tbuckley/cabot-search huggingface dataset:
Bronchial colonisation in patients with lung cancer: a prospective study
Authors: Sophie Laroumagne, Benoît Lepage, Christophe Hermant, Gavin Plat, Michael Phelippeau, Laurence Bigay-Game, Stéphanie Lozano, Nicolas Guibert, Christine Segonds, Valérie Mallard, Nathalie Augustin, Alain Didier, Julien Mazieres
Journal: European Respiratory Journal (2012)

Bronchial colonisation is frequently reported in patients with lung cancer, and has a potential impact on therapeutic management and prognosis. We aimed to prospectively define the prevalence and nature of bronchial colonisation in patients at the time of diagnosing lung cancer. 210 consecutive patients with lung cancer underwent a flexible bronchoscopy for lung cancer. The type and frequency of bacterial, mycobacterial and fungal colonisation were analysed and correlated with the patients' and tumours' characteristics. Potential pathogens were found in 48.1% of samples: mainly the Gram-negative bacilli Escherichia coli (8.1%), Haemophilus influenzae (4.3%) and Enterobacter spp. (2.4%); Gram-positive cocci, Staphylococcus spp. (12.9%) and Streptococcus pneumoniae (3.3%); atypical mycobacteria (2.9%); Candida albicans (42.9%); and Aspergillus fumigatus (6.2%). Aged patients (p=0.02) with chronic obstructive pulmonary disease (p=0.008) were significantly more frequently colonised; however, tumour stage, atelectasis, bronchial stenosis and abnormalities of chest radiography were not associated with a higher rate of colonisation. Squamous cell carcinoma tended to be more frequently colonised than other histological subtypes. Airway colonisation was reported in almost half of patients presenting with lung cancer, mainly in fragile patients, and was significantly associated with worse survival (p=0.005). Analysing colonisation status of patients at the time of diagnosis may help improve the management of lung cancer.
Summary and agreement statement of the first International Conference on Concussion in Sport, Vienna 2001
Authors: M Aubry, R Cantu, J Dvorak, T Graf-Baumann, K Johnston, J Kelly, M Lovell, P McCrory, W Meeuwisse, P Schamasch
Journal: British Journal of Sports Medicine (2002)

Assessment and Research Centre (FIFA, F-MARC), and the International Olympic Committee Medical Commission (IOC).The aim of the symposium was to provide recommendations for the improvement of safety and health of athletes who suffer concussive injuries in ice hockey, football (soccer), and other sports.To this end a range of experts were invited to address specific issues of epidemiology, basic and clinical science, grading systems, cognitive assessment, new research methods, protective equipment, management, prevention, and long term outcome, and to discuss a unitary model for understanding concussive injury.At the conclusion of the conference, a small group of experts were given a mandate by the conference delegates and organising bodies to draft a document describing the agreement position reached by those in attendance at that meeting.For the purpose of this paper, this group will be called the Concussion in Sport Group (CISG).
Health campaigners condemn alcohol price cuts for prioritising business interests
Authors: M. Limb
Journal: BMJ (2015)

Health experts and campaigners have condemned new tax breaks for the alcohol industry in the UK government’s Budget as “shameful” and “perverse.”

Chancellor George Osborne declared a penny off the price of a pint, 2p off cider, a 2% cut in excise duty on Scotch whisky, and a freeze on wine duty in his Budget statement on 18 March.

Ian Gilmore, chair of the Alcohol Health Alliance UK, said that “prioritising” the interests of big business over public health was “disgraceful” and a “slap in the face” to doctors, nurses, and emergency services on the front line. The alliance is a group of more than 40 organisations including the Royal College of Physicians, Royal College of General Practitioners, the BMA, Alcohol Concern, and the Institute of Alcohol Studies.

