tbuckley/cabot-search huggingface dataset:
Reply to ‘Staging for distant metastases in operable breast cancer: a suggested expansion of the ESMO guideline recommendation for staging imaging of node-negative, hormonal receptor-negative disease’ by U. Gueth et al
Authors: S. Aebi, T. Davidson, G. Gruber, F. Cardoso
Journal: Annals of Oncology (2013)

Dr Güth et al. [1.Güth U. Vetter M. Huang D.J. et al.Staging for distant metastases in operable breast cancer: A suggested expansion of the ESMO guideline recommendation for staging imaging of node negative, hormonal receptor negative disease.Ann Oncol. 2013; (in press)Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar] report an analysis of postoperative staging of patients with breast cancer in the University of Basel cohort. Their main message is that their patients with ER-negative apparent stage I breast cancer have a similar probability of distant metastases as patients with apparent stage II disease. Based on their data, it would seem logical to apply the same protocols of staging to patients with ‘high-risk stage I’ breast cancer. The rationale of adjuvant therapy is the eradication of distant metastases at a time when they are not detectable by clinical methods. In the last decade, adjuvant therapy has become more effective with the introduction of taxanes, trastuzumab, and aromatase inhibitors; this implies that a higher number of micrometastases can be eliminated by therapy. Thus, the traditional concept of ‘cM0’ in TNM terminology is open to question, and the naïve use of sophisticated staging methods changes or undermines the meaning of the term ‘adjuvant’. The threshold probability of distant metastases above which staging procedures are considered useful depends not only on the cost and convenience of screening, but also on the efficacy of current therapeutic options. The conventional staging procedures such as bone scans, chest radiographs, and abdominal ultrasound examinations have been used in most clinical trials of adjuvant therapy. They traditionally directed therapy by identifying patients with advanced disease who were not amenable to medical cure. This is not the case for other staging methods such as the detection of epithelial cells in bone marrow aspirates. In the context of current adjuvant therapies, it is conceivable that overdiagnosis of distant disease by more sensitive staging techniques including computed tomography with positron emission tomography may not prevent overtreatment of incurable disease but lead to undertreatment of potentially curable patients. The performance of most staging methods has been evaluated only in terms of diagnostic accuracy but not in terms of patient outcome. At present, the relative merits of different staging methods are subject to numerous biases as is reflected in the range of recommendations in different clinical guidelines. Clinical trials investigating the value of different staging algorithms are needed to avoid over- and undertreatment. In this context, Dr Güth's comments are well taken and will be considered in the development of a future update of the guidelines. The authors have declared no conflicts of interest.
Relapse rate of psoriasis worsened by adding steroids to a dithranol regime*
Authors: R.H. SEVILLE
Journal: British Journal of Dermatology (1976)

Journal Article Relapse rate of psoriasis worsened by adding steroids to a dithranol regime Get access R.H. SEVILLE R.H. SEVILLE Department of Dermatology, Beaumont Hospital, Lancaster Accepted for publication 29 March 1976 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue 6, 1 December 1976, Pages 643–646, https://doi.org/10.1111/j.1365-2133.1976.tb07038.x Published: 01 December 1976
Evidence based checklists for objective structured clinical examinations
Authors: Christopher Frank
Journal: BMJ (2006)

