tbuckley/cabot-search huggingface dataset:
US drug maker resisted changes to its opioid dosing recommendations to protect revenue, newspaper alleges
Authors: Michael McCarthy
Journal: BMJ (2016)

The drug manufacturer Purdue Pharmaceuticals resisted efforts to change the dosing recommendations for its long acting opioid OxyContin to protect its revenues, the Los Angeles Times has alleged in an investigative report published on 5 May.1

The company, however, has strongly rejected the paper’s claims. “In an attempt to resurrect a long-discredited theory, the paper ignores the clinical and regulatory data that directly contradicts their story,” Purdue said in a statement.

The report stated that Purdue …
Video capsule endoscopy in the diagnosis of gastrointestinal Kaposi’s sarcoma
Authors: S. Nagri, S. Duddempudi, S. Anand, Y. Arya
Journal: Endoscopy (2007)

A 47-year-old Hispanic man who had no significant past medical history was admitted to the Wyckoff Heights Medical Center with nausea and headache, which were followed by seizures. The patient had had significant weight loss and an abdominal computed tomographic scan revealed thickening of the stomach wall ([Figure 1]). The patient initially refused upper endoscopy but agreed to undergo video capsule endoscopy, which showed lesions suggestive of Kaposi’s sarcoma in the small bowel ([Figure 2]). He subsequently agreed to undergo upper endoscopy for biopsy of the lesion and this examination revealed purplish nodular lesions in the esophagus, stomach, and duodenum. Push-enteroscopy showed typical Kaposi’s lesions in the jejunum ([Figure 3]). A biopsy of one of the lesions showed spindle-cell proliferation with vascular splits, an appearance consistent with a diagnosis of Kaposi’s sarcoma ([Figure 4]). Immunohistochemical testing for human herpesvirus 8 (HHV-8) showed a strong positive reaction ([Figure 5]). The patient was subsequently found to have a very low absolute CD4 count and he tested positive for human inmmunodeficiency virus, with a high viral load. The patient was started on highly active antiretroviral therapy (HAART) and was feeling much better when seen on follow-up 2 weeks later.
PTU-036 The immunomodulatory effects of vitamin d on low-density cells and monocyte-derived dendritic cells from human peripheral blood in vitro
Authors: A N Milestone, D Bernado-Ordiz, N R English, E R Mann, A L Hart, S C Knight, H O Al-Hassi
Journal: Gut (2010)

<h3>Introduction</h3> Emerging evidence suggests Vitamin D (VD) possesses a wide range of immunomodulatory properties. Epidemiological evidence also implicates VD insufficiency in Inflammatory Bowel Disease (IBD).1 Dendritic Cells (DC) are conductors of the immune system, uniquely capable of primary antigen presentation to naïve T cells, determining either immune response or tolerance. Studies on laboratory-generated monocyte-derived dendritic cells (MoDC) demonstrate 1,25-dihydroxyvitaminD3 (1,25(OH)2D3), the biologically active form of VD, induces an immature and tolerogenic DC phenotype.2 In vivo studies on murine models of IBD suggest therapeutic potential for VD.3 <h3>Methods</h3> We determined the immunomodulatory effects of 1,25(OH)2D3 on maturation and functional phenotype of blood DC, in particular DC-enriched Low-Density Cells (LDC). Peripheral blood mononuclear cells (PBMC) were isolated on Ficoll gradients from blood of healthy volunteers. LDC enriched for DC were isolated on a NycoPrep gradient from non-adherent cells after overnight PBMC culture. MoDC were obtained from magnetically sorted CD14+ monocytes of PBMC, incubated for 5 days with IL-4 and GM-CSF. LDC and MoDC were cultured for another 24 h in complete medium with and without 1,25(OH)2D3 and/or LPS. LDC and MoDC maturation was determined by flow cytometry using monoclonal antibodies to maturation markers including CD14, CD40, HLA-DR and ILT-3, which is an inhibitory receptor and a marker of DC immaturity. MoDC functional phenotype was determined by phagocytotic capacity (FITC-Dextran uptake) which is reduced in mature DC. Cell morphology was also assessed by electron microscopy (EM). <h3>Results</h3> VD-conditioned LDC demonstrated an immature phenotype compared with controls with significantly increased expression of monocyte marker CD14 (&lt;0.01, n=10) and ILT-3 (p&lt;0.02, n=10), but significantly decreased CD40 (p&lt;0.001, n=14) and HLA-DR (p&lt;0.03, n=7), even when co-cultured with the antigen LPS for 4 or 24 h. Furthermore, FITC-Dextran uptake by VD-conditioned MoDC was enhanced dose dependently, correlating with increased CD14 expression, suggesting reversion to a monocyte-like state (p&lt;0.001). EM revealed a greater proportion of morphologically immature LDC cells in the VD groups compared with controls. <h3>Conclusion</h3> 1,25(OH)2D3 promotes an immature phenotype in both LDC and MoDC in vitro inducing a tolerogenic-type phenotype and monocyte-like state. These immunomodulatory effects suggest a potential therapeutic role for VD in IBD possibly by promotion of oral tolerance.
Cognitive Dysfunction: Part and Parcel of the Diabetic Foot
Authors: Rachel Natovich, Talma Kushnir, Ilana Harman-Boehm, Daniella Margalit, Itzhak Siev-Ner, Daniel Tsalichin, Ilia Volkov, Shmuel Giveon, Deborah Rubin-Asher, Tali Cukierman-Yaffe
Journal: Diabetes Care (2016)