Gilmore said that there were more than a million alcohol related …
Prion infectivity in variant Creutzfeldt-Jakob disease rectum
Authors: J D F Wadsworth, S Joiner, K Fox, J M Linehan, M Desbruslais, S Brandner, E A Asante, J Collinge
Journal: Gut (2006)

<b>Background:</b> Disease-related prion protein (PrP<sup>Sc</sup>) is readily detectable in lymphoreticular tissues in variant Creutzfeldt–Jakob disease (vCJD), but not in other forms of human prion disease. This distinctive pathogenesis, with the unknown population prevalence of asymptomatic vCJD infection, has led to significant concerns that secondary transmission of vCJD prions will occur through a wide range of surgical procedures. To date PrP<sup>Sc</sup>:prion infectivity ratios have not been determined in vCJD, and it is unknown whether vCJD prions are similar to experimental rodent prions, where PrP<sup>Sc</sup> concentration typically reflects infectious prion titre. <b>Aim:</b> To investigate prion infectivity in vCJD tissue containing barely detectable levels of PrP<sup>Sc</sup>. <b>Methods:</b> Transgenic mice expressing only human PrP (Tg(HuPrP129M<sup>+/+</sup><i>Prnp</i><sup>o/o</sup>)-35 and Tg(HuPrP129M<sup>+/+</sup><i>Prnp</i><sup>o/o</sup>)-45 mice) were inoculated with brain or rectal tissue from a previously characterised patient with vCJD. These tissues contain the maximum and minimum levels of detectable PrP<sup>Sc</sup> that have been observed in vCJD. <b>Results:</b> Efficient transmission of prion infection was observed in transgenic mice inoculated with vCJD rectal tissue containing PrP<sup>Sc</sup> at a concentration of 10<sup>4.7</sup>-fold lower than that in vCJD brain. <b>Conclusions:</b> These data confirm the potential risks for secondary transmission of vCJD prions via gastrointestinal procedures and support the use of PrP<sup>Sc</sup> as a quantitative marker of prion infectivity in vCJD tissues.
Abacavir-Lamivudine-Zidovudine vs Indinavir-Lamivudine-Zidovudine in Antiretroviral-Naive HIV-Infected Adults&lt;SUBTITLE&gt;A Randomized Equivalence Trial&lt;/SUBTITLE&gt;
Authors: Schlomo Staszewski
Journal: JAMA (2001)

HE CURRENT GOAL OF ANTIRETroviral therapy is to achieve prolonged suppression of human immunodeficiency virus (HIV) replication.The rational selection of antiretroviral agents used to initiate the treatment of HIV infection is critical for 2 reasons.First, the magnitude and duration of antiretroviral response is greatest for initial therapy, and second, sequencing of therapy must allow for effective second-line treatment regimens if the initial therapy fails.
microRNAs as Mediators of Drug Toxicity
Authors: Tsuyoshi Yokoi, Miki Nakajima
Journal: The Annual Review of Pharmacology and Toxicology (2012)

microRNAs (miRNAs) represent the most abundant class of gene expression regulators that bind complementarily to transcripts to repress their translation or mRNA degradation. These small ( 21 , 22 , 23 nucleotides in length) noncoding RNAs are derived through a multistep process by miRNA genes located in genomic DNA. Because miRNAs regulate fundamental cellular functions, their dysregulation affects a large range of physiological processes, such as development, immune responses, metabolism, and diseases as well as toxicological outcomes. Cancer-related miRNAs have been extensively studied; however, the roles of miRNAs in xenobiotic metabolism and in toxicology have only recently been explored. This review focuses on the current knowledge of miRNA-dependent regulation of drug-metabolizing enzymes and nuclear receptors and the associated potential toxicological implications. The potential modulation of toxicology-related changes in miRNA expression, the role of miRNA in immune-mediated drug-induced liver injuries, the use of circulating miRNAs in body fluids as potential toxicological biomarkers, and the link between miRNA-related pharmacogenomics and adverse drug reactions are highlighted.
Doctors’ leaders partly to blame for recruitment chaos, MPs told
Authors: Adrian O’Dowd
Journal: BMJ (2007)

Doctors’ leaders are partly to blame for the disruption caused by the chaotic recruitment system for junior doctors earlier this year, MPs have been told.

The pressure groups Remedy UK and Fidelio, which took up the cause of junior doctors and senior doctors, respectively, told the parliamentary health select committee that their own existence and success was evidence of failings of the medical profession’s leaders.

The committee questioned representatives from the two organisations as part of its inquiry into the Modernising Medical Careers (MMC) programme.

