bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized trial of solvent/detergent‐treated and standard fresh‐frozen plasma in the coagulopathy of liver disease and liver transplantation
Authors: Williamson L.M. , Llewelyn C.A. , Fisher N.C. , Allain J.P. , Bellamy M.C. , Baglin T.P. , Freeman J. , Klinck J.R. , Ala F.A. , Smith N. , Neuberger J. , Wreghitt T.G.
Published: March 2003

BACKGROUND: Virus inactivation of pooled fresh‐frozen plasma (FFP) by the solvent/detergent (SD) method results in a loss of approximately 20 percent of factor VIII. This study aimed to assess the efficacy of SD‐treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation.

STUDY DESIGN AND METHODS: Forty‐nine patients with coagulation deficits due to liver disease, who required FFP for invasive procedures or liver transplantation, were randomly assigned to receive either FFP or SD‐treated plasma. Patients were assessed for side effects, correction of coagulopathy over 24 hours, and seroconversion for viral markers 6 to 18 months after treatment.

RESULTS: In the liver disease group, equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD‐treated plasma, with a similar return to baseline values over 24 hours. There was greater correction of the International Normalised Ratio in patients receiving SD‐treated plasma (p = 0.037), but this patient group had higher baseline values than recipients of FFP (p = 0.024). Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD‐treated plasma. The use of other blood components during transplantation was identical in the two treatment groups. No seroconversions were seen for HIV or hepatitis B or C virus. One patient who had received FFP seroconverted for human parvovirus B19. Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies, as later testing of these patients gave negative results. Minor side effects were rare in both groups.

CONCLUSION: SD‐treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation. Assessment of seroconversion for viral markers in recipients of plasma‐derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected.
Simultaneous genotyping of human platelet antigens (HPA) 1 through 6 using new sequence‐specific primers for HPA‐5
Authors: Meyer O. , Hildebrandt M. , Schulz B. , Blasczyk R. , Salama A.
Published: March 2003

BACKGROUND: Polymerase chain reaction using sequence‐specific primers is widely used for genotyping human platelet antigens (HPA). However, the results of HPA‐5 genotyping are still problematic.

STUDY DESIGN AND METHODS: New sequence‐specific primers were designed for HPA‐5 that, together with already published primers, allow simultaneous genotyping of HPA‐1, ‐2, ‐3, ‐4, ‐5, and ‐6. The reliability of the described protocol was determined by using reference DNA samples as well as samples from healthy blood donors.

RESULTS: All primers produced specific amplification products. The genotype and the previously ascertained phenotype of the tested specimens were in concordance in all cases.

CONCLUSION: The described polymerase chain reaction protocol allows rapid, reliable, simultaneous genotyping of HPA‐1, ‐2, ‐3, ‐4, ‐5, and ‐6.
Frequency of immediate adverse effects associated with therapeutic apheresis
Authors: McLeod Bruce C. , Sniecinski Irena , Ciavarella David , Owen Helen , Price Thomas H. , Randels M. Joleen , Smith James W.
Published: March 2003

BACKGROUND: Therapeutic apheresis was found to be reasonably safe in prior studies using instruments that are now largely obsolete. The incidence of adverse effects with current instruments and techniques has not been assessed in a large multicenter study.

STUDY DESIGN AND METHODS: A survey was conducted in 1995 using a uniform questionnaire that asked about 32 specific events but excluded transient paresthesia and mild vasovagal events. Eighteen centers returned 3429 responses concerning 125 to 500 therapeutic apheresis procedures per center.

RESULTS: Two hundred forty‐two adverse events were reported in 163 procedures (4.75% of all procedures; 6.87% of first‐time procedures and 4.28% of repeat procedures). The numbers (incidence) of selected specific events were transfusion reaction, 56 (51 in plasma exchange [PE] with plasma replacement) (1.6%); citrate‐related nausea and/or vomiting, 41 (1.2%); systolic blood pressure <80 mmHg, 34 (1.0%); vasovagal nausea and/or vomiting, 17 (0.5%); pallor and/or diaphoresis, 16 (0.5%); pulse >120, 14 (0.4%); respiratory distress, 9 (0.3%); tetany or seizure, 9 (0.2%); and chills or rigors, 6 (0.2%). Rates for other specific events were <0.1 percent. Vasovagal phenomena were more frequent in procedures done in neurologic patients than in those done in hematology or oncology patients (p = 0.011) or renal or rheumatic patients (p = 0.038). Procedure‐specific rates were red cell exchange, 8 (10.26%) of 78; PE (plasma), 89 (7.81%) of 1140; PE (no plasma), 42 (3.35%) of 1255; leukapheresis, 4 (5.71%) of 70; plateletpheresis, 0 of 18; and autologous peripheral blood progenitor cell collection, 11 (1.66%) of 664. Three deaths were reported; all were attributed to primary disease.

CONCLUSION: Therapeutic apheresis procedures are relatively safe, with a 4.75‐percent overall incidence of mostly reversible adverse effects. Among the most commonly performed procedures, the risk is higher for blood component exchanges, especially if allogeneic red cell or plasma transfusion occurs, and lower for peripheral blood progenitor cell collection.
IgG titer, subclass, and light‐chain phenotype of pregnancy‐induced HPA‐5b antibodies that cause or do not cause neonatal alloimmune thrombocytopenia
Authors: Kurz Martin C. , Stöckelle Eugen , Eichelberger Beate , Panzer Simon
Published: March 2003

BACKGROUND: The most common pregnancy‐induced platelet‐specific antibody is HPA‐5b. Neonatal alloimmune thrombocytopenia that results from anti‐HPA‐5b may cause severe hemorrhage in only a few infants, but the sequelae for the affected children can be severe. It is therefore essential that infants at risk for neonatal alloimmune thrombocytopenia are identified.

