tbuckley/cabot-search huggingface dataset:
French health staff strike over budget cuts
Authors: A. Dorozynski
Journal: BMJ (2000)

Hospital staff throughout France staged massive demonstrations last Friday to protest against staff shortages and health budget restrictions imposed by the government. About 8000 doctors and other staff in Paris stopped work for three hours to attend rallies, and thousands marched through Rennes, Marseilles, Lyons, and a dozen other cities.

Demonstrators denounced the “rationing of health care,” first introduced by former right wing prime minister Alain Jupp in 1995 to reduce the growing deficit of the health …
Roth's Spots
Authors: Zsolt Varga, Jiri Pavlu
Journal: New England Journal of Medicine (2005)

A 24-year-old man presented with a three-day history of a blurred patch near the center of his left visual field. He reported no fatigue or weight loss. Ophthalmoscopy showed venous dilatation and multiple Roth's spots in both retinas (arrows in Panel A, showing the fundus of the left eye). Physical examination revealed splenomegaly extending to the right iliac fossa. No fever and no cardiac murmurs were noted. When blood was examined to measure the erythrocyte sedimentation rate, an elongated buffy-coat zone was observed (Panel B, bracket); a similar examination of blood from a healthy person is shown on the left. . . .
Long-acting Glyceryl Trinitrate in Angina Pectoris of Out-patients
Authors: T. R. E. Pilkington, M. J. Purves
Journal: BMJ (1960)

was in a study designed to show the effect of byssinosis in flax-workers during the course of the working day, as had been previously demonstrated by Schilling (1956) in cotton-workers.Otherwise the instrument has been found to give results comparable to those obtained using more sophisticated apparatus.It is fully portable, and can be used without lengthy preparations.It is speedy in operation, the time needed to take three readings and explain the use of the instrument being only three minutes, as contrasted with five minutes for the Gaensler apparatus, its nearest rival.The peak flow meter measures a component of respiration slightly different from that measured by the spirometers.It measures the initial peak, lasting about one-hundredth of a second, compared with the three- quarter second measured on the spirometer, and it is more sensitive to the muscular element in respiration.It does, however, separate respiratory conditions with an efficiency equal to that of other instruments in common use.
Abstract LB-228: Association of XRCC1 SNPs with clinical response in AML patients
Authors: Amit K. Mitra, Kristine Crews, Stanley Pounds, Xueyuan Cao, Jeffrey Rubnitz, Raul Ribeiro, Jatinder K. Lamba
Journal: Cancer Research (2012)

Abstract DNA repair system is critical in maintaining genome stability and integrity in response to various exogenous and endogenous stress factors. It is a multistep processes involving several enzymes including XRCC1 (X-ray repair cross-complementing group1) protein which plays a vital role in DNA repair activities and therefore is important for maintenance of genetic stability. The current study involves investigation of single nucleotide polymorphisms (SNPs) in the XRCC1 gene and their association with clinical response in pediatric acute myeloid leukemia (AML) patients treated with cytarabine (ara-C) based anti-leukemic chemotherapy in the St. Jude AML02 clinical trial. The St. Jude AML02 trial enrolled 232 AML patients less than 22 years of age, randomized to receive induction I therapy containing high-dose cytarabine or low-dose cytarabine plus daunorubicin and etoposide. A total of eighteen XRCC1 SNPs were genotyped using MALDI-TOF based Sequenom assay and screened for association with 3 endpoints, namely: in vitro ara-C LC50 determined in leukemic cells obtained at diagnosis (which was measured by treating leukemic cells in vitro with varying concentrations of ara-C), event free survival (EFS) and overall survival (OS). Jung statistic was used to determine association of the number of minor alleles with EFS and OS. Association of genotypes with EFS and OS was measured using Cox regression models while considering previously identified prognostically important variables. Our results showed significant association of 4 XRCC1 SNPs with survival and ara-C LC50 in pediatric AML patients. Three of these were present in the coding region, while one was a regulatory SNP located in the promoter region of the XRCC1 gene. XRCC1 SNPs have also been shown to be associated with cancer susceptibility and survival in previous studies. Our results now demonstrate clinical significance of XRCC1 SNPs in pediatric AML and suggest a role of these SNPs as prognostic factors in AML chemotherapy. These results might open up opportunities for tailored chemotherapy based on genomic markers to improve therapeutic outcome. 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 LB-228. doi:1538-7445.AM2012-LB-228
NICE updates guidance on early and advanced breast cancer
Authors: S. Mayor
Journal: BMJ (2009)

People with early invasive breast cancer should have minimal surgery without removal of lymph nodes unless there is evidence that cancer has spread to them, recommends new guidance for the NHS in England and Wales.