The committee chairman, Kevin Barron, Labour MP for Rother Valley, asked whether the leaders of the medical profession …
Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure
Authors: Milton Packer, Philip A. Poole-Wilson, Paul W. Armstrong, John G. F. Cleland, John D. Horowitz, Barry M. Massie, Lars Rydén, Kristian Thygesen, Barry F. Uretsky
Journal: Circulation (1999)

Background —Angiotensin-converting enzyme (ACE) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure. It is unclear, however, if low doses and high doses of ACE inhibitors have similar benefits. Methods and Results —We randomly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction ≤30% to double-blind treatment with either low doses (2.5 to 5.0 mg daily, n=1596) or high doses (32.5 to 35 mg daily, n=1568) of the ACE inhibitor, lisinopril, for 39 to 58 months, while background therapy for heart failure was continued. When compared with the low-dose group, patients in the high-dose group had a nonsignificant 8% lower risk of death ( P =0.128) but a significant 12% lower risk of death or hospitalization for any reason ( P =0.002) and 24% fewer hospitalizations for heart failure ( P =0.002). Dizziness and renal insufficiency was observed more frequently in the high-dose group, but the 2 groups were similar in the number of patients requiring discontinuation of the study medication. Conclusions —These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor (unless these are the only doses that can be tolerated) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor (if any) is likely to be very small.
Hemolysis of “stress” reticulocytes: a source of erythropoietic bilirubin formation
Authors: Stephen H. Robinson, Maria Tsong
Journal: Journal of Clinical Investigation (1970)

The formation of bilirubin-(14)C was measured in rats given transfusions of red blood cells containing (14)C-labeled hemoglobin heme. Per cent conversion of hemoglobin-(14)C to bilirubin was 4 times greater with transfusion of "stress" reticulocytes from rats responding to hemorrhage than with normal reticulocytes from unstimulated donors. When the increased number of labeled reticulocytes produced by hemorrhaged donors was also considered, the total magnitude of labeled bilirubin formation was almost 20 times higher with stress as compared to normal reticulocytes. The findings were not influenced by splenectomy of either donor or recipient rats, iron loading of donors, or bleeding of recipients. However, bilirubin-(14)C formation fell off progressively as studies were performed at longer intervals after erythroid stimulation. Total bilirubin-(14)C formation in rats transfused with stress reticulocytes was compared to the production of early-labeled bilirubin from all potential sources in intact rats bled according to the same schedule used in the transfusion experiments. It is estimated that degradation of hemoglobin from sress reticulocytes accounts for virtually the entire rise in erythropoietic bilirubin formation from 24 to 96 hr after glycine-2-(14)C administration, but that additional sources make a major contribution before that time. These findings are consistent with the concept that destruction of immature erythroid cells in the peripheral blood, and probably in the bone marrow, accompanies the physiologic response to erythroid stimulation.
Administration of Pentosan Polysulfate to Patients With Human Immunodeficiency Virus-Associated Kaposi's Sarcoma
Authors: J. M. Pluda, L. E. Shay, A. Foli, S. Tannenbaum, P. J. Cohen, B. R. Goldspiel, D. Adamo, M. R. Cooper, S. Broder, R. Yarchoan
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : Neovascularization induced by basic fibroblast growth factor (basic FGF) or FGF-like cytokines is thought to play a substantial role in the pathogenesis of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma. Pentosan polysulfate has been shown to inhibit basic FGF and FGF-like dependent tumor growth both in vitro and in vivo. Moreover, it has been found to inhibit the growth of Kaposi's sarcoma-derived spindle cells in vitro. These observations suggested that pentosan polysulfate might be worth exploring as a potential agent for the treatment of Kaposi's sarcoma. Purpose : The purpose of this phase I clinical trial was to determine the maximum tolerated dose of pentosan polysulfate in patients with HIV-associated Kaposi's sarcoma and whether or not this compound had activity against this neoplasm. Methods : Sixteen HIV-seropositive patients with Kaposi's sarcoma received pentosan polysulfate via continuous venous infusion for 3–6 weeks and then received a subcutaneous dose three times per week. Three different doses of pentosan polysulfate were administered: 2 mg/kg per day by infusion followed by 2 mg/kg per dose given subcutaneously (six patients), 3 mg/kg per day by infusion followed by 3 mg/kg per dose given subcutaneously (five patients), and 4 mg/kg per day by infusion followed by 4 mg/kg per dose given subcutaneously (five patients). Five of the 16 patients in the study also received injections of 1 mg of pentosan polysulfate into two different lesions two times a week for 3 weeks, followed by intralesional therapy once weekly. After receiving pentosan polysulfate for 6 weeks, patients were administered 100 mg zidovudine (AZT) orally every 4 hours in conjunction with pentosan polysulfate. Results : The maximally tolerated dose of pentosan polysulfate given by continuous venous infusion was found to be 3 mg/kg per day. No patient had an objective clinical antitumor response to either systemic or intralesional pentosan polysulfate administration; however, three patients had stable Kaposi's sarcoma for 3–27 weeks. No statistically significant effect on CD4 cells or serum HIV p24 antigen was noted during pentosan polysulfate administration. Dose-limiting toxic effects were characterized by anticoagulation and thrombocytopenia and were reversible. Conclusion : Pentosan polysulfate was well tolerated in this patient population. However, no objective tumor response or evidence of anti-HIV activity was noted; therefore, no claim of activity can be made in this trial. Implication : Continued investigation into the use of angiogenesis inhibitors with improved activity and toxicity profiles or different mechanisms of action is warranted. [J Natl Cancer Inst 85: 1585–1592, 1993]
Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial
Authors: Milagritos D Tapia, Samba O Sow, Kirsten E Lyke, Fadima Cheick Haidara, Fatoumata Diallo, Moussa Doumbia, Awa Traore, Flanon Coulibaly, Mamoudou Kodio, Uma Onwuchekwa, Marcelo B Sztein, Rezwanul Wahid, James D Campbell, Marie-Paule Kieny, Vasee Moorthy, Egeruan B Imoukhuede, Tommy Rampling, Francois Roman, Iris De Ryck, Abbie R Bellamy, Len Dally, Olivier Tshiani Mbaya, Aurélie Ploquin, Yan Zhou, Daphne A Stanley, Robert Bailer, Richard A Koup, Mario Roederer, Julie Ledgerwood, Adrian V S Hill, W Ripley Ballou, Nancy Sullivan, Barney Graham, Myron M Levine
Journal: The Lancet Infectious Diseases (2015)