STUDY DESIGN AND METHODS: The IgG titer, subclass, and light‐chain composition of pregnancy‐induced anti‐HPA‐5b were determined by the monoclonal antibody‐specific immobilization of platelet antigens assay. Sera were from 12 mothers, who among them had 16 pregnancies that resulted in an HPA‐5‐mismatched fetus (positive for HPA‐5b). Eight mothers gave birth to an infant with a normal platelet count. Three maternal sera were obtained after delivery of a severely thrombocytopenic infant. Three alloimmunized women were followed repeatedly during the course of a subsequent pregnancy, again with an HPA‐5‐mismatched infant.

RESULTS: There was no difference in the antibody titer or its subclass in mothers who had a thrombocytopenic child and the titer or subclass in mothers compared with those who had a child with a normal platelet count. All pregnancy‐induced HPA‐5b antibodies were of a predominant, lambda, light‐chain type. The IgG subclass did not change during pregnancy.

CONCLUSION: Neither the antibody titer nor the subclass composition predict the occurrence of thrombocytopenia in a newborn whose mother is alloimmunized against HPA‐5b.
Reactions and platelet increments after transfusion of platelet concentrates in plasma or an additive solution: a prospective, randomized study
Authors: De Wildt‐Eggen J. , Nauta S. , Schrijver J.G. , Van Marwijk Kooy M. , Bins M. , Van Prooijen H.C.
Published: March 2003

BACKGROUND: Reactions after platelet transfusions are rather common and frequently are caused by plasma constituents. In recent developments, the preparation and storage of platelet concentrates (PCs) in a platelet additive solution (PAS‐2) have been shown to result in acceptable storage conditions. A major drawback of the use of these PCs is the progressive increase of P‐selectin‐positive platelets during storage. The clinical benefit of transfusions of PCs in PAS‐2 was studied.

STUDY DESIGN AND METHODS: PCs prepared from buffy coats were suspended in either plasma or PAS‐2 and stored for up to 5 days. Clinical responses were evaluated in a prospective study in 21 patients treated with intensive chemotherapy for hematologic malignancies. Eligible patients were randomly assigned to receive prophylactic transfusions of PCs prepared in either plasma or PAS‐2. Reactions and CCIs were recorded after each transfusion.

RESULTS: The incidence of reactions in 12 patients given PCs in plasma (n = 192) was 12 percent. Transfusions to 9 patients of PCs in PAS‐2 (n = 132) showed a reduction in the incidence of reactions to 5.3 percent (p<0.05). The average 1‐hour and 20‐hour CCIs after transfusion of PCs in plasma were 20.7 ± 8.5 and 11.5 ± 8.0, respectively. CCIs after transfusion of PCs in PAS‐2 were significantly lower: the average 1‐hour CCI was 17.1 ± 6.6 (p<0.001) and the average 20‐hour CCI was 9.5 ± 7.0 (p<0.05). Storage conditions of PCs were optimal: in each group, average 1‐hour CCIs of both fresh and stored PCs were similar. The 20‐hour CCIs after the transfusion of fresh and stored PCs in PAS‐2 also were similar.

CONCLUSION: Transfusion of PCs in PAS‐2 significantly reduces the incidence of reactions. The 1‐hour and 20‐hour CCIs after transfusion of PCs in PAS‐2 were significantly lower than the CCIs after transfusion of PCs in plasma. Because storage conditions of both PCs were found to be optimal, the decrease in CCIs after transfusion of PCs prepared in PAS‐2 may be caused by rapid elimination of a subpopulation of P‐selectin‐positive platelets from the circulation.
Analysis of the Turin Umbilical Cord Blood Bank Registry
Authors: Rendine S. , Curtoni E.S. , Di Celle P. Francia , Berrino M. , Bertola L. , Barbanti M. , Saracco P. , Fazio L. , Gay E. , Dall'Omo A.M.
Published: March 2003

BACKGROUND: The polymorphic nature of the HLA system reduces a patient's probability of finding an HLA‐compatible unrelated bone marrow (BM) donor, even though more than 6 million individuals are enrolled in international registries. Recently, umbilical cord blood (UCB) has been successfully employed as a source of HPCs. The use of such cells reduces the risk of GVHD and allows transplants with one or two HLA mismatches. UCB represents an expensive resource: therefore, it is necessary to carefully manage the UCB unit inventory.

STUDY DESIGN AND METHODS: The current study analyzed the genetic heterogeneity of HLA‐A, ‐B, and ‐DR gene frequencies between pools of UCB and unrelated‐donor BM in the Piedmont (an administrative region of Italy). An Italian hematology patient's probability of finding complete or partial matches as a function of donor pool size was determined by considering subsamples randomly selected from the local unrelated BM donors.

RESULTS: The HLA gene frequencies in UCB and unrelated‐donor BM pools were not significantly different. The search simulation, based on actual HLA phenotypes, showed that the percentage of Italian patients matched with an HPC unit increases remarkably if 1 or 2 mismatches are accepted, reaching a proportion of 90 percent with an inventory of only about 500 units, while the increment is not so remarkable if the number of UCB units is greater.

CONCLUSION: To optimize economic resources and to be internationally competitive, UCB banks should aim to increase the genetic heterogeneity of their units rather than increasing the UCB inventory, acquire efficient quality control systems, and acquire and preserve UCB units with a greater number of nucleated cells.
In vitro studies of the impact of transfusion on the detection of alloantibodies after autoadsorption
Authors: Laine Edward P. , Leger Regina M. , Arndt Patricia A. , Calhoun Loni , Garratty George , Petz Lawrence D.
Published: March 2003

BACKGROUND: In a patient with warm autoantibodies who has recently received a transfusion, it is not recommended to perform adsorptions using autologous RBCs to detect alloantibodies. Although not scientifically documented, this position is based on the theory that transfused RBCs in the patient′s circulation would be capable of adsorbing alloantibodies that may be present. This in vitro study was designed to determine what percentage of transfused RBCs might completely remove alloantibodies in vivo.

