bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive direct antiglobulin tests and haemolytic anaemia following therapy with beta‐lactamase inhibitor containing drugs may be associated with nonimmunologic adsorption of protein onto red blood cells
Authors: Garratty George , Arndt Patricia A. 
Published: March 2003

A high incidence (39%) of positive direct antiglobulin tests (DATs) has been reported in patients taking Unasyn [ampicillin sodium plus sulbactam sodium (a beta‐lactamase inhibitor)]. Three of four patients, with positive DATs, receiving Unasyn or Timentin [ticarcillin disodium plus clavulanate potassium (also a beta‐lactamase inhibitor)] developed a haemolytic anaemia (HA) associated with a positive DAT, which resolved when drug therapy was stopped. The patients' sera did not react with red blood cells (RBCs) in the presence of Unasyn or Timentin, but when drug‐treated RBCs were tested, patients' sera and normal sera reacted equally by indirect antiglobulin test. Following incubation in normal sera, RBCs treated with Unasyn, Timentin, Augmentin (amoxicillin + clavulanate), sulbactam and clavulanate reacted with anti‐human globulin and anti‐human albumin (an index of non‐specific adsorption); RBCs treated with ampicillin and amoxicillin were nonreactive.The beta‐lactamase inhibitors sulbactam and clavulanate seem to cause nonimmunologic adsorption of protein onto RBCs in vitro. This may explain the high incidence of positive DATs detected in patients taking Unasyn, which contains sulbactam. It was not possible to prove that there was a direct association between the nonspecific uptake of protein onto drug‐treated RBCs in vitro with the positive DATs or the HA.
IDA‐FLAG (idarubicin, fludarabine, cytarabine, G‐CSF), an effective remission‐induction therapy for poor‐prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial
Authors: Fleischhack  , Hasan  , Graf  , Mann  , Bode  
Published: March 2003

A phase II trial was designed to explore the potential feasibility and efficacy of a reinduction therapy consisting of fludarabine, cytarabine, idarubicin and granulocyte colony stimulating factor (G‐CSF) for acute myelogenous leukaemia (AML) patients with poor prognosis.Twenty‐three patients aged 1.2–17.5 years with refractory (n = 3), relapsed (n = 19) or secondary (n = 1) AML were treated with the IDA‐FLAG regimen, a combination therapy of idarubicin (days 2–4, 12 mg/m2/d), fludarabine (days 1–4, 30 mg/m2/d), cytarabine (days 1–4, 2000 mg/m2/d) and G‐CSF (day 0 up to ANC > 1 × 109/l, 400 μg/m2/d). They received a total of 37 courses of IDA‐FLAG and/or FLAG (IDA‐FLAG without idarubicin). 17/23 patients achieved a complete remission (CR) with a median duration of 13.5 months (1–39 months), one patient showed a partial remission, and five were nonresponders while in CR, 11 patients underwent bone marrow or PBSC (peripheral blood stem cells) transplantation. Overall, nine patients remain in continuous complete remission with a median duration of 17.5 months (9.5–39 months). The toxicity of the IDA‐FLAG courses was more severe than for the FLAG courses with marked neutropenia and thrombocytopenia (for IDA‐FLAG: median 22.5 and 25 d respectively; for FLAG: median 10.5 and 14 d respectively). Pulmonary infections were the main nonhaematological toxicity. One patient died in CR from invasive aspergillosis.The IDA‐FLAG regimen produced a CR of >12 months in more than half of the patients and can be recommended as a therapeutic option prior to allogeneic or autologous bone marrow transplantation.
Gamma‐irradiation does not impair ATRA‐induced maturation of myeloid leukaemic cells: implication for combined radiation and differentiation therapy
Authors: Neildez‐Nguyen Thi My Anh , Chapel Alain , Arock Michel , Vétillard Jérôme , Thierry Dominique 
Published: March 2003

