tbuckley/cabot-search huggingface dataset:
P267 The effects of Apelin on serum NT-proBNP levels in Pulmonary Hypertension Patients versus Controls
Authors: GS Reid, KS Wilson, K Suveizdyte, L Brash, AJ Peacock, DJ Welsh
Journal: Thorax (2015)

<h3>Background</h3> Pulmonary Hypertension has a poor prognosis and therapy is limited to symptomatic relief. Apelin, a new therapy, has the potential to address the underlying pathology whilst also providing relief of symptoms. NT-proBNP a marker of disease severity is commonly used to assess treatment effect. <h3>Aims and objectives</h3> This study aimed to investigate, for the first time, the effects of apelin on serum NT-proBNP concentration in groups of pulmonary hypertension patients and controls. The hypothesis of the study was that apelin would cause a change in NT-proBNP. <h3>Methods</h3> Serum samples from patients recruited for a haemodynamic investigation of apelin were used. The groups studied were controls, pulmonary arterial hypertension and pulmonary hypertension due to left heart failure. In the haemodynamic study each patient was given an apelin and placebo infusion separately over a period of several minutes. Serum samples were taken pre and post infusion. NT-proBNP concentration in the samples was determined using the ABNOVA ELISA kit. <h3>Results</h3> There was no significant change in NT-proBNP levels due to apelin infusion across all groups (P = 0.830). On sub group analysis there was no significant change detected in any group as shown in Figure 1. <h3>Conclusion</h3> NT-proBNP levels do not immediately change in response to several minutes of apelin infusion. This is consistent amongst control and pulmonary hypertension patients. Despite the lack of change in NT-proBNP levels seen in this study, the haemodynamic response pattern reported for apelin<sup>1</sup> has been associated with NT-proBNP changes in other drug studies. The main difference between these studies and this study was investigation of therapy effect over a longer time period. From our results we cannot conclude that apelin has no effect on NT-proBNP levels. Investigation of therapy over a longer time period is required. <h3>Reference</h3> 1 Brash L, Church C, Gibbs JS, Howard LSGE, Johnson MK, Welsh DJ, Wilkins MR, Newby DE, Peacock AJ. Apelin improves cardiac output in patients with pulmonary arterial hypertension. Submitted to ERS 2015 Conference
Cardiotoxicity of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cells Transplantation in Patients with Malignant Lymphomas. what is Worse - Beam or Cbv?
Authors: V. Sarzhevskiy, D. Kolesnikova, V. Melnichenko, M. Vakhromeeva
Journal: Annals of Oncology (2014)
The toxin biliatresone causes mouse extrahepatic cholangiocyte damage and fibrosis through decreased glutathione and SOX17
Authors: Orith Waisbourd‐Zinman, Hong Koh, Shannon Tsai, Pierre‐Marie Lavrut, Christine Dang, Xiao Zhao, Michael Pack, Jeff Cave, Mark Hawes, Kyung A. Koo, John R. Porter, Rebecca G. Wells
Journal: Hepatology (2016)

Biliary atresia, the most common indication for pediatric liver transplantation, is a fibrotic disease of unknown etiology affecting the extrahepatic bile ducts of newborns. The recently described toxin biliatresone causes lumen obstruction in mouse cholangiocyte spheroids and represents a new model of biliary atresia. The goal of this study was to determine the cellular changes caused by biliatresone in mammalian cells that ultimately lead to biliary atresia and extrahepatic fibrosis. We treated mouse cholangiocytes in three‐dimensional (3D) spheroid culture and neonatal extrahepatic duct explants with biliatresone and compounds that regulate glutathione (GSH). We examined the effects of biliatresone on SOX17 levels and determined the effects of Sox17 knockdown on cholangiocytes in 3D culture. We found that biliatresone caused disruption of cholangiocyte apical polarity and loss of monolayer integrity. Spheroids treated with biliatresone had increased permeability as shown by rhodamine efflux within 5 hours compared with untreated spheroids, which retained rhodamine for longer than 12 hours. Neonatal bile duct explants treated with the toxin showed lumen obstruction with increased subepithelial staining for α‐smooth muscle actin and collagen, consistent with fibrosis. Biliatresone caused a rapid and transient decrease in GSH, which was both necessary and sufficient to mediate its effects in cholangiocyte spheroid and bile duct explant systems. It also caused a significant decrease in cholangiocyte levels of SOX17, and Sox17 knockdown in cholangiocyte spheroids mimicked the effects of biliatresone. Conclusion: Biliatresone decreases GSH and SOX17 in mouse cholangiocytes. In 3D cell systems, this leads to cholangiocyte monolayer damage and increased permeability; in extrahepatic bile duct explants, it leads to disruption of the extrahepatic biliary tree and subepithelial fibrosis. This mechanism may be important in understanding human biliary atresia. (H epatology 2016;64:880‐893)
Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury
Authors: Conrad A. Farrar, David Tran, Ke Li, Weiju Wu, Qi Peng, Wilhelm Schwaeble, Wuding Zhou, Steven H. Sacks
Journal: Journal of Clinical Investigation (2016)

Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.
Alcohol Use Disorder and Mortality Across the Lifespan
Authors: Kenneth S. Kendler, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist
Journal: JAMA Psychiatry (2016)

Excess alcohol consumption and alcohol use disorders (AUDs) are associated with substantially increased mortality. Efforts to reduce this toll require an understanding of their causes.To clarify the degree to which the excess mortality associated with AUDs arises (1) from the predispositions of the person who develops AUD (and which would likely be shared by close relatives) and (2) as a direct result of AUD itself.A prospective cohort and co-relative design study involving all individuals born in Sweden from 1940 to 1965 who had neither died nor migrated prior to 1973 or age 15 years (N = 2 821 036). They were followed up from January 1, 1973, until December 31, 2010. Alcohol use disorder was assessed from medical, criminal, and pharmacy registries. Half-siblings, full-siblings, and monozygotic twin pairs discordant for AUD were obtained from the Multi-Generation and Twin Register.Death obtained from the Swedish Death registry.Our cohort (1 447 887 males and 1 373 149 females) included 131 895 males and 42 163 females registered with AUD. The mean (SD) age at first AUD registration was 39 (13.4) years. We ascertained 127 347 and 76 325 deaths in the male and female subsamples, respectively. Controlling for sex, educational status, and year of birth, the mortality hazard ratio associated with AUD was 5.83 (95% CI, 5.76-5.90) and varied-with an inverted U-shaped function-by age. Examining the AUD-mortality association in the general population and in relative pairs discordant for AUD exposure demonstrated substantial familial confounding in early to mid-adulthood: the AUD-associated mortality hazard ratio was much lower in discordant close relatives than in the general population. In middle to late adulthood, evidence for familial confounding decreased with increasing evidence for a direct effect of AUD on elevated mortality. In the oldest age group (65-70 years), the mortality hazard ratios were similar across the population and all relative pairs, suggesting that the excess mortality was largely a result of having AUD. Adding years since onset of AUD to the model showed that both increasing age and increasing years of duration of AUD contributed to the reduction of familial confounding in the association between AUD and elevated mortality.Excess mortality associated with AUD arises both from the predispositions of the person who develops AUD and the direct result of having AUD. The effect of predisposition is more prominent early in the life course and in the early years of AUD. The direct effect of AUD becomes progressively more important later in life and with longer duration of AUD. These results have implications for interventions seeking to reduce the elevated AUD-associated mortality.
MPTH-14PROGNOSTIC ROLE OF METHYLATION STATUS OF MGMT PROMOTER ON GLIOBLASTOMA PATIENTS ESTIMATED QUANTITATIVELY BY PYROSEQUENCING
Authors: Dae Cheol Kim, Young Jin Song, Eun Hee Lee, Ki Uk Kim, Young Zoon Kim
Journal: Neuro-Oncology (2015)

OBJECTIVE: This study was aimed to determine whether pyrosequencing might be useful to determine methylation status of MGMT promoter using relatively old archival tissue samples of glioblastomas as a clinical biomarker.Additionally, we examined other prognostic factors for survival of glioblastoma patients.METHODS: The available study set included FFPE tissue from Overall survival
Next Generation Sequencing-Based Molecular Dissection Of Lineage-Specific Mutational Hierarchies In Oligoclonal Primary and Xenografted Myelodysplasia
Authors: Johann-Christoph Jann, Daniel Nowak, Florian Nolte, Claudia Haferlach, Marita Staller, Verena Nowak, Bettina Zens, Katja Müdder, Corinna Klein, Julia Obländer, Stephanie Fey, Jovita Vogler, Alice Fabarius, Alexander Kohlmann, Wolf-Karsten Hofmann, Andreas Trumpp, Hind Medyouf, Maximilian Mossner
Journal: Blood (2013)
What about the impact on patient health?
Authors: Mark Strong, John Radford
Journal: BMJ (2007)

McDonald et al's report of general practitioners' and nurses' views of the quality and outcomes framework (QOF) highlights the “box ticking” nature of this pay-for-performance contract.1 We have therefore proposed that incentives are linked more directly to positive health outcomes.

