Vincenzo Martinelli

University of Naples Federico II, Napoli, Campania, Italy

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Publications (29)135.24 Total impact

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    ABSTRACT: Background In essential thrombocythemia (ET) patients, history of thrombosis and age over 60 y are validated risk factors for occurrence of thrombosis during the follow-up. Leukocytosis, JAK2 V617F mutation, cardiovascular (CV) general risk factors, and male gender are candidate risk factors for thrombosis. The thrombocytosis, a constitutive abnormality in ET, is associated with both thrombotic and hemorrhagic complications.
    No preview · Article · Nov 2013 · Blood
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    ABSTRACT: Givinostat, a histone-deacetylase inhibitor (HDACi), inhibits proliferation of cells bearing the JAK2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms (MPN). In this multicentre, open-label, phase II study, 44 patients with polycythaemia vera (PV), unresponsive to the maximum tolerated doses (MTD) of hydroxycarbamide (HC), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients.
    Preview · Article · Apr 2013 · British Journal of Haematology
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    ABSTRACT: Background. Interferon-alpha (IFN) has shown significant activity in MPN. In Essential Thrombocythemia (ET) this drug is able to rapidly normalize platelet and leukocyte counts, as well as organomegaly. IFN is the only therapy known to induce complete molecular remission with the reduction or the suppression of tumor burden.Despite its effectiveness, many patients discontinue IFN therapy due its side effects. Their incidence and severity are dose-related and the most common are flu like syndrome, myalgia, headache, fatigue, myelosuppression, liver abnormalities, autoimmune disease and depression. IFN has no leukemogenic effects and is safe in pregnancy.We hereby report our monocentric experience. Methods. From 1992 until today, the Division of Hematology of the Federico II University Medical School, Naples, Italy, followed 365 ET patients (diagnosis according to PVSG criteria and subsequently with 2008 WHO criteria); 257 patients were treated with cytoreduction: 64.5% with hydroxyurea, 23.5 % with IFN, 10% with anagrelide and 2% with busulfan.Patients treated with IFN received subcutaneous injection at induction dose of 3x106 units 5 times a week, reduced on the basis of clinical-hematological response. Results. After a median follow up of 36 months, of the 60 patients receiving IFN, 60% achieved complete hematological response (CHR) according to the European Leukemia Net criteria; of these 13% were taken off therapy and 39% are still receiving very low doses of IFN (3x106 units every 7-15 days). As many as 20% experienced partial hematological response (PHR). The median time to response was 2.6 months.Response was not influenced by age (p=0.06), gender (p=0.4), baseline values of hematocrit and hemoglobin normalized for the gender, platelet count (p=0.29), WBC count (p=0.1). Furthermore JAK2V617F mutational status does not influence the response.Under IFN therapy no patients had thromboembolic or hemorrhagic event, independently of their cardiovascular risk. As many as 22 patients experienced flu-like symptoms, 3 dermatitis, 3 alopecia, 7 autoimmune thyroiditis; of them only 2 patients had hypothyroidism and had to suspend IFN treatment.Average spleen volume at the baseline was 495 ml; after a median follow-up of 18 months it was 472 ml, with no differences in volume enlargement in CHR/PHR compared to non responsive patients.Bone marrow fibrosis grade (according to Thiele) did not worsen after IFN treatment in either patients who achieved CHR or PHR. We are unable to evaluate data about non responsive patients, because this parameter could be influenced by their second line treatment. Conclusions. IFN was safe and effective for patients with ET. The ability of IFN therapy to control and modify the clinical course of the disease is confirmed by our data. This response is sustained for prolonged periods in some patients, even after therapy discontinuation. IFN should be considered as election treatment even in young patients, for its lack of leukemogenic and teratogenic effects.
