bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in serum osteocalcin and bone‐specific alkaline phosphatase are associated with bone pain in donors receiving granulocyte–colony‐stimulating factor for peripheral blood stem and progenitor cell collection
Authors: Froberg M. Kent , Garg Uttam C. , Stroncek David F. , Geis Michael , McCullough Jeffrey , Brown David M.
Published: March 2003

BACKGROUND: Granulocyte–colony‐stimulating factor (G–CSF) has been used to increase the number of CD34+ peripheral blood stem and progenitor cells collected by apheresis for use in autologous or allogeneic progenitor cell transplantation. The most frequent side effect of G–CSF treatment is bone pain, which occurs in over 80 percent of healthy progenitor cell donors.

STUDY DESIGN AND METHODS: The possible mechanism of bone pain was investigated by measuring serum levels of osteocalcin (OC), bone‐specific alkaline phosphatase (BAP), acid phosphatase (ACP), and tartrate‐resistant acid phosphatase (TRAP) in seven healthy progenitor cell donors treated with human recombinant G–CSF administered subcutaneously for 5 consecutive days.

RESULTS: All seven patients experienced bone pain during the treatment period. Serum levels of OC, BAP, ACP, and TRAP were measured in blood samples drawn on Days 0, 4, 5, 6, and 14. Levels of BAP were increased (p<0.05) over baseline on Days 4, 5, and 6, while those of OC decreased on Days 4, 5, and 6 (p<0.05). No significant changes occurred in ACP or TRAP levels. OC and BAP are considered markers of bone formation (osteoblast activity), and they correlate in many patients with metabolic bone disorders. The pattern of increased BAP and decreased OC has been reported in patients with osteolytic bone metastases.

CONCLUSION: G–CSF treatment in healthy stem and progenitor cell donors may affect osteoblastic activity, and this activity may be associated with bone pain.
B‐lymphoblastoid cell lines as a source of reference DNA for human platelet and neutrophil antigen genotyping
Authors: Carl B. , Kroll H. , Bux J. , Bein G. , Santoso S.
Published: March 2003

BACKGROUND: Human platelet and neutrophil antigens (HPAs, HNAs) are targets for platelet or granulocyte antibodies causing immune thrombocytopenia or neutropenia, respectively. Currently, genotyping is replacing phenotyping as the preferred method of diagnosis of immune cytopenia. To establish a reliable genotyping analysis, however, the availability as reference DNA of genomic DNA from persons of known genotype is essential.

STUDY DESIGN AND METHODS: By the use of Epstein‐Barr virus transformation, panels of B‐lympho‐blastoid cell lines (B‐LCLs) from HPA‐ and HNA‐phenotyped individuals were developed. Genomic DNA was isolated from these cell lines and tested as reference DNA for genotyping of persons for HPAs and HNAs.

RESULTS: DNA derived from these B‐LCLs was typed by polymerase chain reaction‐restriction fragment length polymorphism and ‐sequence‐specific primers. The results were in accordance with the genotyping from peripheral blood cells. These results were confirmed by 24 laboratories in Germany in a blind study.

CONCLUSION: The inexhaustible source of reference DNA derived from B‐LCLs allowed the evaluation of reliable HPA and HNA genotyping for quality control purposes. It should facilitate the development of DNA typing in blood centers and clinical laboratories.
A prospective, randomized, sequential crossover trial oflarge‐volume versus normal‐volume leukapheresis procedures:effects on serum electrolytes, platelet counts, and other coagulation measures
Authors: Humpe A. , Riggert J. , Munzel U. , Köhler M.
Published: March 2003

BACKGROUND: LVL procedures with the administration of heparin as an additional anticoagulant are increasingly performed because of the potentially higher yield of autologous peripheral blood HPCs. A prospective, randomized crossover trial was performed to evaluate the influence of leukapheresis volume—that is, large versus normal—on serum electrolytes, platelet count, and other coagulation measures in 25 patients with breast cancer and 14 patients with non‐Hodgkin's lymphoma.

STUDY DESIGN AND METHODS: Patients were randomly assigned to start either with an LVL on Day 1 followed by a normal‐volume leukapheresis (NVL) on Day 2 or vice versa. In LVL, heparin was administered in addition to ACD‐A. Bleeding complications, transfusion support, whole‐blood counts, and several coagulation measures as well as plasma heparin levels were evaluated.

RESULTS: Although the duration, the infused amount of ACD‐A, the flow rate, the drop in platelet count, and the drop in potassium were significantly greater in LVL, and although LVL patients also received heparin, there was no significant difference in clinical tolerance or bleeding complications. After LVL, patients exhibited a significantly longer activated partial thromboplastin time (APTT), with a median of 70 seconds (range, 44–100 sec), and a median anti‐factor Xa activity of 0.69 IU per mL (range, 0.10–1.29 IU/mL). The value of the APTT after LVL correlated with anti‐factor Xa activity (r = 0.37, p<0.05), but not with platelet count or heparin infusion rate. Markers for coagulation activation did not increase during NVL or LVL.

CONCLUSION: LVL with heparin as an additional anticoagulant seems to be a safe procedure in patients with low preleukapheresis platelet counts. No activation of coagulation occurred after NVL or LVL procedures.
Variations in genes encoding neutrophil antigens NA1 and NA2
Authors: Matsuo K. , Procter J. , Stroncek D.
Published: March 2003

BACKGROUND: Neutrophil‐specific antigens NA1 and NA2 are located on Fcγ receptor IIIb (FcγRIIIb). NA1 and NA2 forms of FcγRIIIb differ by four amino acids and the corresponding genes by five nucleotides. Variations in NA gene frequencies are encountered among ethnic groups. Altered forms of the genes are expected among individuals.

