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Low‐density lipoprotein and other predictors of response with telaprevir‐based therapy in treatment‐experienced HCV genotype 1 patients: REALIZE study
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Thomas Berg Pietro Andreone Stanislas Pol Stuart Roberts Zobair Younossi Moises Diago Eric J. Lawitz Roberto Focaccia Graham R. Foster Andrzej Horban Isabelle Lonjon‐Domanec Ralph DeMasi Gaston Picchio Donghan Luo Sandra De Meyer Stefan Zeuzem 《Liver international》2015,35(2):448-454
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Takahisa Hirose Takeshi Ogihara Shusaku Tozaka Sami Kanderian Hirotaka Watada 《Journal of diabetes investigation.》2013,4(3):287-296
Aims/Introduction
Many patients with diabetes now use 5‐, 6‐ or 8‐mm needles for insulin injection. However, it is unclear whether needle length, particularly for shorter needles, affects the pharmacokinetic properties of insulin.Materials and Methods
This was a three‐way, randomized, cross‐over, single‐center study involving 12 healthy Japanese adult males (age 27.4 ± 4.14 years; weight 64.2 ± 5.2 kg; body fat percentage 18.2 ± 1.5%). Participants received a subcutaneous (abdomen) dose of insulin lispro (1.5 U for participants weighing 55 to <65.0 kg; 2.0 U for participants weighing 65.0 to <80.0 kg) delivered using a 32‐G × 4 mm (32G × 4), 31‐G × 8 mm (31G × 8) or 32‐G × 6 mm (32G × 6) needle with a 3–7‐day washout between doses. Pharmacokinetic parameters of exogenous insulin were identified using non‐linear least squares, where the total insulin concentration was fit to the measured plasma insulin concentration using an overall combined model that accounted for C‐peptide/insulin secretion in addition to the injected dose.Results
Maximum concentration and area under the curve for 0 to infinity min for insulin were bioequivalent for the 32G × 4 needle relative to the 32G × 6 and the 31G × 8 needles. The time to the maximum insulin concentration was bioequivalent for the 32G × 4 needle relative to the 32G × 6 needle, but not the 31G × 8 needle.Conclusions
The use of 4‐mm needles is unlikely to change the pharmacokinetic properties of insulin when injected subcutaneously in adults. This trial was registered with UMIN‐CTR (no. UMIN000004469). 相似文献4.
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Recent studies have associated genetic variation near the interleukin 28B (IL28B/IFN‐λ3) gene with natural clearance of the hepatitis C virus (HCV) infection, and a common variant in the DEP domain containing 5 (DEPDC5) locus on chromosome 22 has been shown to affect susceptibility to hepatocellular carcinoma (HCC) in Japanese individuals with chronic HCV infection. This study was conducted to determine whether polymorphisms near or in interferon‐lambda (IFN‐λs) genes and their receptor genes such as interleukin 28 receptor, alpha (IL28RA) and interleukin 10 receptor, beta (IL10RB) as well as p21_activated kinases 4 (PAK4) and iron/zinc purple acid phosphatase‐like protein (PAPL), which are locate upstream of IFN‐λs, and lastly the DEPDC5 gene are associated with hepatitis B virus‐related liver disease in Han Chinese. The study subjects included 507 normal healthy controls, 350 individuals with natural clearance of HBV and 792 HBV‐infected patients. The patients were categorized into 157 inactive carriers (Case I), 216 active carriers (Case II), 111 cirrhotics (Case III) and 308 HCC patients (Case IV) subgroups. Seven single nucleotide polymorphisms (SNPs) were genotyped using the Matrix‐assisted Laser Desorption/Ionisation mass spectrometric (MALDI‐TOF MS) SNP genotyping assay. Rs423058 upstream of PAPL, rs2834167 in IL10RB and rs1012068 in DEPDC5 were associated with chronic HBV status, HBV natural clearance and the presence of HCC (P = 0.0004–0.024), respectively. PAPL, IL10RB and DEPDC5 polymorphisms have an impact on progression of HBV‐related liver disease. However, IFN‐λs genes as a tool to differentiate between different clinical courses of HBV infection were not useful in the Han Chinese population. 相似文献
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Interventions to significantly improve service uptake and retention of HIV‐positive pregnant women and HIV‐exposed infants along the prevention of mother‐to‐child transmission continuum of care: systematic review
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Alexandra C. Vrazo Jacqueline Firth Anouk Amzel Rebecca Sedillo Julia Ryan B. Ryan Phelps 《Tropical medicine & international health : TM & IH》2018,23(2):136-148
