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TL;DR: In this paper, the authors evaluated sevelamer hydrochloride and calcium acetate for peritoneal dialysis patients with serum phosphorus ≥ 5.5 mg/dl and found that sevelamed hydrochlorides provided a reduction in serum phosphorus compared to that of calciumacetate.
Abstract: Background. Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported. Methods. In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0–5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed. Results.Atotalof253patientswerescreened,143ofwhom were randomized (sevelamer hydrochloride, n = 97; calciumacetate,n =46).Treatmentgroupswerewellbalanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001). Conclusions. In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that
68 citations
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TL;DR: In vitro, the removal of PSA from adult‐derived neural progenitors significantly enhanced neuronal differentiation, strengthening in vivo findings and indicating that PSA removal on isolated progenitor cells, apart from a complex in vivo environment, induces neuronal maturation.
Abstract: Newborn cells of the adult dentate gyrus in the hippocampus are characterized by their abundant expression of polysialic acid (PSA), a carbohy- drate attached to the neural cell adhesion molecule (NCAM). PSA+ newborn cells of the dentate gyrus form clusters with proliferating neural progenitor cells, migrate away from these clusters, and terminally differ- entiate. To identify the roles of PSA in the development of adult progenitors of the dentate gyrus, we injected endoneuraminidase N (endoN) into the hippocampus of adult rats to specifically cleave PSA from NCAM. Two days later, we administered the mitotic marker, 5- bromo-2 0 -deoxyuridine (BrdU). Three days after BrdU injection, BrdU+ cells were found inside and outside the clusters of newborn cells. In endoN-treated animals, the total number of BrdU+ cells was not changed but signifi- cantly more BrdU+ cells were present within clusters, suggesting that PSA normally facilitates the migration of progenitors away from the clusters. Seven days post- BrdU injection, endoN-treated animals had significantly more BrdU+ cells which were also positive for the mature neuronal nuclear marker NeuN compared with controls, indicating that the loss of PSA from progenitor cells increases neuronal differentiation. This report is the first demonstration that PSA is involved in control- ling the spatio-temporal neuronal maturation of adult hippocampal progenitors in the normal brain. In vitro, the removal of PSA from adult-derived neural progeni- tors significantly enhanced neuronal differentiation, strengthening our in vivo findings and indicating that PSA removal on isolated progenitor cells, apart from a complex in vivo environment, induces neuronal maturation. ' 2008 Wiley Periodicals, Inc. Develop Neurobiol 68: 1580-1590, 2008
68 citations
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TL;DR: Application of biocompatible polymer solutions during surgery could reduce the technical difficulty and risk of repeat cardiac surgical procedures and potentially inhibit adhesion formation following cardiac surgery.
68 citations
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TL;DR: No new or unexpected safety signals beyond those detected in individual trials were identified in this pooled analysis with treatment duration exceeding 12 years and a cumulative exposure to teriflunomide exceeding 6800 patient-years.
Abstract: Background Teriflunomide, a once-daily oral immunomodulator for the treatment of relapsing-remitting multiple sclerosis, has demonstrated consistent efficacy on clinical and MRI parameters in clinical trials. Objective To summarize the safety and tolerability profile of teriflunomide based on data from four placebo-controlled trials. Methods Safety and tolerability were assessed using two teriflunomide clinical program data pools. Pool 1 contained 3044 patients randomized to teriflunomide (14 mg or 7 mg) or placebo in the core studies of one phase 2 trial and three phase 3 trials, with cumulative treatment exposure >1500 patient-years per group. Pool 2 comprised 2338 patients who received teriflunomide treatment in the above trials, including those continuing in extension studies, with a duration of treatment up to 12 years, representing >6800 patient-years. Safety assessments included adverse events, laboratory parameters, and physical examinations. Results In Pool 1, the number of patients experiencing adverse events and serious adverse events was similar in the three treatment groups. Common events occurring in ≥10% of patients in either teriflunomide group, and with an incidence ≥2% compared with placebo, were alanine aminotransferase (ALT) increase, headache, diarrhea, hair thinning, and nausea. Overall, the nature of events observed in Pool 2 was similar to Pool 1. The majority of events in both pools were of mild-to-moderate intensity, were self-limiting, and infrequently resulted in discontinuation of therapy. The most common reason for treatment discontinuation in all treatment groups was ALT elevation, reflecting the protocol requirement to discontinue treatment on confirmation of ALT>3×the upper limit of normal. Conclusions No new or unexpected safety signals beyond those detected in individual trials were identified in this pooled analysis with treatment duration exceeding 12 years and a cumulative exposure to teriflunomide exceeding 6800 patient-years. Overall, both doses of teriflunomide had consistent and manageable safety profiles.
68 citations
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TL;DR: In this comparative study of 22 hepatocyte-specific expression cassettes, the DC172 promoter in combination with two copies of the hepatic control region-1 induces the highest expression levels following hydrodynamic and adenoviral transfer.
Abstract: Hepatocytes are a key target for treatment of inborn errors of metabolism, dyslipidemia and coagulation disorders. The development of potent expression cassettes is a critical target to improve the therapeutic index of gene transfer vectors. Here we evaluated 22 hepatocyte-specific expression cassettes containing a human apo A-I transgene following hydrodynamic transfer of plasmids or adenoviral transfer with E1E3E4-deleted vectors in C57BL/6 mice. The DC172 promoter consisting of a 890 bp human alpha(1)-antitrypsin promoter and two copies of the 160 bp alpha(1)-microglobulin enhancer results in superior expression levels compared to constructs containing the 1.5 kb human alpha(1)-antitrypsin promoter, the 790 bp synthetic liver-specific promoter or the DC190 promoter containing a 520 bp human albumin promoter and two copies of the 99 bp prothrombin enhancer. The most potent expression cassette consists of the DC172 promoter upstream of the transgene and two copies of the hepatic control region-1. Minicircles containing this expression cassette induce persistent physiological human apo A-I or human factor IX levels after hydrodynamic transfer. In conclusion, in this comparative study of 22 hepatocyte-specific expression cassettes, the DC172 promoter in combination with two copies of the hepatic control region-1 induces the highest expression levels following hydrodynamic and adenoviral transfer.
68 citations
Authors
Showing all 3085 results
Name | H-index | Papers | Citations |
---|---|---|---|
George M. Whitesides | 240 | 1739 | 269833 |
Stephen J. O'Brien | 153 | 1062 | 93025 |
Robert B. Jackson | 132 | 458 | 91332 |
Glenn M. Chertow | 128 | 764 | 82401 |
Jon Clardy | 116 | 983 | 56617 |
John J. Fung | 115 | 1011 | 52924 |
Robert B. Colvin | 111 | 556 | 52034 |
Sergio Giralt | 109 | 1024 | 48513 |
Paul Saftig | 107 | 356 | 49929 |
Robert J. Desnick | 102 | 694 | 39698 |
Robert A. Soslow | 87 | 427 | 29014 |
Richard J. Roman | 84 | 461 | 23760 |
Diana W. Bianchi | 81 | 405 | 24554 |
Paolo Raggi | 80 | 439 | 33332 |
Helmut G. Rennke | 77 | 256 | 33959 |