STUDY DESIGN AND METHODS: RFLPs associated with four recognition sites were used to determine NA genotypes of 232 individuals. When atypical NA genotypes were identified, FcγRIIIB and FcγRIIIA regions were sequenced.

RESULTS: NA1 FcγRIIIB frequency in 100 Japanese (0.66) was greater than that in 53 African Americans (blacks) (0.40; p<0.01) and 79 whites (0.32; p<0.001). Sequencing of atypical FcγRIIIB in 16 people confirmed that four blacks had G→A substitutions at 227; 7 blacks had A→G substitutions at 277; and 1 Japanese person had C→G at 141 and G→T at 227. A at 227 and G at 277 represent expected nts of NA1 FcγRIIIB. One black had an NA1 FcγRIIIB with a G→A substitution at 349; A is normally found in NA2 FcγRIIIB at 349. Sequencing atypical FcγRIIIA in three persons revealed that two blacks had G→A substitutions at 277 plus C→A substitutions at 266 and 1 white had previously described T→G at 230. Two blacks with atypical NA2 FcγRIIIB had T→G FcγRIIIA at 230. One black was NAnull.

CONCLUSION : NA2 FcγRIIIB is more polymorphic in blacks than in whites or Japanese persons. Chimeric FcγRIIIB alleles are most similar to NA2 FcγRIIIB. One alternate allele of NA1 (NA1*02) and four alternate alleles of NA2 (NA2*02, NA2*03, NA2*04, and NA2*05) are described.
l‐carnitine decreases glycolysis in liquid‐stored platelets
Authors: Sweeney Joseph D. , Blair Abbe‐Jane , Cheves Tracey A. , Dottori Secondo , Arduini Arduino
Published: March 2003

BACKGROUND: The platelet storage lesion is characterized metabolically by a pH decrease associated with lactic acid generation; a change in platelet morphology from discoid to spherical; a diminished response to in vitro challenge tests, such as the hypotonic shock response (HSR) and extent of shape change (ESC); increased surface P‐selectin expression; and decreased in vivo recovery and survival. Altering storage conditions to improve these measures could allow for extension of the duration of in vitro storage.

STUDY DESIGN AND METHODS: ABO‐identical paired platelet concentrates were pooled and then equally divided into two plastic bags. Either l‐carnitine (LC) or an equal volume of saline (control) was added to one container of each pair. Platelets were stored at 20 to 24°C for 5 to 10 days or at 1 to 6°C for 5 days at various concentrations of LC between 0.1 and 15 mM. At the end of storage, pH, glucose consumption, lactate generation, HSR, ESC, and surface P‐selectin expression were measured. In different experiments, paired platelet concentrates were spiked with a Staphylococcus epidermidis suspension in the presence and absence of l‐carnitine at a concentration of 5 mM.

RESULTS: At 20 to 24°C and concentrations of LC between 0.1 and 5 mM, there was evidence of better pH preservation, less glucose consumption, and less lactate generation. Only with storage beyond 5 days was a difference present in either surface P‐selectin expression or HSR. An l‐carnitine concentration of 5 mM appeared optimal. l‐carnitine did not enhance the growth of bacteria after 7 to 8 days of storage.

CONCLUSION: LC at 5 mM may improve the quality of platelet concentrates that are stored beyond 5 days. There was no indication that LC at this concentration would promote bacterial growth. it may be a useful additive to platelet preservation.
PBPC mobilization with paclitaxel, ifosfamide, and G‐CSF with or without amifostine: results of a prospective randomized trial
Authors: Rick Oliver , Schwella Nimrod , Beyer Jörg , Dubiel Mark , Krusch Andreas , Hildebrandt Martin , Schleicher Jan , Serke Stefan , Siegert Wolfgang
Published: March 2003

BACKGROUND: The impact of amifostine on PBPC mobilization with paclitaxel and ifosfamide plus G‐CSF was assessed.

STUDY DESIGN AND METHODS: Forty patients with a median age of 34 years (range, 19‐53) who had germ cell tumor were evaluated for high‐dose chemotherapy. Patients were randomly assigned to receive either a single 500‐mg dose of amifostine (Group A, n = 20) or no amifostine (Group B, n = 20) before mobilization chemotherapy with paclitaxel (175 mg/m2) given over 3 hours and ifosfamide (5 g/m2) given over 24 hours (TI) on Day 1. G‐CSF at 10 μg per kg per day was given subsequent to TI with or without amifostine from Day 3 until the end of leukapheresis procedures.

RESULTS : In 2 (10%) of 20 patients receiving amifostine and 3 (15%) of 20 patients not receiving it, no PBPC separation was performed because of mobilization failure. No significant differences were observed in the study arms with regard to the time from chemotherapy until first PBPC collection or the number of apheresis procedures needed to harvest more than 2.5 × 106 CD34+ cells per kg. Furthermore, leukapheresis procedures yielded comparable doses of CD34+ cells per kg (3.4 × 106 vs. 3.6 × 106; p = 0.82), MNCs per kg (2.7 × 108 vs. 2.6 × 108; p = 0.18), and CFU‐GM per kg (15.9 × 104 vs. 19.3 × 104; p = 0.20). Patients in Group A had higher numbers of circulating CD34+ cells on Day 10 (103.0/μL vs. 46.8/μL; p = 0.10) and on Day 11 (63.0/μL vs.14.3/μL; p = 0.04) than did patients in Group B.

CONCLUSION: Administration of a single dose of amifostine before chemotherapy with TI mobilized higher numbers of CD34 cells in the circulation, but did not enhance the overall collection efficiency in the present trial.
Hyperhemolytic transfusion reaction in sickle cell disease
Authors: Win Nay , Doughty Heidi , Telfer Paul , Wild Barbara J. , Pearson T.C.
Published: March 2003

BACKGROUND: An atypical form of life‐threatening hemolytic transfusion reaction (HTR) in patients with sickle cell disease (SCD) has been well described in the literature. Continuation of blood transfusion may be lethal, as it can further exacerbate hemolysis. The pathophysiologic mechanism of HTR is not well understood.

