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Institution

University of Perugia

EducationPerugia, Umbria, Italy
About: University of Perugia is a education organization based out in Perugia, Umbria, Italy. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 13365 authors who have published 39516 publications receiving 1265601 citations. The organization is also known as: Universitá degli Studi di Perugia & Universita degli Studi di Perugia.


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Journal ArticleDOI
TL;DR: In this paper, a population pharmacokinetic model was developed using plasma samples from these patients and various simulations were conducted to explore the pharmacokinetics of rivaroxaban in patients with DVT and to predict exposure in those with atrial fibrillation.
Abstract: Background and objective Rivaroxaban is an oral, direct Factor Xa inhibitor, which is at an advanced stage of clinical development for prevention and treatment of thromboembolic disorders. Two phase II studies, ODIXa-DVT and EINSTEIN DVT, assessed the efficacy and safety of oral rivaroxaban (once daily or twice daily) for treatment of acute deep-vein thrombosis (DVT). Population pharmacokinetic and pharmacodynamic analyses of rivaroxaban in patients in these two phase II studies were conducted to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban and the relationship between important patient covariates and model parameters. Exposure simulations in patients with atrial fibrillation (AF) were also performed in order to predict the exposure of rivaroxaban, using modified demographic data reflecting the characteristics of a typical AF population. Methods A population pharmacokinetic model was developed using plasma samples from these patients. Various simulations were conducted to explore the pharmacokinetics of rivaroxaban in patients with DVT and to predict exposure in those with AF. Correlations between plasma rivaroxaban concentrations and the prothrombin time, Factor Xa activity, HepTest® and activated partial thromboplastin time were also described. Results The pharmacokinetics of rivaroxaban in patients with DVT were found to be consistent and predictable across all doses studied. The area under the plasma concentration-time curve (AUC) increased dose dependently. The same total daily doses given once daily achieved higher maximum plasma concentration (C(max)) values (∼20%) and lower trough (minimum) plasma concentration (C(trough)) values (∼60%) than when given twice daily; however, the 5th-95th percentile ranges for these parameters overlapped. Rivaroxaban clearance was moderately influenced by age and renal function, and the volume of distribution was influenced by age, body weight and sex; the effects were within the observed interindividual variability. Simulations in virtual patient populations with AF showed that a rivaroxaban dose of 15 mg once daily in patients with creatinine clearance of 30-49 mL/min would achieve AUC and C(max) values similar to those observed with 20 mg once daily in patients with normal renal function. The prothrombin time correlated almost linearly with plasma rivaroxaban concentrations (≤500 μg/L). Conclusion Population analyses of phase II clinical data indicated that the pharmacokinetics and pharmacodynamics of all rivaroxaban doses were predictable and were affected by expected demographic factors in patients with acute DVT.

298 citations

Journal ArticleDOI
J. P. Lees1, V. Poireau1, E. Prencipe1, V. Tisserand1  +463 moreInstitutions (76)
TL;DR: In this article, the authors measured the gamma gamma* > pi0 transition form factor in the momentum transfer range from 4 to 40 GeV^2 with the BABAR detector at e+e-center-of-mass energies near 10.6 GeV.
Abstract: We study the reaction e+e- --> e+e-pi0 and measure the gamma gamma* --> pi0 transition form factor in the momentum transfer range from 4 to 40 GeV^2. The analysis is based on 442 fb^-1 of integrated luminosity collected at PEP-II with the BABAR detector at e+e- center-of-mass energies near 10.6 GeV.

297 citations

Journal ArticleDOI
TL;DR: The high load of V(H) gene mutations and signs of intraclonal diversity suggest a relation between L&H cells and germinal-center B cells at the centroblastic stage of differentiation.
Abstract: Background The atypical cells of nodular lymphocyte-predominant Hodgkin's disease, designated lymphocytic and histiocytic (L&H) cells, have a B-cell phenotype. To clarify the clonality of these cells, we studied rearranged immunoglobulin genes for the variable region of the heavy chain (V H genes) in individual L&H cells from 11 patients with nodular lymphocyte-predominant Hodgkin's disease. We also studied the expression of immunoglobulin light chains by those cells in six of the same patients. Methods Single CD20+ L&H cells were isolated from frozen sections by a technique of micromanipulation. The rearranged V H genes of these cells were amplified by the polymerase chain reaction (PCR), sequenced, and compared with germ-line V H genes. Immunoglobulin light-chain messenger RNA (mRNA) was detected by in situ hybridization. Results Of 615 L&H cells isolated from all the frozen sections, 160 yielded PCR products. In each of the 11 patients, the L&H cells that could be evaluated had identically rearranged V...

297 citations

Journal ArticleDOI
TL;DR: White-coat hypertension was not associated with a definitely increased risk of stroke during the total follow-up period, however, WCH might not be a benign condition for stroke in the long term.
Abstract: White-coat hypertension (WCH) has been associated with a low risk for stroke, but long-term data are scanty. We analyzed individual data from 4 prospective cohort studies from the United States, Italy, and Japan that used comparable methodology for 24-hour noninvasive ambulatory blood pressure monitoring (ABPM). Overall, 4406 subjects with essential hypertension and 1549 healthy normotensive controls who were untreated at the time of initial ABPM were followed for a median of 5.4 years up to censoring or occurrence of a first stroke. At entry, mean age of subjects was 56 years (range 18 to 97). Prevalence of WCH was 9%. During follow-up, there were 213 new cases of stroke. Stroke rate (×100 person years) was 0.35 in the normotensive group, 0.59 in the WCH group, and 0.65 in the group with ambulatory hypertension. In a multivariate analysis, the adjusted hazard ratio for stroke was 1.15 (95% confidence interval [CI], 0.61 to 2.16) in the WCH group ( P =0.66) and 2.01 (95% CI, 1.31 to 3.08) in the ambulatory hypertension group ( P =0.001) compared with the normotensive group. After the sixth year of follow-up, the incidence of stroke tended to increase in the WCH group, and the corresponding hazard curve crossed that of the ambulatory hypertension group by the ninth year of follow-up. In conclusion, WCH was not associated with a definitely increased risk of stroke during the total follow-up period. However, WCH might not be a benign condition for stroke in the long term.

297 citations


Authors

Showing all 13488 results

NameH-indexPapersCitations
Michael Grätzel2481423303599
Luigi Ferrucci1931601181199
Tobin J. Marks1591621111604
Johan Auwerx15865395779
Tony Pawson15042585196
Jack Hirsh14673486332
Alexander Belyaev1421895100796
R. L. McCarthy1411238115696
Harvey B Newman139159488308
Guido Tonelli138145897248
Elias Campo13576185160
Alberto Messineo134151196492
Franco Ligabue134140495389
Roberto Tenchini133139094541
R. Bartoldus132162497405
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023108
2022226
20212,487
20202,594
20192,362
20182,274