bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction to Antibody Engineering and Phage Display
Authors: Watkins Nicholas A. , Ouwehand Willem H.
Published: December 2004

The vertebrate immune system, capable of rapidly producing highly specific antibodies upon immunisation, has been used to produce murine monoclonal antibodies (mAbs) via immortalisation and isolation of antibody–secreting cells. These mAbs have had a profound impact in the fields of diagnostics and therapeutics. However, the therapeutic use of murine mAbs is complicated by their immunogenicity. To circumvent this immunogenicity, antibody engineering techniques which render murine mAbs more compatible with the human immune system have been devised. Over the last decade, the technique of antibody phage display, which facilitates the production of human mAbs, has been developed. This review serves as an introduction to antibody engineering, phage display and the development of antibody fragments into viable diagnostic and therapeutic reagents.
Transfusion Thresholds in Common Elective Surgical Procedures in Finland
Authors: Capraro L. , Nuutinen L. , Myllylä G.
Published: December 2004

Background and Objectives:
Transfusion practices and thresholds in common elective surgical procedures were investigated in a nationwide multicenter survey in Finland. Materials and Methods: The records of 764 total hip replacement (THR), 397 total knee replacement (TKR) and 343 transurethral resection of the prostate (TURP) patients were reviewed by four anesthesiologists. Results: The allogeneic red cell (RBC) transfusion rates in THR, TKR and TURP operations were 92, 84 and 18%, respectively. In THR and TKR, 74% of patients who lost 20% or less of their blood volume during hospitalization were transfused with RBCs. Postoperatively, the median pretransfusion hemoglobin values were 9.6 g/dl in orthopedic operations and 10.7 g/dl in TURP. In some hospitals, the median transfusion threshold in TURP patients was as high as 11.2 g/dl. Conclusion: The transfusion thresholds in all operations were liberal compared to recent international recommendations. Inappropriate thresholds were reflected in the high transfusion rates. This study accentuates the need for continuous discussion and educational measures to find optimal indications for transfusion in surgery, and to rationalize the transfusion policy in Finland.
Thrombopoietin Levels in Patients Undergoing Autologous Peripheral Blood Stem Cell Transplantation
Authors: Yoshimura Chie , Nomura Shosaku , Katsura Kaoruko , Yamaguchi Kazuyuki , Fukuhara Shirou
Published: December 2004

Background and Objectives:
High–dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. Several reports on endogeneous production of thrombopoietin (TPO) in patients undergoing intensive chemotherapy have been published. We measured TPO levels in patients undergoing autologous PBSCT in order to elucidate the role of TPO in megakaryopoiesis and platelet recovery following stem cell transplantation. We also examined whether PBSC from different patient groups (patients with lung cancer and malignant lymphoma) had different effects on TPO levels. Materials and Methods: Serum levels of TPO and other cytokines were determined by ELISA before and after PBSCT in 10 patients with lung cancer and 18 patients with malignant lymphoma. Results: Compared to platelet counts at 1 week after transplantation, those at 3 weeks were significantly increased (p<0.001). In contrast, serum TPO levels were significantly decreased 3 weeks after PBSCT (p<0.01). There were no significant differences in levels of other cytokines between 1 and 3 weeks after transplantation. A strong correlation was found between serum TPO levels and circulating platelet counts (r =–0.675; p<0.0001). Platelet counts exhibited a significant recovery and TPO levels also decreased significantly in malignant lymphoma patients after transplantation. There were no significant differences in TPO levels in lung cancer patients, although the same tendencies as for malignant lymphoma patients were observed for both platelet count and TPO level. On analysis of transfused PBSC, we found that the numbers of CFU–GM were similar in lung cancer and malignant lymphoma patients. However, the numbers of CD34+ cells were significantly higher in lung cancer patients than in malignant lymphoma patients. Conclusion: Our findings suggest that TPO plays a critical role in the reconstitution of megakaryopoiesis and platelet production following PBSCT, and that the type of stem cell, tumor, and preceding chemotherapy affect serum TPO levels after transplantation.
Flow‐Cytometric Method for the Quantitation of the Fc Function of Intravenous lmmunoglobulin Preparations
Authors: Ramasamy Indra , Tran Em , Charnock Alison , Farrugia Albert
Published: December 2004

Objectives:
We have developed and optimised a new flow‐cytometric method for the measurement of the Fc function of intravenous immunoglobulin (IVlg) preparations, which is important in predicting the effector function of immunoglobulin (Ig) in such preparations. Materials and Methods: Ig was bound to a monocytic cell line, THP‐1 with FcγRl and FcγRll cell surface receptors, and the bound Ig detected by FITC‐conjugated F(ab)2 fragment of rabbit anti‐human IgG. Results: Validation studies showed that Ig bound to the cell line through the Fc portion. The method detected alterations in Fc function caused by reduction with dithiothreitol or by storage. The method was reproducible (CV<11%) and a limited comparison study showed that it correlated with the European Pharmacopoeia reference method. Conclusions: This technically simple method is suitable for the quantitation of the Fc function of Ig preparations.
Collection Efficiencies of CD34+ Progenitor Cells and Mononuclear Cells in Leukapheresis Products Quantified by Flow Cytometry and Calculated on the Basis of a New Formula
Authors: Schlenke Peter , Frohn Christoph , Hennig Holger , Weber Klaus , Kisro Jens , Saballus Martin , Kirchner Holger , Klüter Harald
Published: December 2004

