Ultrasensitive Sub-monolayer Palladium Induced Chirality Switching and Topological Evolution of Skyrmions.

Chiral spin textures are fundamentally interesting, with promise for device applications. Stabilizing chirality is conventionally achieved by introducing Dzyaloshinskii-Moriya interaction (DMI) in asymmetric multilayers, where the thickness of each layer is at least a few monolayers. Here we report an ultrasensitive chirality switching in (Ni/Co)n multilayer induced by capping with only 0.22 monolayer of Pd. Using spin-polarized low-energy electron microscopy, we monitor the gradual evolution of domain walls from left-handed to right-handed Néel walls and quantify the DMI induced by the Pd capping layer. We also observe the chiral evolution of a skyrmion during the DMI switching, where no significant topological protection is found as the skyrmion winding number varies. This corresponds to a minimum energy cost of <1 attojoule during the skyrmion chirality switching. Our results demonstrate the detailed chirality evolution within skyrmions during the DMI sign switching, which is relevant to practical applications of skyrmionic devices.

Zygomatic implant penetration to the central portion of orbit: a case report.

BACKGROUND: Zygomatic implants have been proposed in literature for atrophic maxillary fixed oral rehabilitations. The aim of the present research was to evaluate, by a clinical and tomography assessment, a surgical complication of a zygomatic implant penetration to the orbit. CASE PRESENTATION: A 56 year-old female patient was visited for pain and swelling in the left orbit after a zygomatic implant protocol. The orbit invasion of the zygomatic implant screw was confirmed by the CBCT scan. The patient was treated for surgical implant removal and the peri- and post-operative symptoms were assessed. No neurological complications were reported at the follow-up. The ocular motility and the visual acuity were well maintained. No purulent secretion or inflammatory evidence were reported in the post-operative healing phases. CONCLUSION: The penetration of the orbit during a zygomatic implant positioning is a surgical complication that could compromise the sight and movements of the eye. In the present case report, a zygomatic implant removal resulted in an uneventful healing phase with recovery of the eye functions.

Tuning the Properties of Zero-Field Room Temperature Ferromagnetic Skyrmions by Interlayer Exchange Coupling.

Magnetic materials offer an opportunity to overcome the scalability and energy consumption limits affecting the semiconductor industry. New computational device architectures, such as low-power solid state magnetic logic and memory-in-logic devices, have been proposed which rely on the unique properties of magnetic materials. Magnetic skyrmions, topologically protected quasi-particles, are at the core of many of the newly proposed spintronic devices. Many different materials systems have been shown hosting ferromagnetic skyrmions at room temperature. However, a magnetic field is a key ingredient to stabilize skyrmions, and this is not desirable for applications, due to the poor scalability of active components generating magnetic fields. Here we report the observation of ferromagnetic skyrmions at room temperature and zero magnetic field, stabilized through interlayer exchange coupling (IEC) between a reference magnet and a free magnet. Most importantly, by tuning the strength of the IEC, we are able to tune the skyrmion size and areal density. Our findings are relevant to the development of skyrmion-based spintronic devices suitable for general-use applications which go beyond modern nanoelectronics.

Influence of Nonuniform Micron-Scale Strain Distributions on the Electrical Reorientation of Magnetic Microstructures in a Composite Multiferroic Heterostructure.

Composite multiferroic systems, consisting of a piezoelectric substrate coupled with a ferromagnetic thin film, are of great interest from a technological point of view because they offer a path toward the development of ultralow power magnetoelectric devices. The key aspect of those systems is the possibility to control magnetization via an electric field, relying on the magneto-elastic coupling at the interface between the piezoelectric and the ferromagnetic components. Accordingly, a direct measurement of both the electrically induced magnetic behavior and of the piezo-strain driving such behavior is crucial for better understanding and further developing these materials systems. In this work, we measure and characterize the micron-scale strain and magnetic response, as a function of an applied electric field, in a composite multiferroic system composed of 1 and 2 µm squares of Ni fabricated on a prepoled [Pb(Mg1/3Nb2/3)O3]0.69-[PbTiO3]0.31 (PMN-PT) single crystal substrate by X-ray microdiffraction and X-ray photoemission electron microscopy, respectively. These two complementary measurements of the same area on the sample indicate the presence of a nonuniform strain which strongly influences the reorientation of the magnetic state within identical Ni microstructures along the surface of the sample. Micromagnetic simulations confirm these experimental observations. This study emphasizes the critical importance of surface and interface engineering on the micron-scale in composite multiferroic structures and introduces a robust method to characterize future devices on these length scales.

