tbuckley/cabot-search huggingface dataset:
Impact of current good manufacturing practices and emission regulations and guidances on the discharge of pharmaceutical chemicals into the environment from manufacturing, use, and disposal.
Authors: Ranga Velagaleti, Philip K Burns, Michael Gill, James Prothro
Journal: Environmental Health Perspectives (2002)

The current Good Manufacturing Practice (cGMP) and effluent emission (use and disposal) regulations of the U.S. Food and Drug Administration (FDA) and manufacturing effluent discharge and emission regulations of the U.S. Environmental Protection Agency (U.S. EPA) require contained manufacture, use, and disposal of pharmaceuticals with the goal of minimizing the release of pharmaceutical chemicals into the environment. However, debate has recently arisen in several scientific forums over whether these regulations adequately protect human and environmental health from the new pharmaceutical drugs introduced each year into the marketplace and the multitude of existing products, each with many distinct biochemical modes of actions. To address this issue, it is important to understand the relevance of current cGMP regulations and emission regulations that have a direct bearing on the releases of pharmaceutical chemicals into the environment during the manufacture, use, and disposal of active pharmaceutical ingredients (drug substances) and drug products. This knowledge may help us assess the quantity of residues that may be released into the environment. Additionally, the information on physical, chemical, and degradation and sorption properties of the pharmaceutical chemicals may help determine the net residue levels that could persist in the environment to evaluate if such residues have any bearing on human and environmental health. The scientific and regulatory aspects of issues related to the manufacture, use, and disposal of pharmaceutical chemicals are discussed in this article, with special emphasis on potential environmental exposure pathways during the life cycle of an active pharmaceutical ingredient or drug product. The mechanisms of degradation (transformation or depletion) and dilution of pharmaceutical residues that may be released into aquatic or terrestrial environmental compartments are described. Such degradation and dilution of pharmaceutical chemicals in the environment may significantly reduce the residues. It is important to evaluate whether such residue levels have any measurable impact on human and/or environmental health.
Membrane permeability, a pivotal function involved in antibiotic resistance and virulence in Enterobacter aerogenes clinical isolates
Authors: J.-P. Lavigne, A. Sotto, M.-H. Nicolas-Chanoine, N. Bouziges, G. Bourg, A. Davin-Regli, J.-M. Pagès
Journal: Clinical Microbiology and Infection (2011)
beta blockade and intermittent claudication: placebo controlled trial of atenolol and nifedipine and their combination.
Authors: S A Solomon, L E Ramsay, W W Yeo, L Parnell, W Morris-Jones
Journal: BMJ (1991)

To determine the effects of the beta 1 selective adrenoceptor blocker atenolol, the dihydropyridine calcium antagonist nifedipine, and the combination of atenolol plus nifedipine on objective and subjective measures of walking performance and foot temperature in patients with intermittent claudication.Randomised controlled double blind four way crossover trial.Royal Hallamshire Hospital, Sheffield.49 patients (40 men) aged 39-70 with chronic stable intermittent claudication.Atenolol 50 mg twice daily; slow release nifedipine 20 mg twice daily; atenolol 50 mg plus slow release nifedipine 20 mg twice daily; placebo. Each treatment was given for four weeks with no washout interval between treatments.Claudication and walking distances on treadmill; skin temperature of feet as measured by thermistor and probe; blood pressure before and after exercise; subjective assessments of walking difficulty and foot coldness with visual analogue scales.Atenolol did not significantly alter claudication distance (mean change -6%; 95% confidence interval 1% to -13%), walking distance (-2%; 4% to -8%), or foot temperature. Nifedipine did not alter claudication distance (-4%; 3% to -11%), walking distance (-4%; 3% to -10%), or foot temperature. Atenolol plus nifedipine did not alter claudication distance but significantly reduced walking distance (-9%; -3% to -15% (p less than 0.003)) and skin temperature of the more affected foot (-1.1 degrees C; 0 to -2.2 degrees C (p = 0.05)). These effects on walking distance and foot temperature seemed unrelated to blood pressure changes.There was no evidence of adverse or beneficial effects of atenolol or nifedipine, when given singly, on peripheral vascular disease. The combined treatment, however, affected walking ability and foot temperature adversely. This may have been due to beta blockade plus reduced vascular resistance, which might also explain the reported adverse effects of pindolol and labetalol on claudication.
Contact dermatitis from organophosphorus Pesticides
Authors: R.J.G. RYCROFT
Journal: British Journal of Dermatology (1977)