OBJECTIVE The presence of a foot ulcer increases the self-treatment burden imposed on the individual with diabetes. Additionally, this condition increases the cognitive demands needed for adherence to medical recommendations. A potential gap could exist between medical recommendations and the individual’s ability to implement them. Hence, the goal of this study was to examine whether the cognitive profile of people with diabetic foot ulcers differs from that of people with diabetes without this complication. RESEARCH DESIGN AND METHODS This was a case-control study. Ninety-nine individuals with diabetic foot ulcers (case patients) and 95 individuals with type 2 diabetes (control subjects) (age range 45–75 years), who were matched for diabetes duration and sex, underwent extensive neuropsychological evaluation using a NeuroTrax computerized battery, digit symbol, and verbal fluency tests. A global cognitive score after standardization for age and education was computed as well as scores in the following six cognitive domains: memory, executive function, reaction time, attention, psychomotor abilities, and estimated premorbid cognition. RESULTS Individuals with diabetic foot ulcers had significantly (P &amp;lt; 0.001) lower cognitive scores than individuals with diabetes without this complication, in all tested cognitive domains, excluding estimated premorbid cognition. Individuals with diabetic foot ulcers demonstrated a significant difference between precognitive and current cognitive abilities, as opposed to the nonsignificant difference among control subjects. The differences persisted in multivariable analysis after adjusting for depression and smoking. CONCLUSIONS Individuals with diabetic foot ulcers were found to possess fewer cognitive resources than individuals with diabetes without this complication. Thus, they appear to face more self-treatment challenges, while possessing significantly fewer cognitive resources.
I wait for you
Authors: Patricia J. Wentzel
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Influence of some clinical parameters in the tolerance to treatment in elderly patients with advanced lung cancer.
Authors: N. G. Pilnik, M. Ibero M, D. Carri, O Mareca
Journal: Journal of Clinical Oncology (2010)

e19600 Background: Cancer represents a major clinical problem in the elderly. Two thirds of the population with lung cancer is 65 yrs or older. Lung cancer represents the first cause of death by cancer in older people.They are also more likely to present multiple comorbid conditions. They use three times more medications than younger pts. Besides, age affects the pharmacokinetics of antineoplasic agents and increases the susceptibility to complications. Methods: 130 lung cancer pts with PS (0,1,2) were included. Pts selection was conducted using General Geriatric Assessment. ADL(Activity of Daily Living) and IADL(Instrumental of Daily Living) was studied before and after treatment . Pts underwent Ch/Rxt . Pts were divided in older and younger than 70. All pts had adequate cardiac, hepatic, renal and bone marrow functions. Comorbidities studied were: hypertension, diabetes, OCLD, arrhythmia, coronary disease and digestive disease. Toxicities were studied following the WHO criteria and correlated according to age, ADL, IADL, PS, WL, comorbidities, and the use of more than 3 drugs (Polypharmacy), in addition to the treatment. QoL was assessed through the evolution of ADL, IADL and PS .Statistical Methods: Pearson's Chi-Square, Kaplan Meier's Survival tests. Results: The most frequent toxicity level in the whole sample was Grade I. No relationship was found between toxicities and age, irrespective of type and level. Toxicity level was found to be higher in the patients who used more than 3 other medications p=0.03. Pts with PS 0-1 had lower toxicity level than pts with PS 2. Statistically significant association was found between comorbidities and toxicity levels. There was improvement in Qol through ADL, PS, and IADL evolution after treatment p= 0.001. Conclusions: Older lung cancer pts in good general condition and with controlled comorbidities may receive Ch/ Rxt, if this treatment modality results in improvement of their QoL. The reason why the majority of pts had low toxicities may be attributed to the fact that all of them were properly selected. Treatment options should be tailored to older patients based on the same selection process and benefits seen in the population as a whole. No significant financial relationships to disclose.
Is intra-operative touch preparation cytology more accurate than permanent pathology?
Authors: E. K. Valdes, S. K. Boolbol, I. Ali, J.-M. Cohen, S. M. Feldman
Journal: Journal of Clinical Oncology (2005)

