tbuckley/cabot-search huggingface dataset:
Long-term renoprotective effect of nisoldipine and lisinopril in type 1 diabetic patients with diabetic nephropathy.
Authors: L Tarnow, P Rossing, C Jensen, B V Hansen, H H Parving
Journal: Diabetes Care (2000)

OBJECTIVE: To compare the long-term effect on kidney function of a long-acting calcium antagonist (nisoldipine) versus a long-acting ACE inhibitor (lisinopril) in hypertensive type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We performed a 4-year prospective, randomized, double-dummy controlled study comparing nisoldipine (20-40 mg once a day) with lisinopril (10-20 mg once a day). The study was double-blinded for the first year and single-blinded thereafter. The study included 51 hypertensive type 1 diabetic patients with diabetic nephropathy. Three patients dropped out during the first month; results for the remaining 48 patients are presented. RESULTS: At baseline, the two groups were comparable: glomerular filtration rate (GFR) was 85 +/- 5 and 85 +/- 6 ml x min(-1) x [1.73 m](-2); mean 24-h ambulatory blood pressure was 108 +/- 3 and 105 +/- 2 mmHg, and albuminuria was 1,554 mg/24 h (95% CI 980-2,465) and 1,033 mg/24 h (760-1,406) in the lisinopril and nisoldipine groups, respectively. Mean 24-h arterial blood pressure during the study did not differ between the lisinopril and nisoldipine groups (100 +/- 2 and 103 +/- 1 mmHg, respectively). The time-course of albuminuria differed between groups (P &amp;lt; 0.001). Whereas initiation of treatment with lisinopril resulted in a reduction from baseline albuminuria by 52% (95% CI 14-73), albuminuria in the nisoldipine group did not change throughout the study GFR declined in a biphasic manner with an initial (0-6 months) reduction of 1.3 +/- 0.3 ml x min(-1) x month(-1) in the lisinopril group compared with 0.2 +/- 0.4 ml x min(-1) x month(-1) in the nisoldipine group (P &amp;lt; 0.01). The subsequent sustained decline (6 to 48 months or the end of treatment) was identical in the two groups: 0.5 +/- 0.1 ml min(-1) x month(-1) (NS). Two patients in the lisinopril group and three patients in the nisoldipine group entered therapy for end-stage renal failure. CONCLUSIONS: Long-term treatment with lisinopril or nisoldipine has similar beneficial effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients.
FGL2/Fibroleukin mediates hepatic reperfusion injury by induction of sinusoidal endothelial cell and hepatocyte apoptosis in mice
Authors: Nazia Selzner, Hao Liu, Markus U. Boehnert, Oyedele A. Adeyi, Itay Shalev, Agata M. Bartczak, Max Xue-Zhong, Justin Manuel, Ori D. Rotstein, Ian D. McGilvray, David R. Grant, Melville J. Phillips, Gary A. Levy, Markus Selzner
Journal: Journal of Hepatology (2011)
Angiogenesis and Cardiac Hypertrophy
Authors: Toru Oka, Hiroshi Akazawa, Atsuhiko T. Naito, Issei Komuro
Journal: Circulation Research (2014)

Cardiac hypertrophy is an adaptive response to physiological and pathological overload. In response to the overload, individual cardiac myocytes become mechanically stretched and activate intracellular hypertrophic signaling pathways to re-use embryonic transcription factors and to increase the synthesis of various proteins, such as structural and contractile proteins. These hypertrophic responses increase oxygen demand and promote myocardial angiogenesis to dissolve the hypoxic situation and to maintain cardiac contractile function; thus, these responses suggest crosstalk between cardiac myocytes and microvasculature. However, sustained pathological overload induces maladaptation and cardiac remodeling, resulting in heart failure. In recent years, specific understanding has increased with regard to the molecular processes and cell–cell interactions that coordinate myocardial growth and angiogenesis. In this review, we summarize recent advances in understanding the regulatory mechanisms of coordinated myocardial growth and angiogenesis in the pathophysiology of cardiac hypertrophy and heart failure.
Cardiovascular Disease Risk Factors Predict the Development of Type 2 Diabetes
Authors: Ralph B. D’Agostino, Richard F. Hamman, Andrew J. Karter, Leena Mykkanen, Lynne E. Wagenknecht, Steven M. Haffner
Journal: Diabetes Care (2004)

