tbuckley/cabot-search huggingface dataset:
Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension
Authors: Marijke Wynants, Rozenn Quarck, Alicja Ronisz, Ernesto Alfaro-Moreno, Dirk Van Raemdonck, Bart Meyns, Marion Delcroix
Journal: European Respiratory Journal (2012)

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by proximal pulmonary vascular obstruction by thrombo-fibrotic material, the origin of which has not been elucidated. Enhanced inflammation could contribute to persistent obstruction by impairing pulmonary vascular cell function in CTEPH. We investigated C-reactive protein (CRP) effects on pulmonary vascular cell function <i>in vitro</i>. Primary cultures of proximal pulmonary endothelial cells (ECs) and smooth muscle cells (SMCs) from CTEPH and nonthromboembolic pulmonary hypertension (PH) patients were established. Recombinant CRP effects on mitogenic activity, adhesion capacity, endothelin-1 and von Willebrand factor (vWF) secretion and intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1 expression were investigated in ECs and/or SMCs. Expression of the CRP receptor, lectin-like oxidised low-density lipoprotein receptor (LOX)-1, was evaluated in proximal pulmonary arterial tissue and cells by Western blotting and immunofluorescence. CRP increased CTEPH-SMC proliferation by 250%. CRP increased adhesion capacity, endothelin-1 and vWF secretion by CTEPH-ECs by 37%, 129% and 694%, respectively. CRP-induced adhesion of CTEPH-ECs to monocytes was mediated by ICAM-1. CRP had no effect on cells from nonthromboembolic PH patients, probably because of overexpression of LOX-1 in CTEPH. Local expression of CRP was detected in ECs and SMCs within pulmonary arterial tissue. CRP may contribute to persistent obstruction of proximal pulmonary arteries in CTEPH by promoting vascular remodelling, endothelial dysfunction and <i>in situ</i> thrombosis.
Hemiarthroplasty or internal fixation for intracapsular displaced femoral neck fractures: randomised controlled trial
Authors: Frede Frihagen, Lars Nordsletten, Jan Erik Madsen
Journal: BMJ (2007)

<b>Objective</b> To compare the functional results after displaced fractures of the femoral neck treated with internal fixation or hemiarthroplasty. <b>Design</b> Randomised trial with blinding of assessments of functional results. <b>Setting</b> University hospital. <b>Participants</b> 222 patients; 165 (74%) women, mean age 83 years. Inclusion criteria were age above 60, ability to walk before the fracture, and no major hip pathology, regardless of cognitive function. <b>Interventions</b> Closed reduction and two parallel screws (112 patients) and bipolar cemented hemiarthroplasty (110 patients). Follow-up at 4, 12, and 24 months. <b>Main outcome measures</b> Hip function (Harris hip score), health related quality of life (Eq-5d), activities of daily living (Barthel index). In all cases high scores indicate better function. <b>Results</b> Mean Harris hip score in the hemiarthroplasty group was 8.2 points higher (95% confidence interval 2.8 to 13.5 points, P=0.003) at four months and 6.7 points (1.5 to 11.9 points, P=0.01) higher at 12 months. Mean Eq-5d index score at 24 months was 0.13 higher in the hemiarthroplasty group (0.01 to 0.25, P=0.03). The Eq-5d visual analogue scale was 8.7 points higher in the hemiarthroplasty group after 4 months (1.9 to 15.6, P=0.01). After 12 and 24 months the percentage scoring 95 or 100 on the Barthel index was higher in the hemiarthroplasty group (relative risk 0.67, 0.47 to 0.95, P=0.02. and 0.63, 0.42 to 0.94, P=0.02, respectively). Complications occurred in 56 (50%) patients in the internal fixation group and 16 (15%) in the hemiarthroplasty group (3.44, 2.11 to 5.60, P&lt;0.001). In each group 39 patients (35%) died within 24 months (0.98, 0.69 to 1.40, P=0.92) <b>Conclusions</b> Hemiarthroplasty is associated with better functional outcome than internal fixation in treatment of displaced fractures of the femoral neck in elderly patients. <b>Trial registration</b>NCT00464230.
Pulmonary hypersensitivity to Ramin (Gonystylus bancanus).
Authors: A D Howie, G Boyd, F Moran
Journal: Thorax (1976)