where the goal is not to be better than the others but to be better today than you were yesterday.We have described four major challenges in medical education.One conclusion from all of these is that a close collaboration between doctors and educationalists is indispensable for good medical education and development of better education.Any monodisciplinary endeavour will lead to a suboptimal result.Contributors and sources: LWTS and CPMvdV have the key responsibility for the development, implementation, and quality control of the assessment system of the medical school of the Maastricht University and are consultants
Dendritic Cell Infiltration and Prognosis of Early Stage Breast Cancer
Authors: Isabelle Treilleux, Jean-Yves Blay, Nathalie Bendriss-Vermare, Isabelle Ray-Coquard, Thomas Bachelot, Jean-Paul Guastalla, Alain Bremond, Sophie Goddard, Jean-Jacques Pin, Clarisse Barthelemy-Dubois, Serge Lebecque
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Although dendritic cells (DC) and T cells can infiltrate primary breast carcinoma, it remains unclear whether the immune response influences the clinical outcome. Experimental Design: T lymphocytes and DC infiltration within primary tumors was investigated in 152 patients with invasive nonmetastatic breast cancer. CD1a, CD3, CD68, CD123, CD207/Langerin, and CD208/DC-LAMP expression was assessed with semiquantitative immunohistochemical analysis. Expression of chemokines involved in DC migration (MIP-3a/CCL20, MIP-3b/CCL19, and 6Ckine/CCL21) was also examined. The correlation between these markers and the characteristics of the tumors, as well as relapse-free and overall survival was analyzed. Significant prognostic parameters were then tested in a validation series. Results: Infiltration by immature CD207/Langerin+ DC was found in a third of the cancers and did not correlate with clinicopathological data. Presence of mature CD208/DC-LAMP+ DC (56%) and CD3+ T cells (82%) strongly correlated with lymph node involvement and tumor grade. Among the chemokines analyzed, only the presence of MIP-3b/CCL19 in 57% of the tumors correlated with prolonged overall survival. CD123+ plasmacytoid DC (pDC) infiltrated 13% of the primary tumors. Their presence was strongly associated with shorter overall survival (93% versus 58% at 60 months) and relapse-free survival (90% versus 37% at 60 months) and was found to be an independent prognostic factor for overall survival and relapse-free survival and confirmed in an independent validation series of 103 patients. Conclusions: Infiltration by pDC of primary localized breast tumor correlates with an adverse outcome, suggesting their contribution in the progression of breast cancer.
Downregulation of mdr-1 expression by 8-Cl-cAMP in multidrug resistant MCF-7 human breast cancer cells.
Authors: S Scala, A Budillon, Z Zhan, Y S Cho-Chung, J Jefferson, M Tsokos, S E Bates
Journal: Journal of Clinical Investigation (1995)

8-Cl-cAMP, a site-selective analogue of cAMP, decreased mdr-1 expression in multidrug-resistant human breast cancer cells. A sixfold reduction of mdr-1 mRNA expression by 8-Cl-cAMP began within 8 h of treatment and was associated with a decrease in the synthesis of P-glycoprotein and with an increase in vinblastine accumulation. A reduction in mdr-1 expression after 8-Cl-cAMP treatment was also observed in multidrug-resistant human ovarian cancer cell lines. 8-Cl-cAMP is known to change the ratio between the two regulatory subunits, RI and RII, of protein kinase A (PKA). We observed that RI alpha decreased within 24 h of 8-Cl-cAMP treatment, that RII beta increased after as few as 3 h of treatment, and that PKA catalytic activity remained unchanged during 48 h of 8-Cl-cAMP treatment. The results are consistent with the hypothesis that mdr-1 expression is regulated in part by changes in PKA isoenzyme levels. Although 8-Cl-cAMP has been used to differentiate cells in other model systems, the only differentiating effect that could be detected after 8-Cl-cAMP treatment in the MCF-7TH cells was an increase in cytokeratin expression. Evidence that the reduction of mdr-1 mRNA occurred at the level of gene transcription was obtained by measuring chloramphenicol acetyltransferase (CAT) mRNA in MCF-7TH cells transfected with an mdr-1 promoter-CAT construct prior to 8-Cl-cAMP treatment. Thus, 8-Cl-cAMP is able to downregulate mdr-1 expression and suggests a new approach to reversal of drug resistance in human breast cancer.
291 RELATION WITH SMALL INTESTINAL BACTERIAL OVERGROWTH AND BACTERIAL TRANSLOCATION IN CIRRHOTIC PATIENTS
Authors: D.W. Jun, K.T. Kim, J.D. Chae, K.O. Lee, S.J. Jeong, M.H. Song, S.H. Kim, Y.J. Jo, Y.S. Park
Journal: Journal of Hepatology (2008)
Introducing the &lt;emph type="ital"&gt;JAMA&lt;/emph&gt; Clinical Challenge
Authors: Huan J. Chang
Journal: JAMA (2011)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Transcriptional regulation of early oogenesis: in search of masters
Authors: Stephanie A. Pangas, Aleksandar Rajkovic
Journal: Human Reproduction Update (2005)