STUDY DESIGN AND METHODS: Selected D, E, K, Fya, and Jka antibodies were adsorbed with mixtures of antigen‐positive and antigen‐negative RBCs to determine the lowest concentration of antigen‐positive RBCs capable of removing all alloantibody reactivity. The percentage of antigen‐positive RBCs in each mixture was determined by flow cytometry.

RESULTS: Small amounts of antigen‐positive RBCs (2‐6%, as determined by flow cytometry) completely removed anti‐D, ‐E, and ‐Fya reactivity. Reactivity of two examples of anti‐K was removed by 11 percent and 17 percent of K+ RBCs, respectively. Anti‐Jka reactivity was completely removed by 4 to 5 percent Jk(a+) RBCs using a PEG adsorption; the endpoint (>11%) was estimated, but complete adsorption with ZZAP‐treated RBCs was not performed.

CONCLUSION: Small amounts of antigen‐positive RBCs are generally capable of removing all alloantibody reactivity. Thus, waiting for 3 months after transfusion before performing autologous adsorptions is a prudent policy.
Detection of microchimerism by PCR is a function of amplification strategy
Authors: Reed William F. , Lee Tzong‐Hae , Trachtenberg Elizabeth , Vinson Margaret , Busch Michael P.
Published: March 2003

BACKGROUND: Suitable detection methods are needed to support larger studies of microchimerism and the allogeneic exposures that may be etiologically related to it.

STUDY DESIGN AND METHODS: A twotier PCR strategy for microchimerism detection was developed on the basis of the observation that assay sensitivity for the detection of microchimerism depends on the specificity with which primer pairs recognize sequences unique to the minor population. First, specimens are tested to determine the host HLA class II genotype by using a locus‐specific PCR strategy with low sensitivity for microchimerism. Then, a sequence‐specific PCR analysis having high sensitivity for detection of microchimerism is applied to detect and quantitate the minor population. Locus‐specific, group‐specific, and sequence‐specific amplification strategies for the detection of distinct minor WBC populations prepared ex vivo were compared. In addition, 39 clinical samples from patients with known transfusion‐associated microchimerism and 20 umbilical cord blood (CB) specimens containing maternal WBCs were studied.

RESULTS: Locus‐specific amplification detected 17 (94%) of 18 cases in which microchimerism was present at 10 percent, but only 1 of 51 cases with microchimerism ≤1 percent. Group‐specific amplification detected all 63 cases with minor populations present at ≥0.10 percent, but only 16 of 21 cases at the 0.01 percent level. Sequence‐specific amplification detected 100 percent of cases down to the 0.01 percent level. When applied to clinical samples, locus‐specific amplification reliably identified the major population but proved insensitive to low‐level minor populations.

CONCLUSIONS: For the detection of microchimerism, assay sensitivity is a function of amplification strategy. These results suggest a simple approach to population screening for microchimerism: the background population of WBCs is typed by a locus‐specific method, while minor population(s) can then be sought by using one or several sequence‐specific amplifications.
A new flow cytometric method for simultaneous measurement of residual platelets and RBCs in plasma: validation and application for QC
Authors: Jilma‐Stohlawetz Petra , Marsik Claudia , Horvath Michaela , Siegmeth Heinz , Höcker Paul , Jilma Bernd
Published: March 2003

BACKGROUND: Guidelines for the preparation of FFP in Austria and Germany require the quantification of residual RBCs in plasma. However, currently there is no validated method for enumeration of RBC counts as low as 1 × 109 per L.

STUDY DESIGN AND METHODS: A new flow cytometric method was developed for QC, to simultaneously determine if fresh unfrozen plasma contains residual platelets and RBCs. This method uses test tubes (TruCount, Becton Dickinson Immunocytometry Systems) that contain a known number of brightly fluorescent polystyrene beads. Plasma is pipetted into these tubes and mixed with FITC‐labeled anti‐CD41 and PE‐conjugated anti‐glycophorin A MoAbs. Acquisition can be performed on a flow cytometer after an incubation period of 15 minutes.

RESULTS: Individual standard curves for platelet counts revealed excellent correlation coefficients (r>0.998). Platelet counts were validated against simultaneous measurements by using a cell counter and a hemocytometer. While the flow cytometric method slightly overestimated platelet counts of >40 × 109 per L by 10 percent, its precision in the critical range was very good—that is, a deviation of platelets ≤1 × 109 per L from target values, which was even better than microscopic enumeration. The limit of sensitivity was <0.5 × 109 per L of platelets. RBC counts were also validated against simultaneous measurements made with a second cell counter. Standard curves for RBC counts also revealed excellent correlation coefficients (r>0.997). The limit of sensitivity was <0.25 × 109 RBCs per L. Platelet counts in plasma obtained by plateletpheresis or plasmapheresis ranged from 3 to 60 × 109 per L. About 25 percent of all plasma samples had platelet counts greater than the allowed upper limit of 25 × 109 per L, while all plasma samples contained fewer RBCs than the upper limit of 6 × 109 per L.

