FLT3-targeted therapy restores GATA1 pathway function in NPM1/FLT3-ITD mutated acute myeloid leukaemia.

One-third of newly diagnosed adult acute myeloid leukaemia (AML) carry FLT3 mutations, which frequently occur together with nucleophosmin (NPM1) mutations and are associated with worse prognosis. FLT3 inhibitors are widely used in clinics with limitations due to drug resistance. AML cells carrying FLT3 mutations in both mouse models and patients present low expression of GATA1, a gene involved in haematopoietic changes preceding AML. Here, we show that FLT3 inhibition induces cellular responses and restores the GATA1 pathway and functions in NPM1/FLT3-ITD mutated AML, thus providing a new mechanism of action for this drug.

A geo-chemo-mechanical study of a highly polluted marine system (Taranto, Italy) for the enhancement of the conceptual site model.

The paper presents the results of the analysis of the geo-chemo-mechanical data gathered through an innovative multidisciplinary investigation campaign in the Mar Piccolo basin, a heavily polluted marine bay aside the town of Taranto (Southern Italy). The basin is part of an area declared at high environmental risk by the Italian government. The cutting-edge approach to the environmental characterization of the site was promoted by the Special Commissioner for urgent measures of reclamation, environmental improvements and redevelopment of Taranto and involved experts from several research fields, who cooperated to gather a new insight into the origin, distribution, mobility and fate of the contaminants within the basin. The investigation campaign was designed to implement advanced research methodologies and testing strategies. Differently from traditional investigation campaigns, aimed solely at the assessment of the contamination state within sediments lying in the top layers, the new campaign provided an interpretation of the geo-chemo-mechanical properties and state of the sediments forming the deposit at the seafloor. The integrated, multidisciplinary and holistic approach, that considered geotechnical engineering, electrical and electronical engineering, geological, sedimentological, mineralogical, hydraulic engineering, hydrological, chemical, geochemical, biological fields, supported a comprehensive understanding of the influence of the contamination on the hydro-mechanical properties of the sediments, which need to be accounted for in the selection and design of the risk mitigation measures. The findings of the research represent the input ingredients of the conceptual model of the site, premise to model the evolutionary contamination scenarios within the basin, of guidance for the environmental risk management. The study testifies the importance of the cooperative approach among researchers of different fields to fulfil the interpretation of complex polluted eco-systems.

Spatial energy transfer with observation of bimolecular singlet oxygen emission using quantum dots as donors and zinc-phthalocyanine as acceptors.

This study reports the influence of CdSe-ZnS core-shell quantum dots (QDs) for formation of singlet oxygen using zinc-phthalocyanine (ZnPc) dyes in colloidal solutions. Using a microluminescence surface scan technique it was possible to measure accurately the photon diffusion length, or photon mean free path, inside the medium. Analyses were performed for a range of QD concentrations. Photon diffusion length was assigned to the bimolecular singlet oxygen emission at 707 nm. Related singlet oxygen emission was predicted by observing quenching of the photon diffusion length measured at the specific oxygen emission as a function of QD concentration, being a nontrivial phenomenon related to the QD donors. Diffusion length measured at 707 nm increased with QD concentration; in the absence of QDs, as in pure ZnPc samples, the emission peak at 707 nm was not observed.

General model for depth-resolved estimation of the optical attenuation coefficients in optical coherence tomography.

We present the proof of concept of a general model that uses the tissue sample transmittance as input to estimate the depth-resolved attenuation coefficient of tissue samples using optical coherence tomography (OCT). This method allows us to obtain an image of tissue optical properties instead of intensity contrast, guiding diagnosis and tissues differentiation, extending its application from thick to thin samples. The performance of our method was simulated and tested with the assistance of a home built single-layered and multilayered phantoms (~100 µm each layer) with known attenuation coefficient on the range of 0.9 to 2.32 mm-1 . It is shown that the estimated depth-resolved attenuation coefficient recovers the reference values, measured by using an integrating sphere followed by the inverse adding doubling processing technique. That was corroborated for all situations when the correct transmittance value is used with an average difference of 7%. Finally, we applied the proposed method to estimate the depth-resolved attenuation coefficient for a thin biological sample, demonstrating the ability of our method on real OCT images.

Bioelectrode applied to diagnosis of cardiac disease.

