tbuckley/cabot-search huggingface dataset:
Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study
Authors: Francesco Lapi, Laurent Azoulay, Hui Yin, Sharon J Nessim, Samy Suissa
Journal: BMJ (2013)

<b>Objectives</b> To assess whether a double therapy combination consisting of diuretics, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers with addition of non-steroidal anti-inflammatory drugs (NSAIDs) and the triple therapy combination of two of the aforementioned antihypertensive drugs to which NSAIDs are added are associated with an increased risk of acute kidney injury. <b>Design</b> Retrospective cohort study using nested case-control analysis. <b>Setting</b> General practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. <b>Participants</b> A cohort of 487 372 users of antihypertensive drugs. <b>Main outcome measures</b> Rate ratios with 95% confidence intervals of acute kidney injury associated with current use of double and triple therapy combinations of antihypertensive drugs with NSAIDs. <b>Results</b> During a mean follow-up of 5.9 (SD 3.4) years, 2215 cases of acute kidney injury were identified (incidence rate 7/10 000 person years). Overall, current use of a double therapy combination containing either diuretics or angiotensin converting enzyme inhibitors or angiotensin receptor blockers with NSAIDs was not associated with an increased rate of acute kidney injury. In contrast, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio 1.31, 95% confidence interval 1.12 to 1.53). In secondary analyses, the highest risk was observed in the first 30 days of use (rate ratio 1.82, 1.35 to 2.46). <b>Conclusions</b> A triple therapy combination consisting of diuretics with angiotensin converting enzyme inhibitors or angiotensin receptor blockers and NSAIDs was associated with an increased risk of acute kidney injury. The risk was greatest at the start of treatment. Although antihypertensive drugs have cardiovascular benefits, vigilance may be warranted when they are used concurrently with NSAIDs.
Molecular Basis of the Synergistic Antiangiogenic Activity of Bevacizumab and Mithramycin A
Authors: Zhiliang Jia, Jun Zhang, Daoyan Wei, Liwei Wang, Ping Yuan, Xiangdong Le, Qiang Li, James Yao, Keping Xie
Journal: Cancer Research (2007)

Abstract The impact of antiangiogenic therapy on the Sp1/vascular endothelial growth factor (VEGF) pathway and that of alteration of Sp1 signaling on the efficacy of antiangiogenic therapy is unclear, yet understanding their interactions has significant clinical implications. Treatment with bevacizumab, a neutralizing antibody against VEGF, suppressed human pancreatic cancer growth in nude mice. Gene expression analyses revealed that this treatment substantially up-regulated the expression of Sp1 and its downstream target genes, including VEGF and epidermal growth factor receptor, in tumor tissues, whereas it did not have this effect on pancreatic cancer cells in culture. Treatment with mithramycin A, an Sp1 inhibitor, suppressed the expression of Sp1 and its downstream target genes in both cell culture and tumors growing in nude mice. Combined treatment with bevacizumab and mithramycin A produced synergistic tumor suppression, which was consistent with suppression of the expression of Sp1 and its downstream target genes. Thus, treatment with bevacizumab may block VEGF function but activate the pathway of its expression via positive feedback. Given the fact that Sp1 is an important regulator of the expression of multiple angiogenic factors, bevacizumab-initiated up-regulation of Sp1 and subsequent overexpression of its downstream target genes may profoundly affect the potential angiogenic phenotype and effectiveness of antiangiogenic strategies for human pancreatic cancer. Therefore, this study is the first to show the significance and clinical implications of alteration of Sp1 signaling in antiangiogenic therapy for pancreatic cancer and other cancers. [Cancer Res 2007;67(10):4878–85]
Psychiatric Treatment in Primary Care Patients With Anxiety Disorders: A Comparison of Care Received From Primary Care Providers and Psychiatrists
Authors: Risa B. Weisberg, Ingrid Dyck, Larry Culpepper, Martin B. Keller
Journal: American Journal of Psychiatry (2007)