It also suggests that women who are being advised to have a mastectomy should be offered breast reconstruction, even if it is not available locally, and it updates recommendations on choice of hormonal therapy, on the basis of the latest research.

The new guidance on early breast cancer from the National Institute for Health and Clinical Excellence (NICE) advises against lymph node clearance in people in whom no evidence is shown on ultrasonography or needle biopsy of lymph node involvement. It suggests that sentinel lymph node biopsy should be used to assess whether …
Effect on the canine Eck fistula liver of intraportal TGF-β alone or with hepatic growth factors
Authors: Antonio Francavilla, Alessandro Azzarone, Guiseppe Carrieri, Carlo Scotti-Fogueni, Qia-Hua Zeng, Umberto Cillo, Kendrick Porter, Thomas E. Starzl
Journal: Hepatology (1992)

Transforming growth factor-beta canceled the hepatocyte proliferation caused by transforming growth factor-alpha when the two substances were mixed and administered through a disconnected central portal vein branch after creation of an Eck fistula. In contrast, transforming growth factor-beta had no antidotal action on the stimulatory effects of insulin or full test doses of insulinlike factor-2, hepatocyte growth factor, epidermal growth factor or triiodothymanine. A minor antidotal effect on hepatic stimulatory substance activity could be detected, but only with hepatic stimulatory substance was given in doses smaller than those known to cause maximum stimulatory response. These results suggest a highly specific pharmacological and physiological interaction between transforming growth factor-alpha and transforming growth factor-beta in the modulation of liver growth control.
Abstract 3118: Regulation of SDF-1 (CXCL12) production by mesenchymal stromal cells
Authors: Sohrab Amiri
Journal: Cancer Research (2011)

Abstract The tumor microenvironment is made up of a number of cell types including neoplastic epithelial cells, myofibroblasts, smooth muscle cells, pericytes, adipocytes, endothelial cells and their precursors, fibroblasts and immune cells. The interaction between cellular components of the microenvironment is critical for processes such as tumor progression, growth, angiogenesis, and metastasis. Mesenchymal stromal cells (MSCs) are an important component of the tumor microenvironment with roles in key aspects of tumor development such as cell growth and metastasis. Stromal-derived factor -1 (SDF-1) has been identified as a key-signaling molecule in the interaction between MSCs and neoplastic cells. SDF-1 acting through its cognate receptors CXCR4 and CXCR7 is known to mediate diverse processes such as chemotaxis, angiogenesis, hematopoiesis, metastasis, and tumor growth. In this study, we investigated the regulation of SDF-1 production by MSCs. We show that the tumor suppressor p53 is an important regulator of SDF-1 signaling in MSCs within the tumor stroma. A decrease in p53 function leads to increased SDF-1 production by MSCs and increased migration of MSCs in response to tumor cells. An improved understanding of the molecular mechanisms controlling SDF-1 production by MSCs may identify novel ways to therapeutically target tumor – stromal interactions. 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 3118. doi:10.1158/1538-7445.AM2011-3118
Abstract 3575: Dovitinib (TKI258), a dual inhibitor of FGFR and VEGFR, induces tumor growth suppression in xenograft models of human bladder cancer
Authors: Michael M. Shi, Ronald Linnartz, Richard Versace, Joseph Brueggen, Christian Chatenay-Rivauday, Christelle Stamm, Margaret Dugan, Diana Graus Porta
Journal: Cancer Research (2011)