CONCLUSION: This newly developed method provides a simple, quick, precise, and easily reproducible tool for simultaneous measurement of residual platelets and RBCs in fresh plasma.
Flow cytometric determination of RBC survival in autoimmune hemolytic anemia
Authors: Zeiler Thomas , Müller Jan Tobias , Hasse Christian , Kullmer Johannes , Kretschmer Volker
Published: March 2003

BACKGROUND: In cases of warm autoimmune hemolytic anemia (WAIHA), crossmatch incompatible RBCs are most often used for transfusion. The determination of the in vivo survival of transfused and autologous RBCs in WAIHA is helpful in the assessment of the efficacy of transfusion and other therapeutic interventions.

CASE REPORT: A 38‐year‐old man presented with acute WAIHA, thrombocytopenia, and neutropenia. Steroids and IVIG therapy were ineffective, and the patient received RBCs. Because of increasing hemolysis and persisting thrombocytopenia, splenectomy was performed, resulting in partial remission. Further improvement was achieved by immunosuppressive therapy.

MATERIALS AND METHODS AND RESULTS: Survival of transfused and autologous RBCs was determined, using a flow cytometric method based on the determination of different blood group antigens of patient and donor RBCs. The survival of autologous and transfused RBCs before splenectomy was determined on two consecutive days. The life span of autologous RBCs remained rather stable at 69 and 64 hours on Days 10 and 11, respectively, whereas the life span of transfused RBCs decreased from 186 hours to 25 hours. After splenectomy, the life span of transfused RBCs almost normalized: 43 days at postsplenectomy Day 3 and 87 days at postsplenectomy Day 69.

CONCLUSION: Flow cytometry was successfully used to determine changing hemolytic activity during the clinical course of WAIHA. Additionally, the survival of transfused RBCs could be measured, which may be helpful to judge for the compatibility of allogeneic RBCs. Thus, we were able to show the therapeutic inefficacy of steroids and immunoglobulins, and quick improvement after splenectomy.
Performance characteristics of the COBAS AmpliScreen HIV‐1 test, version 1.5, an assay designed for screening plasma mini‐pools
Authors: Yang Yanfeng , Lamendola Misty‐Hope , Mendoza Miguel , Xu Dick , Nguyen Minh , Yeh Sheria , Wu Yiqiao , Ku Joanne , Rosenstraus Maurice , Sun Rita
Published: March 2003

BACKGROUND: The COBAS AmpliScreen HIV‐1 test, version 1.5 (v1.5) (Roche Molecular Systems), is designed for screening pools composed of samples from 24 individual units of blood or plasma. A specimen‐processing procedure (Multiprep) simultaneously concentrates and extracts HIV‐1, HCV, and HBV particles from plasma and incorporates an HIV‐1 internal control (IC) RNA. Processed samples are amplified by RT‐PCR using HIV‐1‐specific primers and detected by hybridization of the amplified products to HIV‐1‐ and IC‐specific oligonucleotide probes.

STUDY DESIGN AND METHODS: Plasma samples containing known quantities of HIV‐1 were used to evaluate analytical sensitivity and precision and to validate a pool testing algorithm. Analytical specificity was evaluated by adding various viruses and bacteria to HIV‐1‐negative plasma. Seroconversion panels were tested to estimate the window‐period reduction achieved by RNA testing.

RESULTS: The analytical sensitivity of the test (concentration that yields ≥95% positive results in a set of replicate tests) was 25 copies of HIV‐1 RNA per mL of pooled plasma. Representative strains from all HIV‐1 group M subtypes were reproducibly detected (>95% positive results) at concentrations of 20 to 200 viral particles per mL. The test did not cross‐react with a set of 31 viral and 5 bacterial isolates, and it yielded negative results on a panel of 500 blood samples from HIV‐1‐seronegative donors. Plasma samples containing abnormally high levels of Hb, albumin, triglycerides, or bilirubin did not interfere with the test. HIV‐1 RNA was detected 2 to 14 days before HIV‐1 antibody and 0 to 28 days before p24 antigen. The test specifically detected pools containing a single positive unit with 2400 HIV‐1 RNA copies per mL and correctly identified the positive unit.

CONCLUSION: The COBAS AmpliScreen HIV‐1 test, v1.5, has sufficient sensitivity to detect a single infected unit containing 600 copies of HIV‐1 per mL in a pool with 23 uninfected units and should reduce the window period between infection and seroconversion by at least 2 to 14 days.
Immune reconstitution after autologous selectedperipheral blood progenitor cell transplantation:comparison of two CD34+ cell‐selection systems
Authors: Laurenti Luca , Sorà Federica , Piccirillo Nicola , Chiusolo Patrizia , Cicconi Silvia , Rutella Sergio , Serafini Riccardo , Garzia Maria Grazia , Leone Giuseppe , Sica Simona
Published: March 2003

BACKGROUND: Selection of CD34+ PBPCs has been applied as a method of reducing graft contamination from neoplastic cells. This procedure seems to delay lymphocyte recovery, while myeloid engraftment is no different from that with unselected PBPC transplants.

STUDY DESIGN AND METHODS: Lymphocyte recovery was studied in two groups of patients who underwent autologous CD34+ PBPC transplant with two different technologies (Ceprate SC, Cellpro [n = 17]; CliniMACS, Miltenyi Biotech [n = 13]). The median number of CD34+ cells transfused was 3.88 × 106 per kg and 3.32 × 106 per kg, respectively. Residual CD3 cells × 106 per kg were 4.97 and 0.58, respectively (p = 0.041). Residual CD19 cells × 106 per kg were 1.33 and 0.73, respectively (NS).

RESULTS: No differences were found between the two groups in total lymphocyte recovery to >0.5 × 109 per L, which achieved a stable count by Day 30. During the study period, the CD4+ cell count remained below 0.2 × 109 per L, and the B‐cell subset showed a trend toward normalization. CD3/HLA‐DR+ and CD16/56 increased markedly in both groups by Day 30. An increase in CMV (13%) and adenovirus (17.4%) infection was found in both groups.

