tbuckley/cabot-search huggingface dataset:
Phase II Evaluation of Docetaxel-Modulated Capecitabine in Previously Treated Patients with Non–Small Cell Lung Cancer
Authors: Tamila Kindwall-Keller, Gregory A. Otterson, Donn Young, Anterpreet Neki, Tamara Criswell, Gerard Nuovo, Richie Soong, Robert Diasio, Miguel A. Villalona-Calero
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Based on the preclinical observation of upregulation of thymidine phosphorylase, the last enzymatic step in the conversion of capecitabine to 5-fluorouracil, by docetaxel along with good clinical tolerability of the combination of docetaxel and capecitabine using an optimized schedule in a previous phase I trial, we conducted this phase II study of this combination in patients with refractory or relapsed non–small cell lung cancer (NSCLC). Patients and Methods: Patients with NSCLC previously treated with at least one platinum- or paclitaxel-based regimen received docetaxel 36 mg/m2 on days 1, 8, and 15 and capecitabine 625 mg/m2 twice daily on days 5 to 18, every 4 weeks. The primary objective of the study was evaluation of progression-free survival (PFS) 26 weeks from initiation of treatment. Results: Thirty-six evaluable patients received 104 cycles of the combination. Severe toxicities were infrequent with only one patient requiring toxicity-related hospitalization. The 26-week PFS rate was 25% (95% confidence interval, 12-42) with an intent to treat median survival and 1-year survival rate of 9.1 months and 37%, respectively. Among 31 patients with measurable disease (Response Evaluation Criteria in Solid Tumors criteria), eight (26%; 95% confidence interval, 12-45) achieved partial responses. Conclusion: The combination of capecitabine and weekly docetaxel is well tolerated in previously treated patients with NSCLC. The relatively high 26-week PFS and 1-year survival, as well as the high response rate observed, encourages further evaluation of this regimen in NSCLC, either in randomized trials for refractory patients or as a potential treatment option for chemotherapy naive patients.
480 FAVOURABLE IL28B GENOTYPES AND LIVER FIBROSIS IN HIV/HEPATITIS C (HCV) CO-INFECTED INDIVIDUALS FROM THE CANADIAN CO-INFECTION COHORT
Authors: N. Moqueet, C. Lisle, R. Carter, R. Platt, M. Hull, C. Cooper, S. Walmsley, M. Potter, M.B. Klein
Journal: Journal of Hepatology (2013)
Increased Prevalence of Abnormalities in Glucocorticoid Pharmacokinetics Among Clinically Steroid Resistant Obese Asthmatics
Authors: E. Goleva, R. Covar, E.R. Sutherland, R.J. Martin, S.J. Szefler, D.Y. Leung
Journal: Journal of Allergy and Clinical Immunology (2009)
BRAIN ABSCESS WITH UNUSUAL FEATURES: REPORT OF TWO CASES
Authors: E. G. Collins
Journal: BMJ (1930)

TYPES OF ACUTE MASTOID INFECTION, EHC JRomRA develop septicaemia, and the muortality is probably 10 per cent.Tlhe inifectioni is these cases does not, however, seem prone to invade the respiratory tr act..The diagiiosis is based on the coexistence of an acute sore throat, the high temperature, rapid pulse, furred tongule, pirofuse bloody discharge, and widespread mastoid tenderness.Early operationi is indicated with provision of the freest possible drainage.Scarlatinal antitoxin some- tinmes seems to be helpfuil in septicaemic cases.Mastoudtis in I/laints with En teritis.It has been p)ointed out recenitly that miany inifanits dyinig of an acuite gastiro-elnteritis show, at niecropsy, the piesence of ani acute otitis miedia and mastoiditis.It has been-.suggested that this latter inifection is the primary one, and that the gastro-enteritis is a seconidary result of the acute toxaemia of the middle-ear infection.I am not prel)ared to offer any opinioni on this, hut wouild only emlphasize the importan-ce of examininlg the ears of inlfants suffering from aniy acute febrile inifectioni.Parotid MHastoiditis.Cases are occasionally miiet with ini whlich ani inflammatory swelling occurs in froont of oir above the ear as a result of mastoiditis.Suchi swellinig is often associated wL ithi some oedema of the eyelids on the same side, and erri ors in diagnosis are commoni.The explanationi of suchl cases is that the infection reaches the surface through cells at the root of the zygonma.If this possibility is recogniized the diag,nosis cani be established by the signs or lhistory of the nmiddle-ear (lisease, togethtl witlr the pireseiic of some teniderness over the mastoid process.Bezold's Mastoiditis.This is a similar type, in which, however, the swelling occIIrs in the neck, the explaniationi being that tlhe supp)uration buirsts through a cell at the apex of the mastoid -process and on the deep side of the sterlno-mastoid inser- tioni.The remalrks just made as to diagnosis apply hlere also.
Adjuvant chemo-hormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive cancer patients. Update at 7-year follow-up
Authors: P. Hupperets, J. Wils, L. Volovics, L. Schouten, M. Fickers, H. Bron, H. Schouten, J. Jager, J. de Jong, L. Beex, H. Hillen, G. Blijham
Journal: Annals of Oncology (1995)
Multimedia presentation of lung sounds as a learning aid for medical students
Authors: P Sestini, E Renzoni, M Rossi, V Beltrami, M Vagliasindi
Journal: European Respiratory Journal (1995)