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Priscilla A. van Riet Djuna L. Cahen Katharina Biermann Bettina Hansen Alberto Larghi Guido Rindi Giovanni Fellegara Paolo Arcidiacono Claudio Doglioni Nicola Liberta Decarli Julio Iglesias‐Garcia Ihab Abdulkader Hector Lazare Iglesias Masayuki Kitano Takaaki Chikugo Satoru Yasukawa Hans van der Valk Nam Quoc Nguyen Andrew Ruszkiewicz Marc Giovannini Flora Poizat Schalk van der Merwe Tania Roskams Erwin Santo Silvia Marmor Kenneth Chang Fritz Lin James Farrell Marie Robert Juan Carlos Bucobo Alan Heimann Francisco Baldaque‐Silva Carlos Fernndez Moro Marco J. Bruno 《Digestive endoscopy》2019,31(6):690-697
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Relative expression analysis of IL‐5 and IL‐6 genes in tropical sheep breed Pelibuey infected with Haemonchus contortus
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Z. M. Estrada‐Reyes A. G. López‐Reyes A. Lagunas‐Martínez G. Ramírez‐ Vargas S. Olazarán‐Jenkins J. Hernández‐Romano P. Mendoza‐de‐Gives M. E. López‐Arellano 《Parasite immunology》2015,37(9):446-452
Haemonchus contortus is a parasitic nematode of Pelibuey sheep, a meat breed used in tropical regions. Due to anthelmintic problems, the identification of hosts resistant to H. contortus is another option of control. The aim of this study was to analyse the relative expression of IL‐5 and IL‐6 genes in Pelibuey sheep after H. contortus infection. Nineteen lambs infected with H. contortus and three more lambs without infection were studied. The haemonchosis was determined by the number of eggs per gram of faeces (epg) and by the estimation of the percentage of the packed cell volume (%pcv). Peripheral blood mononuclear cells (PBMCs) were obtained to extract RNA at 0, 1, 2, 7, 14, 21 and 28 days after infection to quantify the relative expression of IL‐5, IL‐6 and GAPDH by real‐time PCR. Five lambs were classified as low responders (lr) to haemonchosis with averages of 1519 ± 315·3 epg and 31·49 ± 5·13%pcv, and 14 lambs were identified as high responders (hr) with averages of 530 ± 132 epg and 34·88 ± 3·75%pcv. The expression ratio of IL‐5 was significantly different compared with control lambs at 2, 7 and 14 days post‐infection (PI), and IL‐6 was significantly different after 14 days. The highest level of relative expression for IL‐5 and IL‐6 genes was 9·9‐fold and 12‐fold after 2 and 14 days for hr hosts (P < 0·05) compared with control group, respectively. In conclusion, the Pelibuey breed in grazing areas exhibited different expression of IL‐5 and IL‐6 obtained from PBMCs against H. contortus, suggesting the importance of these cytokines in regulating the nematode infection. 相似文献
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Neutrophil‐To‐Lymphocyte Ratio: An Emerging Marker Predicting Prognosis in Elderly Adults with Community‐Acquired Pneumonia
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![点击此处可从《Journal of the American Geriatrics Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Emanuela Cataudella MD Chiara M. Giraffa MD Salvatore Di Marca MD Alfredo Pulvirenti PhD Salvatore Alaimo PhD Marcella Pisano MD Valentina Terranova MD Thea Corriere MD Maria L. Ronsisvalle MD Rosario Di Quattro MD Benedetta Stancanelli MD PhD Mauro Giordano MD Carlo Vancheri MD PhD Lorenzo Malatino MD 《Journal of the American Geriatrics Society》2017,65(8):1796-1801
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Visit‐to‐visit HbA1c variability and systolic blood pressure (SBP) variability are significantly and additively associated with mortality in individuals with type 1 diabetes: An observational study
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Stuart S. Wightman Christopher A. R. Sainsbury MD Gregory C. Jones MBChB 《Diabetes, obesity & metabolism》2018,20(4):1014-1017
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Sofosbuvir and ledipasvir improve patient‐reported outcomes in patients co‐infected with hepatitis C and human immunodeficiency virus
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Z. M. Younossi M. Stepanova M. Sulkowski S. Naggie L. Henry S. Hunt 《Journal of viral hepatitis》2016,23(11):857-865
A fixed‐dose combination of ledipasvir and sofosbuvir (LDV/SOF) has been approved for treatment of HCV patients. We assessed the effect of LDV/SOF on patient‐reported outcomes (PROs) in HIV–HCV‐co‐infected patients. Patient‐reported outcomes data from HIV–HCV‐co‐infected patients who were treated with LDV/SOF for 12 weeks were collected as a part of a clinical trial (ION‐4). Historical controls were HIV–HCV‐co‐infected patients treated with SOF and ribavirin (RBV) in PHOTON‐1. We included 335 HIV–HCV‐co‐infected patients (SVR‐12 in HCV genotype 1 was 96%) who received LDV/SOF, while 223 patients (SVR‐12 in HCV genotype 1 was 76.3%) received SOF/RBV. During treatment, patients receiving LDV/SOF showed improvement in all of their PRO scores (+6.0% in activity/energy of CLDQ‐HCV, +5.0% in fatigue score of FACIT‐F, +6.8% in physical component of SF‐36; all P < 0.0001) while those receiving SOF+RBV showed moderate decline in some of their PRO scores (?4.8% in physical functioning of SF‐36, ?4.4% in fatigue score of FACIT‐F, both P < 0.001). Patients who achieved sustained virologic response with LDV/SOF also showed improvement of PROs (average +5.1%) while those treated with SOF/RBV showed less or no improvement (average +1.4%). In a multivariate analysis, in addition to depression and fatigue, receiving SOF+RBV (vs LDV/SOF) was independently associated with more PRO impairment during treatment (beta ?6.1 to ?12.1%, P < 0.001). Hence, HIV–HCV patients treated with LDV/SOF show significant improvement of their health‐related quality of life and other patient‐reported outcomes during treatment and after treatment cessation. 相似文献
