bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitating Donor Behaviour to Model the Effect of Changes in Donor Management on Sufficiency in the Blood Service
Authors: Whyte Gordon
Published: December 2004

Background and Objective:
To describe donor behaviour quantitatively and apply the information on actual donations derived during observed changes in blood collection in Melbourne between July 1990 and June 1996 to construct a logical model to examine the effects of changes in donor management on the sufficiency of the blood supply. Method: Computerised donation data files were searched to determine time to next or previous donation for donors giving blood between 1990 and 1996 stratified by age, donation history and venue. Actual numbers of whole blood donation given by new and repeat donors, July 1990 to June 1996, and numbers of donors refused were used to construct and test a logical predictive model. Results: 558,682 donation intervals were analysed. Donor return rates at 2 years were shown to increase with donor donation history and donor age. The prediction model showed that a 25% decline in whole blood collections over 2 years could be explained by the cumulative effect of a decrease in donor return rates of 2–4%. Between 1990 and 1996 many donors moved from static city collection sites to suburban mobiles. New donor attendance correlated with repeat donor attendance. Donor complaints correlated with donor deferral numbers. Conclusions: The model showed that large shifts in nett blood collections can be explained by relatively small shifts in donor return rates at 2 years.
Effect of Heat on Stored Red Cells during Non‐Flow Conditions in a Blood‐Warming Device
Authors: Eastlund Ted , Van Duren Albert , Clay Mary E.
Published: December 2004

Background and Objectives:
While blood is flowing within a transfusion‐warming device, the blood temperature is usually less than that applied externally. If the flow is temporarily stopped, the temperature can rise above 37°C in some warming devices. We sought to determine whether temperatures near 45°C achieved during prolonged non‐flow conditions in a blood warmer are harmful to red cell integrity. Materials and Methods: After 42 days of storage at 4°C, red cells were exposed to 44.7°C for 30 min while stationary in a blood warming device (Augustine Medical, Inc., 241 Fluid Warming Set) and examined for cell counts, hemolysis and osmotic fragility. Results: Red cell, white cell and platelet counts, hemoglobin, PCV and potassium were unchanged following heat treatment. Plasma hemoglobin was 508±132 mg/dl following heat treatment compared to 396±188 for the control (p>0.05). In the osmotic fragility test, hemolysis remained within normal limits when tested at 0.60 and 0.65% sodium chloride (NaCl) and was unchanged at the 0.5% NaCl level. At the 0.75% NaCl level, there was 16±5.1% hemolysis of heated 42‐day‐old red cells compared to 11±3.4% for the control (both of which being above the 9% upper limit for fresh control red cells). Conclusions: We conclude that elevated temperatures achieved during temporary cessation of flow in the Augustine Medical, Inc., 241 Fluid Warming Set for as long as 30 min do not cause notable hemolysis or other damage to red cells.
Reduction of Platelet Transfusion Associated Sepsis by Short‐Term Bacterial Culture
Authors: Liu Hing‐wing , Yuen Kwok‐yung , Cheng Tammy Shui‐ying , Lee Kwan‐bun , Chua Elizabeth Kin‐ming , Ho Pak‐leung , Lin Che‐kit
Published: December 2004

Background and Objectives:
There is as yet no suitable routine laboratory test for a blood transfusion service to detect bacterial contamination in platelets. This study evaluates the effectiveness and the applicability of short‐term bacterial culture for such a purpose. Materials and Methods: Samples from 5‐unit platelet pools were inoculated into an aerobic culture bottle, then monitored for 48 h at 35°C in an automated monitoring and detection system. Results: 26,210 whole‐blood‐derived platelet components were tested, of which 14 (0.053%) platelet units were found to be contaminated. In addition, nine of the associated red cell units and 4 fresh‐frozen plasma units grew the same organisms on culture. Conclusion: Short‐duration bacterial culture by an automated system is effective and suitable for routine screening in a regional transfusion center.
Transfusion‐Associated Hepatitis in a Tertiary Referral Hospital in India
Authors: Saxena R. , Thakur V. , Sood B. , Guptan R.C. , Gururaja S. , Sarin S.K.
Published: December 2004

Background and Objectives:
In Indian blood banks, screening for hepatitis B virus (HBV) is currently done by the EIA method, but no routine screening is done for hepatitis C virus (HCV). Materials and Methods: To determine the incidence of transfusion‐associated HCV hepatitis, and of any residual transfusion‐associated hepatitis (TAH) after HBsAg screening, we prospectively studied 182 patients who underwent surgery and received blood transfusion. These recipients had normal alanine aminotransferase (ALT) and were negative for HBsAg (monoclonal EIA), and anti‐HCV (third‐generation EIA) before receiving transfusion. Results: Of the 818 blood units transfused after routine screening (average 4.49±3.3 U/patient, range 1–14), 14 (1.7% of units) were found to be infected. Of the 182 recipients, 14 (7.69%) developed TAH during a follow‐up of 6 months, 3 (21.4%) from HBV, 10 (71.5%) from HCV, and 1 (1.7%) from a coinfection of HBV and HCV. All patients with TAH due to HCV were asymptomatic. One patient with TAH due to HBV (33%) and 5 with TAH due to HCV (50%) developed chronic infection with persistently elevated ALT at 6 months. Conclusions: With the current screening practices, the incidence of TAH remains high in India and is mainly due to HCV infection. Furthermore, the screening methods for HBV also need to be improved.
HPA Genotyping by PCR‐SSP: Report of 4 Exercises
Authors: Metcalfe P. , Cavanagh G. , Hurd C. , Ouwehand W.H.
Published: December 2004