Journal Article Contact dermatitis from organophosphorus Pesticides Get access R.J.G. RYCROFT R.J.G. RYCROFT St John's Hospital for Diseases of the Skin, Lisle Street, London WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue 6, 1 December 1977, Pages 693–695, https://doi.org/10.1111/j.1365-2133.1977.tb14280.x Published: 01 December 1977
Pilot Randomized Phase II Study of Celecoxib in Oral Premalignant Lesions
Authors: Vassiliki A. Papadimitrakopoulou, William N. William, Andrew J. Dannenberg, Scott M. Lippman, J. Jack Lee, Frank G. Ondrey, Douglas E. Peterson, Lei Feng, Anthea Atwell, Adel K. El-Naggar, Cherie-Ann Nathan, Joseph I. Helman, Baoheng Du, Bevan Yueh, Jay O. Boyle
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cyclooxygenase-2 (COX-2)–specific inhibition suppresses carcinogenesis in preclinical models and is a promising strategy for preventing oral cancer. In this pilot randomized phase II study, we evaluated the efficacy and safety of the COX-2 inhibitor celecoxib in patients with oral premalignant lesions (OPL). Experimental Design: Patients were randomly assigned to placebo (n = 18), celecoxib 100 mg twice daily (n = 17), or celecoxib 200 mg twice daily (n = 15) for 12 weeks. Six additional patients received celecoxib (400 mg twice daily) in an unblinded extension of the study. Biopsies were obtained at baseline and week 12. All patients entering the study were required to have at least one histologically confirmed early (atypical hyperplasia, atypical hyperkeratosis, or mild dysplasia) or advanced (moderate to severe dysplasia) OPL. Results: Forty-nine patients (46 of 50 randomized and 3 of 6 open label) were evaluable for efficacy analyses. There were no statistically significant differences between the response rates of the randomly assigned arms: placebo, 33.3% (6 of 18); celecoxib 100 mg twice daily, 41.2% (7 of 17); and celecoxib 200 mg twice daily, 20.0% (3 of 15). Two patients responded on celecoxib 400 mg twice daily. Celecoxib was generally well tolerated. Patients with higher baseline COX-2 mRNA levels had an increased risk of disease progression within 3 months. Conclusions: Celecoxib at 100 or 200 mg twice daily was ineffective in controlling OPLs in this randomized controlled trial. This result and cardiovascular toxicity results of other (large scale) randomized controlled trials of selective COX-2 inhibitors have discouraged the continued investigation of these agents in oral cancer chemoprevention. Better methods for identifying high-risk patients and more active interventions are needed for future oral cancer chemoprevention trials.
Rescue of Daudi cell HLA expression by transfection of the mouse beta 2-microglobulin gene.
Authors: R H Seong, C A Clayberger, A M Krensky, J R Parnes
Journal: The Journal of Experimental Medicine (1988)

The Daudi cell line is a B-lymphoblastoid line derived from a Burkitt lymphoma. Daudi cells lack cell surface expression of class I HLA molecules despite the presence of intracellular class I heavy chains. They have a defect in the gene encoding beta 2-microglobulin (beta 2m), resulting in lack of translatable mRNA for this protein. It has been thought that this deficiency is responsible for the lack of cell surface class I expression. However, data have recently been presented demonstrating that at least one mouse class I heavy chain can be expressed on the cell surface in the absence of beta 2m. These results raised the questions of whether the lack of beta 2m is the only defect in Daudi and whether transfer of this single gene could restore surface class I expression. We found that transfection of the mouse beta 2m gene into Daudi indeed rescued cell surface expression of class I HLA molecules, and that these molecules could be recognized both by monomorphic and allospecific mAbs. CTL clones specific for HLA-B17 or a determinant shared by HLA-B17 and HLA-A2 killed the Daudi cells transfected with the beta 2m gene, but not untransfected Daudi or Daudi transfected with vector alone. Mouse beta 2m on the transfected Daudi cells could exchange with human beta 2m when the cells were incubated in human serum. This exchange did not alter the ability of the cells to be killed by the specific CTLs. These results demonstrate that the lack of beta 2m is the sole reason for lack of surface class I molecules in Daudi cells, and that beta 2m is required for cell surface expression of the specific class I heavy chains of Daudi.
Massive haemoptysis complicating prosthetic patch pulmonary embolism after atrial septal defect repair.
Authors: M Haro, J Ruiz, J Ribas, J Maestre, J Perez-Piteira, J Morera
Journal: Thorax (1995)

