tbuckley/cabot-search huggingface dataset:
Ifosfamide, Fanconi's syndrome, and rickets.
Authors: C B Pratt, W H Meyer, J J Jenkins, L Avery, C P McKay, R J Wyatt, M L Hancock
Journal: Journal of Clinical Oncology (1991)

Three of 218 children treated with ifosfamide plus the uroprotectant mesna, in single- or combination-agent protocols, have developed Fanconi's renal syndrome, all of whom were in a subgroup of 86 children who had also received cisplatin or carboplatin therapy. Patients receiving ifosfamide who have received prior cisplatin (or carboplatin) are at significantly higher risk of developing Fanconi's syndrome than are those who have received no prior nephrotoxic therapy (P = .04). The role of prior nephrotoxic therapy, including cisplatin and its derivatives, and the total dose of ifosfamide should be considered in the assessment of this rare but serious and apparently irreversible side effect.
Efficacy of dasatinib in chronic phase chronic myelogenous leukemia patients after imatinib failure according to baseline BCR- ABL mutations
Authors: A. Hochhaus, S. Branford, J. Radich, M. C. Mueller, N. Shah, P. Erben, T. Ernst, M. Acevedo, C. Nicaise, T. Hughes
Journal: Journal of Clinical Oncology (2007)

7023 Background: Dasatinib is an oral, multi-targeted BCR-ABL and SRC kinase inhibitor with preclinical activity against 20/21 imatinib (Im) resistant BCR-ABL mutations. Clinical efficacy was demonstrated in phase I, II, and III studies in patients (pts) with chronic myelogenous leukemia (CML) in all phases of the disease and BCR-ABL positive acute lymphoblastic leukemia (ALL). We sought to establish a relationship between type of BCR-ABL mutations associated with Im resistance and efficacy of dasatinib in chronic phase (CP) CML pts. Methods: Between 10/03 and 03/06, dasatinib was commenced in 1,093 CP-CML pts recruited for three consecutive trials and administered for a median of 8.7 months (range &lt;1–25.9). BCR-ABL mRNA was screened for mutations of amino acids 207–517 by D-HPLC and/or regular sequencing and data are available from 961 cases (88%). ABL polymorphisms K247R and E499E were excluded from analysis. Results: Prior to dasatinib, 75 different BCR-ABL mutations involving 56 amino acids were detected in 18/240 Im intolerant (7.5%) and 324/721 (45%) Im resistant pts. 267 pts showed one, 53 pts two, 16 pts three, and six pts four mutations. In Im resistant pts, response was not different between 370 pts with and 351 pts without baseline mutations: Complete hematologic response (CHR) was achieved in 89% vs 92%; major cytogenetic response (MCR) in 48% vs 52% being complete (CCR) in 38 vs 36%, respectively. Response dynamics were associated with preclinical activity of dasatinib: classifying mutations for IC 50 values &lt;2, 2–20 and &gt;1,000nM (T315I), CHR was achieved in 93, 85 and 28%; MCR in 48, 42 and 0%; and CCR in 37, 35 and 0% of cases, respectively. During follow up, new mutations were detected in 30 cases, predominantly T315I (n=10), Y253H/F (n=4), and F317L (n=3). Conclusions: We conclude that dasatinib is capable of inducing hematologic and cytogenetic remissions in a significant proportion of Im resistant pts associated with BCR-ABL mutations, except T315I, but also in pts with BCR-ABL independent causes of resistance. Quality of response depends on the individual type of the mutation which is consistent with preclinical observations. No significant financial relationships to disclose.
Vinorelbine: a horse of a different color?
Authors: H M Pinedo, C J Van Groeningen
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.9.1745 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8083696 Vinorelbine: a horse of a different color? H M PinedoxH M PinedoSearch for articles by this author , C J Van GroeningenxC J Van GroeningenSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.9.1745 First Page PDF © 1994 by American Society of Clinical Oncology
Two cases of primary hyperparathyroidism associated with primary cutaneous lymphoma
Authors: C.M. Owen, R.W. Blewitt, P.V. Harrison, V.M. Yates
Journal: British Journal of Dermatology (2000)