Background and Objectives:
Polymerase chain reaction with sequence specific primers (PCR‐SSP) is widely used for the determination of the alleles encoding the human platelet antigens (HPA)‐1 to 5. In order to evaluate and improve performance with this technique, four exercises were organised during 1996‐1998. Materials and Methods: Coded DNA samples were distributed from the National Institute for Biological Standards and Control (NIBSC) as follows: exercise one, 18 samples; two, 12 samples; three, 6 samples, and four, 4 samples. Results: Performance improved over the four exercises following the adoption of a consensus protocol and the re‐design of one primer. The percentage of incorrect results in each exercise was as follows: exercise one, 9%; two 3.2%, three, 0.8%, and four, 0.3% Conclusion: The modified PCR‐SSP protocol is a reliable method for genotyping HPA‐1 to 5 in reference laboratories. DNA‐based HPA genotyping has an important role in platelet immunology and further exercises will be included in the bi‐annual platelet immunology exercises organised by NIBSC.
Application of a Time‐Resolved Fluoroimmunoassay for the Analysis of Normal Prion Protein in Human Blood and Its Components
Authors: MacGregor Ian , Hope James , Barnard Geoff , Kirby Louise , Drummond Olive , Pepper Duncan , Hornsey Valerie , Barclay Robin , Bessos Hagop , Turner Marc , Prowse Christopher
Published: December 2004

Background and Objectives:
To quantify the cellular isoform of prion protein (PrPc) in human blood using a new time‐resolved dissociation‐enhanced fluoroimmunoas‐say (DELFIA®). Materials and Methods: The DELFIA was optimised for human blood samples and applied to isolated cell and plasma fractions from blood donations. The physicochemical properties of PrPc were analysed. Results: 26.5% of blood PrPc was associated with the platelet fraction, 0.8% with polymorphonuclear leucocytes, 2.4% with mononuclear leucocytes, 1.8% with red cells and 68.5% with plasma (mean values from 4 processed donations). Conclusion: The majority of blood PrPc is found in the platelet and plasma compartments.
A New Method for Phenotyping Red Blood Cells Using Microplates
Authors: Llopis F. , Carbonell‐Uberos F. , Montero M.C. , Bonanad S. , Planelles M.D. , Plasencia I. , Riol C. , Planells T. , Carrillo C. , De Miguel A.
Published: December 2004

Background and Objectives:
The supply of phenotyped red blood cells (RBC) for patients with several RBC antibodies presents a difficult task to hospital blood banks and regional blood centers. The aim of this study was to establish a low‐cost typing system to allow extensive phenotyping of regular blood donors for clinically significant RBC antigens. Materials and Methods: We developed a new buffer that greatly intensifies the antigen‐antibody reaction and thus reduces the quantity of serum needed for phenotyping. The procedure was carried out on microplates. Results: A total of 20,435 regular blood donors have been typed to date. For 752 units required for transfusion, 3,584 phenotyping tests were performed, validating the results by tube or gel typing methods; agreement was achieved in all cases. Conclusion: This technique seems adequate for phenotyping a large number of RBC units at very low cost, thus facilitating the availability of phenotyped blood.
The Direct Antiglobulin Test: Still a Place for the Tube Technique?
Authors: Tissot Jean‐Daniel , Kiener Cèline , Burnand Bernard , Schneider Philippe
Published: December 2004

Objectives:
Antibodies of different immunoglobulin isotypes, or complement, may coat red blood cells in vivo. They are detected by the direct antiglobulin test (DAT), usually performed by the conventional tube technique. The purpose of this study was to compare the latter technique with the gel test. Methods: Three hundred and ninety‐eight consecutive samples, sent to our laboratory for direct antiglobulin testing, were analyzed with the tube technique and the gel test, using reagents from different manufacturers. Eighty‐seven samples had been collected from newborns and 23 from fetuses. Results were expressed as positive or negative. Results: In 162 out of 398 cases, the DAT was negative with both methods, whereas in 178 out of 398 cases, the DAT was positive with both techniques using polyspecific antibodies (observed agreement: 84.5%; x = 0.71). Discrepancies between the two methods were observed in 58 cases: 51 samples appeared as DAT positive using the tube method and negative with the gel test, whereas only 7 were positive exclusively with the gel test. Among the 178 samples that were positive with both techniques, 93 samples showed discordant results when evaluated with anti‐lgG and 82 with anti‐C3d, respectively). The sensitivity of the DAT performed by the gel test, in comparison with the conventional tube technique, was 75.4% (95% confidence interval (CI):69.4–80.8).96.8% (95% CI:92.8–99.0), and 16.3% (95% CI: 9.8–24.9) with polyspecific, anti‐IgG and anti‐Cd3 reagents, respectively. Conclusions: The gel test appeared to be less sensitive than the conventional tube technique when utilized for DAT, particularly when C3d was present on red blood cells. These results emphasize that before implementing a new technique in the laboratory, comparison with existing techniques, using different reagents, is mandatory.
Retention of Coagulation Factors in Plasma Frozen after Extended Holding at 1–6°C
Authors: Smith Janis F. , Ness Paul M. , Moroff Gary , Luban Naomi L.C.
Published: December 2004