    Full-text · Conference Paper · Jun 2012
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    ABSTRACT: Hydroxyurea (Hydroxycarbamide; HU) is commonly used for the long-term treatment of patients with Philadelphia-chromosome negative chronic myeloproliferative neoplasms (MPNs). It is considered a first-choice agent for the treatment of these disorders as underlined by the European Leukemia Net Consensus Conference [1], although it is formally approved for this indication in some countries only. The drug is reportedly well tolerated in the large majority of subjects, although systemic and/or localized toxicities have been reported. Consensus criteria for definition of "intolerance" to HU have been described;patients who develop intolerance are candidate for second-line therapy and, more recently, for investigational drugs. However, no epidemiologic information about the occurrence of the most clinically significant HU-associated adverse events is yet available. In this study, the authors report on a multicenter series of 3,411 patients who were treated with HU among which 184, accounting for 5% of total, developed significant drug-related toxicities. These data provide an estimate of the frequency and a detailed characterization of clinically significant HU-related toxicities; these information have relevance for the management of MPN patients who require second-line therapy after developing HU-related intolerance.
    Full-text · Article · May 2012 · American Journal of Hematology
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    ABSTRACT: The JAK2 tyrosine kinase leads to activation of many signaling pathways critical for cell growth and differentiation. A recurrent mutation in the JAK2 (V617F) has been described in the myeloproliferative neoplasm (MPN), giving proliferative and survival advantages to hematopoietic precursors. We previously demonstrated a nuclear localization of JAK2 protein, suggesting a new unexplored JAK2 signaling (Blood. 2010 Dec 23; 116(26)). Here we measured the nuclear and cytoplasmic distribution of JAK2 protein in K562 (JAK2WT) and in HEL (homozygous for JAK2-V617F mutation) cell lines by confocal immunofluorescence (CIF) microscopy. In K562 cell line the total JAK2 protein density was 0.65±0.13 Million pixels of which 50% was a nuclear signaling. The total JAK2 protein density was higher in HEL than K562 cell lines (1.28±0.27 Million pixels) with 20% of protein localized in the nucleus (0.27±0.07 Million pixels). We observed a distinct perinuclear localization of JAK2 in a characteristic spot signal similar to centrosome structure in both cell lines. The centrosome is a small cellular organelle essential for microtubule organization that has been reported to be altered in many MPNs. We hypothesize that the constitutive phosphorylation at this site may alter centrosome function. Therefore, we performed coimmunoprecipitation and co-immunofluorescence assays, by anti- Tubulin (a characteristic centrosome protein), to evaluate whether JAK2 associates to the centrosomes. In addition, CIF microscopy showed that wt JAK2 colocalizes with Tubulin in 92% of K562 cells with normal centrosomes, in a cell cycle independent manner. Notably, we observed an altered number of centrosomes in all remaining K562 cells lacking of JAK2- Tubulin colocalization. By contrast, only 18% of HEL cells had a JAK2- Tubulin colocalization. The remaining HEL cells, lacking of JAK2- Tubulin colocalization in centrosomes, were characterized by structural or numeral centrosomes abnormalities. Interestingly, when we forced the expression of JAK2V617F in K562 cell line by transfection with vector containing the mutant form, the JAK2- Tubulin colocalization was significantly reduced and was restricted to the cells with normal centrosomes. This data strongly suggest that JAK2 protein interacts with centrosome structure and that JAK2V617F is associated with centrosome abnormalities.
    Full-text · Conference Paper · Oct 2011
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    ABSTRACT: This retrospective study of the thrombocythemia Italian registry (RIT) documented that 71 (30.6%) out of 232 ET patients experienced 88 cardiovascular adverse events (CV-AEs) during anagrelide treatment (522 pt-y). The rate of CV-AEs was: 24.1% for palpitations, 4.3% for angina, 3.5% for arterial hypertension, 3.0% for congestive heart failure, 1.8% for arrhythmia, 0.9% for AMI, 0.4% for pericardial effusion. CV-AEs led to treatment discontinuation in nine (3.9%) patients, while in the remaining cases they were managed by pharmacological intervention and/or patient life style improvement. CV-AEs had no relationship with patient characteristics (including older age). A significant relationship was found only with a higher anagrelide induction dose. In the absence of any agreed protocol, a cardiovascular instrumental evaluation (CV-IE) was performed in 102 (44%) patients before commencement of anagrelide (with higher rate after the anagrelide/Xagrid EMA approval of 2004), and in 84 (36%) patients during treatment. Patients with and without CV-IEs, who resulted completely balanced for all their characteristics, did not significantly differ in the occurrence of CV-AEs. In conclusion, this study on ET patients treated with anagrelide shows that CV-AEs, equally distributed in younger and older subjects, were mostly mild and easily manageable, allowing safe treatment continuation in the majority of cases. Moreover, routinely performing a CV-IE did not appear to anticipate the occurrence of CV-AEs.