New educational technologies might help to compensate for the decrease in time and emphasis dedicated to physical examination in medical training. This may, in particular, be applicable for improving the skills in auscultation of the chest. We investigated whether a multimedia presentation of acoustic and graphic characteristics of lung sounds could improve the learning of pulmonary auscultation by medical students, in comparison with conventional teaching methods. We studied 48 medical students without clinical experience, who had received conventional formal teaching on chest examination. Chest auscultation skills were evaluated using an inaccuracy score for the student's auscultation report on three patients, selected according to a standardized procedure. After a baseline evaluation, 27 students in groups of 5-10, participated in a multimedia seminar on lung sounds during which digitized lung sounds were played and the corresponding time-expanded waveform and frequency spectrum were commented on and displayed on a computer. The remaining 21 students received conventional bedside training, acting as control group. The following week, all the students underwent a second evaluation of chest auscultation skills. No differences in the inaccuracy score were observed between the two groups in the preliminary test. However, in the second postintervention assessment, the inaccuracy score of the students who had followed the seminar (11.2 +/- 1.3 points) was significantly lower than that of the controls (16.6 +/- 1.6 points). The answers to a feedback questionnaire confirmed that the great majority of the students found the association of the acoustic signals with their visual image to be useful for learning and understanding lung sounds.(ABSTRACT TRUNCATED AT 250 WORDS)
History of Foot Ulcer Increases Mortality Among Individuals With Diabetes
Authors: Marjolein M. Iversen, Grethe S. Tell, Trond Riise, Berit R. Hanestad, Truls Østbye, Marit Graue, Kristian Midthjell
Journal: Diabetes Care (2009)

