bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fibrinolytic response to venous occlusion and the natural anticoagulants in patients with antiphospholipid antibodies both with and without systemic lupus erythematosus
Authors: Keeling D. M. , Campbell S. J. , Mackie I. J. , Machin S. J. , Isenberg D. A. 
Published: March 2008

SummaryPatients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis and this is increased in the presence of antiphospholipid antibodies (APA). These APA are also associated with thrombosis in patients who do not have SLE. We compared haemostatic parameters in SLE patients with and without APA, and also compared patients who had APA but not SLE with healthy normal controls. No relationships between the natural anticoagulants. anti‐thrombin III, heparin cofactor II, protein C and protein s. and the presence of APA were found. In the patients with SLE both tissue plasminogen activator antigen and plasminogen activator inhibitor (PAI) were increased, but these changes were not due to APA which had no effect on fibrinolysis in these patients. In the patients with APA who did not have SLE the fibrinolytic response to venous occlusion was reduced due to raised levels of PAI; similar changes have, however, been reported in some patients with idiopathic thrombosis.
The incidence of dysfunctional antithrombin variants: four cases in 210 patients with thromboembolic disease
Authors: Harper P. L. , Luddington R. J. , Daly M. , Bruce D. , Williamson D. , Edgar P. F. , Perry D. J. , Carrell R. W. 
Published: March 2008

Summary210 patients, with a history of venous thrombosis, have undergone prothrombotic investigations. In nine cases a consistent deficiency of antithrombin was identified. In five there was a reduction in the plasma antigenic concentration of antithrombin and in a further four cases deficiency was due to the presence of a dysfunctional antithrombin variant. The variants have all been characterized by DNA analysis and in three the mutations have been confirmed by peptide sequencing (antithrombin Basel (41 Pro to LEU), Hamilton (382 Ala to Thr). Cambridge I (384 Ala to Pro) and Cambridge II (384 Ala to Ser). The incidence of antithrombin deficiency in patients with a history of venous thrombosis has previously been quoted at between 2% and 3%: there is no published data available on the incidence of antithrombin variants. In our series 5% of patients who presented before the age of 40 years had antithrombin deficiency, and 2% of the total number of patients investigated had a dysfunctional variant. Our figures indicate that a significant number of cases of antithrombin deficiency are due to dysfunctional variants and that the true incidence of antithrombin deficiency in patients with a history of venous thrombosis is in the order of 5%.
Erythrocyte size, number and haemoglobin content in vertebrates
Authors: Hawkey C. M. , Bennett P. M. , Gascoyne S. C. , Hart M. G. , Kirkwood J. K. 
Published: March 2008

SummaryKelationships between erythrocyte number, size and haemoglobin content were examined in 441 species (101 families) of mammals, birds and reptiles. Whereas the total number of red cells (RBC), the mean cell volume (MCV) and mean cell haemoglobin (MCH) showed much variation, the haemoglobin level (Hb), packed cell volume (PCV) and mean cell haemoglobin concentration (MCHC) were relatively constant in all adult mammals and birds but lower in reptiles. There was a strong positive correlation between MCV and MCH and a strong negative correlation between MCV and RBC across all species. Mammals had more, smaller erythrocytes per unit volume of blood than birds, which, in their turn, had more, smaller erythrocytes than reptiles. The findings confirm that the oxygen‐carrying capacity of the blood is highly conserved in birds and mammals but is lower in exothermic groups such as reptiles. Although the significance of the observed species differences in RBC and MCV has yet to be explained, the findings have considerable evolutionary, physiological and diagnostic interest.
Myelodysplastic syndromes in childhood: a population based study of nine cases
Authors: Hasle Henrik , Jacobsen Bendt Brock , Pedersen Niels Tinggaard 
Published: March 2008

