bluuebunny/crossref_metadata_2025 huggingface dataset:
Four Examples of Anti‐TSEN and Three of TSEN‐Positive Erythrocytes
Authors: Story Jill R. , Lindsay Gwenn , Rolih Susan , Co Asuncion , Rodberg Karen , Harris Teresa , Reid Marion E.
Published: December 2004

Abstract
Background:
TSEN (MNS33) is a low‐incidence antigen in the MNS blood group system encoded by hybrid glycophorin genes. TSEN is expressed by a unique amino acid sequence that results from the junction of GPA58 to GPB27, if the GPB carries S antigen. Until this study, only one example of anti‐TSEN had been found. Antibody screening red blood cells (RBCs) positive for both S and s (ref. No. C873) reacted with four patient sera. Initially, the RBCs had been typed as S+s+, but later were typed as S‐s+ in another laboratory. Two other RBC samples, one from a volunteer blood donor (D.L.), the other from a patient whose serum contained anti‐EnaFR (J.S.), also gave anomalous results when tested with anti‐S. We sus pected the presence of TSEN‐positive hybrids on all three RBC samples. Materials and Methods: Reactive sera (O.B., E.C., S.K., R.F.) were tested against RBCs with normal MNS phenotypes and with TSEN‐positive RBCs. The RBCs of D.L., J.S. and C873 were tested with anti‐S whose reactivity with S+s+ TSEN+RBCs had been established previously, and with the original example of anti‐TSEN. Immunoblotting was performed on the C873, D.L. and J.S. RBC membranes using a monoclonal antibody to an epitope common to both glycophorin A and glycophorin B. Results: The sera from O.B., E.C., S.K. and R.F. were strongly reactive on the indirect antiglobulin test with TSEN+ RBCs. The RBCs of C873, D.L. and J.S. were typed as TSEN+. Immunoblotting pattern of D.L. and C873 were consistent with TSEN heterozygotes, while that of J.S. was consistent with a TSEN homozygote. Conclusions: Based on the estimated number of screening events with C873 RBCs, the incidence of anti‐TSEN is approximately 1 in 20,000 sera. The antibody is found in patients with and without documented exposure to allogeneic RBCs. All known examples of anti‐TSEN are lgG, but their clinical significance is not known.
First Example of Hemolytic Disease of the Newborn Caused by Anti‐Or and Confirmation of the Molecular Basis of Or
Authors: Reid Marion E. , Sausais Laima , Øyen Ragnhild , Storry Jill R. , Shukla Harikrishna , Hsu Tony , Lim Suk‐Mui
Published: December 2004

Abstract
Background and Objectives:
The rare MNS antigen Or (MNS31) is sensitive to ficin, papain and sialidase, but partially resistant to trypsin (0.05%); the effect of α‐chymotrypsin is not known. A point mutation, 204C → T in exon 3 of GYPA, is associated with the Or+ phenotype. We report here the first case of hemolytic disease of the newborn (HDN) caused by anti‐Or, and expand the information on the nature of the Or determinant. Materials and Methods: A woman, gravida 4, para 0, delivered a baby whose red blood cells (RBCs) were positive (2+) on the direct antiglobulin test (DAT). The mother's serum, an eluate made from the baby's RBCs and the RBCs of the baby's father were investigated. Exon 3 of GYPA, extracted from the father's genomic DNA, was amplified and sequenced. Results: The mother's serum reacted at room temperature, 37°C and on the indirect antiglobulin test with RBCs from the baby's father. The father's RBCs were M+N+S‐s+Or+. The antibody in the mother's serum and in the baby's eluate was identified as anti‐Or. The serum did not react with the father's RBCs treated with trypsin (180,000 U/ml), but did react with his α‐chymotrypsin‐treated RBCs. Amplification and sequencing of DNA from the father revealed a single point mutation, 204C → T, in GYPA exon 3. At birth, the baby had clinical symptoms of HDN and was transfused with 36 ml of packed RBCs and received phototherapy for eight days. At week 11, the baby's M+N+S+s+Or+ RBCs were negative on the DAT. Conclusion: This is the first case of HDN caused by anti‐Or. The observed point mutation, 204C → T, confirms that of a previous report and predicts a change of Arg (Or‐) to Trp (Or+) at amino acid 31.
Press Review
Authors: Engelfriet C.P. , Dzik S. , Moroff G. , Dumont L.
Published: December 2004

A Multicenter Study Evaluating Three Methods for Counting Residual WBCs in WBC‐Depleted Blood Components: Nageotte Hemocytometry, Flow Cytometry and Microfluorometry
Evaluation of virus and prion reduction in a new intravenous immunoglobulin manufacturing process
Authors: Trejo S. R. , Hotta J. A. , Lebing W. , Stenland C. , Storms R. E. , Lee D. C. , Li H. , Petteway S. , Remington K. M.
Published: December 2004

Background and Objectives Minimizing the transmission risk of infectious diseases is of primary importance in the manufacture of products derived from human plasma. A novel chromatography‐based intravenous immunoglobulin (IGIV) manufacturing process was developed and the reduction of virus and transmissible spongiform encephalopathies (TSE) during the manufacturing process was assessed. Mechanistically distinct steps that could affect virus reduction were identified, and the robustness of virus reduction over the range of process conditions was determined.

Materials and Methods Virus and TSE reduction by processing steps were assessed using a scaled‐down version of the IGIV manufacturing process.

