tbuckley/cabot-search huggingface dataset:
Pheochromocytoma of the Urinary Bladder
Authors: J. Ernest Lathem
Journal: JAMA (1966)

TWELVE previous cases of pheochromocytoma of the urinary bladder have been reported in English medical literature to our knowledge.<sup>1-10</sup>In most instances it has been mistaken for carcinoma of the bladder and a correct preoperative diagnosis has been unusual. The mortality of surgical procedures on undiagnosed pheochromocytomas in any location may reach 45%. With proper preparation and control during surgery, the mortality may be reduced to as low as 13%.<sup>11</sup> Most pheochromocytomas of the urinary bladder present many of the signs and symptoms of more common bladder tumors (Table 1). A history of headaches, especially when associated with voiding, and either sustained or intermittent hypertension are clues which must be thoroughly and completely evaluated before the possibility of pheochromocytoma can be excluded. The present case demonstrates that the clinical characteristics assume much greater importance when the lesion is located in the bladder than when the tumor is
Tumor necrosis factor and the acute metabolic response to tissue injury in man.
Authors: H F Starnes, R S Warren, M Jeevanandam, J L Gabrilove, W Larchian, H F Oettgen, M F Brennan
Journal: Journal of Clinical Investigation (1988)

Tumor necrosis factor (cachectin), a protein produced by monocytes and macrophages, has been implicated as an important mediator of the lethal effects of endotoxic shock and the cachexia of chronic infection. Recombinant human tumor necrosis factor alpha (rTNF) was given intravenously to patients as part of an antineoplastic trial. Fever, tachycardia, and at higher doses, hypotension occurred after a single injection of rTNF. Metabolic effects after rTNF administration were dose related and included enhanced energy expenditure with elevated CO2 production, increased whole body protein metabolism and peripheral amino acid efflux from the forearm, and decreased total arterial amino acid levels associated with a significant increase in plasma cortisol. Elevated serum triglycerides, as well as increased glycerol and free fatty acid turnover were seen, suggesting increased whole body lipolysis and fat utilization after rTNF. These findings indicate that administration of TNF in man reproduces many of the acute physiologic and metabolic responses to tissue injury, including energy substrate mobilization.
Role of atrial septostomy in the treatment of pulmonary vascular disease
Authors: R J BARST
Journal: Thorax (2000)

Fusidic acid is an antibiotic used in the treatment of staphylococcal infections. Niraparib is an anticancer drug indicated for the treatment of advanced ovarian cancer. The interaction between these two drugs has not been studied and is not referenced in drug databases. We present the case of a patient with pancytopenia who had been treated with fusidic acid and niraparib. No other treatment was taken by this patient. According to the literature, both substances can cause haematological toxicity. It seems unlikely that this is due to niraparib alone because it had been well tolerated by the patient for over a year before the pancytopenia was diagnosed. It was also perfectly well tolerated when it was reintroduced. We cannot determine whether this pancytopenia is due to fusidic acid alone or to a drug interaction between the two treatments. We therefore recommend caution in patients treated with this combination.
CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract
Authors: Jason M. Brenchley, Timothy W. Schacker, Laura E. Ruff, David A. Price, Jodie H. Taylor, Gregory J. Beilman, Phuong L. Nguyen, Alexander Khoruts, Matthew Larson, Ashley T. Haase, Daniel C. Douek
Journal: The Journal of Experimental Medicine (2004)

The mechanisms underlying CD4+ T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4+ and CD8+ T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4+ T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5+ CD4+ T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4+ T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4+ T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.
Nephrologist Caseload and Hemodialysis Patient Survival in an Urban Cohort
Authors: Kevin T. Harley, Elani Streja, Connie M. Rhee, Miklos Z. Molnar, Csaba P. Kovesdy, Alpesh N. Amin, Kamyar Kalantar-Zadeh
Journal: Journal of the American Society of Nephrology (2013)

