bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic Dysfunction in a Population of Antibody‐Deficient Patients: Prevalence, Aetiology and Outcome of PCR Screening for Hepatitis C and G Viruses
Authors: O'Leary P.F.G. , Collingham K. , Skidmore S. , King J. , Bennett C.L. , Williams P.E. , Pillay D. , Thompson R.A. 
Published: December 2004

Abstract
Background and Objectives:
A group of 40 antibody‐deficient patients receiving regular infusions of intravenous immunoglobulin underwent close monitoring in an attempt to identify hepatic dysfunction. The continuing risk of hepatitis virus transmission, especially hepatitis C virus via immunoglobulin products prompted this policy. We report our findings. Methods: Screening included measurement of transaminase levels at each infusion. The patients were also tested for evidence of infection with hepatitis viruses B, C and G. Results: Abnormal liver function tests were identified in 6 cases. However, a blood‐borne viral aetiology was not found in any of these cases. Additional investigation allowed an alternative aetiology to be identified in most cases. One patient found to be positive for hepatitis G virus (HGV)‐RNA by reverse transcriptase‐polymerase chain reaction has no evidence to date of clinical problems as a result. Interpretation: The results are reassuring in that definite iatrogenic hepatitis virus transmission has not been found in this cohort, despite long‐term treatment with a wide range of immunoglobulin products. The source of infection of the single patient infected with HGV remains as uncertain as the pathogenic potential of this virus. However, as long as the risk of immunoglobulin‐associated viral transmission continues, a strict monitoring programme such as ours should continue to facilitate prompt detection of cases with abnormal liver function. Liver dysfunction in this group requires full investigation and we cannot exclude infection with hitherto unidentified blood‐borne viruses.
Removal and Inactivation of Hepatitis B Virus from Contaminated Pooled Plasma in a Large‐Scale Manufacturing Process for Factor VIII and Human Serum Albumin
Authors: Murozuka T. , Aoki M. , Kimura N. , Sotoyama K. , Abe I. , Izumi H. , Emura H. , Takeda Y. , Nanakawa H. , Katsubayashi Y. , Takeuchi T. , Ito H. , Hirakawa S. , Mitsunaga S. , Tadokoro K. , Kanemitsu K. , Miyamoto M. , Yamanaka R. , Nishioka K. 
Published: December 2004

Abstract
Background and Objectives:
The Japanese Red Cross Society recalled one lot of monoclonal‐antibody‐purified factor VIII (F VIII) and two lots of human serum albumin (HSA) 5 months after preparation of the final products, because of a procedural error that led to contamination by a unit of plasma positve for hepatitis B surface antigen (HBsAg). We evaluated the effectiveness of virus inactivation/removal in a large‐scale process for manufacturing F VIII and HSA. Materials and Methods: HBV DNA in the retained samples in process was measured by the polymerase chain reaction (PCR). The kinetics of virus inactivation by solvent‐detergent (S/D) treatment was examined using model viruses. We also did a look‐back survey of the patients who received corresponding products. Results: Contaminated hepatitis B virus (HBV) DNA became undetectable beyond fraction S IV‐I in the albumin process, and immunoaffinity chromatography in the F VIII process, respectively. The model viruses were inactivated within 5 s by S/D treatment. There is no evidence that patients were infected by HBV after transfusion of these products. Conclusion: We conclude that virus inactivation/removal was effectively achieved in a large‐scale manufacturing process for F VIII and HSA.
Comparison of Four HTLV‐I and HTLV‐I + II ELISAs
Authors: Vrielink H. , Reesink H. W. , Habibuw M. R. , Schuller M. , van der Meer C.B.M. , Lelie P. N. 
Published: December 2004

