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X-Ray Photoelectron Spectroscopy (XPS) and X-Ray Absorption Spectroscopy (XAS) provide unique knowledge on the electronic structure and chemical properties of materials. Unfortunately this information is scarce when investigating solid/liquid interfaces and chemical or photochemical reactions under ambient conditions because of the short electron inelastic mean free path (IMFP) that requires a vacuum environment, which poses serious limitation on the application of XPS and XAS to samples present in the atmosphere or in the presence of a solvent. One promising approach is the use of graphene (Gr) windows transparent to both photons and electrons. This paper proposes an innovative system based on sealed Gr nanobubbles (GNBs) on a titanium dioxide TiO

Summary Morphological changes of normal human keratinocyte cellshave been monitored by means of atomic force microscopyafter the exposure at a mercury solution containing HgCl 2 at10 −7 M. The measurements have been carried out in contactmode in a thermostated liquid cell, to reproduce a cellularenvironment similar to the physiologic one. Remarkablealterations of the cellular morphology and volume havebeen revealed after few minutes from starting the exposureexperiment, although the HgCl 2 concentration is severalordersofmagnitudeslowerthanthecytotoxicvalue(10 −4 M).The atomic force microscopy technique results to be apowerful mean to investigate modifications induced in thecellmorphologybyexternalchemicalagents. Introduction The toxic effects of mercury and its compounds for humansand animals have been verified in several studies (Langford& Ferner, 1999; Magos & Clarkson, 2006). They aredue to its high affinity to sulphydryl groups contained inproteins. Recently, the European Union established to castoff some common mercury-containing clinical instruments,as thermometers and sphygmomanometers, because ofpoisoning risk (European Council Directive 2007/51/CE).Mercury is naturally present in the earth’s crust. It isalso present in the atmosphere either derived naturallyfrom the degassing of the earth’s crust, emissions fromvolcanoes,evaporationfromtheworld’sseasorfromindustrialpollution. In addition, several human activities involve

Conventional treatment of symptomatic essential thrombocythemia (ET) consists of long-term administration of myelosuppressive cytotoxic agents which, although efficacious in most cases, are associated with leukemogenic potential. Alpha-interferon (IFN) exerts a dose-dependent inhibitory influence on thrombopoiesis through a direct antiproliferative effect on megakaryocytic precursors. Therefore, it may provide a biologic, potentially non-mutagenic alternative to conventional cytotoxic treatments. At daily doses ranging from 1 to 5 M.U., alpha-IFN is efficacious in inducing a hematologic response in most patients with ET. Response to IFN is a gradual process. The median time to hematologic response varies from 1 to 3 months and a significant proportion of patients reach and maintain normal platelet counts with low doses (1–3 M.U./d). Normalization of marrow megakaryocytosis requires longer treatment (9–12 months). Also patients resistant to cytotoxic drugs may respond to alpha-IFN, suggesting a lack of cross-resistance between the two treatment modalities. Side-effects, although not severe, represents a limit to the administration of adequate doses of IFN in about 25% of cases. Once hematologic response has been obtained, both low-dose IFN and cytotoxic drugs are effective as maintenance. The full potentialities of alpha-IFN in ET in combination with cytotoxic drugs or with other cytokines need to be further investigated.

Background. High oxygen-affinity haemoglobin variants and 2,3-diphosphoglycerate (2,3-DPG) deficiency are inherited diseases generating low tissue oxygen tension and erythropoietin-driven erythrocytosis, that characterizes the clinical phenotype of patients. Level of blood p50 (the oxygen tension at which haemoglobin is 50% saturated) is used to recognize these conditions. Objectives. To define the clinical utility of blood p50 measurement in the diagnosis of isolated erythrocytosis. Subjects and design. Venous blood p50 measurement was included in the diagnostic work-up of 102 consecutive patients with isolated erythrocytosis besides blood cell count, arterial oxygen saturation, serum erythropoietin measurement and screening for JAK2 mutations. Setting. Haematological Outpatient Section at University Hospital. Results. Seven patients had relative erythrocytosis. Among 95 patients with absolute erythrocytosis, 4 (4.2%) had decreased p50 level. The extended study of family members revealed a familial inheritance. Two families had haemoglobin variants already described as Haemoglobin Malmo and Haemoglobin San Diego. In one family, the proband had a new high oxygen-affinity haemoglobin variant (Haemoglobin Safi) resulting from the transversion CA at codon 81 of the α2-globin gene. In the last family, a deficiency of 2,3-DPG was found. Within the 91 patients with normal p50 values, 46 (51%) had secondary erythrocytosis, 13 (14%) polycythemia vera and 32 (35%) idiopathic erythrocytosis. Conclusions. This study suggests that the investigation of blood p50 level may be useful to define diagnosis in patients with isolated erythrocytosis.

Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Human infections due to Bartonella spp. are viewed as emerging diseases typical in, although not exclusive to, immunosuppressed patients, in particular those with AIDS, organ transplants and haematological malignancies. We describe four patients, three children and one adult, who developed vegetating papillomatous lesions exclusively on the oral mucosae. They shared a history of haematological malignancy and allogeneic bone marrow/stem cell transplantation, and later developed chronic graft-versus-host disease, also involving the oral mucosae. Histopathologically, the vegetating lesions were characterized by a diffuse neoangiogenesis, granulation-like tissue, and a mixed cell infiltrate predominantly composed of neutrophils. Gram-negative bacteria were found in the endothelial cells of the vessels in the deeper portion of the corium by electron microscopy. In three cases, DNA of B. henselae was detected by polymerase chain reaction (PCR), and confirmed by sequencing of the PCR products. All the lesions healed after systemic antibiotic therapy, although some recurred after months, and regressed again after systemic antibiotic treatment associated with conservative surgical excision.

Osteonecrosis of the jaw (ONJ) is a reported complication of bisphosphonate use. The incidence ranges between 6 and 13% and seems to be higher in people treated with zoledronic acid (ZA) than with pamidronate. We retrospectively evaluated the incidences of ONJ and skeletal-related events (SRE) in 106 patients with multiple myeloma divided in two groups according to the schedule of administration of bisphosphonates: 51 received monthly administrations until tolerated (group A, standard schedule), 55 were treated monthly during the first year and then every 3 months (group B, reduced schedule). The incidence of SRE was similar (15.1 per 100 person years in group A and 17.7 in group B). ONJ occurred in seven patients, six in group A and one in group B (P=0.049). The risk of ONJ was eight-fold lower with the reduced schedule than with the standard schedule. The only significant risk factor for ONJ was the type of bisphosphonate (P=0.006). The incidence of ONJ was significantly higher with ZA than with pamidronate + ZA (9.1 vs 1.6 per 100 person-years). No ONJ was observed in patients treated only with pamidronate. A reduced schedule of ZA may be safer than the standard schedule while maintaining anti-resorptive efficacy.

We used intermediate doses of Ara-C (IDAra-C) in the treatment of 15 patients with chronic myelogenous leukemia (CML) in blast crisis and, combined with hydroxyurea, in 20 CML patients in accelerated phase. Patients with blastic CML received intensive 5-day courses of IDAra-C 600 mg/m2 every 12 h as a 2-h infusion. Of 15 patients, three achieved complete response (CR) and three partial response (PR), for an overall response rate of 40 per cent. All patients developed severe leukopenia and thrombocytopenia, and two died in hypoplasia. Except nausea and vomiting requiring medication, other nonhematologic toxicities were uncommon. Median response duration was 4 months (range 1 to 7 months). Survival was 5 months for responders and 1.5 months for nonresponders. Patients with CML in accelerated phase were treated with two-day courses of IDAra-C 600 mg/m2 every 12 h by 2-h infusion, every two-three weeks. Daily hydroxyurea 1-1.5 g/day was administered between courses. Of 20 patients, 15 (75 per cent) achieved a good PR with rapid improvement of the symptoms of disease acceleration. The median duration of response was 11 months (range 3 to 38 months); duration was over 24 months in five patients. The median survival from the start of IDAra-C was 13 months for responders and 3.5 months for nonresponders. We conclude that IDAra-C is an effective approach for CML in terminal phase. Its use in 5-day induction courses for blast crisis CML has a response rate comparable to that achieved with high-dose Ara-C. In patients in accelerated phase, the combination of short courses of IDAra-C with hydroxyurea is a well-tolerated treatment able to improve substantially the clinical and hematologic symptoms of disease progression.

Diffuse large B-cell lymphoma (DLBCL) has been correlated to hepatitis C virus (HCV) infection in few series, but characteristics and outcome of these patients remain undefined.We analyzed 156 previously untreated consecutive HCV-positive patients with DLBCL observed between 1994 and 2004 in three major institutions from northern Italy.Median age at presentation was 63 years and 8% of patients had DLBCL transformed from low-grade lymphomas. Spleen was the most frequently involved extranodal site, followed by liver and stomach. Treatment was delivered with cure-intent in 132 patients, while the remaining 24 patients received monochemotherapy or radiotherapy alone due to old age or seriously impaired hepatic function. Only five patients (4%) had to discontinue chemotherapy due to severe liver function impairment. The addition of rituximab did not seem to affect patients' tolerance to treatment. Five-year overall survival of the entire cohort was 72%, while 5-year progression-free survival (PFS) of the 132 patients treated with cure-intent was 51%. Hepatitis B virus co-infection, advanced Ann Arbor stage and nodal origin of the tumor resulted the strongest adverse prognostic factors.Patients with HCV-positive DLBCL share distinctive clinical features. Future studies should prospectively evaluate the association between HCV and aggressive lymphomas.

The impact of clinical parameters, International Prognostic Scoring System (IPSS) scores/cytogenetic categories, and some single cytogenetic defects on overall survival (OS) and time to myelodysplastic syndromes (MDS)/AML progression (progression-free interval (PFI)) was evaluated in 331 MDS patients. Statistical analysis demonstrated that OS and PFI were significantly affected by all these parameters. Since single 7q- showed a better survival than the poor IPSS cytogenetic category (P=0.009), it was considered as a new prognostic entity ('modified IPSS categories'). In multivariate analysis OS was significantly influenced by age, marrow blast cell percentage, number of cytopenias and either modified or standard IPSS cytogenetic categories; hazard ratios for MDS/AML progression were influenced by all the former, except for age and cytopenias. Multivariate analysis of del(7)(q31q35) confirmed the results of univariate analysis, but the Akaike Information Criterion showed no difference in evaluating OS and PFI between the modified and standard IPSS cytogenetic grouping. In conclusion, (i) chromosome defects as grouped by IPSS and blast cell percentage are the most relevant parameters for predicting OS and PFI; (ii) the prognostic power of the IPSS cytogenetic grouping is not ameliorated by the introduction of del(7)(q31q35) as a new entity; (iii) complex karyotypes have a prognostic value independent of blast cell percentage.