A case is presented of a 43 year old woman with massive haemotypsis secondary to non-thrombotic pulmonary embolism complicating atrial septal defect repair with a prosthetic patch. Non-thrombotic embolus must be considered in the differential diagnosis of massive haemoptysis.
Dysregulated Human Myeloid Nuclear Differentiation Antigen Expression in Myelodysplastic Syndromes: Evidence for a Role in Apoptosis
Authors: Robert C. Briggs, Keith E. Shults, Leanne A. Flye, Sara A. McClintock-Treep, Madan H. Jagasia, Stacey A. Goodman, Fouad I. Boulos, James W. Jacobberger, Greg T. Stelzer, David R. Head
Journal: Cancer Research (2006)

Abstract Reduced levels of human myeloid nuclear differentiation antigen (MNDA) gene transcripts have been detected in both familial and sporadic cases of myelodysplastic syndromes (MDS). Numerous reports implicate elevated apoptosis/programmed cell death and death ligands and their receptors in the pathogenesis of MDS. MNDA and related proteins contain the pyrin domain that functions in signaling associated with programmed cell death and inflammation. We tested the hypothesis that MNDA is involved in the regulation of programmed cell death in human myeloid hematopoietic cells. Clones of K562 cells (MNDA-null) that expressed ectopic MNDA protein were established using retroviral transduction. MNDA-expressing K562 clones were resistant to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)–induced apoptosis, but were not protected from programmed cell death induced with genotoxic agents or H2O2. MNDA protein expression assessed in control and intermediate and high-grade MDS marrows showed several patterns of aberrant reduced MNDA. These variable patterns of dysregulated MNDA expression may relate to the variable pathophysiology of MDS. We propose that MNDA has a role regulating programmed cell death in myeloid progenitor cells, and that its down-regulation in MDS is related to granulocyte-macrophage progenitor cell sensitivity to TRAIL-induced programmed cell death. (Cancer Res 2006; 66(9): 4645-51)
Factors Associated With American Board of Medical Specialties Member Board Certification Among US Medical School Graduates
Authors: Donna B. Jeffe, Dorothy A. Andriole
Journal: JAMA (2011)

<h3>Context</h3>Certification by an American Board of Medical Specialties (ABMS) member board is emerging as a measure of physician quality.<h3>Objective</h3>To identify demographic and educational factors associated with ABMS member board certification of US medical school graduates.<h3>Design, Setting, and Participants</h3>Retrospective study of a national cohort of 1997-2000 US medical school graduates, grouped by specialty choice at graduation and followed up through March 2, 2009. In separate multivariable logistic regression models for each specialty category, factors associated with ABMS member board certification were identified.<h3>Main Outcome Measure</h3>ABMS member board certification.<h3>Results</h3>Of 42 440 graduates in the study sample, 37 054 (87.3%) were board certified. Graduates in all specialty categories with first-attempt passing scores in the highest tertile (vs first-attempt failing scores) on US Medical Licensing Examination Step 2 Clinical Knowledge were more likely to be board certified; adjusted odds ratios (AORs) varied by specialty category, with the lowest odds for emergency medicine (87.4% vs 73.6%; AOR, 1.82; 95% CI, 1.03-3.20) and highest odds for radiology (98.1% vs 74.9%; AOR, 13.19; 95% CI, 5.55-31.32). In each specialty category except family medicine, graduates self-identified as underrepresented racial/ethnic minorities (vs white) were less likely to be board certified, ranging from 83.5% vs 95.6% in the pediatrics category (AOR, 0.44; 95% CI, 0.33-0.58) to 71.5% vs 83.7% in the other nongeneralist specialties category (AOR, 0.79; 95% CI, 0.64-0.96). With each $50 000 unit increase in debt (vs no debt), graduates choosing obstetrics/gynecology were less likely to be board certified (AOR, 0.89; 95% CI, 0.83-0.96), and graduates choosing family medicine were more likely to be board certified (AOR, 1.13; 95% CI, 1.01-1.26).<h3>Conclusion</h3>Demographic and educational factors were associated with board certification among US medical school graduates in every specialty category examined; findings varied among specialty categories.
Pet/Ct in the Evaluation of Response to Treatment with Bevacizumab and Chemotherapy in Patients with Advanced Colorectal Cancer
Authors: Encarnación González-Flores, Beatriz González-Astorga, Verónica Conde-Herrero, Javier García-García, Jesús Soberino-García, Cynthia González-Rivas, Julia Ruiz-Vozmediano, Lucia Castillo-Portellano, Raquel Luque-Caro, Juan Ramón lgado De Pérez
Journal: Annals of Oncology (2013)
Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: Report on two double-blind, vehicle-controlled studies
Authors: Jeffrey Bernhard, Claire Whitmore, Cynthia Guzzo, Irwin Kantor, Robert E. Kalb, Charles Ellis, Frederick Urbach, Edmund H. Schwartzel, John R. Gibson
Journal: Journal of the American Academy of Dermatology (1991)
Host Factors, Behaviors, and Clinical Trials: Opportunities and Challenges
Authors: Patricia A. Ganz
Journal: Journal of Clinical Oncology (2012)