To compare mortality rates for individuals with diabetes with and without a history of foot ulcer (HFU) and with that for the nondiabetic population.This population-based study included 155 diabetic individuals with an HFU, 1,339 diabetic individuals without an HFU, and 63,632 nondiabetic individuals who were all followed for 10 years with mortality as the end point.During the follow-up period, a total of 49.0% of diabetic individuals with an HFU died, compared with 35.2% of diabetic individuals without an HFU and 10.5% of those without diabetes. In Cox regression analyses adjusted for age, sex, education, current smoking, and waist circumference, having an HFU was associated with more than a twofold (2.29 [95% CI 1.82-2.88]) hazard risk for mortality compared with that of the nondiabetic group. In corresponding analyses comparing diabetic individuals with and without an HFU, an HFU was associated with 47% increased mortality (1.47 [1.14-1.89]). Significant covariates were older age, male sex, and current smoking. After inclusion of A1C, insulin use, microalbuminuria, cardiovascular disease, and depression scores in the model, each was significantly related to life expectancy.AN HFU increased mortality risk among community-dwelling adults and elderly individuals with diabetes. The excess risk persisted after adjustment for comorbidity and depression scores, indicating that close clinical monitoring might be warranted among individuals with an HFU, who may be particularly vulnerable to adverse outcomes.
Recommendations Regarding Computed Tomography Imaging in Follow-Up for Stage I Nonseminoma Testicular Cancer Remain a Challenge
Authors: Carsten Rusner, Andreas Stang, Klaus-Peter Dieckmann
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: Internationally, there is ongoing concern about the risk of second cancers that are induced by unwarranted radiation exposure from diagnostic imaging. However, Daugaard et al recently stated that “. . . no studies have been able to demonstrate an increased radiation-induced cancer risk caused by CT [computed tomography] scans.” We disagree with this statement. Because of the presumed long latency between radiation-induced carcinogenesis and detection of cancers, this demonstration requires long-term (eg, 20 to 30 years) follow-up studies on patients with testicular cancer who are currently not available. Such long-term studies would have to measure the performed CT scans in relation to newly occurring cancers during follow-up. As Altman and Bland illustrated in 1995, “absence of evidence is not evidence of absence.” That is, the lack of evidence of increased cancer risk after CT imaging does not allow us to conclude that there is evidence of no increased cancer risk after CT. Clinicians caring for patients with testicular cancer should always consider the possible carcinogenic effect of any irradiation. On the basis of a retrospective cohort study of patients with newly diagnosed stage I nonseminoma germ cell cancer, Daugaard et al suggested that five CT scans should be performed, at 4, 8, 12, 36, and 60 months after diagnosis. Yet notably, in the later period of follow-up (eg, after 2 years), they detected relapses much more frequently by CT rather than by tumor markers or clinical symptoms. Apparently, CT becomes progressively more valuable with longer follow-up. Abandoning CT imaging in the later period of follow-up would thus seriously decrease diagnostic capabilities, and detection of relapses might be critically delayed. Notably, in the study by Daugaard et al, less than 50% of the relapsing patients had elevations in beta human chorionic gonadotropin and -fetoprotein tumor markers. This observation compares well with the experience of many series, in which expression of markers has been found in roughly 60% of patients with nonseminoma germ cell cancer. Thus, in the follow-up of marker-negative patients, CT is obviously paramount. The chance of overlooking relapses by reducing CT scans has to be weighed against the risk of second cancer that might result from diagnostic imaging. Surveillance strategies need to be tailored to the particular features of the individual patient.
Inflammatory lipid mediator generation elicited by viable hemolysin-forming Escherichia coli in lung vasculature.
Authors: F Grimminger, M Thomas, R Obernitz, D Walmrath, S Bhakdi, W Seeger
Journal: The Journal of Experimental Medicine (1990)

Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor for E. coli-related extraintestinal infections and sepsis. The possible significance of hemolysin liberation for induction of inflammatory lipid mediators was investigated in isolated rabbit lungs infused with viable bacteria (concentration range, 10(4)-10(7)/ml). Hemolysin-secreting E. coli (E. coli-Hly+), but not an E. coli strain that releases an inactive form of the exotoxin, induced marked lung leukotriene (LT) generation with predominance of cysteinyl LTs. Eicosanoid synthesis was not inhibited in the presence of plasma with toxin-neutralizing capacity. Pre-application of 2 x 10(8) human granulocytes, which sequestered in the lung microvasculature, caused a severalfold increase in leukotriene generation in response to E. coli-Hly+ challenge both in the absence and presence of plasma. Data are presented indicating neutrophil-endothelial cell cooperation in arachidonic acid lipoxygenase metabolism as an underlying mechanism. We conclude that liberation of hemolysin from viable E. coli induces marked lipid mediator generation in lung vasculature, which is potentiated in the presence of neutrophil sequestration and may contribute to microcirculatory disturbances during the course of severe infections.
Stress-Response Protein RBM3 Attenuates the Stem-like Properties of Prostate Cancer Cells by Interfering with CD44 Variant Splicing
Authors: Yu Zeng, Dana Wodzenski, Dong Gao, Takumi Shiraishi, Naoki Terada, Youqiang Li, Donald J. Vander Griend, Jun Luo, Chuize Kong, Robert H. Getzenberg, Prakash Kulkarni
Journal: Cancer Research (2013)