Transcription factors in the germline play important roles in ovary formation and folliculogenesis, and control both oocyte development and somatic cell function. Factor in the germline (Figla) and newborn ovary homeobox gene (Nobox) represent a growing number of oocyte-specific transcription factors that regulate genes unique to oocytes. Studies on oocyte-specific transcription factors are important in understanding the genetic pathways essential for oogenesis, pluripotency, and embryonic development. Likely, these genes regulate reproductive life span and represent candidate genes for reproductive disorders, such as premature ovarian failure, and infertility. Therefore, oocyte-specific transcription factors, and oocyte-specific genes regulated by such factors, are attractive tissue-specific pharmacological targets to regulate human fertility.
Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding
Authors: Guillaume Paré, Niclas Eriksson, Thorsten Lehr, Stuart Connolly, John Eikelboom, Michael D. Ezekowitz, Tomas Axelsson, Sebastian Haertter, Jonas Oldgren, Paul Reilly, Agneta Siegbahn, Ann-Christine Syvanen, Claes Wadelius, Mia Wadelius, Heike Zimdahl-Gelling, Salim Yusuf, Lars Wallentin
Journal: Circulation (2013)

Background— Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations of the active metabolite of dabigatran etexilate and influence the safety and efficacy of dabigatran. Methods and Results— We successfully conducted a genome-wide association study in 2944 Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) participants. The CES1 single-nucleotide polymorphism rs2244613 was associated with trough concentrations, and the ABCB1 single-nucleotide polymorphism rs4148738 and the CES1 single-nucleotide polymorphism rs8192935 were associated with peak concentrations at genome-wide significance ( P &lt;9×10 −8 ) with a gene-dose effect. Each minor allele of the CES1 single-nucleotide polymorphism rs2244613 was associated with lower trough concentrations (15% decrease per allele; 95% confidence interval, 10–19; P =1.2×10 −8 ) and a lower risk of any bleeding (odds ratio, 0.67; 95% confidence interval, 0.55–0.82; P =7×10 −5 ) in dabigatran-treated participants, with a consistent but nonsignificant lower risk of major bleeding (odds ratio, 0.66; 95% confidence interval, 0.43–1.01). The interaction between treatment (warfarin versus all dabigatran) and carrier status was statistically significant ( P =0.002), with carriers having less bleeding with dabigatran than warfarin (hazard ratio, 0.59; 95% confidence interval, 0.46–0.76; P =5.2×10 − 5) in contrast to no difference in noncarriers (hazard ratio, 0.96; 95% confidence interval, 0.81–1.14; P =0.65). There was no association with ischemic events, and neither rs4148738 nor rs8192935 was associated with bleeding or ischemic events. Conclusions— Genome-wide association analysis identified that carriage of the CES1 rs2244613 minor allele occurred in 32.8% of patients in RE-LY and was associated with lower exposure to active dabigatran metabolite. The presence of the polymorphism was associated with a lower risk of bleeding. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00262600.
Treatment of refractory ascites: Is dialytic ultrafiltration better than paracentesis?
Authors: Salvatore Badalamenti, Francesco Salerno
Journal: Hepatology (1992)