This paper describes the assembly of a bioelectrode based on poly(3-aminophenol) and anti-troponin T antibody for recognition of troponin T, which is a specific biomarker for diagnosis of acute myocardial infarction. This disease causes loss of cellular components, allowing the output of molecules such as troponin T. This proteic component acts as biomarker for diagnosis of acute myocardial infarction due to their high sensitivity and specificity. Poly(3-aminophenol) was electrodeposited onto fluorine doped tin oxide (FTO) coated glass and characterized by spectroscopic methods (UV-Visible, fluorescence, infrared), electrochemical methods (cyclic voltammetry and electrochemical impedance spectroscopy) and morphological methods (laser interferometry, field emission scanning electronic microscopy, and atomic force microscopy). UV/Vis analysis indicated that poly(3-aminophenol) presents extension of conjugation, in according with fluorescence studies. Electrochemical studies indicated that poly(3-aminophenol) electrodeposited in FTO is a material with passivating characteristics for anions and capacity of retaining cationic compounds. Laser interferometry showed that poly(3-aminophenol) covers the FTO surface with a thickness off 375 ± 75 nm. Surface images by FE-SEM and AFM have shown a full coverage on the FTO by the polymer film. The incorporation of anti-troponin T antibody on FTO electrode modified with poly(3-aminophenol) allowed effective and selective detection of cardiac biomarker troponin T, by electrochemical impedance spectroscopy (label free) and by photoluminescence, based on CdSe/ZnS quantum dots. This research shows the step by step assembly of the bioelectrode, used for detection of troponin T by impedimetric and fluorescence methods, opening the opportunity for its use in the diagnosis of others diseases.

Ki-67 and vascular endothelial growth factor expression in intracranial meningiomas in dogs.

BACKGROUND: Tumor proliferation in human intracranial meningiomas can be defined by the reactivity of the monoclonal antibody MIB-1 to the Ki-67 antigen. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is a predictive marker for survival of dogs with intracranial meningiomas. HYPOTHESIS: Ki-67 is expressed in canine intracranial meningiomas and is associated with VEGF expression. Ki-67 expression is a prognostic marker for patient outcome. ANIMALS: Seventy client-owned dogs with WHO grade I intracranial meningiomas. METHODS: Retrospective study assessing the degree of immunostaining for Ki-67 by MIB-1 and VEGF expression in intracranial meningioma tissue from dogs. MIB-1 Labeling Index (LI) was calculated with Image J NIH-software. Extent, intensity, and distribution of VEGF-expression was assessed semiquantitatively. Cross tabulations with Fisher's exact tests and nonparametric Spearman's rank correlations were performed to identify associations between VEGF expression and MIB-1 LI. Fifteen dogs underwent postsurgical radiotherapy and were included in survival analysis. The effect of MIB-1 LI on survival was examined by Kaplan-Meier and Cox proportional hazards regression procedures. RESULTS: Ki-67 staining was positive in 91% (64/70) and VEGF expression was detected in 96% (67/70). There was no significant association between VEGF expression and MIB-1 LI. MIB-1 LI was not associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: MIB-1 antibody can be used to document cell proliferation in intracranial meningiomas in dogs, but does not predict outcome. No association between VEGF as a marker of angiogenesis and tumor proliferation was found. Angiogenesis might be a more important predictor of meningioma activity in dogs than is Ki-67.

Psychiatric manifestations as a primary symptom in antiphospholipid syndrome.

Antiphospholipid syndrome is a disorder characterised by recurrent venous or arterial thrombosis and/or foetal losses associated with typical laboratory abnormalities. The initial manifestation of anthiphospholipid syndrome can involve many organ systems either singly or in combination. We describe the case of a 62 yr old female showing schizophrenia-like symptoms in which further evaluations allowed us to diagnose the antiphospolipid syndrome.

Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial.

In this trial, acute myeloid leukemia patients (pts) aged 61-80 years received MICE (mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen (idarubicin, etoposide and cytarabine) given according to either an intravenous (i.v.) or a 'non-infusional' schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events (255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival (median 9 vs 10.4 months, P=0.15, hazard ratio (HR) =1.18, 95% confidence interval (CI) 0.94-1.49) - primary end point - and survival (median 15.7 vs 17.8 months, P=0.19, HR=1.17, 95% CI 0.92-1.50). In the 'non-infusional' arm grade 3-4 vomiting (10 vs 2%; P=0.001) and diarrhea (10 vs 4%; P=0.03) were higher than in the 'i.v.' arm, whereas time to platelet recovery >20 x 10(9)/l (median: 19 vs 23 days; P=0.02) and duration of hospitalization (mean: 15 vs 27 days; P<0.0001) was shorter. The 'non-infusional' consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.

VEPEMB in elderly Hodgkin's lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study.

