tbuckley/cabot-search huggingface dataset:
The Rapid Development of Fluoroquinolone Resistance in<i>M. tuberculosis</i>
Authors: Amy Sarah Ginsburg, Samuel C. Woolwine, Nancy Hooper, William H. Benjamin, William R. Bishai, Susan E. Dorman, Timothy R. Sterling
Journal: New England Journal of Medicine (2003)

3.0 during the first days of treatment with vitamin K antagonists is unknown, and it is mainly a result of a more rapid depression of factor VII. 1 This is the single coagulation factor for which many prothrombin-time reagents are most sensitive.Moreover, because of the difference in the responses of thromboplastin reagents to the reduction of vitamin K-dependent coagulation factors, the INR values are more variable and less reliable during the initial phase of treatment than during long-term anticoagulant therapy. 3
Neonatal Diabetes Mellitus Due to Complete Glucokinase Deficiency
Authors: Pål R. Njølstad, Oddmund Søvik, Antonio Cuesta-Muñoz, Lise Bjørkhaug, Ornella Massa, Fabrizio Barbetti, Dag E. Undlien, Chiyo Shiota, Mark A. Magnuson, Anders Molven, Franz M. Matschinsky, Graeme I. Bell
Journal: New England Journal of Medicine (2001)

Diabetes mellitus is a heterogeneous disorder that can occur at any age.1 Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, is a rare disorder that is usually associated with intrauterine growth retardation.2 Like diabetes in general, neonatal diabetes is heterogeneous and can be either transient or permanent. Transient neonatal diabetes is associated with abnormalities of chromosome 6,2,3 whereas mutations in insulin promoter factor 1 result in pancreatic agenesis and permanent neonatal diabetes.4 We describe two patients in whom complete deficiency of the glycolytic enzyme glucokinase, a key regulator of glucose metabolism in pancreatic beta . . .
THU0006 PDE3A-SLCO1C1 Locus is Associated with the Response to Anti-Tumor Necrosis Factor Therapy in Rheumatoid Arthritis
Authors: I. Acosta-Colman, N. Palau, J. Tornero, A. Fernández-Nebro, F. Blanco, I. Gonzalez-Alvaro, J. D. Cañete, J. Maymó, J. Ballina, B. Fernández-Gutierrez, A. Olivé, H. Corominas, A. Erra, A. Alonso, M. López-Lasanta, R. Tortosa, A. Julià, S. Marsal
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-tumor necrosis factor (anti-TNF) agents have drastically improved the clinical course of Rheumatoid Arthritis (RA). Despite its success, there is a substantial number of patients (20-40%) who do not respond to this therapy. The high costs of these therapies as well as the availability of alternative biological treatments have increased the interest in identifying markers that help predict the response to anti-TNF therapy. <h3>Objectives</h3> The present study was undertaken to identify genes associated with anti-TNF response in Rheumatoid Arthritis. Candidate genes were selected from a recent Genome-Wide Association Study (GWAS) performed in Denmark population. <h3>Methods</h3> Genomic DNA was obtained from 315 Spanish RA patients having received an anti-TNF agent as their first biologic therapy. Treatment response was defined at 12 weeks using both the reduction in the DAS28 activity score and the EULAR treatment response criteria. SNPs the loci having the strongest evidence for statistical association for anti-TNF response (P&lt;5x10<sup>-6</sup> in the Danish population) were selected and genotyped using the Taqman genotyping platform. Statistical association analyses were performed using the chi-square test and linear regression. The statistical results from the two RA patient cohorts were integrated by metaanalysis. <h3>Results</h3> The <i>PDE3A</i>-<i>SLOC1C1</i> locus SNP rs3794271 showed a highly significant association with anti-TNF treatment response in our patient cohort (<i>P</i> &lt; 5e-5). Combining the statistical evidence from the Spanish and Danish RA cohorts, the associated SNP rs3794271 reached a genome-wide significant level of association with the response to anti-TNF therapy (<i>P &lt;5</i> x10<sup>-8</sup>). <h3>Conclusions</h3> The present findings establish the <i>PDE3A-SLOC1C1</i> locus as a strong genetic marker of anti-TNF therapy response. <h3>References</h3> Krintel, SB, G Palermo, JS Johansen <i>et al.</i>: Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNFalpha inhibitors in patients with rheumatoid arthritis. <i>Pharmacogenet Genomics</i> 22, 577-89 (2012) <h3>Acknowledgements</h3> This work was supported by the Spanish Ministry of Economy and Competitiveness Project grants (PSE-010000-2006-6, IPT-010000-2010-36). <h3>Disclosure of Interest</h3> None Declared
The Speed of Cerebral Circulation
Authors: Robert A. Kuhn
Journal: New England Journal of Medicine (1962)

