tbuckley/cabot-search huggingface dataset:
Molecular Markers of Urothelial Cancer and Their Use in the Monitoring of Superficial Urothelial Cancer
Authors: Peter C. Black, Gordon A. Brown, Colin P. Dinney
Journal: Journal of Clinical Oncology (2006)

Multiple molecular markers have been described for use in bladder cancer patients. Some of these have been studied more extensively than others, and it is difficult for the clinician to maintain a perspective over the myriad findings that have been made. We have reviewed a selection of markers used for surveillance with an emphasis on clinical utility. The best studied markers and those with the most promising preliminary results were selected. Only studies that included surveillance for recurrence in patients with a history of bladder cancer were considered. Each marker is briefly described and its performance in monitoring bladder cancer patients is summarized. Several promising markers are available, although only four have obtained US Food and Drug Administration approval. The clinical applications that have been studied include replacement or reduction in the number of cystoscopies performed in the surveillance of bladder cancer patients, substitution for or complementary use with urinary cytology in the same setting, predicting disease recurrence and progression, and predicting and monitoring treatment response. None of the markers have been proved sensitive and specific enough to replace cystoscopy. Others, such as nuclear matrix protein 22 (NMP22) and UroVysion, appear to have some utility when used to complement or replace cytology. The other applications have not been adequately studied for any given marker. While multiple molecular markers exist for bladder cancer, their full clinical utility will not be realized until more multicenter prospective trials are conducted to verify their efficacy and safety in the monitoring of patients with superficial bladder cancer.
Graft-versus-host disease can be separated from graft-versus-lymphoma effects by control of lymphocyte trafficking with FTY720
Authors: Yong-Mi Kim, Teviah Sachs, Wannee Asavaroengchai, Roderick Bronson, Megan Sykes
Journal: Journal of Clinical Investigation (2003)

Graft-versus-host disease (GvHD) mediated by donor T cells recognizing host alloantigens is associated with beneficial graft-versus-tumor effects in recipients of allogeneic hematopoietic cell transplants. Since leukemias and lymphomas reside largely within the lymphohematopoietic system, we have proposed that the desired graft-versus-leukemia or graft-versus-lymphoma effect can be separated from the complication of GvHD by confinement of the graft-versus-host alloresponse to the lymphohematopoietic tissues. Since the new sphingosine-1-phosphate receptor agonist immunosuppressive drug FTY720 leads to trapping of T cells in secondary lymphoid tissues, we evaluated the possibility that this drug could diminish GvHD, a disease involving epithelial target tissues, while permitting a beneficial alloresponse to take place within the lymphohematopoietic system, leading to graft-versus-lymphoma effects. We demonstrate here that FTY720 markedly reduces GvHD in a clinically relevant, haploidentical strain combination, while permitting antitumor effects against a T cell lymphoma of unshared host MHC haplotype to proceed unhindered. These results establish a potential new immunotherapeutic approach to separating graft-versus-leukemia effects from GvHD.
Severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes
Authors: Jeffery C. Woods, Lorraine C. Mion, Jason T. Connor, Florence Viray, Lisa Jahan, Cecilia Huber, Renee McHugh, Jeffrey P. Gonzales, James K. Stoller, Alejandro C. Arroliga
Journal: Intensive Care Medicine (2004)
P3-13-01: Boost Radiation Therapy Not of Value in Reducing IBTR of Invasive or Noninvasive Breast Cancers for Patients with DCIS: Results from the NSABP B-24 Trial.
Authors: TB Julian, FA Vicini, JP Costantino, DW Arthur, KM Kidwell, SR Land, EP Mamounas, N Wolmark
Journal: Cancer Research (2011)