CASE REPORTS: Two cases of severe HTR in SCD after the transfusion of compatible RBC units are reported. Hemolysis of both autologous and transfused cells was documented in Case 1 by urine Hb high‐performance liquid chromotography. Multispecific HLA antibodies were identified in Case 1. Reticulocytopenia was noted in both cases during the acute hemolytic process. This was followed by a rise in reticulocyte count during receipt of IVIG and steroid therapy. Bone marrow examination during reticulocytopenia in Case 2 showed erythroid hyperplasia.

CONCLUSION: In SCD, both mature sickle cells and sickle reticulocytes adhere more readily to macrophages. In view of the bone marrow aspiration results, it appears that the recipients' HbS cells are destroyed by hyperactive macrophages and that the reticulocytopenia observed during HTR is likely to be due to peripheral consumption (i.e., destruction by macrophages), rather than suppression of erythropoiesis. Cessation of hemolysis during IVIG and steroid treatment may be due to IVIG's blocking of the adhesion of sickle cells and reticulocytes to macrophages, together with steroid suppression of macrophage activity.
Transfusion of incompatible RBCs to a patient with alloanti‐Kpb
Authors: Mazzara Roberto , Lozano Miguel , Salmerón Joan M. , Piera Carlos , Ribera Anna , Mas Antonio , Ordinas Antonio
Published: March 2003

BACKGROUND: The finding of an antibody that reacts against a high‐incidence blood group antigen always constitutes a complex transfusion problem because of the difficulty in finding compatible units. When the transfusion of incompatible RBCs is imperative, it would be of great interest to have access to techniques facilitating the prediction of the transfusion outcome.

STUDY DESIGN AND METHODS: The case of a patient with alloanti‐Kpb who required RBC transfusions is reported. The functional activity of this antibody was assessed by both the chemiluminescence test (CLT) and the survival of 51Cr‐labeled RBCs.

RESULTS : The CLT showed an opsonic index of 0.8 with Kpb‐positive RBCs (normal values up to 1.6) in pretransfusion studies. During an elective surgical procedure, the patient required the transfusion of one incompatible unit of RBCs, which did not produce hemolysis. Two weeks after this incompatible transfusion, the opsonic index had risen to 11. Results of the 51Cr in vivo study, also performed at that time, indicated 24.3 percent survival of Kpb‐positive RBCs at 60 minutes and 2.0 percent at 24 hours.

CONCLUSION: Results of the CLT correlated with the in vivo transfusion outcome and later with the 51Cr survival study.
Uncontrolled‐rate freezing and storage at –80°C, with only3.5‐percent DMSO in cryoprotective solution for 109 autologous peripheral blood progenitor cell transplantations
Authors: Halle Pascale , Tournilhac Olivier , Knopinska‐Posluszny Wanda , Kanold Justyna , Gembara Piotr , Boiret Nathalie , Rapatel Chantal , Berger Marc , Travade Philippe , Angielski Stephan , Bonhomme Jean , Deméocq Francois
Published: March 2003

BACKGROUND: Although controlled‐rate freezing and storage in liquid nitrogen are the standard procedure for peripheral blood progenitor cell (PBPC) cryopreserva‐tion, uncontrolled‐rate freezing and storage at –80°C have been reported.

STUDY DESIGN AND METHODS: The prospective evaluation of 109 autologous PBPC transplantations after uncontrolled‐rate freezing and storage at –80°C of apheresis products is reported. The cryoprotectant solution contained final concentrations of 1‐percent human serum albumin, 2.5‐percent hydroxyethyl starch, and 3.5‐percent DMSO.

RESULTS: With in vitro assays, the median recoveries of nucleated cells (NCs), CD34+ cells, CFU–GM, and BFU–E were 60.8 percent (range, 11.2‐107.1%), 79.6 percent (6.3‐158.1%), 35.6 percent (0.3‐149.5%), and 32.6 percent (1.7‐151.1%), respectively. The median length of storage was 7 weeks (range, 1‐98). The median cell dose, per kg of body weight, given to patients after the preparative regimen was 6.34 × 108 NCs (range, 0.02‐38.3), 3.77 × 106 CD34+ cells (0.23‐58.5), and 66.04 × 104 CFU–GM (1.38‐405.7). The median time to reach 0.5 × 109 granulocytes per L, 20 × 109 platelets per L, and 50 × 109 reticulocytes per L was 11 (range, 0‐37), 11 (0‐129), and 17 (0‐200) days, respectively. Hematopoietic reconstitution did not differ in patients undergoing myeloablative or nonmyeloablative conditioning regimens before transplantation.

CONCLUSION: This simple and less expensive cryopreservation procedure can produce successful engraftment, comparable to that obtained with the standard storage procedure.
Kinetics of PBPC mobilization by cyclophosphamide, as compared with that by epirubicin/paclitaxel followed by G–CSF support: implications for optimal timing of PBPC harvest
Authors: Dettke Markus , Greinix Hildegard T. , Kalhs Peter , Kührer Irene , Worel Nina , Höcker Paul
Published: March 2003

BACKGROUND: Limited information is available on the mobilization kinetics of autologous PBPCs after induction with various chemotherapy regimens. With PBPC mobilization in patients with breast cancer used as a model for chemotherapy‐induced PBPC recruitment, the kinetics of progenitor cells mobilized either with cyclophosphamide (CY) or epirubicin/paclitaxel (EPI‐TAX) followed by the administration of G–CSF was compared.