The purpose of this study was to develop a flow cytometric approach to the evaluation of marrow dysplasia in myelodysplastic syndromes (MDS). We first studied a cohort of 103 MDS patients as well as 46 pathological and healthy controls. Flow cytometry data were expressed as percentage of positive cells. Analysis of erythroid cells showed higher proportions of immature cells (P < 0.001) and decreased levels of CD71 expression on nucleated red cells (P = 0.02) in MDS. Analysis of myeloid cells showed lower proportions of CD10+ and higher proportions of CD56+ granulocytes (P < 0.001), and increased ratios of immature to mature cells (P = 0.007). Since no single immunophenotype could accurately differentiate MDS from other conditions, we used discriminant analysis for generating erythroid and myeloid classification functions using combinations of immunophenotypic parameters. These functions were prospectively validated in a testing cohort of 69 MDS patients and 46 pathological controls. A diagnosis of MDS was obtained in 60/69 cases (87%). No false-positive results were noticed among controls. Significant correlations between values of these functions and both degree of morphological dysplasia and the International Prognostic Scoring System were found. These findings indicate that flow cytometry evaluation of marrow dysplasia is feasible and may be useful in the work-up of individual MDS patients.

The aim of this study was to investigate thiotepa (TT) and fludarabine (Fluda) as a preparative regimen for allogeneic peripheral stem cell transplant in patients not eligible for a standard myeloablative regimen due to comorbidities and/or poor performance status. TT was given at a dose of 10 mg/kg over 2 days and Fluda at 125 mg/m(2) over 5 days. In all, 21 patients (14 male, seven female; 10 acute leukaemia, eight myelodysplastic syndrome, two non-Hodgkin's lymphoma, one Hodgkin's disease) were treated. The median age was 51 years (range 30-55 years). All patients achieved full donor-type chimaerism. Adverse events included mild nausea and vomiting in two patients and a slight increase of serum amylase in three. A total of 13 patients received RBC transfusions (median 6 U, range 1-23), and all received platelets (median 4 U, range 1-27). Four patients died of nonrelapse causes and five of relapse. The 1-year probabilities of transplant-related mortality and relapse were 19 and 29%, respectively. In total, 12 patients remain in complete remission (median follow-up: 786 days). The 3-year overall survival probability was 58%. We conclude that this regimen is feasible and well tolerated.

We studied a model of in vivo purging with Rituximab and high-dose (HD) cytarabine in 14 patients with relapsed/refractory follicular lymphoma and two with refractory mantle cell lymphoma enrolled in a program of HD chemotherapy and autotransplant. After two courses of debulking immunochemotherapy with Rituximab, Vincristine and Cyclophosphamide, we used a combination of Rituximab, HD cytarabine and granulocyte colony-stimulating factor for peripheral blood stem cells (PBSC) mobilization. The median number of CD34+ cells collected was 14.69 x 10(6)/kg (range 5.74-73.2). Monitoring of peripheral CD19+ and CD20+ B cells prior to and throughout the purging period showed that a treatment with Rituximab, Vincristine and Cyclophosphamide results in a profound depletion of B cells in peripheral blood. B-cell depletion persists during mobilization with Rituximab and HD cytarabine allowing a collection of PBSC free of B cells (median CD19+ and CD20+ cells counts 0%). Of nine patients PCR positive for bcl-2 or bcl-1 in blood and marrow at the start of immunochemotherapy, all showed PCR-negative PBSC. In conclusion, in patients with indolent lymphoma, the concurrent administration of Rituximab and HD cytarabine is a safe and efficient method to obtain in vivo purged PBSC. Immunochemotherapy prior to mobilization produces B-cell depletion and seems to be a useful preparative step.

Aims: To detail on sequential biopsies the morphological and immunohistochemical features of a case of primary lymph nodal fibroblastic reticulum cell (FBRC) tumour which progressed into a clinically aggressive cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma. Methods and results: A 70-year-old female underwent surgical excision of an enlarged submandibular lymph node. The nodal architecture was effaced by a neoplastic proliferation of medium to large cells, round to oval to spindle in shape, growing in a storiform pattern. The tumour stained for vimentin, CD68, factor XIIIa, α1-antitrypsin, fascin and actin. Dendritic and endothelial cell markers were negative. A diagnosis of FBRC tumour was made by combining pathological and clinical data. The patient received no therapy but 5 months later the tumour relapsed, exhibiting a deceptively pleomorphic cytology, phenotypic changes (strong cytokeratin positivity), intense p53 expression and aggressive clinical course with fatal outcome. In-situ hybridization for Epstein–Barr virus was negative. Conclusions: We speculate that the morphological changes and p53 expression of the relapsing neoplasm might reflect tumour cell dedifferentiation, in keeping with the aggressive clinical course. The intense p53 expression suggests that this oncoprotein might also play a role in reticulum cell tumorigenesis.

