tbuckley/cabot-search huggingface dataset:
Optimizing the Percutaneous Interventional Outcomes for Patients With Diabetes Mellitus
Authors: Steven P. Marso, A. Michael Lincoff, Stephen G. Ellis, Deepak L. Bhatt, Jean-Francois Tanguay, Neal S. Kleiman, Talal Hammoud, Joan E. Booth, Shelly K. Sapp, Eric J. Topol
Journal: Circulation (1999)

Background —Stenting likely decreases the need for target-vessel revascularization procedures in diabetic patients compared with balloon angioplasty. However, the efficacy of stenting with platelet glycoprotein IIb/IIIa blockade has not yet been assessed in diabetics. Methods and Results —We analyzed the outcomes of 491 diabetic patients within the multicenter Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT). Diabetic patients were a prospectively defined subset: 173 were randomized to stent-placebo, 162 to stent-abciximab, and 156 to balloon angioplasty–abciximab. The main end point for this analysis was combined 6-month death, myocardial infarction (MI), or target-vessel revascularization (TVR). The composite end point occurred in 25.2% of stent-placebo, 23.4% of balloon-abciximab, and 13.0% of stent-abciximab patients ( P =0.005). Abciximab therapy, irrespective of revascularization strategy (stent or balloon angioplasty), resulted in a significant reduction in the 6-month death or MI rate: 12.7% for stent-placebo, 7.8% for balloon angioplasty–abciximab, and 6.2% for the stent-abciximab group ( P =0.029). The 6-month TVR rate was 16.6% for stent-placebo, 18.4% for balloon-abciximab, and 8.1% for stent-abciximab ( P =0.021). Compared with stent-placebo, stent-abciximab therapy was associated with a significant increase in angiographic net gain (0.88 versus 0.55 mm; P =0.011) and a decrease in the late loss index (0.40 versus 0.60 mm; P =0.061). The 1-year mortality rate for diabetics was 4.1% for stent-placebo and 1.2% for stent-abciximab patients ( P =0.11). Conclusions —The combination of stenting and abciximab therapy among diabetics resulted in a significant reduction in 6-month rates of death, MI, and TVR compared with stent-placebo or balloon-abciximab therapy.
C-Reactive Protein in Relation to the Development of Microalbuminuria in Type 1 Diabetes
Authors: M. Loredana Marcovecchio, Cosimo Giannini, Barry Widmer, R. Neil Dalton, Stefano Martinotti, Francesco Chiarelli, David B. Dunger
Journal: Diabetes Care (2008)

To perform a longitudinal evaluation of high-sensitivity C-reactive protein (hs-CRP) in young people with type 1 diabetes in relation to the development of microalbuminuria (MA).hs-CRP was measured in 329 blood samples collected from 49 subjects with type 1 diabetes with MA and 49 normoalbuminuric subjects matched for age, sex, and duration of diabetes.In subjects developing MA, a progressive rise in hs-CRP was detected with levels significantly higher in the years after the onset of MA when compared with levels before MA onset (P = 0.003; age-adjusted P = 0.06). After the onset of MA, hs-CRP levels were significantly higher in subjects with MA when compared with normoalbuminuric subjects (median 1.9 mg/l [range 0.2-9.8] vs. 1.1 mg/l [0.2-6.4]; P = 0.02; adjusted P = 0.036).In this population of young subjects with type 1 diabetes, there was a significant increase in hs-CRP levels after the onset of MA, likely reflecting a general state of inflammation.
Genetic Variation and Clinical Heterogeneity in Cystic Fibrosis
Authors: Mitchell L. Drumm, Assem G. Ziady, Pamela B. Davis
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Cystic fibrosis (CF), a lethal genetic disease, is characterized by substantial clinical heterogeneity. Work over the past decade has established that much of the variation is genetically conferred, and recent studies have begun to identify chromosomal locations that identify specific genes as contributing to this variation. Transcriptomic and proteomic data, sampling hundreds and thousands of genes and their products, point to pathways that are altered in the cells and tissues of CF patients. Genetic studies have examined more than half a million polymorphic sites and have identified regions, and probably genes, that contribute to the clinical heterogeneity. The combination of these approaches has great potential because genetic profiling identifies putative disease-modifying processes, and transcript and protein profiling is shedding light on the biology involved. Such studies are providing new insights into the disease, such as altered apoptotic responses, oxidative stress dysregulation, and neuronal involvement, all of which may open new therapeutic avenues to exploration.
Points: Drug-induced cardiovascular disease
Authors: M K Thompson
Journal: BMJ (1979)