    No preview · Article · Jul 2011 · Leukemia research
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    ABSTRACT: In March 2009 a 22-years-old woman presented to our Institution with persistent high platelet count (>650x109/L) and no other peripheral blood alterations. At physical examination splenomegaly was present; headache, erythromelalgia and diarrhea were referred. Blood chemistry was normal and reactive thrombocytosis was excluded. The morphological examination of the bone marrow (BM) aspirate revealed an increase of enlarged megakaryocytes (MK) with emperipolesis phenomena. BM smears showed also spindle shaped mast cells (MC) with oval and eccentric nuclei and focal granule accumulation. Eosinophil forms were increased. Biopsy specimens were hypercellular and showed a marked proliferation of giant MK, preferentially grouped into clusters; in addition to this myeloproliferative pattern, nodules of ovoid or spindle shaped MC were present, surrounded by areas of localized dense network of reticulin fibers. MC identity was confirmed by toluidine-blue and immunohistochemical staining for anti-CD117 (KIT) and CD2. Cytogenetic analysis revealed a normal karyotype. A specific immunophenotypic analysis of MC was not performed at this time. The allele-specific-PCR demonstrated the presence of the JAK2V617F mutation. DNA sequencing did not confirm the G>T substitution on the base 1849 codifying for the Val617Phe mutation, but we detected a G>T substitution on the nucleotide 1851 codifying for a silent Val617Val mutation. FIP1L1-PDGFRA and BCR-ABL transcripts search was negative. DNA sequencing of KIT gene, did not show D816V mutation, but detected a three nucleotides deletion (ACG; bases: 2143-2144-2145), on the exon 15 that bring to a serine 715 deletion. Systemic Mastocytosis (SM) clinical staging showed not skin involvement, normal bone density and a spleen volume of 500 mL by ultrasound; serum tryptase was 17,6 ng/mL. We concluded for SM with Associated clonal Hematological Non-Mast cell lineage Disease (SM-AHNMD), id est Essential Thrombocyhemia. Because of symptoms we began treatment with IFN- α-2a at 3 MU five times a week. The therapy was well tolerated, all symptoms disappeared and the platelet count was lowered to less than 350 x109/L. After four months of therapy, IFN-α dose was tapered to three times a week. The BM aspirate was repeated after eleven months, showed the absence of MC and a MK reduction, while the BM biopsy demonstrated persistence of MC nodules. The specific immunocytofluorimetric assay was negative. The molecular analyses confirmed the Ser715 del on KIT gene but the JAK2V617V silent mutation was undetectable. The tryptase serum level was 20,9 ng/mL. The spleen volume was 290 mL and resulted reduced compared to the baseline. This is the first case of a SM-AHNMD harboring a silent mutation on JAK2 and Ser 715 del on KIT. This KIT deletion has been previously described in GIST and if it is an activating mutation or a gene polymorphism is still matter of debates. The significance of this mutation for myeloproliferative disease is unknown. However this mutation leads to deletion of a polar amino acid placed near Tyr719 which is necessary for KIT PI3K binding and downstreaming; this mutation could induce abnormalities in KIT local folding and signaling and contribute to pathogenesis of both MC and MK disease.