Phase Coexistence of Mn Trimer Clusters and Antiferromagnetic Mn Islands on Ir(111).

Clusters supported by solid substrates are prime candidates for heterogeneous catalysis and can be prepared in various ways. While mass-selected soft-landing methods are often used for the generation of monodisperse particles, self-assembly typically leads to a range of different cluster sizes. Here we show by scanning tunneling microscopy measurements that in the initial stages of growth, Mn forms trimers on a close-packed hexagonal Ir surface, providing a route for self-organized monodisperse cluster formation on an isotropic metallic surface. For an increasing amount of Mn, first a phase with reconstructed monolayer islands is formed, until at full coverage a pseudomorphic Mn phase evolves, which is the most densely packed one of the three different observed Mn phases on Ir(111). The magnetic state of both the reconstructed islands and the pseudomorphic film is found to be the prototypical antiferromagnetic Néel state with a 120° spin rotation between all nearest neighbors in the hexagonal layer.

Antiferromagnetism-driven two-dimensional topological nodal-point superconductivity.

Magnet/superconductor hybrids (MSHs) hold the promise to host emergent topological superconducting phases. Both one-dimensional (1D) and two-dimensional (2D) magnetic systems in proximity to s-wave superconductors have shown evidence of gapped topological superconductivity with zero-energy end states and chiral edge modes. Recently, it was proposed that the bulk transition-metal dichalcogenide 4Hb-TaS2 is a gapless topological nodal-point superconductor (TNPSC). However, there has been no experimental realization of a TNPSC in a MSH system yet. Here we present the discovery of TNPSC in antiferromagnetic (AFM) monolayers on top of an s-wave superconductor. Our calculations show that the topological phase is driven by the AFM order, resulting in the emergence of a gapless time-reversal invariant topological superconducting state. Using low-temperature scanning tunneling microscopy we observe a low-energy edge mode, which separates the topological phase from the trivial one, at the boundaries of antiferromagnetic islands. As predicted by the calculations, we find that the relative spectral weight of the edge mode depends on the edge's atomic configuration. Our results establish the combination of antiferromagnetism and superconductivity as a novel route to design 2D topological quantum phases.

Plant Foliar Geometry as a Biomimetic Template for Antenna Design.

Plant diversity includes over 300,000 species, and leaf structure is one of the main targets of selection, being highly variable in shape and size. On the other hand, the optimization of antenna design has no unique solution to satisfy the current range of applications. We analyzed the foliar geometries of 100 plant species and applied them as a biomimetic design template for microstrip patch antenna systems. From this set, a subset of seven species were further analyzed, including species from tropical and temperate forests across the phylogeny of the Angiosperms. Foliar geometry per species was processed by image processing analyses, and the resultant geometries were used in simulations of the reflection coefficients and the radiation patterns via finite differences methods. A value below -10 dB is set for the reflection coefficient to determine the operation frequencies of all antenna elements. All species showed between 3 and 15 operational frequencies, and four species had operational frequencies that included the 2.4 and 5 GHz bands. The reflection coefficients and the radiation patterns in most of the designs were equal or superior to those of conventional antennas, with several species showing multiband effects and omnidirectional radiation. We demonstrate that plant structures can be used as a biomimetic tool in designing microstrip antenna for a wide range of applications.

Survival Rate of Zygomatic Implants for Fixed Oral Maxillary Rehabilitations: A Systematic Review and Meta-Analysis Comparing Outcomes between Zygomatic and Regular Implants.