by the recent Institute of Medicine (IOM) Report 1 that called for greater operational efficiencies in the conduct of federally supported clinical trials, while also improving the integration of the newest scientific discoveries (eg, molecular diagnostic markers, imaging, biomarkers) into these same trials. Cancer clinical trials are extremely costly to design and conduct. Much of the expense is related to the recruitment, enrollment, delivery of treatment, and follow-up of trial participants, while the cost of therapeutic agents is often born by trial sponsors(usuallythepharmaceuticalindustry).AsnotedbytheIOM
Identifying predictors of high quality care in English general practice: observational study
Authors: S M Campbell, M Hann, J Hacker, C Burns, D Oliver, A Thapar, N Mead, D G. Safran, M O Roland
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To assess variation in the quality of care in general practice and identify factors associated with high quality care. <b>Design:</b> Observational study. <b>Setting:</b> Stratified random sample of 60 general practices in six areas of England. <b>Outcome measures:</b> Quality of management of chronic disease (angina, asthma in adults, and type 2 diabetes) and preventive care (rates of uptake for immunisation and cervical smear), access to care, continuity of care, and interpersonal care (general practice assessment survey). Multiple logistic regression with multilevel modelling was used to relate each of the outcome variables to practice size, routine booking interval for consultations, socioeconomic deprivation, and team climate. <b>Results:</b> Quality of clinical care varied substantially, and access to care, continuity of care, and interpersonal care varied moderately. Scores for asthma, diabetes, and angina were 67%, 21%, and 17% higher in practices with 10 minute booking intervals for consultations compared with practices with five minute booking intervals. Diabetes care was better in larger practices and in practices where staff reported better team climate. Access to care was better in small practices. Preventive care was worse in practices located in socioeconomically deprived areas. Scores for satisfaction, continuity of care, and access to care were higher in practices where staff reported better team climate. <b>Conclusions:</b> Longer consultation times are essential for providing high quality clinical care. Good teamworking is a key part of providing high quality care across a range of areas and may need specific support if quality of care is to be improved. Additional support is needed to provide preventive care to deprived populations. No single type of practice has a monopoly on high quality care: different types of practice may have different strengths. <h3>What is already known on this topic</h3> Quality of care varies in virtually all aspects of medicine that have been studied Most studies look at quality of care from a single perspective or for a single condition <h3>What this study adds</h3> Quality of care varies for both clinical care and assessments by patients of access and interpersonal care Practices with longer booking intervals provide better management of chronic disease; preventive care is less good in practices in deprived areas No single type of practice has a monopoly on high quality care—small practices provide better access but poorer diabetes care Good team climate reported by staff is associated with a range of aspects of high quality care
Different definitions in childhood asthma: how dependable is the dependent variable?
Authors: K.E. Van Wonderen, L.B. Van Der Mark, J. Mohrs, P.J.E. Bindels, W.M.C. Van Aalderen, G. Ter Riet
Journal: European Respiratory Journal (2009)