In the present study we investigated the effects of various doses of γ‐irradiation, followed by induction of granulocytic differentiation with all‐trans‐retinoic acid (ATRA), on proliferative rate, differentiation capability and oxidative metabolism of leukaemic cells from two different myeloid leukaemia cell lines, HL‐60 and PLB‐985.Regarding the effects of such combined treatment on the proliferative capabilities of HL‐60 and PLB‐985 cell lines, we showed that their growth kinetics were similar after 2 Gy γ‐irradiation combined with ATRA. However, with doses >2 Gy, the behaviour of the cell lines differed largely. Indeed, HL‐60 appeared to be more radiosensitive than PLB‐985 regarding cell viability and proliferation. Besides, whatever dose of irradiation (2, 5 or 10 Gy) was applied, ATRA was still able to induce differentiation of HL‐60 and PLB‐985 into granulocytes that retained the capacity to produce superoxide anion.The results of these in vitro studies suggest that leukaemia cell lines retain their ability to respond to ATRA, a granulocytic‐differentiating inducer following high doses of irradiation. This may have implications for the use of radiation therapy in combination with ATRA for the treat‐ment of extramedullary infiltrations of myeloid leukaemias in humans.
Major surgery seems not to influence HIV disease progression in haemophilia patients
Authors: Astermark Jan , Löfqvist Thomas , Schulman Sam , Stigendal Lennart , Lethagen Stefan , Nilsson Inga Marie , Berntorp Erik 
Published: March 2003

The influence of major surgery on HIV disease progression and decline in CD4+ cell count was evaluated in 23 seropositive haemophilia patients. 24 HIV‐infected patients served as non‐operated controls. In addition, 32 age‐matched seronegative subjects were included. The follow‐up time was up to 5 years.During the course of the study, eight of the operated (35%) and 11 of the non‐operated (48%) subjects developed HIV‐related symptoms (P = 0.267). The relative risk for developing HIV‐related symptoms after surgery was 0.60 (95% CI 0.25; 1.48). A significant decline in CD4+ cell counts was observed in both the surgery (4.0 × 106/l/month, 95% CI 2.0; 6.0 × 106, P = 0.001) and the non‐surgery (4.0 × 106/l/month, 95% CI 2.0; 6.0 × 106, P = 0.004) seropositive subgroup, but no difference between the two subgroups was seen (P = 0.793). HIV (6.0 × 106/l/month, 95% CI 2.1; 9.9 × 106, P = 0.0005) but not surgery (−1.0 × 106/l/month, 95% CI −3.0; 0.96 × 106, P = 0.647) was an independent predictor for the decline in CD34+ cell count. No interaction effect was observed between HIV infection and surgery (P = 0.361). The annual amount of factor concentrate used for regular replacement therapy did not influence the decline in CD4+ cell count (P = 0.492).We conclude that major surgery may be considered in symptom‐free HIV‐seropositive haemophilia patients, with CD4+ cell counts 0.20 × 109/l under similar premises as for seronegative subjects.
Magnetic resonance imaging in myelofibrosis and essential thrombocythaemia: contribution to differential diagnosis
Authors: ROZMAN CIRIL , CERVANTES FRANCISCO , ROZMAN MARÍA , MERCADER JOSEP‐MARÍA , MONTSERRAT EMILIO 
Published: March 2003

To ascertain the value of magnetic resonance (MR) imaging in the differential diagnosis between myelofibrosis (MF) and essential thrombocythaemia (ET), 38 patients were analysed. 20 patients had MF (idiopathic myelofibrosis, 15 cases; post‐ET myelofibrosis, four cases; post‐polycythaemic MF, one case) and 18 ET. Mean age was 61.5 years (range 30–89) for patients with MF and 60.9 years (range 26–83) for ET patients. MR imaging was performed in the dorsal vertebrae in all cases, and also in both femurs in 25 of the patients. In most ET cases the MR signal of the dorsal vertebrae was not modified, whereas it was markedly reduced in MF (P = 0.0000001). With regard to femoral marrow, it was usually fatty in ET, with an absent to moderate degree of reconversion seen in the 14 cases analysed, contrasting with the marked degree of reconversion noted in 10/11 patients with MF (P = 0.000007). An inverse correlation was demonstrated between the vertebral signal and the degree of femoral reconversion. These differences were due to the fact that in ET the bone marrow adipose tissue is grossly preserved, whereas in MF it is usually markedly decreased or absent.The above results indicate that MR imaging is a useful tool for the differential diagnosis of ET and MF, with the usefulness of this technique increasing when vertebral and femoral bone marrow studies are combined.
Leukaemic presentation of small cell variant anaplastic large cell lymphoma: report of four cases
Authors: Bayle Chantal , Charpentier Agnès , Duchayne Eliane , Manel Anne‐Marie , Pages Marie‐Pierre , Robert Alain , Lamant Laurence , Dastugue Nicole , Bertrand Yves , Dijoud Frédérique , Emile Jean‐François , Machover David , Brugières Laurence , Delsol Georges 
Published: March 2003