Abstract Background: Whole breast irradiation therapy following lumpectomy for invasive breast cancer (IBC) or noninvasive breast cancer (DCIS) significantly reduces the risk of local recurrence. Boost radiation therapy to the tumor bed has been proven to additionally lower the risk of recurrence for IBC. The benefit of boost therapy in patients with DCIS is less certain. We carried out a review of the NSABP B-24 trial to assess the benefit of boost therapy. Methods: After lumpectomy and radiation therapy, 1804 women with DCIS were randomly assigned to placebo (902) or tamoxifen (902). Whole breast irradiation therapy (50 Gy) was mandatory. Boost radiation therapy was optional, and boost status was known for 1,569 patients. Of these, 1392 patients (86.97%) were identified as having all data sufficient for multivariate analysis. Of these, 613 received boost therapy ranging from 1 Gy −20 Gy, with 81.5% receiving 10 Gy. Mean time of follow-up was 161 months. Results: Patients who received boost radiation therapy were more likely to be younger (p=0.04), have positive margins (p=0.007), and be more likely to have comedo necrosis (p=0.03). Multivariate analysis identified only treatment (tamoxifen vs placebo) (HR=0.74, 95% CI=0.57−0.98, p=0.034), age (≥ 50 verses &amp;lt; 50) (HR=0.47, 95% CI=0.36−0.61, p&amp;lt;0.0001), and margin status (positive vs negative) (HR: 1.79, 95% CI= 1.31−2.43, p&amp;lt;0.001) as significant predictors for ipsilateral breast tumor recurrence (IBTR). Boost had no significant effect on IBTR (HR=0.87, 95% CI=0.66−1.15, p=0.33). The lack of boost effect applied to both invasive (HR=0.86, 95% CI=0.58−1.27, p=0.44) and noninvasive IBTR (HR=0.89, 95% CI=0.60−1.33, p=0.56). No interaction was seen between boost and treatment, age, margin status, or comedo necrosis. Conclusion: In NSABP B-24, the addition of boost radiation therapy was not found to be of value in reducing IBTR of invasive or noninvasive breast cancers for patients with DCIS. Supported by PHS grants NCI-U10-CA-69651, NCI-U10-CA-12027, and NCI P30-CA-14599 from the US NCI and AstraZeneca. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-01.
1120-63 Comparison of intracoronary bolus injection and intracoronary continuous infusion methods for inducing hyperemia
Authors: Tae-Young Choi, Seung-Jea Tahk, Myeong-Ho Yoon, So-Yeon Choi, Min-Cheul Kim, Heung-Mo Yang, Jung-Hyun Choi, Zhen-Guo Zheng, Long Qi, Boung-Joo Choi, Hyuk-Jae Chang, Gyo-Seung Hwang, Joon-Han Shin, Byung-il W Choi
Journal: Journal of the American College of Cardiology (2004)
Randomized, Multicenter, Phase II Study of CO-101 Versus Gemcitabine in Patients With Metastatic Pancreatic Ductal Adenocarcinoma: Including a Prospective Evaluation of the Role of hENT1 in Gemcitabine or CO-101 Sensitivity
Authors: Elizabeth Poplin, Harpreet Wasan, Lindsey Rolfe, Mitch Raponi, Tone Ikdahl, Ihor Bondarenko, Irina Davidenko, Volodymyr Bondar, August Garin, Stefan Boeck, Steffen Ormanns, Volker Heinemann, Claudio Bassi, T.R. Jeffrey Evans, Roland Andersson, Hejin Hahn, Vince Picozzi, Adam Dicker, Elaina Mann, Cynthia Voong, Paramjit Kaur, Jeff Isaacson, Andrew Allen
Journal: Journal of Clinical Oncology (2013)