STUDY DESIGN AND METHODS: The study included a total of 86 patients with breast cancer (stage II‐IV) receiving either CY (n = 39) or EPI‐TAX (n = 47), both followed by G–CSF support. The progenitor cell content in peripheral blood and apheresis components was monitored by flow cytometric enumeration of CD34+ cells. PBPC collection was started when the threshold of >20 × 106 CD34+ cells per L of peripheral blood was reached.

RESULTS: The PBPC collection was begun a median of 9 days after the administration of EPI‐TAX followed by G–CSF support, as compared to a median of 13 days after mobilization with CY plus G–CSF. After treatment with CY, the total numbers of PBPCs peaked on Day 1 of apheresis, and they rapidly declined thereafter. In contrast, treatment with EPI‐TAX followed by G–CSF administration led to a steady mobilization of CD34+ cells during leukapheresis. The difference in the mobilization patterns with CY and EPI‐TAX resulted in a greater yield of CD34+ cells per L of processed blood volume. Compared to EPI‐TAX, mobilization with CY required the overall processing of 30 percent less whole‐blood volume to reach the target yield of ≥10 × 106 CD34+ cells per kg of body weight. After a median of three apheresis procedures, however, both CY+G–CSF and EPI‐TAX+G–CSF were equally effective in obtaining this target yield.

CONCLUSION: These results imply that specific PBPC mobilization as part of a given chemotherapy regimen should be taken into consideration before the planning of a PBPC harvest.
Frequent presence of HBV in the sera of HBsAg‐negative, anti‐HBc‐positive blood donors
Authors: Yotsuyanagi Hiroshi , Yasuda Kiyomi , Moriya Kyoji , Shintani Yoshizumi , Fujie Hajime , Tsutsumi Takeya , Nojiri Noriyoshi , Juji Takeo , Hoshino Hiromi , Shimoda Kazumi , Hino Kunihiko , Kimura Satoshi , Iino Shiro , Koike Kazuhiko
Published: March 2003

BACKGROUND: Recent studies have revealed that HBV may not be cleared even after the disappearance of serum HBsAg. The purpose of this study was to investigate whether the replication of HBV persists in HBsAg‐negative blood donors who lack apparent liver disease.

STUDY DESIGN AND METHODS: Serum HBV was examined by using PCR coupled with Southern blotting in 50 blood donors who were identified to be HBsAg negative but anti‐HBc positive.

RESULTS: HBV DNA was detected in the sera from 19 (38%) of 50 donors. In 11 of the 19, HBV existed exclusively as immune complexes, while HBV presumably did not exist as immune complexes in the remaining eight. The levels of HBV DNA were similar to those in patients who had recovered from acute HBV. Some nucleotide substitutions, which did not confer amino acid changes in the major epitope of HBsAg, were found in the preS‐S regions.

CONCLUSION: The replication of HBV is ongoing in a substantial proportion of healthy blood donors who have anti‐HBc. Blood from such donors may contain very low levels of HBV free of immune complex formation and should be excluded for transfusion. The fact that such blood donors apparently lacked liver disease suggests no pathogenicity of such “occult” HBV.
Different preparation methods to obtain platelet components as a source of growth factors for local application
Authors: Zimmermann Robert , Jakubietz Rafael , Jakubietz Michael , Strasser Erwin , Schlegel Andreas , Wiltfang Jörg , Eckstein Reinhold
Published: March 2003

BACKGROUND: Autologous platelet components were recently used as part of tissue‐engineering strategies in oral and maxillofacial surgery. Various preparation methods were investigated to define standardized blood bank components and to collect data on the growth factor content of human platelets before and after storage.

STUDY DESIGN AND METHODS: Apheresis platelets (AP), buffy coat‐derived platelets (BCP), platelets prepared by tube method (TP), and highly concentrated samples prepared from AP and from BCP were evaluated for standard quality criteria of platelet components and for their concentration of transforming growth factor (TGF)‐ß1, platelet‐derived growth factor (PDGF)‐AB, and PDGF‐BB. AP were stored for 5 days. On Days 3 and 5, these components and freshly prepared, highly concentrated samples were evaluated for the same measures.

RESULTS: Platelet concentration in TP was lower than that in the other groups (p<0.05). However, the concentrations of PDGF‐AB, PDGF‐BB, and TGF‐ß1 were comparable in the three groups. TP showed higher spontaneous CD62 expression than did AP and BCP. The three preparation procedures resulted in significantly different WBC contamination, with the highest levels in TP. For the whole series of measurements, there was a strong correlation between growth factor levels and platelet concentration (p<0.05), which was due to the face that the growth factor content of concentrated platelet samples was tenfold that of AP, BCP, and TP. In TP, the WBC concentration was correlated with PDGF levels (p<0.05). After 5‐day storage, the mean levels of PDGF‐AB, PDGF‐BB, and TGF‐ß1 were 57.1, 43.0, and 72.0 percent of the initial values in AP. Overall, multiple regression analysis revealed the following factors influencing the measured growth factor concentrations: platelet concentration, baseline CD62 expression, lactate production, and WBC contamination.

CONCLUSION: Various methods enable the preparation of platelet components and of highly concentrated components for local use according to standard blood banking criteria. The obtained components differ, particularly in their WBC content and in vitro platelet activation. These findings are relevant for planning and evaluating further studies of locally usable autologous platelet components.
A study of 178 consecutive vasovagal syncopal reactions from the perspective of safety
Authors: Newman Bruce H. , Graves Susan
Published: March 2003

BACKGROUND: While vasovagal syncopal reactions have been studied in the past, there are several safety questions that could be further addressed. The purpose of this study was to address these safety questions.