We report four cases of a rare subtype of CD30‐positive anaplastic large cell lymphoma (ALCL) with a predominant small cell component (small cell variant of ALCL) presenting with a leukaemic feature. Lymph node biopsy showed malignant cells of varying size with a predominant population of small to medium‐sized malignant cells associated with large anaplastic cells strongly positive for CD30 and epithelial membrane antigen (EMA). Both large and small cells were reactive with antibody ALK1, which recognizes the chimaeric NPM‐ALK protein associated with the t(2;5)(p23;q35). All patients presented with hyperleucocytosis with atypical small lymphocytes. Bone marrow involvement was detected on both aspirate and bone marrow trephine where scattered malignant cells were only demonstrated by immunostaining for CD30 and ALK protein. Atypical cells in peripheral blood, lymph node and skin biopsies showed a T or null cell phenotype. Cytogenetic analysis of blood, bone marrow and/or lymph node revealed the t(2;5)(p23;q35) characteristic of ALCL. The patients responded to chemotherapy but showed early relapse without abnormal cells in peripheral blood.This report shows that the small cell variant of ALCL may have a leukaemic presentation with peripheral blood involvement by atypical lymphocytes and provides evidence that, in the small cell variant of ALCL, the small cell component is a part of the malignant clone.
Purine analogues kill resting lymphocytes by p53‐dependent and ‐independent mechanisms
Authors: Pettitt A. R. , Clarke A. R. , Cawley J. C. , Griffiths S. D. 
Published: March 2003

To resolve the controversy concerning the role of p53 in the killing of resting lymphocytes by purine nucleoside analogues, we examined the cytotoxic effects of chlorodeoxyadenosine, fludarabine and deoxycoformycin (plus deoxyadenosine) on unstimulated spleen cells from p53‐knockout versus wild‐type mice.p53‐knockout cells were more resistant to all three nucleosides than were wild‐type cells. However, substantial killing still occurred in the absence of p53, indicating that purine analogues can kill resting lymphocytes by both p53‐dependent and ‐independent mechanisms.We suggest that these results are relevant to chronic lymphoid malignancies, and that characterization of the p53‐independent component of nucleoside action may indicate potential ways of overcoming therapeutic resistance.
Immunologic response to recombinant hirudin in HIT type II patients during long‐term treatment
Authors: Huhle  , Hoffmann  , Song  , Wang  , Heene  , Harenberg  
Published: March 2003

We prospectively investigated 27 patients with heparin‐induced thrombocytopenia (HIT) type II who were subsequently treated with r‐hirudin. Patients with venous or arterial thromboembolism were treated with activated partial thromboplastin time (aPTT)‐controlled intravenous r‐hirudin (n = 19; mean 19.3 d) followed by subcutaneous r‐hirudin (n = 6; mean 22.5 d) and oral anticoagulation. Patients without thromboembolism were treated with subcutaneous r‐hirudin (n = 8; mean 25.9 d). Four patients were readmitted to subcutaneous r‐hirudin for a mean duration of 32 d. The incidence of r‐hirudin antibodies was 84% for intravenously treated patients and 50% in subcutaneously treated patients. The patients (n = 27) showed a 74% overall incidence of r‐hirudin antibodies, mainly of the IgG‐subclass, without seroconversion before day 6 and after day 32 of r‐hirudin treatment or during r‐hirudin treatment. None of the patients showed onset or recurrence of venous or arterial thromboembolism, systemic allergic reactions or IgE‐antibody development.During intravenous and subcutaneous administration of r‐hirudin the aPTT and the ecarin clotting time was increased in the antibody‐positive patients compared to antibody‐negative patients. Therefore we assume that r‐hirudin antibodies may reduce r‐hirudin metabolism.
Molecular, haematological and clinical studies of the −101 C → T substitution of the β‐globin gene promoter in 25 β‐thalassaemia intermedia patients and 45 heterozygotes
Authors: Maragoudaki E. , Kanavakis E. , Traeger‐Synodinos J. , Vrettou C. , Tzetis M. , Metaxotou‐Mavrommati A. , Kattamis C. 
Published: March 2003