Gemcitabine requires transporter proteins to cross cell membranes. Low expression of human equilibrative nucleoside transporter-1 (hENT1) may result in gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). CO-101, a lipid-drug conjugate of gemcitabine, was rationally designed to enter cells independently of hENT1. We conducted a randomized controlled trial to determine whether CO-101 improved survival versus gemcitabine in patients with metastatic PDAC (mPDAC) with low hENT1. The study also tested the hypothesis that gemcitabine is more active in patients with mPDAC tumors with high versus low hENT1 expression.Patients were randomly assigned to CO-101 or gemcitabine, after providing a metastasis sample for blinded hENT1 assessment. An immunohistochemistry test measuring tumor hENT1 was developed. To dichotomize the population, an hENT1 cutoff value was defined using primary PDAC samples from an adjuvant trial, and a high/low cutoff was applied. The primary end point was overall survival (OS) in the low hENT1 subgroup.Of 367 patients enrolled, hENT1 status was measured in 358 patients (97.5%). Two hundred thirty-two (64.8%) of 358 patients were hENT1 low. There was no difference in OS between treatments in the low hENT1 subgroup or overall, with hazard ratios (HRs) of 0.994 (95% CI, 0.746 to 1.326) and 1.072 (95% CI, 0.856 to 1.344), respectively. The toxicity profiles in both arms were similar. Within the gemcitabine arm, there was no difference in survival between the high and low hENT1 subgroups (HR, 1.147; 95% CI, 0.809 to 1.626).CO-101 is not superior to gemcitabine in patients with mPDAC and low tumor hENT1. Metastasis hENT1 expression did not predict gemcitabine outcome.
Tumoral Expression of TXR1 and TSP1 Predicts Overall Survival of Patients with Lung Adenocarcinoma Treated with First-line Docetaxel-Gemcitabine Regimen
Authors: Chara Papadaki, Dimitris Mavroudis, Maria Trypaki, Anastasios Koutsopoulos, Efstathios Stathopoulos, Dora Hatzidaki, Eleftheria Tsakalaki, Vassilis Georgoulias, John Souglakos
Journal: Clinical Cancer Research (2009)

Abstract Purpose: In vitro data suggest that down-regulation of thrombospondin 1 (TSP1) expression from TXR1 is associated with resistance to taxane-based chemotherapy. The prognostic and predictive value of tumoral expression of both genes was evaluated in patients with lung adenocarcinoma treated with first-line docetaxel and gemcitabine. Experimental Design: Tumor samples from 96 patients, with stage IIIB (with pleural effusion) or IV lung adenocarcinomas, were analyzed for TXR1 and TSP1 mRNA levels by quantitative real-time PCR, from microdissected cells derived from patients' primary tumors. Results: The mRNA levels of the two genes were inversely correlated (Spearman's test = -0.49; P &amp;lt; 0.0001). Patients with low TXR1 mRNA levels experienced a longer median time to tumor progression (TTP; P &amp;lt; 0.0001) and median overall survival (mOS; P = 0.001) when compared with patients with high TXR1 expression. Patients with high TSP1 expression presented longer TTP (P = 0.002) and mOS (P &amp;lt; 0.0001) when compared with patients with low TSP1 expression. Moreover, patients with high TSP1 and low TXR1 expression (n = 36) presented higher prolonged TTP (P = 0.009) and mOS (P &amp;lt; 0.0001) compared with patients with high TXR1 and low TSP1 expression. Multivariate analysis showed that high TXR1/low TSP1 expression was an independent prognostic factor for decreased TTP (hazard ratio, 1.7; 95% confidence interval, 1.1-3.27; P = 0.016) and mOS (hazard ratio, 2.55; 95% confidence interval, 1.57-4.15; P &amp;lt; 0.0001). Conclusion: These data confirm the in vitro model of TSP1 and TXR1 effect on taxane resistance in lung adenocarcinomas and merit further evaluation.
Improved Insulin Action and Glycemic Control After Long Term Angiotensin-Converting Enzyme Inhibition in Subjects with Arterial Hypertension and Type II Diabetes
Authors: Elisabetta Torlone, Mariella Britta, Anna Maria Rambotti, Gabriele Perriello, Fausto Santeusanio, Paolo Brunetti, Geremia B Bolli
Journal: Diabetes Care (1993)