Background and Objectives:
Optimal mobilization and harvest of hematopoietic progenitors are essential for peripheral blood stem cell transplantation after myeloablative high‐dose chemotherapy. Conflicting data have been published concerning the most useful, cost‐effective collection strategy which is also convenient for patients. Materials and Methods: A total of 66 leukaphereses in 20 patients were retrospectively evaluated. We assessed the predictive value of the number of white blood cells, mononuclear cells (MNCs) and CD34+ cells in peripheral blood for the yield of CD34+ cells in leukapheresis products. The concentrations of MNCs and CD34+ cells were quantified simultaneously by a flow cytometric procedure using fluorescent microparticles. Their collection efficiencies were calculated based on a newly developed formula. Results: The collected hematopoietic progenitor concentration could be predicted only by the number of peripheral blood CD34+ cells prior to apheresis (r = 0.902; p < 0.01). Furthermore, the mobilization of at least 30 CD34+ cells/μl peripheral blood was a good predictor that a single leukapheresis would yield a minimum of 2.0 × 106 CD34+ cells/kg body weight. The collection efficiencies calculated by the new formula were 55.2±10.7% and 57.7±11.2% for MNCs and CD34+ cells, respectively. Conclusion: The precise quantification of MNCs and CD34+ cells by a direct flow cytometric assay, as well as the new formula to determine the collection efficiencies, has an impact on optimizing high‐quality stem cell products.
Press Review
Authors: Armstrong‐Fisher S.S. , Mc Cann Carter M.C. , Dowing I.
Published: December 2004

Evaluation of a Panel of Monoclonal Antibodies to D and Exploration of the Synergistic Effects of Blending IgG1 and IgG3 Antibodies on Their in vivo Biological Function
Press Review
Authors: Schüttler C.G. , Caspari G. , Jurch C.A.
Published: December 2004

Hepatitis C Virus Transmission by a Blood Donation Negative in Nucleic Amplification Tests for Viral RNA
Press Review
Authors: Mast A.E. , Stadanliick J.E. , Lockett J.M.
Published: December 2004

Solvent/Detergent‐Treated Plasma Has Decreased Antitrypsin Activity and Absent Antiplasmin Activity
Press Review
Authors: Schuh A. , Atoyebi W. , Littlewoord T.
Published: December 2004

Prevention of Worsening of Severe Thrombocytopenia after Red Cell Transfusions by the Use of Leucocyte‐Depleted Blood
Leukoreduction of Platelet Concentrates Using a ‘Polishing’ Filter
Authors: van der Meer P.F. , Pietersz R.N.I. , Reesink H.W.
Published: December 2004

Background and Objectives
: Filters for removal of leukocytes from platelet concentrates (PCs) usually have a large volume to guarantee sufficient leukoreduction. In this study, a small filter, with a volume of only 8ml and therefore minimal platelet loss, for leukoreduction of PCs was investigated. This filter has a ‘limited’ leukoreducing capacity, hence the filter is called a ‘polishing’ filter. Materials and Methods: PCs were made from 5 pooled buffy coats in either plasma or additive solution (PAS‐II). After centrifugation, the platelet‐rich supernatant was expressed on an automated separator (Compomat G4) to an empty transfer bag. The content of this transfer bag was filtered into the platelet storage bag, either by expression by lowering the top press of the Compomat G4, or by gravity by hanging it on a filtration rack. Results: Leukocyte counts before and after filtration revealed a mean leukoreducing capacity for the filter of 2.67 log10 and a platelet loss of only 2% for PCs in PAS‐II (n = 50), and for PCs in plasma a 3.43 log10 leukoreduction with 3% platelet loss (n = 30). Expression of the PCs both in plasma and PAS‐II through the filter using the Compomat G4 resulted in 10/10 units containing <5×106 leukocytes, but 1/10 PCs contained >1×106 leukocytes for both solutions. Filtration by gravity resultet in 40/40 units with <1×106 leukocytes for PCs in plasma, and 60/60 units with <1×106 for PCs in PAS‐II. Conclusion: The ‘polishing’ filter allows relible, standardized and automated production of PCs, both in plasma and additive solution with minimal platelet loss, and containing uniformly <1×106 leukocytes, provided the filtration procedure is performed by gravity.
A Clinically Applicable Method for the ex vivo Generation of Antigen‐Presenting Cells from CD34+ Progenitors
Authors: Ardeshna K.M. , Corney C.P. , Ings S.J. , Watts M.J. , Linch D.C. , Devereux S.
Published: December 2004

Background and Objectives
: Dendritic cells (DCs), the most potent of antigen‐presenting cells, can be generated in vitro from bone marrow or blood progenitor cells. We have developed a method for producing such cells from mobilised peripheral blood CD34+ cells in the absence of bovine products. Methods: The culture system developed used X‐Vivo 10 culture medium with 10% autologous serum, rhGM‐CSF, rhTNF‐α and rhIL‐4. Largescale cultures were performed in Stericell 12 inch X 15 inch culture bags. Results: In 12‐small‐scale experiments, over 14 days, there was a median 38‐fold increase in cell numbers of which 12.8% were DCs as defined by immunophenotyping. These cells had potent DC activity in functional assays. In two clinical‐scale experiments, a 5.7‐ and 10‐fold expansion of total cell numbers was obtained, with 8.2 and 18% of the final population being DCs, respectively. Conclusion: This system is suitable for clinical application.
Retrospective Analysis of Blood Transfusion Recipients: Evidence for Post‐Transfusion Hepatitis E
Authors: Arankalle V.A. , Chobe L.P.
Published: December 2004