Abstract Introduction: The aim of this study was to evaluate the efficacy of dovitinib (TKI258), a small molecule dual inhibitor of fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR) in mouse models of human bladder cancer. Molecular epidemiological studies have implicated FGFR and VEGFR pathways in the pathogenesis of high grade, muscle invasive bladder cancer. Somatic activating mutations in FGFR3 have been identified in 16%-20% of muscle-invasive bladder cancer and FGFR3 overexpression has also been documented in a high fraction of bladder cancers. High microvessel density, serum VEGF levels and urine FGF2 levels have also been associated with high grade bladder cancer and poor disease-free survival. Dual FGFR/VEGFR inhibitory activities of dovitinib make it an attractive molecule targeting advanced bladder cancer. Experimental Design: Dovitinib was evaluated in the RT112 human bladder carcinoma xenograft model. Dovitinib was administered orally at three dose levels (n = 10/group), once daily for 28 consecutive days (qd × 28). A rat RT112 xenograft study was also carried out to evaluate the PK/PD effect of single dose dovitinib administration. Results: Dovitinib at 15, 30, and 60 mg/kg resulted in tumor growth suppression, with mean changes of 60% T/C, 6% T/C (P &amp;lt; 0.01), and -71% T/T0 (P &amp;lt; 0.001), respectively. The 60 mg/kg regimen yielded 6 partial regressions out of 10 animals by day 28. In the rat RT112 model, dovitinib caused dose- and time-dependent inhibition of pFRS2 at 25 and 50 mg/kg after 3, 7 and 24 h of a single oral dose administration. Conclusion: Dovitinib demonstrated significant antitumor effect in a mouse model of human bladder cancer xenograft. This study provides a strong rationale for clinical investigation of dovitinib in patients with advanced bladder cancer. 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 3575. doi:10.1158/1538-7445.AM2011-3575
Formation of Covalently Bound Protein Adducts from the Cytotoxicant Naphthalene in Nasal Epithelium: Species Comparisons
Authors: Christina DeStefano-Shields, Dexter Morin, Alan Buckpitt
Journal: Environmental Health Perspectives (2009)

Naphthalene is a volatile hydrocarbon that causes dose-, species-, and cell type-dependent cytotoxicity after acute exposure and hyperplasia/neoplasia after lifetime exposures in rodents. Toxicity depends on metabolic activation, and reactive metabolite binding correlates with tissue and site susceptibility.We compared proteins adducted in nasal epithelium from rats and rhesus macaques in vitro.Adducted proteins recovered from incubations of nasal epithelium and 14C-naphthalene were separated by two-dimensional (2D) gel electrophoresis and imaged to register radioactive proteins. We identified proteins visualized by silver staining on complementary non-radioactive gels by peptide mass mapping.The levels of reactive metabolite binding in incubations of rhesus ethmo-turbinates and maxillo-turbinates are similar to those in incubations of target tissues, including rat septal/-olfactory regions and murine dissected airway incubations. We identified 40 adducted spots from 2D gel separations of rat olfactory epithelial proteins; 22 of these were non-redundant. In monkeys, we identified 19 spots by mass spectrometry, yielding three non-redundant identifications. Structural proteins (actin/tubulin) were prominent targets in both species.In this study we identified potential target proteins that may serve as markers closely associated with toxicity. The large differences in previously reported rates of naphthalene metabolism to water-soluble metabolites in dissected airways from mice and monkeys are not reflected in similar differences in covalent adduct formation in the nose. This raises concerns that downstream metabolic/biochemical events are very similar between the rat, a known target for naphthalene toxicity and tumorigenicity, and the rhesus macaque, a species similar to the human.
Lidocaine Prophylaxis and Myocardial Infarction-Reply
Authors: Ralph I. Horwitz
Journal: JAMA (1982)

In Reply.—  We apologize for not including details of the criteria that we used for accepting diagnoses of acute myocardial infarction. The criteria, which were modified from the World Health Organization, 1 are briefly summarized as follows: unequivocal serial changes on the ECG or typical or atypical chest pain history, together with an equivocal ECG and elevated cardiac enzymes or a typical chest pain history and elevated cardiac enzymes with a normal ECG. Readers who want to know further details can obtain them by writing to us.  Since our work was done to test the two hypotheses about anticoagulants and lidocaine, the various analytic subgroups were formed according to the principles used for arranging comparisons of patients and results in a randomized trial. We showed the ancestors of those subgroups to demonstrate how erroneous results can be obtained when observational data are analyzed without suitable attention to those principles. Our
An impossible woman
Authors: T. Dalrymple
Journal: BMJ (2009)

