tbuckley/cabot-search huggingface dataset:
Effect of Ganglion-Blocking Agents on Renin Release in Hypertensive Patients
Authors: YOSHIHIRO KANEKO, TADANAO TAKEDA, TAKAO IKEDA, HITOSHI TAGAWA, MASAO ISHII, YUTAKA TAKABATAKE, HIDEO UEDA
Journal: Circulation Research (1970)

In 18 patients with benign essential hypertension, renin release during reduction of arterial pressure due to sodium nitroprusside infusion was measured before and after administration of ganglion-blocking agents (pentolinium or trimethaphan). In 12 patients, renin release induced by reduction in pressure was significantly reduced but not abolished by ganglion blockade. Simultaneously, ganglion blockade significantly reduced renal vascular resistance (RVR) and almost abolished a decrease in renal blood flow (RBF) due to hypotension. In 6 other patients in whom no significant renin release resulted from hypotension, ganglion blockade caused little changes in renin release, RVR or RBF. The results support the hypothesis that renal sympathetic nerve activity is a factor in variations in renin release in patients with essential hypertension. Following ganglion blockade in the responsive patients, the significant reciprocal correlation between renal venous renin activity and sodium excretion rate shifted but still persisted, suggesting that the renin-releasing mechanism related to sodium excretion may be independent of innervation. On the other hand, the correlation between renin activity and the degree of reduction in pressure was insignificant after ganglion blockade. It is concluded that two intrarenal mechanisms, nerve-dependent and nerve-independent, are involved in renin release due to reduction in pressure. Ganglion blockade also exerted an inhibitory effect on renin release due to hypotension in 4 normotensive subjects and 5 patients with renovascular hypertension.
Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6
Authors: James C-H Yang, Lecia V Sequist, Sarayut Lucien Geater, Chun-Ming Tsai, Tony Shu Kam Mok, Martin Schuler, Nobuyuki Yamamoto, Chong-Jen Yu, Sai-Hong I Ou, Caicun Zhou, Daniel Massey, Victoria Zazulina, Yi-Long Wu
Journal: The Lancet Oncology (2015)
Is Prostate-Specific Antigen Velocity Useful in Early Detection of Prostate Cancer? A Critical Appraisal of the Evidence
Authors: R. D. Etzioni, D. P. Ankerst, N. S. Weiss, L. Y. T. Inoue, I. M. Thompson
Journal: JNCI Journal of the National Cancer Institute (2007)

Prostate-specific antigen velocity (PSAV) is one of the oldest concepts in PSA screening, yet today it is one of the most controversial. Publication of a wide range of studies with different designs, study populations, and results has fueled uncertainty about the best way to use PSAV and confused the issue of its utility in the early detection setting. Studies of disease prognosis suggest that PSAV is strongly associated with lethal cancers. However, prospective screening trials find that PSAV is at best a weak predictor of high-risk disease. In this commentary, we synthesize and reconcile the evidence about the value of PSAV in the early detection setting. We review recent studies of PSAV and determine a set of statistical considerations that we believe to be critical in study evaluation and interpretation. We explain why the association between PSAV and disease-specific survival does not necessarily imply that PSAV will be a useful screening tool. In addition, we argue that the standard concept of PSAV--the absolute change in PSA per year--confuses disease aggressiveness with the interval from disease onset to detection. We therefore recommend that other methods be explored to incorporate information about PSA kinetics that could ultimately improve--and even transform--how we detect and treat prostate cancer.
Cyclophosphamide-Using Nonmyeloablative Allogeneic Cell Therapy against Renal Cancer with a Reduced Risk of Graft-versus-Host Disease
Authors: Masatoshi Eto, Masahiko Harano, Katsunori Tatsugami, Mamoru Harada, Yoriyuki Kamiryo, Keijiro Kiyoshima, Masumitsu Hamaguchi, Masazumi Tsuneyoshi, Yasunobu Yoshikai, Seiji Naito
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Much attention has been paid to nonmyeloablative allogeneic stem cell transplantation for the treatment of renal cancer. We recently proposed a cyclophosphamide-using nonmyeloablative cell therapy in which donor lymphocyte infusion (DLI) was carried out after the tolerance induction to donor cells. In considering the clinical application of the cyclophosphamide-using cell therapy, attempts to reduce graft-versus-host disease (GVHD) are crucial. The aim of the present study was to modify the cyclophosphamide-using cell therapy to reduce the risk of GVHD while preserving the antitumor activity against renal cancer. Experimental Design: We assessed whether a delay in performing DLI from day 1 to day 5 after the cyclophosphamide treatment could reduce the risk of GVHD while preserving antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma, in the cyclophosphamide-using cell therapy. Results: Regarding the in vivo antitumor effect, there was no difference between DLI on day 1 and day 5 after the cyclophosphamide treatment, whereas the histologic findings of the small intestine showed that the cyclophosphamide-using cell therapy with DLI on day 5 decreased the risk of GVHD. In addition, the acquired immunity against RENCA was also observed in the RENCA-rejected mice that had been treated with DLI on day 5. Conclusions: Our results show that a delay in DLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate graft-versus-tumor effects from GVHD by reducing the risk of GVHD.
Wilms' Tumor Suppressor Gene WT1
Authors: CHRISTIAN MROWKA, ANDREAS SCHEDL
Journal: Journal of the American Society of Nephrology (2000)