CONCLUSION: Both CD34+ cell selection technologies used here determined an excellent CD34+ cell purity and an optimal depletion of T cells. The high rate of viral complications is probably due to the inability of residual T cells left from the CD34+ cell selection to generate, immediately after transplant, an adequate number of virus‐specific lymphocytes.
Absence of D alloimmunization in D– pediatric oncology patients receiving D‐incompatible single‐donor platelets
Authors: Molnar R. , Johnson R. , Sweat L.T. , Geiger T.L.
Published: March 2003

BACKGROUND: Guidelines are lacking for prophylaxis against D alloimmunization after D‐incompatible platelet transfusion. A rational basis for the application of prophylaxis would be beneficial for institutions in which inventory constraints demand the administration of large numbers of D‐incompatible platelets.

STUDY DESIGN AND METHODS: A retrospective analysis was performed of all D‐incompatible platelet transfusions administered at a pediatric research hospital over a 1.5‐year period. Patients exclusively received single‐donor WBC‐reduced platelets and did not receive RhIg immunoprophylaxis. Numbers, source, ABO type, duration of serologic follow‐up, and level of RBC contamination of D‐incompatible transfusions were analyzed. All positive D serologies in the institution over a 3.5‐year period were examined to determine cause and potential association with platelet transfusion.

RESULTS: Thirty‐five patients not receiving bone marrow transplant and seven bone marrow transplant patients received 490 and 255 D‐incompatible transfusions, respectively, over 1.5 years. Patients had various diagnoses, predominantly malignancies. Seventy‐nine percent of D‐incompatible transfusions were ABO compatible. An estimated 2300 incompatible transfusions were performed over 3.5 years. No case of D alloimmunization was detected.

CONCLUSIONS: D immunoprophylaxis is generally unnecessary in pediatric oncology patients receiving D‐incompatible, WBC‐reduced, single‐donor platelets not visibly contaminated by RBCs. Further studies to validate these observations in the pediatric population and to extend them to other population groups are warranted.
The rare Lu:–6 phenotype in Israel and the clinical significance of anti‐Lu6
Authors: Yahalom Vered , Ellis Martin H. , Poole Joyce , Rahimi‐Levene Naomi , Shinar Eilat , DaCosta Yehudit , Manny Noga , Levene Cyril
Published: March 2003

BACKGROUND: Lu6 is a high‐incidence antigen of the Lutheran blood group. Examples of anti‐Lu6 are rare and are of uncertain clinical significance.

CASE REPORT: Three patients were encountered in whom anti‐Lu6 was detected on pretransfusion screening. The patients were all Iranian Jews and were not known to be related. In vitro studies to ascertain the potential clinical significance of the antibody using the monocyte monolayer assay (MMA) were negative in two patients. The third patient received a two‐unit transfusion of incompatible Lu6 RBCs with no signs of hemolysis. However, after the transfusion, the MMA and a chemiluminescence test were positive, whereas a chromium survival study was normal. Thus, the antibody may have changed in its clinical significance.

CONCLUSION: Although anti‐Lu6 does not appear to be a clinically significant RBC antibody in all circumstances, transfusion of Lu6 RBCs in patients with anti‐Lu6 should be performed cautiously.
Preparation of FFP as a by‐product of plateletpheresis
Authors: Zingsem Jürgen , Weisbach Volker , Zimmermann Robert , Glaser Anke , Bunkens Helena , Eckstein Reinhold
Published: March 2003

BACKGROUND: To reduce the production costs of single‐donor platelets (SDPs), a study was conducted to investigate whether plasma collected as a by‐product of plateletpheresis satisfies the quality requirements for FFP without impairing the quality of the SDP component.

STUDY DESIGN AND METHODS: Ninety‐two donors with platelet (PLT) counts <270 × 109 per L underwent plateletpheresis using an automated cell separator (Spectra Apheresis System with the Leukoreduction System [LRS], Gambro BCT, Lakewood, CO). The machine was programmed to collect 3 × 1011 PLTs in 250 mL of plasma with an additional unit of 350 mL of plasma or 3 × 1011 PLTs in 250 mL of plasma without additional plasma in 10 procedures. FV and FVIII and residual RBCs, WBCs, and PLTs in the plasma were measured for quality control.

RESULTS: FV was 0.87 ± 0.18 IU per mL, and FVIII was 1.32 ± 0.48 IU per mL in the plasma components (n = 41). The recovery was 94.1 ± 5.5 percent for FV and 102.2 ± 9.5 percent for FVIII when compared with the donors' predonation values. Residual cells were 0.002 ± 0.009 × 109 RBCs per L (n = 30), 12 ± 6 × 109 PLTs per L (n = 30), and 0.32 ± 0.37 × 106 WBCs per L (n = 92).

CONCLUSIONS: Using the automated cell separator and special software, it is possible to collect plasma as a by‐product of plateletpheresis that meets the properties requested for FFP without impairing the quality of the SDP components. The content of clotting factors is within the requested range for FFP. Residual cell counts are within all European and U.S. specifications for FFP, and the WBC content even satisfies the criteria for WBC‐reduced blood components. The collection of FFP as a by‐product does not cause any additional costs and thus helps to reduce the costs in preparing blood components.
Ex vivo expansion of long‐term culture initiating marrow cells by IL‐10, SCF, and IL‐3
Authors: Keil Felix , Elahi Fariborz , Greinix Hildegard T. , Fritsch Gerhard , Louda Norbert , Petzer Andreas ;L. , Prinz Erika , Wagner Thomas , Kalhs Peter , Lechner Klaus , Geissler Klaus
Published: March 2003

BACKGROUND: Ex vivo expansion of progentior cells may shorten hematopoietic regeneration after myeloablative chemoradiotherapy, increase target cells for gene therapy, and improve purging of progenitor cell components.