IN modern civilizations an enormous toll of suffering and death is exacted by local disorders of brain blood flow. Regional hemodynamic failure, with unique rapidity, produces anoxic devastation in cerebral tissue. The paralyzed neuronal function is reflected clinically as a stroke.More adults are crippled by hemodynamic failure in the brain than by any other ailment — and the numbers of victims are increasing in a steadily aging population. Vascular lesions of the central nervous system now represent the third leading cause of death in the United States. Disorders of brain circulation have left vast armies of neurologic cripples who . . .
Abstract 1921: Body fatness and sex steroid hormone concentrations in US men – Results from NHANES III
Authors: Sabine Rohrmann, Meredith S. Shiels, David S. Lopez, Nader Rifai, William G. Nelson, Norma Kanarek, Eliseo Guallar, Andy Menke, Corinne E. Joshu, Manning Feinlieb, Siobhan Sutcliffe, Elizabeth A. Platz
Journal: Cancer Research (2011)

Abstract Background: Obesity is associated with a variety of chronic diseases, including cancer, which may partly be explained by its influence on sex steroid hormone concentrations. However, different measures of obesity are not equally strongly associated with the risk of these diseases, and, thus, might also differently influence circulating levels of sex steroid hormones. Objective: To estimate and compare the associations of body mass index (BMI), waist circumference, and percent body fat with circulating sex steroid hormone levels. Methods: In our analysis, we included 1,256 men, aged 20+ years, who attended the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1991). Serum hormones were measured by immunoassay. Weight, height, and waist circumference were measured by trained staff. Percent body fat was estimated from bioelectrical impedance. Linear regression was used to estimate associations between body fatness measures and hormone levels adjusting for age, race/ethnicity, previously identified correlates of hormone levels, and the other hormones. Results. Total and free testosterone and sex hormone binding globulin (SHBG) concentrations decreased with increasing BMI, waist circumference, and percent body fat (all p-trend &amp;lt;0.05), whereas total and free estradiol increased with increasing measures of body fatness (all p-trend &amp;lt;0.05). The magnitude of change in any one of these hormones was similar for a one quartile increase in each body fatness measure. Conclusions: Measured BMI, waist circumference, and percent body fat led to similar inferences about the association between body fatness and hormone levels in men. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1921. doi:10.1158/1538-7445.AM2011-1921
Exogenous Immunoglobulin and the Macrophage Origin of Reed–Sternberg Cells in Hodgkin's Disease
Authors: Marshall E. Kadin, Daniel P. Stites, Ronald Levy, Roger Warnke
Journal: New England Journal of Medicine (1978)

We studied Reed-Sternberg cells from 14 patients with Hodgkin's disease to learn whether they had monoclonal immunoglobulin synthesized by the cell or polyclonal immunoglobulin of external origin. Double-label immunofluorescence with F(ab')2 anti-serums to human light chains showed that cytoplasmic immunoglobulin of individual Reed-Sternberg cells is always polyclonal and usually associated with membrane-bound immunoglobulin of the same type. The predominant immunoglobulin was IgG; in one case IgM was also present. In vitro studies confirmed the internalization of exogenous IgG and phagocytosis of immune complexes by viable Reed-Sternberg cells. Their exclusion of trypan blue dye and lack of albumin and fibrinogen suggests relatively specific uptake of immunoglobulin, mediated by the Fc receptor or antigen (or antigens) associated with Hodgkin's disease at the cell membrane. Our studies support other recent evidence that the Reed-Sternberg cell is derived from a macrophage.
Endoscopic Ultrasound: A Meta-Analysis of Test Performance in Suspected Biliary Disease
Authors: D Garrow, S Miller, J Conway, D Sinha, B Hoffman, J Conway, J Romagnuolo
Journal: Endoscopy (2006)