Normal development of the kidney is a highly complex process that requires precise orchestration of proliferation, differentiation, and apoptosis. In the past few years, a number of genes that regulate these processes, and hence play pivotal roles in kidney development, have been identified. The Wilms' tumor suppressor gene WT1 has been shown to be one of these essential regulators of kidney development, and mutations in this gene result in the formation of tumors and developmental abnormalities such as the Denys-Drash and Frasier syndromes. A fascinating aspect of the WT1 gene is the multitude of isoforms produced from its genomic locus. In this review, our current understanding of the structural features of WT1, how they modulate the transcriptional and post-transcriptional activities of the protein, and how mutations affecting individual isoforms can lead to diseased kidneys is summarized. In addition, results from transgenic experiments, which have yielded important findings regarding the function of WT1 in vivo, are discussed. Finally, data on the unusual feature of RNA editing of WT1 transcripts are presented, and the relevance of RNA editing for the normal functioning of the WT1 protein in the kidney is discussed.
High-resolution ultrasonography of the first metatarsal phalangeal joint in gout: a controlled study
Authors: S. A Wright, E. Filippucci, C. McVeigh, A. Grey, M. McCarron, W. Grassi, G. D Wright, A. J Taggart
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To compare high-resolution ultrasound (HRUS) with conventional radiography in the detection of erosions in the first metatarsophalangeal joints (1st MTPJs) of patients with gout and to identify the characteristic sonographic features of gout. <b>Methods:</b> HRUS examination of the 1st MTPJs of both feet was performed by two independent sonographers. The presence of joint and soft-tissue pathology was recorded. <i>x</i> Ray examination of the feet was performed on the same day and reported by the same radiologist. <b>Results:</b> 39 male patients with gout and 22 age-matched control subjects (14 with an inflammatory arthropathy and 8 disease free) were studied. The agreement on erosion between HRUS and <i>x</i> ray was poor, κ = 0.229 (non-weighted), with McNemar's test being significant (p&lt;0.001) indicating a large number of false negative <i>x</i> rays. 22 MTPJs in patients with gout had never been subjected to a clinical attack of acute gout. In these MTPJs, there were 10 erosions detected by HRUS and 3 erosions on <i>x</i> ray. HRUS features significantly more prevalent in the patients with gout were hard and soft tophus-like lesions (p&lt;0.01) and the double contour sign (p&lt;0.01). <b>Conclusions:</b> These data show that HRUS may assist in the management of gout in two ways: first, by aiding in the diagnosis by identifying the sonographic features that may be representative of the disease, and, second, by allowing the early detection of erosive joint damage and/or tophaceous deposits even in clinically silent joints.
Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study
Authors: Lennart Hansson, Lars H Lindholm, Tord Ekbom, Björn Dahlöf, Jan Lanke, Bengt Scherstén, P-O Wester, Thomas Hedner, Ulf de Faire
Journal: The Lancet (1999)
Improving Survival From Sudden Cardiac Arrest
Authors: John P. Marenco, Paul J. Wang, Mark S. Link, Munther K. Homoud, N. A. Mark Estes III
Journal: JAMA (2001)

