bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Adsol and CPDA‐1 blood preservatives during simulated massive resuscitation after hemorrhage in swine
Authors: Buchholz D.H. , Borgia J.F. , Ward M. , Miripol J.E. , Simpson J.M.
Published: March 2003

BACKGROUND: In recent years, there has been a change from the use of blood stored in CPDA‐1 to the use of red cells (RBCs) stored in electrolyte mixtures, such as Adsol (AS‐1 RBCs). However, because Adsol contains mannitol, as well as increased amounts of glucose relative to CPD and CPDA‐1, concerns have been expressed as to possible harmful effects (recipient hyperglycemia, inappropriate osmotic diuresis) that it might induce under conditions of massive RBC transfusion.

STUDY DESIGN AND METHODS: A hemorrhagic shock animal model was used to evaluate the effects of large‐volume infusion of CPDA‐1 or Adsol on glucose homeostasis and on urinary output under conditions that were devoid of extensive surgical manipulation. Hemorrhage was induced in 10 female Pitman‐Moore mini‐pigs to maintain mean arterial blood pressure at 55 mmHg for 90 minutes. After the return of autologous RBCs plus 1 L of 0.9‐percent sodium chloride, the animals were given solution equivalent to the solute load in either 20 units of CPDA‐1 whole blood (63 mL × 20 = 1260 mL) or 20 units of AS‐1 RBCs (100 mL × 20 = 2000 mL) over a period of 90 minutes. Animals were monitored to determine physiologic and blood chemical responses to infusion of the solutions and to determine if there was hyperglycemia or inappropriate diuresis in the Adsol‐treated group.

RESULTS: Animals that received CPDA‐1 developed significant hypocalcemia, arterial hypotension, and elevated blood glucose concentrations; two of five animals died of circulatory collapse. In contrast, glucose metabolism in the Adsol recipients was well‐regulated, serum ionized calcium concentration was not significantly altered, and all animals survived. No evidence of inappropriate diuresis was observed.

CONCLUSION: Administration of large amounts of Adsol was not associated with hyperglycemia or inappropriate osmotic duiresis in hemorrhaged and resuscitated mini‐pigs. These data suggest that fewer physiologic changes may be associated with the massive transfusion of AS‐1 RBCs than with that of CPDA‐1 whole blood.
Isolation of CD34+ progenitor cells from peripheral blood by use of an automated immunomagnetic selection system: factors affecting the results
Authors: Martín‐Henao G.A. , Picón M. , Amill B. , Querol S. , González J.R. , Martínez C. , Martino R. , Ferrá C. , Brunet S. , Grañena A. , Sierra J. , García J.
Published: March 2003

BACKGROUND: The isolation of CD34+ cells from mobilized peripheral blood is being increasingly used in the setting of allogeneic or autologous hematopoietic cell transplantation. Investigation of variables that may influence the effectiveness of CD34+ cell selection is of interest.

STUDY DESIGN AND METHODS: Fifty‐one CD34+ cell selections from peripheral blood progenitor cells (PBPCs) (39 allogeneic and 12 autologous) were performed using a magnetic cell separator (Isolex 300i, Baxter), including version 2.0 software. The results obtained were analyzed for different processing variables. The feasibility of transplanting these isolated CD34+ cells was also analyzed.

RESULTS: The isolated CD34+ cell fraction had a median purity of 88.9 percent (range, 47.8‐98.3). The median recovery of CD34+ cells was 45.1 percent (13.8‐76.2), and the median colony‐forming unit– granulocyte‐macrophage (CFU–GM) content was 17.2 percent (0.8‐58.6). Logarithms of T‐ and B‐cell depletion had median values of 3.7 and 2.8, respectively. The version 2.0 software of the Isolex 300i gave a higher CD34+ cell recovery in the enriched cell fraction (median 57.8%) than did version 1.11 (39.4%) or 1.12 (44.4%) (p = 0.01). The use of recombinant human deoxyribonuclease I during cell processing yielded more CD34+ cells (53% vs. 41%, p = 0.01) and higher purity (92.8% vs. 87%, p = 0.03). There was a correlation between the percentage of CD34+ cells labeled with the monoclonal antibody 8G12 clone and the percentage of CD34+ cells labeled with the monoclonal antibody used during the processing technique (9C5 clone) in the initial, enriched, and depleted CD34+ cell fractions (R2 = 0.95; 0.92; 0.78, p< 0.005, respectively). Median times for recovering >0.5 × 109 per L of granulocytes and >20 × 109 per L of platelets were 13 and 16 days in the allograft patients and 13 and 14 days in the autograft patients.

CONCLUSION: CD34+ cells can be highly and effectively isolated from allogeneic and autologous grafts by use of this automated technique, with a high grade of T‐ and B‐cell depletion. These purified CD34+ cell components can engraft normally.
Alterations in cytoskeletal organization and tyrosine phosphorylation in platelet concentrates prepared by the buffy coat method
Authors: Estebanell E. , Díaz‐Ricart M. , Escolar G. , Lozano M. , Mazzara R. , Ordinas A.
Published: March 2003

BACKGROUND: Numerous morphologic and biochemical changes occurring during platelet storage may result in the impairment of platelet function.

STUDY DESIGN AND METHODS: The effect of preparation and storage conditions on platelet function was analyzed through evaluation of cytoskeletal organization and signaling mechanisms involved in the activation of platelets by thrombin. Samples of platelets prepared by the buffy coat method were obtained before and after the platelet concentrates were prepared during storage for 1, 3, and 5 days. Thrombin‐induced aggregation was monitored, and changes in the organization of proteins in the cytoskeleton were analyzed by gel electrophoresis. For the analysis of tyrosine phosphorylation, proteins were transferred to nitrocellulose membranes and probed with a specific antibody.