Results Virus and TSE reduction at manufacturing process set points were well within safety standards. Robustness studies verified that the reproducibility of virus reduction was maintained at or beyond operating parameter extremes. Virus reduction across two combined manufacturing steps was lower than the sum of virus‐reduction values across the individual steps, indicating mechanistic similarity of the two steps with respect to virus reduction. Only reduction from mechanistically distinct steps was claimed.

Conclusions This comprehensive approach to pathogen safety provides the new immunoglobulin manufacturing process with a detailed, yet realistic, assessment of the risk of transmission of infectious pathogens.
Human immunodeficiency virus‐1 and hepatitis C virus RNA among South African blood donors: estimation of residual transfusion risk and yield of nucleic acid testing
Authors: Fang C. T. , Field S. P. , Busch M. P. , Heyns A. du P.
Published: December 2004

Background and Objectives South Africa is an endemic area for human immunodeficiency virus 1 (HIV‐1) infection, which has an impact on the safety of the blood supply. We studied the presence of HIV‐1 and hepatitis C virus (HCV) RNA, and recent HIV seroconversion, in blood donors in order to estimate transfusion risk and to determine whether nucleic acid testing (NAT) could effectively improve blood safety.

Materials and Methods Unlinked samples collected in 1999 from 9077 HIV‐low prevalence (LP) and 10 632 HIV‐high prevalence (HP) donors were studied. Donor demographic information and serology results were collected prior to breaking the linkage. All samples were individually tested using a multiplex NAT assay for HIV‐1 and HCV RNA. HIV antibody‐positive samples were further tested using a ‘detuned’ (less sensitive) enzyme immunoassay (EIA) procedure to determine whether a donor had recently acquired infection. Data were used to estimate the residual transfusion risk and to project NAT yield.

Results HIV was 45 times more prevalent in the HP‐ than in the LP donor group; and among the HP group, female donors had a significantly higher prevalence of HIV than male donors. All seven HIV‐1 p24 antigen‐positive samples in the study were also HIV NAT positive. Two HIV NAT‐positive samples were anti‐HIV negative; both of these samples were from HP donors. Assuming that 10% of the 900 000 annual donations in South Africa are from the HP group, we projected an annual NAT yield of 8·5 cases over the current screening of antibody and p24 antigen. However, if p24 antigen testing were to be eliminated, this number would be increased to 17 cases per year. Based on ‘detuned’ EIA results, the incidence rate for HIV infection was estimated at 1·29 and 51·12 per 10 000 per year for the LP and HP donor groups, respectively. Assuming a 15‐day earlier detection by HIV NAT compared with antibody tests, these incidence rates project that NAT may intercept an additional 23 (95% confidence interval: 15–33) HIV‐positive donations per year. For HCV, two viral RNA and antibody‐positive samples (one from the LP group and one from the HP group) and no NAT yield cases were found in the study.

Conclusions Implementation of routine NAT blood screening would allow elimination of HIV‐1 p24 antigen testing and improve the safety of the blood supply in South Africa. However, the cost–benefit ratio of introducing such an expensive technology in a country with a limited health budget will have to be carefully considered.
Additive effects of dipyridamole and Trolox in protecting human red cells during photodynamic treatment
Authors: Besselink G. A. J. , Van Engelenburg F. A. C. , Ebbing I. G. , Hilarius P. M. , De Korte D. , Verhoeven A. J.
Published: December 2004

Background and Objectives Photodynamic treatment (PDT) of red blood cell (RBC) suspensions has been reported to result in virus inactivation, but also in deterioration of cell quality. Recently, we have demonstrated the potential usefulness of the reactive oxygen species scavenger dipyridamole in selectively protecting RBCs against the harmful side‐effects of PDT. Unfortunately, dipyridamole‐conferred protection against long‐term photohaemolysis was incomplete. In the present study, dipyridamole was applied in combination with Trolox (a hydrophilic vitamin E analogue) in order to augment RBC protection.

Materials and Methods Leucodepleted RBC suspensions (30% haematocrit) were treated with 1,9‐dimethylmethylene blue (DMMB) and red light, and the effect of inclusion of dipyridamole and Trolox was assessed on potassium leakage as well as on short‐term and long‐term photohaemolysis. Possible interference of the scavenger cocktail with virus inactivation was examined using extracellular pseudorabies virus (PRV).

Results Treatment of RBC with DMMB and red light resulted in enhanced potassium leakage and both short‐ and long‐term haemolysis. Dipyridamole and Trolox showed additive protective effects against induction of potassium leakage and photohaemolysis, suggesting different protection mechanisms for the two scavengers. Combined inclusion of dipyridamole and Trolox did not interfere with efficacy of PRV inactivation.

Conclusions Combined inclusion of dipyridamole and Trolox results in substantially improved selectivity of photodynamic treatment of RBC suspensions.
A Dc‐ phenotype encoded by an RHCE–D(5–7/8)–CE hybrid allele
Authors: Cotorruelo C. M. , Biondi C. S. , Borrás S. E. García , Di Mónaco R. A. , Racca A.
Published: December 2004

Background and Objectives The Rh system is genetically controlled by the homologous RHD and RHCE genes that encode the RhD and RhCcEe polypeptides, respectively. Deletions, point mutations and rearrangements between both genes are responsible for the great polymorphism of this system. The aim of this work was to analyse the genetic basis of a Dc‐ phenotype.