750 Background: Breast conservation surgery in combination with radiotherapy is a standard of treatment for the majority of breast cancers. It is critical to obtain clear margins to minimize local recurrence. Most centers report a positive margin rate 20–55% for the initial surgical excision. The literature suggests that intra-operative touch preparation cytology (IOTPC) can be useful in evaluation of margins. This report describes our experience with IOTPC for margin assessment in ductal carcinoma by a single surgeon (SMF) at Beth Israel Medical Center (BIMC). The purpose of this study is to determine whether IOTPC can reduce the number of re-excisions. Methods: A retrospective review of 297 patients with ductal carcinoma who have undergone breast conservation surgery by a single surgeon at BIMC was performed. Sixty-one of these patients underwent IOTPC. The specimens were oriented and submitted for cytologic evaluation. This group was then compared to the control group who have undergone breast conservation surgery without the use of IOTPC. The standard of practice for the surgeon was to take additional margins routinely at the time of the lumpectomy in all patients. Results: Sixty-one patients underwent breast conservation surgery with IOTPC for assessment of 366 margins. Eleven of 35 margins with positive IOTPC and negative final pathology contained residual cancer on additional margins and 9 of 35 margins were <=2mm on permanent pathology. There is an association (RR= 1.39) that patients who did not undergo the IOTPC are 39% more likely to have more than one excision than patients who did have IOTPC performed. Conclusions: Intra-operative touch prep cytology for margin assessment in ductal carcinoma has a sensitivity of 65.7%, specificity of 95.5%, positive predictive value of 60.5%, and negative predictive value of 96.3%. Based on our experience IOTPC reduces the re-excision rate and may be more accurate than permanent pathology for assessment of margins. No significant financial relationships to disclose.
How One Thing Led to Another
Authors: Irving Weissman
Journal: Annual Review of Immunology (2016)

I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a "don't eat me" signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.
Small-Cell Lung Cancer, High Growth Rate, High Response Rate to Chemotherapy: Ideal for High-Dose Chemotherapy?
Authors: Eleni Galani, Paul A. Ellis, Peter G. Harper
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.19.3941 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12351589 Small-Cell Lung Cancer, High Growth Rate, High Response Rate to Chemotherapy: Ideal for High-Dose Chemotherapy? Eleni GalanixEleni GalaniSearch for articles by this author , Paul A. EllisxPaul A. EllisSearch for articles by this author , Peter G. HarperxPeter G. HarperSearch for articles by this author Show More Guy’s Hospital, London, United Kingdom https://doi.org/10.1200/JCO.2002.20.19.3941 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Outcome Of Aplastic Anemia In Adolescence. A Survey Of The Severe Aplastic Anemia Working Party (SAAWP) Of The European Blood and Bone Marrow Transplant Group (EBMT)
Authors: Carlo Dufour, Marta Pillon, Jakob Passweg, Gérard Socié, Andrea Bacigalupo, Genny Franceschetto, Rosi Oneto, Antonio M. Risitano, Regis Peffault de la Tour, Andre Tichelli, Alicia Rovo, Christina Peters, Britta Hochsmann, Hubert Schrezenmeier, Mahmoud D. Aljurf, Judith Marsh
Journal: Blood (2013)
Susceptibility genes for lung diseases in the major histocompatibility complex revealed by lung expression quantitative trait loci analysis
Authors: Maxime Lamontagne, Philippe Joubert, Wim Timens, Dirkje S. Postma, Ke Hao, David Nickle, Don D. Sin, Peter D. Pare, Michel Laviolette, Yohan Bossé
Journal: European Respiratory Journal (2016)

The major histocompatibility complex (MHC) has been linked with hundreds of diseases [1]. The MHC is one of the most complex regions of the human genome, because of the high gene density, extended linkage disequilibrium (LD) and sequence diversity [2]. Recent genome-wide association studies (GWAS) have identified polymorphisms located in the MHC that are associated with lung diseases and related traits: asthma, cystic fibrosis, idiopathic interstitial pneumonia, lung cancer and lung function. However, due to the limitations of GWAS and tissue-specific characteristics of gene expression [3], the causal genes and genetic mechanisms mediating the heritable risk within this locus remain to be found. New susceptibility genes for asthma, idiopathic interstitial pneumonia, lung cancer and lung function in the MHC <http://ow.ly/10onzl> The authors would like to thank Christine Racine and Sabrina Biardel at the Institut universitaire de cardiologie et de pneumologie de Québec (Québec, QC, Canada) site of the Respiratory Health Network Biobank of the FRQS for their valuable assistance. At the University of British Columbia (Vancouver, BC, Canada) the authors thank the biobank coordinator Mark Elliott. At the University of Groningen, University Medical Center Groningen (Groningen, the Netherlands) Marnix Jonker is thanked for his support in selecting, handling and sending of lung tissues.
WHO criteria for measles elimination: a critique with reference to criteria for polio elimination
Authors: H Kelly, M Riddell, A Heywood, S Lambert
Journal: Eurosurveillance (2009)

