bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total circulating red cells versus haematocrit as the primary descriptor of oxygen transport by the blood
Authors: Jones J. G. , Holland B. M. , Hudson I. R. B. , Wardrop C. A. J. 
Published: March 2008

Summary Peripheral haematocrit (PCV) is the traditional target and monitor in many transfusion regimens. Without negating the importance of PCV as a determinant of whole blood viscosity, the present article outlines two important reasons why the red cell volume (RCV) should replace PCV in the central target role during blood transfusion in intensive care and other emergency situations:1. PCV reflects both RCV and plasma volume (PV) and is therefore not directly proportional to the total blood oxygen carrying capacity. At best, the relationship between PCV and RCV is hyperbolic and this is often overlooked when relating the two parameters in practice. At worst, the hyperbolic relationship is unreliable because PV and RCV can vary independently and the PCV is a fluctuating ratio of variable numbers.2. PCV is not a good indicator of blood volume (BV), which is another important determinant of oxygen delivery to tissues and a crucial parameter in intensively managed patients. BV is directly proportional to RCV and this relationship also is often overlooked in clinical practice.The recommended values for RCV are 30 ml/kg in men, 25 ml/kg in women and between 30 ml/kg and 45 ml/kg in neonates within the first week of life.
Using teicoplanin for empiric therapy of febrile neutropenic patients with haematological malignancies
Authors: Menichetti F. , Favero A. Del , Bucaneve G. , Aversa F. , Fiorio M. 
Published: March 2008

Summary The cumulative experience with teicoplanin in treating febrile neutropenic patients included in three different comparative clinical trials conducted at a single institution during a 3‐year period, is presented. 1 52 febrile episodes in 129 neutropenic patients were treated with iv. teicoplanin (6 mg/kg/d) combined with amikacin (15 mg/kg/d) plus ceftazidime (90 mg/kg/d). The study population comprised 75 patients with acute leukaemia and 77 marrow recipients: 53(% (81/152) had a central venous catheter in place and 68%) (103/152) had severe neutropenia (< 100/mm3) at the beginning of the febrile episode.The overall response rate of the evaluiable febrile episodes was excellent: 88% (107/122) improved. Bacteraemias due to Gram‐positive cocci accounted for 75% of the total (42/56) and pathogens in the blood isolates were mostly staphylo‐cocci (coagulase‐negative 14, coagulase‐positive 13) and streptococci (131. The response rate of Gram‐positive bacteraemias was good: 88% (37/42) improved and 75% (9/12) of Gram‐positive bacteraemias having teicoplanin as the only antibiotic with in vitro activity against the infective strains were cured. Death due to infection accounted for 7% of total febrile episodes (11/152). Side effects were documented in 14(%, of the episodes. In a setting of high prevalence of Grampositive infections caused by strains with a high rate of resistance to aminoglycoside and betalactam antibiotics, there may be an advantage in including teicoplanin in the initial empiric antibiotic regimen for febrile neutropenic cancer patients.
Treatment of refractory pure red cell aplasia with cyclosporine A: disappearance of IgG inhibitor associated with clinical response
Authors: Means Robert T. , Dessypris Emmanuel N. , Krantz Sanford B. 
Published: March 2008

Summary Remissions were obtained in 6/9 evaluable patients with pure red cell asplasia (PRCA) refractory to other immunosuppresive agents who were treated with cyclosporine A (CsA). Four of these patients have remained in continuous remission off all treatment for 4–19 months. Another patient who stopped CsA abruptly relapsed, but responded to reinstitution of therapy. The sixth patient died of a cerebrovascular accident while in remission on a low dose of CsA. Acute side effects were minimal and were responsive to dose reduction. One patient developed a lymphoma while in an unmaintained remission, and one patient who did not respond to CsA was found to have a lymphoma approximately a year after stopping treatment. In vitro studies of autologous erythroid progenitors in a patient with an IgG inhibitor of erythropoiesis showed a reduction of autoantibody associated with the response to CsA. The antigen to which this inhibitor is directed was expressed only during the marrow erythroid burst‐forming unit (BFU‐E) period of erythroid differentiation.CsA can induce sustained remissions in cases of PRCA refractory to other multiple agents, and these remissions may be associated with a reduction in autoantibody to erythroid progenitor cells. Further studies of patients with PRCA who respond to CsA may lead to an improved understanding of this disorder.
Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (Report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood)
Authors: Eden O. B. , Lilleyman J. S. , Richards S. , Shaw M. P. , Peto J. 
Published: March 2008