We report the clinical, haematological, biosynthetic and molecular data of 25 double heterozygote β‐thalassaemia intermedia patients and 45 β‐thalassaemia heterozygotes with the C → T substitution at nucleotide position −101 from the Cap site, in the distal CACCC box of the β‐globin gene promoter. This mutation is considered the most common amongst the silent β‐thalassaemia mutations in Mediterranean populations. Of the 25 compound heterozygotes for the β−101 C → T and common severe β‐thalassaemia mutations, all but one had mild thalassaemia intermedia preserving haemoglobin levels around 9.5 g/dl and haemoglobin F levels < 25%. The only transfused patient was characterized to have an additional α‐globin gene.Strict assessment of haematological and biosynthetic findings in the heterozygotes for the β−101 C → T mutation (excluding six cases with an α‐globin gene defect) demonstrated that less than half of them had completely normal (silent) haematology; the remainder had either high haemoglobin A2 values (in the range of 3.7–5.1%) and/or low red cells indices and/or raised haemoglobin F values. The α/non‐α‐globin chain synthesis ratios were generally raised, with mean 1.44 (1.07–2.10). Amongst the parents of the compound heterozygotes, who were not selected for molecular analysis following haematological screening, half of the cases were completely silent.Interaction with severe β‐thalassaemia mutations always resulted in the clinical phenotype of mild non‐transfusion‐dependent thalassaemia intermedia.
Familial thrombocytosis as a recessive, possibly X‐linked trait in an Arab family
Authors: Stuhrmann M , Bashawri L. , Ahmed M. A. , Al‐Awamy B. H. , Kühnau W. , Schmidtke J. , El‐Harith E. A. 
Published: March 2003

Familial thrombocytosis (FT) has previously been described as an autosomal‐dominant disorder with manifestations similar to those of sporadic essential thrombocythaemia. We studied an Arab family consisting of four brothers, aged 4–8 years, who had either sustained markedly elevated (> 1000 × 109/l) or moderately elevated (> 500 × 109/l) platelet counts, two healthy sisters and their parents who had normal platelet counts. The four brothers with FT had normal plasma thrombopoietin levels and are currently not presenting with any thrombotic or haemorrhagic complications. Mutation analysis at the thrombopoietin gene (THPO) of the affected family members failed to detect the intron 3 G→C splice mutation that had been described as causing FT. In addition, segregation analysis using a polymorphic CA marker revealed completely discordant THPO alleles among the affected brothers. We postulate the existence of a new locus for FT whereby the disease is transmitted as a recessive, possibly X‐linked trait.
Single site polymorphisms and alternative splicing of the human CD13 gene – different splicing frequencies among patients with acute myeloid leukaemia and healthy individuals
Authors: Dybkær Karen , Kristensen J. S. , Pedersen F. S. 
Published: March 2003

Within the haematopoietic system, CD13/aminopeptidase N (APN), a transmembrane glycoprotein, is expressed on the surface of early committed progenitors of granulocytes and monocytes and by all cells of these lineages as they mature. CD13 is expressed on the majority of leukaemic myeloblasts in acute myeloid leukaemia (AML), and on leukaemic lymphoblasts in a small percentage of acute lymphoid leukaemia cases. Thus, anti‐CD13 monoclonal antibodies are used as diagnostic markers in leukaemia typing. By systematically amplifying overlapping reverse transcription polymerase chain reaction (RT‐PCR) amplicons throughout the CD13 mRNA, we identified two splice variants in which exon 3 and exon 14 were lost. Fourteen healthy individuals and 34 patients with AML were screened for these splice variants. All healthy individuals, and the majority of AML patients, had both splice variants but they represented less than 10% of the total RT‐PCR‐amplified CD13 product. Increased expression of both truncated CD13 mRNA forms were observed in 6% of AML patients, whereas no detectable exon 3 or exon 14 splice variants could be generated in 26% and 9% of AML patients respectively. The different splicing frequencies may reflect altered processing of pre‐mRNA or expansion of certain cell types for some AML patients, even though no correlation existed to blast percentage, FAB classification, surface antigens or cytogenetic characteristics. In addition, we identified an intron of 506 bp between exon 1 and exon 2 as well as two sites of single nucleotide polymorphism with a heterozygosity index of about 0·5, making them useful as genetic markers.
The association of vitamin K status with warfarin sensitivity at the onset of treatment
Authors: Cushman Mary , Booth Sarah L. , Possidente Carl J. , Davidson Kenneth W. , Sadowski James A. , Bovill Edwin G. 
Published: March 2003