Smallpox was formally declared as eradicated in 1979. Smallpox is the only infectious disease of humans that has ever been eradicated. Poliomyelitis has been eliminated from three of the six World Health Organization (WHO) regions although not all countries within those regions always meet the elimination criteria. Elimination criteria for measles are being discussed. We use poliomyelitis and measles as examples to illustrate our assertion that the current approach to documenting measles elimination relies too heavily on criteria for surveillance quality, disadvantaging countries with long established and relatively inflexible surveillance systems. We propose an alternative approach to documenting measles elimination, with the two key criteria being molecular evidence to confirm the lack of a circulating endemic genotype for at least one year and maintenance of 95% coverage of one dose of measles-containing vaccine, with an opportunity for a second dose. Elimination status should be reviewed annually. We suggest four principles that should guide development of final criteria to document measles elimination: countries that have eliminated measles should be able to meet the elimination criteria; quality surveillance criteria are necessary but not sufficient to define elimination; quality surveillance criteria should be guided by elimination criteria, not the other way around; and elimination criteria should not differ between the WHO regions without good reason.
Metabolism of Acyclic and Cyclic N-Nitrosamines in Cultured Human Bronchi2
Authors: Curtis C. Harris, Herman Autrup, Gary D. Stoner, Elizabeth M. McDowell, Benjamin F. Trump, Paul Schafer
Journal: JNCI Journal of the National Cancer Institute (1977)

The metabolism of carcinogenic N-nitrosamines was studied in normal-appearing bronchial specimens obtained from 4 patients. Explants of bronchi were cultured in a chemically defined medium for 7 days. N-Nitrosamines [N-nitrosodimethylamine (DMN), N-nitrosodiethylamine (DEN), NN′dinitrosopiperazine (DNP), N-nitrosopyrrolidine (NPy), and N-nitrosopiperidine (NPd)] labeled with 14C were each then added at 100 μmoles for 24 hours. Measurable CO2 was formed by bronchial explants from: 1) DMN, DEN, and NPy in all 4 patients; 2) DNP In 3 of 4 patients; and 3) NPd in only 1 of 4 patients. In all bronchial specimens, these N-nitrosamines and/or their metabolites bound to bronchial mucosal DNA and protein. Binding levels were higher to protein than to DNA. Binding levels of DNP were as high as those with the two acyclic N-nitrosamines DMN and DEN, but binding levels of NPy and NPd were lower. Human bronchus was shown to metabolize and bind acyclic and cyclic N-nitrosamines found in the environment and in tobacco smoke.
How Good Are Statistical Models at Approximating Complex Fitness Landscapes?
Authors: Louis du Plessis, Gabriel E. Leventhal, Sebastian Bonhoeffer
Journal: Molecular Biology and Evolution (2016)

Fitness landscapes determine the course of adaptation by constraining and shaping evolutionary trajectories. Knowledge of the structure of a fitness landscape can thus predict evolutionary outcomes. Empirical fitness landscapes, however, have so far only offered limited insight into real-world questions, as the high dimensionality of sequence spaces makes it impossible to exhaustively measure the fitness of all variants of biologically meaningful sequences. We must therefore revert to statistical descriptions of fitness landscapes that are based on a sparse sample of fitness measurements. It remains unclear, however, how much data are required for such statistical descriptions to be useful. Here, we assess the ability of regression models accounting for single and pairwise mutations to correctly approximate a complex quasi-empirical fitness landscape. We compare approximations based on various sampling regimes of an RNA landscape and find that the sampling regime strongly influences the quality of the regression. On the one hand it is generally impossible to generate sufficient samples to achieve a good approximation of the complete fitness landscape, and on the other hand systematic sampling schemes can only provide a good description of the immediate neighborhood of a sequence of interest. Nevertheless, we obtain a remarkably good and unbiased fit to the local landscape when using sequences from a population that has evolved under strong selection. Thus, current statistical methods can provide a good approximation to the landscape of naturally evolving populations.
Cultural knowledge is the key to understanding
Authors: E. Webb
Journal: BMJ (1995)

EDITOR,--J A Black and G D Debelle's review of female genital mutilation is superficial in its treatment of the anthropological context and the complexity of the challenges facing professionals in child protection.2 Current beliefs about the function of female genital mutilation are diverse and include easier childbirth and the prevention of infant death. Focusing on female genital mutilation solely as a control on female sexuality not only misrepresents the situation but is unlikely to enable professionals to establish meaningful dialogues with the communities in question—an essential prerequisite to eradication of the practice. Many communities regard the operations performed at initiation essential, to remove …