OBJECTIVE—In a few previous studies, cardiovascular disease (CVD) risk factors (RFs) have been shown to predict diabetes. Our objective was to determine whether the presence of CVD RFs predict the eventual development of diabetes after controlling for known RFs, such as directly measured insulin resistance and obesity. RESEARCH DESIGN AND METHODS—We studied 872 participants with normal or impaired glucose tolerance (IGT) who were enrolled at baseline in the Insulin Resistance Atherosclerosis Study (IRAS). Of these, 143 (16%) developed type 2 diabetes in 5 years. Using these participants, a series of logistic regression models were fit to address the question. RESULTS—Significant RFs for developing type 2 diabetes included high plasminogen activator inhibitor-1, hypertension, high triglycerides, low levels of HDL cholesterol, and IGT. The 5-year cumulative incidence of type 2 diabetes by the number of RFs (0–5) was as follows: no RFs, 11 of 230 = 5%; one RF, 31 of 278 = 11%; two RFs, 36 of 202 = 18%; three RFs, 41 of 110 = 37%; four RFs, 19 of 42 = 45%; and five RFs, 5 of 10 = 50% (P &amp;lt; 0.001). The odds ratio (OR) for conversion to type 2 diabetes for each additional RF was 2.1 (95% CI 1.78–2.46) after adjusting for age, sex, ethnicity, and center. After further adjustment for insulin resistance, determined by the frequently sampled intravenous glucose tolerance test and waist circumference, each additional CVD RF increased the risk of type 2 diabetes significantly (OR 1.81, 95% CI 1.49–2.20). CONCLUSIONS—Individuals with multiple CVD RFs are at increased risk of type 2 diabetes, which is only partially mediated by insulin resistance or central adiposity. This information should be useful for identifying high-risk patients for developing diabetes through RF assessments.
Is air travel safe for those with lung disease?
Authors: E. Marchand
Journal: European Respiratory Journal (2008)

To the Editors: 

I read with interest the article of Coker et al. 1 regarding the safety of commercial air travel for patients with lung disease. This is an area of concern since both the prevalence of chronic obstructive pulmonary disease and the number of people flying for leisure purposes are increasing. The available guidelines are based on very limited scientific evidence. Owing to the lack of data and potential adverse consequences of hypoxaemia induced by air travel, the recommendations proposed by scientific societies and panel guidelines are purposefully cautious.

The prospective evaluation of a large cohort such as …
Dynamic Myocardial Ischemia Caused by Circumflex Artery Stenosis Detected by a New Implantable Left Atrial Pressure Monitoring Device
Authors: Jay L.T. Ritzema-Carter, David Smyth, Richard W. Troughton, Ian G. Crozier, Iain C. Melton, A. Mark Richards, Neal Eigler, James Whiting, Saibal Kar, Henry Krum, William T. Abraham
Journal: Circulation (2006)
Psoriasis, psoriatic arthritis and cardiovascular risk: are we closer to a clinical recommendation?
Authors: Søren Lund Kristensen, Iain B McInnes, Naveed Sattar
Journal: Annals of the Rheumatic Diseases (2014)

The issue of vascular risk in chronic arthropathies and especially the magnitude of such risk and its clinical implications in daily practice are of considerable current importance. Similarly, the relative risk across distinct arthropathies and other chronic inflammatory conditions is debated. Ogdie et al 1 report associations between psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA) and an increased risk of major adverse cardiovascular events (MACE—myocardial infarction, stroke and cardiovascular death) in data derived from the UK primary care registry. Results are stratified by use of disease-modifying antirheumatic drugs (DMARDs). The risk for MACE appeared overall highest among patients with RA, and higher for DMARD users than non-users in RA and psoriasis. By contrast, combined risk of all outcomes was increased less in patients with PsA, and here, DMARD users had lower risks than non-DMARD users.

The statistical and epidemiological methods applied here are apparently sound, and important new information on increased cardiovascular risk in PsA, together with reaffirmation of earlier findings in psoriasis and RA, is presented. Limitations include their categorical adjustments for lipids and hypertension rather than adjustment for continuously measured risk factors. In addition, their somewhat arbitrary use of treatment (DMARDS) as a proxy marker of disease severity is challenging but pragmatic. On the one hand, those not receiving DMARDS should have lower disease activity, but, on the other, DMARDS attenuate inflammation and potentially lower vascular risk. There is also the possibility that some patients with PsA were missed and categorised as having …
The effect of fluticasone on the airway inflammatory response to organic dust
Authors: A. Ek
Journal: European Respiratory Journal (2004)