Rotherham practices achieved highly on the smoking related QOF indicators in both …
Post-Transfusion Purpura: Immunologic Aspects and Therapy
Authors: Neil Abramson, Peter D. Eisenberg, Richard H. Aster
Journal: New England Journal of Medicine (1974)

To determine the mechanisms of post-transfusion thrombocytopenia, platelet antibodies were studied in a 45-year-old woman in whom severe thrombocytopenia with lingual and buccal hemorrhagic bullae and purpura developed seven days after the transfusion of whole blood. Her platelets were later typed as PlA1 negative, and her plasma and serum contained anti-PlA1 and anti-HLA antibodies. Antibody activity was demonstrated by microscopical agglutination and lysis, by aggregation with use of an aggregometer, and by 51Cr release. Antibody activity, as measured with the aggregometer, seemed restricted to the IgG3 class of immunoglobulin. Plasmapheresis resulted in clinical improvement associated with disappearance of antibody activity. Thus, this patient with post-transfusion purpura demonstrated anti-PlA1, and anti-HLA (IgG3) anti-platelet antibodies. Plasmapheresis with removal of the antibody proved effective therapy. (N Engl J Med 291:1163–1166, 1974)
Mutations in the Sarcoglycan Genes in Patients with Myopathy
Authors: David J. Duggan, J. Rafael Gorospe, Marina Fanin, Eric P. Hoffman, Corrado Angelini, E. Pegoraro, S. Noguchi, E. Ozawa, W. Pendlebury, A.J. Waclawik, D.A. Duenas, I. Hausmanowa-Petrusewicz, A. Fidzianska, S.C. Bean, J.S. Haller, J. Bodensteiner, C.M. Greco, A. Pestronk, A. Berardinelli, D.F. Gelinas, H. Abram, R.W. Kuncl
Journal: New England Journal of Medicine (1997)

Some patients with autosomal recessive limb-girdle muscular dystrophy have mutations in the genes coding for the sarcoglycan proteins (alpha-, beta-, gamma-, and delta-sarcoglycan). To determine the frequency of sarcoglycan-gene mutations and the relation between the clinical features and genotype, we studied several hundred patients with myopathy.Antibody against alpha-sarcoglycan was used to stain muscle-biopsy specimens from 556 patients with myopathy and normal dystrophin genes (the gene frequently deleted in X-linked muscular dystrophy). Patients whose biopsy specimens showed a deficiency of alpha-sarcoglycan on immunostaining were studied for mutations of the alpha-, beta-, and gamma-sarcoglycan genes with reverse transcription of muscle RNA, analysis involving single-strand conformation polymorphisms, and sequencing.Levels of alpha-sarcoglycan were found to be decreased on immunostaining of muscle-biopsy specimens from 54 of the 556 patients (10 percent); in 25 of these patients no alpha-sarcoglycan was detected. Screening for sarcoglycan-gene mutations in 50 of the 54 patients revealed mutations in 29 patients (58 percent): 17 (34 percent) had mutations in the alpha-sarcoglycan gene, 8 (16 percent) in the beta-sarcoglycan gene, and 4 (8 percent) in the gamma-sarcoglycan gene. No mutations were found in 21 patients (42 percent). The prevalence of sarcoglycan-gene mutations was highest among patients with severe (Duchenne-like) muscular dystrophy that began in childhood (18 of 83 patients, or 22 percent); the prevalence among patients with proximal (limb-girdle) muscular dystrophy with a later onset was 6 percent (11 of 180 patients).Defects in the genes coding for the sarcoglycan proteins are limited to patients with Duchenne-like and limb-girdle muscular dystrophy with normal dystrophin and occur in 11 percent of such patients.
Prospective evaluation of oral mucositis in solid tumor patients undergoing chemotherapy and its clinical implication
Authors: J. Kim, Y. Cha, S. Han, D. Oh, S. Lee, D. Kim, S. Im, T. Kim, D. S. Heo, Y. Bang
Journal: Journal of Clinical Oncology (2009)