Materials and Methods DNA samples from the Dc‐ propositus and family members were obtained from peripheral blood. RHCE intron 4‐exon 5 and RH exons 4, 5, 6 and 7 were analysed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Exon 9 was studied by PCR–sequence‐specific primers (SSP). The RH locus was further analysed by using a PCR designed for a hybrid allele.

Results No RHCE‐specific fragments were found when analysing exons 5, 6 and 7 of the RH locus from the propositus’ DNA, while exons 4 and 9 of both RH genes were present.

Conclusions The results obtained indicated that the Dc‐ phenotype is encoded by a novel RHCE–D(5–7/8)–CE hybrid allele.
Combining Genotype Groups and Recursive Partitioning: An Application to Human Immunodeficiency Virus Type 1 Genetics Data
Authors: Foulkes A. S. , De Gruttola V. , Hertogs K.
Published: December 2004

Understanding the relationship between human immunodeficiency virus type 1 genotypic markers of resistance and response to therapy presents an analytic challenge because of the high dimensionality of the viral genome and the complex interactions across sites on the genome. Recursive partitioning is a natural approach to classifying patients on the basis of covariates that capture information on the variability of a response variable and is therefore well suited to handling both of these features of the problem. In the human immunodeficiency virus genetics setting, we aim to classify patients on the basis of the genotypic characteristics of their infecting viral population so that the resulting groups explain the most variability in drug susceptibility phenotype. Recursive partitioning is also informative in identifying meaningful genotypic patterns that define the resulting classes. By combining dimension reduction techniques with recursive partitioning we can arrive at different classification schemes which are potentially more informative. Furthermore, the use of weighted distance metrics in the clustering algorithm allows us to update and potentially to improve on this classification scheme. An illustration of the relative benefits of the various approaches is provided by using 2559 protease sequences and the corresponding 50% inhibitory concentrations for Indinavir.
P33Fetal diaphragmatic hernia: our experience of 43 cases
Authors: Galindo A. , Carrera  , Arbues J. , Puente J. M. , Benedicto  , Cano I. , De La Fuente P.
Published: December 2004

Aim

To review our experience with diaphragmatic hernia (DH).

Methods

We review retrospectively 43 cases prenatally diagnosed and 7 postnatally between January 1990 and November 1999.

Results

The incidence was 1/1496 deliveries. Sensitivity was 86%. Mean gestational age at diagnosis was 29 weeks. In 15 cases (38%), diagnosis was ≤ 22 weeks; perinatal mortality rate (PMR) in these did not differ significantly from that in cases of later diagnosis (80% vs. 50%). In 36 cases (83.7%) there was left‐sided DH and in 7 cases (16.3%) was right‐sided without differences in PMR (58.3% vs. 71.4%). In 17 cases (39.5%) associated anomalies were observed; PMR was significantly higher than in isolated cases (94.1% vs. 38.5%). In 14 cases (32.5%) liver herniation was noted; PMR was also significantly higher than in cases without herniation (78.6% vs. 51.7%). The incidence of polyhydramnios was 30% (13/43); differences in PMR between subgroups were statistically significant (76.9% vs. 16.7%). A pseudohypoplasia of the left heart was observed in 9 cases (20.1%); PMR was significantly higher than the observed in cases without it (77.8% vs. 55.9%). Mean weight of the newborns was 2435 g. The PMR in cases < 2500 g was significantly higher than in newborns > 2500 g (75% vs. 26.3%). Overall PMR in cases prenatally diagnosed was 60.5% and in those postnatally diagnosed was 43% (not statistically significant). Considering only prenatally diagnosed isolated cases, the survival rate rose to 65.3% and excluding terminations of pregnancy to 85%.

Conclusion

The prognosis of DH largely depends on the existence of associated defects but there are several prognostic factors associated with a worse outcome. However isolated cases may have a favourable outcome with ‘classical’ management.
WS07: Fetal endoscopy and invasive procedures WS07‐01Fetal hydrolaparoscopy and endoscopic cystotomy in complicated cases of lower urinary tract obstruction
Authors: Quintero R. A. , Bornick P. W. , Morales W. J. , Allen M. H. , Johnson P. K.
Published: December 2004

Background

Vesicoamniotic shunting may be difficult or impossible in selected cases of fetal lower obstructive uropathy (LOU). The purpose of this paper is to describe the performance of fetal hydrolaparoscopy (FHL) and endoscopic fetal cystotomy (EFC) in fetuses with complicated LOU.

Method

FHL‐EFC was performed in one patient with a markedly thickened bladder that could not be entered percutaneously. A peritoneoamniotic shunt was also placed. FHL‐EFC was performed in a second patient with a collapsed bladder from a previous vesicocentesis, as vesicoinfusion resulted in further ascites. Fetal cystoscopy was performed after EFC, and posterior urethral valves were ablated with YAG‐laser. A vesicoamniotic shunt was inserted.

Results

Adequate bladder drainage was obtained in both cases. The first baby required bilateral nephrostomies and a permanent cystotomy at birth, and is scheduled for a bladder expansion procedure at one year of age. The second patient had premature rupture of membranes and fetal demise from treatment of this complication 5 days after the original procedure.