    Full-text · Conference Paper · Jun 2011

  • No preview · Article · May 2011 · Leukemia Research
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    ABSTRACT: Recently, Dawson et al identified a previously unrecognized nuclear role of JAK2 in the phosphorylation of histone H3 in hematopoietic cell lines. We searched nuclear JAK2 in total bone marrow (BM) cells and in 4 sorted BM cell populations (CD34(+), CD15(+), CD41(+), and CD71(+)) of 10 myeloproliferative neoplasia (MPN) patients with JAK2V617F mutation and 5 patients with wild-type JAK2 MPN. Confocal immunofluorescent images and Western blot analyses of nuclear and cytoplasmic fractions found nuclear JAK2 in CD34(+) cells of 10 of 10 JAK2-mutated patients but not in patients with wild-type JAK2. JAK2 was predominantly in the cytoplasmic fraction of differentiated granulocytic, megakaryocytic, or erythroid cells obtained from all patients. JAK2V617F up-regulates LMO2 in K562 and in JAK2V617F-positive CD34(+) cells. The selective JAK2 inhibitor AG490 normalizes the LMO2 levels in V617F-positive K562 and restores the cyto-plasmic localization of JAK2.
    Full-text · Article · Dec 2010 · Blood
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    ABSTRACT: Hepatosplenic T-cell lymphoma is a rare clinicopathologic entity with poor outcome. It is characterized by malignant T-cell proliferation in the liver, spleen and bone marrow. The diagnosis is based on clinicopathological criteria and can be upgraded with immunophenotypic profile and molecular studies as well. We describe the case of a 51-year old woman affected by HSTCL, who underwent a systematic flow cytometric and molecular follow-up. In May 2006, the patient showed massive hepatosplenomegaly and pancytopenia. She underwent splenectomy, hepatic biopsy and BM analysis, for an abnormal lymphoid cells infiltration a diagnosis of HSTCL was made. The patient was treated with six courses of CEOP14 and complete remission was achieved. The first relapse occurred in September 2008 and the second and last in August 2009. Treatment consisted of DHAP, AutoTMO, GEMOX, Nelarabine. She died in December 2009. At diagnosis BM, spleen and liver biopsy had shown, CD45+CD2+CD3+CD7+CD56+TcRd+CD5–CD4–CD8– neoplastic cells at cytofluorimetric analysis. Molecular analysis, performed by denaturing high-performance liquid chromatography (DHPLC), showed a clonal rearrangement of the TcR- chain gene on the same samples and the sequencing analysis of both DNA strands identified the monoclonal rearrangement Vg10-JgP1. At the first relapse BM biopsy was positive for lymphoma infiltration despite the negative cytofluorimetric and morphological analysis, and the liver biopsy was infiltrated by CD45+CD2+CD7+CD56+CD3–CD5–CD4–CD8–TcRd– like-NK-cell abnormal lymphocytes as well. Molecular studies showed the Vg10-JgP1 and a new Vg11-JgP1 clonal rearrangements on BM. At the second relapse, the histological study on the liver biopsy failed to detect any neoplastic cells, although the flow cytometric study showed large neoplastic cells. BM biopsy was positive for lymphoma infiltration and the cytofluorimetric analysis identify a like-NK-cell population. This case seems interesting for many aspects, the main being: (a) the immunophenotype change from Tcell CD45+CD2+CD3+CD7+CD56+TcRd+CD5–CD4–CD8– to a like-NK-cell immunophenotype CD45+CD2+CD7+CD56+CD3–CD5–CD4–CD8–TcRd–, (b) the evidence of two different clonal rearrangements of the TcR- - chain gene (Vg10-JgP1 and Vg11-JgP1). We might hypothesise that neoplastic cells rosed from a clonal proliferation of Natural killer T (NKT) cells. NKT cells are characterized by the expression of both TCR and NK receptors on the cell surface; moreover, recent evidence indicates that they are totipotent and can underlie many diseases. Furthermore, this could be a case of neoplastic proliferation of T lymphocytes subpopulation bearing two distinct TCR. This is supported by the evidence that a proportion of circulating T cells co-expresses two distinct TCR chains, although the T cells are ensured by several allelic exclusion processes operating at either the genotypic or phenotypic levels and expressing two distinct or TCR.
