bluuebunny/crossref_metadata_2025 huggingface dataset:
Description of serologic features in autoimmune lymphoproliferative syndrome
Authors: Carter L.B. , Procter J.L. , Dale J.K. , Straus S.E. , Cantilena C.C.
Published: March 2003

BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a recently recognized and rare disorder associated with inherited defects in the Fas gene or other regulators of lymphocyte apoptosis. It is characterized by massive lymphadenopathy; splenomegaly; autoimmunity including episodes of immune hemolytic anemia, thrombocytopenia, and neutropenia.1 The serologic basis for immune cytopenias associated with ALPS has not been previously characterized.

STUDY DESIGN AND METHODS: RBC, granulocyte, and platelet serologies for ALPS patients and hepatitis C patients were assessed. Medical records were reviewed for clinical, immunologic, serologic, and transfusion history. Testing included: DAT; serum screening for antibodies to RBCs, granulocytes, platelets, cardiolipin, penicillin‐coated RBCs, and human leukocyte antigens; antibody identification and IgG subclass; RBC phenotype.

RESULTS: In a cohort of 11 patients with apoptosis defects (eight with heterozygous Fas gene mutations); many had histories of hemolytic anemia (7), thrombocytopenia (4), and/or leukopenia (11); nine received steroid therapy, seven underwent splenectomy; five had been remotely transfused. On the basis of serologic testing even when they were clinically stable, nine had positive DATs; two had alloantibodies; 6 had IgG and/or IgM antibodies to cardiolipin; seven had platelet‐directed antibodies; three had granulocyte‐directed antibodies; none had HLA antibodies.

CONCLUSIONS: Nearly all ALPS patients have antibodies directed against one or more hematopoietic cell lineages. Serologic testing is critical in the evaluation of these individuals and when transfusion is indicated, red cells that are matched for clinically significant C, E, and K antigens should be considered.
Evaluation of the effectiveness of targeted lookback for HCV infection in the United States—interim results
Authors: Culver David H. , Alter Miriam J. , Mullan Robert J. , Margolis Harold S.
Published: March 2003

BACKGROUND: As part of a nationwide program to identify persons at increased risk for HCV infection, persons who received blood from donors who later tested positive for anti‐HCV are being directly notified.

STUDY DESIGN AND METHODS: In December 1999, all 198 blood collection establishments (BCEs) and 5442 hospital transfusion services (TSs) in the United States were surveyed by mailed questionnaire to evaluate their progress in carrying out this notification.

RESULTS: Eighty‐one percent of the BCEs and 64 percent of the TSs responded. After correcting for nonresponse, an estimated 98,484 components at potential risk for transmitting HCV, according to previous testing of multiantigen‐screened donors, were identified nationwide, of which 85 percent had been transfused to recipients. Lookback for these recipients was completed for 80 percent, of whom 69 percent had died. Of those living, 78 percent were successfully notified. An estimated 49.5 percent of those notified were tested; 18.9 percent of those tested were anti‐HCV positive, and 32 percent of that group knew they were positive before notification. On the basis of an 85.5 percent reported completion rate for component notifications back through 1988, an estimated 1520 persons will have been newly identified as anti‐HCV‐positive when lookback related to multiantigen screening of donors is completed.

CONCLUSION: Targeted lookback related to previous multiantigen screening of donors will identify <1 percent of the estimated 300,000 HCV‐positive persons in the United States who may have acquired their infection via blood transfusion.
Growth of bacteria in inoculated platelets: implications for bacteria detection and the extension of platelet storage
Authors: Brecher Mark E. , Holland Paul V. , Pineda Alvaro A. , Tegtmeier Gary E. , Yomtovian Roslyn
Published: March 2003

BACKGROUND: Recent reports from Europe have advocated the use of bacterial culturing of platelets on Day 2 or 3 of storage to extend the shelf life of platelets to 7 days, thereby reducing the outdating of platelets and preserving a limited medical resource. To assess the optimal timing, the necessary sensitivity, and the possible efficacy of bacterial detection, the bacterial growth characteristics were reviewed in 165 platelet units, each inoculated on the day of collection with one of the following organisms: Bacillus cereus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens, Staphylococcus aureus, and Staphylococcus epidermidis from four previously published studies.

STUDY DESIGN AND METHODS: Quantitative culture data from inoculated platelet concentrates from five sites and four studies were combined into one database and analyzed for bacterial concentration thresholds (≥101, ≥102, ≥103, ≥104, ≥105 CFU/mL) by day of storage.

RESULTS: All examples of B. cereus, P. aeruginosa, K. pneumoniae, S. marcescens, and S. aureus had concentrations ≥102 CFU per mL by Day 3 after inoculation. By Day 4, all units with these organisms contained ≥105 CFU per mL. Units contaminated with S. epidermidis showed slower and more varied growth. By Day 3 after inoculation, 81.3 percent had 102 CFU per mL. By Day 4 after inoculation, 46 (95.8%) of 48 units had concentrations ≥102 CFU per mL.

CONCLUSION: These experiments suggest that an assay capable of detecting 102 CFU per mL on Day 3 of storage would detect the vast majority of bacterially contaminated platelet units, prevent many cases of platelet‐associated bacterial sepsis, and provide a scientific basis for the extension of the current platelet storage time. It would be expected that a rare, slow‐growing organism could escape such a detection scheme.
RBC autoantibodies in autoimmune lymphoproliferative syndrome
Authors: Stroncek David F. , Carter Laura B. , Procter Jo L. , Dale Janet K. , Straus Stephen E.
Published: March 2003

BACKGROUND: Patients with autoimmune lymphoproliferative syndrome (ALPS) have an autosomal dominant genetic defect that affects lymphocyte apoptosis and is associated with chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity, particularly affecting RBCs, WBCs, and platelets.