Background and Objectives:
Of 200 volunteer blood donors we had screened earlier for hepatitis E virus (HEV) RNA, using reverse‐transcription polymerase chain reaction, 3 were positive, raising the possibility of transfusion‐associated hepatitis E in areas endemic for this virus. This retrospective study was to reassess the extent of post‐transfusion hepatitis E among transfusion recipients, investigated in 1982. Materials and Methods: We re‐evaluated 56 recipients followed biweekly for 3 months after transfusion. The controls were 51 normal, healthy persons who gave blood at a 2‐month interval, as well as 412 blood donors from whom blood was taken once in 1982. Results: Of the 56 transfusion recipients, 19 were positive for lgG antibodies against HEV (anti‐HEV) in the pretransfusion sample. Two of the 37 lgG anti‐HEV‐negative recipients seroconverted to lgM and lgG anti‐HEV 5 and 4 weeks after transfusion, 1 with raised serum alanine aminotransferase levels. None showed symptoms of hepatitis. Attempts to detect HEV RNA in transfused blood, from aliquot units stored at −20°C for over 17 years, were not successful. Of the controls, 17 out of 51 were lgG anti‐HEV positive in the initial sample itself. None of the 34 lgG anti‐HEV‐negative controls seroconverted during the 2‐month follow‐up. Of the blood donors, 154 out of 412 were lgG anti‐HEV positive. None of the 412 donors had circulating lgM anti‐HEV antibodies. A significantly higher (p<0.03) proportion of susceptible transfusion recipients were lgM anti‐HEV positive as compared with susceptible blood donors. Conclusion: The results suggest that, in countries where HEV is endemic, the transmission of hepatitis E may be associated with blood transfusion.
Gamma‐Ray‐Irradiated Red Blood Cells Stored in Mannitol‐Adenine‐Phosphate Medium: Rheological Evaluation and Susceptibility to Oxidative Stress
Authors: Cicha Iwona , Suzuki Yoji , Tateishi Norihiko , Shiba Masayuki , Muraoka Masato , Tadokoro Kenji , Maeda Nobuji
Published: December 2004

Background and Objectives:
To evaluate the rheological properties and the oxidative susceptibility of γ‐ray‐irradiated red blood cells (RBCs). Materials and Methods: RBCs in mannitol‐adenine‐phosphate (MAP) medium were irradiated with 35 Gy and stored at 4°C for 4 weeks. The deformability of the RBCs was examined under shear flow in relation to the morphological and biochemical changes. The RBCs were further exposed to 1mM FeSO4 and 5 mM ascorbate to examine the oxidative susceptibility. Results: The RBC deformability was decreased during storage, and the impairment was further enhanced by the irradiation, which promoted cell shrinkage and intracellular hemoglobin condensation accompanying potassium loss. Lipid peroxidation and protein aggregation of the RBC membrane as well as echinocytosis were not enhanced by the irradiation. The exposure to free iron did not stimulate the oxidation of the irradiated RBC membrane. Conclusion: The decreased deformability of γ‐ray‐irradiated RBCs in MAP medium was mainly induced by dehydration due to potassium loss, and the membrane lipids and proteins were stably preserved against oxidative stress.
Variable Leukocyte Composition of Red Blood Cell Concentrates Prepared in Top‐Bottom Systems: Possible Implications for Pre‐Transplant Blood Transfusion
Authors: Weinreich S.S. , Remmerswaal E.B.M. , Laport R. , van Rhenen D.J. , Rombout‐Sastrienkova E. , Smit Sibinga C.T. , Vrielink H. , Boog C.J.P.
Published: December 2004

Background and Objectives:
The beneficial effect of blood transfusion on kidney graft survival requires the presence of leukocytes in the transfusate, but a minimal dose has not been defined, nor has the role of individual leukocyte subsets been investigated. In the Netherlands, a standard pre‐transplant blood transfusion consists of a buffy coat (BC)‐depleted red blood cell concentrate (RBCC) containing a maximum of 1.2 × 109 residual leukocytes per unit. However, leukocyte subset composition is not standardized. Materials and Methods: Using FACS analysis, this study compared the residual leukocyte composition of RBCCs produced by Compomat® and Optipress®, two currently used top‐bottom systems. Results: While the total leukocyte content of the RBCCs was equivalent in both press types (0.5 × 109), the percentage of mononuclear cells (lymphocytes and monocytes) was significantly higher in the Compomat as compared with the Optipress system (p < 0.0001), resulting in significantly higher numbers of transfused T cells, B cells, HLADR‐positive cells, NK cells and stem cells. Conclusions: The leukocyte composition of a pre‐transplant blood transfusion depends on the BC depletion method used; this might differentially affect the tolerizing or immunizing potential of a pre‐transplant blood transfusion.
Transfusion‐Related Acute Lung Injury Associated with Interdonor Incompatibility for the Neutrophil‐Specific Antigen HNA‐1a
Authors: Lucas G. , Rogers S. , Evans R. , Hambley H. , Win N.
Published: December 2004

Background and Objectives:
A patient transfused with two pooled platelet concentrates became breathless. Bilateral infiltrates were seen on chest X‐ray. A diagnosis of transfusion‐related acute lung injury (TRALI) was made. The patient received 100% oxygen and recovered after 5 days. Materials and Methods: Antibody screening, cross‐matching for granulocyte and lymphocyte antibodies and typing for granulocyte antigens was undertaken. Results: The patient typed as HNA‐1b/HNA‐1b. Granulocyte and lymphocyte antibodies were not detected in the patient's serum or in any of the donor sera by cross‐match. In antibody screening against typed panel granulocytes, complement‐fixing anti‐HNA‐1a IgM antibodies were detected in the serum of one femaledonor. Two of the other donors who contributed to the pooled platelet concentrate containing the HNA‐1a IgM antibodies typed as HNA‐1a/HNA‐1b. Conclusion: Anti HNA‐1a IgM antibodies may have formed immune complexes with white cell fragments or soluble FcγRIII from HNA‐1a+ donors in the pooled platelet concentrate and initiated TRALI.
Press Review
Authors: Engelfriet C.P. , Dormoy A. , Hanau D. , Tongoi M.M.
Published: December 2004