STUDY DESIGN AND METHODS: One hundred seventy‐eight vasovagal reactions were reported in 1999 from 194,000 blood donations. The reactions were retrospectively reviewed for 38 variables that included donor demographics, symptoms, injury, and final disposition.

RESULTS: Sixty‐one percent of the syncopal reactions occurred at the refreshment table and 12 percent offsite. Fourteen percent of the donors sustained an injury, usually to the head (10%). Eleven donors (6%) had additional medical care in an emergency room: 4 for injuries, 3 for delayed recovery, and 4 for offsite syncope. None of the donors was admitted to the hospital. One of the injured donors developed postconcussion syndrome and had later sequelae.

CONCLUSION: Syncopal reactions most commonly occur at the refreshment table, where preventive safety measures against trauma could be applied. A significant number of syncopal reactions occur offsite, where the environment is less safe. The injuries that occur, particularly to the head, may in rare cases lead to long‐term sequelae.
Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF‐cleaving protease activity
Authors: Mori Yoshitaka , Wada Hideo , Gabazza Esteban C. , Minami Nobuyuki , Nobori Tsutomu , Shiku Hiroshi , Yagi Hideo , Ishizashi Hiromichi , Matsumoto Masanori , Fujimura Yoshihiro
Published: March 2003

BACKGROUND: Severe deficiency of vWF‐cleaving protease (vWF‐CPase) activity was recently found in patients with thrombotic thrombocytopenic purpura (TTP). Although the survival of patients with TTP has been dramatically improved with plasma exchange (PE), there are still many patients who are refractory to PE and immunosuppressive therapy.

STUDY DESIGN AND METHODS: The activities of vWF‐CPase and its inhibitor were measured in 27 patients with nonfamilial TTP and hemolytic‐uremic syndrome (HUS) to examine the relationship between the clinical variables and vWF‐CPase activity.

RESULTS: Eight of nine patients with HUS had more than 40 percent of vWF‐CPase activity, whereas one had 28 percent of the normal level at the acute phase. Ten of 12 TTP patients with a good outcome had a severe deficiency of vWF‐CPase activity and its inhibitor, whereas four of six patients with a poor outcome had a moderate deficiency of vWF‐CPase activity along with a lack of the inhibitor. PE produced normalization of the vWF‐CPase activity and neutralization of the inhibitor in TTP patients with a good outcome; however, some TTP patients with vWF‐CPase inhibitor had relapsed and required an immunosuppressive therapy. The response to the combination therapy with PE and immunosuppressive treatment was poor in TTP patients without a severe deficiency of vWF‐CPase activity.

CONCLUSION: Assays of vWF‐CPase activity and its inhibitor may be useful for predicting the response to therapy and the outcome of patients with TTP. In some patients, nonfamilial TTP with a poor prognosis may not be caused by a constitutional or acquired deficiency of vWF‐CPase with its inhibitor. Although PE and immunosuppressive therapy are effective in patients with nonfamilial TTP and a vWF‐CPase inhibitor, other therapeutic modalities may be needed for nonfamilial TTP with unknown etiology.
Validation of the NucliSens Extractor combined with the AmpliScreen HIV version 1.5 and HCV version 2.0 test for application in NAT minipool screening
Authors: Jongerius John M. , Sjerps Margret , Cuijpers H. Theo M. , Van Drimmelen Harry A.J. , Van der Poel Cees L. , Reesink Henk W. , Molijn M. Hans J. , Peeters Geert A.H. , Peeters Ton P.W. , Lelie P. Nico
Published: March 2003

BACKGROUND : Routine HCV NAT minipool screening (48 donations) of all blood donations was implemented in July 1999 and was combined with HIV NAT in November 2000. This report describes the validation of the NAT methods and the results of quality control testing.

STUDY DESIGN AND METHODS : Nucleic acid was extracted from 2‐mL plasma samples by using an automated silica‐based extraction method (NucliSens Extractor, Organon Teknika). Eluates were tested with RT‐PCR (AmpliScreen HIV‐1 version 1.5 and AmpliScreen HCV version 2.0 test, Roche Diagnostic Systems). HIV‐1 and HCV RNA reference panels and run controls (PeliCheck and PeliSpy, respectively, Sanquin‐CLB) and human plasma minipools were used for NAT validation.

RESULTS : The 95‐percent detection limit (and 95% CI) for HIV‐1 RNA genotype B, HIV‐1 RNA genotype E, and HCV RNA genotype 1 was 32 (19‐76), 30 (17‐72), and 21 (13‐44) genome equivalents (geq) per mL, respectively. During initial validation, 2332 samples for HIV‐1 RNA and 2644 samples for HCV RNA were analyzed, with 13 (0.56%) and 12 (0.45%) invalid test results, respectively. Thereafter, over 19,600 samples (minipools and run controls) were analyzed during the first 11 months of routine screening. Invalid test results for HIV‐1 RNA and HCV RNA were found in 1.1 and 1.07 percent of the samples tested, respectively. HIV‐1 RNA minipool testing resulted in 27 (0.16%) initial false‐positive results and 3 (0.02%) confirmed positive results. HCV RNA minipool testing resulted in four (0.02%) initial false‐positive results and five (0.02%) confirmed positive results.

CONCLUSION : Routine HIV and HCV NAT minipool screening using the NucliSens Extractor, AmpliScreen HIV‐1 version 1.5, and AmpliScreen HCV version 2.0 meets the sensitivity criteria set by the regulatory bodies and provides sufficient specificity and robustness for timely release of blood donations.
Sensitivity of HCV core antigen and HCV RNA detection in the early infection phase
Authors: Nübling C. Micha , Unger Gabriele , Chudy Michael , Raia Steven , Löwer Johannes
Published: March 2003

BACKGROUND : Various countries have introduced HCV NAT to exclude infectious donations collected during the preseroconversion window phase (PWP). For the same purpose, an ELISA has also been developed to detect HCV core antigen (cAg).