Purpose: EUS achieves high-resolution images of the bile duct (CBD) and pancreas. It avoids the risks of ERCP, and may be comparable to MRCP, although its use is less widely disseminated for biliary disease. We aimed to summarize EUS test performance in suspected biliary disease with a meta-analysis.
Abstract 3356: Loss of breast epithelial hCLCA2 promotes EMT and increases risk of metastasis
Authors: Randolph C. Elble, Vijay Walia, Yang Yu, Deshou Cao, Miao Sun, Louis Premkumar
Journal: Cancer Research (2011)

Abstract Transition between epithelial and mesenchymal states is a feature of both normal development and tumor progression. We report that expression of chloride channel accessory protein hCLCA2 is a characteristic of epithelial differentiation in the immortalized MCF10A and HMLE models, while induction of EMT by cell dilution, TGFbeta, or mesenchymal transcription factor Snail sharply reduces hCLCA2 levels. Attenuation of hCLCA2 expression by lentiviral shRNA caused cell overgrowth and focus formation, enhanced migration and invasion, and increased mammosphere formation in methylcellulose. These changes were accompanied by downregulation of E-cadherin and upregulation of mesenchymal markers such as vimentin and fibronectin. Moreover, hCLCA2 expression is greatly downregulated in breast cancer cells with a mesenchymal or claudin-low profile. These observations suggest that loss of hCLCA2 may promote metastasis. We find that higher-than-median expression of hCLCA2 is associated with a one-third lower rate of metastasis over an 18 year period among breast cancer patients compared to lower-than-median (n=344, unfiltered for subtype). Thus, hCLCA2 is required for epithelial differentiation, and its loss during tumor progression contributes to metastasis. Overexpression of hCLCA2 has been reported to inhibit cell proliferation and is accompanied by increases in chloride current at the plasma membrane and reduced intracellular pH (pHi). We found that knockdown cells have sharply reduced chloride current and higher pHi, both characteristics of tumor cells. These results suggest a mechanism for the effects on differentiation. Loss of hCLCA2 may allow escape from pHi homeostatic mechanisms, permitting the higher intracellular and lower extracellular pH that are characteristic of aggressive tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3356. doi:10.1158/1538-7445.AM2011-3356
Abstract 1891: NF-κB signaling plays a certain role in apoptosis resistance in 3D-cultured <i>EGFR</i>-mutant lung adenocarcinoma cells
Authors: Yuji Sakuma, Yohei Miyagi
Journal: Cancer Research (2012)

Abstract It is generally thought that suspended tumor cells show reduced proliferative activity and are more resistant to conventional chemotherapy compared with adherent tumor cells. Two epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cell lines, HCC827 (E746-A750 deletion) and H1975 (L858R + T790M), cultured in suspension, however, undergo apoptosis much more easily than these two cell lines cultured in conventional monolayer dishes, i.e. anchorage dependent conditions, when the kinase activity of EGFR is completely inhibited by treatment with EGFR tyrosine kinase inhibitors (TKIs) regardless of suspension or monolayer culture conditions. These findings indicate that attached EGFR-mutant lung adenocarcinoma cells appear less dependent on constitutive EGFR signaling for survival than detached cells, probably because integrin ligation enhances cell survival in adherent cells. However, the microenvironment of cells in monolayer culture conditions is considerably different from that of cells in vivo. We thus tested whether EGFR-mutated lung adenocarcinoma cells in three dimensional (3D) conditions using Matrigel resist EGFR TKIs-induced apoptosis compared with suspended cells. We uncovered three major findings in this study as follows: 1) both HCC827 cells and H1975 cells cultured in 3D conditions were significantly less sensitive to EGFR TKIs-induced apoptosis than suspended cells. 2) Marked degradation of IαBβ, the inhibitor of NF-κB pathway, was observed only in 3D-cultured EGFR-mutated lung adenocarcinoma cells, resulting in NF-κB signaling activation. 3) TPCA-1, a potent IKKα inhibitor, can enhance the levels of apoptosis in 3D-cultured EGFR-mutant cells treated with EGFR TKIs. These results suggest that combined EGFR and NF-κB inhibition is required to induce apoptosis effectively in EGFR-mutated lung adenocarcinoma cells in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1891. doi:1538-7445.AM2012-1891
Abstract 2788: Serum steroid hormone levels and risk of lung adenocarcinoma among postmenopausal women in Taiwan
Authors: Yao-Jen Li, Shi-Yi Yang, Chuen-Fei Chen, Kuo-Meng Liao, Chien-Jen Chen
Journal: Cancer Research (2010)