Nine cases of de novo myelodysplastic syndromes (MDS) in childhood from a population based study are presented. The annual incidence of MDS was 3·4/1000 000 in children less than 15 years old, corresponding to 8·7% of all haematological malignancies in childhood. Two patients had Down's syndrome. None of the remaining patients had constitutional anomalies.All patients were classified according to the FAB classification. Five patients presented with refractory anaemia (RA), only one of these did not progress, one showed clonal evolution, and the remaining three patients all progressed to refractory anaemia with excess of blasts (RAEB). Three patients presented with RAEB. Two progressed to overt leukaemia. The last patient was classified as chronic myelomonocytic leukaemia (CMML). Clonal cytogenetic abnormalities were detected in five patients, in three of them as monosomy 7.Five patients have died; two of progressive disease, two of infections, and one of haemorrhage, two of the latter three patients died during therapy induced cytopenia.Of the four patients still alive, one patient showed a complete remission after cyclosporine and later immunoglobulin therapy, one patient is a long‐term survivor after allogeneic bone marrow transplantation, and one patient apparently obtained a spontaneous remission several months after chemotherapy.
A predictive model for the clinical response to low dose ara‐C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia
Authors: Hellström‐Lindberg Eva , Robèrt Karl‐Henrik , Gahrton Gösta , Lindberg Greger , Forsblom Ann‐Mari , Kock Yvonne , Öst Åke 
Published: March 2008

The response to treatment with low‐dose ara‐C was studied in 102 consecutive patients; 79 with myelodysplastic syndromes (MDS) and 23 with acute myelogenous leukaemia (AML) following MDS. The aim was to find variables that could predict the response to treatment. All patients had clinical symptoms related to cytopenia. Peripheral blood values, bone marrow morphology histology and chromosomes were analysed before the start of treatment. The median survival of the patients was 9 months and a poor survival was predicted by advanced age, low platelet counts, the presence of pseudo‐Pelger morphology and <2 chromosomal aberrations.Thirty patients (29%) responded with either a complete remission or a significant increase in haemoglobin level. For the remaining 71%, the treatment was ineffective and in some cases hazardous. The factors associated with a poor response to treatment could be divided into two groups: one included low platelet counts and the presence of chromosomal aberrations, both signs of progressive MDS with a short survival, and the other comprised morphological findings, indicating ineffective haemopoiesis. Patients with platelet counts > 150 × 109/l had a response rate of 55% compared to 23·5% in patients with subnormal platelet counts. Logistic regression identified low bone marrow cellularity, absence of ring sideroblasts and <2 chromosomal aberrations as predictors of a favourable response in patients with platelet counts <150 × 109/l. These factors and the platelet count were combined in a predictive model which can divide patients into three groups with different probabilities of response: a favourable group, 38·6% of the patients, with a response rate of >50%, an intermediate group, 32·7% of the patients, with a response rate of 24%, and an unfavourable group, 28·7% of the patients, with only 3% responses.While low‐dose ara‐C is an effective treatment for some patients, it is ineffective and hazardous for others. We present a model that can facilitate therapeutic decision making in two‐thirds of patients with MDS and MDS‐AML by identifying patients who should not be treated with low‐dose ara‐C as well as patients with a relatively high probability of response.
Mixed phenotype of blasts in acute megakaryocytic leukaemia and transient abnormal myelopoiesis in Down's syndrome
Authors: Yumura‐Yagi Keiko , Hara Junichi , Kurahashi Hiroki , Nishiura Tetsuo , Kaneyama Yoshio , Osugi Yuko , Sakata Naoki , Inoue Masami , Tawa Akio , Okada Shintaro , Kawa‐Ha Keisei 
Published: March 2008

Blasts from eight cases with acute megakaryoblastic leukaemia (AMKL) and seven with transient abnormal myelopoiesis in Down's syndrome (TAM) were investigated to clarify their phenotypic characteristics. CD41 and CD7 were the most frequently expressed in both disorders. CD41 was positive in six TAM and five AMKL cases, and CD7 was positive in five TAM and five AMKL cases, respectively. CD33 was detected in four TAM and five AMKL cases. Other myeloid‐lineage associated antigens such as CD13 and CD11b could not be found in TAM but were expressed in five AMKL cases. Interestingly, CD56, a neural adhesion molecule, was expressed in three of four TAM and one of five AMKL cases. Cytoplasmic CD3 antigen was also noted in three of five examined cases.A short‐term culture study was conducted on blasts from two TAM cases and five AMKL cases. In two cases in which CD41 was not expressed before culture, the expression of CD41 was enhanced after culture with or without 12–0‐tetradecanoyl‐phorbol‐13‐acetate (TPA). The expression of CD7 remarkably was depressed, while that of CD13 was enhanced after culture with TPA.These findings suggest that blasts of TAM and AMKL originate from very immature cells and represent a mixed phenotype. In the present study, distinction of pheno‐typical differences between blast in TAM and AMKL was not possible.
Red blood cells from patients with sickle cell disease exhibit an increased adherence to cultured endothelium pretreated with tumour necrosis factor (TNF)
Authors: Vordermeier S. , Singh S. , Biggerstaff J. , Harrison P. , Grech H. , Pearson T. C. , Dumonde D. C. , Brown K. A. 
Published: March 2008