Journal Article Two cases of primary hyperparathyroidism associated with primary cutaneous lymphoma Get access C.M. Owen, C.M. Owen Departments of Dermatology and C.M.Owen. E‐mail: carolineo@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar R.W. Blewitt, R.W. Blewitt Pathology, Royal Lancaster Infirmary, Lancaster LA1 4RP, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.V. Harrison, P.V. Harrison Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar V.M. Yates V.M. Yates Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 1, 1 January 2000, Pages 120–123, https://doi.org/10.1046/j.1365-2133.2000.03252.x Published: 01 January 2000
The importance of patient confidentiality
Authors: Lucy Mansfield
Journal: BMJ (2001)

As a third year medical student just starting out in clinical medicine, the importance of patient confidentiality has often been emphasised to me. Unfortunately, until now, it is something that I have not considered in detail. I am probably guilty of the odd Friday night pub conversation: “You won't believe what I saw today.” I am sure many of my fellow colleagues would be guilty of the …
Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients: A retrospective case‐matched study
Authors: Fortunato Morabito, Sara Bringhen, Alessandra Larocca, Pierre Wijermans, Maria Victoria Mateos, Peter Gimsing, Carla Mazzone, Daniela Gottardi, Paola Omedè, Sonja Zweegman, Juan José Lahuerta, Renato Zambello, Pellegrino Musto, Valeria Magarotto, Martijn Schaafsma, Albert Oriol, Gunnar Juliusson, Chiara Cerrato, Lucio Catalano, Massimo Gentile, Ana Isabel Turel, Anna Marina Liberati, Maide Cavalli, Davide Rossi, Roberto Passera, Stefano Rosso, Meral Beksac, Michele Cavo, Anders Waage, Jesus San Miguel, Mario Boccadoro, Pieter Sonneveld, Antonio Palumbo, Massimo Offidani
Journal: American Journal of Hematology (2013)

Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six elderly (>65 years) newly diagnosed MM patients from six European randomized trials were retrospectively analyzed and matched for age, albumin, and beta2-microglobulin at diagnosis, 296 patients were selected from the VMP groups, and 294 from MPT. Complete response rate was 21% in the VMP patients and 13% in the MPT patients (P = 0.007). After a median follow-up of 34 months (range, 1-92), VMP significantly prolonged both PFS (median 32.5 vs. 22.9 months, HR 0.65; 95% CI 0.52-0.82; P < 0.001) and OS (median 79.7 vs. 45.1 months, HR 0.44; 95% CI 0.32-0.59; P < 0.001) in comparison with MPT. The benefit in terms of OS of the VMP group was quite similar among patients with different risk factors defined by sex, ISS, ECOG performance status, or serum creatinine but not among patients ≥ 75 years. Multivariate analysis confirmed that VMP was an independent predictor of longer PFS and OS. In a control-case matched analysis, PFS and OS were prolonged in patients who received VMP in comparison with those treated with MPT.
Abstract 1113: Induction of Premature Senescence in Cardiomyocytes by Oxidative Stress as a Novel Mechanism of Myocardial Dysfunction
Authors: Yasuhiro Maejima, Susumu Adachi, Hiroshi Ito, Mitsuaki Isobe
Journal: Circulation (2006)

Objectives- Cellular senescence is an important phenomenon in decreased cellular function. Recently, it was shown that cellular senescence is induced in proliferating cells within a short period of...
<i>BRAF</i> and <i>KRAS</i> mutations in liver-resected metastatic colorectal cancer (mCRC) patients (pts).
Authors: Francesca Bergamo, Marta Schirripa, Fotios Loupakis, Chiara Cremolini, Mariaelena Casagrande, Sara Lonardi, Giuseppe Aprile, Federica Marmorino, Lisa Salvatore, Carlotta Antoniotti, Elisa Sensi, Cristiana Lupi, Giovanna De Maglio, Roberta Bertorelle, Antonella Galiano, Gaia Griguolo, Mariangela Balistreri, Gabriella Fontanini, Vittorina Zagonel, Alfredo Falcone
Journal: Journal of Clinical Oncology (2014)

