tbuckley/cabot-search huggingface dataset:
Time to abolish "gold standard"
Authors: P F. Duggan
Journal: BMJ (1992)

the risk of an increase in tuberculosis related to HIV is small.2An audit of cases of tuberculosis (April 1990-March 1991) in Riverside Health Authority showed two problems with the current surveillance of HIV infection and tuberculosis based on notifi- cation data.Firstly, tuberculosis in HIV infected people is less likely to be notified than that in other people.In our study only four (40%) of 10 dual infections were notified; in contrast, 50 (74%) of 68 cases of tuberculosis in people not known to be infected with HIV were notified.Furthermore, HIV positive patients given antituberculous treat- ment without bacteriological evidence being sought were even less likely to be notified (one (18%) of six).Secondly, a rise in the number of cases of tuberculosis attributable to HIV infection may be masked by the high rates of, and changing trends in, notifications concerning people from the Indian subcontinent (India, Pakistan, Bangladesh)34 owing to the similar age ranges of the two groups of patients (mean ages in our study were 41 and 42 years).Ethnic group and country of origin are not recorded on notifications.Cooperation between the consultant in com- municable disease, microbiologists, and clinicians has corrected the problem of differential reporting from Riverside, and we recommend that other health authorities audit their cases of tuberculosis to ensure that the surveillance data are unbiased.Moreover, to measure the extent of dual infection we have begun locally to record ethnic group and country of origin for all cases of tuberculosis and recommend that other centres with a high preva- lence of HIV infection do likewise.
High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: Long-term follow-up
Authors: Lauren E. Abrey, Barrett H. Childs, Nina Paleologos, Lynne Kaminer, Steven Rosenfeld, Donna Salzman, Jonathan L. Finlay, Sharon Gardner, Kendra Peterson, Wendy Hu, Lode Swinnen, Robert Bayer, Peter Forsyth, Douglas Stewart, Anne M. Smith, David R. Macdonald, Susan Weaver, David A. Ramsay, Stephen D. Nimer, Lisa M. Deangelis, J. Gregory Cairncross
Journal: Neuro-Oncology (2006)

We previously reported a phase 2 trial of 69 patients with newly diagnosed anaplastic or aggressive oligodendroglioma who were treated with intensive procarbazine, CCNU (lomustine), and vincristine (PCV) followed by high-dose thiotepa with autologous stem cell rescue. This report summarizes the long-term follow-up of the cohort of 39 patients who received high-dose thiotepa with autologous stem cell support. Thirty-nine patients with a median age of 43 (range, 18-67) and a median KPS of 100 (range, 70-100) were treated. Surviving patients now have a median follow-up of 80.5 months (range, 44-142). The median progression-free survival is 78 months, and median overall survival has not been reached. Eighteen patients (46%) have relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with risk of relapse. Persistent nonenhancing tumor at transplant was identified in our initial report as a significant risk factor for relapse; however, long-term follow-up has not confirmed this finding. Long-term neurotoxicity has developed only in those patients whose disease relapsed and required additional therapy; no patient in continuous remission has developed a delayed neurologic injury. This treatment strategy affords long-term disease control to a subset of patients with newly diagnosed anaplastic oligodendroglioma without evidence of delayed neurotoxicity or myelodysplasia.
Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: From Structure to Functions
Authors: D Vaudry, B J Gonzalez, M Basille, L Yon, A Fournier, H Vaudry
Journal: Pharmacological Reviews (2000)