Red blood cells (RBCs) from 24 patients with sickle cell disease were more adherent to cultured endothelium pretreated with the inflammatory cytokine, tumour necrosis factor (TNF) than RBCs from 22 healthy subjects. The enhanced sticking was apparent in RBC preparations from patients who were in crisis (mean 190% increase from controls) and out of crisis (mean 220% increase) and was not related to the number of circulating RBCs, reticulocytes, platelets, leucocytes or haemoglobin levels. When irreversibly sickled RBCs, enriched by centrifugation on density gradients, were added to TNF‐treated endothelium they were found to be significantly more adherent (mean 411% increase; P<0·001) than the unfractionated RBCs from the same patients. There was no difference between the adherent properties of sickle RBCs and normal RBCs for untreated endothelium.Contributing factors to the enhanced adhesion to TNF‐treated endothelium may be the low surface change of sickle RBCs, and increased levels of fibrinogen and von Willebrand's factor (vWF) in the patients’plasma. By acting on vascular endothelium to increase its adhesiveness for sickled RBCs, it is concluded that inflammatory cytokines such as TNF may have a prominent role in mediating the events that lead to microvascular occlusions in sickle cell disease.
Impact of active and passive exclusions on the results of a clinical trial in multiple myeloma
Authors: Hjorth Martin , Holmberg Erik , Röder Stig , Westin Jan ,   for the Myeloma Group of Western Sweden
Published: March 2008

Summary. During the 3 years 1984–86, 314 cases of multiple myeloma were diagnosed in the Health Care Region of Western Sweden. 180 of these cases were included in a clinical trial; 71 were notified to the trial but excluded; 49 cases were not reported to the trial; 14 were diagnosed post mortem.The crude incidence rate of myeloma was 6.3 cases per 100000 inhabitants per year, corresponding to an age‐adjusted (world standard population) incidence rate of 2.9 cases per 100000 inhabitants per year.The excluded and the non‐reported patients had a significantly shorter survival than those included in the clinical trial (median survival 22, 13 and 33 months, respectively). This was partly due to differences in age and proportion of actively treeated patients between the groups, but the same tendency remained also after correction for these factors.Considering the included patients separately, the effect of tentative application of presumptive exclusion criteria corresponding to major prognostic factors was studied. Prolonged survival was seen when the upper age limit was lowered and when patients with renal failure or low performance status were excluded.The results illustrate the fact that for multiple myeloma the survival in a trial population is markedly influenced by active and passive exclusion of patient groups with unfavourable prognostic characteristics. When reporting results of clinical trials, discussion of the representativeness of the trial population for the total patient population is recommended in order to facilitate application of the trial results to medical practice and comparisons between trials.
Haematological effects of radioimmunotherapy in cancer patients
Authors: Stein Rhona , Sharkey Robert M. , Goldenberg David M. 
Published: March 2008

Summary. The haematologic effects of radioimmunotherapy (RAIT) in cancer patients have been studied in order to better understand the aetiology of RAIT‐associated myelosuppresion. Evaluations were performed on patients treated with 131I‐anti‐carcinoembryonic antigen (CEA) and 131I‐LL2, a monoclonal antibody (MAb) reactive with non‐Hodgkin's B‐cell lymphoma. Both groups of patients experienced decreases in WBC and platelets. Nadirs were observed 42–51 d post first injection in the lymphoma patients, and 49–66 d post first injection (30–43 d post high‐dose therapeutic injection) in the carcinoma patients. Within the WBC population, B cells were the most radiosensitive. The evaluations of the binding of these MAbs to peripheral blood cells and the effect of RAIT on lymphocyte subpopulations indicated a drop of 26–92% in the percentage of B lymphocytes within 1 week following treatment with both 131I‐LL2 and 131I‐anti‐CEA MAbs even though only LL2 binds to B cells. The percentage of T lymphocytes was not affected by the 131I‐antibody treatments.These observations suggest that the marked drop in circulating B lymphocytes and platelets after the administration of radioiodinated antibodies is a nonspecific radiation effect, and not necessarily related to the binding of MAb to normal B cells. Thus, among WBCs, B cells are uniquely radiosensitive, and will be unusually affected by antibody‐directed internal radiation.
Primary myelodysplastic syndrome in children: the clinical experience in 33 cases
Authors: Tuncer M. A. , Pagliuca A. , Hicsonmez G. , Yetgin S. , Ozsoylu S. , Mufti G. J. 
Published: March 2008