STUDY DESIGN AND METHODS : Using sequential samples from regular plasma donors with very recent HCV infections, a total of 494 samples from 52 anti‐HCV‐negative donors were collected. These panels were used for direct comparison of the performance of PCR and ELISA in detecting viral markers (RNA and cAg) during the PWP of HCV infection. The panels were genotyped, and each sample was analyzed by qualitative and quantitative HCV PCR and by cAg ELISA. The HCV RNA doubling time was calculated from quantitation of viral RNA in consecutive samples during the earliest outbreak of viremia.

RESULTS : Concurrent detection of HCV RNA and cAg in 218 and nondetection in 185 samples yielded 81.6‐percent concordance in the results of 494 samples. Unidirectional discrepancy of results (i.e., PCR positive and cAg negative) was seen in 91 of 494 (18.4%) samples, which was consistent with 65 specimens with RNA concentrations ranging between 300 and 100,000 IU per mL and 26 specimens with less than 300 IU per mL (limit of quantitative PCR). Individual genotyped panels had different kinetics and courses of viremia. The mean doubling time in the early PWP at the onset of viremia was derived to be 10.8 (range, 5.8‐21.0) hours.

CONCLUSION : A majority of HCV RNA‐positive samples were also cAg‐positive during the PWP. The current cAg detection corresponds to 100,000 IU per mL of HCV RNA. Since low‐titer samples would be identified only by single‐donation NAT, which is often affordable only in developed countries, the cAg ELISA could offer a practical alternative for some countries. The doubling time for HCV RNA at the onset of viremia corresponds to a calculated mean delay of cAg detection during the virus burst phase of 2 or 5 days, when compared with minipool (5000 IU/mL) or single‐donation NAT (50 IU/mL), respectively.
Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma
Authors: Stenland Christopher J. , Lee Douglas C. , Brown Paul , Petteway Stephen R. , Rubenstein Richard
Published: March 2003

BACKGROUND: Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster‐adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrPvCJD), human sporadic CJD (PrPsCJD) and Gerstmann‐Sträussler‐Scheinker (PrPGSS) syndrome was compared to the partitioning of hamster scrapie (PrPSc) in three plasma protein purification steps. Sheep scrapie (PrPSc) was similarly evaluated.

STUDY DESIGN AND METHODS: The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrPvCJD, human PrPsCJD, human PrPGSS, sheep PrPSc, and hamster 263K PrPSc. The partitioning of the pathogenic form of the PrP was analyzed.

RESULTS: Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrPSc. A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (≥3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents.

CONCLUSIONS: These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.
A puzzling case of anemia
Authors: Haddad Salim A. , Winer Karen K. , Gupta Anurag , Chakrabarti Sakti , Noel Pierre , Klein Harvey G.
Published: March 2003

BACKGROUND : Iron deficiency anemia in adults is most frequently due to chronic blood loss. When the clinical course is complicated by sudden, severe declines in Hb concentration, the cause, nature, and lo‐ cation of bleeding may require an extensive clinical evaluation.

CASE REPORT : A 39‐year‐old woman was admitted for management of refractory hypoparathyroidism related to total thyroidectomy for Graves' disease. Two weeks before admission, her Hb level was 7.0 g per dL. Despite transfusion with four units of RBCs during this interval, her admission Hb level was 5.7 g per dL. There was no evidence of blood loss or hemolysis. Laboratory values were consistent with an iron‐deficient state. The patient's hospital course included repeated instances of sharp Hb drop and appropriate but unsustained response to RBC transfusion. Extensive work‐up identified no occult source of bleeding. Clinical suspicion raised the possibility of self‐inflicted blood loss. The patient subsequently admitted to repeatedly drawing blood from her indwelling catheter and discarding it in the lavatory.

CONCLUSION : Munchausen syndrome should be considered in cases of unexplained anemia, especially in the target demographic group: young, female, healthcare professionals. Early diagnosis may prevent morbidity, multiple hospitalizations, and the risk of invasive diagnostic procedures.
Long‐term production of pre‐existing alloantibodies to E and c after allogenic BMT in a patient with aplastic anemia resulting in delayed hemolytic anemia
Authors: Izumi Noriko , Fuse Ichiro , Furukawa Tatsuo , Uesugi Yumiko , Tsuchiyama Junjiro , Toba Ken , Togashi Kazue , Yamada Keiko , Ohtake Sachiko , Saitoh Yukiko , Yanagisawa Naoe , Aizawa Yoshifusa
Published: March 2003

BACKGROUND : Delayed hemolysis mediated by long‐term production of pre‐existing recipient‐derived antibodies directed against donor RBC antigens after allogenic BMT is an unusual complication of hematopoietic transplantation.

CASE REPORT : A 26‐year‐old man with aplastic anemia had pre‐existing alloantibodies to E and c. He received BMT from a donor, whose Rh phenotype was E+, c+. From about 1 month after the transplant, he showed mild hemolysis due to the antibodies.

RESULTS : The patient was typed as group B, CCDee and had anti‐E and c alloantibodies before BMT. The donor was typed as group O, ccDEE. Although MNCs from the donor marrow were infused into the patient, DAT became positive on Day 21, and the patient‐origin antibodies remained detectable by both DAT and IAT even 20 months after BMT. However, immunomagnetically isolated peripheral circulating B cells were 100 percent donor origin. The patient received prednisolone from Day 221, and thereafter, the signs of hemolysis disappeared.