Abstract Study goal: Lung cancer is the leading cause of death among women worldwide, ande adenocarcinoma is the most common histological subtype among non-smoking women. Among non-smoking population, the lung cancer incidence is higher than men. Previous studies have shown that hormone related factors, such us menstrual cycle, hormonal replacement therapy are associated with female lung cancer. Hormone related factors may play a role in lung cancer. Therefore, we hypothesized that hormone levels in serum among postmenopausal women may associated with lung adenocarcinoma. Material and methods: This was a case-control study. The study participants came from a medical center which located on Taichung Taiwan, 9 serum steroid hormone markers were determined for 81 women with lung adenocarcinoma and 114 unrelated cancer-free women who were frequently matched by age and sample collecting time from age of menopause. All subjects were postmenopausal and without using hormone replacement therapies. Unconditional logistic regression analysis was used to calculate the odds ratio (OR) and its 95% confidence interval (95% CI) for each hormone markers. Potential confounding factors, such us BMI, age at menarche, parity, and age at enrollment were take into regression models. Results: Compared to lowest tertile groups of hormone levels, the highest tertile groups of progesterone (OR, 0.34; 0.2-0.7), testosterone (OR, 0.37; 0.2-0.8), Free testosterone (OR, 0.40; 0.2-0.9), Androstenedione (OR, 0.29; 0.1-0.7), sex hormone-binding globulin (OR, 0.47; 0.2-1.0) were associated a decrease risk of lung adenocarcinoma among postmenopausal women after adjusted for age at enrollment, BMI. On the other side, serum estradiol (OR, 0.59; 0.3-1.3) and dehydroepiandrosterone sulfate (OR, 0.49; 0.2-1.0) levels showed non-significant decrease risk to female lung adenocarcinoma among postmenopausal subjects. Conclusions: The serum sex steroid hormone levels among postmenopausal women may influence the risk to lung adenocarcinoma in Taiwan. Prospective designs will be necessary to clarify the association between serum hormone levels and risk of female lung adenocarcnoma. Key word: serum, sex steroid hormone, post-menopause, lung adenocarcinoma. 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 2788.
Case 16-2005
Authors: Daniel S. Kohane, Julie R. Ingelfinger, Katherine Nimkin, Chin-Lee Wu
Journal: New England Journal of Medicine (2005)

A nine-year-old girl was admitted to the hospital because of headache, papilledema, visual changes, and vomiting. The headaches had begun 18 months before admission, and enuresis 9 months before admission, followed by decreased visual acuity. A neurologist had found bilateral papilledema. On admission, the blood pressure was 210/130 mm Hg. A pediatric intensivist and a pediatric nephrologist discuss the urgent treatment and diagnostic evaluation of a child with hypertension.
PWE-048 Recurrence Rates Following Piecemeal Resection Of 2 Cm Adenomatous Polyps: Abstract PWE-048 Table 1
Authors: M Harling, K Kandiah, Z Tsiamoulos, G Smith, B Saunders, J Martin
Journal: Gut (2014)