Development and Validation of a Genotyping Kit for the Eight Principal Human Platelet Alloantigen Systems
Benefits and Complications of Regular Blood Transfusion in Patients with Beta‐Thalassaemia major
Authors: Prati Daniele
Published: December 2004

Abstract Early and regular blood transfusion therapy in patients with homozygous β‐thalassaemia decreases the complications of severe anaemia and prolongs survival. In the long term, however, the beneficial effects of transfusions are limited by the organ damage resulting from iron overload, a consequence of the body's limited capacity to excrete iron, and by the complications of infection with blood‐borne agents. Transfusion regimens for β‐thalassaemia have changed substantially during the past four decades. In current protocols, pre‐transfusion haemoglobin concentration should not exceed 95 g/l. This allows adequate control of anaemia, with a relatively low rate of iron accumulation. Although iron chelation therapy has successfully improved survival free from cardiac disease, thalassaemic patients continuously present new clinical challenges. In fact, the vast majority of them suffer from post‐transfusion chronic hepatitis C, which is expected to significantly contribute to morbidity in the forthcoming years. Furthermore, recent studies demonstrated that thalassaemics are at high risk of acquiring several blood‐borne viruses. The potential role of these multiple infections in inducing clinical disease is still uncertain, and needs to be thoroughly clarified in future surveys.
Classification of Standard Alleles of the MN Blood Group System
Authors: Akane Atsushi , Mizukami Hajime , Shiono Hiroshi
Published: December 2004

Abstract
Background and Objectives:
We had classified the M alleles of the MN blood group system into two subtypes, MG (standard M) and MT, based on a G/T substitution in intron 1 of the glycophorin A (GPA) gene. This study provides further study on nucleotide sequences of MG, MT and N alleles to profile the new allele, MT. Materials and Methods: MG, MT and N alleles of the GPA gene were amplified using GPA gene‐specific primers to avoid coamplification of the genes of glycophorins B and E. Then the 5'‐flanking region, exons 1–7 and introns 1–4 of the alleles were analyzed by DNA sequencing. Results: There were 17 nucleotide substitutions and deletions between MG (standard M) and N alleles. Ten of the MT nucleotides were MG‐type but the other 7 were N‐type. MT allele also showed one base change and one deletion that were observed in neither the MG nor the N allele. Moreover, we found nucleotide substitutions within each allele, allowing further classification of the alleles. Conclusion: By the sequence data of MG, MT and N alleles, the three alleles could be further classified into M101 and M102, M201 and N101 and N102, respectively.
Retrospective Study on Red Cell Usage in Primary Total Knee Replacement Surgery
Authors: Boralessa Hari , Boralessa Harsha , Contreras Marcela , Lang‐Stevenson Andrew , Knowles Sue , Cockburn Hazel
Published: December 2004

Background and Objectives:
There is wide variation in the use of red cell transfusions for the same clinical indication. The purpose of the study was to comment on preoperative and discharge haemoglobin (Hb) levels and perioperative blood loss, and to project the Hb level if transfusions were not administered. Materials and Methods: The case notes of 187 patients who underwent primary total knee replacement were reviewed retrospectively. Results: More than 90% of the transfusions were given in the immediate postoperative period as a matter of routine and a significant number of transfusions appeared to be unnecessary. Conclusion: For surgical procedures involving moderate blood loss, transfusions should not be given as a routine and the decision to transfuse should take into consideration the clinical state of the patient, blood loss and pre‐ and postoperative Hb levels.
Effect of manufacturing process parameters on virus inactivation by solvent–detergent treatment in a high‐purity factor IX concentrate
Authors: Roberts P. L. , Dunkerley C.
Published: December 2004

Background and Objectives  Treatment with solvent–detergent is widely used for ensuring the virus safety of plasma products. Laboratory studies have shown this procedure to be effective for inactivating enveloped viruses under manufacturing conditions. In the present study, the effect of different manufacturing process parameters on virus inactivation by treatment with polysorbate 80 and tri‐n‐butyl phosphate were investigated for a high‐purity factor IX concentrate in order to evaluate the robustness of this step.

Materials and Methods Samples of factor IX intermediate were obtained, virus was added and the kinetics of virus inactivation followed during incubation. The effect of altering the conditions on virus inactivation was tested.

Results Solvent–detergent treatment was confirmed to effectively inactivate, i.e. by ≥ 5 log, a wide range of representative enveloped viruses under standard conditions. Virus inactivation was consistently effective in a number of different manufacturing batches. Of the parameters tested, only solvent–detergent concentration and temperature significantly effected virus inactivation.

Conclusions The robustness of the solvent–detergent step for virus inactivation has been confirmed. Using the data generated, appropriate limits can be set for this manufacturing process step.
Associations among nucleated cell, CD34+ cell and colony‐forming cell contents in cord blood units obtained through a standardized banking process
Authors: Aroviita P. , Teramo K. , Westman P. , Hiilesmaa V. , Kekomäki R.
Published: December 2004

Background and Objectives Nucleated cell content is one of the main components used when evaluating cord blood (CB) units for clinical use. However, other indicators of the haematopoietic potential of a CB unit, such as CD34+ cell and colony‐forming cell (CFU‐TOT) content, have also been investigated. The aim of this study was to determine whether the CD34+ cell content could be used in selecting CB collections for banking.