Summary During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial, UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 × 109/l except those aged 3–6 years with white cell counts under 10 × 109/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0–14 years with confirmed ALL.Eight hundred and twenty‐nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event‐free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease‐free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 (‘average risk’patients) and their American counterparts were similar.Daunorubicin was associated with more early deaths but improved disease‐free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year.The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment. Daunorubicin may have provided better disease control, albeit with increased toxicity, and 3 years of maintenance therapy did not confer any advantage in long‐term survival over 2 even though it may have reduced the rate of early relapse.
Antigenic determinants responsible for the reactions of drug‐dependent antibodies with blood cells
Authors: Salama A. , Santoso S. , Mueller‐Eckhardt C. 
Published: March 2008

Summary In an attempt to determine the antigenic combining sites of drug‐dependent antibodies in patients with drug‐related immune haemolysis, we have assessed the reactivity of 35 nomifensine‐induced antibodies against human red blood cells (RBC) in the presence of 11 closely related compounds: nomifensine, its three main metabolites including their methoxylated analogues and diclofensine with its three main metabolites. Three types of antibody reactivity patterns could be differentiated: Firstly, antibodies most strongly reactive with nomifensine (n= 12); secondly, antibodies primarily directed against one of its main metabolites (n= 7), and, thirdly, antibodies optimally reactive with its unknown metabolites (n= 16). The antibodies preferentially directed against nomifensine showed varying cross reactions with nomifensine‐related compounds and in almost all cases also with diclofensine and/or its metabolites. Those antibodies which were optimally reactive with metabolites reacted only with nomifensine‐derived compounds and only one of them was non‐crossreactive. The third group of antibodies showed no (n= 12) or only weak (n= 4) cross reactions with nomifensine and/or its metabolites. Although none of the substances used bound firmly to RBC, certain blood groups have been identified in previous studies to be defined. RBC antigens were required for the reaction in approximately 40% of all antibodies, independent of their reactivity with the compounds. Thus, even when the specificity of some antibodies appeared to be predominantly controlled by certain structural features of the compounds, the actual antigenic combining site of each antibody was different and seemed to comprise parts of the drug‐related determinants as well as different constituents on RBC membranes.These findings indicate firstly that RBCs function as ‘carrier‐like’macromolecules, since they are directly involved in the reaction; secondly, that the drugs and their metabolites act as ‘pseudohaptens’, in as much as they do not bind tightly to the cells; and, thirdly, that the determinants which govern the immune response appear to result from an accidental attachment rather than from a predetermined selection of antigenic membrane structures, since each antibody shows a unique reaction pattern.
CD16 and CR3 receptors distinguish between the two mechanisms of tumour cytotoxicity in neutrophils
Authors: Gavioli Riccardo , Spisani Susanna , Giuliani Anna Lisa , Elisabetta  , Cosulich  , Risso Angela , Traniello Serena 
Published: March 2008

Summary Previous studies have suggested that phorbol ester‐activated neutrophils kill both antibody non‐coated and antibody‐coated K562 target cells. In this report the contribution of the receptors FcγIII (CD16) and CR3 (CD11b/CD18) in the lytic process was investigated. In neutrophils CD16 and CR3 are up‐regulated by the phorbol ester up to 4 and 10 times, respectively. As expected, lysis of non‐immunized K562 targets is not affected by the treatment of neutrophils with anti CD16, AB8.28, whereas lysis of immunized targets is decreased by 50%. In addition, the interaction of CD16 and AB8.28 induces calcium mobilization and increases granule secretion. Surprisingly, the simultaneous binding of AB8.28 and anti‐CR3 0KM1 to neutrophils completely abolishes the lysis of antibody‐coated targets. Unlike CD16, CR3 does not possess a functional role and binding of 0KM1 to CR3 does not affect cytotoxicity of immunized K562 targets, but it blocks lysis of non‐coated target almost completely, indicating a function as adhesion protein for CR3.These studies demonstrate a distinct role of CD16 and CR3 in mediating antibody‐dependent and antibody‐independent cellular cytotoxicity, respectively.
Acute myeloid leukaemia relapsing following interleukin‐2 treatment expresses the alpha chain of the interleukin‐2 receptor
Authors: Macdonald D. , Jiang Y. Z. , Swirsky D. , Vulliamy T. , Morilla R. , And J. Bungey , Barrett A. J. 
Published: March 2008