RESULTS: The aggregation and the cytoskeletal organization induced by thrombin activation were markedly impaired immediately after preparation of platelet concentrates, although they normalized after the first 24 hours of storage and decreased progressively after 3 days of storage. Results in tyrosine phosphorylation paralleled those obtained with cytoskeletal organization, except for samples obtained immediately after processing to obtain platelet concentrates.

CONCLUSION: These data indirectly suggest that the stress induced by the preparation method has an activating effect on platelet function that may imply a delayed platelet response to further stimuli. This effect may result in a deficient redistribution of signaling molecules within platelets.
Cost‐effectiveness of epoetin and autologous blood donationin reducing allogeneic blood transfusions incoronary artery bypass graft surgery
Authors: Marchetti M. , Barosi G.
Published: March 2003

BACKGROUND: Coronary artery bypass graft (CABG) surgery accounts for a substantial portion of all allogeneic units of blood transfused. Drugs and autologous blood donation (ABD) are alternative or adjunctive methods for reducing complications and costs induced by allogeneic blood transfusions. Recombinant human erythropoietin (epoetin) has the potential to decrease perioperative need for allogeneic blood during CABG, but its high cost calls for a careful economic evaluation before it can be recommended for widespread use.

STUDY DESIGN AND METHODS: A decision tree was used to compare a hypothetical strategy of no epoetin with one in which epoetin was utilized to control blood transfusion needs in CABG; each strategy was tested with and without ABD. The impact of these strategies on both the quality‐adjusted life years (QALYs) and costs ($US) was calculated.

RESULTS: Using epoetin alone and with ABD, respectively, avoided the transfusion of 0.61 and 1.35 units of allogeneic blood per patient and saved 0.000086 and 0.000146 QALYs per patient. This made cost‐effectiveness (CE) higher than $7 million and $5 million for each QALY saved, respectively. ABD alone cost more than $1 million per QALY saved. If the risk of bacterial infections following allogeneic transfusions was included in the model, epoetin alone cost $6288 per QALY saved, while ABD, both alone and with epoetin, saved money.

CONCLUSION: On the basis of the existing evidence, neither of the blood‐saving strategies modeled was a cost‐effective means of avoiding the deleterious health effects of perioperative blood transfusions in CABG. However, if allogeneic blood‐related infections were to be considered, both ABD and epoetin would be acceptable interventions.
Preterm birth and the availability of cord blood for HPC transplantation
Authors: Surbek D.V. , Holzgreve W. , Steinmann C. , Hahn S. , Gratwohl A. , Wodnar‐Filipowicz A. , Tichelli A.
Published: March 2003

BACKGROUND: Cord blood from deliveries at term can be used for HPC transplantation. The objective of this study was to determine the amounts of cord blood nucleated cells (NCs) and HPCs that were collectable from preterm deliveries.

STUDY DESIGN AND METHODS: Cord blood collected from preterm deliveries between 22 and 36 weeks of gestation was compared with regard to volume, NC count (/mL), CD34+ cell count (/mL), and the NC and CD34+ cell counts per cord blood sample and at different gestational ages.

RESULTS: A correlation was found between gestational age and NC count (r = 0.52, p<0.001), and an inverse relation was found between gestational age and CD34+ cell count (r = − 0.68, p<0.001). The CD34+ cell count per cord blood sample was independent of gestational age (r = − 0.13, p = NS), and no significant difference between early (22‐32 week) and late (33‐36 week) preterm deliveries was found (p = 0.870). Comparison with published data from cord blood transplantations revealed that up to one‐third of preterm samples contained at least as many NCs (or CD34+ cells) as the median cell dose transplanted (calculated for the median recipient weight) in the respective study. Furthermore, 77 percent of all preterm samples contained at least 1 × 107 NCs (and 42% at least 1 × 105 CD34+ cells) per kg for transplantation in a recipient of 20‐kg body weight, which corresponds to the lower threshold of cells per kg in the graft recommended by Eurocord.

CONCLUSION: Preterm delivery should not be a reason to exclude cord blood collection if allogeneic cord blood transplantation in a sibling is planned.
Transfusion‐transmitted infectious diseases in Argentina, 1995 through 1997
Authors: Schmuñis Gabriel A. , Zicker Fabio , Segura Elsa L. , Del Pozo Ana E.
Published: March 2003

BACKGROUND: Assessment of the safety of the blood supply, the quality of screening procedures, and the risk of transfusion transmission of infectious diseases in any country can be estimated by reviewing the records of blood donations and screening procedures and the prevalence of serologic markers of infectious diseases.

STUDY DESIGN AND METHODS: Information on blood donors, particularly the number of screened donors, and on the prevalence of serologic markers of infectious diseases was available from Argentina for 1995 through 1997. This information permitted the estimation of the risks and costs of preventing transfusion transmission of infectious diseases within the country during this period.

RESULTS: Screening coverage was higher in the private sector. The proportion of donors screened for HIV increased from 84.52 percent in 1995 to 97.97 percent in 1997; in the same period, serologic screening for HbsAg increased from 83.71 percent to 98.48 percent; that for HCV from 69.92 percent to 97.83 percent; and that for syphilis from 87.94 percent to 98.71 percent. One hundred percent of donors were screened for Trypanosoma cruzi throughout the period. The overall prevalence of HIV per year varied from 2.42 to 3.36 per 1,000 donors; that of HBV, from 5.80 to 9.76 per 1,000; of HCV, from 7.39 to 16.61 per 1,000; and of syphilis, from 5.25 to 7.65 per 1,000. The overall prevalence of antibodies to T. cruzi ranged from 36.53 to 49.20 per 1,000 donors. The overall index of the spread of infectious viral disease through blood transfusion decreased from 47.74 per 10,000 donations in 1995 to 4.75 per 10,000 in 1997. The ratio of acquired infections to donations improved from 1:209 to 1:2,102 during the same period. The risk of T. cruzi infection from 1995 through 1997 was, in theory, nil, given the 100‐percent screening. The greatest threat to the quality of the blood supply throughout the period studied was HCV.