Renal failure is one of the worst complications occurring in multiple myeloma (MM) patients. It does not affect survival if reverted by a prompt chemotherapy before the damage becomes irreversible; therefore, the early diagnosis of renal dysfunction is crucial. High and low molecular weight urinary proteins have proved to be helpful in diagnosing initial renal damage since they are more sensitive than urea and creatinine serum levels or creatinine clearance. We studied the renal function of 111 MM patients through serum creatinine, urea, urinary IgG, alpha(1)-microglobulin (alpha(1)-M), and albumin (Alb). Two successive controls were made in a subset of 30 patients, categorized in three groups (improved, stable, worsened) according to the behavior of tumor burden markers (bone marrow plasmacytosis, monoclonal component, and beta(2)-microglobulin). In every group, we evaluated the behavior of urinary proteins. Renal dysfunction evaluated with serum parameters was present in 19 patients (17%), while if studied with urinary proteins was revealed in 71 patients (64.5%). Urinary proteins statistically correlated with each other. They correlated with creatinine, IgG, and alpha(1)-M also with urea. By contrast, they showed a variable correlation with clinical parameters: alpha(1)-M correlated with bone marrow plasmacytosis (BMPC) ( p=0.02) and beta(2)-M ( p=0.000001), IgG with all three disease parameters (MC p=0.0005, BMPC p=0.009, beta(2)-M p=0.007), and Alb only with beta(2)-M ( p=0.0004). In the subset of 30 patients followed with two successive controls, urinary proteins showed a parallel behavior with the indices of tumor burden. In conclusion, IgG, alpha(1)-microglobulin, and albumin are reliable and sensitive to precociously reveal renal damage, and we recommend their routine use for the definition and monitoring of renal function in multiple myeloma patients, mainly those in early stage, to better identify initial signs of progression.

Besides bone pain, pathologic fractures, anaemia, and recurrent infectious diseases, renal failure is one of the most serious complications in multiple myeloma patients. Its incidence is generally underestimated because of the low reliability of the parameters routinely used for the evaluation of renal dysfunction. Other laboratory tests in the literature are reported to be more suitable to better define the extension of the renal impairment, namely urinary proteins or creatinine clearance. We here report on the clinical implication of urinary parameters in defining the renal function in myeloma patients.

Modern integrated circuits require insulating materials with a dielectric constant as low as possible in order to obtain device speed improvements through lower RC delay. We have investigated the electrical and structural properties of PTFE thin films obtained from Algoflon ® -PTFE nanoemulsions, via spin coating deposition, followed by sintering. Films as thin as 160 nm with dielectric strength better than 4 MV/cm have been obtained. Breakdown mechanism is also discussed.

Standard conditioning for allogeneic bone marrow transplantation induces high transplant-related mortality (TRM) in patients with a poor performance status. Less intensive regimens have been tested to reduce the TRM; our purpose was to evaluate the feasibility and tolerability of a new combination: thiotepa and fludarabine (TT-FLUDA). Six patients received 5 mg thiotepa/kg daily from day -8 to -7 and 25 mg fludarabine/m2 daily from day -6 to -2 followed by an allogeneic peripheral blood progenitor cell infusion; three of these patients with signs of overt leukemia received 18 mg idarubicin/m2 i.v. at day -12. Graft-versus-host-disease (GVHD) prophylaxis was performed i.v. with 1 mg cyclosporine A/kg per day from day -5 to the day of marrow engraftment, then 6 mg/kg per day orally up to day +100, and 10 mg methotrexate/m2 at day +1, and 8 mg/m2 at days +3, +6, and +11. Chimerism was studied with fluorescent in situ hybridization for sex chromosomes (XY-FISH) and minisatellite polymerase chain reaction (PCR) at days +30, +100, +180, and +360. Engraftment was achieved in all cases with complete donor chimerism in all but one patient who had refractory acute leukemia. No major toxicity was noticed; only one patient died at day +51 of acute GVHD because of early cyclosporine A discontinuation. One patient with refractory non-Hodgkin's lymphoma (NHL) had a testicular relapse at day +180. Three patients (one with mantle cell lymphoma, two with acute myeloid leukemia) are still in continuous complete remission (CR) with complete donor chimerism at days +180, +210, and +450, respectively. TT-FLUDA seems to be well tolerated, allowing engraftment and stable donor chimerism in patients who are poor candidates for conventional conditioning regimens.

We describe a 73-year-old man diagnosed with acute myelomonocytic leukemia (AML-M4) following myelodysplasia with trisomy 11 and with a t(11;11;22). This is the first case with both abnormalities present in the same cells and with the t(11;11;22) involving a chromosome 11 already duplicated at 11q23. This band contains the MLL gene that undergoes partial tandem duplication in patients with +11, which is "promiscuous," being translocated with a large number of genetic partners. Our patient had a complex karyotype that was completely defined by in situ hybridization. This technique demonstrated that the t(11;11;22) derivative with a duplication of band 11q23 carried from three to four copies of MLL. Two copies of the gene were close to each other and centromeric to the break-point region. Therefore, a partial tandem duplication of the MLL gene might have happened before the occurrence of t(11;11;22). Considering the associated chromosome defects, the monosomy for the long arm of chromosome 7, due to an unbalanced translocation t(7;17), further underlines the possibility that a partial tandem duplication of the MLL gene might have taken place.