Abstract
Background:
Various countries require blood donor screening using assays applying specific HTLV‐I and HTLV‐II antigens. We evaluated the sensitivity and specificity of 4 anti‐HTLV‐I + II ELISAs (Abbott, Murex, Organon Teknika and Ortho). Methods: Panel A consisted of HTLV‐I‐positive individuals (n = 41), panel B of Mixed Titer Performance Panel 204 (Boston Biomedica Inc. panels C and D of dilution series from HTLV‐I‐positive (n = 30) and HTLV‐II‐positive (n = 20) individuals and panel E of sera from first‐time blood donors (n = 1,055). Results: In HTLV‐I and ‐II‐positive samples, a sensitivity of 100% could be observed in all 4 ELISAs. In diluted HTLV‐I‐ and ‐II‐positive samples, probit analysis revealed that the Murex assay had the highest analytical sensitivity, followed by the ELISAs from Ortho, Abbott and Organon Teknika. In specimens from first‐time donors, a specificity of 100% was observed in ELISAs from Murex, Organon Teknika and Ortho, and of 99.7% in the assay from Abbott. Conclusion: The 4 anti‐HTLV‐I + II ELISAs studied were appropriate as screening tests.
International Reference Reagents: Antihuman Globulin
Authors: Case J. , Ford D. S. , Chung A. , Collins R. , Kochman S. , Mazda T. , Overbeeke M. , Perera R. , Sakuldamrongpanich T. , Scott M. , Voak D. , Żupa´nska B. 
Published: December 2004

AbstractAn international working party has conducted a study designed to select a suitable reference reagent for antihuman globulin, to replace those first made available in 1987. The chosen preparation contains levels of anti‐lgG and anti‐C3 (anti‐C3c and anti‐C3d) potency that are considered suitable to serve for reference when evaluating either polyspecific antihuman globulin reagents or those containing their separate monospecific components. The reference material is available in 2‐ml freezedried aliquots from seven assigned distribution centres.
Allele Frequencies of Human Platelet Antigen 1, 2, 3, and 5 Systems in Patients with Chronic Refractory Autoimmune Thrombocytopenia and in Normal Persons
Authors: Thude Hansjörg , Gatzka Elfriede , Anders Olaf , Barz Dagmar 
Published: December 2004

Abstract
Background and Objectives:
Chronic refractory autoimmune thrombocytopenic purpura (AITP) is an autoimmune disorder due to autoantibodies against platelet glycoproteins (GP). Human platelet alloantigenic (HPA) systems are distributed to different platelet GPs. We carried out genotyping of diallelic HPA‐1, ‐2, ‐3, and ‐5 systems to clarify potential associations between HPA alleles and the development of chronic refractory AITP. Patients and Methods: DNA was isolated from 33 unrelated German patients with chronic refractory AITP and from 80 randomly selected German blood donors to determine the phenotype and allele frequencies for the HPA‐1, ‐2, ‐3, and ‐5 systems. Fragments carrying the polymorphic sequences corresponding to those alleles were amplified by the polymerase chain reaction and further characterized by restriction analysis. Results: Whereas HPA‐1, ‐3, and ‐5 allele frequencies were identical in 33 patients with chronic refractory AITP and in controls, HPA‐2 allele frequencies showed a statistically significant difference (p = 0.017). In our group of patients, the HPA‐2a allele frequency was 100%, but HPA‐2b was not seen. In contrast, the allele frequency of HPA‐2a in the control group was 92% (n = 147), and in HPA‐2b it was 8% (n = 13). Conclusion: This study suggests an association between the HPA‐2a allele and chronic refractory AITP. The HPA‐2a allele may be involved in the formation of an AITP‐specific autoepitope.
Clinical Tolerance of Methylene Blue Virus‐Inactivated Plasma
Authors: Simonsen Anne Catrine , Sørensen Henning 
Published: December 2004

Abstract
Objectives:
Baxter's methylene blue (MB) photoinactivation of fresh frozen plasma (FFP) is a method that effectively removes any intracellular potentially infectious agent, such as prions, by filtration combined with an improved photochemical virus inactivation on a single unit of FFP. The purpose of this study was to demonstrate clinical and biochemical tolerance of MB‐treated plasma in healthy human volunteers. Methods: The design was a crossover randomized trial. Twelve subjects received alternatively treated and nontreated autologous FFP. Coagulation parameters were tested as well as clinical and biochemical parameters. Results: No clinical or statistically significant difference was detected for any of the parameters. Conclusion: Transfusion of FFP treated for viral reduction by an improved MB photoinactivation method was shown to be safe and did not affect the normal function of coagulation proteins. We consider this method as a valuable alternative to other methods described as it combines the photoinactivation with a filtration step removing any intracellular infectious agents, such as prions.
Large‐Scale Screening for Human Parvovirus B19 DNA by PCR: Application to the Quality Control of Plasma for Fractionation
Authors: Aubin J.T. , Defer C. , Vidaud M. , Montreuil M. Maniez , Flan B. 
Published: December 2004