BACKGROUND: Zygomatic implants have been proposed alone or in combination with premaxillary conventional implants for severe resorbed maxillary atrophy rehabilitation. The aim of the present investigation was to evaluate through a qualitative systematic review and meta-analysis the survival rate of zygomatic implants in conjunction with regular fixtures for maxillary rehabilitation. METHODS: The article screening was conducted on the PubMed/Medline and EMBASE electronic databases according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. The scientific papers were included for qualitative analysis and risk-of-bias evaluation. Only the papers that included rehabilitation with zygomatic implants in combination with regular implants were considered for the meta-analysis comparative evaluation of the implant survival rate. RESULTS: The paper search screened a total of 137 papers. After the initial screening, a total of 32 articles were considered for the qualitative analysis. There was a similar implant survival rate between zygomatic and premaxilla regular implants (p = 0.02; Z: 2.26). CONCLUSIONS: Zygomatic and conventional implants showed a high long-term survival rate for fixed maxillary rehabilitations, but few included studies reported the marginal bone loss after loading. Further studies are necessary to evaluate the pattern of marginal bone loss between zygomatic and conventional implants after long-term functional loading.

Large Dzyaloshinskii-Moriya interaction induced by chemisorbed oxygen on a ferromagnet surface.

The Dzyaloshinskii-Moriya interaction (DMI) is an antisymmetric exchange interaction that stabilizes chiral spin textures. It is induced by inversion symmetry breaking in noncentrosymmetric lattices or at interfaces. Recently, interfacial DMI has been found in magnetic layers adjacent to transition metals due to the spin-orbit coupling and at interfaces with graphene due to the Rashba effect. We report direct observation of strong DMI induced by chemisorption of oxygen on a ferromagnetic layer at room temperature. The sign of this DMI and its unexpectedly large magnitude-despite the low atomic number of oxygen-are derived by examining the oxygen coverage-dependent evolution of magnetic chirality. We find that DMI at the oxygen/ferromagnet interface is comparable to those at ferromagnet/transition metal interfaces; it has enabled direct tailoring of skyrmion's winding number at room temperature via oxygen chemisorption. This result extends the understanding of the DMI, opening up opportunities for the chemisorption-related design of spin-orbitronic devices.

Condylar dysfunctional remodeling and recortication: a case-control study.

BACKGROUND: Temporo-mandibular disorders (TMD) is a collective term comprehending different clinical issues involving masticatory muscles, temporo-mandibular joint (TMJ) and other associated structures. TMD diagnosis is not made for its pathogenesis or etiology, but mainly on clinical symptoms. Primary dysfunction develops mostly on four factors: individual predisposition, high psychomotor activity (due to stress or parafunction), occlusal instability and low or absent tissue adaptation capability. On the other hand, secondary disorders can be caused by hereditary or congenital diseases, rheumatic inflammatory diseases, autoimmune and tumoral diseases. During their function, the condyles undergo a structural adaptive and physiological remodeling, but when mechanical stress exceeds adaptive capability, dysfunctional remodeling phenomena may occur. It is characterized by significant condylar morphological modifications at the level of the head of the condyle (smaller condyle), break of cortical integrity and reduced mandibular ramus height with subsequent mandibular retrusion and articular function alteration. The aim of this study is to compare condylar recortication amount, and pain reduction after two different therapeutic protocols. METHODS: This is a case-control study. Twenty TMD patients were chosen and each of them underwent a documentation protocol including extraoral and intraoral photographs, dental casts, casts mounting on the articulator to evaluate CPI (CO-CR discrepancy index) and cone beam computed tomography (CBCT) of the mandibular condyles taken in closed mouth position. For the radiographic evaluation, a Planmeca ProMax 3D Mid system was utilized with an acquiring volume of 80×80 mm dimension, exposition 90 kV, 10.0 mA, 12 seconds with a DAP (Dose Area Product) of 1094 mGy·cm2 for each condyle. The acquired volume was elaborated by the Planmeca Romexis software v. 3.2.0.R and TMJ module. Seven coronal cuts and 10 sagittal cuts were performed on the head of the condyle to highlight the amount of cortication, before and after the application of two different therapeutic protocols. Protocol number 1 (N.=10 patients) included the exclusive use of a splint, while protocol number 2 (N.=10 patients) included the use of a splint associated with pharmacological therapy (NSAIDs, antioxidant, omega 3). The revaluation was performed on asymptomatic patient after a period of 6-8 months. The pain for each patient was assessed by a Visual Analogue Scale (VAS) from 0 to 10, 0 meaning no pain and 10 the worst pain ever felt. The VAS was evaluated after 10 days from the beginning of the treatment, after 3 months and after 8 months at the end of the treatment. Statistical analyses were carried using a χ2 test (P value <0.05). RESULTS: No significant differences in the amount of cortication were found in the radiographic revaluation between the two different therapeutic protocols, even though it was noticed that the use of medicaments brought to a resolution of the symptoms in a shorter period of time (P=0.00001 after 10 days; P=0.0251 after 3 months). CONCLUSIONS: According to this study, pharmacological protocol in the therapy of TMD does not seem to affect condylar cortication. Medicaments although seem to accelerate the disappearance of clinic symptomatology, but more researches are needed to valid these findings.