<h3>Introduction</h3> Piecemeal endoscopic mucosal resection (pEMR) is a minimally invasive endoscopic technique for the resection of sessile/flat colorectal polyps (larger than 2 cm). It has been suggested that patients should have a check procedure at 3 or 6 months to ensure complete initial excision of the lesion, and subsequent colonoscopic surveillance at between 1 and 3 years to identify recurrence. <h3>Methods</h3> This is a retrospective observational audit, including all patients with sessile/flat colorectal polyps of more than 20 mm in diameter who underwent pEMR in 2010, across 4 London Teaching Hospitals. Patients were either local or tertiary referrals. Data was obtained from colonoscopy and histology reports. The primary outcome measured was the follow up rate at first, check colonoscopy (3 months, 6 months or 1 year), and at the subsequent surveillance colonoscopy (1, 2 or 3 years). Recurrence rate at both check and surveillance was a secondary outcome. A high-risk recurrence was considered to be more than or equal to 10 mm and a low-risk recurrence less than 10mm. <h3>Results</h3> 153 patients were included in the cohort; 53 (34.6%) patients were local referrals and 100 (65.4%) were tertiary referrals. 128 (83.6%) patients had a check colonoscopy and 74 patients (49.0%) had a surveillance colonoscopy. Adenoma recurrence occurred in 44 (34.4%) patients at check colonoscopy, with 3 (2.4%) polyps having high-risk recurrence, and in 12 (16.3%) patients at surveillance colonoscopy, with 3 (4.1%) polyps having high-risk recurrence. Of the patients with recurrence at surveillance, 5 (41.6%) also had polyp recurrence at check colonoscopy, equating to failure to clear the initial recurrence in 11.4%. In 7 patients the check colonoscopy showed no recurrence. <h3>Conclusion</h3> The rate of check colonoscopy within our cohort was high, but the rate of surveillance colonoscopy was low. The frequency of adenoma recurrence was considerable at the check colonoscopy, but much reduced at the surveillance colonscopy. There was, however, a low rate of high-risk recurrence, suggesting that pEMR is an effective endoscopic technique to excise sessile/flat polyps as, in most cases, treatment of recurrence at the check colonoscopy was effective. A substantial proportion of individuals with recurrence at surveillance had recurrence at check colonoscopy, but recurrence was found at surveillance despite a normal check procedure. Strict adherence to follow-up protocols is, therefore, essential. <h3>Disclosure of Interest</h3> None Declared.
Cutaneous Ureteroileostomy in Children
Authors: Alan B. Retik, Alan D. Perlmutter, Robert E. Gross
Journal: New England Journal of Medicine (1967)

URINARY diversion is essential for the management of certain urologic disorders of childhood. Implantation of the ureters into an isolated segment of ileum, with restoration of intestinal continuity, has found wide application since it was popularized by Bricker1 in 1950. Most reports2 3 4 5 6 have referred primarily to the ileal conduit in adults as a method of urinary diversion associated with the treatment of pelvic cancer. The nature of such underlying diseases and their complications has limited evaluation of the long-term effects of the ileal conduit procedure per se. In children, diversion is most often done for benign diseases involving urinary-tract dysfunction, . . .
PTH-018 Results on the national uptake of the JETS e-Portfolio
Authors: T Mehta, K Dowler, B McKaig, R Valori, P Dunckley
Journal: Gut (2010)

<h3>Introduction</h3> Following a successful pilot, JAG released their new JETS e-Portfolio in September 2009. The JETS e-Portfolio has been designed to support trainees in endoscopy by providing them with a web-based, electronic tool for logging their endoscopic experience. It allows trainees to demonstrate their competence levels, develop a personal development plan and complete JAG DOPS forms. The JETS e-Portfolio has been designed to support and streamline the JAG trainee certification process which is currently under review. <h3>Methods</h3> The JETS e-Portfolio was released nationally in early September 2009. Initially it was released on a Deanery-by-Deanery basis starting in the Severn and West Midlands regions. It can now be used by any trust in any Deanery. Here we present the current uptake data at the time of writing. <h3>Results</h3> Since September 2009, 34 trusts (22.5%) in England have starting using the JETS e-Portfolio. 112 trainees now use the e-Portfolio to log their endoscopic experience. 1096 endoscopy lists have been logged with 5116 procedures added. 412 JAG approved DOPS have also been added to the system. There have been no major IT issues and the feedback from trainees using the system has been excellent. <h3>Conclusion</h3> After 3 months of release, nearly one quarter of English Trusts are using the JETS e-Portfolio. A staged release in Wales and Northern Ireland is also planned. Initial data suggest that trainees are very willing to input data into the JETS e-Portfolio. The e-Portfolio also appears to be supporting the training process through the regular use of DOPS forms. Details on how to set up the JETS e-Portfolio are available on the JAG website.
Cervical Cancer: Following the HPV Pathway
Authors: C. McNeil
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Cervical Cancer: Following the HPV Pathway Get access Caroline McNeil Caroline McNeil Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 18, 20 September 1995, Pages 1354–1355, https://doi.org/10.1093/jnci/87.18.1354 Published: 20 September 1995