There is abundant literature on how to select and statistically deal with predictors in prediction models. Less attention has been paid to the choice of the outcome. We assessed the impact of different asthma definitions on prevalence estimates and on the prediction model's performances. We searched PubMed and extracted data of definitions used to diagnose childhood asthma (between 6 and 18 yrs) in cohort studies. Next, using data from an ongoing cohort study (n = 186), we constructed and compared four prediction models which all predict asthma at age 6 yrs, using a fixed set of predictors and four different definitions in turn. We defined an area of clinical indecision (posterior probability between 25% and 60%) and calculated the number of children who remained inside this area. 122 papers yielded 60 different definitions. Prevalence estimates varied between 15.1% and 51.1% depending on the asthma definition used. The percentage of children whose posterior asthma probability was in the area of clinical indecision varied from 14.9% to 65.3%. Variation in definitions and its effect on the performance of prediction models may be another source of otherwise inexplicable variation in daily clinical decision making. More uniformity of operational asthma definitions seems needed.
Fibreoptic bronchoscopy in smear-negative pulmonary tuberculosis
Authors: R Chawla, K Pant, O P Jaggi, S Chandrashekhar, S S Thukral
Journal: European Respiratory Journal (1988)

Fifty smear-negative pulmonary tuberculosis patients underwent fibreoptic bronchoscopy. Bronchial aspirate smears of twelve patients and post-bronchoscopic sputum smears of fourteen patients were positive for acid-fast bacilli (AFB). Bronchial biopsy provided the diagnosis in 9 out of 30 patients. Brush smears were positive in 28 patients, being the only positive sample in ten cases. A high yield from brush smears was obtained due to their preparation from caseous material wherever visible in the bronchi. With these results a rapid diagnosis was established in 36 of the 50 patients. When culture results were available, a definite diagnosis of tuberculosis was made in 45 of the patients. The yield from brush smears was found to be significantly better when compared to bronchial aspirate smears (p less than 0.01) and post-bronchoscopic sputum smears (p less than 0.01).
Impaired Glucose Tolerance Leads to Delayed Diagnosis of AlstrÖm Syndrome
Authors: Martin Holder, Wolfgang Hecker, Guilio Gilli
Journal: Diabetes Care (1995)

OBJECTIVE To emphasis the need for timely diagnosis of AlstrÖm syndrome. CASE We report a case of late-detected AlstrÖm syndrome in a boy 15 1/2 years of age who was admitted because of poor wound healing and hyperglycemia. RESULTS Diagnosis was made and the patient's impaired glucose tolerance improved by diet. CONCLUSIONS Regular follow-ups are needed to recognize and possibly prevent late-appearing complications.
Homocysteine promotes human endothelial cell dysfunction via site-specific epigenetic regulation of p66shc
Authors: Cuk-Seong Kim, Young-Rae Kim, Asma Naqvi, Santosh Kumar, Timothy A. Hoffman, Saet-Byel Jung, Ajay Kumar, Byeong-Hwa Jeon, Dennis M. McNamara, Kaikobad Irani
Journal: Cardiovascular Research (2011)

Hyperhomocysteinaemia is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial dysfunction. Homocysteine modulates cellular methylation reactions. P66shc is a protein that promotes oxidative stress whose expression is governed by promoter methylation. We asked if homocysteine induces endothelial p66shc expression via hypomethylation of CpG dinucleotides in the p66shc promoter, and whether p66shc mediates homocysteine-stimulated endothelial cell dysfunction.Homocysteine stimulates p66shc transcription in human endothelial cells and hypomethylates specific CpG dinucleotides in the human p66shc promoter. Knockdown of p66shc inhibits the increase in reactive oxygen species, and decrease in nitric oxide, elicited by homocysteine in endothelial cells and prevents homocysteine-induced up-regulation of endothelial intercellular adhesion molecule-1. In addition, knockdown of p66shc mitigates homocysteine-induced adhesion of monocytes to endothelial cells. Inhibition of DNA methyltransferase activity or knockdown of DNA methyltransferase 3b abrogates homocysteine-induced up-regulation of p66shc. Comparison of plasma homocysteine in humans with coronary artery disease shows a significant difference between those with highest and lowest p66shc promoter CpG methylation in peripheral blood leucocytes.Homocysteine up-regulates human p66shc expression via hypomethylation of specific CpG dinucleotides in the p66shc promoter, and this mechanism is important in homocysteine-induced endothelial cell dysfunction.
Imaging of Effector Memory T Cells during a Delayed-Type Hypersensitivity Reaction and Suppression by Kv1.3 Channel Block
Authors: Melanie P. Matheu, Christine Beeton, Adriana Garcia, Victor Chi, Srikant Rangaraju, Olga Safrina, Kevin Monaghan, Marc I. Uemura, Dan Li, Sukumar Pal, Luis M. de la Maza, Edwin Monuki, Alexander Flügel, Michael W. Pennington, Ian Parker, K. George Chandy, Michael D. Cahalan
Journal: Immunity (2008)