Bi-directional coupling in strain-mediated multiferroic heterostructures with magnetic domains and domain wall motion.

Strain-coupled multiferroic heterostructures provide a path to energy-efficient, voltage-controlled magnetic nanoscale devices, a region where current-based methods of magnetic control suffer from Ohmic dissipation. Growing interest in highly magnetoelastic materials, such as Terfenol-D, prompts a more accurate understanding of their magnetization behavior. To address this need, we simulate the strain-induced magnetization change with two modeling methods: the commonly used unidirectional model and the recently developed bidirectional model. Unidirectional models account for magnetoelastic effects only, while bidirectional models account for both magnetoelastic and magnetostrictive effects. We found unidirectional models are on par with bidirectional models when describing the magnetic behavior in weakly magnetoelastic materials (e.g., Nickel), but the two models deviate when highly magnetoelastic materials (e.g., Terfenol-D) are introduced. These results suggest that magnetostrictive feedback is critical for modeling highly magnetoelastic materials, as opposed to weaker magnetoelastic materials, where we observe only minor differences between the two methods' outputs. To our best knowledge, this work represents the first comparison of unidirectional and bidirectional modeling in composite multiferroic systems, demonstrating that back-coupling of magnetization to strain can inhibit formation and rotation of magnetic states, highlighting the need to revisit the assumption that unidirectional modeling always captures the necessary physics in strain-mediated multiferroics.

Ultrastructural characteristics of human mesenchymal stromal (stem) cells derived from bone marrow and term placenta.

Human mesenchymal stromal (stem) cells (hMSCs) isolated from adult bone marrow (BM-hMSCs) as well as amnion (AM-hMSCs) and chorion (CM-hMSCs) term placenta leaves were studied by transmission electron microscopy (TEM) to investigate their ultrastructural basic phenotype. At flow cytometry, the isolated cells showed a homogeneous expression of markers commonly used to identify hMSCs, i.e., CD105, CD44, CD90, CD166, HLA-ABC positivities, and CD45, AC133, and HLA-DR negativities. However, TEM revealed subtle yet significant differences. BM-hMSCs had mesenchymal features with dilated cisternae of rough endoplasmic reticulum (rER) and peripheral collections of multiloculated clear blisters; this latter finding mostly representing complex foldings of the plasma membrane could be revelatory of the in situ cell arrangement in the niche microenvironment. Unlike BM-hMSCs, CM-hMSCs were more primitive and metabolically quiescent, their major features being the presence of rER stacks and large peripheral collections of unbound glycogen. AM-hMSCs showed a hybrid epithelial-mesenchymal ultrastructural phenotype; epithelial characters included non-intestinal-type surface microvilli, intracytoplasmic lumina lined with microvilli, and intercellular junctions; mesenchymal features included rER profiles, lipid droplets, and well-developed foci of contractile filaments with dense bodies. These features are consistent with the view that AM-hMSCs have a pluripotent potential. In conclusion, this study documents that ultrastructural differences exist among phenotypically similar hMSCs derived from human bone marrow and term placenta leaves; such differences could be revelatory of the hMSCs in vitro differentiation potential and may provide useful clues to attempt their in situ identification.