    Full-text · Conference Paper · Oct 2010
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    ABSTRACT: gHepatosplenic T-cell lymphoma (HSTCL) is an uncommon disease. It is characterized by involvement of the spleen, liver and often bone marrow (BM). HSTCL affected Patients usually show hepatosplenomegaly and cytopenias; lymphadenopathy is minimal or absent. The disease has a progressive clinical course and poor prognosis. Here, we describe the case of a 51-years old gamma-delta HSTCL affected female.In May 2006, the Patient showed massive hepatosplenomegaly; blood counts revealed mild pancytopenia. The Patient underwent splenectomy, hepatic biopsy and BM analysis. The three parenchymas were infiltrated by a population of abnormal lymphoid cells. Cytofluorimetric analysis of BM, spleen and liver biopsy showed CD45+ CD2+ CD3+ CD7+ CD56+ TcR-gd+ CD5– CD4– CD8– neoplastic cells. Molecular analysis, performed by denaturing high-performance liquid chromatography (DHPLC), showed clonal rearrangement of TcR-g chain gene on the same samples. Sequencing analysis of both DNA strands confirmed DHPLC results, by allowing us to identify the monoclonal rearrangement Vg10-JgP1. Therapy consisted of six CEOP- 14 regimen. In December 2006 a complete remission (CR) was demonstrated by immunological, histological and molecular analysis of BM and liver biopsy. CR lasted 21 months; in February, 2008 mild pancytopenia appeared. Positron emission tomography - computed tomography (CT-PET), immunophenotipic and histological studies were negative; TcR-g clone was not detectable. In September 2008 anaemia worsened, mild elevation of liver enzyme and abnormal serum ferritin appeared. Histological BM biopsy was positive for lymphoma infiltration, despite negative cytofluorimetric and morphological analysis. Histological and cytofluorimetric analysis of liver biopsy were both positive for T lymphoma with CD45+ CD2+ CD7+ CD56+ CD3– CD5– CD4– CD8– TcRab–, TcRgd– large abnormal lymphocytes. Molecular study showed the Vg10-JgP1 and an additional Vg11-JgP1 clonal rearrangement on bone marrow.The Patient was treated with four cycles of DHAP reaching CR (at liver level as well); in March 2009, she underwent auto-TMO. In August 2009, a second relapse occurred. On liver biopsy, histological study showed absence of neoplastic cells, but cytofluorimetric analysis was positive for large neoplastic cells. BM biopsy was positive for lymphoma infiltration. The Patient was treated with GEMOX regimen. In November 2009, sequencing analysis on bone marrow biopsy detected only the Vg11-JgP1 clone; cytofluorimetric analysis identified a NK-like immunophenotype cell population; one cycle of Nelarabine was administered but the Patient died on December 2009. With the aim to add data in a rare disease like HSTCL we want to point of: (a) immunophenotypic changes from a T-cell (CD45+ CD2+ CD3+ CD7+ CD56+ TcRgd+ CD5– CD4– CD8–, at diagnosis) to a NK-like (CD45+ CD2+ CD7+ CD56+ CD3– CD5– CD4– CD8– TcRgd-, at second relapse) immunophenotype; (b) the evidence of two different clonal rearrangements of TcR-g- chain gene (Vg10-JgP1 and Vg11-JgP1).