STUDY DESIGN AND METHODS: DATs were performed on 34 consecutive patients with ALPS and 37 of their clinically unaffected relatives. The effects of age, sex, race, and immunoglobulin levels on the incidence of autoantibodies and clinical hemolysis were assessed.

RESULTS: The DAT was positive in 21 (62%) of ALPS patients but in only 1 (3%) of their relatives (p = 0.001). The DAT reacted because of IgG alone in 43 percent, complement alone in 5 percent, and IgG plus complement in 19 percent; 33 percent of the patients′ cells had a positive reaction with polyspecific reagent only. All 10 ALPS patients with a history of hemolytic anemia had a positive DAT. Sixty percent of them had only IgG on their cells, 30 percent had IgG and complement, and 10 percent reacted only with polyspecific reagent. Of the 11 patients with a positive DAT and no history of hemolytic anemia, IgG alone was present in 27 percent, complement alone in 9%, and IgG plus complement in 9 percent; 55 percent had positive DATs only with polyspecific reagent. Among ALPS patients, those with a positive DAT had greater quantities of cells with increased α and β T‐cell receptors that phenotyped as CD4–CD8– and higher IgG levels.

CONCLUSIONS: The DAT results in ALPS patients are most similar to those found in warm autoimmune hemolytic anemia. The DAT is useful to distinguish affected and unaffected persons within an ALPS family.
Infectivity of blood from PCR‐positive, HBsAg‐negative, anti‐HBs‐positive cases of resolved hepatitis B infection
Authors: Prince Alfred M. , Lee Dong‐Hun , Brotman Betsy
Published: March 2003

BACKGROUND: Numerous reports have noted the existence of sera, particularly from resolving cases of HBV infection, that are positive for HBV DNA by PCR, despite being negative for HBsAg and IgM anti‐HBc. If such blood is infective and detectable by HBV NAT screening, it seems desirable to introduce such screening for transfused blood.

STUDY DESIGN AND METHODS: Three chimpanzees were inoculated with serum and lymphocytes from three patients who were HBV DNA PCR positive, but HBsAg negative. The animals were tested over a period of 15 months for HBsAg, anti‐HBs, anti‐HBc, and HBV DNA by PCR.

RESULTS: All animals remained uninfected.

CONCLUSION: Small amounts of plasma and MNCs from HBV DNA‐positive HBsAg‐negative blood do not appear to be infectious; however, further studies with larger volumes of inoculum should be conducted.
Accuracy of predonation Hct sampling affects donor safety, eligibility, and deferral rates
Authors: Wood Erica M. , Kim Debora M. , Miller John P.
Published: March 2003

BACKGROUND: Safe blood donation depends upon reliable predonation Hct screening. Earstick (ES) capillary samples are frequently used, but they may not be accurate.

STUDY DESIGN AND METHODS: Predonation ES and fingerstick (FS) and postdonation venous Hct results were compared in 1960 whole‐blood and 210 apheresis donors. The validity of using postdonation venous samples to evaluate predonation ES and FS Hct was assessed in 20 whole‐blood donors. The impact of Hct screening method on donor Hct deferrals was examined during periods when either ES or FS sampling was used exclusively.

RESULTS: All donors were eligible to donate on the basis of a predonation capillary Hct of ≥38 percent. In venous samples obtained immediately after donation, 36 percent of whole‐blood donors had a Hct <38 percent. With correction for a decrease of approximately 2 Hct units during donation, 20 percent of these donors had a predonation Hct <38 percent. The lowest venous Hct was 23.1 percent. FS samples showed better correlation with venous Hct. Hct discrepancies were similar for apheresis donors. Hct deferrals were significantly higher with FS sampling, especially among women.

CONCLUSION: Hct determinations from ES samples overestimate venous Hct. Fingerstick samples are more sensitive in detecting anemia. The accuracy of predona‐tion Hct sampling has implications for donor safety, eligibility, and deferral rates.
Inverse expression of Pk and Luke blood group antigens on human RBCs
Authors: Cooling Laura L. , Kelly Kathleen
Published: March 2003

BACKGROUND: Luke (LKE) is a high‐frequency RBC antigen, related to the P blood group system. A LKE‐negative phenotype is found in 1 to 2 percent of donors and may be associated with increased Pk. Because Pk and similar glycolipids are receptors for shiga toxin on cell membranes, a LKE‐negative phenotype could have implications for infections by Shigella dysenteriae and enterohemorrhagic Escherichia coli.

STUDY DESIGN AND METHODS: Volunteer donors (n = 257) were serologically typed for LKE with a LKE MoAb, MC813‐70. LKE‐strong‐positive, LKE‐weak‐positive and LKE‐negative RBCs were analyzed for Pk, P, LKE, and shiga toxin binding by immunofluorescence flow cytometry, high‐performance thin‐layer chromatography, scanning densitometry, and high‐performance thin‐layer chromatography immunostaining.

RESULTS: Among Iowa donors, 78.6 percent were LKE‐strong‐positive, 20.2 percent were LKE‐weak‐positive, and 1.2 percent were LKE‐negative. There was an inverse expression of Pk and LKE on RBCs. Pk expression was increased on LKE‐negative RBCs and was associated with increased shiga toxin binding. A LKE‐active glycolipid was identified in the ganglioside fraction of LKE‐strong‐positive RBCs.