The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo).
Phlebitis A Study of 979 Cases at the Boston City Hospital
Authors: John J. Byrne
Journal: JAMA (1960)

Pulmonary embolism continues to kill a large number of hospitalized patients. Until adequate prophylactic measures are available, reliance must be placed on early diagnosis and immediate treatment of clinically detectable phlebitis. This is particularly true for patients with heart disease, which is the most common and ominous condition predisposing to thromboembolism. Thrombophlebitis and phlebothrombosis are different clinical manifestations of the same pathological process and should be treated with equal vigor. Carefully planned surgical vein interruption proved superior to anticoagulant therapy at the Boston City Hospital, particularly in the chronic predisposing states such as cardiac disease or hemiplegia. Post-phlebitic symptoms such as edema, varicose veins, and ulcers occurred as frequently after anticoagulant treatment as after surgery and appeared related to the extent of the initial disease rather than its treatment.
Comparison of the efficacy of cicleosonide with budesonide in mild to moderate asthma patients after step-down therapy
Authors: Kuo-Chin Chiu, Jeng-Yuan Hsu, Ming-Shian Lin, Wen-Te Liu, Chun-Hua Wang, Han-Pin Kuo
Journal: European Respiratory Journal (2011)

Inhaled corticosteroids are the most widely used controller treatment for asthma, and is the stepping down level when asthma is controlled with combination therapy. Ciclesonide is an inhaled corticosteroid with on-site lung activation that provides anti-inflammatory activity. The aim of this study was to compare the efficacy of ciclesonide (CIC) with budesonide (BUD) in 142 adult patients with mild to moderate asthma who were well-controlled with a combination of inhaled corticosteroids and long-acting b2-agonist. They were randomized to receive once-daily ciclesonide 320mg (n=73) or twice-daily 2 inhalations of budesonide 200 mg (n=69) for 12 weeks. The forced expiratory volume in one second (FEV1), maximum midexpiratory flow (MMEF) and asthma control test (ACT) score were evaluated. Tolerability and ranked stratification of patient and physician were assessed. At the end of study, the withdrawal rate of CIC group (26.4%) was significantly less than that of BUD group (42.7%, p=0.02). There was no difference of FEV1 and MMEF throughout 12-week treatment period in CIC group. In BUD group, FEV1 decreased significantly at 4-week (1.8±0.1 L, n=59, p=0.0006) and 12-week of treatment (1.9±0.1 L, n=39, p=0.01) compared with baseline (2.0±0.1 L, n=69). MMEF decreased significantly at 4-, 8- and 12-week compared to baseline in BUD group. ACT score decreased significantly at 4-week of treatment in BUD group compared with baseline,. There was no difference of ACT score over the 12-week period in CIC group. In conclusion, cicleosonide was more effective and better drug adherence than budesonide in the stepping-down treatment of asthma from combination therapy.
Comparative radiographic features of community acquired Legionnaires' disease, pneumococcal pneumonia, mycoplasma pneumonia, and psittacosis.
Authors: J T Macfarlane, A C Miller, W H Roderick Smith, A H Morris, D H Rose
Journal: Thorax (1984)

