Drug-induced immune haemolytic anaemia (D-IHA) is probably underestimated as the implicated drug is not promptly recognized while the serological and clinical characteristics are frequently complicated and inconclusive. We present a 57 year-old hypertensive woman who developed autoimmune haemolytic anaemia because of a true antierythrocyte autoantibody with Rhesus (Rh) specificity (anti-e) about five months after the initiation of Atacand plus® (candesartan cilexetil+hydrochlorothiazide). Adequate management required a short period of methylprednisolone treatment. Our patient's course is presented and discussed with emphasis on candesartan cilexetil as its probable implication in causing autoimmune haemolytic anaemia should be demonstrated

A case of a man affected by mediastinal tumour with composite lymphoma (sclerosis nodular Hodgkin lymphoma and diffuse large B cell Lymphoma).

Adamantiades-Behçet's disease is rare in India. CML is the most common leukaemia in the adults in this country. We report concurrent diagnoses of CML and Behçet's disease in a subject, and review the literature

The association of antiphospholipid antibodies (APA) with Non-Hodgkin Lymphoma (NHL) has been reported; complete remission is associated with disappearance of APA. APA are autoantibodies which include anticardiolipin antibody (ACA), anti-beta2-glycoprotein-I (ß2 GPI) antibodies and lupus anticoagulant (LA). The purpose of this study was to determine the prevalence of APA in NHL and its clinical association in our institution. The study was conducted in Hospital University Science Malaysia (HUSM) between June 2003 and July 2004. Fifty-three selected NHL patients were tested for ACA and anti-ß2 GPI at presentation using ELISA technique. They were followed-up over a median period of 6 months to detect the occurrence of thromboembolism (TE) and bone marrow recovery following chemotherapy by full blood counts. APA was found in 23 out of 53 NHL patients, ACA in 35.8% and anti-ß2 GPI antibodies in 18.9%. The incidence of APA increased in cases older than 40 yrs (91.3%). However, positivity for APA was not associated with gender, survival, histology or stage of lymphoma. There were three patients who developed TE and all of them were ACA positive. Positive APA was found to correlate with thrombocytopenia at presentation (p=0.032) and associated with poor platelet recovery following chemotherapy (p=0.001). Although no statistical association was found between APA positive NHL and thrombosis, there was a tendency for TE to occur in APA positive NHL

Dengue infection is a major public health problem, affecting thousands of children in the tropical countries. There is a severe form of dengue infection called dengue hemorrhagic fever. In this case, the host immunological response host is the important factor in the course of disease. However, the actual mechanisms underlying severe bleeding in dengue DHF are not completely understood. The immune mimicking theory is a widely accepted hypothesis. The role of NS1 as an important protein causing the unwanted immunological reaction bringing DHF is hypothesized. In addition, CD61 is observed to have more phylogenetically similar to dengue virus NS1 activity than other thrombocyte protein and fibrinogen; CD61 is believed to be play an important role in immune mimicking process. Here, we performed an analysis to answer the question how dengue virus NS1 proteins of different serotypes, comparing to CD61, bind to immunoglobulin M (IgM) during the early infection of dengue. We performed a molecular structural modeling for the complex between the NS1 proteins of different serotypes as well as CD61 and IgM we predicted for the binding affinity of each complex using computational medicine technique. The predicted affinity for the complex between the NS1 proteins of different serotypes as well as CD61 and IgM was calculated. The binding affinity of the complex ranges from 28.6 to 32.8. The binding affinity between NS1 proteins and IgM is stronger than that between CD61 and IgM. The binding affinity between CD61 and IgM is closed to D-2VNS1 than other NS1. This might reflect that D-2VNS1 might present more homology to CD61 than other NS1 proteins. In addition, the results from this study also support the immune mimicking theory for DHF development in dengue infection

In order to ensure viral safety of human plasma derived proteins, biopharmaceutical manufacturers during the production process adopt one or more viral inactivation steps. One of these, consisting of a heat treatment of lyophilised preparation could determine an increase of high molecular weight aggregates and, as a consequence, a decrease of solubility. Aim of the present work is to characterize the insoluble material present in human plasma derived Factor VIII. The soluble part and insoluble aggregates, derived from rejected lots of Emoclot D.I., a high purity FVIII concentrate (Kedrion S.p.A.), were separated by centrifugation; the supernatant and the pellet, reconstituted in 5M urea, were analysed by gel electrophoresis, Western blot and size exclusion chromatography. The molecular composition of soluble and insoluble FVIII concentrate was compared. The insoluble aggregates found in the plasma derived FVIII concentrates were non-covalently linked high molecular weight (HMW) homo/heteroligomers prevalently composed by fibrinogen, fibronectin, vWF and FVIII. The heat treatment, but not the lyophilisation, determined a significant increase of the HMW material. The molecular composition of the aggregates is quali/quantitatively similar to the soluble material.