CONCLUSION : It is likely that the long‐term production of alloantibodies is due to the existence of long‐lived recipient plasma cells, which survive the conditioning regimen. This case suggests that patients with pre‐ existing alloantibodies that do not belong to the ABO system should be carefully followed up after BMT.
Transvenous Defibrillation Leads: High Incidence of Failure During Long‐Term Follow‐Up
Authors: DORWARTH UWE , FREY BERNHARD , DUGAS MARTIN , MATIS TOMAS , FIEK MICHAEL , SCHMOECKEL MICHAEL , REMP THOMAS , DURCHLAUB ILKA , GERTH ANDREA , STEINBECK GERHARD , HOFFMANN ELLEN
Published: March 2003

Implantable Defibrillator Lead Failure. Introduction: Patients with implantable cardioverter defibrillators (ICD) critically depend on correct functioning of their system. The aim of this study was to determine the incidence and clinical presentation of transvenous ICD lead failures during long‐term follow‐up.

Methods and Results: The study group consisted of 261 consecutive patients who received Medtronic right ventricular polyurethane transvenous leads (models 6884, 6966, 6936) between 1990 and 1998 as part of an abdominal

(n = 70)

or pectoral

(n = 191)

ICD system. During mean follow‐up of

4.0 ± 2.6 years

, 31 patients (12%) developed a lead‐related sensing failure with oversensing of artifacts. All failures except two were compatible with an insulation defect and occurred late after ICD placement (

6.0 ± 1.8 years

after implant). Lead survival decreased from 98% at 4‐year follow‐up to only 62% at 8‐year follow‐up. Lead survival was not related to patient age, sex, venous lead implantation route, or device implantation site. In 26 (87%) of 31 patients, a sensing defect resulted in inappropriate detection of ventricular fibrillation and subsequent delivery of

3 ± 3

(range 1–11) inappropriate shocks in 19 (61%) of 31 patients. Device interrogation showed artifacts classified as nonsustained ventricular tachycardia in 21 patients,

40 ± 43 days

before clinically relevant failure of the system. One patient with a subclavian crush syndrome required resuscitation because of undersensing of true ventricular fibrillation.

Conclusion: Transvenous polyurethane ICD leads showed a high rate of lead insulation failure late after implantation with frequent inappropriate shock deliveries. Close follow‐up is mandatory in patients with these leads. Automated device control features with patient alert function integrated into new devices may contribute to early detection of lead failure.
Effect of Coronary Sinus Electrode on the Optimal Atrial Defibrillation Pathway for an Atrioventricular Defibrillator
Authors: TSE HUNG‐FAT , TIMMERMANS CARL , RODRIGUEZ LUZ‐MARIA , LAU CHU‐PAK , WELLENS HEIN J.J.
Published: March 2003

Atrial Defibrillation Pathway. Introduction: Previous studies have demonstrated significant failure in converting atrial fibrillation (AF) using a conventional ventricular pathway. The aim of this study was to assess the benefit of incorporating a coronary sinus (CS) lead into the atrial defibrillation pathway in atrial defibrillation threshold (ADFT) reduction in patients with persistent AF.

Methods and Results: This study was a prospective, randomized assessment of shock configuration on ADFT in 18 patients undergoing elective internal cardioversion for persistent AF (mean AF duration:

8 ± 9

months). The lead system included a dual‐coil defibrillation lead (Endotak DSP, Guidant) with a distal right ventricular (RV) electrode and a proximal superior vena cava (SVC) electrode, a CS lead (Perimeter, Guidant), and a left pectoral cutaneous electrode (Can). In each patient, dual step‐up ADFTs were determined for each of three vectors: (1) RV → SVC+Can; (2) CS → SVC+Can; and (3) RV → CS+SVC+Can (group 1, n = 8) or RV+CS → SVC+Can (group 2, n = 10), using R wave‐synchronized biphasic shocks. Successful defibrillation was achieved in all patients without any ventricular proarrhythmia. ADFT of CS → SVC+Can

(11.8 ± 5.6 J)

was significantly lower than ADFT of RV → SVC+Can

(16.5 ± 7.8 J, P = 0.021)
. ADFT of CS → SVC+Can was similar to RV → CS+SVC+Can (group 1:12.0 ± 6.5J vs17.4 ± 4.8 J, P = 0.16), but it was significantly higher than RV+CS → SVC+Can (group2: 9.0 ± 3.9J vs11.6 ± 5.0 J, P = 0.049).

Conclusion: Patients with persistent AF of substantial duration can be reliably cardioverted using a conventional implantable cardioverter defibrillator (ICD) lead set; however, the incorporation of a CS lead to the conventional ICD lead configuration significantly lowered ADFT. The optimal shock vector that incorporates a CS lead for atrial defibrillation requires future studies.
Patent Foramen Ovale with Paradoxical Embolism: Mid‐Term Results of Transcatheter Closure in 256 Patients
Authors: ONORATO *EUSTAQUIO , MELZI *GLORIA , CASILLI *FRANCESCO , PEDON † LUIGI , RIGATELLI † GIANLUCA , CARROZZA † ANTONIO , MAIOLINO † PIETRO , ZANCHETTA † MARIO , MORANDI ‡ EVA , ANGELI ‡ SILVIA , ANZOLA ‡ GIAN PAOLO
Published: March 2003

The purpose of this study was to assess the safety and feasibility of percutaneous interventional closure of patent foramen ovale (PFO) with or without atrial septal aneurysm (ASA) in symptomatic patients. Between June 1999 and June 2002, we performed transcatheter closure of PFO in 256 consecutive symptomatic patients (

female/male = 1.45

; mean age

48 ± 16

years; range 14–75): ischemic stroke

(n = 101)

, transient ischemic attack

(n = 144)

, peripheral and coronary arterial embolism

(n = 17)

; multiple events

(n = 23)

; platypnea‐orthodeoxia syndrome

(n = 2)

; refractory hypoxemia

(n = 1)

; and migraine aura

(n = 27)