BACKGROUND: In advanced age the prognosis of Hodgkin's lymphoma (HL) is poor, but, as a consequence of the low incidence of HL in the elderly, prospective studies are lacking and the best treatment strategy is difficult to define. PATIENTS AND METHODS: One-hundred and five HL patients over 65 years of age were treated homogeneously with an original reduced-intensity regimen designed for HL in the elderly containing vinblastine, cyclophosphamide, procarbazine, etoposide, mitoxantrone and bleomycin (VEPEMB). Forty-eight early stage (IA-IIA) patients received three courses of VEPEMB followed by involved field irradiation. Fifty-seven advanced stage (IIB-IV) patients received six courses followed by radiotherapy limited to the areas of bulky disease. RESULTS: Mean age was 71 years (range 66-83). Co-morbidities were present in 39 patients (37%). A treatment plan modification for poor tolerance or toxicity was needed in 18 patients. Results were satisfactory, even if they were better in early rather than in advanced stage disease: complete response rate 98% versus 58% (P <0.01); 5-year failure-free survival 79% versus 34% (P <0.01). The results were affected by advanced stage, systemic symptoms and co-morbidity but they were not influenced by age itself. CONCLUSIONS: VEPEMB is an effective and low toxic regimen for HL in the elderly. Co-morbidity is a prognostic factor more important than age itself.

Bone marrow transplantation in adult thalassemic patients.

One hundred seven adult patients with thalassemia aged from 17 through 35 years and transplanted from HLA-identical siblings between November 1988 and September 1996 were evaluated on December 31, 1997. The outcome experience of 20 consecutive patients transplanted between November 13, 1988 and January 10, 1991 and reported in September 1992 is updated after 5 additional years. The experience on 87 patients transplanted between May 1991 and September 1996 is described and evaluated as of the end of December 1997. Of 107 patients, 69 survive between 1.5 and 9 years after transplantation. Sixty-six of these patients do not have thalassemia and are identified as ex-thalassemic after bone marrow transplantation. The youngest survivor is 20 years old, 6 are older than 30 years, and the oldest is 37 years of age. Patients with chronic active hepatitis at the time of transplant were significantly more likely to die than patients without (P =.05; relative risk, 2.05). Marrow transplantation is a valid treatment option for older patients with thalassemia who have suitable donors and show deterioration with conventional therapy.

Neosporosis in a dog in Italy.

Clinical neosporosis was diagnosed in a 2-month-old Pit Bull Terrier from Italy. Neospora caninum tachyzoites were found in semitendinosus muscle with myositis. The diagnosis was confirmed by immunohistochemical staining with anti-N. caninum specific antibodies. This is the first report of systemic neosporosis in dogs from Italy.

[Plasma and urinary fibrin fibrinogen degradation products in a case of renal thromboembolism]. / Prodotti di degradazione della fibrina-fibrinogeno plasmatici ed urinari in un caso di tromboembolia renale.

The authors examined the trend of plasma (FDPp) and urine (FDPu) fibrin-fibrinogen degradation products in a case of renal thromboembolism during atrial fibrillation. No alterations of FDP are reported in the literature for this renal pathology. This raises the question of whether this laboratory parameter is of diagnostic value during the course of renal embolism. The case concerned a patient who was admitted to the emergency ward with painful symptoms in his right flank. He was initially hospitalised with a diagnosis of right renal colic. A few days later multiple thromboembolism of the right kidney was diagnosed using CAT with i.v. infusion of contrast medium and renal scintigraphy with 99Tc DTPA. From day 6 to day 17 after the start of painful symptoms, a number of assays were made of FDPp and FDPu using the rapid latex test for FDP which uses specific anti-fragment D and E antiserum (Thrombo-Wellcotester). Alterations of plasma and urine FDP were found which also showed an opposite trend: an inversion of the changes was noted on day 8 with normalisation of FDPp and a persistent increase in FDPu by day 17. Earlier tests may confirm the trend of FDP and their value in diagnostic screening for cases of renal thromboembolism.

[Treatment with human tetanus immunoglobulins in the Emergency Department. Effects of informed consent]. / Trattamento con immunoglobuline umane antitetaniche in Pronto Soccorso. Effetti del consenso informato.

BACKGROUND: The impact of informed consent to tetanus prophylaxis with human immunoglobulins on patients treated in the Emergency Department has been evaluated. METHODS: Tetanus vaccination history was investigated in 1435 patients in 1995 and in 1300 patients in 1996 with post-traumatic skin lesions. RESULTS: The study has shown that in 1995, 55% and in 1996 49.5% of the total patients studied had not received vaccine for tetanus or boosters for over 10 years. These patients had been proposed the treatment with human tetanus immunoglobulins (TIG). The research was performed comparing the consent obtained before (from 17/5 to 15/7/1995) and after (from 17/5 to 15/7/1996) the introduction of the informed consent. The survey was divided into 15-day periods. In 1995 prophylaxis with human immunoglobulins was refused by 42 patients out of 831 (5%) while, in the following year, by 284 out of 641 (44.3%). Every period examined has shown highly significant differences (p < 0.000). CONCLUSIONS: Informing the patients that tetanus prophylaxis with human immunoglobulins can expose them to the risk, at present remote, of transmission of viral infections, has caused a heavy rise of denials to the suggestion of treatment with human immunoglobulins. The amount of the treated patients and the time that was devoted to informed consent would make Emergency Department one of the main places for effective and widespread tetanus prophylaxis. However a greater activity of outer structures would also be hoped for.