CONCLUSION: The status of the blood supply in Argentina improved steadily from 1995 to 1997, as shown by the increase in screening coverage.
A randomized trial comparing acute normovolemic hemodilution and preoperative autologous blood donation in total hip arthroplasty
Authors: Goodnough Lawrence T. , Despotis George J. , Merkel Kurt , Monk Terri G.
Published: March 2003

BACKGROUND: The value of acute normovolemic hemodilution (ANH) as compared to preoperative autologous blood donation (PABD) in orthopedic surgery is unknown. Therefore, a prospective, randomized study was conducted to compare these techniques in patients undergoing primary total hip arthroplasty.

STUDY DESIGN AND METHODS: ANH patients underwent phlebotomy for up to 3 units, or to a target Hct level of 28 percent after induction of anesthesia. PABD patients were asked to donate up to 3 units before admission.

RESULTS: Mean baseline Hct levels were not different in ANH and PABD patients (39.7 ± 4.5 vs. 41.8 ± 3.8%, p = 0.09). No difference was found in allogeneic blood exposure among ANH and PABD cohorts: 4 (17%) of 23 ANH patients received a total of 9 allogeneic blood units, compared to no allogeneic transfusions in the PABD cohort (p = 0.30). Total blood costs associated with ANH were significantly (p<0.05) lower than blood costs associated with PABD ($151 ± 154 vs. $680 ± 253, respectively).

CONCLUSION: In patients undergoing total hip arthroplasty, ANH is safe, can be considered equivalent to PABD in effectively reducing exposure to allogeneic RBCs, and is less costly than PABD.
Serum supplement, inoculum cell density, and accessory cell effects are dependent on the cytokine combination selected to expand human HPCs ex vivo
Authors: Xu Ruiling , Medchill Michael , Reems Jo Anna
Published: March 2003

BACKGROUND: The prolonged periods of pancytopenia associated with cord blood transplants suggest that in some cases cell numbers may be limiting. The possibility that limiting cell numbers may be overcome and prolonged periods of pancytopenia abrogated by the transplantation of human umbilical cord blood cells expanded ex vivo has led to efforts to define optimal culture conditions for these cells.

STUDY DESIGN AND METHODS: Cord blood CD34+ cells were cultured with three cytokine combinations: SCF+G–CSF+GM–CSF+MGDF (SGGM); IL‐6+ SCF+MGDF+Flt3‐ligand (6SMF); and IL‐1+IL‐3+IL‐6+G–CSF+GM–CSF+SCF+Epo (GFmix). Serum effects, inoculum concentration (cells/mL) seeding density (cell/cm2) and accessory cell effects on the expansion of CD34+ cells were determined.

RESULTS: Cellular outputs were significantly higher with fetal calf serum (FCS) than with cord blood serum (CBS) or adult group AB serum (ABS) in the presence of 6SMF, however, CBS was as effective as FCS. The best seeding concentrations varied for each of the cytokine combinations, and inoculum densities exceeding 1000 cells per cm2 proved detrimental for cultures containing GFmix and SGGM. Accessory cell studies indicated that populations expressing the CD33 antigen inhibited the expansion of purified CD34+ cells in the presence of GFmix or SGGM, but not in the presence of 6SMF.

CONCLUSION: Serum supplement, inoculum cell concentration, seeding densities, and accessory cell effects are dependent upon the cytokine combination selected to expand cord blood HPCs ex vivo. Thus, each of these measures should be assessed to establish reproducible and reliable conditions for the selection of different cytokine combinations to culture cord blood HPCs.
Automation of nucleic acid extraction for NAT screening of individual blood units
Authors: Lee Dong‐Hun , Prince Alfred M.
Published: March 2003

BACKGROUND: Automation of NAT for single units of blood is currently hampered by the labor‐intensive steps involved in the extraction of nucleic acids from samples before the amplification procedures. A new method has been developed for the automation of these steps using hydrophilic polyvinylidene fluoride (PVDF) filter plates.

STUDY DESIGN AND METHODS: Quantitative nucleic acid recoveries from sera containing HCV, HIV, HBV, HAV, and human parvovirus B19 and from 3H‐labeled HCV RNA were determined in parallel by the semi‐automated PVDF method and a single‐column method (Qiagen). Quantitative PCR was performed.

RESULTS: Similar recoveries of HCV, HIV, and HBV (with silica beads) were observed with the PVDF method and with the Qiagen single‐column method. The sensitivity of the PVDF‐based PCR assay for HCV, HIV, and HBV in serially diluted serum samples was always within two serial dilutions of that obtained when the Qiagen single‐column method was used in the same assays. With the use of 3H‐labeled HCV RNA, recoveries of approximately 70 percent were found by both methods.

CONCLUSION: The PVDF method will permit full automation of the simultaneous extraction of nucleic acid from sera containing HCV, HIV, and HBV. This procedure will permit NAT screening of individual units of blood, will replace the current screening of pools, and will achieve improved blood safety with reduced labor and costs.
A possible role for maternal HLA antibodyin a case of alloimmune neonatal neutropenia
Authors: Hagimoto Rokuro , Koike Kenichi , Sakashita Kazuo , Ishida Takefumi , Nakazawa Yozo , Kurokawa Yumi , Kamijo Takehiko , Saito Satoshi , Hiraoka Asako , Kobayashi Masao , Komiyama Atsushi
Published: March 2003

BACKGROUND: Alloimmune neonatal neutropenia (ANN) is caused by a reaction of maternal alloantibodies with paternally inherited antigens on the fetal neutrophils. While human neutrophil antigens (HNA) antibodies are found in half of ANN cases, specific antibodies have not been defined in the remaining cases.