Summary. Immunotherapy with recombinant human Interleukin‐2 (rhIL‐2) was given to nine patients in first complete remission from acute myeloid leukaemia (AML). Five patients relapsed. The median time to relapse after commencing rhlL‐2 was 26 weeks (range 2‐44).Four patients were studied at relapse. The morphological and cytochemical features at relapse and presentation were similar. Cytogenetic analysis at relapse in patients 1 and 3 showed a normal karyotype. At relapse, patient 4 had the abnormality 46,XY, t(2;3). Patient 2 had the chromosomal abnormality t(8;21) at presentation and relapse.Patients 3 and 4 with M5 AML relapsed rapidly at 2 and 9 weeks after starting rhIL‐2 treatment. Relapse leukaemia cells had features normally associated with lymphoid development. Patient 3 was TdT positive, with rearranged immunoglobulin genes, and a proportion of cells expressing the CD7 antigen; patient 4 also expressed the CD7 antigen.Relapse leukaemic cells from three of four patients expressed the α chain of the IL‐2 receptor as assessed by flow cytometry. After overnight incubation and removal of T‐lymphocytes the proportion of cells from these patients expressing the α chain increased from 15% to 61% (P < 0·01). Using tritiated thymidine uptake to assess cell proliferation, two of three patients who expressed the IL‐2 receptor α chain proliferated in response to 1000 u/ml of rhIL‐2 in vitro, with a stimulation index > 1·95 (P < 0·05).Following rhIL‐2 immunotherapy for AML, relapse cells may express an inducible form of the a chain of the IL‐2 receptor, which can mediate a proliferative response. It is possible that rhIL‐2 when administered to AML patients in remission, may induce relapse. This may be a particular risk in patients with the M5 subtype.
Evaluation of CR1 expression in neutrophils from chronic myeloid leukaemia: relationship between prognosis and cellular activity
Authors: Lanza Francesco , Fagioli Franca , Gavioli Riccardo , Spisani Susanna , Malavasi Fabio , Luigi Castoldi Gian , Traniello Serena 
Published: March 2008

Summary. The expression of the complement receptor CR1 has been evaluated using an immunoalkaline phosphatase staining method on peripheral blood neutrophils and granulocyte precursors from 22 patients with chronic myeloid leukaemia (CML) and 15 healthy subjects. The immunocytochemical labelling pattern of CR1 was evaluated semi‐quantitatively on cell smears using three different anti‐CR1 monoclonal antibodies. The scoring method showed that seven patients with CML had a marked reduction in CR1 expression which did not change with in vitro stimulation of neutrophils with phorbol‐myristate‐acetate (PMA) whereas control cells responded to PMA, increasing the receptor level two‐fold. In addition, functional analysis of neutrophils with low CR1 expression from CML patients showed a very low cytolytic activity against K562 tumour target, suggesting a relationship between the cellular content of CR1 and neutrophil tumouricidal activity. The involvement of CR1 in neutrophil‐mediated lysis is consistent with complete lack of tumour toxicity following receptor neutralization by anti‐CR1 monoclonal antibodies.Interferon therapy improved CR1 expression and the cytolytic response of neutrophils in three out of five CML patients with a moderately low CR1 score. CML patients non‐responding to interferon therapy and those with a very low CR1 score, independent of the clinical stage, progressed more rapidly into the advanced clinical stage and blastic crisis.
Role of leucocyte integrins in phagocyte responses to granulocyte‐macrophage colony stimulating factor (GM‐CSF): in vitro and in vivo studies on leucocyte adhesion deficiency neutrophils
Authors: Yong K. , Addison I. E. , Johnson B. , Webster A. D. B. , Linch D. C. 
Published: March 2008