Primary bone lymphoma is a rare group of lymphomas. Histologically, the most common type of primary bone lymphoma is diffuse large cell type and of intermediate type. We present a case with primary bone lymphoma and treated with 8 cycles of CHOP regimen resulted with partial response with persisting bone lesions. High dose chemotherapy and autologous peripheral blood stem cell transplantation was performed two years after of diagnosis and, osteolytic lesions on the bones completely disappeared after this treatment. The patient is still in remission without any new bone events and with normal clinical and laboratory findings. Complete disappearance and durable complete remission of bone lesions in primary bone lymphoma is very rare, even after high dose chemotherapy.

Blood transfusion is required for severe anaemia due to a haematologic disease, especially in haemoglobin disorders. Iron overload is an important long -term complication in transfusion therapy for thalassaemic patients. To prevent the side effect of excessive accumulation of iron in the body, chelation therapy is recommended in transfusion dependent thalassaemics. Deferiprone is a new widely used oral iron chelator. Although its primary and secondary structures are well described there are only a few data on tertiary structure. In addition, modelling for deferiprone - iron complex, which can be used for further applications in metallopharmacology, is warranted. Here, we perform a chemoinformatic analysis to model three dimensional structure of the deferiprone-iron complex. To address this question, a computer-based study for structure modelling is performed. According to this study, the three dimensional models of deferiprone and deferiprone-iron complex are determined. Here, we show that the complex had the triangular pyramidal geometry.

The demand for anticoagulant treatment is increasing. We compared the benefits of computer- generated anticoagulant dosing with traditional dosing decided by experienced medical staff in achieving target international normalized ratios (INRs). The DAWN AC computer program was used for calculation of doses and times to next visit. Our main endpoint was time spent in target INR range (Rosendaal method). The two dosing systems show no significant difference in the quality of the control of coumarin therapy (time spent in target INR range 51.2%/52.5% p=0.912 in manual and computer dosing respectively). Also the introduction of computerized dose substantially saved medical and administrative time. The study was useful for gaining a better understanding of the basis for the practices noted in the computer algorithm, as well as how these practices will change in this regard

A 67-year-old woman was admitted to our department
because of AML (M2 FAB) relapse, after a short remission.
On admission the physical examination revealed inflammation
and swelling of the right leg. The limb was
sensitive and painful to palpation. Liver was enlarged 3
cm below the costal margin while the spleen was not palpable
and there was no peripheral lymphadenopathy; the
patient was febrile (37.6°C, for 7 days).ntal

The case of a patient with multiple myeloma who had colon adenocarcinoma and an additional three serum M components (IgG? + IgG? + IgM?) was presented. We encountered the association of this rare disorder with colon adenocarcinoma that has been reported to be frequently associated with lymphoproliferative diseases for the first time. Occurrence of colon cancer and triclonal type multiple myeloma was considered to be coincidental for this patient.

Haematopoietic stem cell transplantation (SCT) has
evolved over a period of 50 years. Allogeneic and autologous
transplantations of stem cells from bone marrow,
peripheral blood or cord blood have emerged as effective
therapies for patients with a variety of haematological and
genetic diseases. From 1950 to 1960, haematopoietic SCT
engraftment progressed from an uncertain and often dangerous
curiosity to an important modality. At the end of
the 1960s, tremendous progress has been made in our
understanding of the human histocompatibility gene complex
and the cellular mechanisms giving rise to graft rejection
and graft-versus-host (GVH) disease. This has resulted
in more precise HLA typing that has improved selection
of potential unrelated donors, and has led to the
emergence of more effective strategies to ensure engraftment
and to prevent or ameliorate GVH disease. Marked
progress has also been made in supportive care measures
and in the treatment and prevention of opportunistic infections
following SCT. In the early 1970s the Seattle team
was able to accumulate and report a series of children
with acute leukaemia treated in relapse, of whom 20%
were cured of their disease. With greater understanding
of the cellular basis of haematopoietic SCT has come the
concept that limited immunosuppression may be sufficient
for engraftment and have the potential of reduced toxicity
while maintaining graft-versus-leukaemia (GVL) effects.

