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Human Albumin (human + albumin)
Selected AbstractsEuropean data of a clinical trial with a sucrose formulated recombinant factor VIII in previously treated haemophilia A patientsHAEMOPHILIA, Issue 2002C. Rothschild Summary., To increase the safety of antihaemophilic treatment, the production process of full-length recombinant factor VIII (FVIII) KOGENATE® Bayer (Kogenate®FS)has been modified. Human albumin is no longer added as stabilizer during purification and in final formulation. Instead, the new KOGENATE® Bayer production process uses sucrose as a stabilizer in the formulation and adds solvent/detergent virus inactivation step. An European clinical trial was carried out in Germany and France in previously treated patients with severe haemophilia A who had more than 100 exposure days to exogenous FVIII. Pharmacokinetic data was analysed according to one-stage and chromogenic assays. Efficacy and safety during home therapy and in surgical procedures were evaluated; inhibitor formation was carefully monitored. Safety and efficacy were evaluated in 33 European patients for 24 months. Patients received more than 13 million IU KOGENATE® Bayer. Over 75% of patients accrued more than 100 exposure days with the new product. Of 875 bleeding episodes, 90.7% were treated with 1 or 2 infusions and 75.8% of responses to treatment were rated as ,excellent' or ,good'. Prophylactic treatment was the most common mode of therapy (60.7% of infusions). The product was well-tolerated and FVIII recovery studies were consistent throughout the study period. Only 0.26% of adverse events were reported to be drug related. No evidence of de novo inhibitor formation was observed. Overall, KOGENATE® Bayer was efficacious, safe and well-tolerated for the treatment of haemophilia A in multitransfused patients. [source] The use of therapeutic plasmapheresis in the treatment of poisoned and snake bite victims: An academic emergency department's experiencesJOURNAL OF CLINICAL APHERESIS, Issue 4 2006Cuma Yildirim Abstract The objective of this study is to describe the clinical status, procedural interventions, and outcomes of critically ill patients with poisoning and snake bite injuries presenting to a tertiary-care emergency department for treatment with therapeutic plasmapheresis. Records of 20 patients who presented to our academic emergency department over a 2-year period and who underwent plasmapheresis for poisoning or snake bite were retrospectively reviewed. Plasmapheresis was performed using centrifugation technology via an intravenous antecubital venous or subclavian vein catheter access. Human albumin or fresh frozen plasma were used as replacement fluids. Data extracted from the patient record included demographic data, clinical status, and outcome measures. Sixteen patients underwent plasmapheresis because of toxicity from snake bite. Three patients were treated for drug poisoning (phenytoin, theophylline, bipyridene HCl) and one patient for mushroom poisoning. Haematologic parameters such as platelet count, PT, and INR resolved rapidly in victims of snake bite injuries after treatment with plasmapheresis. Loss of limbs did not occur in these cases. Seven patients required admission to the intensive care unit. One patient with mushroom poisoning died. Mean length of hospital stay was 14.3 days (range 3,28 days) for all cases. Plasmapheresis was a clinically effective and safe approach in the treatment of snake bite envenomation and other drug poisoning victims especially in the management of hematologic problems and in limb preservation/salvage strategies. In addition to established conventional therapies, emergency physicians should consider plasmapheresis among the therapeutic options in treatment strategies for selected toxicologic emergencies. J. Clin. Apheresis 2006. © 2006 Wiley-Liss, Inc. [source] Evaluation of rHA labeled with Gd,DTPA for blood pool imaging and targeted contrast deliveryCONTRAST MEDIA & MOLECULAR IMAGING, Issue 1 2010Jim M. Wild Abstract A new contrast agent was developed by linking Gd,DTPA chelate to recombinant human albumin in the laboratory. The molar relaxivity of the new agent was tested in aqueous solution at B0 1.5,T and temperature 20°C. The soluble compound had a higher molar longitudinal relaxivity and molar transverse relaxivity in water (r1,=,7.2,s,1,mM,1, r2,=,18.4,s,1,mM,1) than those measured for Gd,DTPA solution (r1,=,3.5,s,1,mM,1, r2,=,5.5,s,1,mM,1). The performance of the compound as a blood pool agent was