tbuckley/cabot-search huggingface dataset:
Association between bronchiectasis and smoking in patients with rheumatoid arthritis
Authors: V V Kaushik
Journal: Annals of the Rheumatic Diseases (2004)

There is a well recognised association between rheumatoid arthritis (RA) and bronchiectasis.Walker observed a 10fold increased prevalence of bronchiectasis in RA. 1 The increased incidence of pulmonary disease in his study could not be explained by the greater susceptibility to infection by patients with RA because the symptoms of bronchiectasis preceded those of arthritis in the majority of the cases.Earlier reports found the prevalence of bronchiectasis in RA to be between 1 and 10%. 1 However, with the advent of high resolution computed tomography (HRCT) of the lung, later studies reported a prevalence of 25-30%. 2 3 This is important as HRCT is a more sensitive method of detecting bronchiectasis, and it is generally accepted that a chest radiograph may be normal in patients with bronchiectasis.Secondly, later studies investigated principally lifelong non-smoking patients with RA as opposed to the earlier studies, which investigated patients with RA irrespective of their smoking history.Cigarette smoking, particularly heavy cigarette smoking, is associated with the development of seropositive RA. 4 Likewise, it has been suggested that bronchiectasis may be a trigger for the development of RA. 5 To determine if these two potential risk factors for the development of RA are distinct we used HRCT to study patients with RA to determine if there are differences in the prevalence of smoking in patients with RA and bronchiectasis.
Intramural hemorrhage and endothelial changes in atherosclerotic coronary artery after repetitive episodes of spasm in x-ray-irradiated hypercholesterolemic pigs.
Authors: K Nagasawa, H Tomoike, Y Hayashi, A Yamada, T Yamamoto, M Nakamura
Journal: Circulation Research (1989)

To assess whether coronary spasm affects the progression of atherosclerosis and results in evolution of myocardial infarction, the role of coronary spasm on the fine structure of conduit coronary arteries was studied morphologically. Göttingen miniature pigs were fed a semisynthetic diet containing 2% cholesterol and 1.1% sodium cholate. One month after being on this diet, the pigs were anesthetized and the endothelium of a branch of the left coronary artery was denuded using a balloon catheter. X-ray irradiation in a dose of 1,500 rad was given twice selectively to the area denuded, after 4 and 5 months of cholesterol feeding. Five months after endothelial denudation, transient (group A) and repetitive episodes (group B) of coronary spasm were provoked by single and periodic (five times every 5 minutes) intracoronary injections of serotonin (10 micrograms/kg/injection), respectively. The extent of spasm by serotonin at the previously denuded site was 84 +/- 4% (n = 4) and 90 +/- 5% (n = 6) narrowing in groups A and B (p = NS between groups), respectively. Forty minutes after the final administration of serotonin, the left coronary artery was relaxed by nitroglycerin, and the heart was isolated and perfuse-fixed under physiological pressure. Intramural hemorrhage was noted at the spastic site in six pigs of group B but not in group A. The average percent luminal narrowing, on cross sections at the spastic site in group B, was significantly greater than in group A (56 +/- 7% vs. 23 +/- 5%, p less than 0.01). Scanning electron micrographs revealed that the endothelial lining was intact at the nonspastic site in both groups. In addition to the appearance of intercellular bridges at the spastic site in both groups, squeezing of endothelial cells and adhesion of white blood cells were present at the spastic site exclusively in group B. These findings are consistent with the hypothesis that repetitive spasm may have an important role in the progression of atherosclerosis and/or myocardial infarction.
HIV/AIDS in developing countries
Authors: J. Sachs
Journal: Journal of the Royal Society of Medicine (2002)

The personal views of Mr Loefler (October 2002 JRSM1) are at odds with those of the WHO and inter alia the last two International AIDS Conferences where the rolling out of treatment for HIV/AIDS in developing countries was high on the agenda. The issue is not only one of a basic human right for the recipient, whether they be in developed or developing countries, but also of helping prevent the spread of HIV/AIDS. His experiences in Nairobi, Kenya, do not necessarily speak for the rest of Africa or possibly elsewhere outside his domain in Kenya.