A prospective, open-label phase III study was carried out to evaluate the efficacy and tolerability of a preparation of virus-inactivated normal human intravenous immunoglobulin. Fifteen adult patients suffering from chronic idiopathic thrombocytopenic purpura (ITP), (basal platelet count =50x109/l (response rate was 93.3%), and only 2 out of 10 patients with positive baseline Rumple-Leed test remained positive after treatment (p =0.0022). Interestingly, a close inverse correlation between platelet counts and haemoglobin levels was observed. No side effects were recorded. This study provides evidence of therapeutic efficacy and the good tolerability of the immunoglobulin preparation we used in this trial, and suggests the role of haemolysis as a mechanism for the increase in platelet count.

Thalassaemia intermedia is an ill defined clinical syndrome which usually occurs due to the influence of multiple mutations in the a and ß globin genes. The phenotype is influenced by the combination of different mutations, however it is not possible to predict the clinical phenotype based upon the genotype. The phenotype is also influenced by mutations in the ? gene and the Xmn 1 polymorphisms of the ? gene. The paper reviews the various interactions leading to a silent, mild, moderate and severe ß thalassaemia phenotype and the various interactions between the ß gene and the a gene mutations. The Xmn1 polymorphism and ? gene mutations are also reviewed.

Nitric oxide is an important mediator, which has several roles in both physiological and pathological processes. In this study, we aimed to determine the level of nitrite and nitrate levels representing NO and expression of iNOS in HL 60 model cell line during the differentiation and cytoplasmic extract of blastic cells obtained from 20 de novo AML patients to evaluate any correlation between nitrite and nitrate levels and various prognostic factors and the possible role of NO in leukaemogenesis. Griess method was used to determine the level of nitrite and nitrate. Western blotting was performed by using iNOS expression with polyclonal anti-iNOS antibody. Higher nitrate and nitrite levels were found in HL60 cells before differentiation and in patients compared to control group. When HL 60 cells were treated with methylprednisolone, the level of nitrite and nitrate decreased gradually during differentiation. And also, there was detectable amount of iNOS protein expression in HL60 cells and in patients but not in control samples. Although we could not provide the data related to changes in neither expression level of iNOS nor the amount of nitrite and nitrate after treatment in patients, our findings suggests the possible role of NO in leukaemogenesis.

The purpose of this study was to identify prognostic factors of CD34+ cell mobilization and predictive factors for outcome in a series of 121 consecutive patients with acute myeloid leukaemia (AML) from the same institution enrolled into the autologous peripheral blood stem cell (PBSC) transplantation program. PBSC were collected following mobilization with granulocyte colony- stimulating factor (G-CSF) alone (n=67), or chemotherapy plus G-CSF (n=54). Variable numbers of CD34+ cells were harvested: 67 patients had a low, 26 an intermediate, and 28 a high average yield per day. Mobilization with chemotherapy plus G-CSF was associated with higher CD34+ yields. Cytogenetic risk group were unevenly distributed between the three CD34+ yield groups. Outcome was influenced by CD34+ yields with a higher proportion of relapses and shorter survivals in the group with high average yield as compared to the other groups. Other factors influencing the outcome after aphereses were cytogenetics, the mobilization method, autologous stem cell transplantation (SCT) effectively performed, white blood cell (WBC) count at diagnosis, and leukaemic contamination in aphereses products. Leukaemic contamination on aphereses products showed a correlation to cytogenetics and to mobilization methods. Patients with the highest mobilizing capacity have a poor prognosis due to an increased relapse incidence

In 2 experimental systems, between non-thymectomized (Tx) (DA?Lewis)F1 rat hosts and syngeneic F1 donors, and in another 2 experimental systems, between Tx F1 hosts and DA rat donors, graft versus host reaction (GvHR) and graft rejection due to bone marrow (BM) transplantation were investigated, respectively. All the F1 hosts had congenitally increased ?d T cell receptor (TCR) lymphocytes to about 40% in the spleen. Among the 25 F1 hybrid rats examined, whose spleen DNA was amplified for the Foxa2 gene in polymerase chain reaction (PCR), 5 (20%) rats showed activated expression of the Foxa2 gene. In 1 of the 2 former experiments, 1/5 F1 hybrids died of lateonset acute GvHR after 2.9 months. In the latter 2 experiments, the 16 (14 sub-totally and 2 totally) Tx F1 hosts were protected well from GvHR when magnetically separated DA BM cells contained 31- 42% of Thy-1+/beta-2-microblobuin-negative (ß2M-) cells. Among the latter 2, allogeneic graft rejection was protected when the donor cells were injected into the spleen, but not into the tail vein. Activated and suppressed thymus expression of signal transducers and activators of transcription 1 (Stat1), phospho-tyrosine (P-Tyr) and CD90 (Thy-1), which were measured using a flow cytometer (FCM), clearly indicated GvHR and graft rejection, respectively. All the Tx hosts had a low level of interleukin-2 receptor (IL-2R). Eosinophil colonies in the spleen were detected in all the 2 totally Tx rats. One of the sub-totally Tx hosts with 94% of Fas+ BM cells in the FCM showed activated BM RNA of Fas ligand (FasL) and Pdx-1 according to the reverse transcriptase (RT)-PCR, but 1 of the totally Tx hosts with 52% of FCM Fas+ BM cells did not show the FasL and Pdx-1 RNA activations. BM electron microscopic analyses of the totally Tx rats showed an ineffective erythropoiesis, but the Fas/FasL activation in BM cells did not depend on thymectomy. Three/8 F1 rats in the latter 2 experiments showed activated FasL and Pdx-1 RNA in the BM RT-PCR, which must be induced by a heterozygous gene defect of the Foxa2, as found in the 5/25 hosts with a compensatory activated Foxa2 DNA.