Abstract Stress-response pathways play an important role in cancer. The cold-inducible RNA-binding protein RBM3 is upregulated in several types of cancer, including prostate cancer, but its pathogenic contributions are undetermined. RBM3 is expressed at low basal levels in human fetal prostate or in CD133+ prostate epithelial cells (PrEC), compared with the adult prostate or CD133-PrEC, and RBM3 is downregulated in cells cultured in soft agar or exposed to stress. Notably, RBM3 overexpression in prostate cancer cells attenuated their stem cell-like properties in vitro as well as their tumorigenic potential in vivo. Interestingly, either overexpressing RBM3 or culturing cells at 32°C suppressed RNA splicing of the CD44 variant v8-v10 and increased expression of the standard CD44 (CD44s) isoform. Conversely, silencing RBM3 or culturing cells in soft agar (under conditions that enrich for stem cell-like cells) increased the ratio of CD44v8-v10 to CD44s mRNA. Mechanistic investigations showed that elevating CD44v8-v10 interfered with MMP9-mediated cleavage of CD44s and suppressed expression of cyclin D1, whereas siRNA-mediated silencing of CD44v8-v10 impaired the ability of prostate cancer cells to form colonies in soft agar. Together, these findings suggested that RBM3 contributed to stem cell-like character in prostate cancer by inhibiting CD44v8-v10 splicing. Our work uncovers a hitherto unappreciated role of RBM3 in linking stress-regulated RNA splicing to tumorigenesis, with potential prognostic and therapeutic implications in prostate cancer. Cancer Res; 73(13); 4123–33. ©2013 AACR.
Platelet kinetic studies in patients with hyperlipoproteinemia: effects of clofibrate therapy.
Authors: L A Harker, W Hazzard
Journal: Circulation (1979)

Studies of platelet and fibrinogen kinetics in 27 patients with hyperlipoproteinemia and 28 control subjects demonstrated shortened platelet survival and increased platelet turnover in seven patients with type III and 10 patients with type IV-V hyperlipoproteinemia (p less than 0.01). There was no correlation between platelet survival time and specific lipid levels, vascular disease, sex or age. Platelet kinetics were not significantly altered from control values in eight patients with familial hypercholesterolemia. Platelet aggregation studies and fibrinogen kinetic measurements did not differ in any of the hyperlipoproteinemic groups of patients from those in control subjects. Despite significant changes in plasma lipids induced by clofibrate, platelet survival was significantly extended only in patients with type IV-V hyperlipoproteinemia (p less than 0.05). These results are consistent with the hypothesis that atherogenesis in patients with types III--V hyperlipoproteinemia may be associated with a process of endothelial desquamation, and type IIa hyperlipoproteinemia may involve nondesquamating endothelial injury.
The Biological Activity of Natural and Mutant Ptα Alleles
Authors: Deena Gibbons, Nataki C. Douglas, Domingo F. Barber, Qiang Liu, Renee Sullo, Liping Geng, Hans-Joerg Fehling, Harald von Boehmer, Adrian C. Hayday
Journal: The Journal of Experimental Medicine (2001)

β selection is a major checkpoint in early thymocyte differentiation, mediated by successful expression of the pre-T cell receptor (TCR) comprising the TCRβ chain, CD3 proteins, and a surrogate TCRα chain, pTα. The mechanism of action of the pre-TCR is unresolved. In humans and mice, the pTα gene encodes two RNAs, pTαa, and a substantially truncated form, pTαb. This study shows that both are biologically active in their capacity to rescue multiple thymocyte defects in pTα−/− mice. Further active alleles of pTα include one that lacks both the major ectodomain and much of the long cytoplasmic tail (which is unique among antigen receptor chains), and another in which the cytoplasmic tail is substituted with the short tail of TCR Cα. Thus, very little of the pTα chain is required for function. These data support a hypothesis that the primary role of pTα is to stabilize the pre-TCR, and that much of the conserved structure of pTα probably plays a critical regulatory role.
Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients
Authors: G.F. Joos, W. Vincken, R. Louis, V.J. Schelfhout, J.H. Wang, M.J. Shaw, G.D. Cioppa, R.A. Pauwels
Journal: European Respiratory Journal (2003)

