tbuckley/cabot-search huggingface dataset:
Large Retroperitoneal Lymphadenopathy As a Predictor of Venous Thromboembolism in Patients With Disseminated Germ Cell Tumors Treated With Chemotherapy
Authors: Amirrtha Srikanthan, Ben Tran, Michel Beausoleil, Michael A.S. Jewett, Robert J. Hamilton, Jeremy F.G. Sturgeon, Martin O'Malley, Lynn Anson-Cartwright, Peter W.M. Chung, Padraig R. Warde, Eric Winquist, Malcolm J. Moore, Eitan Amir, Philippe L. Bedard
Journal: Journal of Clinical Oncology (2015)

Cisplatin-based chemotherapy, a mainstay of treatment for disseminated germ cell tumors (GCTs), is associated with venous thromboembolism (VTE). Many patients with disseminated GCTs have large retroperitoneal lymph node (RPLN) metastases that may cause venous stasis and increase the risk of VTE development. We hypothesized that there was an association between large RPLN and chemotherapy-associated VTE risk. The training cohort was composed of patients with disseminated GCT receiving first-line chemotherapy at Princess Margaret Cancer Centre between January 2000 and December 2010. Large RPLN was defined as more than 5 cm in maximal axial diameter. The predictive and discriminatory accuracies of a model using large RPLN in predicting VTE were compared with high-risk Khorana score (≥ 3) using logistic regression and area under receiver operator characteristic curves (AUROCs). The model was externally validated in a cohort of patients treated at the London Health Sciences Centre. The training cohort comprised 216 patients, 21 (10%) of whom developed VTE during chemotherapy. VTE was associated with large RPLN (odds ratio [OR], 5.26; P = .001), high-risk Khorana score (OR, 11.8; P < .001), intermediate-/poor-risk disease (OR, 3.76; P = .005), and hospitalization during chemotherapy (OR, 4.24; P = .002). Large RPLN showed higher discriminatory accuracy than high-risk Khorana score (AUROC, 0.71 v 0.67, respectively). Superior discriminatory accuracy of large RPLN over high-risk Khorana score was validated in the London cohort (AUROC, 0.61 v 0.57, respectively). Large RPLN is associated with VTE in patients with disseminated GCT and provides higher discriminatory accuracy than high-risk Khorana score. Results should be validated in larger, prospective studies. Prophylactic anticoagulation may be considered in high-risk patients.
P-Glycoprotein–Mediated Resistance to Hsp90-Directed Therapy Is Eclipsed by the Heat Shock Response
Authors: Andrea K. McCollum, Cynthia J. TenEyck, Bridget Stensgard, Bruce W. Morlan, Karla V. Ballman, Robert B. Jenkins, David O. Toft, Charles Erlichman
Journal: Cancer Research (2008)

Abstract Despite studies that show the antitumor activity of Hsp90 inhibitors, such as geldanamycin (GA) and its derivative 17-allylamino-demethoxygeldanamycin (17-AAG), recent reports indicate that these inhibitors lack significant single-agent clinical activity. Resistance to Hsp90 inhibitors has been previously linked to expression of P-glycoprotein (P-gp) and the multidrug resistant (MDR) phenotype. However, the stress response induced by GA treatment can also cause resistance to Hsp90-targeted therapy. Therefore, we chose to further investigate the relative importance of P-gp and the stress response in 17-AAG resistance. Colony-forming assays revealed that high expression of P-gp could increase the 17-AAG IC50 6-fold in cells transfected with P-gp compared with parent cells. A549 cells selected for resistance to GA overexpressed P-gp, but verapamil did not reverse the resistance. These cells also overexpressed Hsp27, and Hsp70 was induced with 17-AAG treatment. When the GA and 17-AAG resistant cells were transfected with Hsp27 and/or Hsp70 small interfering RNA (siRNA), the 17-AAG IC50 decreased 10-fold compared with control transfected cells. Transfection with siRNA directed against Hsp27, Hsp70, or Hsp27 and Hsp70 also increased sensitivity to EC78, a purine scaffold-based Hsp90 inhibitor that is not a P-gp substrate. We conclude that P-gp may contribute, in part, to resistance to 17-AAG, but induction of stress response proteins, such as Hsp27 and Hsp70, by Hsp90-targeted therapy plays a larger role. Taken together, our results indicate that targeting of Hsp27 and Hsp70 should be exploited to increase the clinical efficacy of Hsp90-directed therapy. [Cancer Res 2008;68(18):7419–27]
Human neutrophil plasminogen activator is localized in specific granules and is translocated to the cell surface by exocytosis.
Authors: J M Heiple, L Ossowski
Journal: The Journal of Experimental Medicine (1986)