Exposure to organic dust in a swine house causes acute airway inflammation and increased bronchial responsiveness to methacholine in healthy subjects. The aim of this study was to investigate whether an inhaled glucocorticoid, fluticasone propionate, alters the acute airway responses induced by exposure in a swine barn. In 15 healthy subjects, analysis of nasal lavage fluids, serum samples and bronchial methacholine responsiveness were performed before and after exposure to organic dust in a swine house for 3 h. Seven subjects received fluticasone propionate (500 microg b.i.d. by inhalation and 100 microg intranasally once daily) and eight subjects received placebo during the 2 weeks prior to exposure. Post-exposure plasma interleukin (IL)-6 levels and body temperature were significantly lower in the fluticasone group than in the placebo group. Intranasally administered fluticasone propionate significantly attenuated the plasma protein (assessed as albumin concentrations) leakage and IL-8 and tumour necrosis factor-alpha response induced by exposure. Fluticasone propionate inhalation exerted no influence on the increased bronchial responsiveness to methacholine induced by exposure. In conclusion, glucocorticoid treatment attenuated the inflammatory response to inhaled organic dust without influencing the increased bronchial responsiveness to methacholine.
Can diaphragm pacing improve gas exchange? Insights from quadriplegic patients
Authors: Jésus Gonzalez-Bermejo, Capucine Morélot-Panzini, Marjolaine Georges, Alexandre Demoule, Thomas Similowski
Journal: European Respiratory Journal (2013)

To the Editor: 

Diaphragm pacing, as obtained by phrenic nerve stimulation through implanted electrodes, is a valid alternative to positive pressure mechanical ventilation (PPV) in patients with high spinal cord injuries [1]. Diaphragm pacing allows such patients to be weaned from PPV, but, to date, the respective effects of diaphragm pacing and PPV on gas exchange have not been compared. PPV is known to reduce ventilation in the lung bases [2]. By contrast, diaphragm pacing, like spontaneous breathing, should direct a larger proportion of the inspired volume to the lung bases. This should improve ventilation/perfusion matching. If this is the case, diaphragm pacing could be of interest as an adjunct to PPV in patients with lung injury. Indeed, in this setting, preserving diaphragmatic activity during mechanical ventilation can improve arterial oxygenation [3]. However, this can be difficult to achieve from a comfort point of view. In a proof-of-concept perspective, we compared blood gases and energy expenditure during PPV and diaphragm pacing in 10 quadriplegics.

10 consecutive, stable and well-nourished tracheotomised quadriplegic patients were studied (six males, aged 15–46 years, mean±sd body mass index 21.9±4.0 kg·m−2). All had a phrenic nerve stimulator (Atrostim; Atrotech, Tampere, Finland) implanted at least 6 months earlier and were considered fully reconditioned. They were studied during planned routine visits, after approval of the ethics committee of the French Learned Society for Intensive Care Medicine. All patients gave their informed consent. Measurements were performed at least 3 h after a meal, with the tracheal cuff inflated. Oxygen consumption ( V ′O2), carbon dioxide production ( V ′CO2) and respiratory quotient were …
Age-related changes in fibronectin expression in spontaneously hypertensive, Wistar-Kyoto, and Wistar rat hearts.
Authors: W Mamuya, A Chobanian, P Brecher
Journal: Circulation Research (1992)

The effects of age and blood pressure on fibronectin expression in the rat heart were studied in the normotensive Wistar and Wistar-Kyoto (WKY) strains and in the spontaneously hypertensive rat (SHR). Fibronectin mRNA expression decreased threefold between 10 and 40 weeks of age in Wistar hearts, with changes of similar magnitude occurring between 6 and 24 weeks in WKY rats. In contrast, no decrease in fibronectin mRNA was observed in SHR hearts during this time span. These results are in contrast to changes observed previously in the aorta, where an increase in fibronectin mRNA occurred with age in all three rat strains. Ribonuclease protection analysis showed a small age-specific increase in the relative content of EIIIA+ fibronectin mRNA isoforms in hearts from Wistar rats, whereas no change was found in the relative amount of either EIIIA or EIIIB isoforms in SHR hearts. Changes similar to those observed for fibronectin mRNA, although of different magnitudes, were observed in mRNA levels for collagen alpha 1(III) and beta 1 integrin. In Wistar hearts, collagen alpha 1(III) mRNA levels decreased fivefold to sixfold between 10 and 40 weeks of age, whereas a twofold to threefold decrease in beta 1 integrin was observed in WKY hearts between 6 and 24 weeks of age. Western blot analysis revealed a positive correlation between fibronectin mRNA and protein for age-dependent changes in ventricular tissue but not in the atria, suggesting that the regulation of fibronectin expression during the changes common to both aging and hypertrophy could involve both transcriptional and posttranscriptional mechanisms.
Long-Term Results of a Randomized Study Comparing Three Immunosuppressive Schedules with Cyclosporine in Cadaveric Kidney Transplantation
Authors: GIUSEPPE MONTAGNINO, ANTONIO TARANTINO, GIUSEPPE P. SEGOLONI, VINCENZO CAMBI, GAETANO RIZZO, PAOLO ALTIERI, MARCO CASTAGNETO, MAURIZIO SALVADORI, MARIA COSSU, FRANCESCO PISANI, MARIO CARMELLINI, FRANCESCO MASTRANGELO, ROBERTO FERRARA, CLAUDIO PONTICELLI
Journal: Journal of the American Society of Nephrology (2001)