    Full-text · Conference Paper · Jun 2010
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    ABSTRACT: Pregnancy is a high-risk event in women with essential thrombocythemia (ET). This observational study evaluated pregnancy outcome in ET patients focusing on the potential impact of aspirin (ASA) or interferon alpha (IFN) treatment during pregnancy. We retrospectively analyzed 122 pregnancies in 92 women consecutively observed in the last 10 years in 17 centers of the Italian thrombocythemia registry (RIT). The live birth rate was 75.4% (92/122 pregnancies). The risk of spontaneous abortion was 2.5-fold higher than in the control population (P < 0.01). ASA did not affect the live birth rate (71/93, 76.3% vs. 21/29, 72.4%, P = 0.67). However, IFN treatment during pregnancy was associated with a better outcome than was management without IFN (live births 19/20, 95% vs. 73/102, 71.6%, P = 0.025), and this finding was supported by multivariate analysis (OR: 0.10; 95% CI: 0.013-0.846, P = 0.034). The JAK2 V617F mutation was associated with a poorer outcome (fetal losses JAK2 V617F positive 9/25, 36% vs. wild type 2/24, 8.3%, P = 0.037), and this association was still significant after multivariate analysis (OR: 6.19; 95% CI: 1.17-32.61; P = 0.038). No outcome concordance between first and second pregnancies was found (P = 0.30). Maternal complications occurred in 8% of cases. In this retrospective study, in consecutively observed pregnant ET patients, IFN treatment was associated with a higher live birth rate, while ASA treatment was not. In addition, the JAK2 V617F mutation was confirmed to be an adverse prognostic factor.
    No preview · Article · Oct 2009 · American Journal of Hematology
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    ABSTRACT: In this work, we report on a systematic fluidodynamic investigation of red blood cell (RBC) suspensions flowing in microcapillaries with diameters comparable to the cell size in vitro. By using high-speed video microscopy and image analysis, we provide the first simultaneous determination of both cell velocity and shape parameters related to RBCmembrane deformability over an extended range of pressure drops, and the first quantitative comparison with theoretical results from the literature. Good agreement was found with the predicted axisymmetric shapes tending towards an apparent bullet-like asymptotic configuration at increasing cell velocity. A potential application of this work is in the design of flow-based devices to study the pathological conditions affecting cell deformability, thus allowing us to overcome the limits of classical static methods, such as micropipette aspiration, which are not suitable for handling a large number of cells.
    No preview · Article · Sep 2009 · Soft Matter

  • No preview · Article · Aug 2008 · Leukemia & lymphoma
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    ABSTRACT: In this work, the effects of thalassemia, a blood disease quite diffuse in the Mediterranean sea region, have been investigated at single cell level using a Raman Tweezers system. By resonant excitation of hemoglobin Raman bands, we have examined the oxygenation capability of beta-thalassemic erythrocytes. A reduction of this fundamental erythrocyte function has been found. The measurements have been performed on a significant number of red blood cells; the relative statistical analysis is presented. Moreover, the response to photo-induced oxidative stress of diseased cells with respect to the normal ones has been analyzed. Finally, the deformability of thalassemic erythrocytes has been quantified by measuring the membrane shear modulus by using a double-trap system: the measurements have revealed an increase in membrane rigidity of more than 40%, giving evidence that the genetic defect associated to thalassemia, which manly relies on hemoglobin structure, also strongly affects the erythrocyte mechanical properties. Our results demonstrate that the developed set-up may have potential for the monitoring of blood diseases and their response to drug therapies.
    Full-text · Article · Jun 2008 · Optics Express
  • A C De Luca · G Rusciano · G Pesce · A Sasso · E Madonna · R Ciancia · V Martinelli · B Rotoli

    No preview · Article · Oct 2007 · Haematologica
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    ABSTRACT: The deformability of red blood cells flowing in microvessels is essential to maintain optimal blood circulation and to allow gas transfer between blood and tissues. Here, we report on an experimental methodology to investigate the deformability of RBCs flowing in microcapillaries having diameter close to the average cell size. The microcapillaries are placed in a rectangular flow cell, where a suspension of RBCs, properly diluted in albumin-additioned ACD, is fed through a syringe under the action of a liquid head in the physiological range. Video microscopy images of the flowing RBCs are acquired at high magnification and later processed by an automated image analysis macro. It was found that RBCs from healthy donors exhibit the classical parachute shape observed in vivo. Furthermore, all the data of healthy RBC velocity vs liquid head are well represented by the same linear regression, independently on the donor. Preliminary results on beta-thalassemia RBCs are also presented and show, on the average, a reduced velocity compared to healthy samples.