Physician caseload may be a predictor of patient outcomes associated with various medical conditions and procedures, but the association between patient-physician ratio and mortality among patients undergoing hemodialysis has not been determined. We examined whether a higher patient-nephrologist ratio affects patient mortality risk using de-identified data from DaVita dialysis clinics and the U.S. Renal Data System. A total of 41 nephrologists with a caseload of 50-200 hemodialysis patients from an urban California region were retrospectively ranked according to their hemodialysis patient mortality rate during a 6-year period between 2001 and 2007. We calculated all-cause mortality hazard ratios for each nephrologist and compared patient- and provider-level characteristics between the 10 nephrologists with the highest patient mortality rates and the 10 nephrologists with the lowest patient mortality rates. Nephrologists with the lowest patient mortality rates had significantly lower patient caseloads than nephrologists with the highest mortality rates (median [interquartile range], 65 [55-76] versus 103 [78-144] patients per nephrologist, respectively; P<0.001). Additionally, patients treated by nephrologists with the lowest patient mortality rates received higher dialysis doses, had longer sessions, and received more kidney transplants. In demographic characteristic-adjusted analyses, each 50-patient increase in caseload was associated with a 2% increase in patient mortality risk (hazard ratio, 1.02; 95% confidence interval, 1.00 to 1.04; P<0.001). Hence, these results suggest that nephrologist caseload influences hemodialysis patient outcomes, and future research should focus on identifying the factors underlying this association.
Af17 Deficiency Increases Sodium Excretion and Decreases Blood Pressure
Authors: Lihe Chen, Hongyu Wu, Oleh M. Pochynyuk, Mary Rose Reisenauer, Zhijing Zhang, Le Huang, Oleg Leonidovych Zaika, Mykola Mamenko, Weiru Zhang, Qiaoling Zhou, Mingyao Liu, Yang Xia, Wenzheng Zhang
Journal: Journal of the American Society of Nephrology (2011)

The putative transcription factor AF17 upregulates the transcription of the epithelial sodium channel (ENaC) genes, but whether AF17 modulates sodium homeostasis and BP is unknown. Here, we generated Af17-deficient mice to determine whether deletion of Af17 leads to sodium wasting and low BP. Compared with wild-type mice, Af17-deficient mice had lower BP (11 mmHg), higher urine volume, and increased sodium excretion despite mildly increased plasma concentrations of aldosterone. Deletion of Af17 led to increased dimethylation of histone H3 K79 and reduced ENaC function. The attenuated function of ENaC resulted from decreased ENaC mRNA and protein expression, fewer active channels, lower open probability, and reduced effective activity. In contrast, inducing high levels of plasma aldosterone by a variety of methods completely compensated for Af17 deficiency with respect to sodium handling and BP. Taken together, these data identify Af17 as a potential locus for the maintenance of sodium and BP homeostasis and suggest that a particular histone modification is directly linked to these processes. Af17-mediated regulation of BP is largely, but not exclusively, the result of modulating ENaC, suggesting it has potential as a therapeutic target for the control of BP.
Angiopoietin-2 Levels Are Associated with Disease Progression in Metastatic Malignant Melanoma
Authors: Iris Helfrich, Lutz Edler, Antje Sucker, Markus Thomas, Sven Christian, Dirk Schadendorf, Hellmut G. Augustin
Journal: Clinical Cancer Research (2009)

