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S Palmieri

Publications and source records attributed to S Palmieri.

At least 19 recordsLinked to original sources

An antecedent diagnosis of refractory anemia with excess blasts has no prognostic relevance in acute myeloid leukemia of older adult patients.

BACKGROUND: Conflicting results have been reported about the prognostic relevance of antecedent myelodysplastic syndrome (MDS) in acute myeloid leukemia (AML) of older adults. PATIENTS AND METHODS: Data from 87 intensively treated AML patients (median age 69 years) were analyzed, with the aim of comparing therapeutic results and toxicity between de novo and AML secondary to a previous MDS (s-AML). Rate of CD34+ cells mobilization and feasibility of autologous stem cell transplantation (ASCT) were also compared. RESULTS: Complete remission rate, death in induction and primary resistance were not statistically different between the two groups. Median time for neutrophil recovery was similar, while s-AML patients required a longer time for platelet recovery (P = 0.04). There was no difference as to eligibility for consolidation as well as for mobilization and feasibility of ASCT. S-AML had negligible impact on overall survival (OS) and disease-free survival (DFS). In the multivariate analysis the only parameter significantly related to either OS or DFS duration was adverse karyotype (P = 0.02 and 0.04, respectively). CONCLUSIONS: A diagnosis of s-AML does not represent a clinically relevant prognostic factor in elderly AML patients treated with aggressive therapy. Furthermore, s-AML patients can be mobilized and autografted with comparable results as opposed to de novo cases.

Acute Disease↗

A canopy layer model and its application to Rome.

An urban canopy layer model based on four energy balance equations at ground level and at building level was developed to simulate and describe the urban climate and the heat storage in an urban setting. Thermal and radiative characteristics of urban and rural surfaces as well as atmospheric parameters related to the general synoptic conditions were used as data input. In addition, buildings were modelled as parallelepipeds and the hysteresis of materials was taken into account. The model provides as output skin temperature of buildings, air temperature and humidity within the canopy layer and hence the mean surface temperature and the air temperature at 2 m above surface. The latter parameter was used for the comparison with in situ temperature observations. The model was applied to Rome in radiative summer and winter episodes. The results, which agree with observations, show that the Urban Heat Island (UHI) is a nocturnal phenomenon, present both in winter (the greatest difference between urban and rural temperatures is about 2 degrees C) and summer (the temperature difference is about 5 degrees C), mainly resulting from the urban geometry and the thermal properties of materials. The anthropogenic heat does not play an important role in the UHI development. A monthly nocturnal behaviour of temperature differences between urban and surrounding rural areas shows that the maximum mean value of 4.2 degrees C occurs in August. Moreover, the parks in the city centre, where temperatures are lower, define two distinct heat islands, east and west.

Air Pollution↗

In vitro internalization, intracellular transport, and clearance of an anti-CD11a antibody (Raptiva) by human T-cells.

Efalizumab (Raptiva) is a humanized CD11a-specific monoclonal antibody that was recently approved for the treatment of moderate to severe psoriasis. In psoriasis patients, the rate of efalizumab clearance from serum is related to T-cell surface expression of CD11a, suggesting a receptor-mediated clearance model for efalizumab (Bauer et al., 1999). However, limited experimental data are available to explain how the interaction with CD11a results in the systemic clearance of efalizumab. The following studies were designed to test the hypothesis that one mechanism of anti-CD11a antibody clearance is mediated in part by cellular internalization. This was tested in vitro using purified mouse and human T-cells as a model to study the cellular uptake and clearance of anti-CD11a antibodies. Data from these studies suggest that anti-CD11a antibodies are internalized by purified T-cells. Upon internalization, the antibodies appeared to be targeted to lysosomes and were cleared from within the cells in a time-dependent manner. CD11a-mediated internalization and lysosomal targeting of efalizumab may constitute one pathway by which this antibody is cleared in vivo.

Animals↗

Continuous infusion idarubicin and oral busulfan as conditioning for patients with acute myeloid leukemia aged over 60 years undergoing autologous stem cell transplantation.