Transient airways obstruction associated with reduction in the transfer factor (diffusing capacity) of the lungs is reported in a patient with a clinical syndrome in keeping with extrinsic allergic alveolitis after exposure to Ramin dust (Gonystylus bancanus). The alterations in pulmonary function were consistently demonstrated on testing the patient in his working environment and were reproduced in the laboratory after inhalational challenge. The importance of the temporal relationship of changes in pulmonary function to contact with suspected allergenic material is emphasized.
TISSUE RENIN-ANGIOTENSIN SYSTEM:A Site of Drug Action?
Authors: Ben G. Zimmerman and, Earl W. Dunham
Journal: The Annual Review of Pharmacology and Toxicology (1997)

▪ Abstract In this review, we present background material that provides partial support for a tissue renin-angiotensin system (RAS). Evidence for the existence of this system relied in part the use of drugs, which has entailed using low doses or concentrations of angiotensin-converting enzyme inhibitors, renin inhibitors, and angiotensin antagonists to block the RAS in vascular beds and in isolated arteries or organs. Other evidence for a tissue RAS has depended upon measurements of the components of the system, i.e. enzymes, substrates, and mRNAs for these proteins. All of these components were first believed to be present in the heart and blood vessels; however, it is now known that renin in the circulating blood derived from the kidney is used for the local synthesis of angiotensins. The main emphasis of the review is on the renal RAS because it is believed that the local RAS is most prominent in this organ. The renal RAS is probably involved in the long- rather than short-term regulation of renal vascular resistance and maintenance of normal blood pressure through the regulation of sodium reabsorption.
Multicenter Phase II Trial of S-1 in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma
Authors: Seiji Naito, Masatoshi Eto, Nobuo Shinohara, Yoshihiko Tomita, Masato Fujisawa, Mikio Namiki, Masaharu Nishikido, Michiyuki Usami, Taiji Tsukamoto, Hideyuki Akaza
Journal: Journal of Clinical Oncology (2010)

This phase II multicenter trial was conducted to evaluate the activity and safety of S-1 in Japanese patients with metastatic renal cell carcinoma (mRCC). We also examined the relation between response and mRNA expression levels of enzymes involved in the metabolism of fluorouracil (FU).Patients with mRCC who had received nephrectomy in whom cytokine-based immunotherapy was ineffective or contraindicated were studied. S-1 was administered orally at 80-, 100-, or 120-mg daily, assigned according to body surface area, on days 1 to 28 of a 42-day cycle. The primary end point was the objective response rate. The mRNA expression levels of FU-related enzymes were measured by reverse-transcriptase polymerase chain reaction in formalin-fixed, paraffin-embedded specimens of tumors obtained at nephrectomy.A total of 45 eligible patients were enrolled. Eleven (24.4%) of 45 patients had partial responses to S-1, and 28 (62.2%) had stable disease. Median progression-free survival was 9.2 months. The severity of most adverse events was mild to moderate. The most common grade 3/4 drug-related adverse events were neutropenia (8.9%) and anorexia (8.9%). The expression level of thymidylate synthase (TS) mRNA was significantly lower in patients who responded to treatment (t-test, P = .048), and progression-free survival was significantly longer in patients whose TS mRNA expression levels were below the median value, as compared with those with higher levels (log-rank test, P = .006).S-1 is active against cytokine-refractory mRCC. Quantification of TS mRNA levels in tumors before treatment may facilitate prediction of the response of mRCC to S-1.
Angiomyeloproliferative Lesions Following Autologous Stem Cell Therapy
Authors: Duangpen Thirabanjasak, Kavirach Tantiwongse, Paul Scott Thorner
Journal: Journal of the American Society of Nephrology (2010)

Some reports suggest that autologous hematopoietic stem cell transplantation holds potential for treatment of renal diseases such as lupus nephritis, but the safety of delivering various stem cell types (hematopoietic, mesenchymal, and endothelial precursors) is not well established. Here, we report a case of lupus nephritis treated by direct renal injection of autologous stem cells recovered from peripheral blood. The patient developed masses at the sites of injection and hematuria. We suspected transitional cell carcinoma but nephrectomy revealed that the masses were angiomyeloproliferative lesions. We believe that this previously undescribed pathologic entity is stem cell-derived or -induced. The biologic potential, including the neoplastic potential, of this lesion is unknown. This case illustrates that the development of angiomyeloproliferative lesions is a possible complication of stem cell therapy.
The association between kidney function and major bleeding in older adults with atrial fibrillation starting warfarin treatment: population based observational study
Authors: M. Jun, M. T. James, B. J. Manns, R. R. Quinn, P. Ravani, M. Tonelli, V. Perkovic, W. C. Winkelmayer, Z. Ma, B. R. Hemmelgarn
Journal: BMJ (2015)

<b>Objective</b> To determine rates of major bleeding by level of kidney function for older adults with atrial fibrillation starting warfarin. <b>Design</b> Retrospective cohort study. <b>Setting</b> Community based, using province wide laboratory and administrative data in Alberta, Canada. <b>Participants</b> 12 403 adults aged 66 years or more, with atrial fibrillation who started warfarin treatment between 1 May 2003 and 31 March 2010 and had a measure of kidney function at baseline. Kidney function was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation and participants were categorised based on estimated glomerular filtration rate (eGFR): ≥90, 60-89, 45-59, 30-44, 15-29, &lt;15 mL/min/1.73m<sup>2</sup>. We excluded participants with end stage renal disease (dialysis or renal transplant) at baseline. <b>Main outcome measures</b> Admission to hospital or visit to an emergency department for major bleeding (intracranial, upper and lower gastrointestinal, or other). <b>Results</b> Of 12 403 participants, 45% had an eGFR &lt;60 mL/min/1.73m<sup>2</sup>. Overall, 1443 (11.6%) experienced a major bleeding episode over a median follow-up of 2.1 (interquartile range: 1.0-3.8) years. During the first 30 days of warfarin treatment, unadjusted and adjusted rates of major bleeding were higher at lower eGFR (P for trend &lt;0.001 and 0.001, respectively). Adjusted bleeding rates per 100 person years were 63.4 (95% confidence interval 24.9 to 161.6) in participants with eGFR &lt;15 mL/min/1.73m<sup>2</sup> compared with 6.1 (1.9 to 19.4) among those with eGFR &gt;90 mL/min/1.73m<sup>2</sup> (adjusted incidence rate ratio 10.3, 95% confidence interval 2.3 to 45.5). Similar associations were observed at more than 30 days after starting warfarin, although the magnitude of the increase in rates across eGFR categories was attenuated. Across all eGFR categories, adjusted rates of major bleeding were consistently higher during the first 30 days of warfarin treatment compared with the remainder of follow-up. Increases in major bleeding rates were largely due to gastrointestinal bleeding (3.5-fold greater in eGFR &lt;15 mL/min/1.73m<sup>2</sup> compared with ≥90 mL/min/1.73m<sup>2</sup>). Intracranial bleeding was not increased with worsening kidney function. <b>Conclusions</b> Reduced kidney function was associated with an increased risk of major bleeding among older adults with atrial fibrillation starting warfarin; excess risks from reduced eGFR were most pronounced during the first 30 days of treatment. Our results support the need for careful consideration of the bleeding risk relative to kidney function when assessing the risk-benefit ratio of warfarin treatment in people with chronic kidney disease and atrial fibrillation, particularly in the first 30 days of treatment.
One-year cost-effectiveness of tiotropium<i>versus</i>ipratropium to treat chronic obstructive pulmonary disease
Authors: J.B. Oostenbrink, M.P.M.H. Rutten-van Mölken, M.J. Al, J.A. Van Noord, W. Vincken
Journal: European Respiratory Journal (2004)

The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new, once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease (COPD). This prospective cost-effectiveness analysis was performed alongside two 1‐yr randomised, double-blind clinical trials in the Netherlands and Belgium. Patients had a diagnosis of COPD and a forced expiratory volume in one second (FEV 1 ) ≤65% predicted normal. Patients were randomised to tiotropium (18 µg once daily) or ipratropium (2 puffs of 20 µg administered four times daily) in a ratio of 2:1. The mean number of exacerbations was reduced from 1.01 in the ipratropium group (n=175) to 0.74 in the tiotropium group (n=344). The percentages of patients with a relevant improvement on the St. George's Respiratory Questionnaire (SGRQ) were 34.6% and 51.2% respectively. Compared to ipratropium, the number of hospital admissions, hospital days and unscheduled visits to healthcare providers was reduced by 46%, 42% and 36% respectively. Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 (sem 160) in the tiotropium group and 1,541 (SEM 163) in the ipratropium group (difference 180). Incremental cost-effectiveness ratios were 667 per exacerbation avoided and 1084 per patient with a relevant improvement on the SGRQ. Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 per patient per year.
Microrobots for Minimally Invasive Medicine
Authors: Bradley J. Nelson, Ioannis K. Kaliakatsos, Jake J. Abbott
Journal: Annual Review of Biomedical Engineering (2010)

Microrobots have the potential to revolutionize many aspects of medicine. These untethered, wirelessly controlled and powered devices will make existing therapeutic and diagnostic procedures less invasive and will enable new procedures never before possible. The aim of this review is threefold: first, to provide a comprehensive survey of the technological state of the art in medical microrobots; second, to explore the potential impact of medical microrobots and inspire future research in this field; and third, to provide a collection of valuable information and engineering tools for the design of medical microrobots.
Reproducibility of Glucose Measurements Using the Glucose Sensor
Authors: Muriel Metzger, Gil Leibowitz, Julio Wainstein, Benjamin Glaser, Itamar Raz
Journal: Diabetes Care (2002)

Recent studies have confirmed that improved glycemic control decreases the risk of diabetic complications in type 1 and type 2 diabetic patients. The Minimed glucose sensor allows continuous 72-h glucose monitoring and represents a potentially important tool to improve diabetes management. Its use is currently limited to the health care team. Our aim was to evaluate the reproducibility of data provided by the device by comparing data provided by two sensors worn simultaneously by the same subject.A total of 11 subjects (6 type 1 and 3 type 2 diabetic patients and 2 healthy subjects) agreed to wear two sensors and perform at least four daily finger-stick glucose determinations during 72 h. The simultaneous glucose values provided by the sensors were compared. To determine the clinical implications of the glucose data, each day was divided into eight periods, and for each period the glucose range was rated as satisfactory, too high, or too low by a blinded clinician experienced in interpreting glucose sensor data in the clinical setting. The evaluation of glycemic levels based on the recordings of the two sensors were compared for each paired time interval.We discarded 18% of the sensor data for technical reasons. Examined as a group, the remaining 3,370 paired data points in all 11 patients were highly correlated (r = 0.84). However, when individual pairs were evaluated, large differences in the glucose values were apparent, with differences of >10% in 70% of the measurements and >50% in 7% of the measurements. Moreover, clinical evaluation of the glucose range provided simultaneously by two sensors was concordant for only 65% of the evaluation periods.In a real-life setting, the accuracy of data provided by the Minimed glucose sensor may be less than expected. To avoid therapeutic errors, sensor findings should be confirmed by independent means before clinical decisions are made.
Nocturnal Periodic Breathing during Acclimatization at Very High Altitude at Mount Muztagh Ata (7,546 m)
Authors: Konrad E. Bloch, Tsogyal D. Latshang, Alexander J. Turk, Thomas Hess, Urs Hefti, Tobias M. Merz, Martina M. Bosch, Daniel Barthelmes, Jacqueline Pichler Hefti, Marco Maggiorini, Otto D. Schoch
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Quantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m).To investigate whether periodic breathing persists during prolonged stay at very high altitude.A total of 34 mountaineers (median age, 46 yr; 7 women) climbed from 3,750 m within 19-20 days to the summit at 7,546 m. During ascent, repeated nocturnal recordings of calibrated respiratory inductive plethysmography, pulse oximetry, and scores of acute mountain sickness were obtained.Nocturnal oxygen saturation decreased, whereas minute ventilation and the number of periodic breathing cycles increased with increasing altitude. At the highest camp (6,850 m), median nocturnal oxygen saturation, minute ventilation, and the number of periodic breathing cycles were 64%, 11.3 L/min, and 132.3 cycles/h. Repeated recordings within 5-8 days at 4,497 m and 5,533 m, respectively, revealed increased oxygen saturation, but no decrease in periodic breathing. The number of periodic breathing cycles was positively correlated with days of acclimatization, even when controlled for altitude, oxygen saturation, and other potential confounders, whereas symptoms of acute mountain sickness had no independent effect on periodic breathing.Our field study provides novel data on nocturnal oxygen saturation, breathing patterns, and ventilation at very high altitude. It demonstrates that periodic breathing increases during acclimatization over 2 weeks at altitudes greater than 3,730 m, despite improved oxygen saturation consistent with a progressive increase in loop gain of the respiratory control system. Clinical trial registered with www.clinicaltrials.gov (NCT00514826).
FOLFOX4 versus sequential dose-dense FOLFOX7 followed by FOLFIRI in patients with resectable metastatic colorectal cancer (MIROX): a pragmatic approach to chemotherapy timing with perioperative or postoperative chemotherapy from an open-label, randomized phase III trial
Authors: M. Hebbar, B. Chibaudel, T. André, L. Mineur, D. Smith, C. Louvet, J.L. Dutel, M. Ychou, J.L. Legoux, M. Mabro, R. Faroux, D. Auby, D. Brusquant, A. Khalil, S. Truant, A. Hadengue, C. Dalban, B. Gayet, F. Paye, F.R. Pruvot, F. Bonnetain, J. Taieb, P. Brucker, B. Landi, M. Flesch, E. Carola, P. Martin, E. Vaillant, A. de Gramont
Journal: Annals of Oncology (2014)
Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study
Authors: M Bardou
Journal: Gut (2002)

Excessive alcohol consumption is a risk factor for developing colorectal adenomas. This study aimed to investigate the influence of excessive alcohol consumption on the occurrence of high risk polyps (adenoma > or = 10 mm, villous component, high grade dysplasia) or colorectal cancer among patients with at least one colonic adenoma.Three groups of patients with at least one colorectal adenoma were included in a case control study: 401 heavy drinkers (group HD, mean daily alcohol intake 117 (SD 4) g/day for a mean duration of 22 (SD 0.6) years), aged 57 (0.5) years (78% men); 152 patients suffering from irritable bowel syndrome (IBS), aged 61 (0.9) years (57% male); and 108 patients with a family history (FH) of colorectal adenoma or cancer, aged 55 (1) years (64% male). Exclusion criteria were: anaemia, haematochezia, personal history of colorectal adenoma or cancer, and for groups HD and IBS a family history of colorectal adenoma and/or cancer. Relative risks were estimated by the odds ratio (OR) using a logistic regression model and were expressed with 95% confidence interval (CI).After age and sex adjustment, the likelihood of having an adenoma > or = 10 mm was higher in group HD than in the IBS group (OR 1.8, 95% CI (1.2-2.7)) and the likelihood of having high risk adenomas or cancer was higher in group HD compared with the IBS group (OR 1.6, 95% CI (1.2-2.1)) and the FH group although this was not significant (OR 1.6, 95% CI (0.97-2.6) (p=0.081); 90% CI (1.03-2.4)). After age and sex adjustment, the likelihood of having an adenoma with high grade dysplasia or cancer was higher in group HD than in the IBS group (OR 1.7, 95% CI (1.02-2.8)) or group FH, although this was not significant (OR 3.7, 95% CI (0.98-15) (p=0.076); 90% CI (1.10-12.47)).In patients with at least one colorectal adenoma, excessive alcohol consumption increases the likelihood of developing high risk adenomas or colorectal cancer.
Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype–mismatched hematopoietic transplants
Authors: Isabella Volpi, Katia Perruccio, Antonella Tosti, Marusca Capanni, Loredana Ruggeri, Sabrina Posati, Franco Aversa, Antonio Tabilio, Luigina Romani, Massimo F. Martelli, Andrea Velardi
Journal: Blood (2001)
Benchmarking ortholog identification methods using functional genomics data
Authors: Tim Hulsen, Martijn A Huynen, Jacob de Vlieg, Peter MA Groenen
Journal: Genome biology (2006)

The transfer of functional annotations from model organism proteins to human proteins is one of the main applications of comparative genomics. Various methods are used to analyze cross-species orthologous relationships according to an operational definition of orthology. Often the definition of orthology is incorrectly interpreted as a prediction of proteins that are functionally equivalent across species, while in fact it only defines the existence of a common ancestor for a gene in different species. However, it has been demonstrated that orthologs often reveal significant functional similarity. Therefore, the quality of the orthology prediction is an important factor in the transfer of functional annotations (and other related information). To identify protein pairs with the highest possible functional similarity, it is important to qualify ortholog identification methods.To measure the similarity in function of proteins from different species we used functional genomics data, such as expression data and protein interaction data. We tested several of the most popular ortholog identification methods. In general, we observed a sensitivity/selectivity trade-off: the functional similarity scores per orthologous pair of sequences become higher when the number of proteins included in the ortholog groups decreases.By combining the sensitivity and the selectivity into an overall score, we show that the InParanoid program is the best ortholog identification method in terms of identifying functionally equivalent proteins.
Immunopathological aspects of schistosomiasis-associated pulmonary arterial hypertension
Authors: Thais Mauad, Geanette Pozzan, Tatiana Lanças, Maria J. Overbeek, Rogério Souza, Carlos Jardim, Marisa Dolhnikoff, George Mello, Ruy Camargo Pires-Neto, Fabiola del Carlo Bernardi, Katrien Grünberg
Journal: Journal of Infection (2013)