A N Bamji (14 April, p 973) with great interest.We were medical students resident in separate Dublin hospitals in 1966.At this time McIlroy appeared at the casualty department of the Royal City of Dublin Hospital complaining of chest pain.One of us (JRN) was connecting him to an ECG machine which required to be earthed.Unfortunately, this was not done and the patient obviously experienced an electric shock.He leapt from the trolley and, putting his finger over his tracheostomy, confirmed in no uncertain terms that this was the case.He took his own discharge.Later that evening this somewhat ruffled student called at the Adelaide Hospital three kilometres or so away.There CED was found to be examining McIlroy, still complain- ing of chest pain but not referring to his recent experience.When he saw JRN he had the grace to look a little embarrassed.The ECG machine in the Adelaide Hospital evidently caused the patient no further upset-and the tracing showed no abnormality.Nevertheless, he spent a comfortable night in hospital and subsequently took his own discharge.There is no doubt in our minds that this man was McIlroy....
Trajectories of Preschool Disorders to Full DSM Depression at School Age and Early Adolescence: Continuity of Preschool Depression
Authors: Joan L. Luby, Michael S. Gaffrey, Rebecca Tillman, Laura M. April, Andy C. Belden
Journal: American Journal of Psychiatry (2014)

Preschool depression and conduct disorder were stronger risk factors for developing full DSM-5 criteria for major depression in later childhood and early adolescence than well-established risk factors such as maternal history of depression or traumatic life events. Early interventions for preschool depression and conduct disorder could help young children at uniquely high risk for later major depression.
NADPH Oxidase Mediates Hypersomnolence and Brain Oxidative Injury in a Murine Model of Sleep Apnea
Authors: Guanxia Zhan, Faridis Serrano, Polina Fenik, Ray Hsu, Linghao Kong, Domenico Pratico, Eric Klann, Sigrid C. Veasey
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Persons with obstructive sleep apnea may have significant residual hypersomnolence, despite therapy. Long-term hypoxia/reoxygenation events in adult mice, simulating oxygenation patterns of moderate–severe sleep apnea, result in lasting hypersomnolence, oxidative injury, and proinflammatory responses in wake-active brain regions. We hypothesized that long-term intermittent hypoxia activates brain NADPH oxidase and that this enzyme serves as a critical source of superoxide in the oxidation injury and in hypersomnolence.Objectives: We sought to determine whether long-term hypoxia/reoxygenation events in mice result in NADPH oxidase activation and whether NADPH oxidase is essential for the proinflammatory response and hypersomnolence.Methods: NADPH oxidase gene and protein responses were measured in wake-active brain regions in wild-type mice exposed to long-term hypoxia/reoxygenation. Sleep and oxidative and proinflammatory responses were measured in adult mice either devoid of NADPH oxidase activity (gp91phox-null mice) or in which NADPH oxidase activity was systemically inhibited with apocynin osmotic pumps throughout hypoxia/reoxygenation.Main Results: Long-term intermittent hypoxia increased NADPH oxidase gene and protein responses in wake-active brain regions. Both transgenic absence and pharmacologic inhibition of NADPH oxidase activity throughout long-term hypoxia/reoxygenation conferred resistance to not only long-term hypoxia/reoxygenation hypersomnolence but also to carbonylation, lipid peroxidation injury, and the proinflammatory response, including inducible nitric oxide synthase activity in wake-active brain regions.Conclusions: Collectively, these findings strongly support a critical role for NADPH oxidase in the lasting hypersomnolence and oxidative and proinflammatory responses after hypoxia/reoxygenation patterns simulating severe obstructive sleep apnea oxygenation, highlighting the potential of inhibiting NADPH oxidase to prevent oxidation-mediated morbidities in obstructive sleep apnea.
Biological Significance of Prolactin in Gynecologic Cancers
Authors: Vera V. Levina, Brian Nolen, YunYun Su, Andrew K. Godwin, David Fishman, Jinsong Liu, Gil Mor, Larry G. Maxwell, Ronald B. Herberman, Miroslaw J. Szczepanski, Marta E. Szajnik, Elieser Gorelik, Anna E. Lokshin
Journal: Cancer Research (2009)