Background and Objectives:
The ability to use plasma, isolated form units of whole blood and frozen within 24 h of phlebotomy, as a substitute for plasma forzen within 8 h of phlebotomy would have several advantages for blood centers. It should provide increased flexibility pertaining to the freezing of plasma for clinical use. We have conducted studies to assess the influence of an extended holding time for separated plasma, prior to freezing, on the retention of coagulation factor activity. Study Design and Methods: Freshly harvested plasma from each of 10 units of CPD‐whole blood was divided into four equal aliquots. These aliquots were held in plastic packs at 1–6°C for a total of 0, 8,15 and 24 h. Susequently, the plasma aliquots were forzen rapidly and stored at −20°C for 4 months. The thawed plasma was tested for coagulant factors V and IX, factor VIII coagulant activity (factor VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin cofacotor of von Willebrand factor. Results: The levels of factor V, factor vWF: Ag, factor IX and ristocetin cofactor were not influenced by holding the plasma for up to 24 h prior to freezing. Factor VIII:C activity was reduced with extended holding at 1–6°C; the percentage at time zero activity was 75.9±2.4% for samples forzen immediately after a 24‐hour period. Conclusions: The data indicate that coagulation factor properties of harvested plasma are retained except for factor VIII for at least 24 h prior to freezing.
Evans Antigen: A New Hybrid Structure Occurring on Background of D·· and D–– Rh Complexes
Authors: Cheng G.‐J. , Chen Y. , Reid M.E. , Huang C.‐H.
Published: December 2004

Background and Objectives:
Previously, the Evans antigen (RH37) of the Rh blood group system was shown to be specified by a novel CE‐D‐CE hybrid gene. We studied further the heterogeneity of Evans and report here its new molecular type resulting from a novel intraexon fusion event on the background of D·· and D— complexes. Materials and Methods: A white family with 2 Evans+ and 2 Evans‐ members was analyzed by serological methods and molecular techniques. Results: The Evans+ proband (JD) typed D+C−c−E−e− and showed a partial loss of RHCE but an increased dose of RHD on DNA blots. On sequencing of Rh cDNAs, a normal D and 3 hybrid transcripts were detected. The D‐CE hybrid is characterized by a single breakpoint located in exon 6. The CE‐D hybrid derived its exon 1 (or 1 and 2) from RHCE and exons 2–10 (or 3–10) from RHD. The CE‐D‐CE hybrid had its internal exons 2–7 (or 3–7) from RHD. Family studies showed that the D‐CE and CE‐D hybrids were linked and cotransmitted from JD to his son, whereas RHD and CE‐D‐CE hyrbid were transmitted from JD to his daughter. Conclusion: In this family, Evans is specified by the novel D‐CE intraexon fusion gene which occurs in cis to CE‐D and trans to CE‐D‐CE interexon fusion genes. The observed large duplication of RHD reflects a convergent mosaicism underlying the enhancement of D and ablation of CcEe antigens.
Effects of Handling and Storage of Blood on the Stability of Hepatitis C Virus RNA: Implications for NAT Testing in Transfusion Practice
Authors: Grant P.R. , Kitchen A. , Barbara J.A.J. , Hewitt P. , Sims C.M. , Garson J.A. , Tedder R.S.
Published: December 2004

Background and Objectives:
To determine the stability of hepatitis C virus (HCV) RNA during transport and storage of blood samples from donors, prior to screening for HCV by nucleic acid amplification technology. Materials and Methods: Various blood and plasma sample types were stored for up to 120 h at different temperatures and the HCV RNA level was measured using an in house quantitative reverse transcription‐polymerase chain reaction. Results: No decline in HCV RNA level was observed after 72 h of storage of whole bood at 4°C in EDTA tubes (Greiner) and Plasma Preparation Tubes (PPT; Becton Dickinson), while insignificant declines of 0.2 log10 and 0.25 log10 occurred at 25°C after 72 h in the EDTA tubes and PPT tubes, respectively. When whole blood was stored with mixed anticoagulants CPDA‐1 and EDTA for up to 120 h, no decline in HCV RNA level was observed at 4°C and 25°C, while a significant decline of 0.37 log10 occurred at 37°C after 120 h. The temperature during transportation was investigated with a 12‐hour period at 25°C and 37°C before storage at 4°C for 108 h. Neither temperature resulted in any loss of HCV RNA in comparison with 120 h of storage at 4°C. Conclusion: Whole blood anticoagulated with EDTA or CPDA‐1/EDTA may be stored at up to 25°C (room temperature) for up to 5 days without any significant loss in plasma HCV RNA level.
Results of Viral Marker Screening of Unpaid Blood Donations and Probability of Window Period Donations in 1997
Authors: Müller‐Breitkreutz K.
Published: December 2004

Background and Objectives:
To monitor the safety of the blood supply and evaluate the potential benefits of additional measures, the likelihood of virus transmission must be assessed. The European Plasma Fractionation Association and its member organisations have therefore developed a surveillance system to monitor infection markers among unpaid blood and plasma donors. We report and analyse the results of this surveillance for 1997. Materials and Methods: Data from the screening of unpaid donations for anti‐HIV, anti‐HCV and HBsAg during 1997 were collected retrospectively by EPFA member organisations. We identified serocon verters and estimate the probability of window period donations. Results: Data included screening results from 11 million unpaid donations in Europe, the USA and Australia. Prevalence of viral markers varied, with marker rates from repeat donations in Europe and Australia being significantly lower than in the USA. For first time donations, in contrast, prevalence of HBsAg in the USA was within the ranges of those measured in Europe and Australia. Screening data of about 5 million European and 0.5 million Australian repeat donations were used to identify seroconverters. From the seroconverters that were detected among the European organisations, we estimated that 1 in every 2,323,778 repeat donations (range: 707,090–20,922,520) was made during the window period of anti‐HIV screening. One in 620,754 (201,216–2,316,805) and 1 in 398,499 (155,209 to >1,088,511) repeat donations were made during the anti‐HCV or HBsAg window period, respectively. Probabilities of window period donations in Australia were within the ranges of those measured in Europe. Conclusions: The collated surveillance data of 1997 illustrate the high degree of safety in blood and plasma products from unpaid donors.
Are All Leucodepleted Platelet Concentrates Equivalent?
Authors: Krailadsiri P. , Seghatchian J.
Published: December 2004