The subcellular localization of plasminogen activator (PA) in human neutrophils was studied. The cells were disrupted by nitrogen cavitation and fractionated on Percoll density gradients into three major components containing the plasma membranes, the specific granules, and the azurophilic granules. The biochemical markers we used to identify these organelles were alkaline phosphatase, vitamin B12-binding protein, and beta-glucuronidase, respectively. Using the radioactive fibrin plate method, PA activity and plasminogen-independent fibrinolytic activity were measured. In resting neutrophils, PA was associated mainly with the membranes of the specific granules. In five individual experiments the activity of this fraction varied from 79 to 100% of the total; the remaining activity was found to be associated with the plasma membrane, and no activity was present in the azurophilic granules. In neutrophils that were activated by exposure to PMA (20 ng/ml for 15 min at 37 degrees C), the total recoverable PA activity remained unchanged; however, the main peak of activity (85% of total) shifted from the specific granules to the plasma membranes. The magnitude of the reduction of the enzyme in the specific granules paralleled that of vitamin B12-binding protein. PMA-activated, intact neutrophils had approximately 12-fold more surface-bound PA activity than resting cells. Recovery of PA activity from neutrophils was critically dependent on pretreatment of the intact cells with DFP before cavitation; 100-fold more PA activity was detected in DFP-pretreated cells. At the same time, this pretreatment reduced the plasminogen-independent fibrinolytic activity by approximately sevenfold. We determined that PA present in the neutrophils is of the urokinase (UK) type and that the enzyme is produced and stored as a pro-UK, a form insensitive to DFP inhibition. The reduction in the level of proteases (measured as fibrinolytic activity) and the resistance of pro-UK to DFP are most likely the two major reasons for the greatly improved recovery of PA from the DFP-pretreated cells. These findings show that in resting neutrophils PA is stored in the specific granules, and that during activation, it translocates to the outer surface of the plasma membranes, thus equipping the cell with an ecto-proteolytic potential.
Renal biopsy collagen I mRNA predicts scarring in rabbit anti-GBM disease: Comparison with conventional measures
Authors: Sang-Koo Lee, Meera Goyal, Mariano De Miguel, Peedikayil Thomas, Bryan Wharram, Robert Dysko, Sem Phan, Paul D. Killen, Roger C. Wiggins
Journal: Kidney International (1997)
Percutaneous Transluminal Septal Myocardial Ablation in Hypertrophic Obstructive Cardiomyopathy: Acute Results and 3-Month Follow-Up in 25 Patients
Authors: Hubert Seggewiss, Ulrich Gleichmann, Lothar Faber, Dieter Fassbender, Henning K Schmidt, Stefan Strick
Journal: Journal of the American College of Cardiology (1998)
One fifth of samples of unpasteurised milk are contaminated with bacteria
Authors: J. de Louvois, A. Rampling
Journal: BMJ (1998)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following One fifth of samples of unpasteurised milk are contaminated with bacteria Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Return of Renal Function After Varying Periods of Ureteral Occlusion
Authors: Alexander Brunschwig, Hugh R. K. Barber, Stuart Roberts
Journal: JAMA (1964)