In this randomized controlled trial started in October 1990, 354 cadaveric kidney transplant recipients were assigned to receive either cyclosporine (CsA) monotherapy (115 patients), CsA + steroids (117 patients), or CsA + steroids + azathioprine (122 patients). The median follow-up was 85.1 mo. Thirty-one deaths occurred (infection, 12; cardiovascular disease, 11; neoplasia, 4; and others, 4), and 65 grafts were lost, mostly due to acute (15) or chronic rejection (50). The cumulative graft half-life was 18.1 yr. According to the "intention-to-treat," the 9-yr actuarial patient and graft survival were 94.0% and 73.3%, respectively, in monotherapy, 87.3% and 65.9% in dual therapy, and 87% and 72.2% in triple therapy (P = 0.647). At the last follow-up, the percentage of patients who remained with the original treatment was 51.2% in monotherapy, 81.7% in dual therapy, and 63.3% in triple therapy. At the seventh year, the mean creatinine clearances were 54.9 ± 17.6 ml/min in monotherapy, 57.9 ± 23.4 in dual therapy, and 60.6 ± 20.7 in triple therapy (P = 0.375). Cataracts (P = 0.000), osteoporosis (P = 0.000), and cardiovascular complications (P = 0.000) were more frequent in dual or triple therapy than in monotherapy. Actuarial graft survival at 9 yr in patients on monotherapy who had to have steroids added was similar to that of the other two groups (62.2% versus 69.3%, P = 0.134). In conclusion, actuarial patient and graft survivals did not differ among the three schemes. The long-term renal function and survival were not affected in the patients on monotherapy who needed the addition of steroids. Monotherapy was associated with a lower incidence of extrarenal complications than the other two regimens.
Inflame On!
Authors: Gerald W. Dorn
Journal: Circulation Research (2012)

M itochondria are derived from primordial bacterial endosymbionts and retain partial genomes.In mammalian cells, damaged or dysfunctional mitochondria are recognized, targeted for elimination, then neatly packaged and eliminated via mitophagy.A recent paper from Oka et al describes how interrupting normal mitophagic mitochondrial DNA degradation after pressure overload can activate Toll-like receptor-9 mediated innate immunity, causing myocardial inflammation that contributes to cardiomyopathic decompensation.
Rituximab is associated with improved survival for aggressive B cell CNS lymphoma
Authors: G. Gregory, A. Arumugaswamy, T. Leung, K.-L. Chan, M. Abikhair, C. Tam, A. Bajel, L. Cher, A. Grigg, D. Ritchie, S. Opat
Journal: Neuro-Oncology (2013)

The optimal treatment strategy in patients with aggressive B cell central nervous system lymphoma suitable to receive intensive therapy is unknown. The benefit of incorporating rituximab in systemic therapy remains unclear. We performed a retrospective study examining the impact of rituximab in the context of concomitant therapies, including methotrexate, cytarabine, and radiotherapy, in patients treated with curative intent at 4 university teaching hospitals during 1996–2011. A retrospective study of CNS lymphoma cases treated at the participating institutions was performed in accordance with institutional ethical guidelines. Patients were included if they received a diagnosis of primary diffuse large B cell lymphoma of the CNS, were HIV negative, and were treated with curative intent. One hundred twenty patients aged 21–81 years were identified. Rituximab recipients and nonrecipients were similar, except for rituximab recipients being more likely to have received a diagnosis after 2004. The median follow-up of surviving patients was 30 months. The 5-year overall survival was 46%. Univariate analysis revealed age ≤60 years, ECOG performance status ≤1, normal lactate dehydrogenase, diagnosis after 2004, and treatment with cytarabine and rituximab as predictive of favorable overall survival. Multivariate analysis identified age to be an independent predictor of overall survival, with a trend toward improved survival from the other variables that were significant in univariate analyses. In this retrospective analysis, the addition of rituximab to high-dose methotrexate-based chemotherapy in patients with aggressive B cell CNS lymphoma was associated with improved overall survival. Further studies are underway to prospectively validate these findings.
Hemorrhagic cystitis in patients treated with cabazitaxel: a radiation recall syndrome?
Authors: T. Grellety, Nadine Houédé, J. L. Hoepffner, Jérôme Rivière, C. Merino, V. Lieutenant, M. Gross-Goupil, P. Richaud, C. Dupin, P. Sargos, G. Roubaud
Journal: Annals of Oncology (2014)
Epidermal growth factor in the lungs of infants developing chronic lung disease
Authors: A.E. Currie, J.R. Vyas, J. MacDonald, D. Field, S. Kotecha
Journal: European Respiratory Journal (2001)