Dendritic cells of immune thrombocytopenic purpura (ITP) show increased capacity to present apoptotic platelets to T lymphocytes.

OBJECTIVE: Altered self-antigen processing/presentation of apoptotic cells by DCs and/or modifications of autoantigens may lead to the development of autoantibodies. Increasing evidence indicates that platelets may undergo apoptosis. Therefore, in the present study we investigated whether platelet apoptosis and/or dendritic cells (DCs) may play a role in the stimulation of the immuno-mediated anti-platelet response in chronic immune thrombocytopenic purpura (ITP). METHODS AND RESULTS: Twenty-nine patients with active ITP and 29 healthy adult volunteers were enrolled into the study. Freshly washed platelets and platelets aged in a plasma-free buffer for 72 hours at 37 degrees C were assessed by flow cytometry for phosphatidylserine exposure using annexin V-FITC, caspase activation, and platelet activation markers. CD14-derived DCs were characterized by immunophenotyping, cytokine production, and ability to present fresh and aged platelets to T lymphocytes. We demonstrated that platelets from ITP patients, either fresh or in vitro aged, show increased apoptosis (with low levels of activation) in comparison to their normal counterparts. We also found that immature DCs readily ingest apoptotic platelets. Furthermore, in ITP patients DCs, prepulsed with autologous/allogeneic fresh and aged platelets, are highly efficient in stimulating autologous T-cell proliferation as compared to DCs derived from healthy donors. This finding may be related to the upregulated expression of CD86 in DCs from ITP patients and not to higher phagocytic activity. CONCLUSION: These results suggest that DC dysfunction, together with increased propensity of platelets to undergo apoptosis, may play a role in the stimulation of the immune system in ITP.

Phase II study of a single pegfilgrastim injection as an adjunct to chemotherapy to mobilize stem cells into the peripheral blood of pretreated lymphoma patients.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy of pegfilgrastim, in combination with salvage chemotherapy, in mobilizing CD34(+) stem cells into the peripheral blood of pretreated lymphoma patients. DESIGN AND METHODS: This was an open-label phase II study including 25 pretreated patients (Hodgkin's disease=4; aggressive non-Hodgkin's lymphoma=21). The primary end-point of the study was the successful mobilization of a target cell dose of 2x10(6) CD34(+) cells/kg in lymphoma patients receiving ifosfamide, epirubicin and etoposide (IEV) chemotherapy and a fixed dose (6 mg) of pegfilgrastim given as single subcutaneous injection. RESULTS: Following chemotherapy, all patients had grade 4 neutropenia that lasted a median of 1.5 days (1-3). Pegfilgrastim treatment was well tolerated and only 2/25 patients required pain-control medication. CD34+ cells were mobilized in all patients. The median (range) peak value of peripheral blood CD34+ cells after IEV chemotherapy and pegfilgrastim was 141x10(6)/L (12.8-386) and occurred almost invariably on day +14 (13-16). Twenty-three of the 25 patients underwent a single standard volume leukapheresis to collect a median of 8.7x10(6) CD34(+) cells/kg (1.78-17.3). Twenty four/25 patients (96%) reached the target cell dose of 2x10(6) CD34(+) cells/kg. High concentrations of circulating CD34+ cells (> 50x10(6)/L) were observed for several days after the achievement of the peak value. All the study patients were transplanted with their pegfilgrastim-mobilized CD34(+) cells and showed a rapid and sustained engraftment after high-dose chemotherapy. INTERPRETATION AND CONCLUSIONS: Our results show that pegfilgrastim as an adjunct to chemotherapy is a predictable and highly effective mobilization regimen in pretreated lymphoma patients.

Detection of a novel specificity (CTLA-4) in ATG/TMG globulins and sera from ATG-treated leukemic patients.