Al/ZnSe(100) Schottky barriers fabricated on $c(2\ifmmode\times\else\texttimes\fi{}2),$ $2\ifmmode\times\else\texttimes\fi{}1,$ and $1\ifmmode\times\else\texttimes\fi{}1$ reconstructed surfaces were studied by means of photoemission spectroscopy and first-principles calculations. Relatively similar values of the Schottky barriers were found for interfaces fabricated on Zn-stabilized $c(2\ifmmode\times\else\texttimes\fi{}2)$ and Se-dimerized $2\ifmmode\times\else\texttimes\fi{}1$surfaces, while substantially lower values of the $p$-type barriers were predicted theoretically and observed experimentally for junctions grown on the Se-rich $1\ifmmode\times\else\texttimes\fi{}1$ surface.

Since in vitro observations indicated that all-trans retinoic acid (ATRA), especially in combination with IFNalpha, can exert significant suppressive effects on Ph+ cells, we investigated the effects and the pharmacokinetic profile of ATRA in a selected cohort of patients with Ph+ chronic myeloid leukemia (CML) in chronic phase. Eighteen patients were treated with ATRA at a dose of 80 mg/m2/day (p.o.), divided into two equal doses after meals, for 7 consecutive days every other week for a maximum of 12 courses (1 course = 1 week on and 1 week off). Pharmacokinetic profiles of ATRA were evaluated during intermittent therapy on days 1 and 7 of course 1; on day 1 of course 2; on day 1 of course 6. Out of the 18 patients treated with ATRA, 11 (61%) went off study before the sixth course of treatment because of progressive hyperleukocytosis (seven cases), or thrombocytosis (one case), or refusal (three cases). Seven (39%) patients completed the first six courses (12 weeks) of treatment with ATRA and two of them (11%) maintained a white blood cell (WBC)

The presenting features of 356 previously untreated multiple myeloma (MM) patients grouped according to age were analyzed in order (a) to elucidate the possible differences in initial clinical and laboratory features between patients younger than 50 years and the older ones and (b) to statistically assess the prognostic value of the parameters considered, with particular emphasis on the prognostic impact of age. Patients were divided into two groups: group I included 61 patients aged less than 50, group II comprised 295 patients aged 50 or more. No significant differences were found between the two groups in terms of either clinical or laboratory initial characteristics. The treatments adopted and the response to therapy did not differ in the two groups. The prognostic value of presenting features was evaluated for the whole cohort by univariate and multivariate analysis, considering both the observed survival rates and survival rates corrected for the effect of other independent causes of death, using a Poisson model. In both models, calcium level (RR 2.33), performance status (RR 1.83), and creatinine (RR 1.69) maintained their independent negative prognostic value. In contrast, the impact of age was different in the two models. In fact, patients younger than 50 seem to have a better prognosis when the observed survival rates are considered, but they show an increased risk of death when the model takes into account the expected mortality of the underlying population. In conclusion, this study shows that the younger cohort of MM patients has no distinctive initial characteristics with respect to older patients. In multivariate analysis, creatinine levels, calcemia, and performance status show a relevant negative independent prognostic value. Regarding the prognostic impact of age, survival seems to be better among patients younger than 50 than in older patients when the observed survival rates are considered but is significantly worse when the mortality of the corresponding general population, is taken into account.

In 1− x Ga x As buffer layers grown on GaAs(0 0 1) wafers can be used as novel substrates lattice matched to the Zn 1− y Cd y Se active layers employed in blue-green lasers. Photoluminescence studies of Zn 1− y Cd y Se alloys ( x = 0.15 and 0.25) grown by molecular beam epitaxy on such substrates show a dramatic reduction in the deep-level emission as compared to Zn 1− y Cd y Se/GaAs(0 0 1) heterostructures. The surface of the epilayers, however, exhibits a cross-hatched morphology as a result of ∼ 10 nm deep surface corrugations oriented along perpendicular 〈1 1 0〉 directions.

The oxygenation process of the GdBa2 Cu3O(6+y) thin films was investigated by resistivity measurements in the temperature interval 650–1050 K and oxygen pressure 1 mbar. An iteration procedure is proposed for calculating the diffusion relaxation times from the curves of resistance decay with time. All samples showed a linear Arrhenius plot with an activation energy E0 close to 1.5 eV. The diffusion resulted concentration independent for y≈0.4–0.9.

The Schottky barrier at Al/Zn 1-x Cd x Se junctions was determined through high resolution synchrotron radiation photoemission studies of interfaces fabricated in situ on atomically clean, Se-rich surfaces. A gradual decrease in the n-type barrier with increasing x reflects the bandgap variation in the ternary alloy and the band alignment in Zn 1-x Cd x Se/ZnSe heterojunctions. Correspondingly, transport studies of Al/n-Zn 1-x Cd x Se contacts fabricated ex situ show a dramatic decrease of the specific contact resistance with increasing x. Improved performance of Al/n-ZnSe contacts can therefore be achieved through fabrication of graded Zn 1-x Cd x Se layers at the interface.