Valvular heart disease (VHD) is highly relevant in the aircrew population as it may limit appropriate augmentation of cardiac output in high-performance flying and predispose to arrhythmia. Aircrew with VHD require careful long-term follow-up to ensure that they can fly if it is safe and appropriate for them to do so. Anything greater than mild stenotic valve disease and/or moderate or greater regurgitation is usually associated with flight restrictions. Associated features of arrhythmia, systolic dysfunction, thromboembolism and chamber dilatation indicate additional risk and will usually require more stringent restrictions. The use of appropriate cardiac imaging, along with routine ambulatory cardiac monitoring, is mandatory in aircrew with VHD. Aortopathy in aircrew may be found in isolation or, more commonly, associated with bicuspid aortic valve disease. Progression rates are unpredictable, but as the diameter of the vessel increases, the associated risk of dissection also increases. Restrictions on aircrew duties, particularly in the context of high-performance or solo flying, are usually required in those with progressive dilation of the aorta.
Iliolumbar Ligament Ossification Demonstrated on Bone Scintigraphy
Authors: Myung-Hee Sohn, Seok Tae Lim, Hwan-Jeong Jeong, Dong Wook Kim, Chang-Yeol Yim
Journal: Clinical Nuclear Medicine (2009)

Horizontally-directed, bilaterally-symmetric, increased linear uptake connecting the L5 vertebra to the iliac crest was incidentally demonstrated on bone scintigraphy in a 51-year-old woman without any radiologic signs or clinical symptoms of spondylitis or arthritis. Plain radiography and computed tomography (CT) revealed ossification of both iliolumbar ligaments in the corresponding sites. This uptake is thought to represent a normal variant on bone scintigraphy.
Effect of oral bisphosphonates on bone mineral density and body composition in adult patients with cystic fibrosis: a pilot study
Authors: S P Conway
Journal: Thorax (2004)

Approximately two thirds of adult patients with cystic fibrosis have reduced bone mineral density and up to one quarter have osteoporosis at one or more sites. Any bone mineral deficits are likely to be exacerbated in patients following lung transplantation by their immunosuppressive regimen. Vertebral collapse and rib fractures will impair the ability to cough and the efficacy of physiotherapy treatments.Patients attending the Leeds Regional Adult Cystic Fibrosis Unit with either osteopenia or osteoporosis on dual energy x ray absorptiometry (DXA) scanning were offered treatment with oral bisphosphonates after exclusion of abnormal vitamin D, calcium, or phosphate levels, abnormal thyroid function, or hypogonadism. Those declining treatment or patients with a normal initial DXA scan formed the control group. A second DXA scan was performed after a mean of 2.4 years in the treatment group and 2.9 years in the non-treatment group. Patients in the active group were asked to complete a short questionnaire detailing their adherence to treatment.The medians of the differences in annual changes in bone parameters between treatment and control groups showed significant differences in bone mineralisation in favour of the treatment group at the lumbar spine (L2-L4), the femoral neck, and for total body measurements. There were no significant differences in weight, height, or body composition in either patient group. Most treated patients stated that they adhered to treatment most of the time.Treatment with oral bisphosphonates may improve bone mineralisation in adult patients with cystic fibrosis. The results of this pilot study need to be further explored in a randomised controlled trial.
Abstract C15: CRMP1 functions to suppress epithelial-mesenchymal transition and invasion capacity of prostate cancer cells
Authors: Ganhui Cai, Shan Yu, Yanping Ji, Franky Leung Chan
Journal: Cancer Research (2013)