476 Background: Up today there are no molecular markers to identify mCRC pts candidate to curative liver surgery at high risk of relapse. There are conflicting results about the prognostic role of KRAS mutation in mCRC pts, while BRAF mutation is a well-known negative prognostic factor characterizing a subgroup of mCRCs with a distinct metastatic spread. We analyzed the impact of BRAF and KRAS mutations on relapse free-survival (RFS) and overall survival (OS) in pts undergoing liver resection with curative intent. Methods: Medical records of pts referred to 3 Italian institutions between 1995 and 2012 were reviewed. 3024 mCRC pts were identified. 401 pts (13.3%) underwent liver resection with curative intent and had adequate follow-up. Mutational status was assessable on 360 samples from primary tumors (n=63), metastases (mts) (n=59) or both (n=238). Primary objective was to evaluate the impact of BRAF mutation on RFS in mCRC pts candidate to liver resection. Secondary objectives were to evaluate the prognostic role of BRAF status on OS, and of KRAS status on RFS and OS in this population. Results: BRAF and KRAS were mutated in 11 (3%) and 116 (32%) out of 360 cases respectively. In 238 cases in which paired samples from primary and metastases were available, no discordance was found in BRAF status while 18 cases (7.6%) showed a discrepancy in KRAS status and were thus excluded from analysis. Pts with BRAF mutation had significantly shorter median RFS compared to pts with BRAF wt tumor (5.7 mos vs 11.7 mos, HR=4.25; 95%CI: 1.52-11.88, p=0.005). OS was significantly reduced in pts with BRAF mutated tumors vs wt (HR=5.39; 95%CI: 1.59-18.27, p=0.007). Mutated KRAS was not prognostic for RFS (HR=1.14; 95%CI: 0.87-1.49, p=0.34), while demonstrated a weak prognostic impact on OS (HR=1.52; 95%CI: 1.05-2.21, p=0.03). In this cohort high-risk Fong score were significantly associated with shorter RFS (p&lt;0.0001) and OS (p&lt;0.0001). Conclusions: BRAF mutation is associated with higher probability of relapse and worse outcome in liver resected mCRC. KRAS mutation was not associated with RFS after liver resection. BRAF mutational status may become a new prognostic marker when planning liver resection in mCRC pts.
Value of pulse oximetry in screening for long-term oxygen therapy requirement
Authors: CM Roberts, None Bugler, R Melchor, MR Hetzel, SG Spiro
Journal: European Respiratory Journal (1993)

Pulse oximetry, combined with spirometry, was evaluated as a method of selecting chronic obstructive pulmonary disease (COPD) out-patients requiring definitive arterial blood gas analysis for long-term oxygen therapy (LTOT) assessment. A relatively high screening arterial oxygen saturation by pulse oximetry (SaO2) level was set, in order to maximize sensitivity. All 113 COPD out-patients attending the hospital clinic over a 6 month period were screened. Sixty had a forced expiratory volume in one second < 1.5 l and 26 had an SaO2 < or = 92%. These 26 underwent arterial blood gas analysis. Nine had an arterial oxygen tension < 7.3 kPa all with an arterial carbon dioxide tension (PaCO2) > 6 kPa. A further eight had a PaO2 < 8 kPa. This produced a sensitivity of 100% and specificity of 69% for oximetry in the detection of PaO2 < 7.3 kPa determined by direct arterial puncture and 100% and 86% respectively for detecting a PaO2 < 8 kPa. Although the poor specificity of oximetry in the crucial PaO2 range makes it unsuitable, when used alone, for prescription of LTOT, it may prove valuable in selecting patients who require further definitive arterial blood gas analysis.
Clinical Management of Urticaria and Anaphylaxis
Journal: Thorax (1993)

Chronic urticaria is to the allergist what dizziness is to the neurologist-a complaint which frequently leads to frustration on the part of both the doctor and patient.Anaphylaxis is the nightmare of every doctor.The stated aim of this volume, which is one of a series on allergic disease in therapy under series editor David G Tinkelman, is to provide a practical guide to the investigation and treatment of these difficult conditions.In fact it is a series of detailed chapters covering various aspects, mostly lucidly written and intensively referenced.
Increased Production of Interleukin‐17 Over Interleukin‐10 by Treg Cells Implicates Inducible Costimulator Molecule in Experimental Spondyloarthritis
Authors: Luiza M. Araujo, Ingrid Fert, Quentin Jouhault, Karine Labroquère, Muriel Andrieu, Gilles Chiocchia, Maxime Breban
Journal: Arthritis & Rheumatology (2014)