This study examined psychiatric treatment received by primary care patients with anxiety disorders and compared treatment received from primary care physicians and from psychiatrists.Primary care patients at 15 sites were screened for anxiety symptoms. Those screening positive were interviewed to assess for anxiety disorders. Information on psychiatric treatment received and provider of pharmacological treatment were collected.Of 539 primary care participants with at least one anxiety disorder, almost half (47.3%) were untreated. Nearly 21% were receiving medication only for psychiatric problems, 7.2% were receiving psychotherapy alone, and 24.5% were receiving both medication and psychotherapy. Patients receiving psychopharmacological treatment received similar medications, often at similar dosages, regardless of whether their prescriber was a primary care physician or a psychiatrist. One exception was that patients were less likely to be taking benzodiazepines if their provider was a primary care physician. Those receiving medications from a primary care provider were also less likely to be receiving psychotherapy. Overall, patients with more functional impairment, more severe symptoms, and comorbid major depression were more likely to receive mental health treatment. Members of racial/ethnic minority groups were less likely to be treated. Frequently endorsed reasons for not receiving pharmacological treatment were that the primary care physician did not recommend it and the patient did not believe in taking medication for emotional problems.Nearly half the primary care patients with anxiety disorders were not treated. However, when they were treated, the care received from primary care physicians and psychiatrists was relatively similar.
Some Theoretical Aspects of Quantification of Mitral Valve Regurgitation by the Indicator-Dilution Method
Authors: MILTON J. POLISSAR, ELLIOT RAPAPORT
Journal: Circulation Research (1961)

A theoretical analysis of indicator-dilution curves produced by a pulsatile, two-chamber mathematical model simulating a normal in vivo heart and one with atrioventricular valve regurgitation is presented. A set of difference equations is developed expressing the concentrations within the chambers at the end of each cycle in terms of the number of cycles or beats. It is shown theoretically that the downstroke slope of the dilution curve is insensitive to the extent of regurgitation. Solution of the difference equations for the parameters of the heart governing the curve (chamber volumes, forward output, and regurgitant flow), when the dilution curve is sampled from the chamber in which the injection is made, is achieved through a system of four equations in four unknowns. Sampling of the concentration curve from the chamber which does not receive the injection produces a theoretical curve giving three equations in four unknowns and results in an indeterminate solution. As a consequence, quantification of atrioventricular valve regurgitation through analysis of a single distal indicator-dilution curve following proximal injection cannot be accomplished.
A CASE OF TUMOUR OF THE CEREBRAL CORTEX
Authors: H. C. Barlow
Journal: BMJ (1902)

As to the colouring, most had brown hair and brown or grey eyes.Very few had dark hair, only two had red hair.Several were described as having fair hair, but brown and dark brown greatly predominated.The colour of the eyes was noted as either dark, brown, hazel, grey, and blue.Brown hair with hazel or grey eyes greatly predominated, so also does this type normally in the London area; the dark Iberian-Mediterranean type
Mutant Adenosine Deaminase 2 in a Polyarteritis Nodosa Vasculopathy
Authors: Paulina Navon Elkan, Sarah B. Pierce, Reeval Segel, Tom Walsh, Judith Barash, Shai Padeh, Abraham Zlotogorski, Yackov Berkun, Joseph J. Press, Masha Mukamel, Isabel Voth, Philip J. Hashkes, Liora Harel, Vered Hoffer, Eduard Ling, Fatos Yalcinkaya, Ozgur Kasapcopur, Ming K. Lee, Rachel E. Klevit, Paul Renbaum, Ariella Weinberg-Shukron, Elif F. Sener, Barbara Schormair, Sharon Zeligson, Dina Marek-Yagel, Tim M. Strom, Mordechai Shohat, Amihood Singer, Alan Rubinow, Elon Pras, Juliane Winkelmann, Mustafa Tekin, Yair Anikster, Mary-Claire King, Ephrat Levy-Lahad
Journal: New England Journal of Medicine (2014)