BACKGROUND: T-cell costimulation has been shown to provide positive signals for T-cell activation and generation of effector activity. In this study, we analyzed the presence of antibodies (Abs) against the T-lymphocyte costimulatory molecules CD28, CTLA-4, CD80, and CD86 in anti-T-lymphocyte (ATG) and antithymocyte (TMG) globulin preparations to address their mechanism of action. We focused our attention on the role of CTLA-4-specific Abs in the immunosuppressive effect of ATG/TMG, because anti-CTLA-4 agonistic Abs may suppress T-cell proliferation and nonagonistic Abs may lead to T-cell depletion through an Ab-dependent cell cytotoxicity mechanism. METHODS: ATG/TMG and patients' sera were tested for binding to recombinant human costimulatory molecules by ELISA techniques. CTLA-4 specificity was also analyzed by cytoplasmic immunofluorescence staining of a CTLA-4 transfectant by competitive inhibition immunofluorescence and by cell proliferation assay in allogeneic mixed lymphocyte reaction (MLR). RESULTS: Either ATG or TMG predominantly contained anti-CTLA-4 Abs, with higher reactivity in ATG followed by anti-CD86 and -CD28 Abs, whereas anti-CD80 Abs were found only in ATG. Anti-CTLA-4 Abs present in ATG/TMG recognized the native form of CTLA-4 molecule, and their removal reduced the effect of ATG in an allogeneic MLR. Kinetic studies indicated that such Abs were present in the sera of 12 ATG-treated leukemic patients up to 21 days after ATG administration. CONCLUSIONS: These data suggest that the novel anti-CTLA-4 Abs found in ATG may greatly contribute to its immunosuppressive effect, thus accounting for the absence of rejection and exceptionally low incidence of graft-versus-host disease in the group of patients analyzed.

Caspase-9 is the upstream caspase activated by 8-methoxypsoralen and ultraviolet-A radiation treatment of Jurkat T leukemia cells and normal T lymphocytes.

BACKGROUND AND OBJECTIVES: A combination of 8-methoxypsoralen and ultraviolet-A radiation (PUVA) is used for the treatment of T cell-mediated disorders, including chronic graft-versus-host disease. The mechanisms of action of this therapy, referred to as extracorporeal phototherapy, have not been fully elucidated. PUVA is known to induce apoptosis in T lymphocytes collected by apheresis, however scarce information is available concerning the apoptotic pathways activated by PUVA. DESIGN AND METHODS: We used Jurkat human T leukemia cells and normal T lymphocytes to analyze the PUVA-triggered caspase activation pattern by means of immunoblot analysis, in vitro caspase activity assays, and selective caspase inhibitors coupled to flow cytometric analysis. RESULTS: PUVA treatment induced activation of apical caspases-9 and -8, and of effector caspases-3 and -7 in Jurkat cells and human T lymphocytes. While activation of caspase-9 occurred as early as 1 h after PUVA treatment of Jurkat cells, procaspase-8 cleavage was delayed and was detected 6 h after the exposure. Also in normal T lymphocytes, cleavage of caspase-8 was subsequent to activation of caspase-9. PUVA-dependent proteolytic cleavage of procaspase-8 was blocked by inhibitors selective for either caspase-9 or -3. Moreover, procaspase-8 was cleaved in vitro by activated caspase-3, which gave rise to proteolytic fragments equivalent to those generated in vivo. INTERPRETATION AND CONCLUSIONS: Activation of caspase-8 in PUVA-treated Jurkat cells and normal T lymphocytes is secondary to up-regulation of caspase-9. Overall, our results identify caspase-9 as the critical upstream caspase initiating apoptosis by PUVA in Jurkat T-cells and human T lymphocytes.

High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience.

BACKGROUND AND OBJECTIVES: In this work we examine the characteristics and outcome of patients with Hodgkin's disease (HD) treated with high-dose therapy (HDT) and autologous transplantation at our Institute between 1982 to 2000. DESIGN AND METHODS: A retrospective analysis was performed examining patients' characteristics, prior chemotherapy regimens, pre-transplant disease status, HDT regimen, source of stem cells, time for hematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and relapse-free survival (RFS). RESULTS: Ninety-seven patients with HD were treated and had estimated 10-year OS and RFS rates of 32% and 60%, respectively. Disease status (sensitive vs. refractory) before HDT was the most powerful predictive parameter for OS and RFS in both univariate and multivariate analyses. The rate of transplant-related mortality in the whole cohort was only 1% whereas the rate of second malignancies was 3%. INTERPRETATION AND CONCLUSIONS: Our results confirm that HDT with autologous transplantation is associated with a durable RFS in a remarkable proportion of HD patients and that the procedure has a very low global early and late toxicity.