Materials and Methods The collection data, as well as cellular contents of 588 CB collections obtained using a standardized CB banking process, were analysed.

Results Altogether, 526 CB units from the 588 collections accepted for processing were included in international search registries. The volume collected was, as expected, 69 ml (range 28–116 ml). The correlation between total CD34+ cell and CFU‐TOT (n = 88) content in the CB collection was higher (r = 0·87) than the correlation between the total nucleated cell and CFU‐TOT content (r = 0·69, both P < 0·0001). The correlations of pre‐ and postvolume reduction values of the total nucleated cell and CD34+ cell numbers were highly significant (r = 0·96, P < 0·0001, both). The total CFU‐TOT content of the CB collection correlated significantly with the total CD34+ cell content of the CB unit before cryopreservation (but after volume reduction) (r = 0·89, P < 0·0001).

Conclusions CD34+ cell content predicts the haematopoietic potential of a CB unit better than nucleated cell content. Accordingly, the CD34+ cell content of CB could be used to select CB for banking purposes and for transplantation.
Collaborative studies to establish the first WHO Reference Reagent for detection of human antibody against human platelet antigen‐5b
Authors: Metcalfe P. , Ouwehand W. H. , Sands D. , Barrowcliffe T. W.
Published: December 2004

Background and Objectives This report describes the production of a freeze‐dried preparation of pooled human plasma, coded 99/666, containing immunoglobulin G (IgG) antibodies against human platelet antigen 5b (HPA‐5b).

Materials and Methods The material is intended for use as a minimum sensitivity reagent in the assays currently used for detection of antibodies to HPA‐5b. Laboratories can use it to assess the sensitivity of their ‘in‐house’ assays for antibodies to HPA‐5b and to calibrate local controls for routine use in each batch of tests.

Results Two collaborative studies demonstrated that the two candidate materials contained antibodies to HPA‐5b and that there were no other HPA or human leucocyte antigen (HLA) antibodies which might confuse the detection of antibodies to HPA‐5b. The two samples were pooled and freeze‐dried in 1‐ml ampoules.

Conclusions The minimum dilution of the antibody against 5b required to yield a positive result was determined, by two international collaborative studies involving a total of 49 laboratories in 26 countries, to be 1 in 2.
Inflammatory mediators in autotransfusion drain blood after knee arthroplasty, with and without leucocyte reduction
Authors: Dalén T. , Bengtsson A. , Brorsson B. , Engström K. G.
Published: December 2004

Background and Objectives The aim of this study was to evaluate whether leucocyte‐reducing filters influenced complement activation and the formation of pro‐inflammatory cytokines in autotransfusion drain blood after knee arthroplasty.

Materials and Methods Twenty‐three patients undergoing knee arthroplasty were divided into two groups. All patients were given salvage blood postoperatively. In Group A, a leucocyte filter was connected between the wound and the drain blood container. In Group B the drain blood was not leucocyte filtered. Complement split products and cytokines were analysed in circulating blood and in drain blood, together with blood‐cellular differential counts.

Results Drain blood showed activation vs. venous blood, with elevated concentrations of C3a, SC5b‐9, interleukin (IL)‐6, IL‐8, polymophonuclear (PMN) elastase and tumour necrosis factor‐α (TNF‐α) (P < 0·05 to P < 0·001). The leucocyte filter reduced TNF‐α (P < 0·01), but triggered complement activation (P < 0·05). Room‐temperature incubation increased the concentration of IL‐8 (P < 0·01), which was seen in both venous and drain blood. The leucocyte filter prevented formation of IL‐8 (P < 0·01). In drain blood at 24 h the inflammatory reactions accelerated (P < 0·05–0·001), although the filter reduced the leucocyte counts and TNF‐α concentrations.

Conclusions The leucocyte filter reduced IL‐8 and TNF‐α in drain blood, but at the same time triggered complement activation. Incubation affected the inflammatory spectrum of both drain blood and control venous blood, and the filtering reduced this activation.
Restoration of red blood cell volume following 2‐unit red blood cell apheresis
Authors: Valeri C. R. , Ragno G. , Srey R.
Published: December 2004

Background and Objectives Blood donors who weigh at least 130 lbs (59 kg) and have a haematocrit of at least 40 V per cent can donate 2 units of blood, from which a 360‐ml volume of red blood cells (RBC) can be isolated. This study was carried out in seven healthy male blood donors to assess the restoration of the RBC volume 1 month following a 2‐unit RBC apheresis procedure.

Materials and Methods RBC volumes were measured prior to donation and 4 weeks after the 2‐unit RBC apheresis procedure without oral iron supplementation.

Results Four weeks after the removal of 2 units of RBC from the male donors not supplemented with oral iron, the RBC volume was restored to 92% of the precollection value. The 360‐ml volume of RBC collected represented 12–19% of the donor's original RBC volume.