Polyarteritis nodosa is a systemic necrotizing vasculitis with a pathogenesis that is poorly understood. We identified six families with multiple cases of systemic and cutaneous polyarteritis nodosa, consistent with autosomal recessive inheritance. In most cases, onset of the disease occurred during childhood.We carried out exome sequencing in persons from multiply affected families of Georgian Jewish or German ancestry. We performed targeted sequencing in additional family members and in unrelated affected persons, 3 of Georgian Jewish ancestry and 14 of Turkish ancestry. Mutations were assessed by testing their effect on enzymatic activity in serum specimens from patients, analysis of protein structure, expression in mammalian cells, and biophysical analysis of purified protein.In all the families, vasculitis was caused by recessive mutations in CECR1, the gene encoding adenosine deaminase 2 (ADA2). All the Georgian Jewish patients were homozygous for a mutation encoding a Gly47Arg substitution, the German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations, and one Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations. In the endogamous Georgian Jewish population, the Gly47Arg carrier frequency was 0.102, which is consistent with the high prevalence of disease. The other mutations either were found in only one family member or patient or were extremely rare. ADA2 activity was significantly reduced in serum specimens from patients. Expression in human embryonic kidney 293T cells revealed low amounts of mutant secreted protein.Recessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression. (Funded by the Shaare Zedek Medical Center and others.).
Let's act on the best available evidence on obesity
Authors: J. L. Veerman
Journal: BMJ (2013)

Taubes argues that we “start anew” in obesity research.1 From a public health perspective, I have five reflections on his essay.

Firstly, he juxtaposes the energy balance against a failure of hormonal/metabolic regulation. However, the two are not mutually exclusive. Did previous generations of researchers really consider energy imbalance as the “cause” of obesity without thinking that other factors might influence …
Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study
Authors: RM du Bois, PM Greenhalgh, AM Southcott, NM Johnson, TA Harris
Journal: European Respiratory Journal (1999)

Pulmonary sarcoidosis is a disease in which the pathological processes are distributed along lymphatic pathways, particularly those around the bronchovascular bundles. Delivery of disease-modulating drugs by the inhaled route is therefore an attractive option. The aim of this study was to determine the efficacy of inhaled fluticasone propionate 2 mg x day(-1) in adults with stable pulmonary sarcoidosis. Forty-four adult patients (22 from each centre) were enrolled from outpatient clinics in two London teaching hospitals in a two centre, double-blind, randomized, placebo-controlled trial. Primary end points were home recordings of peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Secondary end points were symptom scores, use of rescue bronchodilator medication, and clinic values for PEFR, FEV1, FVC, forced mid-expiratory flow (FEF25-75%), diffusion capacity of the lung for carbon monoxide (DL,CO), and total lung capacity (TLC). Symptom scores of cough, breathlessness and wheeze were lower in the active treatment group, but this did not reach statistical significance, and a general health perception assessment (Short Form (SF)-36) showed a difference between active and placebo treatment. No significant differences were found between the two groups in any physiological outcome measure. No new adverse reactions were detected. The results of this pilot study do not show an objective benefit of inhaled fluticasone propionate in pulmonary sarcoidosis where the disease is stable and is controlled without the use of inhaled corticosteroids.
Metastasis Suppressors Regulate the Tumor Microenvironment by Blocking Recruitment of Prometastatic Tumor-Associated Macrophages
Authors: Casey Frankenberger, Daniel Rabe, Russell Bainer, Devipriya Sankarasharma, Kiran Chada, Thomas Krausz, Yoav Gilad, Lev Becker, Marsha Rich Rosner
Journal: Cancer Research (2015)