STUDY DESIGN AND METHODS: Reported here is a neonate with omphalitis due to neutropenia. To elucidate the cause of ANN, flow cytometric and PCR analyses were used. Reactions of the patient's and mother's sera with neutrophils, lymphocytes, and platelets were examined by lymphocytotoxicity test (LCT), anti‐human immunoglobulin‐LCT, and mixed passive hemagglutination test.

RESULTS: The maternal sera reacted with neutrophils, lymphocytes, and platelets of the patient and father. The platelet adsorption eliminated the reaction of the maternal serum with the patient's neutrophils. The HLA typing of the family and an LCT using a panel of lymphocytes of 20 HLA‐typed donors showed HLA‐A2 antigen as a target of antibodies in the maternal serum. According to anti‐human immunoglobulin‐LCT, the anti‐HLA‐A2 was present in the neonatal serum. On the other hand, HNA antibodies were not detectable in the patient's or the mother's serum.

CONCLUSION: These results suggest that the transplacental passage of the maternal HLA antibody caused neutropenia in this patient.
Donor WBCs can persist and transiently mediateimmunologic function in a murine transfusion model:effects of irradiation, storage, and histocompatibility
Authors: Lee Tzong‐Hae , Reed William , Mangawang‐Montalvo Leilani , Watson Jessica , Busch Michael P.
Published: March 2003

BACKGROUND: Donor WBCs are responsible for numerous transfusion complications, but little is known concerning the natural history of their clearance following transfusion or of their function in the recipient's circulation. A murine transfusion model was developed to investigate the effects of blood component characteristics and histocompatibility on donor WBC survival kinetics and function.

STUDY DESIGN AND METHODS: To investigate the effects of storage and irradiation, fresh whole blood and blood stored for 1, 2, and 6 weeks at 4°C, all from male C57b (H2Kb) mice, was transfused to female Balb/c (H2Kd) mice. To study the effect of histocompatibility, blood was also transfused from C57b mice to Balb/c, FVB, C3H, and SW (outbred) mice. To investigate the xenogeneic setting, blood from humans, rats, and rabbits was transfused to Balb/c mice. Samples were collected weekly after transfusion, and the donor WBCs were analyzed, targeting the Y‐chromosome with quantitative PCR. To investigate donor WBC function, dinitrochlorobenzene (DNCB) sensitivity was induced in donor and recipient mice, and the transfusion recipients were observed for hypersensitivity to DNCB.

RESULTS: Donor WBCs had reduced in vivo survival equivalent to their period of storage ex vivo at 4°C. Irradiation of donor blood produced no observable difference in donor WBC survival. Allogeneic male donor WBCs persisted (100‐<1 cell/μL) in female Balb/c recipient mice blood over 6 weeks. Donor WBC survival kinetics displayed an early MHC‐dependent phase, which was followed by a more rapid phase that was not influenced by donor‐recipient MHC differences. All donor WBCs were cleared within 24 to 48 hours. DNCB sensitivity was passed through transfusion, where it was transiently expressed in naive recipients.

CONCLUSION: The clearance of donor WBCs in the murine transfusion model is much slower than that in humans. Allogeneic donor WBC clearance may be biphasic, involving MHC‐dependent as well as MHC‐independent mechanisms. DNCB sensitivity can be transferred transiently to a naive recipient.
Absence of risk factors for false‐positive test results inblood donors with a reactive test result inan automated treponemal test (PK‐TP) for syphilis
Authors: Orton Sharyn L. , Dodd Roger Y. , Williams Alan E. ,   for the ARCNET Epidemiology Group
Published: March 2003

BACKGROUND: Screening and confirmatory serologic tests for syphilis are known to generate false‐positive results in low‐risk populations, which include blood donors. This study assessed whether conditions previously reported to cause biological false‐positive (BFP) test results for syphilis are relevant to contemporary syphilis testing of blood donors and the extent to which seropositive donors report a history of syphilis.

STUDY DESIGN AND METHODS: A history of conditions reported to be associated with BFP syphilis tests or a history of syphilis infection was assessed by a case‐control study of donors with reactive and nonreactive automated treponemal test results, using an anonymous mail survey. Analysis of cases was stratified by fluorescent treponemal antibody absorption (FTA‐ABS) result.

RESULTS: Adjusted ORs (95% CIs) for reported BFP‐associated conditions were 1.3 (0.8‐2.1) for FTA‐ABS‐positive cases and 0.8 (0.3‐1.9) for FTA‐ABS‐negative cases. Among responding blood donors, syphilis history was reported in 78 (51%) of 153 FTA‐ABS‐positive cases, 0 of 142 FTA‐ABS‐negative cases, and 3 (0.4%) of 716 automated treponemal test (PK‐TP)‐negative controls.