Abstract Collapsin response mediator protein 1 (CRMP1) is originally identified and characterized as a cytoplasmic phosphoprotein involved in the Semaphorin 3A (Sema3A)-regulated growth cone collapse during neural development, via its regulation of cytoskeleton dynamics, and then also characterized as an invasion suppressor in lung cancer. Thus, we hypothesize that CRMP1 may be involved in the epithelial-mesenchymal transition (EMT) process and invasion or metastasis via its regulation on cytoskeleton organization in prostate cancer cells. Results of immunohistochemistry study showed that CRMP1 exhibited a reduced expression pattern in high Gleason-scored clinical prostate cancer tissues. In vitro functional studies showed that stable CRMP1-knockdown could induce EMT in prostate cancer cells (DU145), while its ectopic expression could induce the reverse process mesenchymal-epithelial transition (MET) in both DU145 and PC-3 prostate cancer cells, as evidenced by significant change of cellular morphology and altered expression levels of epithelial and mesenchymal markers. Confocal immunofluorescence showed that reorganization of F-actin was seen after shRNA-mediated CRMP1-knockdown in DU145 cells. It was also revealed that CRMP1 overexpression could confer the resistance to TGF-β1- and Snail-induced EMT in prostate cells. Results of CRMP1 promoter-driven luciferase reporter and ChIP assays indicated that Snail was a direct transrepressor of CRMP1 gene, which showed a downregulation pattern in both prostate cancer cells (DU145) and immortalized prostatic epithelial cells (BPH1) with overexpression of Snail. Furthermore, wound healing and Matrigel invasion assays showed that CRMP1 could inhibit cell migration and invasion capacity in DU145 and PC-3 cells. Taken together, our findings suggest that CRMP1 could play a role in prostate cancer invasion and metastasis, via its regulation on EMT and MET process. (This work was supported by a Direct Grant for Research and a RGC-GRF grant 2009/2010) Citation Format: Ganhui Cai, Shan Yu, Yanping Ji, Franky Leung Chan. CRMP1 functions to suppress epithelial-mesenchymal transition and invasion capacity of prostate cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C15.
The drug of choice for major seizures?
Authors: D P Addy
Journal: BMJ (1979)

treat local swelling with oral antihistamines.A patient with any systemic manifestations should be given a Medihaler-Epi as well as antihistamine tablets, although it is doubtful if any medication will be absorbed by the gastric mucosa after a sting.Although there may be few actual fatalities from insect stings, the number of nearfatalities and of incidents terrifying to patients and their relatives must, to judge by the number seen at our clinic, be high.Some attempt should therefore be made to protect acutely sensitive patients.The best method available at present is hyposensitisation and the pure venom extracts mentioned in your article should become available in a few weeks.
The Chemokine and Chemokine Receptor Profile of Infiltrating Cells in the Wall of Arteries With Cardiac Allograft Vasculopathy Is Indicative of a Memory T–Helper 1 Response
Authors: Jorg van Loosdregt, Matthijs F.M. van Oosterhout, Annette H. Bruggink, Dick F. van Wichen, Joyce van Kuik, Erica de Koning, Carla C. Baan, Nicolaas de Jonge, Frits H.J. Gmelig-Meyling, Roel A. de Weger
Journal: Circulation (2006)

Despite improvement in short-term patient survival after heart transplantation (HTx), long-term survival rates have not improved much, mainly because of cardiac allograft vasculopathy (CAV). Cytokines and chemokines are considered to play an important role in CAV development.We focused on coronary arteries of HTx patients and made an inventory of the infiltrating cells and the expression of cytokines as well as chemokines and chemokine receptors (C+CR) in the different layers of the vessel wall with CAV. Tissue slides were stained for a variety of cell markers (CD3, CD4, CD8, CD20, CD68, CD79a), chemokines (monokine induced by interferon [MIG], interferon-inducible protein 10 [IP-10], interferon-inducible T cell-alpha chemoattractant [ITAC], RANTES [regulated on activation normal T cell expressed and secreted], and fractalkine), and chemokine receptors (CXCR3, CCR5, and CX3CR1). In reference coronary arteries (not transplanted), almost no infiltrating cells were found, and in transplanted hearts with CAV (HTx+CAV), a large number of T cells were observed (CD4:CD8=2:1), mainly localized in the neointima and adventitia. Most of these T cells appeared to be activated (human leukocyte antigen DR positive). Coronary arteries from transplanted hearts without CAV (HTx-CAV), HTx+CAV, and references were also analyzed for cytokine and C+CR mRNA expression with the use of quantitative polymerase chain reaction. Interferon-gamma was highly expressed in HTx+CAV compared with HTx-CAV. Interleukin-4 and interleukin-10 were expressed at the same level in both HTx groups and references. In HTx+CAV, all C+CR, but especially the T-helper 1 (TH1) C+CR, were more abundant than in the HTx-CAV and references. However, TH2 CCR4 expression did not differ significantly between both HTx groups.In coronary arteries with CAV, most T cells are CD4+ and express human leukocyte antigen DR. These activated TH cells are mainly memory TH1 cells on the basis of their C+CR profile and cytokine expression.