Abstract Triple-negative breast cancer (TNBC) patients have the highest risk of recurrence and metastasis. Because they cannot be treated with targeted therapies, and many do not respond to chemotherapy, they represent a clinically underserved group. TNBC is characterized by reduced expression of metastasis suppressors such as Raf kinase inhibitory protein (RKIP), which inhibits tumor invasiveness. Mechanisms by which metastasis suppressors alter tumor cells are well characterized; however, their ability to regulate the tumor microenvironment and the importance of such regulation to metastasis suppression are incompletely understood. Here, we use species-specific RNA sequencing to show that RKIP expression in tumors markedly reduces the number and metastatic potential of infiltrating tumor-associated macrophages (TAM). TAMs isolated from nonmetastatic RKIP+ tumors, relative to metastatic RKIP− tumors, exhibit a reduced ability to drive tumor cell invasion and decreased secretion of prometastatic factors, including PRGN, and shed TNFR2. RKIP regulates TAM recruitment by blocking HMGA2, resulting in reduced expression of numerous macrophage chemotactic factors, including CCL5. CCL5 overexpression in RKIP+ tumors restores recruitment of prometastatic TAMs and intravasation, whereas treatment with the CCL5 receptor antagonist Maraviroc reduces TAM infiltration. These results highlight the importance of RKIP as a regulator of TAM recruitment through chemokines such as CCL5. The clinical significance of these interactions is underscored by our demonstration that a signature comprised of RKIP signaling and prometastatic TAM factors strikingly separates TNBC patients based on survival outcome. Collectively, our findings identify TAMs as a previously unsuspected mechanism by which the metastasis-suppressor RKIP regulates tumor invasiveness, and further suggest that TNBC patients with decreased RKIP activity and increased TAM infiltration may respond to macrophage-based therapeutics. Cancer Res; 75(19); 4063–73. ©2015 AACR.
Complete Response to Neoadjuvant Chemoradiotherapy in Esophageal Carcinoma Is Associated With Significantly Improved Survival
Authors: Adam C. Berger, Jeffrey Farma, Walter J. Scott, Gary Freedman, Louis Weiner, Jonathan D. Cheng, Hao Wang, Melvyn Goldberg
Journal: Journal of Clinical Oncology (2005)

Purpose Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence. Patients and Methods All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. Results Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P &lt; .0001 and P &lt;.0002, respectively). Conclusion Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.
Quantitative relation between hemodynamic changes during intravenous adenosine infusion and the magnitude of coronary hyperemia
Authors: Rakesh K. Mishra, Sharmila Dorbala, Giridhar Logsetty, Alita Hassan, Therese Heinonen, Heinrich R. Schelbert, Marcelo F. Di Carli
Journal: Journal of the American College of Cardiology (2005)
Tumor cell anti-oxidant defenses. Inhibition of the glutathione redox cycle enhances macrophage-mediated cytolysis
Authors: CF Nathan, BA Arrick, HW Murray, NM DeSantis, ZA Cohm
Journal: The Journal of Experimental Medicine (1981)