CONCLUSION: Approximately half of donors with FTA‐ABS‐positive test results reported a syphilis history. There was no difference between reported BFP conditions for FTA‐ABS‐positive or FTA‐ABS‐negative cases and controls. This information may be useful when providing donors with better predonation or post‐test counseling information about syphilis testing.
Frozen‐stored granulocytes can be used for an immunofluorescence test to detect granulocyte antibodies
Authors: Nishimura Motoko , Mitsunaga Shigeki , Juji Takeo
Published: March 2003

BACKGROUND: Donor‐ and/or recipient‐derived granulocyte antibodies are considered to be the main cause of transfusion‐related acute lung injury (TRALI), neutropenia, and febrile transfusion reactions. Several types of tests are performed to detect antibodies in donated blood and/or the serum of a transfusion recipient. Because granulocytes cannot endure the freezing‐thawing process, they cannot be stored in liquid nitrogen (LN2). Therefore, testing is time‐consuming, because freshly prepared granulocytes are needed for each testing. An attempt has been made to develop a method that uses granulocytes stored in LN2 for the granulocyte immunofluorescence test (GIFT).

STUDY DESIGN AND METHODS: Freshly prepared granulocytes were suspended in a solution of 90‐percent fetal bovine serum (FBS) plus 10‐percent DMSO and then frozen and stored in LN2. In the case of GIFT, frozen‐stored granulocytes were rapidly thawed, washed, and fixed with 1‐percent paraformaldehyde (PFA) and then treated with MoAbs or serum containing antibodies that were reactive to granulocytes. After staining of granulocytes with FITC or PE, FACS analysis was performed.

RESULTS: A comparison of FACS profiles of freshly prepared granulocytes stained with MoAbs or serum with FACS profiles of frozen‐thawed‐fixed granulocytes showed that the surface antigen expression was restored. Comparable results from FACS profiles of freshly prepared and frozen‐thawed‐fixed granulocytes were obtained.

CONCLUSION: By being fixed with 1‐percent PFA, frozen‐stored‐thawed granulocytes can be used in the GIFT. With this method, the testing time can be shortened. Moreover, because representative panel granulocytes can be stored in several aliquots, uniform granulocytes can be used as panel cells for each testing.
Recurrent transfusion‐related acute lung injury
Authors: Win Nay , Montgomery Julia , Sage Deborah , Street Martin , Duncan John , Lucas Geoff
Published: March 2003

BACKGROUND:Transfusion‐related acute lung injury (TRALI) is a rare condition that is commonly associated with the transfusion of donor plasma containing WBC antibodies. Biologically active lipids that accumulate during storage of RBCs and platelets may also cause TRALI. There has been only one previously reported case of recurrent TRALI.

CASE REPORT:A patient received a transfusion 2 days after undergoing hysterectomy; she developed TRALI after receiving the transfusion. The patient recovered after being on ventilation for 6 days but received an additional transfusion and had a second episode of TRALI, which required further ventilation.

RESULTS:Laboratory investigation of the first episode of TRALI suggested the presence of HLA‐A2 (N = 1) and granulocyte‐specific IgM antibodies (N = 2) in the sera from three of the donors. All three sera reacted in crossmatch studies with the patient's granulocytes and lymphocytes. Lymphocyte‐specific IgG antibodies were detected in the patient's serum. There was no evidence to suggest the involvement of WBC antibodies in the second episode of TRALI. Antibody screening of the donors' samples and both forward and reverse crossmatch studies were negative.

CONCLUSION:The first episode of TRALI seems to be due to the action of HLA‐A2 and granulocyte‐specific IgM antibodies. The second episode may have been due to the action of lipid neutrophil‐priming agents in the donors' units in association with the patient's underlying pulmonary condition (i.e., recovering from lung injury). TRALI can recur if a patient requires further transfusion support shortly after an initial episode of TRALI.
The effect of the transfusion of stored RBCs on intestinal microvascular oxygenation in the rat
Authors: Van Bommel Jasper , De Korte Dirk , Lind Albert , Siegemund Martin , Trouwborst Adrianus , Verhoeven Arthur J. , Ince Can , Henny Christiaan P.
Published: March 2003

BACKGROUND: Although it is known that the transfusion of stored RBCs does not always improve tissue O2 consumption under conditions of limited tissue oxygenation, the efficiency of O2 delivery to the microcirculation by stored RBCs has never been determined.

STUDY DESIGN AND METHODS: In a rat hemorrhagic shock model, the effects of resuscitation with fresh or 28‐day‐old RBCs stored in CPD plasma, saline‐adenine‐glucose‐mannitol, and CPDA‐1 plasma were investigated. Systemic hemodynamic and intestinal oxygenation measures were monitored. Intestinal microvascular PO2 was determined with the O2‐dependent quenching of palladium‐porphyrin phosphorescence, and the RBC deformability was measured with a Laser‐assisted optic rotational cell analyzer.

RESULTS: Hemodynamic and oxygenation measures were significantly decreased during hemorrhagic shock. Intestinal oxygen consumption and mesenteric venous pO2 were restored with the transfusion of both fresh and stored RBCs, except for CPD‐stored RBCs. The intestinal microvascular pO2 improved only with the transfusion of fresh RBCs. Deformability of the stored RBCs was significantly decreased.

CONCLUSION: In contrast to that of fresh RBCs, the transfusion of stored RBCs did not restore the microcirculatory oxygenation, possibly because of impaired O2 unloading, but, except for CPD‐stored RBCs, the storage‐induced changes were not enough to impair intestinal VO2 and mesenteric venous pO2.
Rapid down modulation of P‐selectin glycoprotein ligand‐1 (PSGL‐1, CD162) by G–CSF in humans
Authors: Jilma Bernd , Hergovich Nicole , Homoncik Monika , Marsik Claudia , Kreuzer Claudia , Jilma‐Stohlawetz Petra
Published: March 2003

BACKGROUND: In vitro and animal studies suggest a critical role for P‐selectin glycoprotein ligand‐1 (PSGL‐1) in the regulation of WBC adhesion and neutrophil counts. As WBC activation decreases PSGL‐1 expression on WBCs in vitro, the effects of G–CSF on PSGL‐1 expression were examined.