Osteoprotegerin serum levels in multiple myeloma and MGUS patients compared with age- and sex-matched healthy controls

Channel-spark pulsed electron beam deposition (CS), a new deposition method based on a simple and inexpensive system, has been used for preparation of high-quality GdBa2Cu3O7-x, Gd1-xEuxBa2Cu3O7-x and YBa2Cu3O7-x thin films epitaxially grown on NdGaO3 and SrTiO3 substrates. Typical critical temperatures for zero DC resistance lie in the intervals 87-89 K for Y-based films and 91.0-92.6 K for Gd- and GdEu-based ones. The transition widths for the best films are less than 0.5 K. The critical current densities reach the values of 3*106 A cm-2 at 77 K, zero field.

HAEMATHOLOGICA, VOL 86 (SUPPL) N.RO 10

Summary Background A prospective study was conducted to assess the efficacy and toxicity of a salvage regimen consisting of CCNU, Melphalan, and VP-16 (CAV) given at 28-day intervals in patients with Hodgkin's disease (HD) relapsing after primary therapy or refractory to the alternating MOPP/ABVD regimen. Patients and methods This study included 58 patients (median age: 34 years), with resistant or relapsing HD. Primary therapy had consisted of alternating MOPP/ABVD (81%) or MOPP alone (19%); 38% of patients were relapsing from prior complete remission (CR) while 62% had resistant disease. Extranodal disease was present in 55% and B-symp-toms in 72% of patients; one-fifth had bulky disease and/or bone marrow involvement. The CAV was used as first salvage in half of the patients. Results Complete remission was obtained in 17 patients (29%); unfavorable factors for CR in univariate analysis were the presence of bulky disease and the failure to achieve CR with prior therapy. Nine patients (53% of remitters) have subsequently relapsed with a 10-month median duration of CR. The 3-year overall survival after CAV was 25% with an 18-month median survival; significant differences in survival were found according to the extent of disease, the presence of B-symptoms and the HD status (prior sensitive or resistant disease, first or subsequent relapse). Seven patients are long-term remitters (12%), and one of them has been given high-dose chemotherapy and autologous bone marrow transplantation at relapse after CAV. The CAV toxicity was mostly hematological; severe pancytopenia occurred in six cases with two cases of fatal infections and one of fatal hemorrhage. Conclusion CAV therapy was moderately effective as third-line salvage in patients with HD resistant to alternating MOPP/ABVD or previously given two different regimens for relapse; the toxicity was mostly hematological and supportive therapy was needed in one-third of the patients.

Summary Background A prospective study was conducted to assess (a) the long-term results and toxicity of the alternating MOPP/ABVD regimen in advanced Hodgkin's disease; (b) the prognostic value of pretreatment variables and of drug dose intensity. Patients and methods A total 138 consecutive patients with advanced Hodgkin's disease entered this study; patient selection included stages IIB (33% of total), IIIB (26%), IV (25%), and stages EA-IIIA (16%) with bulky disease and pulmonary hilum involvement. The MOPP/ABVD program was delivered in an 8-month program; adjuvant radiotherapy on sites of bulky disease was delivered in 24 patients. Results Complete remission was obtained in 106 (77%) patients; significant factors for CR in univariate analysis were stage, symptoms, histology, and bone marrow involvement. The five-year relapse-free survival (RFS) was 83%; in a multivariate analysis, histology only correlated with RFS (p = 0.04). The five-year freedom from tumor mortality and overall survival (OS) were 79% and 67%, respectively. An adverse prognostic significance for OS was observed for B symptoms and bone marrow involvement. The median percentage of relative dose intensity (RDI) was as follows: Adriamycin 86, mechlorethamine 85, vincristine 73, vinblas-tine 84, bleomycin 79, procarbazine 74, dacarbazine 81. No significant association was found between RDI and clinical outcome. No severe pancytopenia or life-threatening complications occurred during therapy. Conclusions Alternating MOPP and ABVD cured more than 65% of patients with advanced HD; acute and late tox-icity were acceptable. Prognostic analysis defined subgroups with a lower chance of cure which may deserve a more intensive initial therapy.

Background: An increased incidence of second cancers has been reported in lymphoproliferative disorders. Patients and methods: We assessed the frequency, characteristics and predictive factors of second cancers in 230 patients with Waldenstrom macroglobulinemia (WM) and compared the incidence of second cancers in WM with that of an age- and sex-matched control population. Results: Twenty-two patients (10%) developed solid cancers and 10 (4%) second hematologic malignancies. In a competing risk model, the cumulative incidence of solid cancers was 12% at 10 years and 17% at 15 years while the incidence of hematologic malignancies was 6% and 8%, respectively. The overall risk of second cancer in WM was 1.69 times higher than expected (P 5 0.002). WM patients were at increased risk for diffuse large B-cell lymphoma (standardized incidence ratio (SIR) 9.24, P < 0.0001), myelodisplastic syndrome/acute myeloid leukemia (SIR 8.4, P < 0.0001), brain cancer (SIR 8.05, P 5 0.0004). The risk of a second hematologic malignancy was fourfold higher in patients previously treated, though not reaching statistical significance (P 5 0.19). Conclusions: WM patients are at higher risk of second cancers as compared with the general population. The sample size does not allow firm conclusions about the effect of therapy on the development of second cancers.