The basis of resistance to oxidative injury was studied in six murine tumor cell lines that differed 54-fold in their resistance to enzymatically generated H(2)0(2). The tumors varied 56.7-fold in their specific activity of catalase, 5.3-fold in glutathione peroxidase (GPO), 3.3-fold in glutathione reductase (GR), and 2.7-fold in glutathione. There was no correlation among the levels of the three enzymes, and tumor cell resistance to lysis by H(2)0(2). However, the logarithm of the flux of H(2)0(2) necessary to cause 50 percent lysis of the tumor cells correlated with their content of glutathione (r = 0.91). The protective role of glutathione was analyzed by blocking GR and GPO, the catalysts of the glutathione redox cycle. This was facilitated by the demonstration that the anti-neoplastic agent 1,3-bis-(2- chloroethyl)-l-nitrosourea (BCNU) was a potent inhibitor of GR in intact tumor cells. BCNU inactivated tumor cell GR with a 50 percent inhibitory dose of 11 μM and a t(l/2) of inhibition of 30 s. Complete inhibition of GR was attained with no effect on GPO or catalase. Tumor cells whose GR was inactivated by BCNU could be lysed by fluxes of H(2)0(2) to which they were otherwise completely resistant. They could be killed by phorbol myristate acetate (PMA)-stimulated, bacilli Calmette-Guerin-activated macrophages in numbers which were otherwise insufficient, and by nonactivated macrophages, which otherwise were ineffective. BCNU-treated target cells were also much more sensitive to antibody-dependent, macrophage-mediated cytolysis. However, such tumor cells were no more sensitive than controls to lysis by alloreactive T cells or by antibody plus complement. Next, we deprived tumor cells of selenium by passage in selenium-deficient mice. GPO was inhibited 85 percent in such cells, with no effect on GR or catalase. Tumor cells with reduced GPO activity were markedly sensitized to lysis by small fluxes of H(2)0(2) or by PMA-stimulated macrophages or granulocytes. In contrast, inhibition of catalase with aminotriazole had no effect on the sensitivity of three tumors to peroxide-mediated lysis, and had modest effects with two others. Thus, the oxidation-reduction cycle of glutathione serves as one of the major defense mechanisms of tumor cells against three related forms of oxidant injury: lysis by fluxes of H(2)0(2), by PMA-triggered macrophages, and by macrophages in the presence of anti-tumor antibody.
Heat Shock Proteins and Their Use as Anticancer Vaccines
Authors: Giorgio Parmiani, Alessandro Testori, Michele Maio, Chiara Castelli, Licia Rivoltini, Lorenzo Pilla, Filiberto Belli, Vincenzo Mazzaferro, Jorgelina Coppa, Roberto Patuzzo, Mario R. Sertoli, Axel Hoos, Pramod K. Srivastava, Mario Santinami
Journal: Clinical Cancer Research (2004)

Despite the improvement in the outcome of anticancer therapy achieved during the last few years, several metastatic tumors remain resistant to therapy. This is particularly true for metastatic melanoma, renal and lung carcinoma, and, although to a lesser extent, for colorectal carcinoma. For these
Advocating for the woman with breast cancer
Authors: P. A. Ganz
Journal: CA A Cancer Journal for Clinicians (1995)

Health care workers and breast cancer survivors have an important role to play as advocates for breast cancer patients. At the most basic level, advocates must ensure that the patient has access to medical care. In addition they must help to ensure that the quality of care is optimal, enhancing the likelihood of survival, rehabilitation, and psychological adaptation. This article describes important advocacy issues for women with breast cancer, including informational needs, patient-physician communication, choice of primary surgical treatment, reconstructive surgery, adjuvant therapy, psychosocial issues, and employment and insurance problems.
Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007
Authors: Jeff Bronstein, Paul Carvey, Honglei Chen, Deborah Cory-Slechta, Donato DiMonte, John Duda, Paul English, Samuel Goldman, Stephen Grate, Johnni Hansen, Jane Hoppin, Sarah Jewell, Freya Kamel, Walter Koroshetz, James W. Langston, Giancarlo Logroscino, Lorene Nelson, Bernard Ravina, Walter Rocca, George W. Ross, Ted Schettler, Michael Schwarzschild, Bill Scott, Richard Seegal, Andrew Singleton, Kyle Steenland, Caroline M. Tanner, Stephen Van Den Eeden, Marc Weisskopf
Journal: Environmental Health Perspectives (2008)

BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk.MethodsIn June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD.ResultsWe describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs.ConclusionsPD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for &lt; 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.
Cancer Cell Metabolism: There Is No ROS for the Weary
Authors: Chi V. Dang
Journal: Cancer Discovery (2012)

Abstract Using a high-throughput short-hairpin RNA library screen targeting 222 metabolic nodes, Ros and colleagues identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4), a glycolytic enzyme that shunts glucose into the pentose phosphate pathway for NADPH production, as a critical node for the survival of prostate cancer cells. Blocking PFKFB4 induces reactive oxygen species and cancer cell death, suggesting that PFKFB4 could be therapeutically targeted. Cancer Discov; 2(4); 304–7. ©2012 AACR. Commentary on Ros et al., p. 328.