investigated with soluble and microparticulate forms of the compound and comparisons were made with Gd,DTPA and the polymeric blood-pool agent, Gadomer. T1 -weighted imaging experiments show that the soluble compound acts as a highly effective blood pool agent with hyperintensity in the vasculature persisting beyond 2,h post administration, compared with free Gd,DTPA, which was cleared from the blood pool after approximately 10,min. The clearance kinetics of the new agents were examined, due to the incomplete elimination within 14 days post injection; both rHA labeled compounds are probably not suitable for development as routine blood pool contrast media. However, with free sites on the Gd-loaded rHA molecule, there are possibilities for binding the agent to antibodies in the laboratory, which was demonstrated, and thus there exist potential applications for in vivo molecular imaging with this agent. Copyright © 2010 John Wiley & Sons, Ltd. [source] B-domain deleted recombinant factor VIII preparations are bioequivalent to a monoclonal antibody purified plasma-derived factor VIII concentrate: a randomized, three-way crossover studyHAEMOPHILIA, Issue 2 2005C. M. Kessler Summary., Background:, Deletion of the B-domain of recombinant blood coagulation factor VIII (BDDrFVIII) increases the manufacturing yield of the product but does not impair in vitro or in vivo functionality. BDDrFVIII (ReFacto®) has been developed with the additional benefit of being formulated without human albumin. Objective:, The primary objective of this three-way crossover-design study was to compare the pharmacokinetic (PK) parameters of two BDDrFVIII formulations (one reconstituted with 5 mL of sterile water, the other reconstituted with 4 mL sodium chloride 0.9% USP) with those of a plasma-derived, full-length FVIII preparation (Hemofil® M) in patients with haemophilia A to determine bioequivalence. Methods:, A series of blood samples were collected over a period of 48 h after i.v. administration of each of the FVIII preparations. Plasma FVIII activity was determined using a validated chromogenic substrate assay. Plasma FVIII activity vs. time curves was characterized for a standard set of PK parameter estimates. Two parameter estimates, the maximum plasma concentration (Cmax) and the area under plasma concentration vs. time curves (AUCs), were used to evaluate bioequivalence. The two preparations were considered bioequivalent if the 90% confidence intervals for the ratio of geometric means for Cmax and AUCs fell within the bioequivalence window of 80% to 125%. Results/Conclusion:, Results show that each BDDrFVIII formulation is bioequivalent to Hemofil M and the two formulations of BDDrFVIII are bioequivalent to each other. [source] Concentrate safety and efficacyHAEMOPHILIA, Issue 3 2002C. K. KASPER Safety from transmission of infections through plasma-derived clotting factor concentrates is assured by improved donor screening, serological testing of individual donations and direct viral testing of small plasma pools. Modern viral-inactivation techniques are highly effective. Recombinant concentrates stabilized in human albumin are being superaeded by those with other stabilizers. Recently reported discrepancies between estimates of concentrate potency from in vitro assays versus in vivo recovery, depending upon type of assay and reference standard used, are not fully resolved. [source] Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with genotype 1 chronic hepatitis C,,HEPATOLOGY, Issue 2 2008Stefan Zeuzem The efficacy and safety of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin, was evaluated in a phase 2b, open-label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN-alfa treatment-naïve patients were randomized to 48-week treatment with peginterferon alfa (PEG-IFN,)-2a 180 ,g one time per week (qwk), or alb-IFN 900 or 1,200 ,g once every two weeks (q2wk), or 1,200 ,g once every four weeks (q4wk), administered subcutaneously, plus weight-based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real-time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA <10 IU/mL 24 weeks after the end of treatment). By intention-to-treat analysis, sustained virologic response rates were 58.5% (69/118) with alb-IFN 900 ,g q2wk, 55.5% (61/110) with 1,200 ,g q2wk, and 50.9% (59/116) with 1,200 ,g q4wk, and 57.9% (66/114) with PEG-IFN,-2a (P = 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 ,g q2wk, 18.2% with 1,200 ,g q2wk and 12.1% with 1,200 ,g q4wk, and 6.1% with PEG-IFN,-2a (P = 