There is increasing evidence that prolactin (PRL), a hormone/cytokine, plays a role in breast, prostate, and colorectal cancers via local production or accumulation. Elevated levels of serum PRL in ovarian and endometrial cancers have been reported, indicating a potential role for PRL in endometrial and ovarian carcinogenesis. In this study, we show that serum PRL levels are significantly elevated in women with a strong family history of ovarian cancer. We show dramatically increased expression of PRL receptor in ovarian and endometrial tumors as well as in endometrial hyperplasia, signifying the importance of PRL signaling in malignant and premalignant conditions. PRL mRNA was expressed in ovarian and endometrial tumors, indicating the presence of an autocrine loop. PRL potently induced proliferation in several ovarian and endometrial cancer cell lines. Binding of PRL to its receptor was followed by rapid phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, mitogen-activated protein kinase/ERK kinase 1, signal transducer and activator of transcription 3, CREB, ATF-2, and p53 and activation of 37 transcription factors in ovarian and endometrial carcinoma cells. PRL also activated Ras oncogene in these cells. When human immortalized normal ovarian epithelial cells were chronically exposed to PRL, a malignant transformation occurred manifested by the acquired ability of transformed cells to form clones, grow in soft agar, and form tumors in severe combined immunodeficient-beige mice. Transformation efficiency was diminished by a Ras inhibitor, providing proof that PRL-induced transformation uses the Ras pathway. In summary, we present findings that indicate an important role for PRL in ovarian and endometrial tumorigenesis. PRL may represent a risk factor for ovarian and endometrial cancers.
Stimulatory Effect of 3′,5′-Adenosine Monophosphate on Protein Synthesis in Heat-Shocked Murine Leukemia Lymphoblasts 2
Authors: J. E. Fuhr, M. Overton, T. J. Yang
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Stimulatory Effect of 3′,5′-Adenosine Monophosphate on Protein Synthesis in Heat-Shocked Murine Leukemia Lymphoblasts Get access J. E. Fuhr, J. E. Fuhr Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Overton, M. Overton Search for other works by this author on: Oxford Academic PubMed Google Scholar T. J. Yang T. J. Yang 3Memorial Research Center, University of Tennessee, 1924 Alcoa Highway, Knoxville, Tenn. 37920. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 1, January 1976, Pages 189–191, https://doi.org/10.1093/jnci/56.1.189 Published: 01 January 1976 Article history Received: 11 June 1975 Accepted: 22 August 1975 Published: 01 January 1976
Altered Brain Microstructure Assessed by Diffusion Tensor Imaging in Patients With Diabetes and Gastrointestinal Symptoms
Authors: Jens Brøndum Frøkjær, Lars Wiuff Andersen, Christina Brock, Magnus Simrén, Maria Ljungberg, Eirik Søfteland, Georg Dimcevski, Yousef Yavarian, Hans Gregersen, Asbjørn Mohr Drewes
Journal: Diabetes Care (2012)