STUDY DESIGN AND METHODS: Marrow cells were incubated for 1 week in suspension culture with and without IL‐10, IL‐3, and SCF. As long‐term culture initiating cells (LTC‐ICs) represent early hematopoietic progenitors in vitro, these cells were quantified at initiation and after a 1‐week culture period in a limiting dilution assays. Additionally, immunophenotyping of cells before and after culture was performed.

RESULTS: In six experiments, marrow cells cultured for 1 week with IL‐10, IL‐3, and SCF showed a significant increase (almost doubling) in LTC‐ICs as compared with marrow cells before expansion. Additionally, an increased proliferative capacity of LTC‐ICs was achieved with a sevenfold increase of committed colony‐forming cells and a 10‐fold proliferation of high proliferative potential colony‐forming cells. Immunophenotyping revealed a sevenfold increase of CD34+ CD45 RA– cells in IL‐10‐, IL‐3‐, SCF‐stimulated suspension cultures. In unstimulated cultures, no LTC‐ICs were maintained after 1 week.

CONCLUSION: Expansion of LTC‐ICs by IL‐10, IL‐3, and SCF has not been shown so far. This in vitro model allows expansion of LTC‐IC if compared with the input of progenitor cells without extensive progenitor cell manipulation. This should be an attractive model for in vitro purging, gene transfer, or expansion of progenitor cells to allow rapid engraftment after myeloablative chemotherapy.
Semiautomated data analysis of flow cytometric estimation of fetomaternal hemorrhage in D− women
Authors: Greiss M.A. , Armstrong‐Fisher S.S. , Perera W.S. , Brown P.M. , Urbaniak S.J.
Published: March 2003

BACKGROUND : Accurate and reliable measurement of the volume of fetal D+ cells in D− women is required for adequate anti‐D prophylaxis. A semiautomated flow cytometry assay based on a standardized calibration curve that was created with simulated fetomaternal hemorrhage (FMH) mixtures was developed.

STUDY DESIGN AND METHODS : A calibration range of 0.083‐ to 2‐percent D+ cells in the D−RBC mixtures (2‐44 mL calculated FMH) was analyzed by use of a flow cytometer (XL‐MCL, Coulter Electronics Ltd). Linear regression analysis of the calibration curve data with computer software (Excel, Microsoft) allowed semiautomated determination of the FMH volume. To optimize the assay, fresh versus frozen and thawed RBCs, RBCs from adults who are heterozygous for D or cord RBCs, and indirect‐ or direct‐labeling techniques were evaluated by use of MoAbs.

RESULTS
: Fresh RBCs from adults heterozygous for D were chosen for routine use, although equivalent calibration curves were obtained with all cells tested (n = 12 calibration assays; r

2
= 0.999; mean SD, 14%). A monoclonal anti‐D reagent (Therad 10, Diagnostics Scotland) worked well in both indirect‐(anti‐IgG F(ab)‐FITC) and direct‐(anti‐D‐FITC) labeling methods compared to the use of BRAD‐3 FITC. In routine practice, the FMH volumes obtained were mainly lower than those obtained in the Kleihauer Betke test when there was less than 4 mL of FMH.

CONCLUSION : Semiautomated data acquisition and calibration curve analysis represents a further step toward standardization of flow cytometry for accurate FMH quantification and facilitates evaluation and control of day‐to‐day variations between laboratories, flow cytometers, and operators.
Residual risk of transfusion‐transmitted HCV and HIV infections by antibody‐screened blood in Italy
Authors: Velati Claudio , Romanò Luisa , Baruffi Lorella , Pappalettera Marco , Carreri Vittorio , Zanetti Alessandro R.
Published: March 2003

BACKGROUND: This study was designed to assess the risk of transmitting HCV and HIV by transfusion of antibody‐screened blood and to estimate the additional reduction in risk that may be achieved through the implementation of direct viral detection assays in Italy.

STUDY DESIGN AND METHODS: Clinical and laboratory data of 2,411,800 blood donations collected from repeat volunteer donors from 1996 through 2000 were analyzed. The risk of transmitting HCV or HIV from screened blood donated during the window period was estimated using a mathematical model.

RESULTS: The residual risk of donating antibody‐ negative infectious blood was estimated at 1 in 127,000 donations for HCV and 1 in 435,000 for HIV. The use of NAT should further reduce such risk by 83 percent for HCV and 50 percent for HIV.

CONCLUSION: The residual risk of HCV or HIV transmission through screened blood is currently very small in Italy. The implementation of direct viral detection assays can further improve the safety of blood supply.
Hypotensive reaction during staphylococcal protein A column therapy in a patient with anomalous degradation of bradykinin and Des‐Arg9‐bradykinin after contact activation
Authors: Molinaro Giuseppe , Adam Albert , Lepage Yves , Hammerschmidt Dale , Koenigbauer Ulrike , Eastlund Ted
Published: March 2003

BACKGROUND: Hypotensive reactions have occurred in patients taking angiotensin converting enzyme (ACE) inhibitors after infusion of blood previously in contact with negatively charged surfaces capable of generating kinins, which accumulate when ACE, a kininase, is inhibited. A patient with anomalous bradykinin (BK) metabolism who experienced hypotension during extracorporeal staphylococcal protein A (SPA) therapy while on an ACE inhibitor was studied.