Pelvic exenteration with diversion of both ureters was performed in 40 patients with advanced pelvic cancer and one ureter occluded on preoperative intravenous pyelograms (IVP). In 29 instances, renal function returned. Preoperative periods of occlusion were not always determinable; where they were, the average occlusion time followed by functional return was three to four months. Among those that did not show functional return, the average estimated occlusion time was 7 1/2 months. In 11 patients who had preoperative IVP over varying periods, it was possible to fix rather accurately dates of complete ureteral occlusion. There was return of function in seven patients with periods of occlusion varying from two to four weeks, and in one patient with 3 1/2 months occlusion. In two patients with occlusion. for 165 days, impaired function returned. In one patient with 100 days occlusion, function returned slowly and remained impaired.
Tumor emergence is sensed by self-specific CD44hi memory Tregs that create a dominant tolerogenic environment for tumors in mice
Authors: Guillaume Darrasse-Jèze, Anne-Sophie Bergot, Aurélie Durgeau, Fabienne Billiard, Benoît L. Salomon, José L. Cohen, Bertrand Bellier, Katrina Podsypanina, David Klatzmann
Journal: Journal of Clinical Investigation (2009)

Early responses of Tregs and effector T cells (Teffs) to their first encounter with tumor cells have been poorly characterized. Here we have shown, in both implanted and in situ–induced mouse tumor models, that the appearance of tumor cells is immediately sensed by CD44hi memory Tregs that are specific for self antigens. The rapid response of these Tregs preceded and prevented activation of naive antitumor Teffs. The relative speed of the Treg versus the Teff response within the first 2–4 days determined the outcome of the antitumor immune response: tolerance or rejection. If antitumor memory Teffs were present at the time of tumor emergence, both Tregs and Teffs were recruited and activated with memory kinetics; however, the Tregs were unable to control the Teffs, which eradicated the tumor cells. This balance between effector and regulatory responses did not depend on the number of Tregs and Teffs, but rather on their memory status. Thus, in the natural setting, dominant tolerogenic immunosurveillance by self-specific memory Tregs protects tumors, just as it protects normal tissues. More generally, our results reveal that the timing of Treg and Teff engagement, determined by their memory status, is an important mode of regulation of immune responses.
Endoscopy and small-bowel biopsy in celiac disease: indications and implications
Authors: K. Rostami, M. Danciu
Journal: Endoscopy (2007)

There is a need to clarify some issues with regard to the indications for endoscopy in the follow-up of patients with celiac disease [1]. To start with, we are not performing routine endoscopy in order to assess or monitor histological recovery in celiac disease. This practice is out of date and it belongs firmly in the last millenium. In 2001 we agreed that further endoscopies are not necessary in patients who show clinical improvement and who respond to a gluten-free diet [2] [3]. Endoscopy is indicated only when a patient is not doing well on a gluten-free diet or in patients who deteriorate despite treatment.
Heterodimeric IL-15 regulates the differentiation and survival of different populations of memory T cells and the balance of effector and regulatory cells
Authors: George N Pavlakis, Cristina Bergamaschi, Jinyao Li, Antonio Valentin, Stephanie Chen, Sinnie S Ng, Rachel E Kelly Beach, Jenifer Bear, Margherita Rosati, Candido Alicea, Raymond Sowder, Elena Chertova, Barbara K Felber
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts The common γ-chain cytokine interleukin-15 (IL-15) regulates immune homeostasis and the fate of many lymphocyte subsets, and holds potential in fighting infections and cancer. We have previously showed that co-expression of IL-15 and IL-15 Receptor alpha (IL-15Rα) in the same
Review and Notes: Cardiology: Sudden Cardiac Death
Authors: Stephen M. Ayres
Journal: Annals of Internal Medicine (1996)