In patients with long-standing diabetes mellitus (DM), there is increasing evidence for abnormal processing of gastrointestinal sensations in the central nervous system. Using magnetic resonance diffusion tensor imaging, we characterized brain microstructure in areas involved in visceral sensory processing and correlated these findings to clinical parameters.Twenty-six patients with DM and gastrointestinal symptoms and 23 healthy control subjects were studied in a 3T scanner. The apparent diffusion coefficient (i.e., diffusivity of water) and fractional anisotropy (FA) (i.e., organization of fibers) were assessed in the "sensory matrix" (cingulate cortex, insula, prefrontal and secondary sensory cortex, amygdala, and corona radiata) and in corpus callosum.Patients had decreased FA values compared with control subjects in 1) all areas (P = 0.025); 2) anterior (P < 0.001), mid- (P = 0.001), and posterior (P < 0.001) cingulate cortex; 3) prefrontal cortex gray matter (P < 0.001); 4) corona radiata (P < 0.001); 5) secondary sensory cortex (P = 0.008); and 6) anterior white matter (P = 0.045), anterior gray matter (P = 0.002), and posterior gray matter (P = 0.002) insula. No difference was found in corpus callosum (P > 0.05). The microstructural changes in some areas correlated with clinical parameters such as bloating (anterior insula), mental well-being (anterior insula, prefrontal cortex, and mid-cingulated and corona radiata), autonomic function based on electrocardiographic results (posterior insula and anterior cingulate), and presence of gastroparesis (anterior insula).The findings of this explorative study indicate that microstructural changes of brain areas involved in visceral sensory processing are associated with autonomic dysfunction and therefore may be involved in the pathogenesis of gastrointestinal symptoms in DM patients.
Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis
Authors: Lutz Wollin, Eva Wex, Alexander Pautsch, Gisela Schnapp, Katrin E. Hostettler, Susanne Stowasser, Martin Kolb
Journal: European Respiratory Journal (2015)

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease characterised by fibrosis of the lung parenchyma and loss of lung function. Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. A number of profibrotic mediators including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and transforming growth factor-β are believed to play important roles in the pathogenesis of IPF. Nintedanib is a potent small molecule inhibitor of the receptor tyrosine kinases PDGF receptor, FGF receptor and vascular endothelial growth factor receptor. Data from in vitro studies have shown that nintedanib interferes with processes active in fibrosis such as fibroblast proliferation, migration and differentiation, and the secretion of ECM. In addition, nintedanib has shown consistent anti-fibrotic and anti-inflammatory activity in animal models of lung fibrosis. These data provide a strong rationale for the clinical efficacy of nintedanib in patients with IPF, which has recently been demonstrated in phase III clinical trials.
Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat.
Authors: L C Racusen, H J Binder
Journal: Journal of Clinical Investigation (1979)

Perfusion of the colon with ricinoleic acid produces fluid and electrolyte accumulation. The mechanism of these changes in water and electrolyte movement is uknown. These studies were designed to determine whether ricinoleic acid effects active ion transport across isolated rat colonic mucosa. 0.5 mM Na ricinoleate produced significant increases in potential difference (3.8 +/- 0.5 mV) and short-circuit current (Isc) (99.2 +/- 10.1 muA/cm2). The increases in Isc produced by Na ricinoleate were inhibited by both removal of bicarbonate and chloride and by the presence of theophylline. The hydroxy fatty acid also resulted in a significant decrease in net Na absorption from 4.7 +/- 0.8 to 0.1 +/- 0.7 mueq/h cm2 and reversed net Cl transport from absorption (+ 4.5 +/- 0.9) to secretion (-2.2 +/- mueq/h cm2). In parallel studies 0.5 mM Na ricinoleate increased mucosal cyclic AMP content by 58%. The concentrations of Na ricinoleate required to produce detectable and maximal increases in both Isc and cyclic AMP were the same. These results provide evidence in support of the concept that hydroxy fatty acid-induced fluid and electrolyte accumulation is driven by an active ion secretory process.
Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys
Authors: M Innes Asher, Stephen Montefort, Bengt Björkstén, Christopher KW Lai, David P Strachan, Stephan K Weiland, Hywel Williams
Journal: The Lancet (2006)
Carcinoid tumours of the bronchus: a 33 year experience.
Authors: R Hurt, M Bates
Journal: Thorax (1984)