Background and Objectives:
A number of technologies are available for the production of leucocyte‐depleted platelet concentrates (PCs). This study compared the characteristics of PCs prepared by three commonly used techniques. Materials and Methods: In total, fifteen units of leucoyte‐depleted PCs prepared by the Cobe LRS Turbo apheresis system, Haemonetics MCS+ with in‐line filter and filtration of PCs derived from pooled buffy coats (BCs) were transferred into the same standard container. Markers to assess status/activation and microvesiculation of platelets as well as platelet injury were measured. Results: pH was well maintained in all types of PCs. The expression of CD62P was higher in Cobe LRS Turbo on day 1 but became equivalent between the three methods on day 5. A significant correlation was found between the expression of CD62P on platelet surface and soluble CD62P in the plasma. The degree of phosphatidylserine (PS) exposure was slightly higher in Cobe LRS Turbo and BC‐PCs than Haemonetics MCS+ on day 1. However, on day 5 both apheresis PC values were higher than BC‐PCs. A significant correlation was found between PS exposure and microvesiculation. Conclusion: Leucodepleted PCs prepared by the three methods were different in terms of storage lesion and microvesiculation. The clinical significance of these findings remains to be investigated.
Press Review
Authors: Regan F.A.M. , Hewitt P. , Barbara J.A.J. , Contreras M. ,   TTI Study Group
Published: December 2004

Prospective Investigation of Transfusion‐Transmitted Infection in Recipients of over 20,000 Units of Blood
Increase in Glycocalicin Levels in Platelet Concentrates Stored in Plasma or Synthetic Medium for 8 Days: Comparison with Other Platelet Activation Markers
Authors: Kostelijk E.H. , Folman C.C. , Gouwerok C.W.N. , Kramer C.M. , Verhoeven A.J. , de Korte D.
Published: December 2004

Background and Objectives:
Glycocalicin (GC) is a proteolytic fragment of Gplb and can conveniently be measured in supernatants of platelet concentrates (PCs) by means of a sandwich ELISA. Because of the convenience of the assay and easy sample storage, we tested its suitability as a sensitive platelet activation parameter during PC storage. Material and Methods: Filtered PCs in plasma or additive solution were made from 5 pooled buffy coats and were subsequently stored during 8 days at 22±2°C. Correlation coefficients (r) were calculated after comparison of GC levels with platelet parameters. Results: A significant increase in GC concentration was found on all subsequent sampling days. PC stored in plasma showed GC levels that correlated well with the soluble P‐selectin levels (r = 0.7506), P‐selectin (CD62P) expression on platelet membranes (r = 0.8843), morphology scores according to Kunicki (r =−0.7102), lactate concentrations (r = 0.9216), glucose concentrations (r =−0.8913) and β‐thromboglobulin (β‐TG) concentrations (r = 0.8913). In PCs stored in additive solution, the correlation coefficients with these markers were 0.9209 with soluble P‐selectin, 0.7161 with CD62P expression, −0.7474 with morphology score, −0.8908 with glucose concentrations, 0.8923 with lactate concentrations and 0.8908 with β‐TG concentrations. Conclusions: The GC concentration correlates well with sensitive platelet (activation) parameters, rendering it a sensitive and convenient parameter for platelet activation.
Erythrocytapheresis with Recombinant Human Erythropoietin in Hereditary Hemochromatosis Therapy: A New Alternative
Authors: Kohan Abraham , Niborski Ricardo , Daruich Jorge , Rey Jorge , Bastos Fabiana , Amerise Graciela , Herrera Roberto , García Marcelo , Olivera Walter , Santarelli María Teresa , Avalos Julio Sánchez , Findor Jorge
Published: December 2004

Background and Objectives
: The purposes of this study were to evaluate the tolerance, efficacy and safety of isovolemic erythrocytapheresis (EA) in nonanemic patients with hereditery hemochromatosis (HH), and to assess the usefulness of recombinant human erythropoitein (rHuEPO) associated with EA to reduce treatment duration. Materials and Methods: In 10 asymptomatic patients with serum ferritin >400 μ/l, transferrin satuaration >50%, and GPT elevation, EA with rHuEPO and folic acid was performed. Results: Red Cell indices, serum ferritin, and other iron metabolism parameters (serum iron, transferrin, and transferrin satuaration)l; GPT and other laboratory data were considerably improved. Conclusion: This method offers better results in less time than traditional phlebotomy. EA with rHuEPO is an effective therapeutic alternative for patients with HH.
PCR Detects HCV RNA in a Plasma Pool Contaminated by a Single Preseroconversion Donation of Genotype 5a
Authors: Thomas I. , Branckaert T. , Mathys E. , Vranckx R. , Laub R.
Published: December 2004

Background and Objectives:
To determine the prevalence of HCV‐RNA‐positive plasma pools in Belgium, to validate our PCR method and to increase the safety of the released blood products. Materials and Methods: Plasma pools consisting each of about 5,000 donations from Belgian unpaid volunteer blood donors were analysed by PCR for the presence of HCV RNA. Two different extraction methods were compared and validated. Results: Two out of 367 plasma pools were found to be HCV RNA postive and were discarded. For one of these two pools, the look‐back procedure identified an anti‐HCV‐ negative contaminated donation. The HCV genotype of both the contaminated pool and the donation was 5a, a genotype rare in Europe. The viral load of the preseroconverted donation was 2.9 × 107 gEq/ml according to the bDNA method. Conclusion: In the case of plasma derivatives, various important steps are already included to increase safety. Nucleic acid testing of manufacturing plasma pools ensures that viral load in the starting material is as low as possible.
Press Review
Authors: Engelfriet C.P. , Garner S.F. , Smethurst P.A. , Merieux Y.
Published: December 2004