CONCLUSION: A LKE‐negative phenotype is associated with increased expression of Pk on RBCs. Differences in Pk and LKE expression may play a role in host susceptibility to infection with S. dysenteriae and E. coli.
Comparison of the sensitivity of NAT using pooled donor samples for HBV and that of a serologic HBsAg assay
Authors: Sato Shinichiro , Ohhashi Wataru , Ihara Hiromi , Sakaya Shinichi , Kato Toshiaki , Ikeda Hisami
Published: March 2003

BACKGROUND : Studies were conducted using samples from early and late‐stage HBV‐infected persons to determine the pool size at which PCR had better sensitivity than a sensitive HBsAg chemoluminescence immunoassay (CLIA‐HBsAg).

STUDY DESIGN AND METHODS: HBV seroconversion panels were tested for HBsAg by CLIA and for HBV DNA by nested PCR (95% hit rate: 100 copies/mL); PCR was carried out at various dilutions. HBV serologically positive samples that were detected from the simultaneous screening of 540,161 routine whole‐blood donations using CLIA‐HBsAg and agglutination assays were also characterized for additional markers of HBV infection.

RESULTS: In 9 of 10 HBV seroconversion panels, PCR had better sensitivity than CLIA‐HBsAg at dilutions of 1‐in‐25 or lower. Of 65 CLIA‐only confirmed‐positive donor samples (agglutination assay‐negative), 8 represented early infection, 2 of which were PCR positive at a 1‐in‐50 dilution but negative at a 1‐in‐100 dilution. Only 2 of 47 samples from probable late‐stage HBV infection that were positive on CLIA only were PCR positive with 0.1‐mL sample volume and the S‐region primer; the remaining 45 samples required a 1.0‐mL sample input and C‐region primer for increased PCR positivity. The remaining 10 CLIA‐only confirmed‐positive donor samples were from HBV vaccine recipients. None of the 12 CLIA‐ and HBsAg‐negative donor samples that were strongly anti‐HBc reactive could be detected by PCR at any dilution; all 12 were PCR positive when undiluted, but 4 required a 1.0‐mL input volume for PCR positivity.

CONCLUSION: For the detection of samples representing early‐stage HBV infection, PCR at dilutions of 1‐in‐25 or lower (equivalent to a pool of ≤25 members) had greater sensitivity than CLIA‐HBsAg. In contrast, samples from late‐stage HBV infection were detected by PCR only with undiluted samples (0.1‐mL or 1.0‐mL input volumes), regardless of CLIA‐HBsAg reactivity. Therefore, although NAT using minipools of 25 donations or less may be effective for the detection of early‐stage HBV infection, it may not be effective for the detection of persistent HBV infection.
RBC alloantibody specificity and antigen potency in Olmsted County, Minnesota
Authors: Winters Jeffrey L. , Pineda Alvaro A. , Gorden Lemuel D. , Bryant Sandra C. , Melton L. Joseph , Vamvakas Eleftherios C. , Moore S. Breanndan
Published: March 2003

BACKGROUND: While RBC antigen frequencies for whites of Northern European ancestry are known, the relative frequencies of RBC antibodies within this population have not been determined. The distribution of RBC alloantibodies by sex and age was studied, as were the immunogenicity of RBC antigens and the occurrence of RBC alloantibody clusters in a geographically defined population.

STUDY DESIGN AND METHODS: RBC alloimmunization among patients and donors in Olmsted County, MN, was determined for the period from 1975 to 1995. Alloantibody frequencies were used to calculate the potency of each antigen relative to K. Cluster analysis was applied to the data to identify natural groupings of antibodies.

RESULTS: The frequency and potency of 33 alloantibodies from 1345 alloimmunized subjects were estimated. The most frequent alloantibodies were E (20.8%), Lea (18.6%), K (14.7%), D (12.9%), Leb (9.4%), M (7.2%), P1 (6.7%), Fya (6.3%), C (6.8%), and c (3.5%). The most potent antigens were Wra (0.363), Cw (0.078), Lea (0.03), E (0.028), V (0.025), Jsa (0.023), Kpb (0.023), Goa (0.023), JMH (0.023), and Rd (0.023). Greater frequency of overall alloimmunization (M:F = 1:2.7), anti‐D (p<0.0001), and anti‐Lea (p = 0.003) was seen among females. Warm autoantibodies were more frequent among males with positive antibody screens (p<0.0001). No other gender differences were observed. Alloimmunization increased with age for K, Kpa, Fya, D, C, E, and warm autoantibodies. Frequencies of alloimmunization to Lea, Leb, M, and P1 decreased with age. The cluster analysis showed grouping of the antibodies to C and D as well as to Lea and Leb, but the other RBC alloantibodies did not form clusters.

CONCLUSION: Less than 1 percent of residents tested had positive antibody screens. Anti‐E and anti‐Lea were more common than anti‐K. Wra and Cw were more potent antigens than K. Most antibodies showed an increase in frequency with increasing age. Except for anti‐C and ‐D and anti‐Lea and ‐Leb, RBC alloantibodies did not occur in clusters.
Evaluation of a reporting system for bacterial contamination of blood components in the United States
Authors: Roth Virginia R. , Kuehnert Matthew J. , Haley N. Rebecca , Gregory Kay R. , Schreiber George B. , Arduino Matthew J. , Holt Stacey C. , Carson Loretta A. , Elder Kathleen V. , Jarvis William R.
Published: March 2003

BACKGROUND:The transfusion of blood components contaminated with bacteria may have serious clinical consequences, but few data are available on the incidence of these events. A national effort to assess the frequency of blood component bacterial contamination associated with transfusion reaction (the BaCon Study) was initiated to better estimate their occurrence.