Here in South Africa, the Government has now accepted that a coordinated countrywide response is necessary to confront the spread of HIV/AIDS. Its National Strategic Plan 2000-2005 embraces the five thrusts of the WHO—treatment, care and attention; research, evaluation and monitoring; prevention; ethical and human rights considerations; and communication and education. The treatment component includes the use of antiretrovirals. Several successful interventions with antiretrovirals as part of holistic thrusts within and outside reproductive health have been reported, not only here in South Africa but throughout developing countries in Africa and other parts of the world.

The spread of HIV/AIDS is reaching epidemic proportions in South-east Asia, India, China and some areas of Central and Eastern Europe, fuelled by prejudices of the kind expressed by Mr Loefler. Notably two developing countries, which had embarked on coordinated responses, have managed to contain their countries' epidemics—i.e. Brazil and Thailand. Now here in South Africa as well as in Brazil it was the ground-swell from rural and urban communities, labour and other grass-roots levels that positively influenced the national response.
Epidermal EGFR Controls Cutaneous Host Defense and Prevents Inflammation
Authors: Beate M. Lichtenberger, Peter A. Gerber, Martin Holcmann, Bettina A. Buhren, Nicole Amberg, Viktoria Smolle, Holger Schrumpf, Edwin Boelke, Parinaz Ansari, Colin Mackenzie, Andreas Wollenberg, Andreas Kislat, Jens W. Fischer, Katharina Röck, Jürgen Harder, Jens M. Schröder, Bernhard Homey, Maria Sibilia
Journal: Science Translational Medicine (2013)

The epidermal growth factor receptor (EGFR) plays an important role in tissue homeostasis and tumor progression. However, cancer patients treated with EGFR inhibitors (EGFRIs) frequently develop acneiform skin toxicities, which are a strong predictor of a patient's treatment response. We show that the early inflammatory infiltrate of the skin rash induced by EGFRI is dominated by dendritic cells, macrophages, granulocytes, mast cells, and T cells. EGFRIs induce the expression of chemokines (CCL2, CCL5, CCL27, and CXCL14) in epidermal keratinocytes and impair the production of antimicrobial peptides and skin barrier proteins. Correspondingly, EGFRI-treated keratinocytes facilitate lymphocyte recruitment but show a considerably reduced cytotoxic activity against Staphylococcus aureus. Mice lacking epidermal EGFR (EGFR(Δep)) show a similar phenotype, which is accompanied by chemokine-driven skin inflammation, hair follicle degeneration, decreased host defense, and deficient skin barrier function, as well as early lethality. Skin toxicities were not ameliorated in a Rag2-, MyD88-, and CCL2-deficient background or in mice lacking epidermal Langerhans cells. The skin phenotype was also not rescued in a hairless (hr/hr) background, demonstrating that skin inflammation is not induced by hair follicle degeneration. Treatment with mast cell inhibitors reduced the immigration of T cells, suggesting that mast cells play a role in the EGFRI-mediated skin pathology. Our findings demonstrate that EGFR signaling in keratinocytes regulates key factors involved in skin inflammation, barrier function, and innate host defense, providing insights into the mechanisms underlying EGFRI-induced skin pathologies.
Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system
Authors: K. Öberg, L. Kvols, M. Caplin, G. Delle Fave, W. de Herder, G. Rindi, P. Ruszniewski, E.A. Woltering, B. Wiedenmann
Journal: Annals of Oncology (2004)
Neoadjuvant Chemotherapy With High-Dose Ifosfamide, High-Dose Methotrexate, Cisplatin, and Doxorubicin for Patients With Localized Osteosarcoma of the Extremity: A Joint Study by the Italian and Scandinavian Sarcoma Groups
Authors: Stefano Ferrari, Sigbjorn Smeland, Mario Mercuri, Franco Bertoni, Alessandra Longhi, Pietro Ruggieri, Thor A. Alvegard, Piero Picci, Rodolfo Capanna, Gabriella Bernini, Cristoph Müller, Amelia Tienghi, Thomas Wiebe, Alessandro Comandone, Tom Böhling, Adalberto Brach Del Prever, Otte Brosjö, Gaetano Bacci, Gunnar Sæter
Journal: Journal of Clinical Oncology (2005)