STUDY DESIGN AND METHODS: Two different G–CSF doses (1 and 5 μg/kg IV) were compared with high‐dose dexamethasone (1 mg/kg twice daily) and placebo in a randomized, double‐blind, four‐way crossover trial in eight healthy volunteers. Surface expression of WBC adhesion molecules was quantified by flow cytometry.

RESULTS: Both G–CSF and dexamethasone led to a delayed down regulation of L‐selectin. In contrast, G–CSF rapidly down regulated PSGL‐1 expression on neutrophils within 90 minutes, whereas neither dexamethasone nor placebo had an effect. Similarly, incubation of WBCs with clinically relevant G–CSF concentrations (60 μg/L) for 90 minutes down modulated PSGL‐1 expression on neutrophils and enhanced CD11b expression, compatible with a direct PSGL‐1 down regulation by G–CSF‐induced neutrophil activation. Similar to G–CSF, GM–CSF down regulated PSGL‐1 in vitro. Both drugs induced shedding of soluble PSGL‐1, supporting the concept that proteolytic cleavage is a potential mechanism of PSGL‐1 down regulation on neutrophils.

CONCLUSION: G–CSF, but not dexamethasone, down regulates PSGL‐1 expression on the surface of neutrophils in humans. This could also partly explain the synergistic effects when both drugs are combined for optimal mobilization of neutrophils for clinical granulocyte transfusion programs.
Point mutations causing the McLeod phenotype
Authors: Russo David C.W. , Lee Soohee , Reid Marion E. , Redman Colvin M.
Published: March 2003

BACKGROUND: The McLeod phenotype is defined by absence of Kx, weakening of Kell system antigens, and acanthocytosis. Individuals with the McLeod phenotype usually develop late‐onset neuromuscular abnormalities. Gene deletions, insertions, and point mutations that affect RNA splicing or that lead to premature stop codons have been reported to cause the McLeod phenotype. The McLeod phenotype may also be caused by mutations at a different splice site and by a novel mutation encoding an amino acid substitution that prevents transport to the cell surface.

STUDY DESIGN AND METHODS: The coding and flanking intron regions of XK from four male, unrelated individuals with the McLeod phenotype and nonchronic granulomatous disease were sequenced and compared with the wild type sequence. Genomic DNA was amplified by PCR, and the products were sequenced. In one case, the mutant cDNA was expressed in a heterologous cell, and cell surface expression was determined.

RESULTS: Three individuals with the McLeod phenotype had mutations that disrupted conserved GT sequences present at RNA splice sites. Two of them had G>C mutations at the 5′ splice site of intron 1, and one had a G>A mutation at the 5′ splice site of intron 2. One person with the McLeod phenotype had a 746C>G mutation in exon 3 encoding an R222G substitution. In a transfected cell, the expressed protein from the latter mutant did not travel to the cell surface.

CONCLUSION: The McLeod phenotype may be caused by several different mutations.
Investigation of transfusion transmission of a WA1‐type babesial parasite to a premature infant in California
Authors: Kjemtrup Anne M. , Lee Brian , Fritz Curtis L. , Evans Cherie , Chervenak Michael , Conrad Patricia A.
Published: March 2003

BACKGROUND: A premature infant in California developed respiratory distress associated with infection with a protozoal parasite, Babesia. The infant had received two blood transfusions, one from the father and one from an anonymous donor (Donor A). This study describes the follow‐up required to identify the source and species of Babesia that infected the infant.

STUDY DESIGN AND METHODS: At the time of the infant's illness, whole blood from the infant, father, and mother was evaluated for Babesia infection. Similar evaluation of whole blood from Donor A was performed 2 months after the suspected donation to the infant. Samples were tested using blood smear examination, serology, PCR, and hamster inoculation. Identity of the recovered Babesia parasites was confirmed by DNA amplification by PCR, genetic sequencing of the 18S gene, and phylogenetic analysis.

RESULTS: WA1‐type Babesia was recovered from the infant. Neither parent was the source of infection. Serology and hamster inoculation confirmed WA1‐type Babesia infection in Donor A. DNA sequences of the 18S gene from the infant and donor isolates were 100% identical.

CONCLUSION: WA1‐type Babesia infections may be difficult to detect among blood donors because such infections can be subclinical. This is the second WA1‐type Babesia transmission via blood transfusion and the first in an infant. Physicians in the western United States should consider Babesia as a possible cause of nonspecific febrile illness after a blood transfusion.
An objective structured clinical examination to evaluate health historian competencies
Authors: Lee Stacy J. , Wilkinson Susan L. , Battles James B. , Hynan Linda S.
Published: March 2003

BACKGROUND : Post‐donation information events in the blood‐collection process account for the majority of errors reported to the FDA. An eight‐station objective structured clinical examination (OSCE) based on information reported after donation was developed as a competency examination for health historians.

STUDY DESIGN AND METHODS : The OSCE measured two individual skill components: history‐taking technique (HXE) and ability to record and interpret a medical history (HXI). Donor historians at the Hoxworth Blood Center, University of Cincinnati Medical Center, were examined (n = 56).

RESULTS : In general, staff performance was acceptable, but several areas for improvement were identified. Of particular concern were the deferrals associated with the malaria scenarios. The overall reliability score was greater than 0.8 for the total OSCE and HXI. Using the cut score of 0.9, or 90 percent, 10 subjects would not have passed the exam based on the HXE score and one person would not have demonstrated competency based on the HXI score.