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK 1 and NK 2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK 1 /NK 2 receptor antagonist, DNK333, on NKA‐induced bronchoconstriction in asthma. A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled, crossover trial. Increasing concentrations of NKA (3.3×10 −9 to 1.0×10 −6 mol·mL −1 ) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo. It was observed that DNK333 did not affect baseline lung function but did protect against NKA‐induced bronchoconstriction in those patients. The mean log 10 provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was −5.6 log 10 mol·mL −1 at 1 h after DNK333 treatment and −6.8 log 10 mol·mL −1 after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment. The results shown in this report indicate that DNK333 blocks neurokinin A‐induced bronchoconstriction in patients with asthma.
Evaluation of the Effect of Aflibercept (Z) on Os by Timing of 1st Line Disease Progression: A Post-Hoc Analysis of the Velour Trial
Authors: Mitchell Edith, van Hazel Guy, Cunningham David, Arnold Dirk, Schmoll Hans-Joachim, ten Tije Albert, Mckendrick Joe, Joulain Florence, Andria Michael, Vishwanath Raghu, Hoff Paulo
Journal: Annals of Oncology (2014)
The quality and stability of essential drugs in rural Zimbabwe: controlled longitudinal study
Authors: H. Nazerali, H. V Hogerzeil
Journal: BMJ (1998)

higher response rates have reported similar levels of distress. 2A study carried out as part of the NHS workforce survey found no difference in the levels of distress between responders and non-responders, 4 suggesting that non-response was not systematically related to psychological health.Our results may not be generalisable to non-teaching hospitals and might be confounded by the fact that consultants and house officers were selected from different trusts.In fact, one hospital was a source of both consultants and house officers for this study, and the occupational group differences at this hospital remained significant.Some of these data are three years old.The continued upheaval in the health service and further reductions in junior house doctors' working hours mean that the differences in psychological distress between senior hospital doctors and their most junior colleagues may now be more pronounced.One approach to addressing this problem could be to tackle specific sources of occupational stress in different groups.For example, our results suggest consultants might benefit from a reduction in their workload, while house officers might benefit if they had greater autonomy.We would like to thank the consultants and house officers.Contributors: NK coordinated and collected data for the house officer study, helped analyse the data, and wrote the initial draft of the paper.CB coordinated the consultant study and commented on drafts of the paper.CS helped to extract and analyse
Identification of Novel Nasopharyngeal Carcinoma Biomarkers by Laser Capture Microdissection and Proteomic Analysis
Authors: Ai-Lan Cheng, Wei-Guo Huang, Zhu-Chu Chen, Fang Peng, Peng-Fei Zhang, Mao-Yu Li, Feng Li, Jian-Ling Li, Cui Li, Hong Yi, Bin Yi, Zhi-Qiang Xiao
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To identify novel nasopharyngeal carcinoma (NPC) biomarkers by laser capture microdissection and a proteomic approach. Experimental Design: Proteins from pooled microdissected NPC and normal nasopharyngeal epithelial tissues (NNET) were separated by two-dimensional gel electrophoresis, and differential proteins were identified by mass spectrometry. Expression of three differential proteins (stathmin, 14-3-3σ, and annexin I) in the above two tissues as well as four NPC cell lines was determined by Western blotting. Immunohistochemistry was also done to detect the expression of three differential proteins in 98 cases of primary NPC, 30 cases of NNET, and 20 cases of cervical lymph node metastases, and the correlation of their expression levels with clinicopathologic features and clinical outcomes were evaluated. Results: Thirty-six differential proteins between the NPC and NNET were identified. The expression levels of stathmin, 14-3-3σ, and annexin I in the two types of tissues were confirmed and related to differentiation degree and/or metastatic potential of the NPC cell lines. Significant stathmin up-regulation and down-regulation of 14-3-3σ and annexin I were observed in NPC versus NNET, and significant down-regulation of 14-3-3σ and annexin I was also observed in lymph node metastasis versus primary NPC. In addition, stathmin up-regulation and down-regulation of 14-3-3σ and annexin I were significantly correlated with poor histologic differentiation, advanced clinical stage, and recurrence, whereas down-regulation of 14-3-3σ and annexin I was also significantly correlated with lymph node and distant metastasis. Furthermore, survival curves showed that patients with stathmin up-regulation and down-regulation of 14-3-3σ and annexin I had a poor prognosis. Multivariate analysis revealed that the expression status of stathmin, 14-3-3σ, and annexin I was an independent prognostic indicator. Conclusion: The data suggest that stathmin, 14-3-3σ, and annexin I are potential biomarkers for the differentiation and prognosis of NPC, and their dysregulation might play an important role in the pathogenesis of NPC.