraction); cariporide treatment completely prevented this development of fibrosis. Left ventricular catheterization showed that cariporide also prevented the loss of contractile function in beta(1)-adrenergic receptor transgenic mice: whereas untreated transgenic mice showed a significant decrease in left ventricular contractility (5250+/-570 mm Hg/s TG versus 7360+/-540 mm Hg/s WT, dp/dt(max)), this decrease was completely prevented by cariporide (8150+/-520 mm Hg/s TG cariporide). Inhibition of NHE1 prevented the development of heart failure in beta(1)-receptor transgenic mice. We conclude that the cardiac Na(+)-H(+) exchanger 1 is essential for the detrimental cardiac effects of chronic beta(1)-receptor stimulation in the heart.
Signal Transduction by the B Cell Antigen Receptor and its Coreceptors
Authors: J C Cambier, C M Pleiman, M R Clark
Journal: Annual Review of Immunology (1994)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Association of Valine and Leucine at HLA–DRB1 Position 11 With Radiographic Progression in Rheumatoid Arthritis, Independent of the Shared Epitope Alleles but Not Independent of Anti–Citrullinated Protein Antibodies
Authors: H. W. van Steenbergen, S. Raychaudhuri, L. Rodríguez‐Rodríguez, S. Rantapää‐Dahlqvist, E. Berglin, R. E. M. Toes, T. W. J. Huizinga, B. Fernández‐Gutiérrez, P. K. Gregersen, A. H. M. van der Helm‐van Mil
Journal: Arthritis & Rheumatology (2015)

For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status.A total of 4,911 radiograph sets from 1,878 RA patients included in the Leiden Early Arthritis Clinic (The Netherlands), Umeå (Sweden), Hospital Clinico San Carlos-Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US) cohorts were studied. HLA was imputed using single-nucleotide polymorphism data from an Immunochip, and the amino acids listed above were tested in relation to radiographic progression per cohort using an additive model. Results from the 4 cohorts were combined in inverse-variance weighted meta-analyses using a fixed-effects model. Analyses were conditioned on SE and ACPA status.Val and Leu at HLA-DRB1 position 11 were associated with more radiographic progression (meta-analysis P = 5.11 × 10(-7)); this effect was independent of SE status (meta-analysis P = 0.022) but not independent of ACPA status. Phe at HLA-DPB1 position 9 was associated with more severe radiographic progression (meta-analysis P = 0.024), though not independent of SE status. Asp at HLA-B position 9 was not associated with radiographic progression.Val and Leu at HLA-DRB1 position 11 conferred a risk of a higher rate of radiographic progression independent of SE status but not independent of ACPA status. These findings support the relevance of these amino acids at position 11.
Ca2+ preconditioning elicits a unique protection against the Ca2+ paradox injury in rat heart. Role of adenosine. Fixed.
Authors: M Ashraf, J Suleiman, M Ahmad
Journal: Circulation Research (1994)

Repeated Ca2+ depletion and repletion of short duration, termed Ca2+ preconditioning (CPC), is hypothesized to protect the heart from lethal injury after exposing it to the Ca2+ paradox (Ca2+ PD). Hearts were preconditioned with five cycles of Ca2+ depletion (1 minute) and Ca2+ repletion (5 minutes). These hearts were then subjected to Ca2+ PD, ie, one cycle of Ca2+ depletion (10 minutes) and Ca2+ repletion (10 minutes). Hearts subject to the Ca2+ PD underwent rapid necrosis, and myocytes were severely injured. CPC hearts showed a remarkable preservation of cell structure; ie, 65% of the cells were normal in CPC hearts compared with 0% in the Ca2+ PD hearts. LDH release was significantly reduced in CPC hearts compared with Ca2+ PD hearts (2.45 +/- 0.18 and 8.02 +/- 0.7 U.min-1 x g-1, respectively). ATP contents of CPC hearts were less depleted compared with the Ca2+ PD hearts (5.9 +/- 0.8 and 3.0 +/- 0.16 mumol/g dry weight, respectively). Addition of the adenosine A1 receptor agonist R-phenylisopropyl adenosine before and during Ca2+ PD provided protection similar to that in CPC hearts, whereas the nonselective adenosine A1 receptor antagonist, 8-(p-sulfophenyl)-theophylline, blocked the beneficial effects of CPC. CPC-mediated protection was aborted when hearts subjected to CPC were treated with pertussis toxin (the guanine nucleotide or G-protein inhibitor). The present study suggests that Ca2+ preconditioning confers significant protection against the lethal injury of Ca2+ PD in rat hearts. Cardioprotection appears to result from adenosine release during preconditioning and by Gi-protein-modulated mechanisms.
Comparison of tumour markers in malignant mesothelioma and pulmonary adenocarcinoma.
Authors: A R Gibbs, R Harach, J C Wagner, B Jasani
Journal: Thorax (1985)

Immunohistological methods were used to investigate the presence of carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin in formalin fixed tissue from 29 malignant mesotheliomas and 27 pulmonary adenocarcinomas. Malignant mesotheliomas were negative for tumour markers except for the beta subunit of human chorionic gonadotrophin and keratin, one and 13 cases respectively being positive for these. Pulmonary adenocarcinomas, however, were frequently positive for tumour markers--namely, carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin. The presence of carcinoembryonic antigen and beta 1 pregnancy specific glycoprotein within an intrathoracic tumour is strong evidence against its being of mesothelial origin.
PMO-144 Experience of managing patients with hepatitis C in outreach: Abstract PMO-144 Table 1
Authors: A Elsharkawy, C Miller, A Hearn, G Buerstedde, A Price, S McPherson
Journal: Gut (2012)