Sudden cardiac death is a major public health problem in the United States, and improving survival after out-of-hospital cardiac arrest has been the subject of intense study. Early defibrillation has been shown to be critical to improving survival. Use of automated external defibrillators (AEDs) has become an important component of emergency medical systems, and recent advances in AED technology have allowed expansion of AED use to nontraditional first responders and the lay public.To examine advancements in AED technology, review the impact of AEDs on time to defibrillation and survival, and explore the future role of AEDs in the effort to improve survival following sudden cardiac arrest.MEDLINE was searched for articles from 1966 through December 2000 (Medical Subject Headings: electric countershock, heart arrest, resuscitation, emergency medical services; keywords: automatic external defibrillator, automated external defibrillator, public access defibrillation). Reference lists of relevant articles, news releases, and product information from manufacturers were also reviewed.Initial MEDLINE search produced 4816 articles, from which 101 articles were selected for referencing based on having been published in a peer-reviewed journal and on relevance to the subject of the manuscript as determined by all 5 authors.All studies were critically reviewed for relevance, accuracy, and quality of data and study design by all authors.Recent advances in AED technology and design have resulted in marked simplification of AED operation, improvements in accuracy and effectiveness, and reductions in cost. Use of AEDs by first responders and laypersons has reduced time to defibrillation and improved survival from sudden cardiac arrest in several communities. Initial studies of the cost-effectiveness of AED use in comparison with other commonly used treatments are favorable.The AED represents an efficient method of delivering defibrillation to persons experiencing out-of-hospital cardiac arrest and its use by both traditional and nontraditional first responders appears to be safe and effective. The rapidly expanding role of AEDs in traditional emergency medical systems is supported by the literature, and initial studies of public access to defibrillation offer hope that further improvements in survival after sudden cardiac death can be achieved.
A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease
Authors: Krisztina B Gecse, Willem Bemelman, Michael A Kamm, Jaap Stoker, Reena Khanna, Siew C Ng, Julián Panés, Gert van Assche, Zhanju Liu, Ailsa Hart, Barrett G Levesque, Geert D'Haens
Journal: Gut (2014)

<h3>Objective</h3> To develop a consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn9s disease (pCD), based on best available evidence. <h3>Methods</h3> Based on a systematic literature review, statements were formed, discussed and approved in multiple rounds by the 20 working group participants. Consensus was defined as at least 80% agreement among voters. Evidence was assessed using the modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. <h3>Results</h3> Highest diagnostic accuracy can only be established if a combination of modalities is used. Drainage of sepsis is always first line therapy before initiating immunosuppressive treatment. Mucosal healing is the goal in the presence of proctitis. Whereas antibiotics and thiopurines have a role as adjunctive treatments in pCD, anti-tumour necrosis factor (anti-TNF) is the current gold standard. The efficacy of infliximab is best documented although adalimumab and certolizumab pegol are moderately effective. Oral tacrolimus could be used in patients failing anti-TNF therapy. Definite surgical repair is only of consideration in the absence of luminal inflammation. <h3>Conclusions</h3> Based on a multidisciplinary approach, items relevant for fistula management were identified and algorithms on diagnosis and treatment of pCD were developed.
Impact of Immune Parameters on Long-Term Survival in Metastatic Renal Cell Carcinoma
Authors: Frede Donskov, Hans von der Maase
Journal: Journal of Clinical Oncology (2006)

The purpose of this study was to evaluate the impact of immunologic prognostic factors in combination with established clinical prognostic factors in patients with metastatic renal cell carcinoma (mRCC).A total of 120 consecutive patients with mRCC received interleukin-2 (IL-2) -based immunotherapy. Baseline tumor biopsies were available from 85 of these patients. Potential prognostic factors were analyzed by univariate and multivariate analyses.Multivariate analysis (N = 120) identified high lactate dehydrogenase, lymph node metastases, low hemoglobin, low Karnofsky performance status, and bone metastases as independent poor prognostic clinical factors. The impact of these clinical factors has been demonstrated by others. Multivariate analysis (n = 85) also identified a high blood neutrophil count (> 6.0 x 10(9)/L; hazard ratio, 2.0; P = .015), the presence of intratumoral neutrophils (> 0 cells/mm2 tumor tissue; hazard ratio, 2.3; P = .001), and low intratumoral CD57+ natural killer cell count (< 50 cells/mm2 tumor tissue; hazard ratio, 2.1; P = .01) as independent poor prognostic immunologic factors. These three independent immunologic parameters had significant discriminatory power as supplemental risk factors in prognostic models based on the clinical risk factors, identifying subgroups within the favorable clinical group with estimated 5-year survival rates of 60%, 25%, and 0%, respectively. These findings were apparent in both our own prognostic model and in an extended Memorial Sloan-Kettering Cancer Center (New York, NY) prognostic model.This study points on five clinical and three supplemental immunologic independent prognostic factors of survival in patients with mRCC receiving IL-2.
Bone abnormalities and severe arthritis in pachydermoperiostosis.
Authors: R G Cooper, A J Freemont, M Riley, P J Holt, D C Anderson, M I Jayson
Journal: Annals of the Rheumatic Diseases (1992)