CASE REPORT: A patient with mitomycin‐associated hemolytic‐uremic syndrome received SPA treatments after her ACE inhibitor, lisinopril, was held. Lisinopril was restarted before her 18th SPA treatment, and immediately after return of treated plasma she developed facial redness and hypotension, which resolved after the return stopped and recurred when restarted. To study formation and degradation of kinins, exposed her plasma to glass beads. We found a normal kinin formation rate but an abnormal degradation and accumulation of Des‐Arg9‐BK. The kinin degradation enzymes ACE, aminopeptidase P (APP), and carboxypeptidase N (CPN) were measured while on an ACE inhibitor, showing absence of ACE activity, low APP, but normal CPN.

CONCLUSION: This patient's vasodilation and hypotension during SPA therapy was associated with a pre‐ existing anomaly of BK metabolism. Her ACE inhibitor shifted degradation toward Des‐Arg9‐BK formation, and her low APP was associated with a prolonged t50 and accumulation of the vasoactive Des‐Arg9‐BK.
Assessing the accuracy of three viral risk models in predicting the outcome of implementing HIV and HCV NAT donor screening in Australia and the implications for future HBV NAT
Authors: Seed Clive R. , Cheng Anthea , Ismay Susan L. , Bolton Wayne V. , Kiely Philip , Cobain Trevor J. , Keller Anthony J. ,   Virology Subcommittee of the National Donor and Product Safety Committee, Australian Red Cross Blood Service
Published: March 2003

BACKGROUND : Risk modeling is now the most practical method of estimating the residual risk of viral transmission in developed countries. One method of assessing the accuracy of a risk model is to measure the observed against the predicted outcome after implementing a new screening method. The primary objective of this paper is to assess the accuracy of three published models in predicting the impact of implementing HIV and HCV NAT in Australia.

STUDY DESIGN AND METHODS : Viral screening data on Australian donors for 2000 and 2001 were retrospectively analyzed. The data were applied to the three models to estimate the risk of transmission and predicted NAT yield for HIV, HCV, and HBV.

RESULTS : The median risk estimates for the three models were 1 in 3,415,000 for HIV NAT, 1 in 911,000 for HCV NAT, and 1 in 483,000 for HBsAg. The predicted NAT yield for the three models ranged from 0.17 to 0.30 per million donations for HIV, 1.20 to 5.55 for HCV, and 0.47 to 1.01 for HBV. The observed NAT yield was not significantly different from the expected yield with any of the three models for either HIV or HCV.

CONCLUSIONS : First, the residual risk in Australian donors is small in comparison with other transfusion complications and comparable to or lower than the risk in US and European nonremunerated donors. Second, mathematical risk modeling has sufficient precision to be used as a predictive tool for risk‐benefit assessments of novel screening procedures. Finally, in relation to the case for implementing HBV NAT and/or anti‐HBc in Australia, we conclude that at present, there is inadequate information about our donor population to perform an evidence‐based risk‐benefit analysis.
Body Surface Laplacian Electrocardiogram of Ventricular Depolarization in Normal Human Subjects
Authors: LI GUANGLIN , LIAN JIE , SALLA PRATHYUSHA , CHENG JIA , RAMACHANDRA INDIRESHA , SHAH PARTHIV , AVITALL BOAZ , HE BIN
Published: March 2003

Body Surface Laplacian Map. Introduction: The body surface Laplacian electrocardiogram (ECG) mapping provides a noninvasive means for spatiotemporal mapping of cardiac electrical events. The aim of the present study was to explore the relationship between the Laplacian ECG and the underlying cardiac activities during ventricular depolarization in healthy human subjects.

Methods and Results: A 95‐channel body surface potential ECG was recorded over the anterolateral chest from 11 healthy male subjects. The surface Laplacian (SL) ECG was estimated from the recorded potentials during QRS complex by means of a novel spline SL estimator, as well as by the conventional 5‐point SL estimator for comparison purpose. A simulation study was also conducted using a realistic geometry heart‐torso model in an attempt to qualitatively interpret the experimental results. For all subjects, more spatial details were observed in the SL ECG maps compared with the potential ECG maps, with spline SL more robust against noise than the 5‐point SL. In total, three positive activities (denoted as P1, P2, P3) and four negative activities (denoted as N1, N2, N3, N4) in the spline SL ECG maps were observed during ventricular depolarization. Initial localized P1 and N1 activities were observed in 11 and 8 subjects, respectively. Then, the initial P1 was divided into three positive activities (P1, P2, P3) in 9 subjects. After the appearance of multiple positive activities, three negative activities (N2, N3, N4) appeared in 11, 8, and 9 subjects, respectively. Similar findings were obtained in the computer simulation study.

Conclusion: The present study demonstrates that the SL ECG provides more spatial details than the potential ECG, and multiple simultaneously active ventricular activities could be revealed in the SL ECG maps. The results suggest that the SL ECG may provide an alternative for noninvasive mapping of cardiac electrical activity.
Postmodernism versus the Standpoint of Action
Authors: Roberts Geoffrey
Published: March 2003

On “What is History”: From Carr and Elton to Rorty and White. By Keith Jenkins
Historical Orientation: Jörn Rüsen’s Answer to Nietzsche and His Followers
Authors: De Jong Henk
Published: March 2003

Historische Orientierung: Über die Arbeit des Gescichtsbewusstseins, sich in der Zeit zurechtzufinden. By Jörn Rüsen.
On the Problem of Laws in Nature and History: A Comparison
Authors: Berry Stephan
Published: March 2003