There is growing interest in autologous stem cell transplantation (ASCT) for elderly patients with acute myeloid leukemia (AML). While mortality and toxicity from ASCT have been reduced, relapse rate is still high. In a prospective study, we investigated the feasibility of a new conditioning regimen consisting of high-dose idarubicin plus busulfan in AML patients aged over 60 years undergoing ASCT. A total of 14 patients (median age: 64 years) received 2 days continuous infusion of idarubicin at 20 mg/m2/day, followed by 3 days of oral busulfan (4 mg/kg/day) as conditioning. No case of transplant-related mortality occurred. The median number of days to neutrophil ( > 0.5 x 10(9)/l) and platelet ( > 20 x 10(9)/l) recovery was 11 and 12, respectively. Cardiac toxicity was absent, while 12 patients (86%) had grade 3-4 mucositis. After a median follow-up of 9 months from ASCT, nine of 14 patients are alive in continuous complete remission (CR), four have relapsed at 3, 6, 8 and 9 months, and one died in CR1 from gastric cancer. Our data demonstrate the feasibility of a conditioning regimen based on high-dose idarubicin plus busulfan in elderly AML patients. Results concerning reduction of relapse rate need confirmation in a larger series with longer follow-up.

Acute Disease↗

Rituximab: a useful drug for a repeatedly relapsed hairy cell leukemia patient.

We describe a case of complete response in a patient with hairy cell leukemia, relapsed after treatment with interferon-alpha, 2'-deoxycoformicin, and 2-chlorodeoxyadenosine, and then successfully treated with rituximab. A fourfold reduction of leukemic cells was observed concomitantly with restoration of normal blood count and differential.

Adult↗

Vincristine as treatment for recurrent episodes of thrombotic thrombocytopenic purpura.

The clinical course of thrombotic thrombocytopenic purpura has dramatically improved after the introduction of plasma-based therapy, including plasma exchange and plasma infusion. However, a considerable number of patients still experience relapse after initial successful treatment. In this study, vincristine (VCR) was given as salvage treatment in 12 episodes of recurrent thrombotic thrombocytopenic purpura in seven patients, concomitantly with short-term plasma infusion. Complete remission (CR) was defined by normal platelet, hemoglobin, and serum lactic dehydrogenase (LDH) values as well as by absence of clinical signs. Of 12 patients, 12 achieved CR following therapy with VCR. The median duration of CR was 15 months (range: 2-16). Toxicity was mild consisting of paresthesias in three cases, leukopenia in one case, and autonomic neuropathy leading to paralytic ileus in one case. We conclude that VCR is remarkably effective for recurrent thrombotic thrombocytopenic purpura with acceptable toxicity.

Adult↗

Preparation and biological activity of four epiprogoitrin myrosinase-derived products.

(5R)-5-Vinyl-1,3-oxazolidine-2-thione, (2S)-1-cyano-2-hydroxy-3-butene, and two diastereoisomeric erythro-(2S)- and threo-(2S)-1-cyano-2-hydroxy-3,4-epithiobutanes were prepared in pure form starting from (2S)-2-hydroxybut-3-enyl glucosinolate (epiprogoitrin). This glucosinolate was isolated in almost pure form using ripe seeds of Crambe abyssinica and then hydrolyzed under different conditions. The hydrolysis was carried out using either myrosinase immobilized on nylon, to produce (5R)-5-vinyl-1,3-oxazolidine-2-thione, or the endogenous myrosinase contained in defatted crambe meals, to produce the other epiprogoitrin-derived products. After purification and physicochemical characterization, all four myrosinase degradation products were tested for their biological activity. A bioassay on Lactuca sativa was chosen as a simple test to determine their apparent action on living tissues. (5R)-5-Vinyl-1,3-oxazolidine-2-thione negatively affected mainly root growth, whereas (2S)-1-cyano-2-hydroxy-3-butene affected the early phase of germination, and both (2S)-1-cyano-2-hydroxy-3,4-epithiobutane diastereoisomers appeared to negatively affect both germination and root growth at doses 5-10 times lower than those of (2S)-1-cyano-2-hydroxy-3-butene or (5R)-5-vinyl-1,3-oxazolidine-2-thione.