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Comparative analysis between RQ‐PCR and digital‐droplet‐PCR of immunoglobulin/T‐cell receptor gene rearrangements to monitor minimal residual disease in acute lymphoblastic leukaemia
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Irene Della Starza Vittorio Nunes Marzia Cavalli Lucia Anna De Novi Caterina Ilari Valerio Apicella Antonella Vitale Anna Maria Testi Ilaria Del Giudice Sabina Chiaretti Robin Foà Anna Guarini 《British journal of haematology》2016,174(4):541-549
Real‐time quantitative polymerase chain reaction (RQ‐PCR) is a standardized tool for minimal residual disease (MRD) monitoring in acute lymphoblastic leukaemia (ALL). The applicability of this technology is limited by the need of a standard curve based on diagnostic DNA. The digital droplet PCR (ddPCR) technology has been recently applied to various medical fields, but its use in MRD monitoring is under investigation. In this study, we analysed 50 ALL cases by both methods in two phases: in the first, we established analytical parameters to investigate the applicability of this new technique; in the second, we analysed MRD levels in 141 follow‐up (FU) samples to investigate the possible use of ddPCR for MRD monitoring in ALL patients. We documented that ddPCR has sensitivity and accuracy at least comparable to those of RQ‐PCR. Overall, the two methods gave concordant results in 124 of the 141 analysed MRD samples (88%, P = 0·94). Discordant results were found in 12% borderline cases. The results obtained prove that ddPCR is a reliable method for MRD monitoring in ALL, with the advantage of quantifying without the need of the calibration curves. Its application in a cohort of patients with a longer FU will conclusively define its clinical predictive value. 相似文献
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More improvement than progression of liver fibrosis following antiretroviral therapy in a longitudinal cohort of HIV‐infected patients with or without HBV and HCV co‐infections
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Y. Ding S. Duan R. Ye Y. Yang S. Yao J. Wang D. Cao X. Liu L. Lu M. Jia Z. Wu N. He 《Journal of viral hepatitis》2017,24(5):412-420
We examined the effect of combination antiretroviral therapy (cART) on liver fibrosis among HIV‐infected patients with or without hepatitis B (HBV) or C virus (HCV) co‐infection. This was a retrospective cohort study of HIV‐infected patients receiving cART during 2004‐2016. Liver fibrosis was assessed using Fibrosis‐4 (FIB‐4) score with three classifications: Class 1, <1.45; Class 2, 1.45‐3.25; Class 3, >3.25. Of 3900 participants, 68.6% were HIV mono‐infected, 5.3% were HIV/HBV co‐infected, 23.8% were HIV/HCV co‐infected and 2.3% were HIV/HBV/HCV co‐infected. Participants received follow‐up treatment (median was 3.3 years). Improvement to a lower class was observed in Class 2 (52.6%) and Class 3 (74.2%), respectively. Progression to a higher class was observed in 12.8% and 5.0% in Class 1 and Class 2, respectively, and with a median time of 5.7 months. For improvement to lower classes, older age, male, Dai ethnicity, injection drug use, HCV co‐infection and tenofovir for treatment were negative predictors, but in Class 3 of FIB‐4 and time‐updated increases in CD4 count from baseline were positive predictors. For progression to higher classes, older age, male, Jingpo ethnicity and HCV co‐infection were positive predictors, while baseline CD4 count and in Class 2 of FIB‐4 were negative predictors. Improvement to lower class linked with decreased mortality risk among patients in Class 3. Early cART initiation for HIV‐infected patients with and without hepatitis co‐infections may mitigate or slow down some of liver fibrosis, but special attention should be given to those who are older, male, co‐infected with HCV. 相似文献
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Benjamin Heidrich Beatriz C. Serrano Ramazan Idilman Gökhan Kabaçam Birgit Bremer Regina Raupach Fatih O. Önder Katja Deterding Behrend J. Zacher Andrzej Taranta Hakan Bozkaya Kalliopi Zachou Hans L. Tillmann Abdurrahman M. Bozdayi Michael P. Manns Cihan Yurdaydın Heiner Wedemeyer 《Liver international》2012,32(9):1415-1425