Summary. We describe the clinicomorphological features in 33 cases of primary myelodysplastic syndrome classified according to the FAB classification which presented to a single centre over a 12 year period. Presenting features were typically related to pancytopenia although hepatosplenomegaly and granulocytic sarcomas were far more prevalent than in the adult population.Morphological assessment of the peripheral blood and the bone marrow showed seven patients had refractory anaemia (RA), 13 patients had RA with excess of blasts (RAEB), nine patients had RAEB in transformation (RAEB‐t) and four patients had chronic myelomonocytic leukaemia (CMML). The overall mean survival was short (9.9 months) in all the subgroups and the leukaemic transformation rate was high. None of the patients scored 0–1 according to the Bournemouth Scoring System; four patients scored 2 whereas 29 patients scored 3 or 4. We conclude that unlike adults, the myelodysplastic syndromes in children run an aggressive clinical course, irrespective of the FAB subtype, and the pathogenesis of these diseases in paediatric practice warrants scientific scrutiny. Intensive chemotherapy such as the one used in de novo— AML lead to complete remission in some children and these early results suggest that this should be the treatment of choice in paediatric MDS.
Regulation of iron absorption in iron loaded subjects with end stage renal disease: effects of treatment with recombinant human erythropoietin and reduction of iron stores
Authors: Hughes R. T. , Smith T. , Hesp R. , Hulme B. , Dukes D. C. , Bending M. B. , Pearson J. , Raja K. B. , Cotes P. Mary , Pippard M. J. 
Published: March 2008

Summary. The effects on iron absorption of variation in erythroid activity, haemoglobin and iron stores were studied in six anaemic dialysis‐dependent subjects in whom iron stores were increased from previous red cell transfusions. Gastrointestinal mucosal uptake and whole body retention of oral iron were measured at the beginning of the study, after starting treatment with recombinant erythropoietin (but before significant increase in haemoglobin), after partial correction of anaemia, after further reduction of iron stores by repeated phlebotomy, and when erythropoiesis decreased from the discontinuation of treatment with erythropoietin. Between successive measurements, valid comparisons were made in five subjects.Correction of anaemia decreased whole body retention of iron through decreased mucosal uptake (P=0.032). Further reduction in iron stores through repeated phlebotomy whilst the increase in haemoglobin was maintained by treatment with erythropoietin, tended to increase whole body retention of iron through an increase in mucosal transfer (P= 0.010). With initial enhancement of erythropoiesis in anaemic iron‐loaded subjects there was no change in any measured component of iron absorption. However, after correction of anaemia and reduction of iron stores, a decrease in erythropoiesis was associated with decreased whole body iron retention in all subjects through decreased mucosal transfer (P= 0.028). The data suggest that anaemia upregulates mucosal iron uptake, and that erythroid activity upregulates mucosal transfer but that this latter effect may be counterbalanced by iron overload which downregulates mucosal transfer.
Long‐term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassaemia: Indian trial
Authors: Agarwal M. B. , Gupte S. S. , Viswanathan C. , Vasandani D. , Ramanathan J. , Desai Neena , Puniyani R. R. , Chhablani A. T. 
Published: March 2008

Summary. From August 1989 to May 1991. 52 patients with transfusion dependent thalassaemia major received L1 (1.2‐dimethyl‐3‐hydroxypyrid‐4‐one), the oral iron chelator, for a period of 3–21 months (mean±SD: 14.2±6.8). Mean (±SD) urinary iron excretion varied from 6.2±4.6 mg/d on 25 mg/kg/d of L1 to 42.3±37.1 mg/d on 100 mg/kg/d of L1. Mean (±SD) drop in S ferritin was 1465±990 μg/l after 5.0±0.8 months to 3641.2 ±2299.3 μg/l after 20.1 ±0.9 months of therapy. There was no evidence of neutropenia, thrombocytopenia, ear or eye toxicity. L1‐related arthralgia, which was reversible on dose reduction or stoppage, was seen in 20 patients (38.5%), while minor gastrointestinal (GI) tract symptoms occurred in seven (3.5%) cases.We conclude that although L1 is an effective iron chelator, further studies are required to understand the mechanism of L1 related arthralgia and also to find a safer but effective dose on which incidence of L1 related arthralgia is minimal.
β2‐glycoprotein 1 (β2GP1) enhances cardiolipin binding activity but is not the antigen for antiphospholipid antibodies
Authors: Pierangeli S. S. , Harris E. N. , Davis S. A. , DeLorenzo G. 
Published: March 2008