Conclusion

FHL‐EFC can be performed in complicated LOU cases. The procedure involves the creation of a defect in the bladder dome under direct endoscopic visualization within a hydroperitoneum. Peritoneo or vesicoamniotic shunting, or ablation of posterior urethral valves may then be performed. FHL‐EFC should be reserved only for complicated cases of LOU where conventional vesicoamniotic shunting is not possible.
F02Sonographic preoperative assessment of myometrial invasion in endometrial cancer
Authors: Exacoustòs C. , Romanini M. E. , Rinaldo D. , Carusotti C. , Arduini D. , Benedetti‐Panici P. , Romanini C.
Published: December 2004

Background

The purpose of this study was to assess the accuracy of transvaginal sonography (TVS) and Color/Power Doppler (CFD/PD) in evaluating the depth of myometrial invasion and preoperative staging of endometrial cancer.

Method

All patients (pts) with histological confirmed endometrial cancer were evaluated sonographically before surgery. In all patients the endometrium was scanned by TVS to evaluate thickness, echogenicity, border, intraluminal fluid and intracavitary masses. CFD/PD were used to evaluate vessels distribution and resistance indices: Myometrial infiltration was evaluated more or less than 50%. Sonographic results were compared to histological staging obtained after surgery.

Results

53 patients were enrolled. All had endometrial thickness > 5 mm, mean thickness 19.5 ± 10.5 mm. Myometrial invasion was < 50% in 35 pts, TVS evaluation was exact in 33 cases, with a sensitivity of 94% and a positive predictive value (PPV) of 94%. An infiltration > 50% was seen with TVS in 12 pts and was histologically confirmed in 11, with a sensitivity of 82% and PPV of 75%. Other 3 pts had a cervical infiltration, 3 had stage 3, one had stage 4. TVS evaluated correctly 48 patients with a sensitivity of 91%.

Conclusions

TVS seems to be a valuable, noninvasive and unexpensive diagnostic method for the assessment of myometrial invasion.
Upward migration of cultured autologous keratinocytes in Integra™ artificial skin: a preliminary report
Authors: Jones Isabel , James S. Elizabeth , Rubin Philip , Martin Robin
Published: December 2004

The combination of cultured autologous keratinocytes with the dermal regeneration template Integra™ could offer increased possibilities for reconstructive surgery and wound healing. A single‐step application of cells, centrifuged deep into an Integra™‐like matrix at the silicone–matrix junction, has been described but might prove technically complex for clinical use. We have investigated the possibility of simplifying this procedure by applying cultured cells directly to the underside of the Integra™ or directly to the wound bed immediately prior to grafting. The objective was to see whether cells would migrate through the matrix in an upward direction. We tested the principle of this concept using a pig wound healing model. Integra™ was seeded directly with cultured cells and grafted onto fresh full‐thickness wounds, or unseeded Integra™ was applied to freshly excised wound beds that had just been seeded with the same number of cells. Biopsies were taken at 3, 7, 11, and 14 days. Histological sections showed that the cells moved through the Integra™ to give a confluent surface epithelium. Direct seeding onto the Integra™ was the most efficient method. Transduction of cultured autologous keratinocytes in vitro with a MFGlacZnls retrovirus confirmed that the epidermis was derived from the cultured autologous keratinocytes. (WOUND REP REG 2003;11:132–138)
Hyperbaric oxygen treatment prevents up‐regulation of angiogenesis following partial‐thickness skin grafts in the pig
Authors: Kalns John E. , Dick Edward J. , Scruggs Julie P. , Kieswetter Kris , Wright Jim K.
Published: December 2004

We hypothesized that hyperbaric oxygen treatment (HBO) would reduce neovascularization following partial‐thickness skin grafting in the Yucatan pig. Results show that capillary density 4 days postgraft is increased twofold in grafts not treated with HBO, compared to normal, ungrafted skin or skin grafts from pigs treated with HBO, p < 0.05. Similarly, the expression of vascular endothelial growth factor, a growth factor associated with neovascularization, was also reduced by HBO. Cell density in the graft boundary increased gradually after grafting, reaching a maximum 2.7‐fold increase, relative to normal skin, at day 4, p < 0.05. Cell nuclei positive for proliferating cell nuclear antigen, a marker of proliferation, increased threefold by day 2, p < 0.05, and then declined to normal levels by day 7. HBO had no effect on cell density or proliferation in the boundary region or on shear strength of the graft. In the epidermis, proliferation declined 80% 2 days after grafting and then returned to levels observed in normal skin by day 4, p < 0.05; however, in pigs treated with HBO, we observed no decline in proliferation. These findings confirm the hypothesis that HBO reduces neovascularization in the partial‐thickness skin graft while preserving regenerative capacity in the graft boundary and normal proliferative capacity of the epidermis. (WOUND REP REG 2003;11:139–144)
THE CLINICAL EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES IN CHRONIC KIDNEY DISEASE: Hemodynamic Cardiovascular Risk Factors in Chronic Kidney Disease: What are the Effects of Intervention?
Authors: McMahon Lawrence P.
Published: December 2004

Left ventricular (LV) volume and pressure overload occur frequently in chronic kidney disease (CKD). Anemia is a risk factor for left ventricular hypertrophy (LVH) and dilatation, heart failure, and death. Normalization of hemoglobin with erythropoietin may prevent LVH and dilatation in CKD, but in patients in later phases of their cardiac disease, this intervention is not of benefit. Increased vascular volume causes hypertension, which in turn causes LVH, cardiac failure, and ischemic heart disease (IHD). Manifestations of arteriosclerosis are associated with adverse cardiac outcomes, and angiotensin converting enzyme (ACE) inhibitors may improve LVH and markers of arteriosclerosis. Aortic stenosis in dialysis patients occurs infrequently, but may deteriorate rapidly. The hemodialysis milieu is the quintessential model of LV overload cardiomyopathy.
Bilirubin Adsorption Column Medisorba BL‐300
Authors: Nakaji Shuhei , Hayashi Nobuyuki
Published: December 2004