We compared the clinical efficacy and safety of large-volume paracentesis and dialytic ultrafiltration in the treatment of refractory ascites in cirrhotic patients. A group of cirrhotic subjects (age 49-80 years) were randomly allocated to either continuous paracentesis (1-1.5 l/hour) or dialytic ultrafiltration until disappearance of ascites. Each patient was maintained on bed rest, fluid restriction (1 l/day) and a low (25 mmol/day) sodium diet for 14 days. Five patients (three in the paracentesis group and two in dialytic ultrafiltration group) developed massive ascites 3-5 months later, and received the crossover treatment. The average volume of fluid removed was similar in the two groups (4.70 ± 1.47 l for dialytic ultrafiltration versus 4.69 ± 1.84 l for paracentesis), but the treatment period was significantly shorter with dialytic ultrafiltration. The plasma creatinine significantly increased three days after paracentesis but did not increase in patients treated with dialytic ultrafiltration. There was an initial fall in mean arterial pressure during the first two hours of either treatment; a further fall in blood pressure was observed with paracentesis but not with dialytic ultrafiltration. Pretreatment plasma renin activity was elevated, but was not altered by either treatment. Plasma atrial natriuretic peptide levels were in the high-normal range before treatment. Paracentesis was associated with a delayed fall in plasma atrial natriuretic peptide, while dialytic ultrafiltration induced a modest but significant rise. No complication was experienced with dialytic ultrafiltration in the two weeks following treatment, but four of the eight patients who underwent paracentesis had developed severe complications. Dialytic ultrafiltration of ascitic fluid is a safe procedure in cirrhotic patients. Large-volume paracentesis without intravenous colloid reinfusion causes complications and carries the potential risk of reducing the effective intravascular volume.
Hypoxia Enhances Lysophosphatidic Acid Responsiveness in Ovarian Cancer Cells and Lysophosphatidic Acid Induces Ovarian Tumor Metastasis <i>In vivo</i>
Authors: Kwan-Sik Kim, Saubhik Sengupta, Michael Berk, Yong-Geun Kwak, Pedro F. Escobar, Jerome Belinson, Samuel C. Mok, Yan Xu
Journal: Cancer Research (2006)

Abstract Lysophosphatidic acid (LPA) is elevated in ascites of ovarian cancer patients and stimulates growth and other activities of ovarian cancer cells in vitro. Tissue hypoxia is a critical factor for tumor aggressiveness and metastasis in cancers. We tested whether the ascites of ovarian cancer is hypoxic and whether hypoxia influences the effects of LPA on ovarian cancer cells. We found that ovarian ascitic fluids were hypoxic in vivo. Enhanced cellular responsiveness to LPA, including migration and/or invasion of ovarian cancer cells, was observed under hypoxic conditions. This enhancement could be completely blocked by geldanamycin or a small interfering RNA targeting hypoxia-inducible factor 1α (HIF1α). LPA-induced cell migration required cytosolic phospholipase A2 (cPLA2) and LPA stimulates cPLA2 phosphorylation in a HIF1α-dependent manner under hypoxia conditions. Furthermore, we show for the first time that exogenous LPA enhances tumor metastasis in an orthotopic ovarian cancer model and HIFα expression in tumors. 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (an inhibitor of the heat shock protein 90) effectively blocked LPA-induced tumor metastasis in vivo. Together, our data indicate that hypoxic conditions are likely to be pathologically important for ovarian cancer development. HIF1α plays a critical role in enhancing and/or sensitizing the role of LPA on cell migration and invasion under hypoxic conditions, where cPLA2 is required for LPA-induced cell migration. (Cancer Res 2006; 66(16): 7983-90)
Videomicroscopy of methacholine-induced contraction of individual airways in precision-cut lung slices
Authors: C Martin, S Uhlig, V Ullrich
Journal: European Respiratory Journal (1996)