The blood vessel-destabilizing Tie2 ligand angiopoietin-2 (Ang-2) acts in concert with the vascular endothelial growth factor/vascular endothelial growth factor receptor system to control vessel assembly during tumor progression. We hypothesized that circulating soluble Ang-2 (sAng-2) may be involved in melanoma progression.Serum samples (n=98) from melanoma patients (American Joint Committee on Cancer stages I-IV), biopsies of corresponding patients, and human melanoma cell lines were analyzed for expression of Ang-2 and S100beta. Multiple sera of a subcohort of 33 patients were tested during progression from stage III to IV. Small interfering RNA-based loss-of-function experiments were done to assess effects of Ang-2 on melanoma cells.Circulating levels of sAng-2 correlate with tumor progression in melanoma patients (P<0.0001) and patient survival (P=0.007). Analysis of serum samples during the transition from stage III to IV identified an increase of sAng-2 up to 400%. Comparative analyses revealed a 56% superiority of sAng-2 as predictive marker over the established marker S100beta. Immunohistochemistry and reverse transcription-PCR confirmed the prominent expression of Ang-2 by tumor-associated endothelial cells but identified Ang-2 also as a secreted product of melanoma cells themselves. Corresponding cellular experiments revealed that human melanoma-isolated tumor cells were Tie2 positive and that Ang-2 acted as an autocrine regulator of melanoma cell migration and invasion.The experiments establish sAng-2 as a biomarker of melanoma progression and metastasis correlating with tumor load and overall survival. The identification of an autocrine angiopoietin/Tie loop controlling melanoma migration and invasion warrants further functional experiments and validate the angiopoietin/Tie system as a promising therapeutic target for human melanomas.
Recent advances in the chemistry of parainfluenza‐1 (Sendai) virus inhibitors
Authors: Raffaele Saladino, Umberto Ciambecchini, Lucia Nencioni, Anna Teresa Palamara
Journal: Medicinal Research Reviews (2003)

Abstract Purine and pyrimidine derivatives, antioxidants, fusion inhibitors, statins, prostaglandins, antibiotic nucleosides, inhibitors of Ca 2+ homeostasis, carbohydrate derivatives, antisense polynucleotides and chimeras, are described as inhibitors of parainfluenza‐1 (Sendai) viral infections. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 4, 427–455, 2003
Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study
Authors: Jan A Burger, Michael J Keating, William G Wierda, Elena Hartmann, Julia Hoellenriegel, Nathalie Y Rosin, Iris de Weerdt, Ghayathri Jeyakumar, Alessandra Ferrajoli, Marylou Cardenas-Turanzas, Susan Lerner, Jeffrey L Jorgensen, Graciela M Nogueras-González, Gracy Zacharian, Xuelin Huang, Hagop Kantarjian, Naveen Garg, Andreas Rosenwald, Susan O'Brien
Journal: The Lancet Oncology (2014)
Sequential Therapy for 10 Days Versus Triple Therapy for 14 Days in the First-line Treatment of Helicobacter pylori Infection— A Multicenter, Open-label, Randomized Trial
Authors: Jyh-Ming Liou, Chieh-Chang Chen, Chi-Yang Chang, Jeng-Yi Wu, You-Jen Fang, Jing-Chung Luo, Yi-Chia Lee, Jaw-Town Lin, Ming-Shiang Wu
Journal: Clinical Gastroenterology and Hepatology (2013)
MicroRNAs Regulate Tumor Angiogenesis Modulated by Endothelial Progenitor Cells
Authors: Prue N. Plummer, Ruth Freeman, Ryan J. Taft, Jelena Vider, Michael Sax, Brittany A. Umer, Dingcheng Gao, Christopher Johns, John S. Mattick, Stephen D. Wilton, Vito Ferro, Nigel A.J. McMillan, Alexander Swarbrick, Vivek Mittal, Albert S. Mellick
Journal: Cancer Research (2012)

Abstract Bone marrow–derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow–mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth factor stimulation and show elevated expression in human high-grade breast tumor vasculature. Strikingly, targeting miR-10b and miR-196b led to significant defects in angiogenesis-mediated tumor growth in mice. Targeting these miRNAs may constitute a novel strategy for inhibiting tumor angiogenesis. Cancer Res; 73(1); 341–52. ©2012 AACR.
Ovariectomy increases the formation of prostanoids and modulates their role in acetylcholine-induced relaxation and nitric oxide release in the rat aorta
Authors: A. Martorell, A. Sagredo, R. Aras-Lopez, G. Balfagon, M. Ferrer
Journal: Cardiovascular Research (2009)

AimsThis study examines the effect of ovarian function on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF2α, and PGE2 release as well as the role of these substances in nitric oxide (NO) release and acetylcholine (ACh)-mediated relaxation.
Novel use of rituximab in hypersensitivity pneumonitis refractory to conventional treatment
Authors: Harpreet K Lota, Gregory J Keir, David M Hansell, Andrew G Nicholson, Toby M Maher, Athol U Wells, Elisabetta A Renzoni
Journal: Thorax (2013)

Hypersensitivity pneumonitis (HP) is treated by removal of the inciting antigen, if identified, and with corticosteroids and immunosuppressive agents in extensive or progressive disease. A minority of patients continue to decline and suffer outcomes comparable to idiopathic pulmonary fibrosis. Rituximab, a B cell depleting anti-CD20 antibody, has shown benefit in interstitial lung diseases (ILDs) associated with connective tissue diseases (CTDs).1–3 We report a novel use of rituximab in a case of HP refractory to conventional treatment.