The features of the chest radiographs of 49 adults with legionnaires9 disease were compared with those of 91 adults with pneumococcal pneumonia (31 of whom had bacteraemia or antigenaemia), 46 with mycoplasma pneumonia, and 10 with psittacosis pneumonia. No distinctive pattern was seen for any group. Homogeneous shadowing was more frequent in legionnaires9 disease (40/49 cases) (p less than 0.005), bacteraemic pneumococcal pneumonia (25/31) (p less than 0.01) and non-bacteraemic pneumococcal pneumonia (42/60) (p less than 0.05) than in mycoplasma pneumonia (23/46). Multilobe disease at presentation was commoner in bacteraemic pneumococcal pneumonia (20/31) than in non-bacteraemic pneumococcal pneumonia (15/60) (p less than 0.001) or legionnaires9 disease (19/49) (p less than 0.025). In bacteraemic pneumococcal pneumonia multilobe disease at presentation was associated with increased mortality. Pleural effusions and some degree of lung collapse were seen in all groups, although effusions were commoner in bacteraemic pneumococcal pneumonia. Cavitation was unusual. Lymphadenopathy occurred only in mycoplasma pneumonia (10/46). Radiographic deterioration was particularly a feature of legionnaires9 disease (30/46) and bacteraemic pneumococcal pneumonia (14/27), and these groups also showed slow radiographic resolution in survivors. Radiographic resolution was fastest with mycoplasma pneumonia; psittacosis and non-bacteraemic pneumococcal pneumonia cleared at an intermediate rate. Residual intrapulmonary streaky opacities remained in over a quarter of survivors from legionnaires9 disease (12/42) and bacteraemic pneumococcal pneumonia (5/19).
SPECIFIC HETEROLOGOUS ENHANCEMENT OF IMMUNE RESPONSES
Authors: Arnold S. Rubin, A. Bruce MacDonald, Albert H. Coons
Journal: The Journal of Experimental Medicine (1974)

The mixing of two histoincompatible human lymphocyte cell lines generated the release of a soluble factor which was capable of nonspecifically enhancing the in vitro immune response of normal mouse spleen cells against sheep erythrocytes. When active supernates were subjected to exclusion chromatography on Sephadex G-150 and BioGel P-150, the active principle eluted with molecules of approximately 35,000 mol wt. Column aliquots from similarly treated supernates from independent cultures of each lymphoid cell line were inactive. The human enhancing factor was concentrated and purified by ammonium sulfate fractionation, followed by Sephadex gel filtration and polyacrylamide gel electrophoresis.
Effect of cyclosporin A (CyA) on the immunopathological lesion of the labial minor salivary glands from patients with Sjogren's syndrome.
Authors: Y A Dalavanga, B Detrick, J J Hooks, A A Drosos, H M Moutsopoulos
Journal: Annals of the Rheumatic Diseases (1987)

Labial minor salivary gland biopsy specimens from 14 patients with Sjögren9s syndrome treated either with cyclosporin A (CyA) or placebo (5 mg/kg body weight day for six months) were studied to determine T lymphocyte subsets and HLA-DR antigen expression using the avidin-biotin-peroxidase technique. In all CyA treated patients we observed a decrease in the number of T lymphocytes and in the number of T helper cells, while the percentage of T suppressor cells and B cells was the same in both treated and untreated groups. It was also shown that the HLA-DR antigen expression on the epithelial cells was eliminated in the CyA treated patients. These findings suggest that the HLA-DR antigen expression on the epithelial cells is the result rather than the triggering factor of this T cell mediated process and is probably related to decreased lymphokine production by activated T lymphocytes.