Abstract
Background and Objectives:
Because human parvovirus B19 (B19) has been transmitted by various plasma‐derived medicinal products, the ‘Laboratoire français du Fractionnement et des Biotechnologies’ (LFB) implemented PCR screening of plasma pool samples for B19 DNA as part of the quality control of plasma source material. Materials and Methods: Plasma pool samples (average of 46.5 donations) were tested for B19 DNA by PCR and by immunological detection of PCR products. The viral DNA content was determined by means of a TaqManTM‐based, quantitative PCR. Results: From plasma corresponding to 2‐year collections in France, and representing 4.26 million donations from approximately 1.25 million voluntary unpaid donors, the average frequency of positive donations was 1/5,950 and reached 1/1,420 during an epidemic. Levels of B19 DNA in positive pools ranged from <102 to 1011 copies/ml. Conclusion: A large‐scale PCR plasma screening increased the safety of LFB's wide range of products with respect to B19, a virus particularly resistant to physicochemical inactivation procedures.
Plasma Levels of Eicosanoids after Transfusion of Intraoperatively Salvaged Blood
Authors: Jacobi K. , Walther A. , Lörler H. , Neidhardt B. 
Published: December 2004

Abstract
Background:
The interest in autologous red blood cell salvage is increasing rapidly, but it is well known that platelets and white cells are activated during cell washing. Therefore, we aimed to determine whether or not eicosanoids transfused together with the salvaged blood are responsible for nonhemolytic immunological transfusion reactions. Materials and Methods: In 11 patients who underwent radical prostatectomy we studied the release of eicosanoids, prostaglandin E2 (PGE2) and thromboxane B2 (TxB2), in association with reinfusion of intraoperatively salvaged blood. Blood samples were taken before operation, on days 1 and 3 after operation and before and after cell washing. Results: There was a twofold increase in PGE2 and a twentyfold increase in TxB2 in the unwashed salvaged blood. Washing caused a reduction in eicosanoid plasma levels of up to 95%, but a significantly lower level in relation to its corresponding preoperative value was only found for PGE2. After transfusion of an average of 420 ml RBC sediment from washed blood, the patients' plasma concentrations of PGE2 and TxB2 on the 1st and 3rd postoperative day did not significantly differ compared to baseline values. Conclusion: Our data support the notion that RBC sediment from ‘salvaged’ and washed autologous blood contains increased amounts of PGE2 and TxB2. It remains, however, questionable if these passively infused eicosanoids become biologically active. According to our study, the PGE2 and TxB2 transfused are apparently not responsible for nonhemolytic immunological transfusion reactions.
Introduction to Antibody Engineering and Phage Display
Authors: Watkins Nicholas A. , Ouwehand Willem H. 
Published: December 2004

AbstractThe vertebrate immune system, capable of rapidly producing highly specific antibodies upon immunisation, has been used to produce murine monoclonal antibodies (mAbs) via immortalisation and isolation of antibody–secreting cells. These mAbs have had a profound impact in the fields of diagnostics and therapeutics. However, the therapeutic use of murine mAbs is complicated by their immunogenicity. To circumvent this immunogenicity, antibody engineering techniques which render murine mAbs more compatible with the human immune system have been devised. Over the last decade, the technique of antibody phage display, which facilitates the production of human mAbs, has been developed. This review serves as an introduction to antibody engineering, phage display and the development of antibody fragments into viable diagnostic and therapeutic reagents.
Transfusion Thresholds in Common Elective Surgical Procedures in Finland
Authors: Capraro L. , Nuutinen L. , Myllylä G. 
Published: December 2004