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was first isolated from ovine hypothalamic extracts on the basis of its ability to stimulate cAMP formation in anterior pituitary cells. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-glucagon-growth hormone releasing factor-secretin superfamily. The sequence of PACAP has been remarkably well conserved during the evolution from protochordate to mammals, suggesting that PACAP is involved in the regulation of important biological functions. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, and respiratory and urogenital tracts. Characterization of the PACAP precursor has revealed the existence of a PACAP-related peptide whose activity remains unknown. Two types of PACAP binding sites have been characterized. Type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP whereas type II binding sites have similar affinity for PACAP and VIP. Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes, the PACAP-specific PAC1 receptor, which is coupled to several transduction systems, and the two PACAP/VIP-indifferent VPAC1 and VPAC2 receptors, which are primarily coupled to adenylyl cyclase. PAC1 receptors are particularly abundant in the brain and pituitary and adrenal glands whereas VPAC receptors are expressed mainly in the lung, liver, and testis. The wide distribution of PACAP and PACAP receptors has led to an explosion of studies aimed at determining the pharmacological effects and biological functions of the peptide. This report reviews the current knowledge concerning the multiple actions of PACAP in the central nervous system and in various peripheral organs including the endocrine glands, the airways, and the cardiovascular and immune systems, as well as the different effects of PACAP on a number of tumor cell types.
Decreased Cancer Risk After Iron Reduction in Patients With Peripheral Arterial Disease: Results From a Randomized Trial
Authors: L. R. Zacharski, B. K. Chow, P. S. Howes, G. Shamayeva, J. A. Baron, R. L. Dalman, D. J. Malenka, C. K. Ozaki, P. W. Lavori
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundExcess iron has been implicated in cancer risk through increased iron-catalyzed free radical–mediated oxidative stress.
Sweet's syndrome and malignancy in the U.K.
Authors: J.F. BOURKE, S. KEOHANE, C.C. LONG, D. KEMMETT, M. DAVIES, I. ZAKI, R.A.C. GRAHAM-BROWN
Journal: British Journal of Dermatology (1997)

Acute febrile neutrophilic dermatosis (Sweet's syndrome) is reported to be a marker for underlying malignancy. Much of the evidence for this is based on case reports, small series of cases and reviews of the literature. In order to clarify the association with malignancy and determine the common clinical features of Sweet's syndrome, we reviewed the case notes of patients presenting to six dermatology units in the U.K. Eighty-seven cases of histologically proven Sweet's syndrome were reviewed. Fourteen patients (16%) developed associated malignancy, predominantly haematological, two patients (2%) had a history of previous malignancy and four patients (5%) had premalignant conditions (monoclonal gammopathy, two: myelodysplasia, two). Malignancy developed up to a year after presentation with Sweet's syndrome. Patients with associated malignancy were more likely to be anaemic (P < 0.01) at presentation, had a lower mean platelet count (207 x 10(9)/L vs. 332 x 10(9)/L; P < 0.003) and were, on average, older (59 years vs. 49 years; P = 0.002). Contrary to previous reports, a greater percentage of females developed malignancy than males.
Anti HMGB1 treatment reduces inflammation in models of experimental autoimmunity
Authors: P Lundbäck, L Klevenvall, L Ottosson, H Schierbeck, K Palmblad, U Andersson, H Erlandsson Harris
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> High mobility group box protein 1 (HMGB1) is a nuclear protein present in all cells. HMGB1 is passively released extracellularly during cell death and, similarly, HMGB1 can be actively secreted from activated cells. Extracellular HMGB1 mediates multiple inflammatory processes. High levels of extracellular HMGB1 have been demonstrated in synovial joints of arthritis patients, intraarticular injection of HMGB1 causes synovitis in mice and neutralisation of HMGB1 by peptide inhibitors or polyclonal antibodies ameliorates experimental arthritis. In this study, we investigated and compared the effects of an HMGB1 peptide inhibitor and a mouse monoclonal antibody (mAb) targeting HMGB1 in an experimental model of arthritis and in acute autoimmune hepatitis. Defining a mAb or peptide inhibitor with ameliorative effects will forward the development of HMGB1 blockade suitable for clinical trials. <h3>Methods</h3> Collagen induced arthritis (CIA) was induced in DBA/1 mice. Arthritis severity was evaluated by clinical grading of inflammation. Mice with established arthritis were treated every other day with mAb 2G7 or irrIgG and monitored for 7 days. Autoimmune hepatitis was induced by ConcavalinA injection in C57/bl6 mice pretreated with Abox, mAb 2G7 or PBS. After 8 h, sera and liver biopsies were collected. Serum ALT levels, along with HTX staining of liver biopsies were assessed. Liver myeloid peroxidase (MPO) were measured as an indication of neutrophil infiltration. Pro-inflammatory mediator levels were quantified by ELISA. HMGB1 levels were evaluated by ELISA and immunohistochemistry. <h3>Results</h3> mAb 2G7 treatment significantly ameliorated inflammation in CIA mice and also reduced destruction, as assessed by histological analysis. In mice with autoimmune hepatitis, we recorded an upregulated HMGB1 expression damaged liver lobules. Abox treatment minimised liver damage and mAb 2G7 reduced neutrophil infiltration. Reduced interferon γ and CXCL1 levels were demonstrated in both Abox and mAb 2G7 treated mice. <h3>Conclusion</h3> By these studies, we have for the first time defined a mAb targeting HMGB1 that effectively reduces inflammation and destruction during CIA. Beneficial effects of this mAb were also demonstrated in a model of autoimmune hepatitis. Furthermore, we could confirm the inhibitory effects of the peptide inhibitor A box, previously demonstrated in CIA, in experimental autoimmune hepatitis. Hence, our current work with humanisation of mAb 2G7 and assessements of its therapeutic effects can be performed in the autoimmune hepatitis model. This allows us to rapidly screen multiple humanised mAb clones and also avoids xenoreactivity effects. Hence, we have facilitated the development of HMGB1 blockade for clinical use.
Prognostic factors in restoration of pulmonary flow after submassive pulmonary embolism: a multiple regression analysis
Authors: R Menendez, D Nauffal, MJ Cremades
Journal: European Respiratory Journal (1998)