Summary. Some investigators have reported that a serum protein, β2‐glycoprotein 1 (β2GP1), either alone or in combination with negatively charged phospholipid, may be the antigen for anticardiolipin (aCL) antibodies. To examine these reports further, ELISA tests, inhibition experiments, Ouchterlony and Western blot techniques were used to examine anticardiolipin binding to β2GP1. Sera from patients with the antiphospholipid syndrome (APS) and syphilis were studied, as well as whole IgG immunoglobulin and affinity purified (a.p.) IgG aCL antibodies. Results showed no binding of aCL antibodies to β2GP1 in the absence of cardiolipin.β2GP1 caused enhanced binding of aCL antibodies to cardiolipin, but this enhancement was not observed in inhibition experiments. Binding to cardiolipin occurred in the absence of β2GP1. Enhancement of cardiolipin binding activity by β2GP1 was observed for APS, but not for syphilis.We conclude that β2GP1 is not the antigen for aCL antibodies, nor is it likely that the antibody recognizes shared β2GP1‐cardiolipin epitopes. Instead, this protein may make cardiolipin more available for aCL binding on solid surfaces by some yet undefined mechanism. This effect may not extend to aqueous suspensions.
Homozygosity for dominant form of hereditary spherocytosis
Authors: Duru Feride , Gürgey Aytemiz , ÖZtürk Gülyüz , Yörükan Selma , Altay Cišdem 
Published: March 2008

Summary. A 6‐month‐old male infant with hereditary spherocytosis (HS) who was the first child of a cousin marriage is presented. The patient had splenomegaly and severe anaemia. Examination of the peripheral blood smear revealed spherocytes and the osmotic fragility of red blood cells was greatly increased.Physical examination of the parents revealed that both parents had mild anaemia, jaundice and splenomegaly. Their peripheral blood smears showed spherocytes and a few acanthocytes. Osmotic fragility of red blood cells of both parents were increased. Red cell membrane electrophoresis indicated a deficiency of ankyrin in the propositus: mild deficiency was also detected in both parents. Electrophoretic patterns of red cell membrane proteins suggested that the child was homozygous for the dominant form of HS associated with ankyrin deficiency, while both parents had the simple dominant form of the disease.Red blood cell transfusions were given to the patient starting at the age of 1 month until splenectomy was performed at the age of 1 year that resulted in complete haematological response. This observation indicates that homozygosity for dominant type of HS associated with ankyrin deficiency is life compatible and splenectomy may cure the anaemia.
The production of Steel factor mRNA in Diamond‐Blackfan anaemia long‐term cultures and interactions of Steel factor with erythropoietin and interleukin‐3
Authors: Sieff C. A. , Yokoyama C. T. , Zsebo K. M. , Trammell Joel , Andersen J. W. , Nathan D. G. , Williams D. A. 
Published: March 2008

Summary. Diamond‐Blackfan anaemia (DBA) is a congenital macrocytic anaemia. To investigate whether DBA is due to hyporesponsiveness to or hypoproduction of Steel factor (SF). we compared the in vitro responsiveness of the BFU‐E contained in the Ficoll‐Hypaque non‐adherent cell fraction of six DBA marrows with that of four normal marrows and one transient erythroblastopenia of childhood (TEC) marrow. In addition, we studied the effect of soluble SF on long‐term marrow cultures (LTMC) and analysed the stromal cells from these cultures for SF mRNA transcripts. All the patients showed an erythropoietin dose‐related increase of small BFU‐E. The number and size of BFU‐E was increased with the addition to the epo of IL‐ 3 or SF: IL‐ 3 + SF was not synergistic. The addition of soluble SF to LTMC of DBA patients was associated with a small but consistent increase in non‐adherent cell production and an increase in the number of progenitors. Messenger RNA from immortalized stromal cell lines of three patients and from primary bone marrow stromal cells of one patient showed the presence of expected SF transcripts by PCR analysis. These results demonstrate that this group of DBA patients responds to SF and produces SF mRNA normally, indicating that SF itself is not involved in DBA pathophysiology. The effects observed suggest that, despite the lack of evidence for a causative role. SF may prove to be effective treatment for such patients.