To determine the long-term effects of the angiotensin-converting enzyme inhibitor captopril on insulin sensitivity in subjects with type II diabetes and arterial hypertension. The chronic effects of angiotensin-converting enzyme inhibition on insulin-sensitive individuals are presently controversial.Sixteen subjects, with type II diabetes (on diet and/or diet plus oral hypoglycemic agents) and arterial hypertension, were studied. During a 1-mo run-in period no antihypertensive drugs were administered, but oral hypoglycemic agents were continued in subjects already in therapy. The subjects were then randomly assigned to two 3-mo treatment periods, with either captopril or placebo (single blind, cross-over design). At the end of each treatment period, insulin sensitivity was assessed by means of a euglycemic-hyperinsulinemic clamp (2 sequential steps, 2-h each, insulin infusion 0.25 and 1 mU.kg-1.min-1, steps 1 and 2, respectively), combined with infusion of [3-3H]glucose (for calculation of hepatic glucose output and peripheral glucose utilization, rates of glucose disappearance), and indirect calorimetry (for calculation of glucose oxidation, nonoxidative glucose metabolism, and lipid oxidation). The percentage of HbA1c was measured to assess long-term glycemic control.Comparing data at the end of placebo and captopril treatment, captopril resulted in: lower blood pressure (systolic 154 +/- 2 vs. 163 +/- 3 mmHg and diastolic 93 +/- 2 vs. 101 +/- 2 mmHg); greater insulin sensitivity in hyperglycemic conditions (total amount of insulin infused and time of insulin infusion required to reach euglycemia, 1.73 +/- 0.54 vs. 2.08 +/- 0.60 U and 58 +/- 8 vs. 70 +/- 11 min, captopril and placebo, respectively, P < 0.05); greater insulin sensitivity in euglycemic conditions at liver level (hepatic glucose output 4.11 +/- 0.55 vs. 5.2 +/- 0.4 mumol.kg-1.min-1, step 1 of the clamp), muscle level (rates of glucose disappearance 26.1 +/- 2.3 vs. 23.8 +/- 2.1 mumol.kg-1.min-1 step 2 of the clamp), primarily attributable to approximately 29% increase in nonoxidative glucose metabolism, and adipose tissue level (plasma free fatty acid 0.185 +/- 0.03 vs. 0.24 +/- 0.02 mM and lipid oxidation 1.9 +/- 0.3 vs. 2.21 +/- 0.04 mumol.kg-1.min-1 in step 1); and lower HbA1c (6.7 +/- 0.2 vs. 7.3 +/- 0.2%, P < 0.05).Long-term captopril administration in type II diabetic subjects improves insulin sensitivity in the postprandial state, not in the fasting state, and improves glycemic control.
Mechanisms of Ca(2+)-independent contraction in single permeabilized ferret aorta cells.
Authors: H Katsuyama, K G Morgan
Journal: Circulation Research (1993)

The mechanisms by which prostaglandin F2 alpha (PGF2 alpha) can cause contractions at constant intracellular Ca2+ were investigated by the direct measurement of force from single saponin-permeabilized smooth muscle cells from the ferret aorta. The size of PGF2 alpha contractions did not change between pCa 9.0 and pCa 6.6. The remainder of the experiments were carried out at pCa 7.0. At pCa 7.0, PGF2 alpha (0.1-100 microM) induced sustained force in a dose-dependent manner, reaching a maximum (2.61 +/- 0.20 microN, n = 14) in 10 minutes. Both protein kinase C pseudosubstrate inhibitor (3 microM) and staurosporine (1 microM) significantly inhibited PGF2 alpha (100 microM)-induced contractions, but staurosporine was more effective. Staurosporine caused 88.8 +/- 13.3% inhibition, whereas protein kinase C pseudosubstrate inhibitor inhibited 62.3 +/- 9.6% of the PGF2 alpha-induced contraction. An inhibitor of type-1 and type-2A protein phosphatases, microcystin-LR, at a concentration of 1 microM induced a gradual and sustained contraction (1.53 +/- 0.21 microN). A lower concentration of microcystin-LR (100 nM) also induced a small but significant contraction (0.36 +/- 0.26 microN). Pretreatment with both 1 microM and 100 nM microcystin-LR caused significant inhibition of the PGF2 alpha-induced contraction from 2.61 +/- 0.20 microN (n = 14) to 0.32 +/- 0.20 microN (n = 6) (p &lt; 0.01) and 1.52 +/- 0.21 microN (n = 6) (p &lt; 0.01), respectively. These results indicate that the part of the PGF2 alpha-induced contraction that occurs at a constant, low intracellular Ca2+ is the combined result of activation of protein kinase C and phosphatase inhibition.
Clinical Impact of Persistent Left Bundle-Branch Block After Transcatheter Aortic Valve Implantation With CoreValve Revalving System
Authors: Luca Testa, Azeem Latib, Federico De Marco, Marco De Carlo, Mauro Agnifili, Roberto Adriano Latini, Anna Sonia Petronio, Federica Ettori, Arnaldo Poli, Stefano De Servi, Angelo Ramondo, Massimo Napodano, Silvio Klugmann, Gian Paolo Ussia, Corrado Tamburino, Nedy Brambilla, Antonio Colombo, Francesco Bedogni
Journal: Circulation (2013)