Abstract:  Bilirubin adsorption column Medisorba BL‐300 (Kuraray MedicalInc.) for the treatment of hyperbilirubinemia is introduced. Theadsorbent packed in this column is the porous anion exchange resincoated with hydrophilic 2‐hydroxyethyl methacrylate copolymer in orderto improve blood compatibility. The adsorbent showed a high adsorptionrate for direct bilirubin and indirect bilirubin in patient plasmain vitro. This column is used in plasmaperfusion therapy in clinicaluse. BL‐300 showed high removal rate for direct bilirubin, indirectbilirubin and bile acid in clinical evaluation. BL‐300 is approvedin Japan and it has been used for the treatment of hyperbilirubinemiacaused by many diseases such as liver failure and hepatitis.
Plasma Separator Plasmaflo OP
Authors: Hirata Noriko , Shizume Yasumasa , Shirokaze Jun‐ichi , Suemitsu Junsuke , Yoshida Hajime , Yamawaki Naokuni
Published: December 2004

Abstract:  In recent years, polyethylene and polysulfone membranes havebeen used for plasma separation in Japan. The polyethylene membrane,manufactured by melt spinning method, has a sponge‐like symmetricstructure. The plasma separator Plasmaflo OP (Asahi Medical, Tokyo, Japan)with a polyethylene membrane shows excellent performance and safetyfor plasma separation. More than 20 indications for therapeuticplasmapheresis are reimbursed in Japan. Future development is expectedin new membrane designs for new indications or advanced plasmapheresis methodologies.
β2‐Microglobulin‐selective AdsorbentColumn (Lixelle) for the Treatment of Dialysis‐related Amyloidosis
Authors: Suzuki Kazuo , Shimazaki Masami , Kutsuki Hidetoshi
Published: December 2004

Abstract:  Lixelle is a direct hemoperfusion‐type adsorbent column developedfor selective elimination of β2‐microglobulin(β2‐m) from the circulating blood of patientswith dialysis‐related amyloidosis (DRA). Lixelle S‐35, that has a column volume of 350 mL, efficiently eliminates β2‐m andimproves symptoms of DRA such as joint pain and nocturnal awakening.The performance of Lixelle S‐15, that has a column volume of 150 mL,is dependent on the dialysis membrane used in combination with theadsorbent column in a hemodialysis circuit. The combination of S‐15 anda dialysis membrane with a high β2‐m clearance eliminatesan amount of β2‐m that is nearly equal to the amount removed by using S‐35. Treatment with S‐15 for 6 months improved joint pain with an efficacy similar to that observed when using S‐35. The major adverse effectswere hypotension and decrease in hematocrit, and these incidenceswere much less in S‐15 compared to S‐35.
Immunotherapy Exploiting the Versatility of Dendritic Cells
Authors: Kadowaki Norimitsu
Published: December 2004

Abstract: Dendritic cells (DC) are the most potent antigen‐presenting cells that initiate T cell‐mediated immune responses. The development of methods to generate a large number of DC in vitro has facilitated their application to immunotherapy. Adding tumor antigens to DC in vitro and administering them to cancer patients is expected to induce effective immune responses to cancers, which are poorly immunogenic in most cases. There are several parameters that need to be optimized to improve the efficacy of DC‐based immunotherapy. Because the immune system has developed in order to eliminate microbial pathogens and is thus well equipped with machinery for that purpose, reproducing events occurring during anti‐infection immune responses for antitumor immunity may lead to the development of effective tumor immunotherapy.
Development of a Device for Selective Removal of CD4+ T Cells
Authors: Onodera Hirokazu , Ninomiya Kasumi , Yoshida Makoto , Matsuo Hidenori , Shibuya Noritoshi
Published: December 2004

Abstract: To control antigen (Ag)‐specific immune cells is important in the treatment of autoimmune diseases. In particular, controlling the immune response of autoimmune T cells is effective in the treatment of these diseases. The development of a device that can remove CD4+ T cells specifically by extracorporeal circulation is now in progress, with the aim to deplete autoimmune T cells. We developed a removal material made of polypropylene non‐woven fabrics with anti human CD4 monoclonal antibody immobilized on the surface. Using a column packed with the removal material, we succeeded in removing CD4 + T cells specifically from peripheral whole blood by direct perfusion. Moreover, CD4+ T cells can be specifically removed even from blood with lower surface antigen density by in vitro activation.
A Clinical Role for Peripheral Blood Lymphocyte Infusions and Perspectives on Collection
Authors: Hester Jeane
Published: December 2004

Abstract: Molecular remissions were observed in some relapsed post allogeneic transplant chronic myeloid leukemia (CML) patients who received donor peripheral blood lymphocyte infusions (DLI). This was indirect evidence of immune‐mediated tumor cell killing, and the process was termed graft‐versus‐leukemia (GVL). Mechanisms were hypothesized to be direct T cell mediated cell lysis or augmented programmed cell death. These observations formed the basis for exploring the role of DLI first in relapsed allogeneic transplant patients with other hematologic malignancies, then as prophylaxis for patients at high risk for relapse and then as adjunctive therapy for transplant strategies utilizing non‐myeloablative conditioning regimens. Multiple clinical trials are underway to define dose, schedule, clinical and molecular response and laboratory assays to distinguish lymphocyte subsets mediating GVL and those responsible for graft‐versus‐host disease (GVHD) toxicity. This review outlines some of the donor/patient and therapy variables involved and some principles of mononuclear cell collection for cellular immunotherapy.
Brief History of Low‐density Lipoprotein Apheresis
Authors: Yokoyama Shinji
Published: December 2004