    No preview · Article · Feb 2007 · Annali dell'Istituto superiore di sanita
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    ABSTRACT: Posttransplant erythrocytosis (PTE; i.e., hematocrit [Ht] >=51%) may be responsible for cardiovascular events. Angiotensin-converting enzyme inhibitors (ACEIs) are increasingly employed in PTE treatment. Diverse ACEIs have been administered at variable doses and with erratic follow-up. In addition, guidelines recommend the administration of ACEIs as first-line therapy for PTE but do not give information on dosage. In this study the dose-response of a single ACEI was assessed, and patients were followed up for 1 year. The role of ACE gene polymorphism in both prevalence of PTE and successful response to ACEI therapy was also tested. At study entry, blood chemistry and ACE-gene polymorphism were measured. ACEI (ramipril) was initiated at 1.25 mg/day; if Ht was still >=51%, ramipril was increased every 6 weeks to ensuing greater dosages. Scheduled dosages were 1.25, 2.5, 5.0, 7.5 and 10 mg/day. Blood chemistry was repeated every 6 weeks. Serum erythropoietin (EPO) concentration was assayed at the start and end of the study. Follow-up was extended for 1 year. PTE developed 12.6 +/- 16.0 months after transplantation in 40 out of 400 patients; 27 patients completed the study. Initial Ht was not correlated with any variable. Final Ht appeared normalized in 26 out of 27 patients. Mean dose (+/- SD) of ramipril was 4.6 +/- 3.6 mg. Mean time for correction of PTE was 135 days, and was not dependent on baseline Ht, hemoglobin or EPO. PTE relapsed in 4 patients. Prevalence of PTE and successful response to ramipril was not dependent on ACE-gene polymorphism. Ramipril was effective in PTE; low doses normalized Ht in most patients. No clinical characteristics or biochemical variables predicted the response to ramipril. PTE may relapse; thus long-term follow-up is mandatory.
    Full-text · Article · Jan 2007 · Journal of nephrology
  • R Orlando · G Tosone · D Tiseo · M Piazza · G Portella · R Ciancia · V Martinelli · B Montante · B Rotoli
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    ABSTRACT: The reverse seroconversion to hepatitis B virus infection has been sporadically described in onco-haematological patients receiving cytotoxic therapy or allogeneic bone marrow transplantation and can be associated with the development of acute icteric hepatitis. We present a male HBsAg-negative, anti-HBc-positive patient with Hairy Cell Leukemia who developed acute B hepatitis more than 1 year after the last course of 2-CdA and 6 months after splenectomy, while the patient was receiving therapy with alphaIFNr. The acute B hepatitis promptly responded to lamivudine therapy followed by viral clearance.
    No preview · Article · Nov 2006 · Infection
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    ABSTRACT: Chuvash polycythemia (MIM 263400) is an autosomal recessive disorder characterized by a high hemoglobin level, relatively high serum erythropoietin, and early death. It results from a Von Hippel-Lindau (VHL) gene mutation (C598T) that causes increased HIF-1alpha activity and erythrocyte production in the face of normoxia. This polycythemia is endemic in Chuvashia, whereas its worldwide frequency is very low. We investigated the incidence of the Chuvash-type VHL mutation in Campania (South Italy) and identified 14 affected subjects (5 families). Twelve live on the island of Ischia (Bay of Naples). From analysis of the mutated allele, we found that the disease was more frequent on Ischia (0.070) than in Chuvashia (0.057). The haplotype of all patients matched that identified in the Chuvash cluster, thereby supporting the single-founder hypothesis. We also found that nonaffected heterozygotes had increased HIF-1alpha activity, which might confer a biochemical advantage for mutation maintenance. In conclusion, we have identified the first large cluster of Chuvash erythrocytosis outside Chuvashia, which suggests that this familial polycythemia might be endemic in other regions of the world.
    Preview · Article · Feb 2006 · Blood