Background— Conduction disturbances are relatively common after transcatheter aortic valve implantation. Previous data demonstrated an adverse impact of persistent left bundle-branch block (LBBB) after surgical aortic valve replacement. It is unclear whether new-onset LBBB may also impact the prognosis of patients after transcatheter aortic valve implantation. Methods and Results— Among 1060 patients treated with a CoreValve Revalving System transcatheter aortic valve implantation between October 2007 and April 2011 in high-volume centers in Italy, we analyzed those without LBBB or pacemaker at admission (879 patients [82.9%]). We further excluded those who underwent permanent pacemaker implantation within 48 hours after the procedure (61 patients [7%]), for a final study population of 818 patients. Among them, 224 patients (group A; 27.4%) developed a persistent LBBB and the remaining 594 (group B; 72.6%) did not. Clinical characteristics were similar between groups. A low implantation was significantly more frequent in group A (15% versus 9.8%, P =0.02). No patients were censored before 1 year (median follow-up period 438 days, interquartile range 174–798 days). Survival analyses and inherent log-rank tests showed that LBBB was not associated with higher all-cause mortality, cardiac mortality, or hospitalization for heart failure at 30 days or 1 year. At 30 days, but not at 1 year, group A had a significantly higher rate of pacemaker implantation. Conclusions— In this registry of high-volume centers, persistent LBBB after CoreValve Revalving System transcatheter aortic valve implantation showed no effect on hard end points. On the other hand, LBBB was associated with a higher short-term rate of pacemaker implantation.
Cytokines Tumor Necrosis Factor and Interleukin–6 in Experimental Biliary Obstruction in Mice
Authors: M. H.A. Bemelmans, D. J. Gouma, J. W. Greve, W. A. Buurman
Journal: Hepatology (1992)

The putative role of the cytokines interleukin-6 and tumor necrosis factor in the pathophysiology of the complications and mortality after surgery in jaundiced patients was studied in a murine model. Cytokine serum levels were determined in mice with experimental biliary obstruction. As an indicator of the activation status of macrophages, cytokine release by mononuclear phagocytes obtained from such mice was assessed. Following surgery, interleukin-6 levels increased to 2 to 3 ng/ml after 3 to 4 hr, but declined rapidly afterward to levels of 60 pg/ml after 10 days. After 12 days, substantial interleukin-6 levels were observed in jaundiced mice (100 pg/ml), whereas levels in sham mice further decreased (p less than 0.001). The cytokine tumor necrosis factor was frequently present in the serum of jaundiced mice. After 22 days, when killed, all jaundiced mice showed significant tumor necrosis factor levels (p less than 0.001). This was in contrast to sham mice in which tumor necrosis factor was never detected. The presence of an activated state of macrophages in jaundiced mice was concluded from the observed high spontaneous cytokine release and significantly higher release after stimulation (p less than 0.05). The presence of circulating cytokines was discussed in the context of the postoperative complications observed in jaundiced patients.
Mechanisms of Altered Water Metabolism in Psychotic Patients with Polydipsia and Hyponatremia
Authors: M B Goldman, D J Luchins, G L Robertson
Journal: New England Journal of Medicine (1988)