[The role of echography in the diagnosis of pelvic masses]. / Ruolo dell'ecografia nella diagnostica delle tumefazioni pelviche.

The authors confirm the fundamental role of the pulse-echo technique in the study of pelvic masses; they outline the usefulness of the ultrasonography in the early presumptive diagnosis of the possible neoplastic alterations of such masses. The authors present five clinical cases in which the use of the pulse-echo technique has allowed to locate, in spite of a scanty clinical symptomatology, the presence of pathologies requiring a rapid surgical resolution.

Effectiveness of fludarabine in advanced B-cell chronic lymphocytic leukemia.

AIMS: The study was carried out to investigate the efficacy and toxicity of fludarabine phosphate in the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in previously treated patients. METHODS: Sixteen patients, 11 males and 5 females, 9 in stage B and 7 in stage C, according to the Binet Staging System, were treated with a maximum of 6 cycles of fludarabine (25 mg/m2) for 5 days, every 4 weeks. All patients had been pretreated, 10 were refractory to standard regimens, 5 were in relapse, and 1 patient was in partial remission. RESULTS: Thirteen patients were judged suitable for evaluation. Overall 9 patients were responsive to treatment; 4 complete and 5 partial responses were observed. Of the 4 patients in complete remission, 3 were alive at 6, 10 and 13 months, respectively, from the beginning of treatment. One patient died after 11 months for acute graft-versus-host disease after allogenic bone marrow transplantation by an HLA sibling donor. Two of the 5 patients in partial remission were alive at 7 and 17 months, respectively, and the other 3 died (2 of disease reexpansion after 14 and 16 months and 1 of septic shock following pneumonia). Four patients were not responsive to treatment: 1 died from disease progression after 8 months from the beginning of therapy, 1 from cardiac failure after 9 months, 1 from septic shock following meningitis, and 1 was alive after 7 months of follow-up. Treatment was well tolerated, with nausea and vomiting in only one patient. We observed two episodes of pneumonitis, without any evidence of the responsible agent, a tumor lysis syndrome with acute renal failure, a recurrence of autoimmune thrombocytopenia, and a Coombs-positive hemolytic anemia. CONCLUSIONS: Fludarabine phosphate is effective in the treatment of patients with advanced B-CLL, even in those refractory to multiple chemotherapy regimens.

Polyclonal hemopoiesis in leukemia patients following molecularly documented remission.

We performed clonality studies of hemopoietic reconstitution in 24 female patients (pts) with leukemias characterized by specific tumor markers. Thirteen pts had Acute Promyelocytic Leukemia (APL) with rearrangements of the RAR-a and PML genes, 8 BCR rearranged (BCR+)/Ph+ Chronic Myeloid Leukemia (CML) and 3 BCR+/Ph+ Acute Lymphoid Leukemia (ALL). Bone marrow (BM) DNA samples were obtained at diagnosis and at remission after Southern blot documented suppression of specific markers. The clonal or non-clonal nature of hemopoietic reconstitution was assessed by hybridizing the same DNAs with the M27 beta probe, in order to detect methylation differences at the X-linked DXS255 locus. Twenty four pts showed a polyclonal methylation pattern at remission, whereas in 3 cases an apparently clonal pattern was observed despite no evidence of specific gene rearrangement. In 2 of these 3 cases, however, DNAs derived from non-affected tissues (T lymphocytes, skin and BM fibroblasts) revealed the presence of the same DXS255 unmethylated allele detected at diagnosis, while in the third case we found the same apparently clonal pattern in blood mononuclear cells obtained from her healthy female BM donor. These data indicate that polyclonal hematopoiesis occur in APL and CML pts after therapy induced suppression of specific tumor markers, and that unbalanced or aberrant X chromosome methylation patterns are observed in some cases, most likely reflecting constitutional features.

[Biophysical control of pregnancies at risk: our experience]. / Controllo biofisico della gravidanza a rischio: nostra esperienza.

The perinatal medicine has substantially improved the monitoring of the risk pregnancy thanks to the biological control of the pregnancy and labour. After examining the main systems of fetal monitoring, the authors report their own case load related to the monitoring and to the result of 100 postdate pregnancies examined at their ward.