SummaryThe role of leucocyte integrins in phagocyte function has been studied by comparing normal neutrophils with those from a patient with partial leucocyte adhesion deficiency (LAD), in whom the levels of CD11b and CD11c were 10% of controls, whereas CD11a levels were normal. Unstimulated LAD neutrophils exhibited defective adhesion to plastic (4·4 ± 1·5% cf. 14·4 ± 3·8% in controls), but not to human umbilical vein endothelial cells (HUVECs). The adhesion to HUVECs could be further upregulated by granulocyte‐macrophage colony stimulating factor (GM‐CSF), but not by 12‐0‐tetradecanoylphorbol 13‐acetate (TPA) which, in normal cells, is a more potent ‘pro‐adhesive agonist’. The normal neutrophil‐endothelial interaction induced by GM‐ CSF in LAD neutrophils was confirmed in vivo when administration of GM‐CSF resulted in rapid phagocyte marginatum. Neutrophil migration and phagocytosis/killing were defective in LAD neutrophils, and some improvement in phagocytosis/killing was seen following in vivo administration of GM‐CSF. These studies illustrate that the degree to which the leucocyte integrins mediate adherence‐related phagocyte functions varies not only with the particular function, but also with the conditions of stimulation. High levels of CD11b and CD11c expression appear not to be required for unstimulated or GM‐CSF‐stimulated neutrophil‐endothelial interactions, either In vitro or in vivo. Other neutrophil functions, on the other hand, such as migration and phagocytosis/killing are much more dependent on the leucocyte integrins.
Immunophenotypic heterogeneity of multiple myeloma: influence on the biology and clinical course of the disease
Authors: San Miguel J. F. , Gonzáalez M. , Gascón A. , Moro Ma J. , Hernáandez J. M. , Ortega F. , Jimenez R. , Guerras L. , Romero M. , Casanova F. , Sanz M. A. , Sáanchez J. , Portero J. A. , Orfao A. 
Published: March 2008

SummaryIn 112 untreated myeloma patients we have analysed the immunophenotype of plasma cells both by immunofluorescence (IF) and immunocytochemistry (APAAP). Both techniques yielded similar results pointing to aH important degree of heterogeneity in antigenic expression not only between different patients but also within the same patient. The expression of CD38 and Han‐PCl antigens (Ags) was almost constant (> 90% positive cases), while CD9 was detected in 66% of the cases. On the other hand, less than one third of patients were positive for CD 10, CD20 and HLA‐DR and generally with a weak expression (< 30% positive plasma cells). In occasional cases plasma cells were weakly positive for the myelomonocytic markers CD13 (9%), CD15 (25%) and CD14 (6%). The possibility that this heterogeneity might be the result of different stages of differentiation of the neoplastic clone is suggested both by the positive correlation in the expression of some of these antigens (CD10, CD9, CD20, HLA‐DR) and by the relationship between CD10 and myeloid antigens with immature plasma cell morphology. Finally, the cALLA antigen does not seem to be of significant value in predicting survival. Moreover, none of the other markers explored showed a clear influence in the course of the disease, although the tendency towards a lower survival found for the CD20+ cases as well as the association of the expression of some antigens and advanced clinical stage, may warrant further studies in a larger series of patients.
Electrokinetic properties and surface membrane sialic acid status of platelets in idiopathic thrombocytopenic purpura (ITP)
Authors: Crook M. , Machin S. , Crawford N. 
Published: March 2008

SummaryContinuous flow electrophoresis has been used to investigate heterogeneity in the circulating platelets from patients with idiopathic thrombocytopenia (ITP) and from age‐ and sex‐matched control donors. The ITP patients’platelet counts ranged from 15 to 80 × 109/1 and they had much higher mean volumes and significantly higher (twofold) total cell and neuraminidase‐labile surface sialic acid contents expressed per unit cell than normal. After volume normalization the mean difference between the two groups was not statistically significant. The relationships of these findings to abnormal thrombopoiesis and to molecular recognition for reticuloendothelial system (RES) removal are discussed.
Intestinal transferrin receptors and iron absorption in the neonatal rat
Authors: Anderson Gregory J. , Walsh Michael D. , Powell Lawrie W. , Halliday June W. 
Published: March 2008