Brassicaceae↗

Soluble and total myrosinase activity in defatted Crambe abyssinica meal.

Crambe defatted meal contains 4-6% w/w of glucosinolates, with epiprogoitrin accounting for >90% of the total. This feature limits the use of the meal as feed due to the antinutritional properties of myrosinase-glucosinolate breakdown products. In this context, myrosinase activity assumes particular importance. In this study the total and soluble myrosinase activities have been evaluated directly on defatted meals of eight Crambe abyssinica varieties. The pH-stat method, which is the most suitable for assays in heterogeneous solid-water systems, was used. The total myrosinase activity in C. abyssinica varieties, determined using epiprogoitrin as substrate, ranged from 288 to 653 units g(-1). These activity values were up to 26 times higher than those obtained using other substrates, namely, sinigrin, glucosinalbin, glucotropaeolin, progoitrin, and glucoraphenin. Crambe myrosinase is unusual in that, unlike other Brassicaceae containing a typical main glucosinolate, it does not show the same specificity toward its natural substrates.

Animal Feed↗

High-dose idarubicin and busulphan as conditioning for autologous stem cell transplantation in acute myeloid leukemia: a feasibility study.

INTRODUCTION: Between 30 and 50% of patients with acute myeloid leukemia still relapse after autologous stem cell transplantation. We investigated the feasibility of a new conditioning regimen consisting of high dose IDA plus oral busulphan in patients undergoing autologous transplantation. MATERIALS AND METHODS: Patients (n = 13) were given three days continuous infusion IDA, followed by four days conventional dose oral busulphan as conditioning. Peripheral blood stem cells were used in all cases. Eleven patients were in CR1. Patients with t(8;21) and inv(16) as well as those with acute promyelocytic leukemia were excluded from the study. The median of CD34+ cells infused was 6.2 x 10(6)/l (2.6-16.1). RESULTS: No case of transplant-related mortality occurred. The median number of days to neutrophil (>0.5 x 10(9)/l) and platelet (>20 x 10(9)/l) recovery was 10 (7-21) and 20 (9-26), respectively. Patients needed a median of 3 platelet units (1-6) and 3 blood units (0-12), respectively. Left ventricular ejection fraction remained unmodified after ASCT. Twelve out of 13 patients (92%) had variable grade of mucositis (two grade 2, five grade 3 and five grade 4). Total parenteral nutrition was needed in nine patients (69%). After a median follow-up of 14 months from ASCT, 11 patients out of 13 (85%) are alive in continuous CR; the other two patients experienced relapse at 12 and 14 months. CONCLUSION: Our data demonstrate the feasibility of a conditioning regimen based on high-dose IDA plus Busulphan in AML. Results concerning antileukemic efficacy are promising, but need confirmation on larger series with longer follow-up.

Acute Disease↗

Aggressive salvage treatment is not appropriate for the majority of elderly patients with acute myeloid leukemia relapsed from first complete remission.

BACKGROUND AND OBJECTIVES: The prognosis of acute myeloid leukemia (AML) in the elderly is still poor because of different reasons, including a high incidence of relapse. The aim of this study was to investigate whether aggressive salvage chemotherapy (CHT) results in an actual survival advantage in elderly patients with relapsed AML, as well as to compare hospitalization and load of supportive treatment between patients receiving aggressive management or only palliation. DESIGN AND METHODS: One hundred and fifty consecutive patients with relapsed AML (median age 66 years) were analyzed. At relapse, 99 (66%) were treated with CHT, and 51 had palliative management. RESULTS: Second complete remission (CR2) was achieved in 36/99 patients (36%) receiving CHT, while no CR was observed in the other group (p<0.001). Induction death rate was 22%, while 41% were resistant to CHT. The median survival from relapse was 4 months for the whole patient population; according to management, it was 5 months and 3 months for CHT and palliation, respectively (p=0.01). As to patients given CHT, a CR1 duration of more than 12 months was the only parameter significantly related to a better clinical outcome (survival from relapse: 8 vs. 4 months, p=0.002; CR2 duration: 11 vs. 5 months, p=0.001, respectively). Finally, patients managed with palliation required less hospitalization and less supportive therapy as compared to the CHT group. INTERPRETATION AND CONCLUSIONS: Aggressive chemotherapy results in an actual survival advantage only for a minority of elderly patients with relapsed AML, i.e. those with CR1 lasting for more than 12 months.

Acute Disease↗

Hydrolysis of glucosinolates using nylon-immobilized myrosinase to produce pure bioactive molecules.

Bioactive compounds were produced from natural glucosinolates, secondary plant metabolites, using myrosinase (thioglucoside glucohydrolase EC 3.2.3.1) isolated from ripe seeds of Sinapis alba. The enzyme was immobilized on granular nylon 6.6 with the crosslinking technique. Immobilized myrosinase displayed extraordinary operational and storage stability. Using a small thermostatted continuous packed-bed bioreactor, the enzyme activity was unchanged after 15 days of continuous use at 37 degrees C and after >1 year of storage at room temperature. The bioreactor was particularly efficient in producing pure isothiocyanates, but it was less efficient for pure nitrile production.

Bioreactors↗

Isolation of the epithiospecifier protein from oil-rape (Brassica napus ssp. oleifera) seed and its characterization.

The epithiospecifier protein (ESP) is a myrosinase (MYR) cofactor, which is necessary to drive the MYR-catalyzed hydrolysis of some specific glucosinolates towards the production of cyanoepithioalkanes instead of isothiocyanates and nitriles. ESP was isolated from Brassica napus seeds by anionic exchange and gel filtration chromatography. ESP showed a molecular weight of about 39 kDa and pI 5.3. The amino acid sequence of several tryptic peptides of ESP (accounting for about 50% of the total sequence) made it possible to establish the high similarity (81% identity) with a hypothetical 37 kDa protein (TrEMBL data base accession number Q39104) and several jasmonate-inducible proteins from Arabidopsis thaliana. This observation suggests that ESP is likely to be involved in jasmonate-mediated defence and disease resistance mechanisms.

Amino Acid Sequence↗

In vitro antiproliferative activity of isothiocyanates and nitriles generated by myrosinase-mediated hydrolysis of glucosinolates from seeds of cruciferous vegetables.

A comparison of the effect of isothiocyanates and nitriles derived from some glucosinolates, namely, epi-progoitrin, sinalbin, glucotropaeolin, glucocheirolin, and glucoraphenin, on human erythroleukemic in vitro cultured cells was studied. Many studies have in fact evidenced that a consumption of vegetable containing glucosinolates could reduce the development of colorectal cancer. In the experimental conditions used, the production of isothiocyanates and nitriles from glucosinolates is almost quantitative as confirmed by HPLC or GC-MS analysis. The obtained results demonstrated that in general nitriles are considerably less potent than the corresponding isothiocyanates in inhibiting cancer cell growth. Particularly, the isothiocyanates inhibitory activity on K562 cells growth is higher in the case of products derived from epi-progoitrin, glucotropaeolin, glucoraphenin, and glucocheirolin; while for nitriles the higher activity in inhibiting K562 cells growth is showed by sinalbin-derived product. Considering the antiproliferative activity found for isothiocyanates and nitriles, further studies will be aimed to the possible application of glucosinolate-derived products as chemopreventive cancer agents for the reduction of colorectal cancer.

Brassicaceae↗

Characterization and natural history of ventricular septal defects in the fetus.