A 57-year-old female never-smoker, with no previous medical history, presented with a 6-month history of progressive breathlessness and dry cough. Pulmonary function tests (PFTs) were impaired, with 26% of diffusing capacity for carbon monoxide (DLco) and 44% of forced vital capacity (FVC). A high-resolution CT (HRCT) showed changes suggestive …
The Retinal Vasculature as a Fractal: Methodology, Reliability, and Relationship to Blood Pressure
Authors: Gerald Liew, Jie Jin Wang, Ning Cheung, Yong Ping Zhang, Wynne Hsu, Mong Li Lee, Paul Mitchell, Gabriella Tikellis, Bronwen Taylor, Tien Yin Wong
Journal: Ophthalmology (2008)
Textbook of Lung Cancer. Second Edition
Authors: L.N.A. Willems
Journal: European Respiratory Journal (2009)

Edited by H. Hansen    Published by Informa Healthcare UK    Page: 342. Price: $229.92. ISBN: 978-0145385105

Textbook of Lung Cancer. Second Edition    This comprehensive textbook on lung cancer comprises 274 pages of text, excluding appendix and index, with tables and some figures. All the relevant aspects of lung cancer are dealt with, from aetiology to therapy, cost-effectiveness of therapy and the future of lung cancer. There are even two chapters on tobacco. As no cure can be …
Vaccine protection against<i>Staphylococcus aureus</i>pneumonia
Authors: Juliane Bubeck Wardenburg, Olaf Schneewind
Journal: The Journal of Experimental Medicine (2008)

Staphylococcus aureus pneumonia causes significant mortality in hospitalized or healthy individuals, and recent increases in morbidity are attributed to the rapid spread of methicillin-resistant S. aureus (MRSA) strains, which are often not susceptible to antibiotic therapy. α-Hemolysin (Hla), a secreted pore-forming toxin, is an essential virulence factor of MRSA in a mouse model of S. aureus pneumonia. We show that the level of Hla expression by independent S. aureus strains directly correlates with their virulence. Active immunization with a mutant form of Hla (HlaH35L), which cannot form pores, generates antigen-specific immunoglobulin G responses and affords protection against staphylococcal pneumonia. Moreover, transfer of Hla-specific antibodies protects naive animals against S. aureus challenge and prevents the injury of human lung epithelial cells during infection. Thus, Hla vaccination or immunotherapy may prevent S. aureus pneumonia in humans.
Supervised and Unsupervised Self-Testing for HIV in High- and Low-Risk Populations: A Systematic Review
Authors: Nitika Pant Pai, Jigyasa Sharma, Sushmita Shivkumar, Sabrina Pillay, Caroline Vadnais, Lawrence Joseph, Keertan Dheda, Rosanna W. Peeling
Journal: PLoS Medicine (2013)