Advanced age is one of the variables more frequently considered to be associated with an adverse prognosis in Waldenstrom's macroglobulinemia (WM). In a series of 238 symptomatic and asymptomatic WM patients, we retrospectively identified an age cut-off distinguishing two groups of patients with different outcome in terms of overall survival (OS), disease-specific survival (DSS) and treatment-free survival (TFS). Although for the OS the best cut-off was identified at 65 years with shorter OS for elderly patients, no difference was detected in terms of DSS between the two groups. Furthermore, patients over 65 years showed a longer TFS compared with patients under 65 years. Clinical and laboratory disease characteristics did not significantly differ between the two groups of patients except for β2M level. Therefore, the poorer survival of patients over 65 years at diagnosis should probably be attributed to the higher number of no disease-related deaths and is independent from WM.

Morphological changes of normal human keratinocyte cells have been monitored by means of atomic force microscopy after the exposure at a mercury solution containing HgCl(2) at 10(-7) M. The measurements have been carried out in contact mode in a thermostated liquid cell, to reproduce a cellular environment similar to the physiologic one. Remarkable alterations of the cellular morphology and volume have been revealed after few minutes from starting the exposure experiment, although the HgCl(2) concentration is several orders of magnitudes lower than the cytotoxic value (10(-4) M). The atomic force microscopy technique results to be a powerful mean to investigate modifications induced in the cell morphology by external chemical agents.

PURPOSE To evaluate the clinical features of presentation, the morphologic and immunohistochemical pattern, the modality of spread, and the response to current treatments of patients with primary mediastinal B-cell lymphoma, a recently documented subtype of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty consecutive patients (14 males, 16 females; median age, 26 years) with primary mediastinal B-cell lymphoma with sclerosis were studied. RESULTS The clinical aspects were largely homogeneous: 93% presented with chest symptoms of a rapidly enlarging mass of the anterior mediastinum; the tumor was bulky in 73%, and superior vena cava syndrome (SVCS) was present in 57%. Also, patients without SVCS symptoms showed subclinical venacaval compression at computed tomographic (CT) scan, for a total incidence of caval obstruction of 80%. Intrathoracic extension to adjacent organs was seen in 47% of patients. Despite its invasive behavior, only four patients showed extrathoracic spread at diagnosis. In 23 cases, the tumor presented with morphologic features that resembled follicular center-cell lymphomas. In seven, the neoplastic population was composed mainly of centrocyte-like cells with abundant clear cytoplasm not referable to any known B-cell lymphoma subtype. All cases showed huge sclerosis. Of 29 patients assessable for response, 16 (55%) achieved a complete response (CR): five of 14 (36%) treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 11 of 15 (73%) treated with methotrexate plus leucovarin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) or etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) (P = .047). We could identify no clinical, biologic, or histopathologic features significantly correlated with response. After chemotherapy, 14 of 16 remitters received consolidation radiotherapy to the mediastinum. At 3 years, the actuarial survival rate is 38% for all cases and 72% for remitters. None of the 13 patients who did not achieve CR responded to salvage treatments. CONCLUSION This study shows that primary mediastinal B-cell lymphoma with sclerosis is a distinctive subtype of NHL with unique clinicopathologic aspects and aggressive behavior. Prompt recognition and aggressive treatment may provide long survival in a good proportion of cases. However, a subset of patients is extremely refractory to first- and second-line treatment. Conventional prognostic factors seem inadequate to identify these very-poor-risk cases.

HAEMATOLOGICA N.RO 7

We present studies of Al/n-GaAs(001) and Al/p-GaAs(001) diodes in which the Schottky barrier height was varied by fabricating Si bilayers at the interface under either Ga or Al flux. Comparison of the effect of each interlayer on the n- and p-type barrier height allowed us to rule out any major role of interface reactions and test the predictions of the local interface-dipole model of Schottky barrier tuning.

Molecular remission after allo-SCT in a patient with post-essential thrombocythemia myelofibrosis carrying the MPL (W515A) mutation

Background: There are few data on the incidence and prognosis of extramedullary (EM) multiple myeloma (MM). There are concerns about a possible increase of EM relapses with the expanding use of high-dose therapy (HDT) and biological agents. Patients and methods: The incidence of EM disease, its relationship with prior exposure to HDT or novel agents, and its prognostic impact were analyzed in 1003 MM patients. Based on the different therapies available, three periods were considered: 1971-1993, conventional-dose chemotherapy; 1994-1999, HDT for younger patients; and 2000-2007, introduction of novel agents. Results: Overall, 13% of patients had EM disease, 7% at diagnosis and 6% later. In the 2000-2007 period, there was a significant increase of EM involvement, at diagnosis (P = 0.02) and during follow-up (P = 0.03). The risk of EM spread was not significantly increased after HDT [hazard ratio (HR 0.6)], bortezomib (HR 1.62), or thalidomide/ lenalidomide (HR 1.07). EM disease was associated with shorter overall (HR 3.26, P < 0.0001) and progression-free (HR 1.46, P = 0.04) survival. Conclusions: The incidence of EM disease has increased, probably due to the availability of more sensitive imaging techniques and the prolongation of patients' survival. HDT or novel agents seem not to increase the risk of EM disease. EM involvement confers a poor prognosis.