Water intoxication is a serious problem in many patients with chronic psychiatric illness. In an effort to determine the mechanism of this disorder, we investigated the osmoregulation of water intake and antidiuretic function in psychiatric patients with polydipsia and hyponatremia and in matched controls with psychiatric illness but neither polydipsia nor hyponatremia. We found that a water load suppressed plasma osmolality and vasopressin and urine osmolality in both groups, but that urinary dilution and free water clearance were impaired in the patients with hyponatremia, even though plasma levels of vasopressin and solute clearance were similar in the two groups. Moreover, during water loading and infusion of hypertonic saline, the plasma level of vasopressin was higher at any given plasma osmolality in the test patients than in the controls, indicating a downward resetting of the osmostat. Patients' estimates of the amount of water they desired were shown to correlate significantly with the amount of water consumed and, at any given level of plasma osmolality, appeared to be higher in the test patients than in the controls. We conclude that psychiatric patients with polydipsia and hyponatremia have unexplained defects in urinary dilution, the osmoregulation of water intake, and the secretion of vasopressin.
How to Slip the Capsule Down a Narrow Throat: Reply to Tóth et al.
Authors: S. Hollerbach, F. Wiedbrauck
Journal: Endoscopy (2004)

In the space of only 3 years since its introduction, video capsule endoscopy (CE) of the small bowel has rapidly emerged as a novel, noninvasive imaging method for detecting previously undiagnosed small-bowel diseases such as obscure bleeding sources, polyps, and regional Crohn’s disease. However, the potential role for capsule endoscopy in the management of such diseases is still being clarified. A number of peer-reviewed studies [1] [2] [3] [4] [5] [6] have now appeared that compare CE with previous standard methods such as radiographic studies and push enteroscopy, and this may finally allow scientifically based use of this quite expensive diagnostic method. All of the studies so far published show that with regard to its diagnostic capacities, capsule endoscopy is better than push enteroscopy and better than standard radiographic examinations for detecting lesions located along the entire length of the small bowel. However, the method is also providing new insights into what happens in the small bowel in physiological conditions [6] and indicating which findings are clearly pathological in nature [1] [2] [3] [4] [7].
Actinomycosis of the trachea affecting the right supraclavicular region.
Authors: O Maiwand, A R Makey, A Khagani
Journal: Thorax (1982)

Actinomycosis ofthe trachea affecting the right supraclavicular region 0 MAIWAND, AR MAKEY, A KHAGANI Colindale Hospital, London Actinomycosis is a worldwide chronic infection caused by an anaerobic Gram-positive organism.The human disease is most commonly caused by Actinomyces israelii, described by Israel in 1878.The organism is a normal commensal ofthe mouthand is found especially in the tonsils and in carious teeth.This endogenous infection is characterised by granulation formation and by fibrous infiltration and may present as a pseudotumour mass.' Classically there are multiple small, coalescent abscesses with communication sinuses and "sulphur"granules, which when recognised are diagnostic.A normocytic normochromic anaemia is frequently seen.2Actinomyces is a difficult organism to isolate and the infection is difficult to treat.Treatment consists of surgical drainage of the infected abscesses and administration of antibiotics.Penicillin is the on July 27,
Book: Integrated Cancer Care: Holistic, Complementary and Creative Approaches
Authors: S. Baron
Journal: BMJ (2001)

Ed Jennifer Barraclough Oxford University Press, £29.95, pp 312 ISBN 0 19 263095 4 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Hype, hope, or healing? Complementary and alternative medicine is becoming increasingly popular in the United Kingdom, with a fifth of the population using it. Britons spend £1.6bn a year on complementary medicine (in the United States the figure is £21bn) and there are now 49 000 practitioners. Complementary medicine adopts a different philosophy to conventional medicine. The idea is that a healthy body is … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif