tbuckley/cabot-search huggingface dataset:
Medically Significant Infections Are Increased in Patients With Juvenile Idiopathic Arthritis Treated With Etanercept: Results From the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study
Authors: Rebecca Davies, Taunton R. Southwood, Lianne Kearsley‐Fleet, Mark Lunt, Kimme L. Hyrich
Journal: Arthritis & Rheumatology (2015)

The association between anti-tumor necrosis factor therapy and increased rates of infection is widely documented in adults with rheumatoid arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have been less well documented. The aims of this analysis were to compare the rates of medically significant infections (MSIs) in children with JIA treated with etanercept (ETN) versus methotrexate (MTX) and to compare the rates between combination therapy with ETN plus MTX and monotherapy with ETN.A total of 852 ETN-treated children and 260 MTX-treated children had been recruited to the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN). MSIs included infections that resulted in death or hospitalization or were deemed medically significant by the clinician. This on-drug analysis followed the patients until the first MSI, treatment discontinuation, the last followup, or death. Cox proportional hazards models, which were adjusted using propensity deciles, were used to compare rates of MSI between cohorts. Sensitivity analyses were conducted specifically with regard to serious infections (SIs), which were defined as those requiring hospitalization or treatment with intravenous antibiotics/antivirals.The ETN-treated cohort was older and had a longer disease duration, but the disease activity was similar between the cohorts. A total of 133 first MSIs were reported (109 with ETN and 24 with MTX). Patients receiving ETN had higher rates of MSI than did the controls (propensity decile adjusted hazard ratio 2.13 [95% confidence interval 1.22-3.74]). The risk of MSI was higher whether patients were receiving combination or monotherapy. Sensitivity analysis showed no between-group difference in the rate of SIs, which were much less common.ETN therapy is associated with an increased risk of MSI; however, this increased risk disappears when considering only SIs, which suggests that either there were differences in the severity of infections and/or there was a possible reporting bias.
Natural zoonotic infections of two marmosets and one domestic rabbit with herpes simplex virus type 1 did not reveal a correlation with a certain gG-, gI- or gE genotype
Authors: K. Sekulin, J. Janková, J. Kolodziejek, H.P. Huemer, A. Gruber, J. Meyer, N. Nowotny
Journal: Clinical Microbiology and Infection (2010)
5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study
Authors: T P van Staa
Journal: Gut (2005)

<b>Background and aims:</b> The objective of this study was to evaluate the risk of colorectal cancer (CRC) in patients taking aminosalicylates (5-ASA) for inflammatory bowel disease (IBD). <b>Methods:</b> The General Practice Research Database (GPRD) which contains the primary care records of five million people in the UK was used to identify users of mesalazine, balsalazide, olsalazine, or sulfasalazine with a history of IBD. In a nested case control analysis, each incident CRC case with any use of a 5-ASA in the six months before the CRC diagnosis was matched by age, sex, and calendar time to six control patients who were also currently using a 5-ASA. Patients were then classified according to regularity of use. The analysis was controlled for body mass index, IBD duration, history of colorectal polyps, use of non-steroidal anti-inflammatory drugs, paracetamol, aspirin, immunosuppressants, oral and rectal glucocorticoids, prior gastrointestinal hospitalisation, recorded colonoscopy, and number of visits to the general practitioner for IBD symptoms in the 6–24 months before diagnosis. <b>Results:</b> The study population included 18 969 patients, of whom 100 had developed CRC during 5-ASA exposure. Most of these cases had a history of ulcerative colitis (76 patients). In the case control analysis, regular users, defined as having six or more 5-ASA prescriptions in the previous 12 months, were found to have a decreased risk of CRC compared with irregular users (crude odds ratio (OR) 0.7 (0.44–1.03); adjusted OR 0.60 (0.38–0.96)). Regular users of sulfasalazine with 6–12 prescriptions before had an adjusted OR of 0.95 (0.22–4.11); with 13–30 prior prescriptions this was 0.41 (0.14–1.20) and with &gt;30 prior prescriptions this was 0.77 (0.37–1.60). For mesalazine users, these values were 1.13 (0.49–2.59), 0.30 (0.11–0.83), and 0.31 (0.11–0.84), respectively. <b>Conclusion:</b> These results show that regular 5-ASA use is associated with some reduction in the risk of CRC developing in ulcerative colitis.
Bronchodilator response in adult patients with cystic fibrosis: effects on large and small airways
Authors: EH van Haren, JW Lammers, J Festen, CL van Herwaarden
Journal: European Respiratory Journal (1991)

Spirometry, body plethysmography, maximal expiratory flow-volume curves (MEFV-curves) with air and with heliox (80% He + 20% O2) before and after inhalation of bronchodilators were studied in a group of 20 adult cystic fibrosis (CF) patients. Most of them showed prominent bronchial obstruction and seven also had evidence of restrictive pulmonary disease. Large differences were observed between total lung capacity as measured with body plethysmography and with a helium dilution technique. A calculated air trapping index correlated well with parameters of peripheral airway obstruction. Both inhalation of terbutaline and ipratropium bromide caused dose-related bronchodilatation. Density dependence of expiratory flow increased significantly after terbutaline but not after ipratropium bromide. We conclude that adult CF patients with varying degrees of obstructive and restrictive pulmonary function limitation show a dose-related improvement of lung function after terbutaline and ipratropium bromide with terbutaline being probably more effective on peripheral airways than ipratropium bromide.
Prevalence of latent tuberculosis infection among household contacts and community controls in South India
Authors: Padmanesan Narasimhan, James Wood, Robinson Peter, Ramkumar Ranganathan, Anand Manoharan, C.R. MacIntyre, Dilip Mathai
Journal: European Respiratory Journal (2013)

Introduction: Household contacts (HHC) are at higher risk of tuberculosis, but in endemic countries most of the burden occurs outside case households. This study examines differences at baseline infection rates between HHC and community controls (CC) and assesses the influence of risk factors.  Methods: Tuberculin skin test (TST) and Quantiferon test (QFT) were collected from prospectively recruited HHC and CC in South India at baseline. Comparisons between positivity rates were conducted along with logistic regression adjusted for household correlations using generalised estimated equations.  Results: We recruited 359 HHC of 114 index TB cases and 363 CC with similar demographics. High rates of positivity were observed in both groups (56% using TST ≥10mm and 44% using QFT in HHC) and 54% using TST ≥10mm and 44% using QFT in CC. Four active TB cases were also detected among HHC (prevalence-1.14%, (CI=0.3-3.7)) with none among the CC. HHC (  Conclusion: TB exposure in both arms were similar at baseline but this masked a significant difference in rates of exposure in child contacts. This data will inform estimates of the force of infection with applications to modelling studies. Risk factor results and incidence of active TB were in line with previously identified results, with the study not powered to detect the influence of multiple factors.
Sequential Histologic Changes During Gastric Carcinogenesis Induced by N-Methyl-N′-nitro-N-nitrosoguanidine in Susceptible ACI and Resistant BUF Rats2
Authors: Hiroko Ohgaki, Kaoru Kusama, Hirokazu Hasegawa, Shigeaki Sato, Shozo Takayama, Takashi Sugimura
Journal: JNCI Journal of the National Cancer Institute (1986)

Sequential histologic changes of the stomach during carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG; CAS: 70-25-7) were studied in susceptible ACI and resistant BUF strain rats. Rats were given MNNG at a concentration of 83 μg/ml in their drinking water for 32 weeks and then tap water and were sacrificed sequentially between weeks 1 and 57. In ACI rats, erosions, regenerative changes, focal and slightly atypical changes, and diffuse and severe atypical changes were observed sequentially in the pyloric region during the period of MNNG administration, where adenocarcinomas were observed after the cessation of MNNG treatment. In BUF rats, the main histologic changes induced by MNNG were erosions and hyperplasia of the glandular portion of pyloric glands at the margin of erosions. After the cessation of MNNG treatment, the hyperplasia of the pyloric glands subsided and was followed by atrophy of these glands. The results suggested that the responses of the gastric mucosa to MNNG in ACI and BUF rats were qualitatively different.
Accurate Identification of Experimental Pulmonary Metastases2
Authors: Hilda Wexler
Journal: JNCI Journal of the National Cancer Institute (1966)

The accurate counting and sizing of small, lightly pigmented tumor metastases in the lungs of experimental mice have been facilitated by the development of a method whereby the lungs were insufflated with a 15 percent solution of India ink. After being washed with Fekete's solution, which is a bleach preservative, these tiny implants, not detected in the unstained fresh lung, became discretely visible. The accuracy and time-saving features of this method aid in the verification of lung metastases and permit a much wider range of spontaneous and induced animal tumors in studies of experimental tumor metastases.
Second hand smoke exposure impairs CD39 expression and function in the lung
Authors: Adelheid Kratzer, Jonas Salys, Jean Sévigny, Martin Zamora, Laima Taraseviciene-Stewart
Journal: European Respiratory Journal (2012)

Chronic second hand smoke (SHS) exposure is the main risk factor for non-smokers to develop chronic obstructive pulmonary disease COPD. The mechanisms behind the chronic inflammation and lung destruction are not completely understood. In response to injury vascular and blood cells release ATP that is implicated in regulating cellular and immune responses. Plasma membrane ecto-nucleotidase CD39 hydrolyzes ATP to ADP and AMP. Ecto-59nucleotidase CD73 hydrolyzes AMP to adenosine. Here we investigated the contribution of CD39/73 expressing inflammatory cells in lung remodeling in response to SHS exposure.  Sprague Dawley rats were exposed to SHS in a smoking chamber (total particulate matter levels 115 mg/m3). The expression levels of CD39 and CD73 in the inflammatory cells and lung tissue were determined by flow cytometry, real time PCR and Western blot analysis.  Chronic second hand smoke exposure resulted in the development of emphysema in rats as measured by MLI (87.2 ± 1.5 mm after 2 month of exposure versus 73.4 ± 1.1 mm in room air exposed controls). The CD39 expression was significantly downregulated in the whole lung tissue on mRNA and protein levels. Moreover, CD39 expression was decreased in the lung tissue from COPD patients. Cigarette smoke extract in vitro almost abolished CD39 and CD73 expression in the alveolar macrophages and vascular endothelial cells.  Second hand smoke exposure impairs ectonucletidase expression in the lungs and leads to accumulation of extracellular ATP that confers increased proinflammatory responses leading to the development of emphysema.  Funded by AHA 0735388N, 11GRNT7520020, FAMRI CIA 072053, Emphysema Research Fund and Bixler Family Foundation.
Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group.
Authors: R C Coombes, J M Bliss, J Wils, F Morvan, M Espié, D Amadori, P Gambrosier, M Richards, M Aapro, A Villar-Grimalt, C McArdle, F R Pérez-López, P Vassilopoulos, E P Ferreira, C E Chilvers, G Coombes, E M Woods, M Marty
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine whether a combination chemotherapy regimen that contains epirubicin (fluorouracil, epirubicin, and cyclophosphamide [FEC]) is superior to the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in premenopausal women with axillary node-positive operable breast cancer. PATIENTS AND METHODS The International Collaborative Cancer Group (ICCG) conducted a large randomized trial in which two alternative schedules were used according to participating center: CMF1 versus FEC1 and CMF2 versus FEC2. RESULTS Seven hundred fifty-nine patients were entered onto the trial. At a median follow-up time of 4.5 years, no significant benefit for the anthracycline-containing regimen was observed in terms of relapse-free (P = .61) or overall survival (P = .13). FEC1 and CMF1 appear to be of similar efficacy, but there is a suggestion that FEC2 may be superior to CMF2, since patients who received FEC2 had improved overall (P = .02) and relapse-free survival (P = .03) rates. Nausea and vomiting and alopecia were more common in the epirubicin-containing regimen (P = .001). CONCLUSION We conclude that the FEC2 regimen, in which epirubicin replaced the methotrexate in CMF, is the preferable adjuvant chemotherapy regimen for premenopausal patients with operable axillary node-positive breast cancer.
Antimicrobial susceptibility trends among Escherichia coli and Shigella spp. isolated from rural Egyptian paediatric populations with diarrhoea between 1995 and 2000
Authors: S.D. Putnam, M.S. Riddle, T.F. Wierzba, B.T. Pittner, R.A. Elyazeed, A. El-Gendy, M.R. Rao, J.D. Clemens, R.W. Frenck
Journal: Clinical Microbiology and Infection (2004)
Expression analysis of apoptosis-related genes BCL2L12 and PDCD4 in patients with leukemia
Authors: Nur Buyru, Banu Tomekce
Journal: Clinical Cancer Research (2008)

A30   Apoptotic cell death is a highly regulated process, which plays a crucial role in many biological events.The apoptosis-related gene BCL2L12 is located on 19q13.3-13.4 and encodes the BCL2L12 protein which is effective during apoptosis like other Bcl-2 family proteins.The other apoptosis-related gene Pdcd4 is located on 10q24 and encodes the Pdcd4 protein. PDCD4 is a tumor suppressor gene that is overexpressed during apoptosis. Hematologic cancers arise from the stem cells in hematopoetic organs. Chronic myeloid leukemia is a disease mostly seen in adults with rate of 15-20% in overall cancers. Although there is evidence that the BCL2L12 protein is effective on apoptotic pathways, the data with regard to whether it exerts a pro-apoptotic or anti-apoptotic effect are controversial.  In our study, we investigated in the difference expression of BCL2L12 and PDCD4 genes in patients with CML. 57 CML patients and 50 healthy control subjects were involved in the study.  BCL2L12 and PDCD4 gene expression were investigated by RT-PCR. RNA was extracted from peripheral blood lymphocytes using the High Pure RNA Isolation Kit (Roche), following the manufacturer’s instructions and stored at -80 0 C prior to cDNA synthesis. RNA concentration was determined spectrophotometrically. 2.5 µg of total RNA were reverse-transcripted into the cDNA using the Transcriptor First Strand cDNA Synthesis Kit (Roche). Spesific primers for the actin, BCL2L12 and PDCD4 genes were used and PCR was carried out for 35 cycles. Equal amounts of PCR products were electrophoresed on 2% agarose gels and visualised by ethidium bromide staining. The actin gene was used as an internal control for the integrity of the mRNA.  From the 57 CML patients examined, 34 (60%) were classified positive for expression of the BCL2L12 gene and 31 (54%) were classified positive for PDCD4 overexpression. On the other hand, among the 50 healthy subjects, 42 (84%) were positive for BCL2L12 gene expression and 35 (70%) were positive for overexpression of the PDCD4 gene. The associations between the gene expression and clinical variables, including age, sex, Bcr-Abl translocation and survival rate have been compared. No significant assosiations were found between the BCL2L12 gene expression or PDCD4 gene overexpression and clinical variables.  We found that the number of people who express BCL2L12 in the control group was approximately 5 times higher than the number of the people in the patients group (p=0.06). On the other hand, PDCD4 expression frequency was approximately 3 times higher in the patiens group ( p=0.011).
Less is more? Today's economics and its challenge to psychiatry
Authors: Sharfstein Ss, Beigel A
Journal: American Journal of Psychiatry (1984)

Escalating costs of medical and psychiatric care have prompted a reevaluation of the health care delivery system and practice styles. There are several "procompetition" or market-based solutions that seek to make the consumer of care more price conscious and the provider of care more cost conscious. Diagnosis-related groups (DRGs), preferred provider organizations (PPOs), the growth of for-profit hospital systems, and the expansion of health maintenance organizations (HMOs) are reshaping the organization and financing of psychiatric care. Psychiatry's adaptation to the new medical economics must emphasize the quality of patient care.
The enhancement of Stanniocalcin-1 (STC1) secretion increases the ability of mesenchymal stem cells (MSCs) to reduce bleomycin-induced lung fibrosis in a mouse model through inhibition of endoplasmic reticulum stress (ER-stress)/TGFβ1 pathway
Authors: Shinya Ohkouchi, Manabu Ono, Masakazu Ichinose
Journal: European Respiratory Journal (2014)

RATIONALE: Mesenchymal-stem-cells (MSCs) ameliorate fibrosis in bleomycin-induced-lung-injury model. MSCs diminish oxidative stress and rescue alveolar-epitelial-cells (AECs) from apoptosis through secretion of Stanniocalcin-1 (STC1). We hypothesized STC1 contributes to abilities of MSCs ameliorating bleomycin-induced-lung-injury via the protection from oxidative-stress and anti-fibrotic effects by diminishing the endoplasmic-reticulum (ER) stress.  METHODS: C57BL/6 mice were intratracheally injected with bleomycin. After 24 hrs, human MSCs transfected with STC1 plasmid or control were injected into the tail vein.14 days after instillation, pathologic findings were evaluated with immunohistochemistry of TGF-β1 and the ER stress marker, BiP. Anti-fibrotic effects were evaluated by measuring total lung collagen. Oxidative stress was evaluated by 8-Hydroxydeoxyguanosine (8-OHdG) staining.  RESULTS: STC1-overexpressing MSCs enhanced the abilities to ameliorate bleomycin-induced-lung-fibrosis through the reduction of collagen accumulation, oxidative stress and ER-stress on the dependency of STC1 secretion. STC1 secretion in MSCs was controlled by mTOR induced by TGF-β1 in MSCs microenvironments.  CONCLUSIONS: These results suggest that STC1 enhanced the ability of MSCs to ameliorate lung fibrosis via the inhibition of ROS production, reduction of ER stress and decrease of TGF-β1.
Depression, alcohol abuse and orocaecal transit time Reply
Authors: G ADDOLORATO, E CAPRISTO, G GASBARRINI, G F STEFANINI, D A GORARD, J E GOMBORONE, G W LIBBY, M J G FARTHING
Journal: Gut (1997)

Editor,—We read with great interest the paper by Gorard et al ( Gut 1996; 39: 551–5) on intestinal transit in patients with anxiety and depression. The authors used the lactulose hydrogen breath test to evaluate 21 consecutive outpatients attending a general psychiatry clinic who fulfilled DSM III R criteria for major depression or generalised anxiety disorders, or both. They reported a significantly prolonged orocaecal transit time (OCTT) in depressed patients compared with anxious patients, and a significant correlation between whole gut transit time and the score of the psychometric tests used to assess depression, showing evidence for an association between severity of depression and colon inertia. The authors conclude that depressed patients tend to be constipated and that mood has an effect on intestinal motor function, although mechanisms by which mood can alter colonic motility remain unknown.

Recently, we found a significantly prolonged OCTT in patients with chronic alcoholism without severe liver disease compared with social drinkers and teetotal subjects.1 Thirty one alcoholic patients without diseases which …
The Role of Drug Transporters at the Blood-Brain Barrier
Authors: A.G. de Boer, I.C.J. van der Sandt, P.J. Gaillard
Journal: The Annual Review of Pharmacology and Toxicology (2003)

The blood-brain barrier (BBB) is a dynamic interface between the blood and the brain. It eliminates (toxic) substances from the endothelial compartment and supplies the brain with nutrients and other (endogenous) compounds. It can be considered as an organ protecting the brain and regulating its homeostasis. Until now, many transport systems have been discovered that play an important role in maintaining BBB integrity and brain homeostasis. In this review, we focus on the role of carrier- and receptor-mediated transport systems (CMT, RMT) at the BBB. These include CMT systems, such as P-glycoprotein, multidrug-resistance proteins 1–7, nucleoside transporters, organic anion transporters, and large amino-acid transporters; RMT systems, such as the transferrin-1 and -2 receptors; and the scavenger receptors SB-AI and SB-BI.
A randomized controlled study of upper airway stimulation therapy withdrawal effect in treatment of obstructive sleep apnea
Authors: Patrick Strollo, Ryan Soose, Kingman Strohl
Journal: European Respiratory Journal (2013)

Introduction:  Upper Airway Stimulation is a promising treatment option for obstructive sleep apnea (OSA) patients. The primary aim of this randomized controlled trial was to determine the therapy withdrawal effect on polysomnographic (PSG) and quality of life (QOL) outcome measures.   Methods:  The STAR trial enrolled participants with moderate to severe OSA. Participants with BMI    Results:  In the therapy ON (Tx ON) maintenance group, all outcome measures remained unchanged at one week. In the therapy OFF (Tx OFF) withdrawal group, all outcome measures returned towards baseline levels after one week (Table).   Conclusions:  Acute withdrawal of therapy resulted in a return of OSA severity and a decline in quality of life measures compared to therapy maintenance after 12 months of upper airway stimulation treatment.   Support:  Inspire Medical Systems, Minnesota. (ClinicalTrials.gov NCT01161420)