STUDY DESIGN AND METHODS:Standard reporting criteria, data collection forms, and a standardized reporting protocol were developed in collaboration with the American Red Cross, AABB, and the Department of Defense. Episodes reported to the BaCon Study were compared with those reported to the FDA's national reporting systems to estimate the extent to which all serious reactions associated with bacterial contamination were captured.

RESULTS:During the first 2 years, 38 episodes meeting study criteria were reported; 21 were laboratory‐confirmed. The estimated proportion of episodes reported to the BaCon Study (i.e., completeness of coverage) was lower than that reported to the FDA during the same period (0.33 vs. 0.68), but the positive predictive value was higher (0.66 vs.0.28).

CONCLUSION:Despite the complexity of obtaining reports from a large number of United States hospitals and transfusion centers, the feasibility and usefulness of the BaCon Study were shown. This study was the only national study in the United States to monitor adverse clinical events associated with bacterial contamination of blood components. By building on hospital‐based reporting of transfusion‐related adverse events, the BaCon Study serves as a model for the study of other complications associated with blood and blood components.
C‐reactive protein and IL‐6: new marker proteins for the diagnosis of CJD in plasma?
Authors: Völkel Dirk , Zimmermann Klaus , Zerr Inga , Lindner Thomas , Bodemer Monica , Poser Sigrid , Schwarz Hans Peter
Published: March 2003

BACKGROUND: CJD is usually diagnosed by clinical and neuropathological findings. A number of proteins regarded as markers for neuronal damage in plasma or serum have recently been described. Markers typical for tissue damage, although not usually associated with CJD, are another possibility. An evaluation of the relative usefulness of markers of neuronal and tissue damage in identifying CJD could be beneficial.

STUDY DESIGN AND METHODS: Plasma samples were collected from 46 patients with sporadic CJD and from a control group of 42 healthy subjects. The samples were analyzed with tests that were specific for C‐reactive protein (CRP), IL‐6, neuron‐specific enolase (NSE), S‐100 proteins, and cellular prion protein (PrPc). The results were compared, and a cutoff level for each test used was defined as the 90th percentile from the control group.

RESULTS: The assay specific for NSE identified only 13 percent of the sporadic CJD patients as positive. The identification rate of the other markers was significantly higher: S‐100, 76.1 percent; PrPc, 76.1 percent; CRP, 78.3 percent; and IL‐6, 73.3 percent. Only three of the samples were positive in all five tests.

CONCLUSION: The markers for tissue damage, CRP and IL‐6, are as useful as the previously described markers for neuronal damage in the diagnosis of CJD in plasma. All the markers tested are, however, of only limited value in the diagnosis of CJD in plasma. A combination of all surrogate markers improves the specificity but still provides no definitive diagnosis of the disease.
Kinetics of fetal cellular and cell‐free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis
Authors: Ariga Hiromichi , Ohto Hitoshi , Busch Michael P. , Imamura Shinya , Watson Robert , Reed William , Lee Tzong‐Hae
Published: March 2003

BACKGROUND: Fetal genetic material is detectable in the maternal circulation and has been used for noninvasive prenatal diagnosis. However, few data are available concerning its quantity and natural history during gestation.

STUDY DESIGN AND METHODS: This study prospectively characterized the kinetics of cellular and cell‐free fetal DNA in the circulation of 25 healthy women during and after uncomplicated pregnancy. Real‐time kinetic PCR was used to quantitate human Y‐chromosome sequences, and liquid oligomer hybridization with 32P‐labeled probes was used to verify the identity of amplified products.

RESULTS: In all male pregnancies, but no female pregnancies, low‐level fetal Y‐chromosome DNA was detected in both cellular and cell‐free compartments beginning at 7 to 16 weeks but increasing steadily after 24 weeks and reaching a peak at parturition. The fetal DNA decreased rapidly after birth.

CONCLUSION: Fetal genetic material can be detected throughout pregnancy, and its quantity is a function of gestational age and of whether the plasma or cellular compartment is examined. Both the absolute quantity of fetal DNA and its ratio to total DNA (maternal + fetal) are greater in the plasma than in the cellular compartment. Fetal DNA is cleared rapidly from both compartments after parturition, which suggests that turnover is dynamic. Because they provide prospective and quantitative data concerning fetal DNA levels, these observations and kinetic PCR methods may have implications for noninvasive prenatal diagnosis. Further studies will be needed to determine the immunologic implications of fetal‐maternal DNA exchange and cellular microchimerism.
ABO mismatch may affect engraftment in multiple myeloma patients receiving nonmyeloablative conditioning
Authors: Badros Ashraf , Tricot Guido , Toor Amir , Morris Christopher , Guo Chuanfa , Munshi Nikhil , Barlogie Bart , Cottler‐Fox Michele
Published: March 2003

BACKGROUND: Blood group incompatibility does not appear to affect the overall outcome in patients undergoing myeloablative conditioning before allogeneic BMT. Data on ABO‐mismatched transplantation in the nonmyeloablative setting are limited.

STUDY DESIGN AND METHODS: A retrospective analysis of the effects of ABO mismatches in multiple myeloma patients who received a nonmyeloablative conditioning regimen was conducted.