Conclusions Male donors can safely donate 2 units of RBC and will restore a mean of 92% of their RBC volume within 1 month without iron supplementation.
Structure and presumptive function of the iridocorneal angle of the West Indian manatee (Trichechus manatus), short‐finned pilot whale (Globicephala macrorhynchus), hippopotamus (Hippopotamus amphibius), and African elephant (Loxodonta africana)
Authors: Hatfield Jessie R. , Samuelson Don A. , Lewis Patricia A. , Chisholm Mae
Published: December 2004

The iridocorneal angles of prepared eyes from the West Indian manatee, short‐finned pilot whale, hippopotamus and African elephant were examined and compared using light microscopy. The manatee and pilot whale demonstrated capacity for a large amount of aqueous outflow, probably as part of a system compensating for lack of ciliary musculature, and possibly also related to environmental changes associated with life at varying depths. The elephant angle displayed many characteristics of large herbivores, but was found to have relatively low capacity for aqueous outflow via both primary and secondary routes. The hippopotamus shared characteristics with both land‐ and water‐dwelling mammals; uveoscleral aqueous outflow may be substantial as in the marine mammals, but the angular aqueous plexus was less extensive and a robust pectinate ligament was present. The angles varied greatly in size and composition among the four species, and most structures were found to be uniquely suited to the habitat of each animal.
P52Ultrasonographic diagnosis of an approach to a case with intrauterine clitoromegaly
Authors: Tekin B. , Hassa H. , Şenses T.
Published: December 2004

Introduction

Adrenal androgens are one of the important determinants of sexual differentiation in fetal period. Increased circulating levels of adrenal androgens as seen in congenital adrenal hyperplasia, interact with genital skin androgen receptors and induce clitoral enlargement, fusion of labial folds and cause migration of the urethral‐vaginal perineal orifice resulting in ambiguous genitalia. We are reporting a female newborn with clitoromegaly from a nulliparous mother at term pregnancy.

Case report

The mother was followed up from 22 weeks of gestation with no signs of hyperandrogenism. Because of late application for antenatal follow up and since clitoromegaly was observed at 29 weeks of pregnancy, amniocentesis could not be done. During ultrasonographic evaluation at 29 weeks of gestation, clitoris with a size of 13 × 18 mm was detected and dexamethasone 1 × 0.5 mg orally was started to use. In reevaluation at 33 weeks of gestation clitoral size was measured as 4.8 × 6.8 mm and treatment was stopped. At 40 weeks of gestation a female neonate with 10–10 apgar scores, weighing 4040 g was delivered with caesarian section due to cephalopelvic disproportion. After delivery physical examination of the neonate revealed clitoral measurements consistent with clitoromegaly. Hyperandrogenic state of the case persists and evaluation of the newborn is going on in Pediatrics Clinic.

Discussion

Although adrenal androgen secretion starts at 6–8 weeks of gestation and dexamethasone therapy was shown to be effective in regression of virilization if it was used as early as 6–8 weeks of gestation, our case was diagnosed later in the course of pregnancy. But when similar regimen was applied similar result was obtained. So we propose that patients with intrauterine virilization signs like clitoromegaly and ones with risk of congenital adrenal hyperplasia should take glucocorticoid therapy whenever it is determined in order to ameliorate genital ambiguity in female fetuses.
P82Fetal death in pregnancies with absent or reversed end‐diastolic velocity waveforms in the umbilical artery
Authors: Yamamoto R. M. , Francisco R. P. V. , Sakamoto K. , Miyadahira S. , Zugaib
Published: December 2004

Background

Description of pregnancies with fetal death following absent or reversed end‐diastolic velocity (AREDV).

Method

Between 1992 and 2000, 249 singleton high risk pregnancies with AREDV were followed. Twenty‐nine cases of intrauterine fetal death (IUFD) were reviewed. All the patients were hospitalized after the AREDV diagnosis, and followed with intensive surveillance of fetal vitality.

Results

The results are shown in the table:

AREDV diagnosis
19–24 week  (n = 14)
25–28 week  (n = 15)
Total  (n = 29)

Fetal weight
454 + 180
694 + 194
578 ± 221

GA at AREDV diagnosis
22.8 + 1.5
26.5 + 1.1
24.8 + 2.3

Interval AREDV‐IUFD   (days)
12.4 + 12.2
6.3 + 6.4
9.2 + 9.9

Reversed flow
7  (50%)
9  (60%)
16 (55%)

Interval reversed flow‐IUFD   (days)
5.0 ± 4.1
4.8 ± 5.5
4.9 ± 4.8

Conclusion

Pregnancies with severe placental insufficiency that presented fetal death showed a high incidence of reverse flow in the umbilical artery. The cases that presented early fetal death showed a higher time interval between the AREDV diagnosis and IUFD
P84Early neonatal death according to metabolic acidosis at birth in pregnancies with absent or reversed end‐diastolic velocity flow in the umbilical artery
Authors: Yamamoto R. M. , Francisco R. P. V. , Okatani D. , Miyadahira S. , Zugaib M.
Published: December 2004

Background

An analysis, in pregnancies with absent or reversed end‐diastolic velocity (AREDV) flow in the umbilical artery, of the relation between blood gas values at birth and the occurrence of early neonatal death (until 7 days after delivery).

Method

Between 1992 and 2000, 146 high risk pregnancies with AREDV where it was possible to obtain blood gas analysis results at birth were studied. The criteria used for delivery included: fetal distress, fetal maturity, worsening of maternal condition and severe oligohydramnios. The umbilical arterial blood gas values at birth were compared to early neonatal death.