Two patients with pachydermoperiostosis were studied in whom the predominant features at presentation were severe and disabling knee and ankle joint pain in association with distal long bone pain. Analysis of synovial fluid from the knee joints showed non-inflammatory changes. In one patient a bicortical iliac crest bone biopsy specimen, taken after labelling with demeclocycline, showed appositional rates which were increased in cortical bone but reduced in trabecular bone. This mismatching resulted in trabecular osteoporosis, which occurred in association with increased numbers of osteoclasts, findings which suggest differential functional changes affecting the two bony envelopes.
Deployment and the Use of Mental Health Services among U.S. Army Wives
Authors: Alyssa J. Mansfield, Jay S. Kaufman, Stephen W. Marshall, Bradley N. Gaynes, Joseph P. Morrissey, Charles C. Engel
Journal: New England Journal of Medicine (2010)

Military operations in Iraq and Afghanistan have involved the frequent and extended deployment of military personnel, many of whom are married. The effect of deployment on mental health in military spouses is largely unstudied.We examined electronic medical-record data for outpatient care received between 2003 and 2006 by 250,626 wives of active-duty U.S. Army soldiers. After adjustment for the sociodemographic characteristics and the mental health history of the wives, as well as the number of deployments of the personnel, we compared mental health diagnoses according to the number of months of deployment in Operation Iraqi Freedom in the Iraq-Kuwait region and Operation Enduring Freedom in Afghanistan during the same period.The deployment of spouses and the length of deployment were associated with mental health diagnoses. In adjusted analyses, as compared with wives of personnel who were not deployed, women whose husbands were deployed for 1 to 11 months received more diagnoses of depressive disorders (27.4 excess cases per 1000 women; 95% confidence interval [CI], 22.4 to 32.3), sleep disorders (11.6 excess cases per 1000; 95% CI, 8.3 to 14.8), anxiety (15.7 excess cases per 1000; 95% CI, 11.8 to 19.6), and acute stress reaction and adjustment disorders (12.0 excess cases per 1000; 95% CI, 8.6 to 15.4). Deployment for more than 11 months was associated with 39.3 excess cases of depressive disorders (95% CI, 33.2 to 45.4), 23.5 excess cases of sleep disorders (95% CI, 19.4 to 27.6), 18.7 excess cases of anxiety (95% CI, 13.9 to 23.5), and 16.4 excess cases of acute stress reaction and adjustment disorders (95% CI, 12.2 to 20.6).Prolonged deployment was associated with more mental health diagnoses among U.S. Army wives, and these findings may have relevance for prevention and treatment efforts.
Role of bronchoscopy in diagnosis, treatment and follow-up of vascular anomalies: A multidisciplinary approach
Authors: Paola Serio, Valentina Fainardi, Roberto Leone, Denise Colosimo, Luigi Arcieri, Bruno Murzi, Marco Di Maurizio, Laura Grisotto, Annibale Biggeri, Roberto Baggi, Lorenzo Mirabile
Journal: European Respiratory Journal (2014)

Background .Vascular anomalies of aortic arch complex can cause compression of tracheobronchial tree and airway obstruction. While increasing evidence suggests the value of bronchoscopy in the diagnosis and during surgery to guide airway decompression, its role in managing residual symptoms after surgical correction is not well defined.

Aim .To assess the role of bronchoscopy in diagnosis, surgical treatment and follow-up of patients with vascular anomalies by multidisciplinar approach.

Design. Retrospective review of clinical records of children with endoscopic finding of vascular anomalies who required surgical correction.