A Rapid One‐Stage Whole Blood HPA‐1a Phenotyping Assay Using a Recombinant Monoclonal lgG1 Anti‐HPA‐1a
Long‐Term Hematopoietic Engraftment after Autologous Peripheral Blood Progenitor Cell Transplantation in Pediatric Patients: Effect of the CD34+ Cell Dose
Authors: Diaz Miguel Angel , Vicent Marta G. , Garcia‐Sanchez Felix , Vicario Jose Luis , Madero Luis
Published: December 2004

Abstract
Background and Objectives:
We analyzed the relationship between long‐term hematopoietic recovery and the number of CD34+ cells infused in order to determine the optimal dose of CD34+ cells for rapid and stable engraftment. Patients and Methods: Between November 1993 and December 1998, 96 consecutive autologous transplantations were performed in 92 pediatric patients with different malignancies. Peripheral blood progenitor cells (PBPC) were mobilized by G‐CSF alone (12 μg/kg/day s.c., Neupogen®, Amgen, Thousand Oaks, Calif., USA) and collected using a Cobe Spectra blood cell separator (Cobe, Denver, Colo., USA) through a central venous catheter with double lumen. The CD34+ cell contents of apheresis products were assessed by means of flowcytometric analysis using an Epics Elite flow cytometer (Coulter, USA). Results: The median number of CD34+ cells infused was 3.2 × 106/kg (range 0.17‐44.4). The median times for short‐term engraftment (neutrophil count >0.5 × 109/1 and platelet count >20 × 109/1) was 9 (range: 7–16) and 13 days (range: 7–91), respectively. The median times for long‐term engraftment (platelet count>50 × 109/1 and >100 × 109/1) was 21 (range: 10–249) and 45 days (range: 12–288). When the infused CD34+ cell dose was ≥5 × 106/kg (median 7.99, range 5.01–44.4), there was a statistically significant increase in the rate of short‐ and long‐term hematopoietic recovery compared to patients transplanted with a lower number of CD34+ cells (p < 0.0001). The earlier recovery in the high CD34+ cell group resulted in less transfusional support, fewer days on intravenous antibiotics and shorter hospitalization. Conclusions: This study confirms that G‐CSF‐mobilized PBPC provide rapid short‐and long‐term hematopoietic engraftment in pediatric patients undergoing autologous transplantation if a CD34+ cell dose ≥5.0 × 106/kg is infused. As this PBPC dose seems to have clinical and potentially economic implications, it should be considered the optimal dose for apheresis.
Evaluation of Solvent/Detergent‐Treated Plasma in Patients with a Prolonged Prothrombin Time
Authors: Lerner R.G. , Nelson J. , Sorcia E. , Grima K. , Kancherla R.R. , Zarou‐Naimo C.M. , Pehta J.C.
Published: December 2004

Abstract
Objectives:
To compare the laboratory and clinical out‐come of patients who received solvent/detergent‐treated plasma (SDP) and fresh‐frozen plasma (FFP). Methods: A randomized, double‐blinded study to assess the ability of SDP and FFP to reduce a prolonged prothrombin time (PT to ≤ 15 s in patients with acquired coagulation deficits. Results: 45 patients (22 SDP vs. 23 FFP) were treated with 71 infusions. There were no significant differences in mean dose of plasma infused (7.8 ml/kg for SDP vs. 8.0 ml/kg for FFP, p = 0.46), percentage of patients who corrected their PT to ≤ 15 s (32% for SDP vs. 26% for FFP, p = 0.67), or percentage of patients whose bleeding ceased (27% for SDP vs. 22% for FFP). Conclusion: No clinical or statistically significant differences were observed after infusion with SDP or FFP in patients with acquired coagulation deficits.
Press Review
Authors: Engelfriet C.P. , Beck K.H. , Mertelmans Y. , Kretschmer V.
Published: December 2004

Comparison of Solvent/Detergent‐Inactivated Plasma and Fresh Frozen Plasma under Routine Clinical Conditions
Red Blood Cell Function and Blood Storage
Authors: Hamasaki Naotaka , Yamamoto Masaaki
Published: December 2004

Red blood cells are ideal vehicles for delivering oxygen to tissues, but their functions deteriorate during liquid preservation. In this article, we review the role of red blood cells in oxygen delivery and methods to evaluate the effectiveness of red blood cell transfusion. Quantitative estimation of transfusion effects could avoid unnecessary transfusion and reduce the risk of transfusion‐associated disorders. We also describe the benefits of transfusion of red blood cells having a higher oxygen‐delivering capacity. Phosphoenolpyruvate is a promising component to prepare red blood cells having a higher oxygen‐delivering capacity.
TT Virus Infection in Screened Taiwanese Blood Donors
Authors: Ho T.‐F. , Yang S.‐C. , Huang Y.‐T. , Hsieh M.‐H.
Published: December 2004

