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71.
Pingitore A Picano E Varga A Gigli G Cortigiani L Previtali M Minardi G Colosso MQ Lowenstein J Mathias W Landi P 《Journal of the American College of Cardiology》1999,34(6):1769-1777
OBJECTIVES: The study compared the prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease. BACKGROUND: Extensive information is available on the relative diagnostic accuracy of the two tests assessed in a head-to-head fashion, whereas comparative data on their prognostic yield are largely preliminary to date. METHODS: Dipyridamole (up to 0.84 mg/kg over 10 min) atropine (up to 1 mg over 4 min) (DIP) and dobutamine (up to 40 microg/kg/min)-atropine (1 mg over 4 min) (DOB) stress tests were performed in 460 patients with known or suspected coronary artery disease. Patients were followed up for 38+/-21 months. RESULTS: The DIP was negative in 253 and positive in 207 patients. The DOB was negative in 242 and positive in 218 patients. During the follow-up, there were 80 cardiac events. For all cardiac events, the negative and positive predictive value were 83% and 17% for DOB, 84% and 19% for DIP, respectively (p = NS). Considering only cardiac death, by univariate analysis Wall-Motion Score Index (WMSI) at DIP peak dose (chi-square 13.80, p<0.0002) was the strongest predictor, followed by WMSI DOB (chi2 = 8.02, p<0.004) and WMSI at rest (chi2 = 6.85, p<0.008). By stepwise analysis, WMSI at DIP peak dose was the most important predictor (RR [relative risk] 7.4, p<0.0001). CONCLUSIONS: In patients at low-to-moderate risk of cardiac events, pharmacological stress echocardiography with either dobutamine or dipyridamole allows effective and grossly comparable, risk stratification on the basis of the presence, severity and extension of the induced ischemia. 相似文献
72.
Preethne B?ser Dietmar Seemann Michael J. Liguori Leimin Fan Lili Huang Mathias Hafner Andreas Popp Bernhard K. Mueller 《The AAPS journal》2015,17(4):930-938
High levels of hepcidin, the main regulator of systemic iron metabolism, lead to various diseases. Targeting hepcidin and lowering its concentration is a possible form of intervention in order to treat these diseases. High turnover rate of hepcidin is a major drawback of therapies directly targeting this peptide. We developed two monoclonal antibodies ABT-207 and h5F9-AM8 which inhibit hemojuvelin/repulsive guidance molecule C (RGMc) and downregulate hepcidin. We conducted single-application and dose response studies to understand the antibodies’ mechanism and subchronic toxicology studies to exclude safety-related concerns. Investigation was carried out at different biological levels through qPCR, Affymetrix, liquid chromatography coupled with mass spectrometry (LC-MS/MS), histopathology, serum iron, unsaturated iron binding capacity (UIBC), and drug concentration measurements. After a single application of these antibodies, hepcidin expression in liver and its serum protein levels were reduced. Serum iron increased for several weeks. The RGMc antibodies show a pronounced dose response relationship in rats with h5F9-AM8 having an IC50 (UIBC) of approximately 80-fold higher than ABT-207. When hepcidin levels were downregulated, iron deposition in the liver was visible histologically 1 week post application. These antibody-mediated iron depositions were not associated with any adverse toxicologically relevant effect at the doses and time points evaluated. Iron depositions seen after 14 weekly treatments with ABT-207 were reversible in rats and in cynomolgus monkeys. Due to their long-lasting effects and excellent safety profile, both RGMc-blocking antibodies ABT-207 and h5F9-AM8 are favorable clinical candidates for diseases characterized by high serum hepcidin levels like anemia of chronic disease.
Electronic supplementary material
The online version of this article (doi:10.1208/s12248-015-9770-4) contains supplementary material, which is available to authorized users.KEY WORDS: ABT-207, h5F9-AM8, hepcidin, PK/PD analysis, safety assessment 相似文献73.