In the philosophy of science there has traditionally been a tendency to regard physics as the incarnation of science per se. Consequently, the status of other disciplines has been evaluated according to their ability to produce laws resembling those of physics. This view has yielded a considerable bias in the discussion of historical laws. Philosophers as well as historians have tended to discuss such laws mostly with reference to the situation in physics; this often led to either one of two conclusions, namely that (1) history is epistemologically completely separated from natural science because it does not have universal laws, or that (2) the ultimate goal of the study of history must be the formulation of such universal laws. I maintain that neither conclusion is necessary. To substantiate this position, I discuss several aspects of natural laws. One aspect that is often neglected is that there are many kinds of statistical laws in nature; there is no close link between laws and determinism. Moreover, natural systems exist that have a history, that is, systems that are, like human history, shaped by irreversible, singular events. One important case is biological evolution; accordingly I discuss the relation between evolutionary theory and historiography. However, since we are part of the living world, and in addition to considering the methodological similarities between the two fields, one could also ask whether the laws of evolution are of direct relevance for understanding our history. This issue of history as evolution is investigated in detail in the final section of the paper.
Iron City Blues
Authors: Tilly Charles
Published: March 2003

S. N. Eisenstadt, Fundamentalism, Ectarianism, and Revolution: The Jacobin Dimension of Modernity
Barbarism and Religion: Where Is Gibbon the Historian?
Authors: Jordan David P.
Published: March 2003

Book reviewed:

J. G. A. Pocock, Barbarism and Religion
Essentialism and Historicism in Danto's Philosophy of Art
Authors: Kelly Michael
Published: March 2003

Arthur C. Danto has long defended essentialism in the philosophy of art, yet he has been interpreted by many as a historicist. This essentialism/historicism conflict in the interpretation of his work reflects the same conflict both within his thought and, more importantly, within modern art itself. Danto's strategy for resolving this conflict involves, among other things, a Bildungsroman of modern art failing to discover its essence, an essentialist definition of art provided by philosophy which is indemnified against history, and a thesis about the end of art once it has been defined. Is this strategy successful, or does it result, as I argue, in a philosophical disenfranchisement of art of precisely the type that Danto himself has criticized?
Danto on Representation, Identity, and Indiscernibles
Authors: Ankersmit F. R.
Published: March 2003

Arthur Danto has made important contributions to both aesthetics and philosophy of history. Furthermore, as I shall try to show in this essay, his aesthetics is of great relevance to his philosophy of history, while his philosophy of history is of no less interest for his aesthetics.

By focusing on the notions of representation, identity, and the identity of indiscernibles we shall discover how fruitful this cooperation of aesthetics and philosophy of history may be. Crucial to all historical writing and, hence, to all philosophy of history, is the notion of identity through time and change. How could the historian write the history of x if x cannot be said to remain the same in the course of its history? It will become clear that aesthetics will provide us with a satisfactory solution for the problem, for the aestheticist notion of representation will enable us to define the notion of identity that the historian needs.

Nevertheless, a certain friction can be observed between Danto's aesthetics and his philosophy of history. At the end of this essay I hope to show that Danto's philosophy of history will be our best guide to dealing adequately with this friction.
According to What: Art and the Philosophy of the “End of Art”
Authors: Kudielka Robert
Published: March 2003

In 1964, when Danto first encountered Warhol's Brillo Box, Jasper Johns made a painting titled According to What. Danto's new book After the End of Art also provokes this question because in his restatement of Hegel's verdict on art's historical role he drops an essential part of the implied definition of art: the issue of adequacy between content and presentation. Why dispense with this crucial point of quality judgment? My critique falls into three parts. The first part shows how the whole historical argument rests upon a shift of criteria. According to Hegel art reached its highest point of achievement in classical antiquity when adequate embodiment seemed indispensable to the presence of the spirit. It subsequently lost this exclusive rank—first through Christianity, then through modern philosophy—when a new spiritual self‐awareness emerged which no longer seemed to need external manifestation. Although Danto disputes the concept of absolute self‐possession as the metaphysical vanishing point of Hegel's construction, he nevertheless subscribes to its apparent evidence in late twentieth‐century art and culture. In the second part I discuss the characteristic distortions of Hegelian‐type historicism and confront them with both the obvious misrepresentation of the works of art themselves and the different code of conduct in practical art history. This leads to a rather disenchanting conclusion: according to an old, deeply ingrained philosophical prejudice there is no problem about quality in art, because the true yardstick and fulfillment of art is philosophy itself. The final part tries to unpick this tangle by showing that there was in fact, contemporaneous with Hegel, a remarkably different interpretation of the self‐same auspices of modern art which comes much closer to its actual achievements, and this without denying the basic philosophical predicament of which Danto has reminded us.
Occupational and Internal Labor Markets in Japan
Authors: Ohkusa Yasushi , Brunello Giorgio , Ariga* Kenn
Published: March 2003

The distinction between internal and occupational labor markets requires the development of informative indicators that go beyond standard measures such as firm size, which are too vague. This article develops an alternative measure, based on the comparison between firm‐specific and occupation‐specific tenure, and applies it to Japanese occupational data. We believe that the proposed measure is useful not only in classifying different occupations according to the degree of labor market internalization but also in documenting changes over time in job definition, “reengineering” of the corporation, and the like.
Editorial
Authors: Levine David I.
Published: March 2003

It is rare for this Journal to present an editorial. An article in this issue on discrimination in Thailand leads us to present some extensions of the findings and to discuss broader implications.
Meritocracy in America: Wages Within and Across Occupations
Authors: Cawley John , Heckman James , Vytlacil Edward
Published: March 2003

In The Bell Curve, Herrnstein and Murray argue that the U.S. economy is a meritocracy in which differences in wages (including differences across race and gender) are explained by differences in cognitive ability. In this article we test their claim for wages conditional on occupation using a simultaneous model of occupation choice and wage determination. Our results contradict Herrnstein and Murray's claim that the U.S. labor market operates only on meritocratic principles.