To explore the effect of high-dose ifosfamide in first-line treatment for patients < or = 40 years of age with nonmetastatic osteosarcoma of the extremity.From March 1997 to September 2000, 182 patients were evaluated. Primary treatment consisted of two blocks of high-dose ifosfamide (15 g/m2), methotrexate (12 g/m2), cisplatin (120 mg/m2), and doxorubicin (75 mg/m2). Postoperatively, patients received two cycles of doxorubicin (90 mg/m2), and three cycles each of high-dose ifosfamide, methotrexate, and cisplatin (120 to 150 mg/m2). Granulocyte colony-stimulating factor support was mandatory after the high-dose ifosfamide/cisplatin/doxorubicin combination.No disease progression was recorded during primary chemotherapy, 164 patients (92%) underwent limb-salvage surgery, four patients (2%) underwent rotation plasty, and 11 patients (6%) had limbs amputated. Three (1.6%) patients died as a result of treatment-related toxicity, and one died as a result of pulmonary embolism after pathologic fracture. Grade 4 neutropenia and thrombocytopenia followed 52% and 31% of all courses, respectively, and mild to severe nephrotoxicity was recorded in 19 patients (10%). The median received dose-intensity compared with protocol was 0.82. With a median follow-up of 55 months, the 5-year probability of event-free survival was 64% (95% CI, 57% to 71%) and overall survival was 77% (95% CI, 67% to 81%), whereas seven patients (4%) experienced local recurrence.The addition of high-dose ifosfamide to methotrexate, cisplatin, and doxorubicin in the preoperative phase is feasible, but with major renal and hematologic toxicities, and survival rates similar to those obtained with four-drug regimens using standard-dose ifosfamide. Italian Sarcoma Group/Scandinavian Sarcoma Group study I showed that in a multicenter setting, more than 90% of patients with osteosarcoma of the extremity can undergo conservative surgery.
Detection and functional assessment of regulatory T cells in clinical samples
Authors: Saskia Santegoets, Marij JP Welters, Sjoerd H van der Burg
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Regulatory T cell (Treg)-mediated immunosuppression is considered a major obstacle for successful cancer immunotherapy. Given their profound effect on the outcome of immunotherapy trials, Treg frequency and function are being studied extensively. Unfortunately, no consensus has
Dabigatran and Warfarin in Vitamin K Antagonist–Naive and –Experienced Cohorts With Atrial Fibrillation
Authors: Michael D. Ezekowitz, Lars Wallentin, Stuart J. Connolly, Amit Parekh, Michael R. Chernick, Janice Pogue, Timothy H. Aikens, Sean Yang, Paul A. Reilly, Gregory Y.H. Lip, Salim Yusuf
Journal: Circulation (2010)

The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients.Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (≤62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA.Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin.http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
β-Adrenoceptor Blocker Carvedilol Provides Cardioprotection via an Adenosine-Dependent Mechanism in Ischemic Canine Hearts
Authors: Hiroshi Asanuma, Tetsuo Minamino, Shoji Sanada, Seiji Takashima, Hisakazu Ogita, Akiko Ogai, Masanori Asakura, Yulin Liao, Yoshihiro Asano, Yasunori Shintani, Jiyoong Kim, Yoshiro Shinozaki, Hidezo Mori, Koichi Node, Soichiro Kitamura, Hitonobu Tomoike, Masatsugu Hori, Masafumi Kitakaze
Journal: Circulation (2004)