Background: Among marginal zone lymphomas (MZLs), bone marrow (BM) involvement features are well established in the splenic marginal zone lymphoma (SMZL); few data are available for extranodal marginal zone lymphoma (EMZL) and nodal marginal zone lymphoma (NMZL). Patients and methods: Incidence and patterns of histologic BM involvement are studied in 120 MZL patients (48 SMZL, 59 EMZL, 13 NMZL) at onset and during follow-up; relationships between clinical features, BM histology and flow cytometry (FC) are analyzed. Results: At diagnosis, BM involvement occurs in 90% SMZL, 22% EMZL and 54% NMZL (P < 0.0001); at reevaluation, incidence raises to 96% in SMZL and 34% in EMZL. Concordance between histology and FC is found in 87% of cases; most discordant cases have positive histology but negative FC. SMZL and EMZL show a nodular BM infiltration; the interstitial pattern is frequent in NMZL (P < 0.0001); sinusoidal localization is typical of SMZL, frequent in NMZL and occasional in EMZL (P = 0.0001). Stage, leukemic disease, B symptoms, more than one extranodal involved site, splenomegaly, elevated b2-microglobulin, serum monoclonal component, International Prognostic Index (IPI) and age-adjusted IPI are directly related to BM infiltration. Conclusions: The different prevalence of BM involvement in MZL subtypes reflects their heterogeneous dissemination modalities; histology seems more sensible than FC to detect BM infiltration; development of BM

Background: To evaluate the clinical outcome of patients with relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and high-dose therapy with autotransplant. Patients and methods: Sixty-four patients were enrolled in the trial. Primary end point was progression-free survival (PFS). Secondary end points were the in vivo purging effect on stem-cell harvest and the impact of molecular response on the outcome. Results: At enrollment, 59% of patients were PCR+ for bcl-2 rearrangement in bone marrow (PCR-informative). After the immunochemotherapy, before mobilization, 97% obtained complete response or partial response and 87% of patients informative for bcl-2 were molecularly negative. Sixty-one patients proceeded to in vivo purging and peripheral blood stem cell (PBSC) mobilization with rituximab and high-dose AraC. The median number of CD34+ cells collected was 16.6 · 10 6 /kg. Of 33 PCR-informative patients, the harvests resulted in PCR2 in all. Fifty-eight patients received high-dose therapy and autotransplant of in vivo purged PBSC. After a median follow-up of 3.5 years, 41 patients are in complete remission. Five-year PFS is 59%. Conclusion: This study demonstrates that patients with advanced relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and autotransplant may obtain long-lasting PFS. In bcl-2-positive patients, in vivo purging allows the harvest of lymphoma-free PBSC. Absence of the bcl-2 rearrangement after autotransplant is associated with persistent clinical remission.

Circulating endothelial cells (CECs) are associated with neoangiogenesis in various malignant disorders. Using flow cytometry, we studied CECs in 128 patients with myelodysplastic syndrome (MDS). MDS patients had higher CEC levels than controls (P

Giving the impact of complete response (CR) on outcome of multiple myeloma patients addressed to high-dose melphalan, we explored the role of a pre-transplant intensification with 3 months thalidome plus dexamethasone therapy (Thal-Dex), after pulse-VAD induction. Seventy-four multiple myeloma patients (MM pts) uniformly treated, were retrospectively studied. The response rate after pulse-VAD were: CR 6%, VGPR 40%, PR 23%, MR 23%, and progression 8%. The response rate after Thal-Dex were similar: CR 11%, VGPR 39%, PR 17%, MR 9%, and progression 24%. Giving no advantage in terms of response rate with an additive toxicity, Thal-Dex does not seem useful for intensification before transplant.

The Pauli exclusion principle is one of the fundamental tenets of quantum mechanics and determines the structure of matter at the atomic and molecular levels. Here, we show that Pauli blocking, a consequence of the exclusion principle according to which electron transitions are inhibited if the arrival state is occupied by another electron, has an observable effect on shot noise in resonant tunneling diodes. We measure a double valley feature in the plot of the noise suppression factor (the ``Fano'' factor) as a function of the applied voltage, which has been theoretically predicted a few years ago but has never been observed, and which suggests that Pauli blocking must be considered in the evaluation of transport in mesoscopic and nanoelectronic devices.

We report on the growth of microns long Mn‐catalyzed GaAs nanowires. α‐Mn is found on top of the wires, demonstrating that Mn acts as the growth catalyst. Transport measurements show that the wires have a p‐behavior. Luminescence shows a peak at 1.522 eV. The blue shift with respect to bulk GaAs is not due to quantum effects.

We present two different methods to pattern the band gap of dilute nitrides in their growth plane by exploiting the unique capability of H to passivate N in these materials. By deposition of metallic masks on and subsequent H irradiation of GaAs1-xNx, we artificially create zones of the crystal having the band gap of untreated GaAs1-xNx well surrounded by GaAs-like barriers. Alternatively, by focusing an energetic e(-)-beam on the surface of hydrogenated GaAs1-xNx we displace H atoms from their N passivation sites, thus leading to a controlled decrease in the crystal band gap in the spatial region where the e(-)-beam is steered.