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatment-associated missed workdays were significantly lower with alb-IFN 900 ,g q2wk versus PEG-IFN,-2a (1.1 versus 4.3 days; P = 0.006). Conclusion: Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFN,-2a. (HEPATOLOGY 2008;48:407,417.) [source] Starch and albumin mixture as replacement fluid in therapeutic plasma exchange is safe and effectiveJOURNAL OF CLINICAL APHERESIS, Issue 5 2008Gladys P. Agreda-Vásquez Abstract Therapeutic plasma exchange (TPE) is an effective treatment in Myasthenia gravis (MG) and Guillain-Barré syndrome (GBS) and 5% human albumin is the replacement fluid of choice; however, it is expensive. More recently, it has been suggested that starch is a safe and cheaper choice to human albumin. Objective: To evaluate our 5-year experience using 3% hydroxyethyl starch (HES) and 5% human albumin mixture, as replacement fluid in TPE for these diseases. Materials and methods: Retrospective study carried out from January 2001 through September 2006. We included those patients with MG and GBS undergoing TPE. We analyzed clinical outcome (CO) and adverse events (AE) and our results were compared with a previous study which included similar patients undergoing TPE using just 5% human albumin. Results: Thirty-one procedures were carried out in 26 patients, a total of 147 TPE sessions. In the group of MG we had 57% complete responses (CR) and 86% overall response (OR) while in the group of GBS we had 40% CR and 60% OR. When we analyzed our CO with the previous study no statistical differences were found. Mean processed plasma volume (PPV) was 4.2 in MG and 5.5 in GBS. Twenty patients had AE, being hypotension and catheter dysfunction the most frequent ones, while tachycardia, hypertension and paresthesias were statistically more frequent in the HES/albumin group. Conclusions: TPE with a mixture of 3% HES and 5% human albumin is as effective and safe as 5% human albumin alone for patients with these diseases. J. Clin. Apheresis, 2008. © 2008 Wiley-Liss, Inc. [source] Collection of peripheral progenitor cells in paediatric patients with a new programme for the collection of mononuclear cellsJOURNAL OF CLINICAL APHERESIS, Issue 3 2003R. Moog Abstract When harvesting peripheral progenitor cells (PPC) in children, the special situation of their circulatory system has to be taken into account. Therefore, extracorporeal blood volume and product volume should be small to avoid side effects. Nine children (age 2,14 years, weight 12.8,58.5 kg) with malignancies underwent 10 PPC collections with the MNC programme of the Amicus blood cell separator. The disposable kit was primed with red blood cells (RBCs) or human albumin to avoid circulatory side effects. The children were monitored for blood pressure and heart rate during the whole apheresis procedure. A median blood volume of 4,577 ml (range 3,536,8,596 ml) was processed in a separation time of 270 min (range 176,331 min). The median product weight was 81 g (range 53,107 g) and the yield of CD 34 antigen expressing cells was 12.5 × 106/kg body weight (range 1.8,26 × 106/kg body weight). Only one child had to undergo a second apheresis to collect the desired transplantation dose. The median platelet contamination of the product was 0.32 × 1011 (0.13,0.85 × 1011). No circulatory side effects were observed. Blood flow alarms occurred in seven of ten aphereses and one collection had to be terminated due to insufficient flow. PPC can be efficiently collected in children with the MNC programme without circulatory side effects. The platelet contamination of the product was low due to the elutriation principle of the collection process, thereby avoiding thrombocytopenic bleeding episodes in the patients. J. Clin. Apheresis, 18:111,114, 2003. © 2003 Wiley-Liss, Inc. [source] Cellular normalization of viral DNA loads on whole blood improves the clinical management of cytomegalovirus or Epstein Barr virus infections in the setting of pre-emptive therapyJOURNAL OF MEDICAL VIROLOGY, Issue 1 2009Céline Bressollette-Bodin Abstract Two quantitative duplex real-time PCR assays were developed for co-amplification of human albumin and cytomegalovirus (CMV) or Epstein Barr virus (EBV) genes after automated extraction on whole blood, and compared two units for expressing viral DNA loads (copies per ml of blood or per 106 peripheral blood leukocytes (PBLs)) on 1,138 positive samples. Both PCRs were characterized by high sensitivity, reproducibility, and linear range. Automated extraction by a MagNA Pure LC Instrument was