Objective HLA–B27/human β 2 ‐microglobulin (hβ 2 m)–transgenic (B27‐transgenic) rats develop an inflammatory disorder resembling spondyloarthritis, with accumulation of proinflammatory Th17 cells. Because Treg cells and Th17 cells have opposing effects in inflammatory disorders, we sought to determine whether biased expansion of Th17 cells could result from altered Treg cell frequency and/or function in B27‐transgenic rats. Methods We characterized the phenotype and function of Treg cells from B27‐transgenic rats in comparison with those from control rats, by examining their expression of cell surface markers, suppressive activity, cytokine production, and differentiation pattern. Results In B27‐transgenic rats, the preferential accumulation of CD4+ Teff cells over Treg cells was not associated with a defect in Treg cell differentiation or suppressive activity. The expression of Treg cell markers was similar between B27‐transgenic and control rats, with the exception of the inducible costimulator (ICOS) molecule, which was overexpressed in B27‐transgenic rats. High levels of ICOS are considered to be a hallmark of Treg cells with heightened suppressive activity and interleukin‐10 (IL‐10) expression. Paradoxically, the production of IL‐10 by Treg cells was reduced in B27‐transgenic rats, whereas the production of IL‐17 was enhanced. Moreover, the addition of anti‐ICOS monoclonal antibodies during Treg cell differentiation in the presence of dendritic cells from B27‐transgenic rats reversed this cytokine profile, restoring the balance between IL‐10 and IL‐17 in Treg cells from B27‐transgenic rats. Conclusion We observed dysregulated production of IL‐10 and IL‐17 by Treg cells from B27‐transgenic rats, which may contribute to disease development. Moreover, our data highlight a key role for ICOS signaling in the generation of imbalanced production of IL‐10 and IL‐17 by Treg cells in this experimental model of spondyloarthritis.
Diabetes Drug Poses Bone Risks
Authors: Rebecca Voelker
Journal: JAMA (2015)

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
Wi-fi is essential for medical education and helps clinicians provide safe and effective patient care
Authors: Scott W Oliver, Kathleen Collins
Journal: BMJ (2015)

Potassium channels activated by intracellular Na<sup>+</sup> ions (<i>K</i><sub>Na</sub>) play several distinct roles in regulating the firing patterns of neurons, and, at the single channel level, their properties are quite diverse. Two known genes, <i>Slick</i> and <i>Slack</i>, encode <i>K</i><sub>Na</sub> channels. We have now found that Slick and Slack subunits coassemble to form heteromeric channels that differ from the homomers in their unitary conductance, kinetic behavior, subcellular localization, and response to activation of protein kinase C. Heteromer formation requires the N-terminal domain of Slack-B, one of the alternative splice variants of the Slack channel. This cytoplasmic N-terminal domain of Slack-B also facilitates the localization of heteromeric <i>K</i><sub>Na</sub> channels to the plasma membrane. Immunocytochemical studies indicate that Slick and Slack-B subunits are coexpressed in many central neurons. Our findings provide a molecular explanation for some of the diversity in reported properties of neuronal <i>K</i><sub>Na</sub> channels.
The efficacy of cytology sampling in the diagnosis of suspected endobronchial lung cancer
Authors: Farhana Shora, Gulam Haji, Haider Ali, Frances Bowen
Journal: European Respiratory Journal (2011)

Introduction:  Fibreoptic bronchoscopy (FOB) is a minimally invasive procedure that is regularly performed on an outpatient basis to aid diagnosis in suspected cases of lung cancer.   Objective:  To review the usefulness of FOB obtained washings and brushings in the presence of an endobronchial lesion in the diagnosis of lung cancer.   Method:  Retrospective analysis of 23 suspected lung cancer cases undergoing FOB (by supervised trainees). 16 cases with a visible endobronchial lesion underwent histological and cytological sampling; the remaining 7 had cytological sampling alone.   Results:  15 (94%) cases with a visible endobronchial lesion were proven to have a cancer. 7 (47%) cases had positive histology and cytology. 5 (33%) cases had positive histology alone. 3 (20%) cases had positive cytology but negative histology in the context of an endobronchial lesion. All 7 patients without an endobronchial lesion had negative cytology and were subsequently found not to have cancer. Only 1 patient with an endobronchial lesion had both negative histology and cytology, and was proven not to have cancer.   Conclusion:  From this retrospective analysis we conclude that 20% of lung cancers would have been missed had cytological samples not been taken in addition to endobronchial biopsies. Therefore we suggest that any patient with an endobronchial lesion should have brushings and washings accompanying a biopsy. We cannot deduce from our small study whether, in the absence of a visible endobronchial lesion, brushings and washings are diagnostically valuable.
Herbimycin A, an inhibitor of tyrosine kinase, prolongs survival of mice inoculated with myeloid leukemia C1 cells with high expression of v-abl tyrosine kinase.
Authors: Yoshio Honma, Junko Okabe-Kado, Takashi Kasukabe, Motoo Hozumi, Hiroaki Kodama, Sachiko Kajigaya, Toshio Suda, Yoshisada Miura
Journal: Cancer Research (1992)