<h3>Introduction</h3> Subjects who acquire Hepatitis C (HCV) from injecting drug use (IDU) and attend drug rehabilitation programs are a “hard to reach” group and often don9t access treatment for HCV. In our experience, their non-attendance at secondary care clinics is ∼60%. In order to improve access to treatment for this group we established three outreach clinics at drug treatment centres in North of Tyne Region. Our aim was to review the outcomes for patients attending these outreach clinics. <h3>Methods</h3> Retrospective review of patients referred to three outreach clinics: 1. Plummer Court (PC), an addiction psychiatry led drug and alcohol centre in Newcastle 2. Bridge View (BV), a GP led drug treatment centre in Newcastle 3. A GP surgery in Blyth, Northumberland associated with the Harm Reduction service. Data were collected on demographics, attendance rates and treatment outcomes. <h3>Results</h3> A total of 133 patients were referred to the three clinics and 96 (72%) attended ≥1 appointment. Their demographic and clinical data are shown in Abstract PMO-144 table 1. Of the 96 seen, 75 (78%) had treatment workup, but 21 (22%) were deemed “not ready” for treatment due to on-going IDU, alcohol excess, psychiatric disease or unfavourable social circumstances. Of the 75 subjects who had treatment workup, 25 (33%) have since either failed to attend appointments, elected to delay treatment or had contraindications (including two decompensated cirrhotics and two with hepatocellular carcinoma). 30 (40%) commenced treatment and 20 (27%) patients are waiting to start treatment. Of the 30 who started treatment, 11 (37%) completed treatment (five had sustained virological response, one relapsed and five awaiting post-treatment results), 13 (43%) are currently in treatment and 6 (20%) did not complete therapy (poor compliance or side effects). <h3>Conclusion</h3> Outreach clinics in drug treatment centres substantially improved attendance rates of for patients with HCV and a history of substance misuse. More than 50% of subjects seen in outreach clinics commenced or are waiting to start HCV treatment. If adopted nationwide, this model of care may improve access to HCV treatment in “hard to reach” groups. <h3>Competing interests</h3> None declared.
Alemtuzumab Induction in Renal Transplantation
Authors: Michael J. Hanaway, E. Steve Woodle, Shamkant Mulgaonkar, V. Ram Peddi, Dixon B. Kaufman, M. Roy First, Richard Croy, John Holman
Journal: New England Journal of Medicine (2011)

There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in renal-transplant recipients. The purpose of the present study was to compare induction therapy involving alemtuzumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk.
International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project
Authors: Aris T Papageorghiou, Eric O Ohuma, Douglas G Altman, Tullia Todros, Leila Cheikh Ismail, Ann Lambert, Yasmin A Jaffer, Enrico Bertino, Michael G Gravett, Manorama Purwar, J Alison Noble, Ruyan Pang, Cesar G Victora, Fernando C Barros, Maria Carvalho, Laurent J Salomon, Zulfiqar A Bhutta, Stephen H Kennedy, José Villar
Journal: The Lancet (2014)
K-ras gene mutation in gall bladder carcinomas and dysplasia.
Authors: T Ajiki, T Fujimori, H Onoyama, M Yamamoto, S Kitazawa, S Maeda, Y Saitoh
Journal: Gut (1996)

Epithelial dysplasia of gall bladder is an important precancerous lesion of gall bladder carcinogenesis. To investigate the frequency of K-ras gene mutation in gall bladder carcinoma and dysplasia, K-ras codon 12 mutations were investigated by the polymerase chain reaction/restriction enzyme based method following direct sequencing. Mutation was detected in 59% (30 of 51) of gall bladder carcinomas, in 73% (8 of 11) of gall bladder dysplasia in gall stone cases, and in 0% of the normal gall bladder epithelium. There was, however, no correlation between K-ras mutation and clinicopathological factors of gall bladder carcinoma. K-ras gene mutation occurs even in gall bladder dysplasia at an incidence similar to that in carcinomas, suggesting that testing for K-ras gene mutation may prove useful as an adjunct to bile cytological or biopsy analysis.
A common major surface antigen on amastigotes and promastigotes of Leishmania species.
Authors: V Colomer-Gould, L Glvao Quintao, J Keithly, N Nogueira
Journal: The Journal of Experimental Medicine (1985)

Enzymatic surface iodination and biosynthetic labeling with [35S]methionine, combined with immunoprecipitation by sera from patients with different forms of Leishmaniasis revealed a 65,000 Mr glycoprotein as the immunodominant moiety in promastigotes and amastigotes of the nine Leishmania species and isolates examined. Sera from patients with one form of Leishmaniasis recognized this component strongly, not only in the homologous, but also in the heterologous species. In addition to the crossreactivity displayed by immune sera, the 65,000 Mr glycoprotein (gp) common to all Leishmania species presented a characteristic shift to Mr 50,000 when samples were run in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. These results are in agreement with our previous studies (7), where a simple and similar profile was obtained for several geographic isolates of L. donovani, with a major surface glycoprotein of 65,000 Mr displaying the same characteristics described here. The structural similarity of the major 65,000 Mr gp of the six Leishmania species was demonstrated by Cleveland mapping. It is suggested that immunological specificities may be contributed by minor differences in glycosylation of this molecule. In keeping with recent data (13-15), where strong cross protection among different Leishmania species has been obtained by prophylactic immunization with irradiated whole promastigotes, this glycoprotein may be a good candidate for an antigen to be used for immunoprophylaxis of all forms of Leishmaniasis.