Carvedilol is a beta-adrenoceptor blocker with a vasodilatory action that is more effective for the treatment of congestive heart failure than other beta-blockers. Recently, carvedilol has been reported to reduce oxidative stress, which may consequently reduce the deactivation of adenosine-producing enzymes and increase cardiac adenosine levels. Therefore, carvedilol may also have a protective effect on ischemia and reperfusion injury, because adenosine mediates cardioprotection in ischemic hearts.In anesthetized dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6 hours. Carvedilol reduced the infarct size (15.0+/-2.8% versus 40.9+/-4.2% in controls), and this effect was completely reversed by the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (45.2+/-5.4%) or by an inhibitor of ecto-5'-nucleotidase (44.4+/-3.6%). There were no differences of either area at risk or collateral flow among the various groups. When the coronary perfusion pressure was reduced in other dogs so that coronary blood flow was decreased to 50% of the nonischemic level, carvedilol increased coronary blood flow (49.4+/-5.6 to 73.5+/-7.5 mL x 100 g(-1) x min(-1); P<0.05) and adenosine release (112.3+/-22.2 to 240.6+/-57.1 nmol/L; P<0.05) during coronary hypoperfusion. This increase of coronary blood flow was attenuated by either 8-sulfophenyltheophylline or superoxide dismutase. In human umbilical vein endothelial cells cultured with or without xanthine and xanthine oxidase, carvedilol caused an increase of ecto-5'-nucleotidase activity.Carvedilol shows a cardioprotective effect against ischemia and/or reperfusion injury via adenosine-dependent mechanisms.
Kas İnvaziv Mesane Kanseri Olan Seçilmiş Hastalarda Komplet Transüretral Mesane Tümörü Rezeksiyonuyla Birlikte Sistemik Kemoterapi ile Mesanenin Korunması: Radikal Sistektomiyle Randomize Olmayan Faz 2 Karşılaştırmalı Çalışma
Authors: Eduardo Solsona a, Miguel A. Climent, Inmaculada Iborra, Argimiro Collado, José Rubio, José V. Ricós, Juan Casanova, Ana Calatrava, Jose L. Monrós
Journal: European Urology (2009)
Organic Anion Transporter 3 Contributes to the Regulation of Blood Pressure
Authors: Volker Vallon, Satish A. Eraly, William R. Wikoff, Timo Rieg, Gregory Kaler, David M. Truong, Sun-Young Ahn, Nitish R. Mahapatra, Sushil K. Mahata, Jon A. Gangoiti, Wei Wu, Bruce A. Barshop, Gary Siuzdak, Sanjay K. Nigam
Journal: Journal of the American Society of Nephrology (2008)

Renal organic anion transporters (OAT) are known to mediate the excretion of many drugs, but their function in normal physiology is not well understood. In this study, mice lacking organic anion transporter 3 (Oat3) had a 10 to 15% lower BP than wild-type mice, raising the possibility that Oat3 transports an endogenous regulator of BP. The aldosterone response to a low-salt diet was blunted in Oat3-null mice, but baseline aldosterone concentration was higher in these mice, suggesting that aldosterone dysregulation does not fully explain the lower BP in the basal state; therefore, both targeted and global metabolomic analyses of plasma and urine were performed, and several potential endogenous substrates of Oat3 were found to accumulate in the plasma of Oat3-null mice. One of these substrates, thymidine, was transported by Oat3 expressed in vitro. In vivo, thymidine, as well as two of the most potent Oat3 inhibitors that were characterized, reduced BP by 10 to 15%; therefore, Oat3 seems to regulate BP, and Oat3 inhibitors might be therapeutically useful antihypertensive agents. Moreover, polymorphisms in human OAT3 might contribute to the genetic variation in susceptibility to hypertension.
Hypercholesterolemia impairs vascular remodelling after porcine coronary angioplasty
Authors: G Theilmeier
Journal: Cardiovascular Research (2002)