shown to be more efficient when peripheral blood cell count was inferior to 5,×,109 PBLs/L. Albumin co-amplification allows the detection of PCR inhibitors and normalization of viral load according to the number of cells calculated in the sample. The two ways of expressing viral load results were highly correlated, but quantitative differences varied in relation to variations of blood cell count. As these two viruses are highly cell associated, viral loads can be underestimated in patients with leucopenia. In the setting of pre-emptive strategies during CMV infection, the units in which results are expressed can influence clinical management, as illustrated in this article. J. Med. Virol. 81:90,98, 2009. © 2008 Wiley-Liss, Inc. [source] Microradiographic study on the effects of salivary proteins on in vitro demineralization of bovine enamelJOURNAL OF ORAL REHABILITATION, Issue 2 2005A. M. KIELBASSA summary, The aim of this investigation was to evaluate the effects of various proteins on in vitro demineralization of bovine enamel. From each of 100 bovine incisors two samples were prepared. The specimens were embedded in epoxy resin and polished up to 4000 grit. Subsequently, the specimens' surfaces were partly covered with nail varnish, thus serving as control of sound enamel. The specimens were divided randomly into five groups (n = 40) and demineralized in a solution of constant composition (pH 5·0; 10 days). For each subgroup of specimens (n = 10) 4 L were taken and either low (50% of medium conc.), medium, or high (150%) concentrations of the proteins [human albumin (100% conc. = 7 mg L,1), mucin (577·5 mg L,1), immunoglobulin G (IgG) (46 mg L,1), casein isolated from bovine milk (1·2 g L,1)] or amino acid [l -Proline (7 mg L,1)] were added to 1 L of the demineralizing solution, whereas 1 L served as control. Mineral loss and lesion depth (LD) were evaluated from microradiographs of thin sections (110 ,m) by a dedicated software package (TMR 1.24). No differences were found between the five control groups (P > 0·05; anova). Albumin, l -Proline, and IgG did not affect enamel demineralization, whereas the addition of both casein and mucin resulted in significant reductions of both mineral loss and LDs (P < 0·01; Tukey's test). Within the limitations of an in vitro study, the present investigation indicates that casein and mucin seem to affect enamel demineralization significantly. Thus, these proteins might be helpful as an additive to saliva substitutes or mouthwashes if the quality of saliva is altered. [source] Structural and ligand-binding properties of serum albumin species interacting with a biomembrane interfaceJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2007Takamitsu Kosa Abstract In the process of drug development, preclinical testing using experimental animals is an important aspect, for verification of the efficacy and safety of a drug. Serum albumin is a major binding protein for endogenous and exogenous ligands and regulates their distribution in various tissues. In this study, the structural and drug-binding properties of albumins on a biomembrane surface were investigated using reverse micelles as a model membrane. In reverse micelles, the secondary structures of all albumins were found, to varying degrees, to be intermediate between the native and denatured states. The tertiary structures of human and bovine albumin were similar to those of the native and intermediate states, respectively, whereas those of the dog, rabbit, and rat were in a denatured state. Thus, bovine albumin is an appropriate model for studying structural changes in human albumin in a membrane-water phase. Binding studies also showed the presence of species difference in the change in binding capacity of albumins during their interaction with reverse micelles. Among the albumins, rat albumin appears to be a good model for the protein-mediated drug uptake of human albumin in a biomembrane environment. These findings are significant in terms of the appropriate extrapolation of pharmacokinetics and pharmacodynamics data in various animals to humans. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3117,3124, 2007 [source] Colloids decrease clot propagation and strength: role of factor XIII-fibrin polymer and thrombin,fibrinogen interactionsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2005V. G. Nielsen Colloid-mediated hypocoagulability is clinically important, but the mechanisms responsible for coagulopathy have been incompletely defined. Thus, my goal was to elucidate how colloids decrease plasma coagulation function. Plasma was diluted 0% or 40% with 0.9% NaCl, three different hydroxyethyl starches (HES, mean molecular weight 450, 220 or 130 kDa), or 5% human albumin. Samples (n = 6 per condition) were activated with celite, and diluted samples had either no additions or addition of fibrinogen (FI), thrombin (FIIa) or activated Factor XIII (FXIIIa) to restore protein function to prediluted values. Thrombelastographic variables measured included clot propagation (angle, ,), and clot strength (amplitude, A; or shear elastic modulus, G). Dilution with 0.9% NaCl significantly decreased ,, A and G -values compared to undiluted samples. Supplementation with FI, but not FIIa or FXIIIa, resulted in 0.9% NaCl-diluted thrombelastographic variable values not different from those of undiluted samples. FI supplementation of HES 450, HES 220, HES 130 and albumin-diluted samples only partially restored ,, A and G -values compared to undiluted samples. FIIa addition only improved clot propagation and strength in albumin-diluted samples. FXIIIa supplementation improved propagation in samples diluted with HES 450, HES 220 and albumin, and clot strength improved in HES 450 and albumin-diluted plasma. Considered as a whole, these data support compromise of FIIa-FI and FXIIIa , fibrin polymer interactions as the mechanisms by which colloids compromise plasma coagulation. Investigation to determine if clinical enhancement of FXIII activity and/or FI concentration (e.g. fresh-frozen plasma, cryoprecipitate) can attenuate colloid-mediated decreases in hemostasis is warranted. [source] Liver-targeted doxorubicin: effects on rat regenerating hepatocytesLIVER INTERNATIONAL, Issue 3 2004Giuseppina Di Stefano Abstract: Background/Aims: The conjugate of doxorubicin (DOXO) with lactosaminated human albumin (L-HSA) has the potential of improving DOXO efficacy in the treatment of hepatocellular carcinomas (HCCs) expressing the asialoglycoprotein receptor (ASGP-R). In view of an adjuvant chemotherapy with L-HSA,DOXO after the surgical removal of the tumour, in the present experiments we verified whether DOXO accumulation produced by the conjugate can impair the liver regeneration following hepatic resection in non-cirrhotic liver. Methods: Using saline-injected hepatectomised rats as controls, we studied the effects of the conjugate on the ultrastructure of regenerating hepatocytes and evaluated [3H]thymidine incorporation, mitotic index and rate of DNA recovery in the liver remnant. Results: L-HSA,DOXO caused a selective drug accumulation in liver remnant, with low DOXO levels in extra-hepatic tissues. It did not change the ultrastructure of hepatocytes and did not increase serum alanine aminotransferase. It decreased [3H]thymidine incorporation and mitotic index, causing a moderate delay in hepatic DNA recovery. Conclusions: The experiments indicate a substantial resistance of rat regenerating hepatocytes to high intracellular concentrations of DOXO. They support the possibility of using L-HSA,DOXO in an adjuvant chemotherapy after the surgical removal of HCCs which maintain the ASGP-R. [source] Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapyPEDIATRICS INTERNATIONAL, Issue 1 2001Shigeharu Hosono Background: The purpose of the present study was to evaluate the effect of intravenous albumin administration on the serum total and unbound bilirubin values in term non-hemolytic hyperbilirubinemic neonates during intensive phototherapy. Methods: Fifty-eight infants (gestational age 39.4~1.4 weeks; birth weight 3245~435 g) were given phototherapy with similar light energy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given human albumin at 1 g/kg bodyweight, i.v., during the first 2 h of phototherapy. Results: When comparing changes in total and unbound bilirubin values 0, 2, 6 and 24 h after entering the study between the albumin-treated group and the control group, there was a significant reduction in the serum unbound bilirubin values at the end of albumin treatment and at 6 and 24 h. However, there was no significant reduction in total serum bilirubin values during the study period. In the albumin-treated group, the mean serum unbound bilirubin reduction from the baseline level at the end of albumin treatment and at 6 and 24 h was 0.40~0.19, 0.41~0.20 and 0.43~0.20 ,g/dL, respectively. Conclusions: The results suggest that albumin priming may be effective for an immediate reduction in serum unbound bilirubin values, the fraction that is potentially neurotoxic. [source] | ||||||||||