Literature of Medicine1 July 1996Review and Notes: Cardiology: Sudden Cardiac DeathStephen M. Ayres, MDStephen M. Ayres, MDVirginia Commonwealth University, Richmond, VA 23298-0549Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-1-199607010-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail S Goldstein, A Bayes-de-Luna, and J Guindo-Soldevila; eds. 343 pages. Armonk, NY: Futura; 1994. $75.00. ISBN 0879935898. Order phone 800-877-8761.Despite the highly publicized sudden cardiac deaths of such celebrities as Russian dissident Andrei Sakharov and Baseball Commissioner Bart Giamatti, there has been little focused research into the cause of sudden cardiac death, and almost no media attention has been paid to this condition, which terminates life in more than 50% of persons with coronary artery disease. Sudden death has been known since antiquity, and this book's historical review of this condition—including the sudden deaths of Count Gaston de Foix ... Author, Article, and Disclosure InformationAuthors: Stephen M. Ayres, MDAffiliations: Virginia Commonwealth University, Richmond, VA 23298-0549 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1996Volume 125, Issue 1 Page: 80 Keywords Coronary arteries Drugs Ejection fraction Electrocardiography Ischemia Myocardial infarction Stable coronary artery disease Sudden cardiac death Thrombosis Ventricular fibrillation ePublished: 15 August 2000 Issue Published: 1 July 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Loss of Sinus Rhythm After Total Cavopulmonary Connection
Authors: Rae-Ellen W. Kavey, Winston E. Gaum, Craig J. Byrum, Frank C. Smith, Daniel A. Kveselis
Journal: Circulation (1995)

Background Total cavopulmonary connection (TCPC) to repair functional single ventricle involves the sinus node area, in contrast to the Fontan procedure. We compared ECG findings after TCPC and Fontan to evaluate the impact of the cavopulmonary connection on sinus rhythm postoperatively. Methods and Results The Fontan group consisted of 17 patients repaired at 7.8±3.1 years of age (mean±SD): 11 for tricuspid or pulmonary atresia (TA/PA) and 6 for single ventricle. The TCPC group consisted of 19 patients repaired at 5.1±3.2 years of age (mean±SD) ( P &lt;.001): 9 for TA/PA, 4 for single ventricle, and 6 for hypoplastic left heart syndrome. Mean follow-up after Fontan was 7.7±2.7 years versus 2.8±1.6 years for TCPC ( P &lt;.001). Preoperative ECGs on all TCPC patients showed sinus rhythm (SR), whereas 16 of 17 Fontan patients had SR and one had nonsinus atrial rhythm (NSAR) since birth. On the first postdischarge ECG, 12 of 19 TCPC patients (63%) were in SR, 4 were in junctional rhythm (JR), and 3 were in NSAR. In comparison, 15 of 17 Fontan patients (88%) were in SR with 1 of 17 in NSAR and 1 in supraventricular tachycardia ( P &lt;.05 with χ 2 test). By 2 years postoperatively, only 6 of 15 TCPC patients available for follow-up (40%) were in SR, with 7 of 15 in JR and 2 of 15 in NSAR. By contrast, 13 of 17 Fontan patients (76%) remained in SR, with 1 in NSAR and 3 in JR ( P &lt;.05 with χ 2 test). TCPC patients with loss of SR did not differ from other patients in the group in age at repair, preoperative diagnosis, or surgeon performing the procedure. Conclusions This significant incidence of loss of SR temporally related to surgery suggests that operative compromise of the sinus node area is common with TCPC.
Herbal medicine might be responsible for high incidence of urinary tract cancer
Authors: N. Hawkes
Journal: BMJ (2012)

Chinese herbal medicines containing extracts from Aristolochia plants might be responsible for the high incidence of urinary tract cancer in Taiwan, a study has suggested.

It adds to growing evidence that herbal preparations using Aristolochia (now banned in Europe) are extremely dangerous and, given the lifelong persistence of the DNA damage they cause, have created “an international public health problem of considerable magnitude,” say the authors of the study published in Proceedings of the National Academy of Sciences (doi/10.1073/pnas.1119920109).

In Taiwan there is a remarkably high incidence of upper urinary tract urothelial carcinoma (UUC), a condition diagnosed four times more often than it was in the early 1980s. Incidence, at nearly four cases per 10 000 people by 2007, is four times higher than in the US, where …
London is more likely to detain people with mental problems
Authors: Z. Kmietowicz
Journal: BMJ (2003)

People with mental health problems in London are being admitted to hospital unnecessarily, because haphazard and uncoordinated community services are unable to cope, says an independent health service watchdog.