The term adenoma of the bronchus is discussed, and 79 cases of bronchial carcinoid seen from 1951 to 1983 are reviewed. The symptoms, radiological findings, and bronchoscopic appearances are described. There was no case of the carcinoid syndrome. In no case did haemorrhage cause any serious problem after biopsy at rigid bronchoscopy. In three patients the tumour was reported to be an oat cell carcinoma-in two on the basis of material obtained at fibreoptic bronchoscopy. Resection was by pneumonectomy in 10 cases, lobectomy in 52, segmentectomy in six, a bronchoplastic procedure without resection of lung in seven cases, enucleation in two, and a wedge resection in one case. There was one case of atypical carcinoid which was found at operation to be unresectable. A 5-30 year follow up in 57 cases revealed a recurrence of tumour in two cases, nine and 16 years after lung resection. No recurrence occurred in the nine cases treated by conservative bronchial resection with conservation of lung tissue. An actuarially assessed life table analysis shows survival rates of 94% after 10 years, 80% after 15 years, and 64% after 25 years without recurrence. The similarity of carcinoid to oat cell carcinoma is noted and the serious clinical implications of this are analysed, especially in view of the increasing use of fibreoptic bronchoscopy. The malignant potential of carcinoid and the extent of pulmonary resection is discussed. It is concluded that a carcinoid tumour of the lung has only slight malignant potential and that it may be treated by bronchotomy or sleeve resection of the bronchus in suitable cases. If serious infective changes have occurred in the lung distal to the tumour or if the tumour has extended into the lung parenchyma (88% of cases in this series) lung resection will be necessary. The follow up period should be for at least 25 years, in view of the incidence of late recurrence.
Absence of allogeneic restriction in human T-cell-mediated cytotoxicity to Epstein-Barr virus-infected target cells. Demonstration of an HLA-linked control at the effector level.
Authors: M Lipinski, W H Fridman, T Tursz, C Vincent, D Pious, M Fellous
Journal: The Journal of Experimental Medicine (1979)

Peripheral T lymphocytes from patients with infectious mononucleosis (IM) are sensitized in vivo against the Epstein-Barr virus (EBV). The expression of HLA-A, B, or C molecules at the target cell surface is necessary for the cytotoxic reaction because (a) EBV-positive Daudi cells lacking HLA-A, B, and C determinants are resistant to anti-EBV T-cell lysis, (b) cytolysis of EBV-positive target cells can be consistently inhibited by anti-HLA-A, B, and C and anti-beta 2 microglobulin antibodies. However, no evidence for allogeneic restriction in this system was apparent as (a) cytotoxic T lymphocytes (CTL) from one given individual could exert a cytotoxicity of a similar magnitude on different EBV-positive target cells, regardless of the number of HLA-A or B specificities shared by the effectors and targets; (b) CTL from IM patients were able to kill target cells without any HLA-A or B antigen in common; and (c) T5-1 variants lacking one or two HLA antigens at the A, B, or D locus are killed to the same extent as the parental cells. 7 of the 9 IM patients with detectable circulating anti-EBV CTL carried the HLA-A1 antigen, whereas none of the 16 IM patients lacking detectable peripheral CTL were HLA-A1 positive (mean specific lysis of T5-1 target cells by T cells from HLA-A1 positive patients: 29.3 vs. 0.6% in HLA-A1-negative patients) (P less than 10(-9)). These data suggest an HLA-A1-linked gene control of the magnitude of the anti-EBV CTL response. Thus, the HLA region appears to act at two different level sin the T-cell-mediated lysis of EBV-infected cells by controlling first, the development of anti-EBV and second, the expression of HLA-A, B, and C molecules involved as recognition structures at the target cell surface.
Randomized, Controlled, Dose-Range Study of Ro 25-8315 Given Before and After a High-Dose Combination Chemotherapy Regimen in Patients With Metastatic or Recurrent Breast Cancer Patients
Authors: P. Viens
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 μg/kg, n = 9; 60 μg/kg, n = 9; 100 μg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 μg/kg/d; part II, 5 μg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 μg/kg. The peak of circulating CD34+ cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 × 109/L by day +15. In part II, high levels of circulating CD34+ cells (> 20 cells/μL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 × 109/L) was similar in the four groups. Ro 25-8315 100 μg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 × 109/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 μg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 μg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.