Contraction of airways of different size can be studied in viable lung slices by videomicroscopy. However, at present, application of this technique is limited by the heterogeneous responses obtained. We investigated the use of precision-cut lung slices to examine contraction of individual airways. Lung slices of 250 +/- 20 microns were prepared from Wistar rats and cultured in a roller incubator in serum-free minimum essential medium (MEM). Under these conditions, the slices were viable for at least 70 h, as indicated by leakage of lactate dehydrogenase into the supernatant, thymidine incorporation and ciliary beating. The slices were placed in a newly developed incubation chamber and mounted by a nylon thread that was fixed to a platinum wire. The whole chamber was positioned on a microscope stage, and contraction of single airways was followed under a microscope that was coupled to a CCD-camera. Reduction in airway area was taken as an index of bronchoconstriction and was determined by a computer program. Addition of methacholine resulted in a concentration-dependent (concentration producing half the maximal effect (EC50) = 0.64 +/- 0.08 (mean +/- SD) microM; n = 64) contraction of single airways. In the presence of hydrocortisone, the EC50 was about six times greater, i.e. 3.7 +/- 0.9 microM (n = 7), and the effect of the steroid was largely abolished by propanolol (EC50 = 1.1 +/- 0.1 microM; n = 7). Airways with an area smaller than 35,000 microns2 were nearly nine times more sensitive to methacholine (EC50 = 0.1 +/- 0.03 microM; n = 20) than larger ones (EC50 = 87 +/- 0.27 microM; n = 22). We conclude that cultured precision-cut lung slices are a useful model for routine study of contraction of individual airways of various sizes. The measurements were precise and reproducible and showed that smaller airways are more sensitive to methacholine than larger ones.
A retrospective study of 150 patients with lentigo maligna and lentigo maligna melanoma and the efficacy of radiotherapy using Grenz or soft X-rays
Authors: A. Farshad, G. Burg, R. Panizzon, R. Dummer
Journal: British Journal of Dermatology (2002)

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are the most common melanocytic neoplasms on sun-exposed skin of elderly patients.To perform a retrospective study of 150 patients with LM and LMM treated with radiotherapy using Grenz or soft X-rays.The information recorded and analysed included gender, age, diagnosis, size of the lesion, localization, X-ray treatment, recurrence rate, other skin malignancies and non-dermatological neoplasms.The 150 patients comprised 78 women and 72 men (mean age 70 years). Ninety-three patients had LM, 54 had LMM and three had both neoplasms. Ninety per cent of lesions were located on the face. Treatment was with Grenz rays in 96 patients with LM and 11 with LMM (70%) and with soft X-rays in 46 patients with LMM (30%). Three patients were treated using both modalities. One hundred and one patients were followed up for at least 2 years after radiotherapy (mean 8 years). The mean time to recurrence was 45.6 months, and the recurrence rate was 7% (seven of 101). Other skin malignancies were observed in 65 of 150 patients, including basal cell carcinoma in 23 (35%) and actinic keratosis in 20 (31%). Four patients developed internal cancers.The study showed that radiotherapy of LM and LMM was curative. In particular, radiotherapy proved to be an excellent treatment for elderly patients. Owing to the high incidence of other skin cancers, LM patients need careful follow-up.
Levels of insulin related growth factor 1 in osteoarthritis of the knee.
Authors: T E McAlindon, J D Teale, P A Dieppe
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES: Insulin related growth factor 1 (IGF1) is an important growth promoting peptide which has anabolic effects on in vitro cartilage metabolism. The fact that serum levels tend to decrease in elderly subjects while osteoarthritis (OA) increases in prevalence suggests that suboptimal levels may play a part in the development of OA. This study therefore considers the hypothesis that IGF1 levels are low in subjects with OA of the knee. METHODS: Serum IGF1 levels in a community derived sample with symptomatic knee OA were compared with those in normal controls matched by age and gender. Overall radiographic score, osteophyte score, sclerosis score, and joint space narrowing score were correlated with IFG1 levels. RESULTS: One hundred and seventy-seven elderly subjects (83 with knee pain, 94 without knee pain) participated, allowing the identification of 78 case-control pairs matched by age and gender (mean 71.8 v 71.9 years, SD 7.6 for the two groups). No difference was found in serum IGF1 levels between the cases and controls (mean(SD) 15.9(4.7) nmol/l, for cases, 16.4(5.4) for controls). Significant negative correlations were found between IGF1 levels and age, total radiographic score, osteophyte score, and sclerosis score. In a multiple regression model, however, only age remained significant. CONCLUSIONS: This study provides no evidence that serum IGF1 levels are low in OA. Apparent correlations with radiographic features of OA may be due to the confounding effects of age.