Objective: To assess the effect of hypercholesterolemia on neointima formation and vascular remodelling after porcine coronary angioplasty.Methods: Left anterior descending coronary angioplasty was carried out in five control and 16 age-matched hypercholesterolemic miniature pigs.Vascular remodelling was measured by intravascular ultrasound.Neointima size and composition were assessed by quantitative image analysis.Coronary smooth muscle cells (SMC) from control and diet pigs were collected 1 h after angioplasty for in vitro study of the effect of hypercholesterolemic serum on SMC migration and of macrophage-induced matrix 2 degradation on SMC adhesion.Results: Twenty-eight days after angioplasty, lumen increase was 0.0861.7 mm in diet and 2.762.7 2 2 mm (P50.016) in control pigs.Lumen increase correlated with vascular remodelling (IEL / IEL ; R 50.59; P,0.001) and with the post pre 2 circumferential gain relative to the neointima (R 50.32;P,0.01) but not with neointimal area that was similar in control and diet pigs.2 Circumferential gain correlated with VSMC deposition at the site of the injury (R 50.28;P,0.01) that correlated with organized collagen 2 (R 50.34;P,0.01).The VSMC and collagen content of neointima in diet pigs was lower whereas the macrophage content was higher.Hypercholesterolemic serum and oxidised LDL reduced migration of VSMC from diet pigs.Macrophage-induced degradation of VSMC extracellular matrix reduced VSMC adhesion (P50.015).Conclusion: Hypercholesterolemia impairs vascular remodelling of balloontreated coronary arteries.It decreases VSMC and collagen accumulation at the site of injury.Our in vitro data suggest that this decrease can be due to macrophage-induced matrix degradation and reduced VSMC adhesion and to impaired VSMC migration.Oxidised LDL mimics the inhibitory effect of hypercholesterolemic serum.
Chimpanzee adenovirus– and MVA-vectored respiratory syncytial virus vaccine is safe and immunogenic in adults
Authors: Christopher A. Green, Elisa Scarselli, Charles J. Sande, Amber J. Thompson, Catherine M. de Lara, Kathryn S. Taylor, Kathryn Haworth, Mariarosaria Del Sorbo, Brian Angus, Loredana Siani, Stefania Di Marco, Cinzia Traboni, Antonella Folgori, Stefano Colloca, Stefania Capone, Alessandra Vitelli, Riccardo Cortese, Paul Klenerman, Alfredo Nicosia, Andrew J. Pollard
Journal: Science Translational Medicine (2015)

The RSV vaccine candidates PanAd3-RSV and MVA-RSV were safe and immunogenic in healthy adults.
Dietary intake and the risk of gastro-oesophageal reflux disease: a cross sectional study in volunteers
Authors: H B El-Serag
Journal: Gut (2004)

<b>Background:</b> Although diet has been associated with gastro-oesophageal reflux disease (GORD), the role of dietary components (total energy, macro and micronutrients) is unknown. We examined associations of GORD symptoms with intakes of specific dietary components. <b>Methods:</b> We conducted a cross sectional study in a sample of employees (non-patients) at the Houston VAMC. The Gastro Esophageal Reflux Questionnaire was used to identify the onset, frequency, and severity of GORD symptoms. Dietary intake (usual frequency of consumption of various foods and portion sizes) over the preceding year was assessed using the Block 98 food frequency questionnaire. Upper endoscopy was offered to all participants and oesophageal erosions recorded according to the LA classification. We compared the dietary intake (macronutrients, micronutrients, food groups) of participants with or without GORD symptoms, or erosive oesophagitis. Stepwise multiple logistic regression analyses were used to examine associations between nutrients and GORD symptoms or oesophageal erosions, adjusting for demographic characteristics, body mass index (BMI), and total energy intake. <b>Results:</b> A total of 371 of 915 respondents (41%) had complete and interpretable answers to both heartburn and regurgitation questions and met validity criteria for the Block 98 FFQ. Mean age was 43 years, 260 (70%) were women, and 103 (28%) reported at least weekly occurrences of heartburn or regurgitation. Of the 164 respondents on whom endoscopies were performed, erosive oesophagitis was detected in 40 (24%). Compared to participants without GORD symptoms, daily intakes of total fat, saturated fat, cholesterol, percentage of energy from dietary fat, and average fat servings were significantly higher in participants with GORD symptoms. In addition, there was a dose-response relationship between GORD and saturated fat and cholesterol. The effect of dietary fat became non-significant when adjusted for BMI. However, high saturated fat, cholesterol, or fat servings were associated with GORD symptoms only in participants with a BMI &gt;25 kg/m<sup>2</sup> (effect modification). Fibre intake remained inversely associated with the risk of GORD symptoms in adjusted full models. Participants with erosive oesophagitis had significantly higher daily intakes of total fat and protein than those without it (p&lt;0.05). <b>Conclusions:</b> In this cross sectional study, high dietary fat intake was associated with an increased risk of GORD symptoms and erosive oesophagitis while high fibre intake correlated with a reduced risk of GORD symptoms. It is unclear if the effects of dietary fat are independent of obesity.