The growth in community mental health services, which help people stay out of hospital, has been too slow in the capital, a new report released this week by the King's Fund, an independent health research body, says.

Inadequate community services—together with high case-loads and a shortage of some types of service, such …
Confidentiality of NIH Research-Project Records
Authors: William J. Curran
Journal: New England Journal of Medicine (1977)

Medical research in this country is predominantly supported by federal grants and contracts. The great fear of investigators is that the government will exact too high a price in regulation to make this research feasible and worthwhile.One major source of anxiety has been the possibility of forced invasion of the confidentiality of research-project records, including the data on individual subjects and patients, on order of the government funding agency or the courts. The National Institutes of Health, in their extramural grant programs, have had the right to examine research-project records, but have rarely exercised this authority. Now, in a . . .
Relation between Surgeons' Practice Volumes and Geographic Variation in the Rate of Carotid Endarterectomy
Authors: Lucian L. Leape, Rolla Edward Park, David H. Solomon, Mark R. Chassin, Jacqueline Kosecoff, Robert H. Brook
Journal: New England Journal of Medicine (1989)

We examined the relation between the number of operative procedures carried out by individual surgeons and the variation in the rate of carotid endarterectomy among Medicare beneficiaries in areas of high, average, and low use of the procedure in 1981. Rates ranged from 48 per 100,000 in the low-use area to 178 per 100,000 in the high-use area. Two variables accounted for most of the differences in the rates: the number of surgeons performing the procedure and the number of endarterectomies performed by surgeons with high practice volumes. Twice as many surgeons in the high-use area and 25 percent more in the average-use area performed carotid endarterectomy as compared with those in the low-use area. If the average number of cases per surgeon had been the same, the differences in the number of surgeons would have accounted for 36 percent and 15 percent, respectively, of the differences in use. Surgeons who performed 15 or more carotid endarterectomies during the year accounted for most of the variation in the rates. These high-volume surgeons represented 15 percent and 17 percent of the surgeons in the areas of high and average use, respectively, as compared with 4 percent of those in the low-use area. They accounted for 60 and 77 percent, respectively, of the additional endarterectomies. Three fourths of the surgeons performing carotid endarterectomies carried out fewer than 10, and 24 percent did only 1. We conclude that most of the geographic variation in the rate of carotid endarterectomy is caused by a few surgeons in high-use areas who perform large numbers of operations.
Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis
Authors: J. S. Ross, T. Tse, D. A. Zarin, H. Xu, L. Zhou, H. M. Krumholz
Journal: BMJ (2012)

<b>Objective</b> To review patterns of publication of clinical trials funded by US National Institutes of Health (NIH) in peer reviewed biomedical journals indexed by Medline. <b>Design </b>Cross sectional analysis. <b>Setting</b> Clinical trials funded by NIH and registered within ClinicalTrials.gov (clinicaltrials.gov), a trial registry and results database maintained by the US National Library of Medicine, after 30 September 2005 and updated as having been completed by 31 December 2008, allowing at least 30 months for publication after completion of the trial. <b>Main outcome measures</b> Publication and time to publication in the biomedical literature, as determined through Medline searches, the last of which was performed in June 2011. <b>Results</b> Among 635 clinical trials completed by 31 December 2008, 294 (46%) were published in a peer reviewed biomedical journal, indexed by Medline, within 30 months of trial completion. The median period of follow-up after trial completion was 51 months (25th-75th centiles 40-68 months), and 432 (68%) were published overall. Among published trials, the median time to publication was 23 months (14-36 months). Trials completed in either 2007 or 2008 were more likely to be published within 30 months of study completion compared with trials completed before 2007 (54% (196/366) <i>v</i> 36% (98/269); P&lt;0.001). <b>Conclusions</b> Despite recent improvement in timely publication, fewer than half of trials funded by NIH are published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion. Moreover, after a median of 51 months after trial completion, a third of trials remained unpublished.