Defects as evaluated by lung perfusion scans may persist even 6 months after pulmonary embolism (PE), when treatment is withdrawn. The aim of this study was to evaluate the effect of several potential factors on the resolution of lung perfusion defects, both during the first days and at 6 months, when patients were discharged. In a retrospective follow-up cohort study we included 102 patients with PE, diagnosed lung from a ventilation/perfusion (V'/Q') scan, following Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria, together with a phlebographic study of lower extremities or angiography. Lung perfusion scan was performed at diagnosis, and in two follow-up evaluations, at 7-10 days and at 6 months. Potential factors studied were: age; sex; presence of underlying cardiac or pulmonary disease; venous insufficiency; alveolar-arterial pressure difference for oxygen; delay in diagnosis; abnormalities in electrocardiogram or chest radiograph; and the size of defects as shown in lung perfusion scans. All factors were studied with regards to the size of the defects at the two follow-up evaluations, through a univariate statistical analysis and two multiple stepwise regression analysis. Multivariate statistical analysis selected four factors: size of defects at diagnosis; prior cardiopulmonary disease; delay in diagnosis; and sex, as synergistic variables to predict defect size at 7-10 days. On the other hand, the defect size at 7-10 days was the only variable selected as a predictor of the size of defects at 6 months. Resolution of pulmonary defects during the first days after diagnosis of pulmonary embolism is influenced by the initial defect size, prior cardiopulmonary diseases and sex. The size of residual defects at 6 months depends mainly on the size of defects at 7-10 days.
Diagnosis of abdominal tuberculosis
Authors: P A Whitehouse
Journal: Journal of the Royal Society of Medicine (2004)

Mr Rai and Mr Thomas (December 2003 JRSM1) outline the difficulties in diagnosing abdominal tuberculosis and suggest that early laparoscopy may aid diagnosis and reduce time for it to be made. In their case series of 36 patients the mean duration of presenting complaint was 18 months. The diagnosis of abdominal TB should be in clinicians' minds even in the acute setting. Recently an Asian woman aged 18 was referred to the gynaecologists with right iliac fossa pain. She spoke little English and history-taking was difficult. She was anaemic and the white cell count and C-reactive protein were raised. The surgeons were then consulted, and diagnosed acute appendicitis. Under anaesthesia a mass could be felt arising from the pelvis on the right, and a low midline incision was made. The entire peritoneal cavity was caked with tuberculous nodules with a normal-looking appendix and ovaries. Unfortunately, the patient died in intensive care a few days later. On further questioning of relatives it was found that the patient had arrived in the UK only a fortnight previously, after her marriage to a UK citizen, and had been experiencing abdominal pain and other symptoms for the past three months. In this patient the diagnosis could have been made at laparoscopy, avoiding the laparotomy. More importantly the case highlights the need for thorough history-taking and inclusion of abdominal TB in the differential diagnosis.
Relation of HIV-I in bronchoalveolar lavage cells to abnormalities of lung function and to the presence of Pneumocystis pneumonia in HIV-I seropositive patients.
Authors: J R Clarke, I K Taylor, J Fleming, J D Williamson, D M Mitchell
Journal: Thorax (1993)