. The implanted devices were an Amplatzer PFO Occluder

(n = 248)

, a Gore‐HELEX Septal Occluder

(n = 4)

, and PFO STAR

(n = 4)

. Most procedures

(n = 176, 69%)

were done under two‐dimensional intracardiac echocardiography (ICE) guidance alone; in the last 30 patients, 3D/4D ICE reconstruction (TomTec Imaging Systems) 6mbH was obtained. In 30 cases, ICE and contrast enhanced‐TCD have been used simultaneously in the catheterization laboratory. The devices were placed correctly in all patients. Mean fluoroscopy time was

9.45 ± 5  minutes  (range = 2.5–35  minutes)

; mean procedural time was

57 ± 21  minutes  (range = 15–135  minutes)

. Total occlusion rate at follow‐up (mean 19 months, range 1–33) was 98.1%. No significant recurrent neurological events were observed. Transcatheter closure of PFO with or without ASA is a safe and effective, minimally invasive procedure that ensures high closure rate and avoids life‐long anticoagulation. Mid‐term follow‐up results appear favorable with respect to recurrent thromboembolic events. (J Interven Cardiol 2003;16:43–50)
E‐commerce policies and customer privacy
Authors: Desai Mayur S. , Richards Thomas C. , Desai Kiran J.
Published: March 2003

The rapid growth of the Internet and the number of online consumers have resulted in increased fears from privacy advocates, legislators and consumer groups regarding the guarantees of privacy when using e‐commerce and the Internet. Some companies collect marketing information on consumers’ Internet habits without their knowledge or consent. This study looks at stated policies appearing on the Web sites of a number of major e‐commerce companies regarding Internet privacy. This was accomplished by the examination of information related to current Internet policies posted on these firms’ Web sites. Also examined was whether these policies have been changed over a three‐year time period. Five policy categories were examined over this three‐year period using a consistent rating scale. These categories were privacy, returns, shipping, warranty, and security.
Customer relationship management (CRM) in business‐to‐business (B2B) e‐commerce
Authors: Zeng Yun E. , Wen H. Joseph , Yen David C.
Published: March 2003

Customer relationship management (CRM) and business‐to‐business (B2B) are essential to the success of modern business. Although they are two different modules, they share many similarities. The integration of CRM and B2B will benefit all related parties in business processes, including sales, marketing, customer service, and information support. This article discusses the characteristics, similarities, and differences of B2B and CRM. It also explores the CRM‐B2B integration strategies, the current issues and their future development trends.
Hayden White (and the Content and the Form and Everyone Else) at the AHA
Authors: Partner Nancy
Published: March 2003

The special session at the January 1997 annual meeting of the American Historical Association honoring the achievement of Hayden White and examining the impact and influence of his work on the historical discipline was an enlightening experience, at least to this participant, in many more ways than had been planned or promised. The session itself, albeit fairly routine by the standard of such occasions, seemed to take on a meta‐narrative of its own as each of the speakers (not excluding the honoree who was present and participating) confidently spoke at length, proceeding from deep premises which bore no relation to any of the others. My own initial anticipation that this event would produce limited variations on a coherent theme—the impact of the linguistic turn and of narrative theory in particular on the practice and self‐definition of academic history—turned gradually to rather disconcerted bemusement, especially when my turn came to listen to myself.

My previous engagement to report on the AHA session in a paper for the Center for the Humanities at Wesleyan University became an opportunity to confide some of my freshest reactions to the event in a fairly small and very select audience. Narrating the ephemeral metanarrative I perceived as spinning itself out over the blunter facts of the AHA occasion, turned out to be the inner topic of my Wesleyan paper (this present essay), not excluding the mysterious impulses of the audience and the existential atmosphere of the never to be forgotten Princess Ballroom.
The Role of Logic and Aesthetics in Constructing Narrative Wholes in Historiography
Authors: Topolski Jerzy
Published: March 2003

The construction of narrative wholes in historiography involves more than logic, but aesthetics as well. It is imagination as well as logic which generates the more or less concretized images constituting the background onto which the historian, “playing” with basic information, imposes some content and portrays some event by means of a narrative. These concretized images incorporate an aesthetic sense of order. Historical narratives also employ general terms which “bind together” the various elements of basic information which, when linked together, form a historical narrative; these general concepts also invoke an aesthetic sense in virtue of which their identity is formed. In both these ways the aesthetic dimension is crucial in the formation of historical wholes.
Capital Punishment for Murderous Theorists?
Authors: Gordon Daniel
Published: March 2003

Book reviewed in this article:

The Killing of History: How Literary Critics and Social Theorists areMurdering our Past, by Keith Windschuttle
Making History, Talking about History
Authors: Barrera José Carlos Bermejo
Published: March 2003

Making history—in the sense of writing it—is often set against talking about it, with most historians considering writing history to be better than talking about it. My aim in this article is to analyze the topic of making history versus talking about history in order to understand most historians' evident decision to ignore talking about history. Ultimately my goal is to determine whether it is possible to talk about history with any sense.

To this end, I will establish a typology of the different forms of talking practiced by historians, using a chronological approach, from the Greek andRoman emphasis on the visual witness to present‐day narrativism and textual analysis. Having recognized the peculiar textual character of the historiographical work, I will then discuss whether one can speak of a method for analyzing historiographical works. After considering two possible approaches—the philosophy of science and literary criticism—I offer my own proposal. This involves breaking the dichotomy between making and talking about history, adopting a fuzzy method that overcomes the isolation of self‐named scientific communities, and that destroys the barriers among disciplines that work with the same texts but often from mutually excluding perspectives. Talking about history is only possible if one knows about history and about its sources and methods, but also about the foundations of the other social sciences and about the continuing importance of traditional philosophical problems of Western thought in the fields of history and the human sciences.