RESULTS: Three of 27 patients received a minor ABO‐mismatched graft, all with evidence of hemolysis before converting to donor ABO group on Days 10, 15, and 6. Six patients received a major ABO‐mismatched graft; of these, three developed GVHD of more than grade 2 and subsequently converted to the ABO blood group of the donor on Days 38, 33, and 43. Of the three patients without GVHD, one rejected the allograft and had autologous reconstitution. One remained a mixed chimera to Day 100 despite three donor lymphocyte infusions, and one developed pure RBC aplasia. None of the ABO‐matched patients rejected the graft, whether they developed GVHD or not. RBC transfusions were significantly higher in the major and minor ABO‐mismatched patients than in the ABO‐matched patients, with medians of 12 units (range, 2‐35), 13 units (range, 5‐18), and 4 units (range, 2‐15), respectively (p = 0.02). ABO‐matched patients had a similar incidence of GVHD, with 5 of 9 ABO‐mismatched patients (56%) having more than grade 2 versus 10 of 18 (56%). Four of 9 ABO‐mismatched patients (44%) were mixed chimeras up to Day 100 versus 2 of 18 ABO‐matched patients (11%), and the difference was significant (p = 0.01).

CONCLUSION: Patients with ABO mismatch had problems with engraftment, including graft rejection, pure RBC aplasia, and mixed‐lineage chimerism. RBC transfusions were significantly higher in the ABO‐mismatched recipients. GVHD may play a role in engraftment, possibly by facilitating the disappearance of native ABO antibodies via graft‐versus‐plasma cell effect. A prospective study to evaluate the effects of ABO mismatch on engraftment in the nonmyeloablative setting is needed.
Kinetics of G–CSF‐induced granulocyte mobilization in healthy subjects: effects of route of administration and addition of dexamethasone
Authors: Stroncek David F. , Matthews Cynthia L. , Follmann Dean , Leitman Susan F.
Published: March 2003

BACKGROUND: Granulocyte donors are frequently given G–CSF with or without dexamethasone approximately 18 hours before apheresis to increase cell yields. The purpose of this study was to assess the kinetics of G–CSF plus dexamethasone neutrophil mobilization to determine whether the neutrophils can be mobilized and collected the same day.

STUDY DESIGN AND METHODS: Sixteen subjects were given four separate mobilization regimens: IV G–CSF (5 μg/kg), subcutaneous G–CSF (5 μg/kg), IV G–CSF (5 μg/kg) plus oral dexamethasone (8 mg), and subcutaneous G–CSF (5 μg/kg) plus oral dexamethasone (8 mg). Blood cell counts were measured before and after G–CSF administration.

RESULTS: Following all four mobilization regimens, neutrophil counts fell 0.5 hour after the mobilizing agents were given, rose above baseline levels at Hour 2, and increased further with each time interval to Hour 8. In the absence of dexamethasone at Hours 2 through 8, there was no difference in neutrophil counts by subcutaneous or IV G–CSF administration routes. The addition of dexamethasone enhanced mobilization of neutrophils from Hours 3 through 24. Through Hour 8, there was no difference in the degree of mobilization among the subcutaneous G–CSF plus dexamethasone and the IV G–CSF plus dexamethasone regimens. However, at Hour 24, neutrophil counts were sustained at higher levels with subcutaneous G–CSF plus dexamethasone than with IV G–CSF plus dexamethasone.

CONCLUSIONS: Granulocyte mobilization response to subcutaneous G–CSF plus dexamethasone is sustained at peak levels for 8 to 24 hours after coadministration of the two drugs. There was no advantage to giving G–CSF intravenously.
Acute nosocomial HCV infection detected by NAT of a regular blood donor
Authors: Larke Bryce , Hu Yu‐Wen , Krajden Mel , Scalia Vito , Byrne Sean K. , Boychuk Lesia R. , Klein Judith
Published: March 2003

BACKGROUND : Routine HCV NAT of blood donors to detect persons in the preseroconversion phase of acute infection was introduced in Canada in October 1999. The source of virus exposure was investigated in the first, and to date only, blood donor found to be HCV NAT positive, anti‐HCV negative in Canada. He was a regular donor with none of the commonly reported risk factors for HCV infection.

STUDY DESIGN AND METHODS : Epidemiologic follow‐up revealed that the blood donor had received antibiotics at an outpatient IV clinic 5 weeks before donation. IV solution bags and tubing for individual patients were stored in the clinic, and then the same equipment was used each time the patient returned for the next dose of antibiotics until it was replaced after every 72‐hour period. Among eight other patients whose clinic visitation times overlapped was a man with chronic HCV infection. Genomic sequencing of HCV isolates from the blood donor, the patient with chronic hepatitis C, and local controls was carried out to study possible nosocomial infection.

RESULTS : Genomic sequencing showed a high degree of relatedness in the hypervariable region of HCV isolates from the blood donor and putative source patient as compared with controls. Detailed molecular analysis of quasispecies of the HCV isolates further indicated that viruses from the two individuals were genetically very close to each other.

CONCLUSION : The introduction of routine screening of blood donors by HCV NAT was directly responsible for the early detection and investigation of an unusual case of HCV infection involving a regular donor. Genomic sequencing studies provided firm evidence of patient‐to‐patient transmission of HCV in an IV clinic. The report clearly demonstrates the value of molecular fingerprinting in tracking nosocomial HCV infections.
Predicting the effect of transfusing only phenotype‐matched RBCs to patients with sickle cell disease: theoretical and practical implications
Authors: Castro Oswaldo , Sandler S. Gerald , Houston‐Yu Patricia , Rana Sohail
Published: March 2003

BACKGROUND : Transfusing only phenotype‐matched RBCs has been recommended to reduce the incidence of alloimmunization to blood group antigens in patients with sickle cell disease (SCD).

STUDY DESIGN AND METHODS : The expected benefit of phenotype matching was determined by identifying which of the existing blood group alloantibodies in patients with SCD who received conventional transfusions would not have been formed if they had received only phenotype‐matched RBCs. By use of each patient's alloantibodies as a baseline, it was possible to identify specific alloantibodies that would not have been formed if each of five different phenotype‐matching protocols had been used.