e20650 Background: Oral mucositis (OM) induced by chemotherapy is a troublesome and debilitating adverse effect in solid tumor patients. OM might influence the complicated aspects such as the poor oral intake and malnutrition over just oral symptom. Therefore we prospectively evaluated the actual incidence of OM and its clinical significance in solid tumor patients. Methods: From October 16, 2007 to September 3, 2008, we consecutively enrolled 344 patients with solid tumor who initiated new chemotherapy. Each patient was prospectively evaluated for two cycles. The data were collected from physician-to-patient interview. And patients’ diary for OM symptom was used as patient-reported measurement. The visual analog scale (VAS) was used to quantify the degree of adverse effects (VAS: 0 point = no symptoms, 4 point = the worst symptom) and FACT-G was used for assessment of the quality of life (QOL). Results: Finally, 322 patients were analyzed. The median age was 51. Breast cancer was the most common (51%). And, stage IV was 137 (43%). OM was 28% per each cycle and 45% per patient during two cycles. Patient-reported OM symptom had peak in one week and was recovered in 9.14±6.77 days. Oral dryness was the most prevalent symptom out of symptoms related with OM such as oral pain, poor oral intake, dysphagia, oral bleeding, scalloping of tongue and ulceration (VAS score 1≤; 47%, 27%, 39%, 15%, 7%, 14%, 13%, respectively). In QOL measured by FACT-G, physical well-being and emotional well-being were significantly dropped in OM-occurred group than in no-OM group (19.09±6.48 vs 22.47±5.95, p&lt;0.001; 16.74±4.10 vs 17.97±3.38, P&lt;0.001, respectively). In addition, higher VAS score for other adverse effects was showed in OM-occurred group than in no-OM group (activity, nausea, vomiting, fever, myalgia and nervous system; p=0.0038, p&lt;0.0001, p=0.0007, p=0.0062, p&lt;0.0001, p&lt;0.0001, respectively). Conclusions: Forty five percent of patients with solid tumor experience OM during 2 cycles of chemotherapy. In case of patients with OM, QOL is worse and the other adverse effects are more prevalent. OM could be an indicator of QOL and other adverse effects during chemotherapy. No significant financial relationships to disclose.
Financial Incentives and Cholesterol Levels
Authors: Lenard I. Lesser, James P. McCormack
Journal: JAMA (2016)

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Abstract 201: Protective Effect of Nicotinamide Mononucleotide Administration Against Cardiac Ischemia-Reperfusion Injury
Authors: Takanobu Yamamoto, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation Research (2012)

Background: Nicotinamide adenine dinucleotide (NAD) participates in redox reactions as an electron-transferring molecule, thereby serving as a cofactor for metabolism. In the NAD biosynthetic salvage pathway, nicotinamide phosphoribosyltransferase (Nampt) which forms nicotinamide mononucleotide (NMN) is the rate-limiting enzyme and exhibits the protective effect against ischemia/ reperfusion (I/R) injury in the hearts of mice with cardiac-specific overexpression of Nampt. In addition, administration of NMN is reported to reverse the pancreatic beta-cell dysfunction observed in Nampt heterozygous knockout mice. Methods: To elucidate the protective effect of NMN against cardiac I/R injury, NMN was administered to mice subjected to I/R injury either before ischemia or immediately before reperfusion. Area at risk (AAR) and infarct area (IA) were evaluated 24 hours after reperfusion. Results: To confirm the distribution of NMN in the heart, NAD and NADH, into which NMN is quickly converted in the heart, were measured. One hour after NMN administration (500mg/ kg body weight, i.p.), the NAD and NADH contents of the NMN group (n=3) were significantly increased, whereas the NAD/NADH ratio was unchanged compared to the vehicle group (n=3) (NAD: NMN=483±42 pmole/mg tissue, vehicle=183±46 pmole/mg tissue, p&lt;0.01; NADH: NMN=262±25 pmole/mg tissue, vehicle=96±17 pmole/mg tissue, p&lt;0.01; NAD/NADH ratio: NMN=1.85±0.09, vehicle=1.82±0.18, n.s.). In the mice administered NMN or vehicle 30 min before ischemia, IA/AAR in the NMN group was smaller than that in the vehicle group (AAR: NMN=26±0.5%, vehicle=27±0.4%, n.s.; IA/AAR: NMN=23±1.8%, vehicle=42±1.5%, p&lt;0.01, n=4). On the other hand, in the mice administered NMN or vehicle immediately before reperfusion, IA/AAR in the NMN group was not different from that in the vehicle group (AAR: NMN=27±0.5%, vehicle=26±1.0%, n.s.; IA/AAR: NMN=37±1.4%, vehicle=34±2.2%, n.s., n=4). Conclusions: NMN administration significantly increased the NAD content in the heart and exhibited a protective effect against cardiac I/R injury. Increasing NAD content before ischemia, rather than after reperfusion, may minimize I/R injury in clinical settings, such as in acute coronary syndrome before coronary intervention.
PTCT-04GERMINOMAS CAN BE DIAGNOSED WITHOUT HISTOLOGICAL VERIFICATION
Authors: Ryuta Saito, Yukihiko Sonoda, Masayuki Kanamori, Tomohiro Kawaguchi, Toshihiro Kumabe, Teiji Tominaga
Journal: Neuro-Oncology (2015)