Objective:
TT virus (TTV) is a newly discovered human DNA virus of uncertain clinical significance. The aim of this study was to determine the prevalence of TTV infection among blood donors in Taiwan. Methods: Viral DNA was studied in 224 healthy blood donors and 118 deferred donors. DNA was extracted from plasma and amplified by seminested polymerase chain reaction with reported primer sets from a conserved region of the TTV genome. Results: The prevalence of TTV DNA in the deferred donors was 24.6%, significantly higher than in the healthy donors (11.9%). TTV was also more prevalent in those with hepatitis B surface antigen than in those without it (p = 0.002). Conclusion: In comparing normal with deferred Taiwanese blood donors, hepatitis B virus infection is linked to a higher prevalence of TTV infection.
Pharmacokinetics of total immunoglobulin G and immunoglobulin G subclasses in patients undergoing replacement therapy for primary immunodeficiency syndromes
Authors: Alyanakian M.‐A. , Bernatowska E. , Scherrmann J.‐M. , Aucouturier P. , Poplavsky J.‐L.
Published: December 2004

Background and Objectives Careful evaluation of the pharmacokinetic properties of a new immunoglobulin G (IgG) preparation is necessary to ensure that the product will not deviate significantly from existing products, in terms of pharmacological activity.

Materials and Methods A prospective, open and uncontrolled trial was performed in 16 patients with primary immunodeficiency syndromes. Patients who had been under replacement therapy with licensed preparations prior to study inclusion, received 280 ± 60 mg/kg of a solution of IgG, ready for intravenous administration, every 3 weeks for 6 months. Trough and peak plasma levels were measured immediately before and 1 h after each infusion, respectively. Pharmacokinetic parameters were calculated for total IgG and IgG subclasses.

Results Total IgG, IgG1, IgG2 and IgG3 declined mono‐exponentially in contrast to IgG4 which showed a bi‐exponential decline. Half‐lives which were highly variable among patients were similar for total IgG, IgG1 and IgG2 (35.9  10.8, 36.3  9.2, and 37.1  13.9 days, respectively) and shorter for IgG3 and IgG4 (28.6  10.4 and 15.6  4.5 days, respectively).

Conclusions The decline of IgG4 probably reflected a complex catabolic pathway specific for this subclass. As the plasma level of IgG4 is low, the decline of total IgG remained unaffected. Pharmacokinetic properties were consistent with results reported elsewhere in patients undergoing replacement therapy for primary immunodeficiency syndromes.
Pharmacokinetics and tolerability of a new intravenous immunoglobulin preparation, IGIV‐C, 10% (Gamunex™, 10%)
Authors: Ballow M. , Berger M. , Bonilla F. A. , Buckley R. H. , Cunningham‐Rundles C. H. , Fireman P. , Kaliner M. , Ochs H. D. , Skoda‐Smith S. , Sweetser M. T. , Taki H. , Lathia C.
Published: December 2004

Background and Objectives A new intravenous immunoglobulin (IGIV) process has been developed that integrates efficient inactivation of enveloped virus, using caprylate, with immunoglobulin G (IgG) purification and caprylate removal by column chromatography. Two clinical studies were conducted to compare the pharmacokinetics of the new product, IGIV‐C, 10% (Gamunex™, 10%), formulated with glycine, with the licensed solvent–detergent (SD)‐treated intravenous immunoglobulin IGIV‐SD, 10% (Gamimune®N, 10%), formulated with glycine, and IGIV‐C, 5%, formulated with 10% maltose.

Materials and Methods Both studies were randomized, multicentre crossover trials of 18 and 20 (respectively) adult patients with primary humoral immune deficiency in which patients received one IGIV product for three consecutive periods (3–4 weeks) before crossing over to the other product. Pharmacokinetic parameters were determined after the third infusion of each product.

Results IGIV‐C, 10% was bioequivalent to IGIV‐SD, 10%, with half‐lives (t1/2) of 35 and 34 days, respectively. IGIV‐C, 5%, was bioequivalent to IGIV‐C, 10%, with t1/2 of 35 and 36 days, respectively. The products had comparable safety profiles.

Conclusions The pharmacokinetic profiles observed in these trials indicate that IGIV‐C, 10% may replace, and be administered in a manner similar to, IGIV‐SD, 10%.
Follow‐up of six blood donors highlights the complementary role and limitations of hepatitis C virus antibody and nucleic acid amplification tests
Authors: Hyland C. , Seed C. R. , Kiely P. , Parker S. , Cowley N. , Bolton W.
Published: December 2004

Background and Objectives The purpose of this study was to analyse the follow‐up results for six blood donors who screened positive for hepatitis C virus (HCV) by nucleic acid amplification technology (NAT) but were non‐reactive in the primary antibody immunoassay (HCV NAT yield).

Materials and Methods Volunteer blood donations were screened, in parallel, for antibodies to hepatitis C virus (anti‐HCV) and for human immunodeficiency virus (HIV)/HCV RNA using the Abbott PRISM HCV Chemiluminescent immunoassay (ChLIA) and the Chiron Procleix HIV‐1/HCV RNA assays, respectively. NAT yield donor samples were further tested using supplemental assays, including an alternate HCV antibody enzyme immunoassay (EIA) (Abbott Murex anti‐HCV Version 4), an immunoblot (Ortho RIBA‐3 or Genelabs Diagnostics HCV Blot 3·0) and two alternative HCV NAT assays [Roche HCV Amplicor and an assembled HCV polymerase chain reaction (PCR)]. Five of the six donors were available for follow‐up testing.