RESULTS
: During a 12‐year period, 351 patients received transfusions with 8939 units of ABO‐ and D‐matched RBCs. Of these, 102 patients (29.1%) formed at least one blood group alloantibody. An additional 35 patients with SCD with alloantibodies were identified by reviewing clinical records, yielding a total of 137 alloimmunized patients for inclusion in this study. If all transfusions had been selected by limited phenotype matching (C, c, E, e, and K, as well as for ABO and D), all alloantibodies would have been prevented for more than half (53.3%) of the 137 alloimmunized patients. If all transfusions had been matched for C, c, E, e, K, S, Fy
a
, and Jk
b , all antibodies would have been prevented for 70.8 percent of the 137 alloimmunized patients. Approximately 13.6 percent of random white blood donors would be expected to match a limited phenotype‐matching protocol, whereas only 0.6 percent would match an extended phenotype‐matching protocol.

CONCLUSION : Limited phenotype matching would have prevented all alloantibodies in 53.3 percent of the patients who formed alloantibodies. This protocol requires RBCs that are readily available. Extended phenotype matching would have prevented alloimmunization in 70.8 percent of patients who formed alloantibodies. However, this would require phenotypes that are 22.7 times less prevalent among random blood donors and is therefore impractical for a long‐term strategy.
Prolonged in vitro hemolysis of EDTA‐anticoagulated blood after a delayed hemolytic transfusion reaction
Authors: Xenocostas Anargyros , Callum J.L. , Coovadia A.S. , Reis M.D.
Published: March 2003

BACKGROUND : A novel case where in vitro hemolysis was observed in plasma, but not in serum samples, obtained after the onset of a severe delayed hemolytic transfusion reaction is presented.

CASE REPORT : A 54‐year‐old woman received 2 units of blood during an orthopedic procedure. She had received transfusion 30 years earlier, and testing before transfusion revealed no alloantibodies. The patient returned 12 days after the transfusion with a Hb level of 54 g per L due to a severe delayed hemolytic reaction caused by anti‐K. The plasma and serum samples were grossly hemolysed on Day 12. On Day 14, the serum samples showed no evidence of hemolysis; however, the EDTA sample remained grossly hemolysed. This discrepancy was not identified until Day 19. Due to concerns of ongoing apparent severe hemolysis, the patient was unnecessarily treated with IVIG and corticosteroids. The in vitro hemolysis was still present at 75 days, despite complete normalization of her Hb, bilirubin, and LDH levels. The phenomenon had resolved by 125 days.

CONCLUSION : This in vitro artifact has not been previously reported and the mechanism remains unclear. Both plasma and serum samples should be observed for hemolysis when evaluating a patient with a severe delayed hemolytic transfusion reaction.
Severe immune hemolysis after minor ABO‐mismatched allogeneic peripheral blood progenitor cell transplantation occurs more frequently after nonmyeloablative than myeloablative conditioning
Authors: Worel Nina , Greinix Hildegard T. , Keil Felix , Mitterbauer Margit , Lechner Klaus , Fischer Gottfried , Mayr Wolfgang , Höcker Paul , Kalhs Peter
Published: March 2003

BACKGROUND : Hemolysis as a result of donor‐recipient minor ABO mismatching is a complication of allogeneic peripheral blood progenitor cell (PBPC) transplantation (PBPCT). The increased B‐lymphocyte content of PBPC grafts and immunosuppressive regimens without methotrexate (MTX) may increase incidence and severity of this event.

STUDY DESIGN AND METHODS : A total of 93 patients were analyzed after allogeneic PBPCT. In 25 (27%) cases, minor (n = 21) or bidirectional (n = 4) ABO mismatching was present. Of these, 15 patients received myeloablative and 10 received nonmyeloablative conditioning regimens. For GVHD, prophylaxis cyclosporin A (CsA) alone (n = 2) or CsA with MTX (n = 13) was given after myeloablative conditioning and CsA with mycophenolate mofetil (MMF) after nonmyeloablative conditioning (n = 10).

RESULTS : Hemolysis occurred in 4 out of 25 (16%) patients with minor or bidirectional ABO mismatching only. Three patients underwent nonmyeloablative conditioning and were given CsA with MMF, and one patient underwent myeloablative conditioning and was given CsA alone for GVHD prophylaxis. Hemolysis began 7 to 10 days after transplantation, and donor type alloantibodies were detectable concomitantly with recipients type RBCs.

CONCLUSION : Patients receiving minor or bidirectional ABO‐mismatched PBPC grafts and GVHD prophylaxis without MTX are at risk of hemolysis. Prophylactic interventions in patients before minor ABO‐mismatched PBPCT not receiving MTX should be taken into con‐ sideration. Careful monitoring of hemolysis parameters during the first 15 days after PBPCT transplantation is mandatory.
Granulocyte transfusion therapy for infections in candidates and recipients of HPC transplantation: a comparative analysis of feasibility and outcome for community donors versus related donors
Authors: Hübel Kai , Carter Rachel A. , Liles W. Conrad , Dale David C. , Price Thomas H. , Bowden Raleigh A. , Rowley Scott D. , Chauncey Thomas R. , Bensinger William I. , Boeckh Michael
Published: March 2003

BACKGROUND: Feasibility, response to granulocyte transfusion therapy, and clinical outcome were compared among HPC transplant recipients enrolled in a prospective study of a community blood bank‐based unrelated donors program, a prospective granulocyte study using family donors, and matched control patients without granulocyte transfusion therapy.