Abstract:  Low‐density lipoprotein (LDL) apheresis is a technology used to remove LDL from hypercholesterolemic patients. The technique includes both specific and non‐specific removal of LDL such as exchange of the whole plasma and selective adorption of LDL. The therapy is mainly used for homozygotes and in severe cases of heterozygotes of familial hypercholesterolemia (FH) (LDL receptor deficiency). Since HMG‐CoA reductase inhibitors, statins, were introduced in late 1980s, the number of patients who required LDL apheresis decreased, in particular for the heterozygous FH patients with more recent powerful statins. Modern LDL apheresis technology is very sophisticated and perhaps expensive, while the number of the patients is very limited. Several companies developed the instruments for this procedure, but found the market is limited. Nevertheless, these companies are expected to remain in the market for an ethical reasons, as the patients using their LDL apheresis machines are entirely dependent on them for their life.
Low‐density Lipoprotein Apheresis: An Overview
Authors: Bambauer Rolf , Schiel Ralf , Latza Reinhard
Published: December 2004

Abstract:  Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp(a)) levels, and coronary heart disease (CHD) refractory to diet and lipid‐lowering drugs is poor. For such patients, regular treatment with low‐density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin‐induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high‐density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low‐density lipoprotein (LDL) apheresis was performed over 95.6 ± 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein (a) (Lp[a]), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side‐effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement in general well‐being and increased performance were experienced by 44 of 45 patients. The present data demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia resistant to maximum conservative therapy is very effective and safe even in long‐term application.
Long‐term Effect of Low‐density Lipoprotein Apheresis in Patients with Homozygous Familial Hypercholesterolemia
Authors: Makino Hisashi , Harada‐Shiba Mariko
Published: December 2004

Abstract:  Patients that are homozygous for familial hypercholesterolemia (FH) exhibit severe hypercholesterolemia, cutaneous and tendon xanthomas and premature atherosclerosis beginning in childhood. They are resistant to drug therapy and low‐density lipoprotein (LDL) apheresis is the practical treatment. Here we review the technique of LDL apheresis treatment, the long‐term effects of LDL apheresis, the effect of apheresis on pregnancy, and the drugs that have proven beneficial in patients with homozygous FH. We also record our experiences of treating eight homozygous FH patients using the LDL apheresis treatment. Among the eight patients, one has been free from cardiovascular disease and two patients have each regressed once. In two patients, aortic valve stenosis developed and the other two patients died for acute myocardial infarction. Furthermore, two patients delivered healthy babies in spite of coronary artery disease. Thus, LDL apheresis therapy has the possibility of preventing the progression of atherosclerosis, but the prognosis assessed by long‐term observation is still not satisfactory. A recent clinical trial showed some efficacy of the combination therapy of LDL apheresis and atorvastatin for reducing serum choresterol levels in homozygous FH, suggesting that this combination therapy may be useful for prevention of atherosclerosis in patients homozygous for FH.
Hypercholesterolemic Valvulopathy: An Aspect of Malignant Atherosclerosis
Authors: Kawaguchi Akito , Yutani Chikao , Yamamoto Akira
Published: December 2004

Abstract:  Hypercholesterolemia affects not only the coronary artery, but also the aortic root, particularly the aortic valve. Aortic stenosis is critical in the prognosis for most patients with homozygous familial hypercholesterolemia (FH) and some heterozygous FH patients who result in aortic valve replacement (AVR). Histopathological examination of their valves shows lipid deposition, inflammatory cell infiltration and calcification in the aortic cusps. These pathological findings are common in non‐FH patients with AVR. In homozygous FH patients, the aortic valves are injured by extreme hypercholesterolemia in a relatively short period of time, whereas in heterozygous FH patients with additional risk factors, the damage to the valves occurs over an intermediate time period. In the non‐FH population with several risk factors, an underlying raised serum cholesterol level results in gradual impairment over a number of years. Aortic valvular dysfunction caused by hypercholesterolemia, which we termed hypercholesterolemic valvulopathy is recognized to be a life‐threatening complication as the primary clinical characteristic of malignant atherosclerosis.
Low‐density Lipoprotein Apheresis in the Prevention of Recurrent Coronary Heart Disease: A Review
Authors: Tasaki Hiromi
Published: December 2004

Abstract:  This article summarizes the clinical evidence for low‐density lipoprotein (LDL) apheresis to improve prognosis of patients with coronary heart disease. Regarding clinical events or angiographic parameters, most trials have revealed favorable effects on coronary artery disease. In the studies with a clinical endpoint, approximately 50% reduction in incidence of major coronary events was achieved by LDL apheresis. Similarly, in the studies with a angiographic parameter, coronary atherosclerosis was suppressed or regressed by LDL apheresis. The mechanisms of these effects by LDL apheresis are attributed to improvement in coronary flow reserve, which is dependent upon increases in hemo‐rheological factor, nitric oxide, vasoactive substances or decrease of oxidized LDL. These new insights into mechanisms will expand the indication of LDL apheresis to other pathophysiological conditions of coronary artery disease and other disorders.
Changes in Oxidative Stress and Microcirculation by Low‐density Lipoprotein Apheresis
Authors: Sato Motoyoshi , Amano Izumi
Published: December 2004