Results The six NAT yield donations were identified as constituents of 24‐member minipools among 2 212 695 donations screened over the 28‐month study period. All samples were positive when tested, undiluted, using the Roche Amplicor and assembled reverse transcription–polymerase chain reaction (RT–PCR) alternate NAT assays. One of the donors, subsequent to seroconversion, showed RNA levels that fluctuated above and below the limit of detection of the NAT screening assay. Three of the six were reactive on the secondary EIA and showed reactivity to the core c22(p) antigen by immunoblot at the index donation. Two others subsequently became reactive in the ChLIA prior to the EIA, showing reactivity against c100 and/or c33c antigens by immunoblot. The remaining donor became reactive in the ChLIA and EIA at the same time, showing RIBA reactivity against all of the following three peptides: c100; c33c; and c22(p).

Conclusions This study demonstrated that at least five of six HCV NAT yield donors were in the pre‐ or early antibody seroconversion phase of infection. The observation that one yield donor demonstrated HCV RNA that fluctuated above and below the limit of detection of the primary NAT‐screening assay supports the maintenance of both NAT and antibody screening for HCV. Follow‐up testing of suspected yield donors revealed that the primary and alternate anti‐HCV immunoassays had different performance characteristics, depending on the specificity of the donor's early anti‐HCV response.
High proficiency in detecting the six major hepatitis C virus genotypes of laboratories involved in testing plasma by nucleic acid amplification technology
Authors: Gentili G. , Pisani G. , Saldanha J. , Cristiano K. , Wirz M. , Bisso G. M. , Mele C. ,   the EQA Participants
Published: December 2004

Summary Since the introduction of mandatory HCV RNA testing of plasma pools for fractionation by nucleic acid amplification technology, we have organised External Quality Assessment studies (EQAs) addressed to blood products manufacturers and blood centres. Here we report the results of a new EQA, the first one to include all six major HCV genotypes. The results, reported by laboratories worldwide, showed that genotypes 1, 2 and 3 were correctly identified in 100% of the tests, genotype 4 in 96·7% and genotypes 5 and 6 in 98·3% of the assays. As detection of all HCV genotypes is critical for laboratories involved in testing plasma for HCV, all six genotypes should continue to be included in the next EQA studies.
Symblepharon with aberrant protrusion of the nictitating membrane in the snowy owl (Nyctea scandiaca)
Authors: Williams David L. , Flach Edmund
Published: December 2004

Two young snowy owl chicks were presented with aberrant protrusion of the nictitating membranes. This was caused by conjunctival adhesions causing symblepharon secondary to a previous septicemia episode. While symblepharon has been noted in birds before, this unusual presentation of the nictitating membrane has not been reported. Surgical intervention ameliorated the clinical signs, allowing vision in one bird by removal of the nictitating membranes, a technique which appeared to have no deleterious effects on the ocular surface.
Ultrasound biomicroscopy of the feline anterior segment
Authors: Aubin Marcia L. , Powell Cynthia C. , Gionfriddo Juliet R. , Fails Anna D.
Published: December 2004

Ultrasound biomicroscopy was performed on enucleated feline globes as a model for usein vivo. Quantitative measurements were obtained from the anterior segment using a 50‐MHz transducer. Mean values from 26 feline globes were axial corneal thickness, 0.74 mm; anterior chamber depth, 4.20 mm; distance from the first ciliary process to the limbus, 3.17 mm; angle recess, 0.38 mm; angle opening distance, 1.05 mm; iris base width 0.38 mm; iris middle width 0.52 mm; iris tip width 0.13 mm, and iris‐lens overlap, 0.69 mm. Distinctive features of the feline anterior segment include a relatively wide iridocorneal angle and deep anterior chamber.
Lens formation in the absence of optic cup in rat embryos irradiated with soft X‐ray
Authors: Inagaki Satoru , Kotani Tadao
Published: December 2004

In order to investigate the effect of soft X‐ray irradiation on ocular development, pregnant rats were exposed to a single 12.5 Gy irradiation on embryonic day 9 (ED 9). The embryos obtained by laparotomy on ED 12 and 21 were examined for ocular abnormalities under a binocular stereo‐microscope and a light microscope. The ED 12 embryos were stained with osmium tetroxide to facilitate the observation. The stereo‐microscopic examination on ED 12 and 21 revealed various types of ocular abnormalities characterized primarily by aplasia or hypoplasia of the optic cup and invaginated lens placode. The light microscopic examination further confirmed these findings histomorphologically, and the hypoplastic abnormalities were classified into three types: (1) hypoplasia of the optic cup and invaginated lens placode, (2) complete malformation of the optic cup and hypoplasia of the invaginated lens placode, and (3) complete malformation of the optic cup and invaginated lens placode. Because the lens was formed in the complete absence of the retina, the development and differentiation of the retina and lens do not seem to be tightly synchronized. Thus, this sequential analysis on ocular abnormalities during the early stage of development supports the notion that the presence of the retina is not always necessary for the development of the lens.
Connections between Temperament and Social Development: A Review
Authors: Sanson Ann , Hemphill Sheryl A. , Smart Diana
Published: December 2004

This paper critically reviews the literature on the links between temperament and social development in children and adolescents. Social development is broadly defined to include externalizing and internalizing behaviour problems, prosocial behaviour and social competence. It concludes that there are clear links between specific dimensions of temperament and particular aspects of social development. Examples include the association of negative reactivity with externalizing behaviour problems, inhibition with internalizing behaviour problems, and attention regulation with school functioning. Theoretical and methodological issues to be confronted in future research are identified, including the need to investigate further the interactions between temperament and social context. Analysis of patterns of change in temperament, in relation to physiological changes and to such factors as parenting and socio‐cultural expectations of children, promise to refine our understanding of how temperament works in context. Some practical implications which can be drawn from the research are also discussed.
Generalized Linear Models with a Coarsened Covariate
Authors: Lipsitz Stuart , Parzen Michael , Natarajan Sundar , Ibrahim Joseph , Fitzmaurice Garrett
Published: December 2004