BACKGROUND--HIV is present in bronchoalveolar lavage cells of some but not all HIV seropositive patients. Abnormalities of lung function have been described in such patients in the absence of clinically overt pneumonia or other respiratory infections. It is possible that the presence of HIV in alveolar macrophages could account for these abnormalities. It is also possible that the presence of HIV in alveolar macrophages contributes to immunosuppression and an increased incidence of opportunistic infections. METHODS--This was a prospective study of 157 HIV seropositive patients requiring diagnostic bronchoscopy for investigation of new respiratory symptoms, chest radiograph abnormality, or pneumonic illness. Presence of HIV in bronchoalveolar lavage cells obtained at diagnostic bronchoscopy was determined by polymerase chain reaction to detect proviral DNA and in vitro cocultivation to detect productive virus infection. With these two techniques the presence or absence of HIV in bronchoalveolar lavage was compared with the presence of abnormalities of lung function or presence of Pneumocystis pneumonia. RESULTS--HIV was detected in bronchoalveolar lavage cells in 65% of patients by means of the polymerase chain reaction and 59% with cocultivation. With both methods of detection there was no association between the presence or absence of HIV and the presence of Pneumocystis pneumonia; nor was there a relation between the presence of HIV and abnormalities of lung function. CONCLUSION--The presence of HIV in bronchoalveolar lavage cells does not predispose to an increased incidence of Pneumocystis pneumonia; nor does it contribute to abnormalities of lung function.
Reporter-Based Isolation of Induced Pluripotent Stem Cell– and Embryonic Stem Cell–Derived Cardiac Progenitors Reveals Limited Gene Expression Variance
Authors: Linda W. van Laake, Li Qian, Paul Cheng, Yu Huang, Edward C. Hsiao, Bruce R. Conklin, Deepak Srivastava
Journal: Circulation Research (2010)

Rationale: Induced pluripotent stem (iPS) cells can differentiate into multiple cell types, including cardiomyocytes and have tremendous potential for drug discovery and regenerative therapies. However, it is unknown how much variability exists between differentiated lineages from independent iPS cell lines and, specifically, how similar iPS cell–derived cardiomyocytes (iPS-CMs) are to embryonic stem (ES) cell–derived cardiomyocytes (ES-CMs). Objective: We investigated how much variability exists between differentiated lineages from independent iPS cell lines and how similar iPS-CMs are to ES-CMs. Methods and Results: We generated mouse iPS cells in which expression of NKX2-5, an early cardiac transcription factor, was marked by transgenic green fluorescent protein (GFP). Isolation of iPS- and ES-derived NKX2-5–GFP + cardiac progenitor pools, marked by identical reporters, revealed unexpectedly high similarity in genome-wide mRNA expression levels. Furthermore, the variability between cardiac progenitors derived from independent iPS lines was minimal. The NKX2-5–GFP + iPS cells formed cardiomyocytes by numerous induction protocols and could survive upon transplantation into the infarcted mouse heart without formation of teratomas. Conclusions: Despite the line-to-line variability of gene expression in the undifferentiated state of ES and iPS cells, the variance narrows significantly in lineage-specific iPS-derived cardiac progenitors, and these progenitor cells can be isolated and used for transplantation without generation of unwanted cell types.
Nonobstructive left ventricular ejection pressure gradients in man.
Authors: A Pasipoularides, J P Murgo, J W Miller, W E Craig
Journal: Circulation Research (1987)