Abstract:  Low‐density lipoprotein apheresis (LDLA) leads to an improvement of microcirculation during the very early stages of treatment, and continued treatment may produce antiatherogenic effects in patients with peripheral arterial disease (PAD). Suppression of oxidative stress, improvement of endothelial functions and alteration in the action of vasoactive compounds may occur with the improvement of the rheological property of blood as a result of aggressive removal of atherogenic factors including LDL, possibly resulting in the suppression of development of atherosclerosis. As these effects of LDLA may ameliorate not only PAD but also ischemia in other organs, it is suggested that repeated LDLA prevents the progression of atherosclerotic diseases and probably improves the long‐term prognosis of patients with PAD.
Comparison of HL‐A Typing with NIH Trays and the NIH Technique with Typing by the Fluorochromasia Cytotoxicity Assay
Authors: Perkins H. A. , Howell E. , Gantan Z. , Ross J.
Published: December 2004

A comparison of HL‐A phenotypes determined with plates containing predispensed typing sera supplied by the NIH Serum Bank with phenotypes determined by the fluorochromasia cytotoxicity assay using local reagents showed that the NIH plates (as dispensed in 1972) had an insufficient number and variety of typing sera. Using NIH trays, it was difficult to detect HL‐A9 and W19, both of which specificities are now known to have subtypes. The NIH trays also appeared to detect more HL‐A antigens than were consistent with the current theory of two segregant series, each expressing a maximum of two antigens. The excess antigens could not be comparatively evaluated in view of the small number of sera defining each. With the NIH technique, it was impossible to interpret the reactions if the preparation had too many dead cells. A high proportion of dead cells was occasionally noted when lymphocytes had been previously frozen or obtained from lymph nodes. When the NIH and fluorochromasia techniques were compared using the same antisera and fresh lymphocytes, they proved equivalent in sensitivity.
An Autoantibody with Anti‐Wrb Specificity in a Patient with Warm Autoimmune Hemolytic Anemia
Authors: Goldfinger D. , Zwicker H. , Belkin G. A. , Issitt P. D.
Published: December 2004

A patient with warm autoimmune hemolytic anemia (AIHA) has been found to possess an autoantibody with Wrb specificity. While this is the first known description of Wrb specificity in this disease, additional studies on the Wrb status of En(a‐) cells indicate that autoantibodies previously thought to be anti‐Ena are in reality also anti‐Wrb. Autoantibodies with Wrb specificity may thus be a rather common finding in patients with AIHA who have been thought to have “panagglutinins” on their red blood cells. Since anti‐Wra alloantibodies are found frequently in patients with AIHA, it seems possible that the Wright system holds some clue to the pathogenesis of this disease.
An En(a–) Red Cell Sample That Types as Wr(a–b–)
Authors: Issitt P. D. , Pavone B. G. , Goldfinger D. , Zwicker H.
Published: December 2004

In the course of investigating a patient with autoimmune hemolytic anemia in which the causative autoantibody had anti‐Wrb specificity, it was demonstrated that an En(a–) red blood cell sample typed as Wr(a–b–). The only known example of Wr(a+b–) blood typed as En(a+) so that anti‐Wrb and anti‐Ena do not have the same specificity.
A New Example of Anti‐LW and Further Studies on Heterogeneity of the System
Authors: White J. C. , Rolih S. , Wilkinson S. L. , Hatcher B. J. , Issitt P. D.
Published: December 2004

A case is reported in which an LW, woman formed anti‐LW. It is shown that the case represents the “genetic” and not the “transient” type of red blood cell LW antigen depletion. Studies have confirmed the quantitative difference of LW antigen on LW3 and LW4 red blood cells and the fact that Rh null individuals produce the only totally LW‐negative red blood cells. The difficulties encountered in the identification of anti‐LW, because of the LW3 and LW, states, are described. It is clear, from this study, that if random donors are typed for LW using anti‐LW made by an LW4individual, those who are LW3 will be classed as unremarkable LW‐positives.
Factor VIII Preservation Following Collection into Commercial Plasmapheresis Systems
Authors: Mishler J. M. , Nicora R. W. , Hamilton J. E. , Caster G. , Kasper C. K.
Published: December 2004

The two‐stage method of Pool and Robinson was used in determining plasma Factor VIII activity following contact with four commercially available plastic blood and pooling bag films. Employing a two‐arm double plasmapheresis technique, it was shown that Factor VIII activity in whole blood initially drawn into BB‐69 and PL‐130 blood bags decreased only slightly from in vivo levels for activity in PL‐130 blood bags (t = 3.2317, p. < 0.01). Factor VIII activity fell to 98 and 90 per cent preservation levels from an initial 104 per cent in vivo activity, for BB‐69 and PL‐130 respectively. Factor VIII activity in plasma collected in Ellay and PL‐146 pooling bags, both decreased significantly to 85 and 86 per cent, respectively, after three hours storage at room temperature (24 to 25.5 C). Following five weeks storage (‐30 C) in Ellay and PL‐146 pooling bags, Factor VIII activity significantly (p < 0.005) fell to 79 and 77 per cent, respectively. No significant differences were observed when Factor VIII activity levels were compared in BB‐69 versus PL‐130 or Ellay versus PL‐146 plastic film systems.
Coagulation Defects in Rabbits after Infusion of Dispersed Fluorochemicals
Authors: Lau P. , Shankar V. S. , Mayer L. L. , Wurzel H. A. , Sloviter H. A.
Published: December 2004