CONCLUSION : An OSCE is a reliable, valid, and practical method for assessing continued competency in health historians. This form of competency assessment and subsequent retraining may reduce the incidence of errors in information reported after donation and should be further studied as a suitable national standard for assessing competency.
Lapsed donors: an untapped resource
Authors: Schreiber George B. , Glynn Simone A. , Damesyn Mark A. , Wright David J. , Tu Yongling , Dodd Roger Y. , Murphy Edward L. ,   Retrovirus Epidemiology Donor Study
Published: March 2003

BACKGROUND : There is a clear need for methods to recruit and retain donors without compromising blood safety. Although prior studies report lower viral prevalence rates in repeat donors than those in first‐time donors, it is unknown if this relationship holds after a lapse of several years between donations.

STUDY DESIGN AND METHODS : A total of 6.4 million allogeneic donations collected at five US blood centers from 1991 through 1998 were classified by donation history (first‐time vs. repeat) and by length of time between donations (lapsed interval length). The prevalence of HCV, HIV, and HBsAg was compared by donation history and lapsed interval length. The relationship between lapsed interval length and donor demographics was explored.

RESULTS : Repeat donors who delayed their return for over 5 years were significantly less likely to test positive for a viral infection than were first‐time donors. The likelihood of a positive test result appeared to increase steadily with lapsed interval length for HCV and HBsAg, but not for HIV. Younger, less educated, and nonwhite donors were less likely to return than others.

CONCLUSIONS : Recruitment of donors who have not returned for several years could be an effective way to increase the blood supply while preserving blood safety. Understanding the relationship of donor demographics to return behavior is important for recruitment efforts.
Impact of changes in viral marker screening assays
Authors: Sharma Usha K. , Stramer Susan L. , Wright David J. , Glynn Simone A. , Hermansen Sigurd , Schreiber George B. , Kleinman Steven H. , Busch Michael P. ,   for the Retrovirus Epidemiology Donor Study
Published: March 2003

BACKGROUND : Monitoring the performance of routinely used infectious disease serologic tests is necessary to evaluate their effectiveness in identifying true‐positive units and erroneously disqualifying safe blood donors.

METHODS : With two large screening test data sets collected between 1991 and 1998 and between 1997 and 2000, the impact of changes in screening assays for HIV, HCV, and HBsAg was analyzed with regard to the prevalence of confirmed‐positive, indeterminate, and confirmed‐negative results and the deferral of donors with an indeterminate or negative results (donor loss).

RESULTS : The prevalence of indeterminate results and donors loss increased significantly in the 6 months after introduction of an HIV‐1/2 EIA. A second‐generation HCV EIA increased the detection of confirmed‐positive donations in repeat donors (p < 0.001) and increased the prevalence of indeterminate donations. Implementation of a third‐generation HCV EIA resulted in a significant decrease in indeterminate results in first‐time donors. Nonspecific test results increased when HBsAg test kits from a different manufacturer were introduced or different lots of HIV antibody screening test kits from the same manufacturer were used.

CONCLUSION : Introduction of newly licensed versions of assays, switching kit manufacturers, and lot‐to‐lot variations have an impact on rates of deferrals of safe donors as well as sensitivity of routine screening. Before considering changes in screening tests, blood centers should be aware of, and evaluate, the potential impact on donor loss.
Evaluation of a transcription‐mediated amplification‐based HCV and HIV‐1 RNA duplex assay for screening individual blood donations: a comparison with a minipool testing system
Authors: Candotti Daniel , Richetin Aline , Cant Barbara , Temple Jillian , Sims Cate , Reeves Ian , Barbara John A.J. , Allain Jean‐Pierre
Published: March 2003

BACKGROUND : NAT was introduced for HCV RNA in 1999 to screen blood donations and improve the safety of the blood supply.

STUDY DESIGN AND METHODS : The performance of a NAT multiplex for HCV and HIV‐1 RNA based on transcription‐mediated amplification (TMA) was assessed with various sensitivity panels and by screening 50,000 serologically unscreened, first‐time donor plasma samples. Results were compared with a routine NAT screening for HCV RNA by RT‐PCR in pools of 96 plasma samples.

RESULTS : The TMA multiplex 95 percent sensitivity ranged between 22 and 54 IU per mL for HIV‐1 and 15 and 20 IU per mL for HCV RNA. The rate of test failure was 8.6 percent but decreased to 4.7 percent when results of two critical periods of equipment malfunction were excluded. Test failure was related to human error, minute control contamination, and insufficient mixing of reagents at the extraction stage. All 31 repeatedly reactive samples (0.06%) were seropositive for HCV (29) or HIV‐1 (2) and contained RNA detectable by discriminatory TMA and confirmatory RT‐PCR, indicating 100 percent specificity. A direct comparison of TMA in individual samples and RT‐PCR in plasma pools was possible on 27 HCV RNA‐containing samples. Twenty‐six samples were detected in plasma pools; the lack of detection of 1 sample was due to an identification error at the pooling stage.

CONCLUSION : The HCV and HIV‐1 multiplex NAT had high specificity and sensitivity.
Emission Ratiometry for Simultaneous Calcium and Action Potential Measurements with Coloaded Dyes in Rabbit Hearts: Reduction of Motion and Drift
Authors: KONG WEI , WALCOTT GREGORY P. , SMITH WILLIAM M. , JOHNSON PHILIP L. , KNISLEY STEPHEN B.
Published: March 2003

Simultaneous Ca and AP Emission Ratiometry. Introduction: Optical measurements of the cardiac calcium transient (Ca) and transmembrane action potential (AP) may be performed simultaneously with emission ratiometry to lessen motion artifacts and photobleaching effects. We examined changes in emission spectrum in perfused rabbit hearts coloaded with Rh237 and a green‐emitting Ca dye (Fluo‐4 or Oregon Green BAPTA 1) to determine wavelength bands for emission ratiometry and to test whether ratiometry reduces motion artifacts and drift.