Growth factors important to lung growth and fibrosis have been poorly studied in chronic lung disease (CLD) of prematurity. Epidermal growth factor (EGF) promotes epithelial cell maturation, and vascular endothelial growth factor (VEGF) is important in angiogenesis. The concentration of these growth factors was determined in 111 bronchoalveolar lavage fluid (BALF) samples from 35 ventilated infants: 13 developed CLD (median gestation 27 weeks, birthweight 820 g), 16 developed and recovered from respiratory distress syndrome (RDS) (31 weeks, 1,415 g) and six control infants (33 weeks, 2,075 g) were ventilated for nonpulmonary reasons. At birth, EGF in BALF from the CLD and RDS infants was lower than in the control infants (control <i>versus</i> CLD, 7.3 <i>versus</i> 0.0 pg·mL<sup>−1</sup>, p&lt;0.01; control <i>versus</i> RDS, 7.3 <i>versus</i> 5.0, p=0.08). EGF increased in all groups with a more rapid increase in control infants. A close relationship was noted between BALF EGF and gestational age (R=0.73). VEGF was undetectable at birth but increased at a similar rate in all three groups and did not correlate with gestation. In conclusion, these data suggest that epidermal growth factor is closely correlated to gestation and that it may predispose preterm infants to develop chronic lung disease.
Gastric and Intestinal Phenotypic Marker Expression in Early Differentiated-Type Tumors of the Stomach: Clinicopathologic Significance and Genetic Background
Authors: Yusuke Tajima, Kimiyasu Yamazaki, Reiko Makino, Nobukazu Nishino, Shigeo Aoki, Masanori Kato, Koji Morohara, Tsutomu Kaetsu, Mitsuo Kusano
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. In the present study, we determined the clinicopathologic significance of phenotypic marker expression in early-stage gastric differentiated-type tumors and the association between marker expression and genetic alterations. Experimental Design: Phenotypic marker expression was determined by examining the expressions of human gastric mucin (HGM), MUC6, MUC2, and CD10 in 63 gastric adenomas, 133 early differentiated-type carcinomas, and 24 follow-up cases with gastric adenoma. Tumors were classified into gastric, gastric and intestinal mixed, or intestinal phenotypes according to the immunopositivity of the above markers. The presence of mutations in APC, K-ras, and p53 and the microsatellite instability status were also determined in all tumors. Results: The expressions of HGM and MUC6, representing gastric or gastric and intestinal mixed phenotypes, were significantly associated with high-grade atypia in the 63 gastric adenomas. Among the 133 early differentiated-type carcinomas, HGM expression was significantly associated with mixed-type (with an undifferentiated-type component) tumors and lymph node metastasis. MUC2 expression was inversely associated with submucosal invasion. A multivariate analysis revealed that gastric adenomas were significantly associated with the intestinal phenotype and were inversely associated with p53 mutation compared with early differentiated-type carcinomas. Among all 196 tumors, APC mutation was significantly associated with CD10 expression and the intestinal phenotype and was inversely associated with the expressions of HGM and MUC6. The microsatellite instability status was significantly associated with MUC6 expression. Malignant transformation from gastric adenoma to carcinoma was shown in 5 of the 24 follow-up cases of gastric adenoma. The malignant transformation was significantly associated with the gastric and intestinal mixed phenotype and was inversely associated with APC mutation. No malignant transformation was found in intestinal phenotype gastric adenomas with APC mutation. Conclusions: Our present findings show that phenotypic marker expression is associated with tumor aggressiveness during the early stage of gastric differentiated-type tumors. Differences in the biological behavior of tumors with different phenotypes may result from differences in the genetic backgrounds during the incipient phase of gastric tumorigenesis.