Martin N Fransson Emmanuelle Rial-Sebbag Mathias Brochhausen Jan-Eric Litton 《European journal of human genetics : EJHG》2015,23(1):22-28
To encourage the process of harmonization, the biobank community should support and use a common terminology. Relevant terms may be found in general thesauri for medicine, legal instruments or specific glossaries for biobanking. A comparison of the use of these sources has so far not been conducted and would be a useful instrument to further promote harmonization and data sharing. Thus, the purpose of the present study was to investigate the preference of definitions important for sharing biological samples and data. Definitions for 10 terms –[human] biobank, sample/specimen, sample collection, study, aliquot, coded, identifying information, anonymised, personal data and informed consent–were collected from several sources. A web-based questionnaire was sent to 560 European individuals working with biobanks asking to select their preferred definition for the terms. A total of 123 people participated in the survey, giving a response rate of 23%. The result was evaluated from four aspects: scope of definitions, potential regional differences, differences in semantics and definitions in the context of ontologies, guided by comments from responders. Indicative from the survey is the risk of focusing only on the research aspect of biobanking in definitions. Hence, it is recommended that important terms should be formulated in such a way that all areas of biobanking are covered to improve the bridges between research and clinical application. Since several of the terms investigated here within can also be found in a legal context, which may differ between countries, establishing what is a proper definition on how it adheres to law is also crucial. 相似文献
74.
Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans 总被引:3,自引:0,他引:3
Fatty acids have both stimulatory and inhibitory effects on insulin secretion. Long-term exposure to fatty acids results in impaired insulin secretion whilst acute exposure has generally been found to enhance insulin release. However, there are conflicting data in the literature as to the relative efficacy of various fatty acids and on the glucose dependency of the stimulatory effect. Moreover, there is little information on the responses of human islets in vitro to fatty acids. We have therefore studied the acute effects of a range of fatty acids on insulin secretion from rat and human islets of Langerhans at different glucose concentrations. Fatty acids (0.5 mM) acutely stimulated insulin release from rat islets of Langerhans in static incubations in a glucose-dependent manner. The greatest effect was seen at high glucose concentration (16.7 mM) and little or no response was elicited at 3.3 or 8.7 mM glucose. Long-chain fatty acids (palmitate and stearate) were more effective than medium-chain (octanoate). Saturated fatty acids (palmitate, stearate) were more effective than unsaturated (palmitoleate, linoleate, elaidate). Stimulation of insulin secretion by fatty acids was also studied in perifused rat islets. No effects were observed at 3.3 mM glucose but fatty acids markedly potentiated the effect of 16.7 mM glucose. The combination of fatty acid plus glucose was less effective when islets had been first challenged with glucose alone. The insulin secretory responses to fatty acids of human islets in static incubations were similar to those of rat islets. In order to examine whether the responses to glucose and to fatty acids could be varied independently we used an animal model in which lactating rats are fed a low-protein diet during early lactation. Islets from rats whose mothers had been malnourished during lactation were still able to respond effectively to fatty acids despite a lowered secretory response to glucose. These data emphasise the complex interrelationships between nutrients in the control of insulin release and support the view that fatty acids play an important role in glucose homeostasis during undernutrition. 相似文献
75.
Simon Rauch Tomas Dal Cappello Giacomo Strapazzon Martin Palma Francesco Bonsante Elisabeth Gruber Mathias Ströhle Peter Mair Hermann Brugger 《The American journal of emergency medicine》2018,36(10):1749-1753
Objective
We investigated pre-hospital times, clinical characteristics and therapeutic interventions in multisystem trauma patients injured in mountainous areas in comparison to both urban and suburban trauma patient admissions.Methods
Pre-hospital and in-hospital data collected from trauma patients included in the International Alpine Trauma Register (IATR) hosted in Bolzano, Italy (aged 16–80?yr with an ISS?≥?16), were compared with trauma patient data published from those urban and suburban areas included in the Trauma Register DGU® (TR-DGU) of the German Trauma Society.Results
A total of 94 patients from the IATR and 11,020 patients from the TR-DGU met the inclusion criteria. Due to longer treatment-free intervals (mean 59.1 vs. 19.7?min), total out-of-hospital time was reportedly longer in individuals injured in mountainous areas, compared to urban/suburban areas (117.4?±?142.9 vs. 68.7?±?28.6?min, p?=?0.002), despite the more frequent helicopter rescue (93% vs. 40%, p?<?0.001). 57% of IATR patients were hypothermic at hospital arrival, mean ISS was higher (38.5?±?15.8 vs. 28.6?±?12.2, p?<?0.001) and patients with a systolic blood pressure (SBP) ≤90?mm?Hg were more frequent (27% vs. 15%, p?=?0.005), yet less patients had received volume therapy (82% vs. 93%, p?=?0.001). However, overall no difference in hospital mortality was observed (11% vs. 17%, p?=?0.159).Conclusion
Trauma incidents in mountainous areas commonly feature significantly increased out-of-hospital time which is associated with a more severe ISS, higher risk of accidental hypothermia and more frequent hypotension compared to urban/suburban trauma. Nonetheless, the mortality rate of IATR patients is comparable to urban/suburban trauma patients. 相似文献76.