STUDY DESIGN AND METHODS: Overall, 40 patients (327 collections) received granulocyte concentrates from unrelated donors, 34 patients (219 collections) received granulocyte concentrates from related donors, and 74 patients served as controls. Study entry criteria for patients included an absolute neutrophil count (ANC) of less than 200 per μL and documented invasive fungal or bacterial infections.

RESULTS: There was a median delay of 3 days (range, 0‐14) in patients receiving transfusions from unrelated donors between day of diagnosis of infection and start of granulocyte transfusion therapy as compared with a median delay of 5 days (range, 0‐25) in patients receiving transfusions from related donors (p = 0.01). The ANC increment after the first, second, and seventh transfusions in patients who had community donors was significantly higher or comparable to patients who had family donors. Overall, clinical outcome was comparable between the three patient groups. Kaplan‐Meier analysis revealed no difference between all cohorts in overall 6‐month survival (p = 0.28, log‐rank) or event‐free survival (p = 0.17, log‐rank).

CONCLUSION: These results suggest that future efficacy trials should consider inclusion of unrelated community donors for timely institution of granulocyte transfusion therapy.
Health and economic impact of posttransfusion hepatitis B and cost‐effectiveness analysis of expanded HBV testing protocols of blood donors: a study focused on the European Union
Authors: Pereira Arturo
Published: March 2003

BACKGROUND : Residual risk of posttransfusion hepatitis B (PT‐HB) may be reduced through implementation of HBV NAT or the new, enhanced‐sensitivity HBsAg assays in routine donor testing. However, there are some doubts about the cost‐effectiveness of these new safety measures, because hepatitis B acquired in adulthood is not regarded as a severe disease in western countries.

STUDY DESIGN AND METHODS : A computer model was designed to estimate the health outcomes and associated costs of patients with PT‐HB. Results from this model and estimations of the residual risk of HBV transmission, the risk reduction yielded by the new assays, and their cost were used to calculate the cost‐effectiveness of including the new HBsAg assays or single‐sample HBV NAT in the routine screening of blood donors.

RESULTS : The model predicts that 0.97 percent of patients with PT‐HB die of liver disease (54% of them due to fulminant hepatitis). The mean loss of life expectancy was 0.178 years per patient, and the present value of the lifetime costs of treating PT‐HB was 4160 euros per patient. Single‐donor HBV NAT or the new HBsAg assays would increase the life expectancy of blood recipients by 16 (95% CI, 8‐40) or 14 (95% CI, 7‐28) years, respectively, per every 10 million donations tested. The projected cost per life‐year gained was 0.79 (95% CI, 0.15‐1.85) million euros for the enhanced‐sensitivity HBsAg assays and 5.8 (95% CI, 1.9‐13.1) million euros for single‐donation HBV NAT, both compared with current HBsAg assays. If single‐donation HBV NAT is compared with the new HBsAg assays, its cost‐ effectiveness ratio increases to 53 (95% CI, 16‐127) million euros.

CONCLUSION : PT‐HB has few health or economic repercussions. Single‐donation HBV NAT would provide a small health benefit at a very high cost. Instead, in some circumstances, the cost‐effectiveness of enhanced‐sensitivity HBsAg assays would be within acceptable ranges for new public health interventions.
Heart rate increases linearly in response to acute isovolemic anemia
Authors: Weiskopf Richard B. , Feiner John , Hopf Harriet , Viele Maurene K. , Watson Jessica J. , Lieberman Jeremy , Kelley Scott , Toy Pearl
Published: March 2003

BACKGROUND : The cardiovascular response to acute isovolemic anemia in humans is thought to differ from that of other species. Studies of anesthetized humans have found either no change or a decreased heart rate. A previous study showed that in 32 healthy unmedicated humans, heart rate increased during acute isovolemic anemia. The hypothesis that heart rate in humans increases in response to acute isovolemic anemia and that the increase is affected by gender was tested.

STUDY DESIGN AND METHODS : Acute isovolemic anemia to a Hb concentration of approximately 5 g per dL in 95 unmedicated healthy humans was produced by simultaneous withdrawal of blood and IV replacement with 5‐percent HSA and autologous platelet‐rich plasma. The relationship between heart rate and Hb concentration was examined using a mixed‐effects linear regression model that allowed each person to have a fitted line with its own slope and intercept. Cubic and quadratic terms were added to determine if these improved the goodness of fit. The effect of gender was tested by including it and its interactions with Hb in the mixed model.

RESULTS : The relationship between heart rate and Hb concentration was linear (p < 0.001) and consistent among the population studied: heart rate = 116.0‐4.0 [Hb] (slope 95% CI: –4.2 to –3.8 beats/min/g Hb). Adding a cubic or quadratic term did not significantly improve the goodness of fit of the mathematical expression to the data, confirming the linear nature of the relationship between heart rate and Hb concentration. For women, the slope of the heart rate response was significantly greater than it was for males (difference ± SE: 0.70 ± 0.23, p < 0.005).