Abstract
Background and Objectives:
Transfusion practices and thresholds in common elective surgical procedures were investigated in a nationwide multicenter survey in Finland. Materials and Methods: The records of 764 total hip replacement (THR), 397 total knee replacement (TKR) and 343 transurethral resection of the prostate (TURP) patients were reviewed by four anesthesiologists. Results: The allogeneic red cell (RBC) transfusion rates in THR, TKR and TURP operations were 92, 84 and 18%, respectively. In THR and TKR, 74% of patients who lost 20% or less of their blood volume during hospitalization were transfused with RBCs. Postoperatively, the median pretransfusion hemoglobin values were 9.6 g/dl in orthopedic operations and 10.7 g/dl in TURP. In some hospitals, the median transfusion threshold in TURP patients was as high as 11.2 g/dl. Conclusion: The transfusion thresholds in all operations were liberal compared to recent international recommendations. Inappropriate thresholds were reflected in the high transfusion rates. This study accentuates the need for continuous discussion and educational measures to find optimal indications for transfusion in surgery, and to rationalize the transfusion policy in Finland.
Thrombopoietin Levels in Patients Undergoing Autologous Peripheral Blood Stem Cell Transplantation
Authors: Yoshimura Chie , Nomura Shosaku , Katsura Kaoruko , Yamaguchi Kazuyuki , Fukuhara Shirou 
Published: December 2004

Abstract
Background and Objectives:
High–dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. Several reports on endogeneous production of thrombopoietin (TPO) in patients undergoing intensive chemotherapy have been published. We measured TPO levels in patients undergoing autologous PBSCT in order to elucidate the role of TPO in megakaryopoiesis and platelet recovery following stem cell transplantation. We also examined whether PBSC from different patient groups (patients with lung cancer and malignant lymphoma) had different effects on TPO levels. Materials and Methods: Serum levels of TPO and other cytokines were determined by ELISA before and after PBSCT in 10 patients with lung cancer and 18 patients with malignant lymphoma. Results: Compared to platelet counts at 1 week after transplantation, those at 3 weeks were significantly increased (p<0.001). In contrast, serum TPO levels were significantly decreased 3 weeks after PBSCT (p<0.01). There were no significant differences in levels of other cytokines between 1 and 3 weeks after transplantation. A strong correlation was found between serum TPO levels and circulating platelet counts (r =–0.675; p<0.0001). Platelet counts exhibited a significant recovery and TPO levels also decreased significantly in malignant lymphoma patients after transplantation. There were no significant differences in TPO levels in lung cancer patients, although the same tendencies as for malignant lymphoma patients were observed for both platelet count and TPO level. On analysis of transfused PBSC, we found that the numbers of CFU–GM were similar in lung cancer and malignant lymphoma patients. However, the numbers of CD34+ cells were significantly higher in lung cancer patients than in malignant lymphoma patients. Conclusion: Our findings suggest that TPO plays a critical role in the reconstitution of megakaryopoiesis and platelet production following PBSCT, and that the type of stem cell, tumor, and preceding chemotherapy affect serum TPO levels after transplantation.
Flow‐Cytometric Method for the Quantitation of the Fc Function of Intravenous lmmunoglobulin Preparations
Authors: Ramasamy Indra , Tran Em , Charnock Alison , Farrugia Albert 
Published: December 2004

Abstract
Objectives:
We have developed and optimised a new flow‐cytometric method for the measurement of the Fc function of intravenous immunoglobulin (IVlg) preparations, which is important in predicting the effector function of immunoglobulin (Ig) in such preparations. Materials and Methods: Ig was bound to a monocytic cell line, THP‐1 with FcγRl and FcγRll cell surface receptors, and the bound Ig detected by FITC‐conjugated F(ab)2 fragment of rabbit anti‐human IgG. Results: Validation studies showed that Ig bound to the cell line through the Fc portion. The method detected alterations in Fc function caused by reduction with dithiothreitol or by storage. The method was reproducible (CV<11%) and a limited comparison study showed that it correlated with the European Pharmacopoeia reference method. Conclusions: This technically simple method is suitable for the quantitation of the Fc function of Ig preparations.
Collection Efficiencies of CD34+ Progenitor Cells and Mononuclear Cells in Leukapheresis Products Quantified by Flow Cytometry and Calculated on the Basis of a New Formula
Authors: Schlenke Peter , Frohn Christoph , Hennig Holger , Weber Klaus , Kisro Jens , Saballus Martin , Kirchner Holger , Klüter Harald 
Published: December 2004