We investigated the association of vitamin K status with warfarin sensitivity among 40 orthopaedic patients beginning perioperative algorithm‐dosed warfarin. Baseline vitamin K status was assessed using plasma vitamin K‐1 and vitamin K‐1 2,3 epoxide concentrations, and a questionnaire‐based estimation of usual vitamin K intake. Warfarin sensitivity was assessed as the increase in the International Normalized Ratio (INR) after two doses of 5 mg of warfarin and as the 4‐d accumulation of under‐γ‐carboxylated prothrombin (PIVKA‐II), adjusted for warfarin dose requirement. Multivariate models were used to assess vitamin K variables as predictors of warfarin sensitivity. The mean INR increase was 0·53 U and the mean PIVKA‐II increase was 771 ng/ml/mg warfarin. Demographic factors were not associated with warfarin response. For each 1 standard deviation (SD) lower value of plasma vitamin K‐1, but not the other vitamin K variables, the INR rose 0·24 U (P ≤ 0·01). A higher usual vitamin K intake and plasma vitamin K‐1, and lower plasma vitamin K‐1 2,3 epoxide, were all associated with a lower PIVKA‐II increase over 4 d. Respective differences in PIVKA‐II accumulation per SD increase of each variable were −165, −218 and 236 ng/ml/mg warfarin (all P ≤ 0·05). We concluded that dietary and biochemical measures of vitamin K status were associated with early warfarin sensitivity.
Pathogenetic analysis of three cases with a bleeding disorder characterized by defective platelet aggregation induced by Ca2+ ionophores
Authors: Fuse Ichiro , Higuchi Wataru , Uesugi Yumiko , Aizawa Yoshifusa 
Published: March 2003

We report three cases of platelet dysfunction characterized by defective Ca2+ ionophore‐induced platelet aggregation without impaired production of thromboxane A2 (TXA2). The patients had mild to moderate bleeding tendencies, and their platelet aggregation and secretion induced by ADP, collagen, arachidonic acid, stable TXA2 (STA2) and Ca2+ ionophore A23187 was defective or much reduced. However, ristocetin‐ or thrombin‐induced platelet aggregation was normal. The analysis of second messenger formation showed that inositol 1,4,5‐triphosphate formation or Ca2+ mobilization induced by thrombin, STA2 or A23187 was normal. Furthermore, the phosphorylation of 47 kDa protein (pleckstrin) and 20 kDa protein (myosin light chain, MLC) in response to those agonists was normal. These findings suggest that the defective site in the patients' platelets lies in the process distal to or independent of protein kinase C activation, Ca2+ mobilization and MLC phosphorylation.
Bone marrow involvement in Whipple's disease: rarely reported, but really rare?
Authors: Walter Roland , Bachmann Stefano P. , Schaffner Andreas , Rüegg Regula , Schoedon Gabriele 
Published: March 2003

Infection with Tropheryma whippelii, the causative agent of Whipple's disease, involves nearly every organ. Involvement of bone marrow may be an overlooked area of Whipple's disease. We report a case of lymphoma‐like Whipple's disease with bone marrow involvement together with a brief review of the literature on this topic. Despite minimal documentation, bone marrow may be commonly involved in Whipple's disease and, although not specific, diastase‐resistant periodic acid‐Schiff (PAS)‐positive macrophages in bone marrow may offer an important clue to diagnosis using PAS histology of upper endoscopic biopsies, polymerase chain reaction or electron microscopy.
Clinical spectrum of hepatitis C‐related liver disease and response to treatment with interferon and ribavirin in haemophilia or von Willebrand disease
Authors: Lethagen Stefan , Widell Anders , Berntorp Erik , Verbaan Hans , Lindgren Stefan 
Published: March 2003

Our aim was to evaluate the severity of liver disease resulting from chronic hepatitis C in haemophilia or von Willebrand disease and the efficacy of 6 months treatment with interferon alpha and ribavirin. Fifty‐five liver biopsies were performed in 43 patients without any bleeding complications, as seen with ultrasound immediately after the biopsy and 48 h thereafter. Histological changes were mild, with low scores for both inflammation and fibrosis, in spite of long exposure to blood products (mean 27 years). Two patients had compensated cirrhosis. Thirty‐five out of 39 included patients completed study treatment. Hepatitis C virus (HCV)‐RNA was negative in 77% (30/39) of patients at the end of treatment, and 36% (14/39) achieved a complete sustained response at follow‐up 6 months after treatment. Treatment failure was more frequent in patients with virus genotype 1 compared with non‐1 (P = 0·0003). The response rate correlated well with that of non‐haemophilic patients. In summary: (1) liver biopsy was safe with our regimen; (2) liver disease in our patients was usually mild and had a slow progress; (3) only HCV genotype 1 predicted treatment failure; (4) our treatment results agreed with those from non‐haemophilic patients.