Results

The results are shown in the table (*P < 0.05):

pH < 7.15
pH < 7.20
BE < −10
pH < 7.15  and BE < −10

ND (≤ 7d)
10/43 (23%)
11/75 (15%)
13/56 (23%)*
9/30 (30%)*

n = 21

ND (total) n = 36
14/43 (32%)
19/75 (25%)
31/56 (55%)
20/30 (67%)

Conclusion

Buffer base depletion (negative base excess‐BE), and when this variable is associated with low pH values (pH < 7.15 and BE < −10) showed a significant statistical correlation with early neonatal death.
P92Early second trimester low umbilical coiling index predicts small for gestational age fetuses
Authors: Degani S. , Leibovich Z. , Shapiro I. , Gonen R. , Ohel G.
Published: December 2004

Objective

To evaluate the role of early second trimester Doppler velocimetric studies, umbilical coiling index and umbilical cord cross‐sectional area as a test for the prediction of small for gestational age (SGA) infants.

Study design

Doppler blood flow studies in 147 singleton pregnancies at risk for delivery of a SGA newborn were performed at 15 ± 1 weeks of gestation from umbilical artery, middle cerebral artery, inferior vena cava and ductus venosus. Pulsatility index (PI) values were calculated for the arteries and preload index (PLI) and S/A values for the veins. The sonographic cross‐sectional area of the umbilical cord was measured in a plane adjacent to the insertion into the fetal abdomen. The umbilical coiling index was calculated using sonographic longitudinal views of cord vessels from several segments antenatally. SGA newborn was identified when the birth weight was below the 10th percentile for gestational age.

Results

Among 147 pregnancies studied, 124 fulfilled the study criteria. 39 of the fetuses were SGA at birth (31.5%). The mean gestational age at delivery (± SD) of the normally grown fetuses was 39.7 ± 1.28 weeks and of the SGA newborns was 34.6 ± 2.9 weeks (range 28–40 weeks). The best single predictor of a SGA infant was the coiling index with a sensitivity of 79% specificity of 86%, positive predictive value of 72% and negative predictive value of 90%.

Conclusion

Umbilical coiling index measured in the early 2nd trimester is useful in predicting birth of a SGA infant and may be a marker of subsequent growth restriction.
F54Different types of umbilical venous pulsations and clinical implications
Authors: Gudmundsson S. , Hofstaetter C. , Dubiel M.
Published: December 2004

Objective

Normally, blood flows evenly in the umbilical vein, without fluctuation. A pulsating pattern has been reported during fetal heart failure and asphyxia. Recently we have noticed different types of pulsating pattern, its physiological implication and relationship to outcome of pregnancy was analysed.

Study design

In a prospective multicenter study, recording of umbilical cord venous blood flow was conducted in high‐risk pregnancies admitted for umbilical artery Doppler. In cases of pulsating flow or signs of vascular resistance in the umbilical artery, the examination was extended to the intra‐abdominal part of the umbilical vein. Venous pulsation, single or double, were noted and correlated to perinatal outcome.

Results

Venous flow pulsatility was noted in 83 fetuses during two years, 26 had a double pulsating pattern, which was closely related to increased vascular resistance in the umbilical artery and perinatal mortality. A single end‐diastolic pulsation only in the cord was noted in some of the fetuses with absent or reversed flow in the umbilical artery, probably due to decreased forward flow over the placenta. A single pulsating venous pattern in one location had good prognosis.

Conclusion

A double pulsating venous pattern, especially if extending to the cord, is an ominous finding associated with poor perinatal outcome in high‐risk pregnancy. A single pulsating pattern predicted a much better outcome and might be an indication for delivery in the high‐risk case.
Nursing documentation of leg ulcers: Adherence to clinical guidelines in a Swedish primary health care district
Authors: Ehrenberg Anna , Birgersson Christina
Published: December 2004

The aim of this study was to investigate the adherence of nursing documentation to clinical guidelines in leg ulcer patients. Using two audit instruments, 100 patient records from primary health care were reviewed. The nursing content in the records was assessed according to instructions for documentation in local clinical guidelines for leg ulcers and the comprehensiveness of the nursing process in recording was reviewed. The results indicated deficiencies in the documentation of aspects of relevance in the care of leg ulcer patients. In addition, the findings indicated flaws in the adoption of the nursing process in recording. Only one problem in one patient record was recorded that consistently used the nursing process. The conclusion is that, despite specific and locally developed guidelines for care of leg ulcer patients, nursing records did not provide a precise audit of the care process. Because patient record information without a clear structure following the nursing process tends to impede communication and evaluation of care, such defective information is likely to have a significant impact on the continuity and quality in patient care.
Validation of a New Approach to Condition Monitoring of Offshore Structures – Aspects of a Scale Model
Authors: Thompson M. , Harper M.
Published: December 2004

Abstract:  Offshore structures have a finite design life and many are approaching that limit. The expected life cannot be extended without some justification, such as the inclusion of a structural monitoring system. This project is aimed at using long‐range propagation of acoustic signals through a structure to detect changes induced by damage, cracking or flooding of hollow members. It is based on the idea that, if a change occurs within the structure, this will induce changes in acoustic signals transmitted between two points on it. These changes will only occur after a certain time in the history of the signal, and this time corresponds to the minimum travel time from the transmission point to the reception point via the point of damage. A scale model in polycarbonate has been used to demonstrate that using acoustic waves to interrogate a multi‐connected structure can successfully locate damage. This has been done with sensors all at the top (reflection mode) and with transmitters at the top and receivers at the bottom (tomographic mode). The method is effective when we use very small numbers of source and sensor positions in proportion to the number of structural members being monitored for damage. The reflection geometry is much more practical from the point of view of application to offshore structures because all transducers and wiring can be located above the splash zone.
THE CLINICAL EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES IN CHRONIC KIDNEY DISEASE: Is Chronic Kidney Disease a Cardiovascular Disease Risk Factor?
Authors: Culleton Bruce F. , Hemmelgarn Brenda R.
Published: December 2004