Testicular diffuse large B-cell lymphoma (DLCL) is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Relapses are observed in uncommon sites, but skin relapse is exceptional. We report a 73-years old patient who presented with left testis swelling and bone marrow involvement (Ann Arbor stage IVA). First remission was achieved with CHOP chemotherapy and irradiation of contralateral testis and pelvic lymph nodes. Three years later, stage IE extranodal skin relapse of DLCL occurred. Second remission was achieved with immunochemotherapy (R-CHOP). We discussed problems regarding optimal treatment of this disease, since testicular lymphoma is the most common testicular malignancy in the elderly, associated diseases are common, and propensity for extranodal relapse is a distinct biological feature.

Myeloproliferative diseases are chronic haematological malignancies with a common origin from the myeloid progenitor cell, which may secondarily cause marrow fibrosis or undergo leukaemic transformation. Myeloproliferative diseases include chronic myelogenous leukaemia, essential thrombocythaemia, polycythaemia vera and agnogenic myeloid metaplasia. Liver diseases have been documented in correlation with myeloproliferative diseases predominately emerging on the ground of hepatic vein thrombosis (Budd-Chiari syndrome), nodular regenerative hyperplasia of the liver, hepatic infiltration with haematopoietic cells or sinusoidal fibrosis and portal hypertension. In fact, myeloproliferative disorders are among the most common prothrombotic disorders secondarily causing Budd-Chiari syndrome. Oesophageal varices, ascites, abdominal pain, progressive splenomegaly, widening abdominal girth, venous collaterals, nausea and vomiting are predominating clinical manifestations of the hepatic syndromes. Diagnosis of liver involvement relies upon the histopathological examination of liver biopsy specimens and/or angiography/venography, whereas the identification of the underlying haematological disorder is accomplished by either bone marrow biopsy or spontaneous endogenous erythroid colony formation. Accordingly, therapeutic options include anticoagulation with heparin, fibrinolysis followed by oral anticoagulation, and appropriate treatment of the underlying myeloproliferative disease. In case of failure, invasive options include local procedures such as angioplasty or stenting, venous decompression by transjugular intra-hepatic portal-systemic stents, or liver transplantation. Finally, in the case of hepatic involvement, clinical suspicion should also be aimed at the therapeutic agents presenting a potential hepatotoxic action. Liver diseases that are caused by the direct effects of chronic myeloproliferative disorders or their treatment are reviewed by this current article.

Thalassemia is the most common hereditary chronic
haemolytic anaemia due to imbalance of the globin chain
synthesis. The severity of impaired globin chain generates
the diversity of thalassaemic phenotypes. The excess
pool of unpaired haemoglobin chains leads to erythrocyte
damage by oxidative means which might be further
exaggerated by the heme1. Severe oxidative damage is
observed in erythrocytes due to the presence of excess
alpha globin chains. The accumulation of excess alpha
chain and iron overloaded will instigate the increases red
blood cell destruction and resulting in decreased antioxidants.
It has been found that the superoxide dismutase
activity of haemoglobin E (HbE) traits was higher than
that of healthy persons2. This indicated that HbE traits
had generated more oxidants in red blood cells than
healthy people. Our previous report has also shown that
HbE traits had a low total antioxidant level in plasma3.
Johnston and Cox (2001)4 have reported that short
term vitamin C supplementation confer maximal antioxidant
protection to plasma in healthy persons. The data
was shown that Heinz body formation was significantly
lower than baseline values.
In this report, we suggested that vitamin E, a potent
antioxidant supplement, might help to reduce this abnormally
elevated oxidant level. Thus, we aim to investigate
the percentage of Heinz body formation, haemoglobin