Herbimycin A, a benzoquinonoid ansamycin antibiotic, reduces intracellular phosphorylation by some tyrosine kinases, including v-abl. The mouse megakaryoblastic cell line C1 expresses v-abl protein at high levels. Herbimycin A at about 20 ng/ml caused 50% inhibition of growth of C1 cells but at 100 ng/ml scarcely affected the growth of another mouse leukemia cell line, M1 cells, or of normal bone marrow cells. Injection of 10(6) C1 cells into nude mice resulted in death of all the mice within 30 days. Administration of herbimycin A significantly enhanced the survival of mice inoculated with C1 cells but scarcely affected the survival of mice inoculated with M1 cells. These results suggest that herbimycin A and/or related compounds may be useful for treatment of some types of leukemia in which tyrosine kinase activity is implicated as a determinant of the oncogenic state.
Smoking and Airway Hyperresponsiveness Especially in the Presence of Blood Eosinophilia Increase the Risk to Develop Respiratory Symptoms
Authors: DÉSIRÉE F. JANSEN, JAN P. SCHOUTEN, JUDITH M. VONK, BERT RIJCKEN, WIM TIMENS, JAN KRAAN, SCOTT T. WEISS, DIRKJE S. POSTMA
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Airway hyperresponsiveness (AHR) constitutes a risk for development of respiratory symptoms. We assessed whether blood eosinophilia ( ⩾ 275 eosinophils/ μ l), skin test positivity (sum score ⩾ 3) and cigarette smoking (never, ex-smoker, 1–14 cig/d, 15–24 cig/d, ⩾ 25 cig/d) at the first of two successive surveys are related to the development of respiratory symptoms (chronic cough or phlegm, bronchitis, persistent wheeze, dyspnea, and asthma) at the second survey, and whether these relations are the same in subjects with (PC10 ⩽ 8 mg/ml histamine) and without AHR. We analyzed data of the longitudinal Vlagtwedde-Vlaardingen Study (1965 to 1990) using logistic regression analyses with paired observations, taking multiple measurements within a person into account. In total, 995 men and 792 women contributed 4,403 paired observations. Eosinophilia in hyperresponsive subjects significantly increased the risk to develop one or more respiratory symptoms (odds ratio [OR] = 3.67, 95% confidence interval [CI] = 1.79 to 7.52), wheeze (OR = 5.06, 95% CI = 2.11 to 12.13), and dyspnea (OR = 2.73, 95% CI = 1.13 to 6.60), independent of smoking, age, sex, area of residence, and time between two successive surveys. Smoking at the first of two successive surveys increased the risk to develop symptoms in a dose-dependent relation. Subjects with positive skin tests in the past were less likely to develop one or more respiratory symptoms (OR = 0.64, 95% CI = 0.46 to 0.88) and chronic phlegm (OR = 0.65, 95% CI = 0.42 to 1.00), independent of AHR. This longitudinal study in the general adult population shows that cigarette smoking and hyperresponsive subjects are at increased risk to develop respiratory symptoms, and especially so when eosinophilia is present in hyperresponsive persons.
Fibroblast Growth Factor-23 and Death, Heart Failure, and Cardiovascular Events in Community-Living Individuals
Authors: Joachim H. Ix, Ronit Katz, Bryan R. Kestenbaum, Ian H. de Boer, Michel Chonchol, Kenneth J. Mukamal, Dena Rifkin, David S. Siscovick, Mark J. Sarnak, Michael G. Shlipak
Journal: Journal of the American College of Cardiology (2012)