Abstract
Background and Objectives:
Optimal mobilization and harvest of hematopoietic progenitors are essential for peripheral blood stem cell transplantation after myeloablative high‐dose chemotherapy. Conflicting data have been published concerning the most useful, cost‐effective collection strategy which is also convenient for patients. Materials and Methods: A total of 66 leukaphereses in 20 patients were retrospectively evaluated. We assessed the predictive value of the number of white blood cells, mononuclear cells (MNCs) and CD34+ cells in peripheral blood for the yield of CD34+ cells in leukapheresis products. The concentrations of MNCs and CD34+ cells were quantified simultaneously by a flow cytometric procedure using fluorescent microparticles. Their collection efficiencies were calculated based on a newly developed formula. Results: The collected hematopoietic progenitor concentration could be predicted only by the number of peripheral blood CD34+ cells prior to apheresis (r = 0.902; p < 0.01). Furthermore, the mobilization of at least 30 CD34+ cells/μl peripheral blood was a good predictor that a single leukapheresis would yield a minimum of 2.0 × 106 CD34+ cells/kg body weight. The collection efficiencies calculated by the new formula were 55.2±10.7% and 57.7±11.2% for MNCs and CD34+ cells, respectively. Conclusion: The precise quantification of MNCs and CD34+ cells by a direct flow cytometric assay, as well as the new formula to determine the collection efficiencies, has an impact on optimizing high‐quality stem cell products.
Leukoreduction of Platelet Concentrates Using a ‘Polishing’ Filter
Authors: van der Meer P.F. , Pietersz R.N.I. , Reesink H.W. 
Published: December 2004

Abstract
Background and Objectives
: Filters for removal of leukocytes from platelet concentrates (PCs) usually have a large volume to guarantee sufficient leukoreduction. In this study, a small filter, with a volume of only 8ml and therefore minimal platelet loss, for leukoreduction of PCs was investigated. This filter has a ‘limited’ leukoreducing capacity, hence the filter is called a ‘polishing’ filter. Materials and Methods: PCs were made from 5 pooled buffy coats in either plasma or additive solution (PAS‐II). After centrifugation, the platelet‐rich supernatant was expressed on an automated separator (Compomat G4) to an empty transfer bag. The content of this transfer bag was filtered into the platelet storage bag, either by expression by lowering the top press of the Compomat G4, or by gravity by hanging it on a filtration rack. Results: Leukocyte counts before and after filtration revealed a mean leukoreducing capacity for the filter of 2.67 log10 and a platelet loss of only 2% for PCs in PAS‐II (n = 50), and for PCs in plasma a 3.43 log10 leukoreduction with 3% platelet loss (n = 30). Expression of the PCs both in plasma and PAS‐II through the filter using the Compomat G4 resulted in 10/10 units containing <5×106 leukocytes, but 1/10 PCs contained >1×106 leukocytes for both solutions. Filtration by gravity resultet in 40/40 units with <1×106 leukocytes for PCs in plasma, and 60/60 units with <1×106 for PCs in PAS‐II. Conclusion: The ‘polishing’ filter allows relible, standardized and automated production of PCs, both in plasma and additive solution with minimal platelet loss, and containing uniformly <1×106 leukocytes, provided the filtration procedure is performed by gravity.
A Clinically Applicable Method for the ex vivo Generation of Antigen‐Presenting Cells from CD34+ Progenitors
Authors: Ardeshna K.M. , Corney C.P. , Ings S.J. , Watts M.J. , Linch D.C. , Devereux S. 
Published: December 2004

Abstract
Background and Objectives
: Dendritic cells (DCs), the most potent of antigen‐presenting cells, can be generated in vitro from bone marrow or blood progenitor cells. We have developed a method for producing such cells from mobilised peripheral blood CD34+ cells in the absence of bovine products. Methods: The culture system developed used X‐Vivo 10 culture medium with 10% autologous serum, rhGM‐CSF, rhTNF‐α and rhIL‐4. Largescale cultures were performed in Stericell 12 inch X 15 inch culture bags. Results: In 12‐small‐scale experiments, over 14 days, there was a median 38‐fold increase in cell numbers of which 12.8% were DCs as defined by immunophenotyping. These cells had potent DC activity in functional assays. In two clinical‐scale experiments, a 5.7‐ and 10‐fold expansion of total cell numbers was obtained, with 8.2 and 18% of the final population being DCs, respectively. Conclusion: This system is suitable for clinical application.