We consider generalized linear models with a coarsened covariate. The term ‘coarsened’ is used here to refer to the case where the exact value of the covariate of interest is not fully observed. Instead, only some set or grouping that contains the exact value is observed. In particular, we propose a likelihood-based method for estimating regression parameters in a generalized linear model relating the mean of the outcome to covariates. We outline Newton–Raphson and EM algorithms for obtaining maximum likelihood estimates of the regression parameters. We also compare and contrast this likelihood-based approach with two somewhat ad hoc procedures: a complete-case analysis in which individuals with coarsened data are excluded and estimation is based on the remaining ‘complete cases’, and a coarsened data regression model in which the covariate values for all the complete cases are coarsened and then included in a regression model relating the mean to the coarsened covariate. The methodology that is presented is motivated by coarsened data on the racial–ethnicity categorization of patients in the US’s National Ambulatory Medical Care Survey, a study to examine the medical care that is provided to a patient in a physician’s office. In this study, the outcome of interest is the level of tests (none, non-invasive tests or invasive tests) ordered for the patient at the doctor’s visit. One of the covariates of interest is the patient’s four-level discrete covariate comprised of four racial–ethnicity categories: white–Hispanic, white–non-Hispanic, African-American–Hispanic and African-American–non-Hispanic. However, of the 19 095 patients in the sample, 14 955 (or 78%) have the exact category of race–ethnicity recorded and 4140 (or 22%) have race–ethnicity coarsened. For the latter group of 4140 individuals, the ethnicity is not recorded, but we know that 3683 are white and 457 are African-American.
Designing Fractional Factorial Split-Plot Experiments with Few Whole-Plot Factors
Authors: Bingham D. R. , Schoen E. D. , Sitter R. R.
Published: December 2004

When it is impractical to perform the experimental runs of a fractional factorial design in a completely random order, restrictions on the randomization can be imposed. The resulting design is said to have a split-plot, or nested, error structure. Similarly to fractional factorials, fractional factorial split-plot designs can be ranked by using the aberration criterion. Techniques that generate the required designs systematically presuppose unreplicated settings of the whole-plot factors. We use a cheese-making experiment to demonstrate the practical relevance of designs with replicated settings of these factors. We create such designs by splitting the whole plots according to one or more subplot effects. We develop a systematic method to generate the required designs and we use the method to create a table of designs that is likely to be useful in practice.
A Hierarchical Modelling Approach for Measuring Reliability of and Agreement Between Two Types Of Magnetic Field Dosimeter
Authors: Brazzale Alessandra Rosalba , Salvan Alberto , Roletti Stefano
Published: December 2004

The paper describes how to use hierarchical models to assess the reliability of and agreement between two or more types of measurement device. The idea is illustrated by fitting a linear model with nested random effects to a set of data that was obtained from the calibration of two samples of extremely low frequency magnetic field meters. The paper focuses on the formulation of a suitable model that accounts for the various aspects of the calibration protocol and the subsequent interpretation of the parameter estimates. The approach is very flexible and can easily be tuned to the various needs arising in the measurement agreement framework. It can be seen as an extension of the common practice of using a one-way random-effects model to retrieve a measure of agreement.
Temporal Pattern in Number of Staff on Sick Leave: The Effect of Downsizing
Authors: Kauermann Göran , Ortlieb Renate
Published: December 2004

The pattern of absenteeism in the downsizing process of companies is a topic in focus in economics and social science. A general question is whether employees who are frequently absent are more likely to be selected to be laid off or in contrast whether employees to be dismissed are more likely to be absent for the remaining time of their working contract. We pursue an empirical and microeconomic investigation of these theses. We analyse longitudinal data that were collected in a German company over several years. We fit a semiparametric transition model based on a mixture Poisson distribution for the days of absenteeism per month. Prediction intervals are considered and the primary focus is on the period of downsizing. The data reveal clear evidence for the hypothesis that employees who are to be laid off are more frequently absent before leaving the company. Interestingly, though, no clear evidence is seen that employees being selected to leave the company are those with a bad absenteeism profile.
Computerized cardiotocography: predictive value of instant variability
Authors: Char Sang Choon , Yamasaki A. A. , Toma O. T.
Published: December 2004

Introduction:  Computerized cardiotocography differs from classic method in measurement of instant variability, also named short‐term variation (STV) which is an important parameter of evaluation of fetal condition. While classic cardiotocography considers an active fetus when in the presence of two transitory accelerations (TA), in computerized method, value of STV is the most important parameter and it must be higher than 4 ms.

Objective:  Correlation between STV and TA.

Methods:  Two hundred and forty traces of computerized cardiotocography were analyzed (SYS 8002), in normal pregnant, between 30 and 36 weeks of gestation. They were divided into two groups: group I (n = 200) represented by pregnant whose exam did not show any TA but STV > 4 ms after 10 min; group II (n = 40) represented by pregnant with no TA and STV < 4 ms after 10 min. In all cases traces were continued until presence of TA, and the longest trace was 60 min of duration.

Results:  In group I, all cases showed TA while in group II in 60% cases initial STV < 4 ms have become more than 4 ms and with presence of TA, showing fetal in good conditions. In the other hand, in 40% cases even after keeping trace until complete 60 min there were not changes in STV or presence of TA.

Conclusion:  Fetuses with STV > 4 ms are related to active fetuses (presence of TA) and the ones with STV < 4 ms does ever not mean altered result as when prolonging trace until 60 min, 60% of these fetuses become active.