OBJECTIVE: To characterize and describe the evolution of ventricular septal defects (VSD) from intra-uterine diagnosis to infancy in a population of fetuses with isolated defects. METHODS: Sixty-eight fetuses with isolated VSD represented the study population. Of these, 28 underwent termination of pregnancy, 14 died in utero or after birth and 26 reached 1 year of age. In this population, the following variables were evaluated: presence of extracardiac or chromosomal anomalies, site and size of the defect, pregnancy outcome. These variables were assessed against closure of the VSD up to 1 year of age. Necropsies were available for all fetuses following termination of pregnancy. All surviving neonates were followed up directly or by telephone until documented echocardiographic closure of the defect or until 1 year of age. RESULTS: There was a significant correlation between type of VSD and type of aneuploidy (P < 0.001). A total of 26 surviving fetuses reached 1 year of age: 46.1% (n = 12) of all defects closed in utero, 23.1% (n = 6) closed during the first year of life and 30.8% (n = 8) remained patent. Only three (15.8%) of the 19 VSDs < 3 mm remained patent in comparison with five (71.4%) of the seven defects > 3 mm (P < 0.05). None of the malalignment VSDs closed, in comparison to 69% of the peri-membranous and 60% of the muscular defects. CONCLUSION: Ventricular septal defect can undergo spontaneous closure during intra-uterine life and this process depends upon the site and the size of the defect. These data may provide useful additional information to aid prenatal counseling.

Adult↗

Solar UV dose patterns in Italy.

Since 1992 solar ultraviolet (UV) spectral irradiance (290-325 nm) has been measured at two Italian stations of Rome (urban site) and Ispra (semirural site) using Brewer spectrophotometry. The data collected under all sky conditions, are compared with the output of a sophisticated radiative transfer model (System for Transfer of Atmospheric Radiation--STAR model). The STAR multiple scattering scheme is able to cope with all physical processes relevant to the UV transfer through the atmosphere. The experience so far acquired indicates that, in spite of the unavoidable uncertainties in the input parameters (ozone, aerosol, surface albedo, pressure, temperature, relative humidity, cloud cover), measured and computed clear sky iradiances are in reasonable agreement. The STAR model is applied to build up the solar UV geographic patterns in Italy: the daily dose in the range 290-325 nm is computed at about 70 sites where a thorough and homogeneous climatology is available. For each month the concept of an idealized "standard day" is introduced and the surface distribution of solar UV field determined. The map of solar UV patterns for Italy, available for the first time, meets the study requirements in the field of skin and eye epidemiology, as well as in other investigations dealing with the impact of UV on the biosphere. The results are interpreted in terms of atmospheric and meteorological parameters modulating UV radiation reaching the ground.

Eye↗

Formation of glucoraphanin by chemoselective oxidation of natural glucoerucin: a chemoenzymatic route to sulforaphane.

A new semi-synthetic way to produce glucoraphanin (2), the bio-precursor of the potential anticarcinogen sulforaphane (3), has been developed. Starting from glucoerucin (1), isolated from ripe seeds of Eruca sativa, glucoraphanin was obtained through chemoselective oxidation. Controlled myrosinase-catalysed hydrolysis of this precursor quantitatively afforded sulforaphane.

Catalysis↗

Complete remission of refractory anemia following a single high dose of cyclophosphamide.

We describe a case of stable complete remission in a patient with refractory anemia complicated by severe autoimmune hemolytic anemia, achieved with a single high dose (4 g/m2) of cyclophosphamide (cyclo). Concomitantly, an effective mobilization of CD34-positive cells was induced. Other immunosuppressive approaches including high-dose methylprednisolone, high-dose immunoglobulin, and cyclosporine had been ineffective. This finding suggests that, in selected cases, an immunologic mechanism may mediate cytopenia in myelodysplastic syndromes (MDS). In addition, it demonstrates that successful mobilization of peripheral blood stem cells can be induced with high-dose cyclo in MDS.

Adult↗

Vincristine as salvage treatment for refractory thrombotic thrombocytopenic purpura.

Vincristine (1.4 mg/m(2) on day 1, followed by 1 mg on days 4 and 7) was given to eight patients with thrombotic thrombocytopenic purpura (TTP) who were refractory to plasma exchange (n=4) or plasma infusion (n=4). Seven of eight patients (87%) achieved a complete response; one was refractory to treatment and died within a few weeks. After a median follow-up of 50 months, all responding patients are alive and well. Two patients relapsed and were successfully retreated with vincristine. Toxicity was mild, consisting of two episodes of leukopenia and one of autonomic neuropathy leading to paralytic ileus in a patient aged 70 years. We conclude that vincristine is highly effective in the treatment of patients suffering from refractory TTP, with negligible toxicity.

Adult↗