Simultaneous intraventricular pressure gradients and ejection flow patterns were measured by a multisensor catheter in 6 patients with normal left ventricular function and no valve abnormalities, at rest and in exercise. Peak measured intraventricular pressure gradients were attained very early in ejection, amounted to 6.7 +/- 1.9 (SD) mm Hg at rest, and were intensified to 13.0 +/- 2.3 mm Hg during submaximal supine bicycle exercise. The augmentation of the gradients during exercise was associated with a pronounced accentuation of the flow acceleration and flow at the instant of peak gradient. A peak flow, the intraventricular gradients amounted to 5.4 +/- 1.7 mm Hg at rest and 10.0 +/- 1.8 mm Hg during submaximal exercise. The exercise-induced enhancement of the measured intraventricular pressure difference at the time of peak flow was underlain by an accentuation of the peak flow itself. A semiempirical fluid dynamic model for ejection was applied to the pressure gradient and simultaneous outflow rate and acceleration data to identify the contributions by local and convective acceleration effects to the instantaneous intraventricular gradient values. The peak intraventricular pressure gradient, which is attained very early in ejection, is mostly accounted for by local acceleration effects (85 +/- 5% of the total). Conversely, at peak flow only convective acceleration effects are responsible for the measured pressure gradient. Thus, when inertial effects are augmented, as in exercise and other hyperdynamic states, the intrinsic component of the total left ventricular systolic load can be substantial, even with no outflow tract or valve abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Global Fund toughens stance against corruption
Authors: Lynn Eaton
Journal: BMJ (2005)

Richard Feachem of the Global Fund to Fight AIDS, Tuberculosis, and Malaria tells Lynn Eaton how the fund sees the enforcement of transparency and accountability as a vital step in ensuring results 

The recent decision by the Global Fund to Fight AIDS, Tuberculosis, and Malaria to suspend grants to Uganda on the grounds that the funds were misappropriated ( BMJ 2005;331: 475) feeds the common perception that corruption is more rife in African countries than elsewhere around the world.

Whether corruption is any worse in an African country than, say, in India or El Salvador, is open to debate. But how do aid agencies ensure that their funds are used for the purposes for which they are intended? And, from a medical viewpoint, what are the ramifications for public health if a funding organisation takes the difficult decision to suspend a grant?

Dr Richard Feachem, executive director of the fund, fully accepts the difficulty of what he described as the “life and death” decision they had to …
Potentiation of Cytotoxicity of Anticancer Agents by Several Different Polyene Antibiotics&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F Valeriote, G Medoff, J Dieckman
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Potentiation of Cytotoxicity of Anticancer Agents by Several Different Polyene Antibiotics Get access Fred Valeriote, Fred Valeriote 4 4Address reprint requests to Dr. Valeriote, Department of Experimental Therapeutics, Michigan Cancer Foundation, Meyer L. Prentis Cancer Center, 110 East Warren Ave., Detroit, Mich. 48201. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerald Medoff, Gerald Medoff Search for other works by this author on: Oxford Academic PubMed Google Scholar Julia Dieckman Julia Dieckman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 72, Issue 2, February 1984, Pages 435–439, https://doi.org/10.1093/jnci/72.2.435 Published: 01 February 1984 Article history Received: 16 June 1983 Accepted: 17 October 1983 Published: 01 February 1984
A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial
Authors: A. Davidson, A.-S. Veillard, A. Tognela, M.M.K. Chan, B.G.M. Hughes, M. Boyer, K. Briscoe, S. Begbie, E. Abdi, C. Crombie, J. Long, A. Boyce, C.R. Lewis, S. Varma, A. Broad, N. Muljadi, S. Chinchen, D. Espinoza, X. Coskinas, N. Pavlakis, M. Millward, M.R. Stockler, Brett Hughes, Michael Boyer, Karen Briscoe, Andrew Davidson, Stephen Begbie, Ehtesham Abdi, Catherine Crombie, Jeremy Long, Kevin Jasas, Craig Lewis, Adam Boyce, Suresh Vama, Adam Broad, Vy. Broaddge, David Gibbs, Robert Blum, Sue-Anne McLachlan, Andrew Haydon, Victoria Bray, Janette Vardy, Girish Mallesara, Ray Lowenthal, Ray Asghari, Susan Tiley, Theresa Hayes, Mohammed Islam, Steven Ackland, Jacqui Adams, Nick Pavlakis, Martin Stockler, Nick Muljadi, Xanthi Coskinas, Sarah Chinchen, Matthew Chan, Annette Tognela, Danielle Ferraro, Rasha Cosman
Journal: Annals of Oncology (2015)
Validation of the Experience with Allergic Rhinitis Nasal Spray Questionnaire (EARNS-Q): A Patient Reported Outcomes (PRO) Questionnaire to measure Experience and Preference with Nasal Sprays
Authors: B CRAWFORD, A DALAL, R STANFORD, M BAYLISS, J LIM, E PHILPOT
Journal: Journal of Allergy and Clinical Immunology (2008)