CONCLUSION : In 95 unmedicated, healthy humans, heart rate was a linear function of Hb during acute isovolemic anemia. Females had a significantly greater slope of increase in heart rate with decreasing Hb concentration than did males. The relationship is consistent among individuals, is similar to that reported for conscious dogs, and differs from that found previously in anesthetized humans.
The Full Hempel
Authors: Roth Paul A.
Published: March 2003

Book reviewed in this article:

The Logic of Historical Explanation by Clayton Roberts
Human Agency and Impersonal Determinants in Historical Causation: A Response to David Lindenfeld
Authors: Turner, Jr. Henry Ashby
Published: March 2003

Lindenfeld's proposed reclassification of causes—offered in lieu of a chaos theory applicable to history—yields paradoxical results when applied to the developments that installed Hitler in power, since these would have to rank as “constraining” rather than “empowering” because of his lack of control over them. The “principle of sensitive dependence,” while an admirable aspiration, proves a counsel of perfection beyond reach of the historian when applied to those same events. As to historical explanations in terms of structural, impersonal determinants, these remain ascendant, to the neglect of human agency. Narrative history, which alone can account for both remote and immediate causes, continues to be unfashionable. Explanations in terms of structures and impersonal forces, which can only imply causation, are attractive because they offer historians wide scope for exercise of erudition and arrive at determinants that appear larger and more powerful than mere actions of humans. Where profound developments are to be explained, such interpretations conform to the assumption that their causes must have been profound. Yet countless turning‐points in history, including Hitler's installation in power, were decisively shaped by acts of a few persons. The frustrating difficulty of accounting for individual behavior contributes to the appeal of impersonal, structural explanations. These tend, however, toward a deterministic view of the past which awakens the impression that what happened had to happen. That obscures the openness of past situations and rules out assignment of personal responsibility to individuals, who seem mere pawns of forces beyond their control. A remedy for such deterministic tendencies lies in counterfactual analysis, which, by drawing attention to feasible, but unrealized, alternatives to what happened, can convey the open‐ended qualities of past situations and the importance of contingency.
History and Other Times
Authors: Carr David
Published: March 2003

Book reviewed in this article:

Other Times: Philosophical Perspectives on Past, Present and Future, by David Cockburn
Does Culture Evolve?
Authors: Fracchia Joseph , Lewontin R. C.
Published: March 2003

The drive to describe cultural history as an evolutionary process has two sources. One from within social theory is part of the impetus to convert social studies into “social sciences” providing them with the status accorded to the natural sciences. The other comes from within biology and biological anthropology in the belief that the theory of evolution must be universal in its application to all functions of all living organisms. The social‐‐scientific theory of cultura evolution is pre‐Darwinian, employing a developmental model of unfolding characterized by intrinsic directionality, by definable stages that succeed each other, and by some criterion of progress. It is arbitrary in its definitions of progress, and has had the political problem that a diachronic claim of cultural progress implies a synchronic differential valuation of present‐day cultures. The biological scheme creates an isomorphism between the Darwinian mechanism of evolution and cultural history, postulating rules of cultural “mutation,” cultural inheritance and some mechanism of natural selection among cultural alternatives. It uses simplistic ad hoc notions of individual acculturation and of the differential survival and reproduction of cultural elements. It is unclear what useful work is done by substituting the metaphor of evolution for history.
A Good Try t Organizing World History Environmentally
Authors: Crosby Alfred W.
Published: March 2003

Books reviewed in this article:

Felipe Fernández‐Armesto, Civilizations: Culture, Ambition, and the Transformation of Nature
Introduction: Danto and His Critics: After the End of Art and Art History
Authors: Carrier David
Published: March 2003

In Bielefeld, Germany in April, 1997 an author conference was devoted to Arthur C. Danto's 1995 Mellon Lectures After the End of Art: Contemporary Art and the Pale of History (Princeton,1997). This essay provides an introduction to seven essays given at that conference and expanded for this Theme Issue of History and Theory. Danto presented his view of the nature of art in The Transfiguration of the Commonplace(1981). He then added in the Mellon lectures a sociological perspective on the current situation of the visual arts, and an Hegelian historiography. The history of art has ended, Danto claims, and we now live in a posthistorical era. Since in his well‐known book on historiography, Analytical Philosophy of History (1965), Danto is unsympathetic to Hegel's speculative ways of thinking about history, his adaptation of this Hegelian framework is surprising. Danto's strategy in After the End of Art is best understood by grasping the way in which he transformed the purely philosophical account of The Transfiguration into a historical account. Recognizing that his philosophical analysis provided a good way of explaining the development of art in the modern period, Danto radically changed the context of his argument. In this process, he opened up discussion of some serious but as yet unanswered questions about his original thesis, and about the plausibility of Hegel's claim that the history of art has ended.

Hegel . . . did not declare that modern art had ended or would disintegrate. . . . his attitude towards future art was optimistic, not pessimistic. . . . According to his dialectic . . . art . . . has no end but will evolve forever with time.
Can a Wrongful Discharge Statute Really Benefit Employers?
Authors: Abraham Steven E.
Published: March 2003

Overall, there is overwhelming empirical support for the hypothesis that the Wrongful Discharge From Employment Act benefited employers in Montana. Shareholder returns were significantly higher given the Act than they would have been absent the law. This reflects shareholders' estimate of the effects of the Act on the future profitability of their firms. The increase in profitability would have been due to the benefits the Act gave to employers in Montana.
Workplace Transformation and Worker Upskilling: The Perspective of Individual Workers
Authors: Leigh Duane E. , Gifford Kirk D.
Published: March 2003

How common is workplace transformation in the American economy? What are its implications for work force skill requirements and training investments? The existing literature addressing these questions is based on firm‐reported survey data. Using new data available in the 1993 wave of the National Longitudinal Survey of Youth (NLSY), this article examines the same questions from the perspective of individual workers. Our empirical results suggest that workplace transformation is commonplace. Fully 40 percent of private‐sector workers surveyed report that in the space of just one year, a change occurred at work that required them to learn new job skills. About 23 percent of all respondents reported experiencing a workplace change we term anorganizational transformation. Incidence of formal training is positively related to indicators of organizational transformation, but the effect of these indicators is found to be sensitive to the inclusion of other important workplace change variables (namely, new products, new equipment, and new government regulations). While we expected to find strong positive relationships with product development and physical capital investment, government regulation has a surprisingly large impact on formal training.