Coagulation parameters were studied in rabbits during and after intravenous infusion of suspensions of dispersed fluorochemicals. Blood samples from rabbits given dispersed perfluorobutyltetrahydrofurane or perfluoro‐tributylamine showed thrombocytopenia, prolongation of activated partial thromboplastin time, and decreases in Factors X and XI. The possible presence of an inhibitor of coagulation was suggested by the prolongation of prothrombin time when measured with serial dilutions of thromboplastin reagent. These abnormalities were not found in whole blood or platelet‐rich plasma after incubation in vitro with dispersed fluorochemical.
A Case Report of a Hemolytic Transfusion Reaction Caused by Anti‐Holley
Authors: Beattie K. M. , Castillo S.
Published: December 2004

Clinical and laboratory investigation of a black male patient, who received emergency transfusion of blood incompatible for a high incidence antigen, provided evidence for the pathogenetic importance of high titer anti‐Holley antibodies with poor avidity. The red blood cells of the patient and two siblings were remarkable in being negative for two high incidence antigens, Hy and hrs, and weak for a third, Gy.
Studies of the Recovery and the Cost of Low‐Glycerol Cryopreserved Human Red Blood Cells
Authors: Bowman H. S. , Oski F. A. , Reihart J. , Simmonds M. A. , Cunningham R. K.
Published: December 2004

Red blood cells were equilibrated with 28 per cent (v/v) glycerol and 3 per cent mannitol in 0.65 g/100 ml sodium chloride. The units were frozen by immersion into liquid nitrogen and stored at ‐160 C. After thawing, they were reconstituted and washed using the IBM 2991 Blood Cell Processor. Freeze‐thaw rate curves, the effect of thawing techniques, the effect of varying postthaw washing and processing techniques, estimates of red blood cell losses because of hemolysis, and in vitro recovery were determined. In vivo recovery was determined by 51Cr techniques 24 hours after infusion and Ashby survivals and subsequent life span were measured. Metabolic, scanning electronmicroscopy, cost estimates and quality control studies were done on the reconstituted red blood cells. Recipients were evaluated before and after transfusion for metabolic erythrocyte characteristics and for evidence of hemolysis.

The modified method requires less wash solution and less technician time than does the standard low‐glycerol method. Two units for the same recipient could be passed through the IBM software with no alteration of cell survival or loss. Revision of the IBM 2991 processing procedure provided excellent recovery of viable previously frozen red blood cells at probably a lower cost.
Exchange Transfusion in Reye's Syndrome with Saline‐Washed Red Blood Cells
Authors: Casper J. T. , Varma R. R. , Lewis J. D. , Harrington G. J. , Aster R. H.
Published: December 2004

Reye's syndrome (RS) consists of encephalopathy, fatty degeneration of viscera, and elevation of ammonia, certain amino acids, and liver enzymes in the blood. It is most characteristically a disease of children and has been considered to have a poor prognosis despite the use of various treatment regimens. Exchange transfusion (ET) with fresh blood (less than 24 hours old) for the removal of toxic metabolic byproducts in RS is a relatively recent development which appears to have improved the survival rates. However, because RS may occur in epidemic proportions at any time the demand for fresh blood can place an excessive stress on blood resources. We have, therefore, utilized saline‐washed (to remove potentially toxic metabolites) red blood cells (RBC's) less than six days old, and fresh frozen citrate‐phosphate‐dextrose (CPD) plasma in treating this disorder. Nine patients in the Milwaukee community with severe encephalopathy secondary to RS were treated with ET.

These patients collectively required 151 units of washed RBC's for 21 ET. Eight of nine patients survived without sequelae. Age of blood used did not correlate with the number of exchanges required or the eventual outcome. A continual computerized EEC in five patients provided objective evidence of the effectiveness of ET. We conclude that ET with saline‐washed RBC's reconstituted with fresh frozen plasma (FFP) is a fast, safe, and effective means of treating patients with RS.
Development and Use of Pediatric Frozen Red Cell Packs
Authors: Staples J. W. , Fritz G. E.
Published: December 2004

Repeated transfusion of small increments of blood are frequently required for the sick and premature newborn infant to correct endogenous hypovolemia and/or to replace blood obtained for laboratory monitoring purposes. Previously fresh group and type specific whole blood was used. To eliminate waste of fresh whole blood, maintain fresh red blood cell properties, eliminate the hazards of transfusing plasma and to provide a more efficient system, a pediatric frozen red cell pack (PFRCP) has been developed.

Units of group O rr red blood cells are glycerolized using a high glycerol method. The glycerolized red blood cells are separated into three equal aliquots and frozen. When needed, the PFRCP are deglycerolized by a modified procedure using the IBM Cell Processor.

During a six month period, 71 infants were given 153 separate transfusions of deglycerolized red blood cells using 102 PFRCP prepared from 34 units of red blood cells. Red blood cell recovery, hematocrit, white blood cell removal, residual glycerol, total protein, and supernatant hemoglobin levels were measured. Clinical response was followed and found to be excellent.