Results .In 61 patients (34 M) evaluated by bronchoscopy a diagnosis of vascular compression obstructing airway lumen by 70% was made. Computed tomography with angiography (CTA) confirmed the type of vascular anomaly hypothesized in 95% of cases. The degree of agreement was evaluated by Kappa statistic (0.96). They underwent surgical correction under bronchoscopic control at median age of 8.7 months (0.2-184.7). Persistent and significant tracheo or bronchomalacia with residual symptoms required silicone (n 12) or metallic stent (n 5) insertion in 17 patients. All silicone stents were successfully removed; metallic stent were considered permanent. At last endoscopic examination (median follow-up 1.6 yrs, 0-8.1) adequate airway patency was described in 93% (n 57) of patients without residual symptoms.

Conclusions .Bronchoscopy can anticipate the specific type of vascular compression showing a very high degree of agreement with CTA, assist the surgeon in airway decompression and provide adequate treatment of patients in follow-up suffering persistent symptoms.
Changes in Basal Insulin Infusion Rates With Subcutaneous Insulin Infusion
Authors: Lutz Heinemann, Leszek Nosek, Christoph Kapitza, Matthias-Axel Schweitzer, Lars Krinelke
Journal: Diabetes Care (2009)

OBJECTIVE Evaluation of the time required until a change in the basal insulin infusion rate with an insulin pump induces subsequent changes in the metabolic effect. RESEARCH DESIGN AND METHODS In this euglycemic glucose clamp study, 10 male subjects with type 1 diabetes received three different subcutaneous insulin infusion rates (0.5, 1.0, and 2.0 units/h; for 4 h each) of insulin lispro (IL) with insulin pumps. RESULTS An increase in insulinemia occurred within 15-30 min after changing the infusion rate. While the serum IL levels reached a steady state at the end of the infusion period, the glucose infusion rates did not always reach steady-state levels with the higher infusion rates. However, an increase in the glucose consumption occurred within 30-60 min after switching the infusion rate. CONCLUSIONS Several hours are required until a new steady state in the metabolic effect is achieved after a significant change in basal insulin infusion.
Phosphoinositide 3-Kinase (PI3K) Pathway Alterations Are Associated with Histologic Subtypes and Are Predictive of Sensitivity to PI3K Inhibitors in Lung Cancer Preclinical Models
Authors: Jill M. Spoerke, Carol O'Brien, Ling Huw, Hartmut Koeppen, Jane Fridlyand, Rainer K. Brachmann, Peter M. Haverty, Ajay Pandita, Sankar Mohan, Deepak Sampath, Lori S. Friedman, Leanne Ross, Garret M. Hampton, Lukas C. Amler, David S. Shames, Mark R. Lackner
Journal: Clinical Cancer Research (2012)

Class 1 phosphatidylinositol 3-kinase (PI3K) plays a major role in cell proliferation and survival in a wide variety of human cancers. Here, we investigated biomarker strategies for PI3K pathway inhibitors in non-small-cell lung cancer (NSCLC).Molecular profiling for candidate PI3K predictive biomarkers was conducted on a collection of NSCLC tumor samples. Assays included comparative genomic hybridization, reverse-transcription polymerase chain reaction gene expression, mutation detection for PIK3CA and other oncogenes, PTEN immunohistochemistry, and FISH for PIK3CA copy number. In addition, a panel of NSCLC cell lines characterized for alterations in the PI3K pathway was screened with PI3K and dual PI3K/mTOR inhibitors to assess the preclinical predictive value of candidate biomarkers.PIK3CA amplification was detected in 37% of squamous tumors and 5% of adenocarcinomas, whereas PIK3CA mutations were found in 9% of squamous and 0% of adenocarcinomas. Total loss of PTEN immunostaining was found in 21% of squamous tumors and 4% of adenocarcinomas. Cell lines harboring pathway alterations (receptor tyrosine kinase activation, PI3K mutation or amplification, and PTEN loss) were exquisitely sensitive to the PI3K inhibitor GDC-0941. A dual PI3K/mTOR inhibitor had broader activity across the cell line panel and in tumor xenografts. The combination of GDC-0941 with paclitaxel, erlotinib, or a mitogen-activated protein-extracellular signal-regulated kinase inhibitor had greater effects on cell viability than PI3K inhibition alone.Candidate biomarkers for PI3K inhibitors have predictive value in preclinical models and show histology-specific alterations in primary tumors, suggesting that distinct biomarker strategies may be required in squamous compared with nonsquamous NSCLC patient populations.