Cardiovascular disease (CVD) is prevalent in patients with chronic kidney disease (CKD) and may account for 50% of all deaths. The recent Dialysis Outcomes Quality Initiative (DOQI) publication on the evaluation, classification, and stratification of CKD states that a reduced glomerular filtration rate (GFR) identifies individuals at greater risk for CVD and death. This risk is the result of traditional and nontraditional CVD risk factors. However, the relative contribution of these risk factors in the CKD population remains uncertain. Recently interest in kidney disease (reduced GFR) as an independent nontraditional risk factor for CVD has come to the forefront. Studies examining this potential link have included community‐based cohort studies, studies in patients with extensive comorbidity, and reports in kidney transplant recipients. Herein, results from these studies are reviewed. The difference between an independent CVD risk factor and a causal CVD risk factor is discussed, with particular emphasis on the temporal association between exposure (GFR) and outcome (CVD and CVD death).
THE CLINICAL EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES IN CHRONIC KIDNEY DISEASE: Clinical Epidemiology of Cardiovascular Disease in Chronic Kidney Disease Prior to Dialysis
Authors: Levin Adeera
Published: December 2004

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with end‐stage renal disease (ESRD). Both in dialysis and in transplant patients, CVD remains the leading cause of death. There is accumulating evidence that the increase in CVD burden is present in patients prior to dialysis, due to both conventional risk factors as well as those specific to kidney disease. Of importance is that even in patients with mild kidney disease, the risk of cardiovascular events and death is increased relative to patients without evidence of kidney disease. The new classification system proposed by the National Kidney Foundation as part of the Dialysis Outcomes Quality Initiative (DOQI) process describes the five stages of kidney disease, as well as those complications associated with chronic kidney disease (CKD), in particular cardiovascular risk factors and disease. Patients with kidney disease are deemed to be at highest cardiovascular risk. CVD, defined as the presence of either congestive heart failure (CHF), ischemic heart disease (IHD), or left ventricular hypertrophy (LVH), is prevalent in cohorts with established CKD (8–40%). The prevalence of hypertension, a major risk factor for coronary artery disease (CAD) and LVH is high in patients with CKD (87–90%). At least 35% of patients with CKD have evidence of an ischemic event (myocardial infarction or angina) at the time of presentation to a nephrologist. The prevalence of LVH increases at each stage of CKD, reaching 75% at the time of dialysis initiation, and the modifiable risk factors for LVH include anemia and systolic blood pressure, which are also worse at each stage of kidney disease. Even under the care of nephrologists, a change in cardiac status (worsening of heart failure or anginal symptoms) occurs in 20% of patients. The presence of CVD predicts a faster decline of kidney function and the need for dialysis, after controlling for all other factors including glomerular filtration rate (GFR), age, and the presence of LVH. This article describes the new classification system for staging of CKD, defines and describes CVD in CKD, and reviews the evidence and its limitations with respect to the current understanding of CKD and CVD. Specifically, methodologic issues related to survival and referral bias limit our current understanding of the complex interaction of conventional and nonconventional kidney disease‐specific risk factors. We identify the importance of well‐conducted studies of patient groups with and without CVD, with and without CKD, in order to better understand the complex physiology so that treatment strategies can be appropriately applied.
Cellsorba
Authors: Shibata Hiroshi , Kuriyama Toshiji , Yamawaki Naokuni
Published: December 2004

Abstract:  Cellsorba is a leukocyte removal filter developed by Asahi MedicalCo., which adsorbs white blood cells through the perfusion of peripheralblood by means of simple extracorporeal circulation. Leukocytapheresis (LCAP)therapy using the Cellsorba column has been reported to show therapeuticeffects for many autoimmune related and inflammatory diseases, suchas inflammatory bowel disease, rheumatoid arthritis, systemic lupuserythematosus, neurologic disease, and so on. At present, Cellsorbais listed as a medical device covered by the Japanesenational health insurance system for the treatment ofactive ulcerative colitis (UC) in Japan, and contributes to the improvement of quality of life in many UC patients.This paper reviews the use of Cellsorba and introduces several reportson therapeutic results.
Early Relapse of Thrombotic Thrombocytopenic Purpura duringTherapeutic Plasma Exchange Associated with Acinetobacter anitratus Bacteremia
Authors: Kanj Nadim A , Mikati Abdel Razzak A , Baz Elizabeth M. Kfoury
Published: December 2004

Abstract:  Thrombotic thrombocytopenic purpura (TTP)/Hemolytic–uremicsyndrome (HUS) is a syndrome characterized by thrombocytopenia,microangiopathic hemolytic anemia, fever, renal failure and neurologic manifestation.Almost all cases are idiopathic. However, secondary TTP/HUSassociated with viral, bacterial and mycobacterial infections, drugs,connective tissue disease, solid tumors, bone marrow transplantationand pregnancy have been described. Early relapse associated withinfection is a rare occurrence. The patient we report had a classic caseof postdiarrheal TTP/HUS that responded to plasmapheresisbut relapsed during treatment as reflected by the increased schistocytosis,decreased hematocrit, increased lactate dehydrogenase, and decreased platelet counts. This relapse may be attributed to Acinetobacteranitratus bacteremia, secondary to central line infection. Administrationof antimicrobial treatment resulted initially in a mild improvement.However, this was followed by a fatal relapse. The importance ofmonitoring the possible bacterial colonization of an indwellingcatheter is thus emphasized.