High-dose therapy with autologous transplantation for aggressive non-Hodgkin's lymphoma: the Bologna experience.

Patients with aggressive non-Hodgkin's lymphoma (NHL) who relapse after initial therapy have a poor prognosis and with standard dose salvage therapy the outlook remains poor. In this work we examine the patient characteristics and outcome of patients with aggressive NHL treated with HDT and autologous transplantation at our Institute from 1982 to 1999. A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for hematopietic recovery, complications of transplantation, response rates, overall survival (OS) and relapse-free survival (RFS). One hundred and thirty-four patients with aggressive NHL were treated with estimated 10-year OS and RFS rates of 50% and 66%, respectively. Disease status (sensitive vs. refractory) pre-HDT was the most powerful predictive parameter for OS and RFS, at both univariate and multivariate analysis. For the entire cohort, transplant-related mortality was only 3.5% without evidence of second malignancies. Our results confirm that HDT with autologous transplantation is associated with a durable RFS in a remarkable proportion of aggressive NHL patients with very low global early and late toxicity. Improved patient selection, transplant timing, ongoing improvements in supportive care, and selected phase III trials should increase outcomes further.

Flow cytometry detection of Shiga toxins in the blood from children with hemolytic uremic syndrome.

BACKGROUND: Hemolytic uremic syndrome (HUS) is the main cause of acute renal failure in early childhood. Most cases are due to intestinal infections from Escherichia coli strains (STEC) which produce by Shiga toxin (Stxs). Stx1 and Stx2 produced by STEC in the gut are absorbed into the circulation and, after binding on polymorphonuclear leukocytes (PMNs), are targeted to renal endothelium. The aim of the present work was the development of a method to detect Stxs bound on circulating PMNs and to diagnose STEC infections in patients with HUS. METHODS: White blood cells isolated after erythrocytic lysis were incubated with anti-Stxs mouse monoclonal antibodies in the presence of human serum to saturate Fc receptors on PMNs. After incubation with fluorescein isothiocyanate-goat anti-mouse immunoglobulin G, flow cytometric analysis was used to demonstrate the cell-bound fluorescence. RESULTS: The method was quick (3 h), sensitive (femtomoles), and capable of detecting both Stxs. The presence of Stxs was detected on PMNs from six patients with HUS: four patients had serologic or microbiological evidence of STEC infection, whereas the other two patients had no evidence of STEC infection when employing the standard diagnostic methods. CONCLUSIONS: The method described is rapid, simple, and based on commercially available reagents, and it might be more sensitive than the standard methods for diagnosis of STEC infection. It also allows the detection of Stxs in blood, a key step to monitor the pathogenesis of HUS.

New laboratory test in flow cytometry for the combined analysis of serologic and cellular parameters in the diagnosis of heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a major complication of heparin therapy. A quick and reliable laboratory assay for the combined determination of pathogenic anti-heparin and platelet factor 4 (H:PF4) antibodies in the serum and platelet activation is not currently available. METHODS: We developed a new single-tube assay in flow cytometry that combines the detection of antibodies in the serum and their activatory properties on platelets. The assay was tested on 13 serum samples from patients with suspected HIT and six samples from normal donors. The presence of anti-H:PF4 antibody complexes was detected by H:PF4-coated beads, and donor platelet activation induced by HIT sera was determined by Annexin V binding. All data were compared with the patients' clinical setting, laboratory tests, and standard enzyme-linked immunosorbent assay detection of anti-H:PF4 antibodies. RESULTS: This flow cytometry assay allowed unequivocal, simultaneous detection of anti-H:PF4 antibodies in sera and their activatory properties on platelets. All cases for which the diagnosis of HIT was confirmed were detected by the flow assay. CONCLUSIONS: This assay, combining for the first time functional and nonfunctional testing on anti-H:PF4 antibodies, is likely to influence the clinical decision for the management of HIT patients.