SummaryThe transferrin receptor is a major protein found on the basolateral membranes of intestinal epithelial cells, yet its possible role in intestinal iron metabolism and also in iron absorption is unclear. We have studied intestinal transferrin receptor expression during the peri‐ and postnatal development of the small intestine of the rat using immunohisto‐chemistry with a monoclonal antibody to the rat receptor. Two major changes in transferrin receptor expression in the developing small intestine were found, a decrease in receptor expression associated with birth, and an increase at the time of weaning. Around the time of weaning there was a large decrease in iron absorption, but there was no direct correlation between absorption and transferrin receptor expression. However, at both birth and weaning there were major changes in intestinal cell kinetics, and the distribution of receptor correlated well with the distribution of proliferating cell populations. In addition, as the intestinal epithelial cells differentiated and stopped dividing, there was a redistribution of transferrin receptors from the cell surface to intracellular sites. These data suggest that the most likely role of the transferrin receptor in the neonatal intestine is in the supply of iron to the developing epithelial cells in the crypts, and that the receptor does not play a direct role in iron transit across the intestinal epithelium.
An alloimmunized, thrombocytopenic patient successfully transfused with acid‐treated, random‐donor platelets
Authors: Shanwell A. , Sallander S. , Olsson I. , Gulliksson H. , Pedajas I. , Lerner R. 
Published: March 2008

Alloimmunized, thrombocytopenic patients, refractory to random‐donor platelet transfusion, often respond to HLA‐identical single‐donor platelets. HLA‐compatible platelets are expensive, take time to prepare, and donors are sometimes not to be found.We have used random‐donor platelets and ‘peeled’ the HLA‐antigen off the platelets, using a modified laboratory method (incubation of platelets with citric acid solution at 0°C). Platelet recovery in two healthy subjects was 72·0% for acid‐treated platelets, and 73·5% for untreated control platelets, using 111In‐labelled autologous platelets. Survival time (multiple hit) was 6·25 and 7·95 d, respectively. Random‐donor platelets that were strongly positive in the crossmatch with serum from a patient became negative after treatment with the acid solution. Furthermore, transfusion of these platelets gave a post‐transfusion, platelet‐count increment comparable with transfusion of HLA‐compatible single‐donor platelets.
Shift in the megakaryocyte ploidy in MDS patients: microcytofluorometry with DAPI staining after destaining of Wright‐Giemsa stain
Authors: Kobayashi Yutaka , Kimura Shinya , Tanaka Koji , Wada Katyuya , Ozawa Masaru , Horiuchi Hirohiko , Maruo Naoyuki , Kondo Motoharu 
Published: March 2008

We applied DAPI (4′,6‐diamidino‐2‐phenylindole) staining to the determination of nuclear DNA content in single megakaryocytes in 12 normal subjects and 12 patients with myelodysplastic syndrome (MDS). After the megakaryocytes had been identified on Wright‐Giemsa stained smear and classified according to modified Feinendegen's classification, they were photographed. Then Wright‐Giemsa stain was removed by immersion in 50% ethanol at 37°C for 1 h and 100% methanol at 37°C for 1 h. The specimens were then stained with DAPI solution (DAPI 0.01 mg/ml, pH 7.4 Tris‐EDTA‐2Na buffer solution and 0.01 M 2‐mercaptoethylamine hydrochloride mixed at the ratio of 0.5:98.5:1.0) for more than 30 min. The amount of nuclear DNA in the previously identified megakaryocytes was measured by microcytofluorometry.The maximum population of megakaryocytes ploidy was in 16N in normal subjects, 8N in 10/12 MDS patients, and 4N in the remaining two patients. These findings suggest impairment of the development of the megakaryocytes nucleus in the MDS patients.