Background Stigma, discrimination, lack of privacy, and long waiting times partly explain why six out of ten individuals living with HIV do not access facility-based testing. By circumventing these barriers, self-testing offers potential for more people to know their sero-status. Recent approval of an in-home HIV self test in the US has sparked self-testing initiatives, yet data on acceptability, feasibility, and linkages to care are limited. We systematically reviewed evidence on supervised (self-testing and counselling aided by a health care professional) and unsupervised (performed by self-tester with access to phone/internet counselling) self-testing strategies. Methods and Findings Seven databases (Medline [via PubMed], Biosis, PsycINFO, Cinahl, African Medicus, LILACS, and EMBASE) and conference abstracts of six major HIV/sexually transmitted infections conferences were searched from 1st January 2000–30th October 2012. 1,221 citations were identified and 21 studies included for review. Seven studies evaluated an unsupervised strategy and 14 evaluated a supervised strategy. For both strategies, data on acceptability (range: 74%–96%), preference (range: 61%–91%), and partner self-testing (range: 80%–97%) were high. A high specificity (range: 99.8%–100%) was observed for both strategies, while a lower sensitivity was reported in the unsupervised (range: 92.9%–100%; one study) versus supervised (range: 97.4%–97.9%; three studies) strategy. Regarding feasibility of linkage to counselling and care, 96% (n = 102/106) of individuals testing positive for HIV stated they would seek post-test counselling (unsupervised strategy, one study). No extreme adverse events were noted. The majority of data (n = 11,019/12,402 individuals, 89%) were from high-income settings and 71% (n = 15/21) of studies were cross-sectional in design, thus limiting our analysis. Conclusions Both supervised and unsupervised testing strategies were highly acceptable, preferred, and more likely to result in partner self-testing. However, no studies evaluated post-test linkage with counselling and treatment outcomes and reporting quality was poor. Thus, controlled trials of high quality from diverse settings are warranted to confirm and extend these findings. Please see later in the article for the Editors' Summary
Characterization of the Porphobilinogen Deaminase Deficiency in Acute Intermittent Porphyria
Authors: Peter M. Anderson, Raman M. Reddy, Karl E. Anderson, Robert J. Desnick
Journal: Journal of Clinical Investigation (1981)

The molecular pathology of the porphobilinogen (PBG)-deaminase deficiency in heterozygotes for acute intermittent porphyria (AIP) was investigated by means of biochemical and immunologic techniques. The stable enzyme-substrate intermediates (A, B, C, D, and E) of PBG-deaminase were separated by anion-exchange chromatography of erythrocyte lysates from heterozygotes for AIP and normal individuals. In normal lysates, the intermediates eluted in a characteristic pattern with decreasing amounts of activity (A > B > C > D > E), the combined A and B intermediates representing >75% of total recovered activity. In contrast, two different profiles were observed in lysates from heterozygotes for AIP. In most heterozygotes, the elution profile was similar to that of normal individuals, but each intermediate was reduced ∼50%. A second profile in which the C intermediate had disproportionately higher activity than the A or B intermediates was observed in asymptomatic heterozygotes with high urinary levels of PBG (>5 μg/ml) as well as in heterozygotes during acute attacks. These findings suggested that the C intermediate (the dipyrrole-enzyme intermediate) may be rate limiting in the stepwise conversion of the monopyrrole, PBG, to the linear tetrapyrrole, hydroxymethylbilane. To investigate further the nature of the enzymatic defect in AIP, sensitive immunotitration and immunoelectrophoretic assays were developed with the aid of a rabbit anti-human PBG-deaminase IgG preparation produced against the homogeneous enzyme. Equal amounts of erythrocyte lysate activity from 32 heterozygotes for AIP from 22 unrelated families and 35 normal individuals were immunoelectrophoresed. There were no detectable differences in the amounts of cross-reactive immunologic material (CRIM) in lysates from the normal individuals and 25 heterozygotes from 21 of the 22 unrelated families with AIP. In contrast, when equal enzymatic activities were coimmunoelectrophoresed, all seven heterozygotes from one family had ∼ 1.6 times the amount of CRIM compared with that detected in normal lysates. Consistent with these findings, immunotitration studies also demonstrated similar quantities of noncatalytic CRIM in lysates from this AIP family. When equal activities of the individual A, B, C, and D enzyme-substrate intermediates from normal and CRIM-positive erythrocytes were immunoelectrophoresed, increased amounts of immunoreactive protein were observed for each intermediate, B > A ≃ C ≃ D, from the CRIM-positive AIP variants. On the basis of these findings, it is hypothesized that the enzymatic defect in the CRIM-positive AIP family resulted from a mutation in the structural gene for PBG-deaminase which altered the catalytic as well as a substrate binding site. These studies of the enzymatic defect provide the first demonstration of genetic heterogeneity in AIP.