Methods and Results: A 488‐nm laser illuminated hearts while a spectrofluorometer collected fluorescence from 489 to 838 nm at 1 kHz. Ratiometry with the Ca‐ and AP‐insensitive emission band 663 to 685 nm (IS) as denominator and the Ca‐sensitive band 510 to 532 nm as numerator lessened motion artifacts, which was quantified as a 1.4‐fold increase in relative amplitude of the Ca

(P < 0.05)

. Ratiometry with the AP‐sensitive band 772 to 794 nm as denominator and the IS as numerator produced a 1.7‐fold increase in relative amplitude of the AP

(P < 0.05)

. The ratiometry decreased photobleaching‐dependent drift by a factor of

0.6 (P < 0.05)

for Ca and 0.45

(P < 0.05)

for AP.

Conclusion: Simultaneous Ca and AP emission ratiometry reduces motion artifacts and drift in hearts with coloaded dyes.
Single‐Center Experience with the Helex™ Septal Occluder for Closure of Atrial Septal Defects in Children
Authors: VINCENT ROBERT N. , RAVIELE ANTHONY A. , DIEHL HELEN J.
Published: March 2003

Catheter closure of atrial septal defects (ASDs) is an accepted procedure among pediatric cardiologists. We report our early experience with the newest of these devices in clinical trials in the United States. Between April and October 2001, 14 patients were enrolled in an FDA phase II multicenter trial comparing the results of ASD closure using the HELEX™ Septal Occluder to a surgical control group. Of the 14 patients, devices were placed and left in 13, one being removed for an excessive residual leak despite placing the largest device available. Of the remaining 13 patients, all patients had successful closure of their defects. An average of 1.8 devices/patient were deployed, reflecting the learning curve for this new device and new delivery style. Six devices were replaced because of excessive residual leaks, three for premature lock release, and two for improper seating of the device. There were no procedural complications, however, one patient required device removal 4 months postimplant for possible allergic reaction to nickel. The same patient had removal of stainless steel sternal wires for the same reason. At the 6‐month follow‐up, 11 of 13 patients had complete closure of the ASD, the other two having small, hemodynamically insignificant left to right shunts. In one of these patients, there was complete closure at the 12‐month follow‐up, whereas the other patient awaits the 1‐year evaluation. Early experience at our institution has demonstrated the ease of use of this device, its complete retrievability, and excellent closure of small to moderate ASDs in children. (J Interven Cardiol 2003;16:79–82)
Breath‐hold Three‐dimensional Lung Perfusion Imaging and Pulmonary Angiography after Contrast Administration1
Authors: Wielopolski P.A. , Hicks S. G. , De Bruin H. G , Oudkerk M.
Published: March 2003

We introduce a new combined approach using contrast‐enhanced magnetic resonance imaging (MRI) that may lead to a better sensitivity and specificity in staging pulmonary embolism (PE). A short protocol involving the application of two breath‐hold three‐dimensional (3D) pulse sequences and contrast agent injection is proposed and assessed on 35 patients following a consensus for anticoagulant therapy treatment under the suspected presence of PE. The protocol considers first the application of a 3D lung perfusion scan (MRPP) with high temporal and moderate spatial resolution to obtain volumetric parenchymal perfusion/ enhancemerit patterns to help localise segmental and sub‐segmental perfusion defects. Secondly, a high resolution 3D pulmonary MRA scan (MRPA) is performed to visualise the entire thoracic vasculature and to permit the inspection of each vessel separately. Multiplanar reformation of the MRPP data made it possible to evaluate the extent of any perfusion defect in all planes. Although a wide range of diffuse perfusion defects on MRPP were observed, PE could be ruled out after a careful inspection of the MRPA data. Perfusion abnormalities with a clear wedge appearance predicted the appearance of PE on MRPA subsequently confirmed with conventional pulmonary arteriography. We feel that this combined protocol provides a better insight to the localisation of PE than the MRPA alone and may play an important role in the assessment of patients with respiratory complications.
Can Histories Be True? Narrativism, Positivism, and the “MetaphoricalTurn”
Authors: Lorenz Chris
Published: March 2003

Narrativism, as represented by Hayden White and Frank Ankersmit, can fruitfully be analyzed as an inversion of two brands of positivism. First, narrativist epistemology can be regarded as an inversion of empiricism. Its thesis that narratives function as metaphors which do not possess a cognitive content is built on an empiricist, “picture view” of knowledge. Moreover, all the non‐cognitive aspects attributed as such are dependent on this picture theory of knowledge and a picture theory of representation. Most of the epistemological characteristics that White and Ankersmit attribute to historical narratives therefore share the problems of this picture theory.

The article's second thesis is that the theories of narrative explanation can also fruitfully be analyzed as inversions of positivist covering‐law theory. Ankersmit's brand of narrativism is the most radical in this respect because it posits an opposition between narrative and causal modes of comprehension while simultaneously eliminating causality from narrativist historical understanding. White's brand of narrativism is more of a hybrid than is Ankersmit's as far as its theory of explanation is concerned; nevertheless, it can also be fruitfully interpreted as an inversion of covering‐law theory, replacing it by an indefinite multitude of explanatory strategies.

Most of the striking characteristics of both White's and Ankersmit's narrativism pre‐suppose positivism in these two senses, especially their claim that historical narratives have a metaphorical structure and therefore no truth‐value. These claims are had to reconcile with the factual characteristics of debates by historians; this problem can be tracked down to the absence in “metaphorical” narrativism of a conceptual connection between historical narratives and historical research.