Mathias Prado Pereira Rafaela de Souza Martins Marcone Augusto Leal de Oliveira Fernanda Irene Bombonato 《RSC advances》2018,8(42):23903
In the present work, we describe the preparation of ten amino acid ionic liquids (AAILs) formed from ammonium salts as cations, derivatives of glycerol, and natural amino acids as anions. All of them are viscous oils, colorless or pale yellow, and hygroscopic at room temperature. They have appreciable solubility in many protic and aprotic polar solvents. The AAILs were used as catalysts in a Morita–Baylis–Hillman (MBH) reaction. The ionic liquids derivative from l-proline and l-histidine demonstrated the ability to catalyze the reaction between methyl vinyl ketone and aromatic aldehydes differently substituted in the absence of an additional co-catalyst under organic solvent-free conditions. The AAIL derivatives from l-valine, l-leucine, and l-tyrosine catalyzed the MBH reaction only in the presence of imidazole. The MBH adducts were obtained in moderate to good yields. Although the catalytic site in the ILs was in its enantiomerically pure form, all the MBH adducts were obtained in their racemic form.In this work, we describe the preparation of ten amino acid ionic liquids (AAILs). The AAILs were used as catalysts in a Morita–Baylis–Hillman (MBH) reaction. The MBH adducts were obtained from moderate to good yields and in their racemic form. 相似文献
77.
Mohamed R. Saber Gomaa Khabiri Ahmed A. Maarouf Mathias Ulbricht Ahmed S. G. Khalil 《RSC advances》2018,8(46):26364
MoS2 is a very attractive material and has been well studied for potential applications in various areas. However, due to the wide variety of factors affecting the molecular and electronic structure of MoS2, several contradictory reports about the adsorptive and photocatalytic properties of such materials have been published. In most of these reports, the effect of the actual phase of the materials on the properties was neglected. Here, different phases of MoS2 nanosheets (1T/2H, 1T/3R and 2H) have been obtained using the hydrothermal method with different Mo : S molar ratios and different autoclave filling ratios. The obtained materials have been thoroughly characterized using Raman, UV-vis, powder XRD, SEM, TEM and XPS measurements in order to accurately identify the existing phases in each material. A comparative study of the photocatalytic organic dye degradation efficiency under white light irradiation has been conducted using methyl orange to correlate the different activity of each material to the respective phase composition. The results indicate a much higher performance of the 1T/2H phase compared to the 2H and 3R phases. Detailed computational studies of the different phases revealed the emergence of mid-gap states upon introducing 1T sites into the 2H lattice. This leads to the improvement of the photocatalytic activity of 1T/2H compared to the other prepared materials.MoS2 is a very attractive material and has been well studied for potential applications in various areas. 相似文献
78.
Dennis Hanke Maria Jenckel Anja Petrov Mathias Ritzmann Julia Stadler Valerij Akimkin Sandra Blome Anne Pohlmann Horst Schirrmeier Martin Beer Dirk H?per 《Emerging infectious diseases》2015,21(3):493-496
Since 2013, highly virulent porcine epidemic diarrhea virus has caused considerable economic losses in the United States. To determine the relation of US strains to those recently causing disease in Germany, we compared genomes and found that the strain from Germany is closely related to variants in the United States. 相似文献
79.
Miedany Yasser El Gaafary Maha El Toth Mathias Hegazi Mohamed Osama Aroussy Nadia El Hassan Waleed Almedany Samah Nasr Annie Bahlas Sami Galal Salwa 《Clinical rheumatology》2021,40(10):4225-4232
Clinical Rheumatology - The prevalence of sarcopenia with osteoporosis results in a higher risk of falling and fractures. It was noted that patients who had completed their planned 5-year denosumab... 相似文献