We have reported that germinomas could be diagnosed from clinical evaluations and radiological imagings, however the specificity was below 100% [J Clin Neurosci. 2014]. In order to precisely diagnose the patients with germinomas, we recently perform advanced MR imaging studies including MR spectroscopy (MRS) and minimum apparent diffusion coefficiency (minADC) study, and evaluation of serum tumor markers, i.e. HCG, beta HCG, HCG-CTP. This retrospective study was carried out to search the possibility of preoperative diagnosis with increased specificity in patients with germinoma-like tumors. Thirty consecutive patients with germinoma-like tumor underwent initial treatment from May 2007 to January 2015. Both minADC value and lipid peak on proton MRS were evaluated in 22 patients, minADC only in 5, and MRS only in 1 patient. Serum level of HCG, beta-HCG, and HCG-CTP were evaluated in 22 cases, HCG and beta-HCG in 5, and only beta-HCG in 1 case. With or without histological verifications, all of these patients received three courses of chemotherapy using ifosfamide, cisplatin, and etoposide or carboplatin and etoposide, and then received 24Gy whole ventricle irradiation. All patient drastically responded to the treatment and are alive with only one events of recurrence. Both low (<0.7x 10(-3)mm(2)/s) minADC value and lipid peak on proton MRS were observed in 20 patients among 22 who received both. Among these 20 patients, some elevations of tumor markers were detected in 7. Consequently, evaluation of minADC and proton MRS are useful to distinguish germinomas from other tumors, but some non-germinomas may show similar characteristics to germinoma. Combination with serum tumor marker evaluation, we may be able to distinguish the germinoma patients with higher specificity. It may be safe to say that unnecessary surgery can be avoided at least in 7 out of 20 patients who demonstrated both MRI and serum characteristics. Prospective study is warranted.
Successful response in a case of severe pustular psoriasis after interleukin‐1β inhibition
Authors: P. Skendros, C. Papagoras, I. Lefaki, A. Giatromanolaki, I. Kotsianidis, M. Speletas, V. Bocly, I. Theodorou, V. Dalla, K. Ritis
Journal: British Journal of Dermatology (2016)

Generalized pustular psoriasis (GPP) is a severe type of psoriasis accompanied by systemic and often life-threatening manifestations. The efficacy of the interleukin (IL)-1 antagonist anakinra in cases of GPP underscores the role of IL-1 in disease pathogenesis. We present a case of a middle-aged man who developed an abrupt and severe form of GPP with severe eosinophilia and cholestatic hepatitis. The patient received salvage treatment with a combination of glucocorticoids, hydroxyurea and imatinib, while administration of the IL-1 inhibitor anakinra resulted in remission of hepatitis and a significant skin improvement. However, due to persistent hypersensitivity skin reactions, anakinra was withdrawn and replaced with the anti-IL-1β antagonist canakinumab. As a result of canakinumab, the patient's skin completely cleared, while no systemic manifestations recurred. After 1 year of continuous canakinumab therapy, the patient remained virtually free of symptoms, while the drug was well tolerated.