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S Sacchi

Publications and source records attributed to S Sacchi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Studies on a new series of THA analogues: effects of the aromatic residues that line the gorge of AChE.

A series of N-monoalkylsubstituted 1,2,3,4-tetrahydro-9-aminoacridines have been prepared after modelling simulation of the AChE-inhibitor complex. Molecular modelling has predicted a number of hydrophobic residues to be involved in the catalytic mechanism of this interaction between the binding sites of AChE and this series of aminoacridines. In these compounds the acridine moiety becomes sandwiched between the rings of PHE330 and TRP84. In particular, the alkyl chain shows the important role of aromatic groups as binding sites. Their in vitro inhibitory properties (enzyme from Electrophorus electricus) confirm the aromatic groups as a general and significant characteristic of the mechanism of AChE inhibition.

Acetylcholinesterase↗
PubMed1997

Long-term follow-up results of alpha-interferon-based regimens in patients with late chronic phase chronic myelogenous leukemia.

The aim of this analysis was to evaluate the efficacy of alpha-interferon (alpha-IFN) regimens in late chronic phase (diagnosis >12 months) chronic myelogenous leukemia (CP-CML). Long-term follow-up results were evaluated in 137 patients with Philadelphia chromosome (Ph)-positive late CP-CML. The alpha-IFN programs were sequential studies with human leukocyte alpha-IFN (seven patients), recombinant alpha-IFN alone (15 patients) or with IFN-gamma (29 patients), hydroxyurea (HU) (19 patients), or low-dose cytarabine (Ara-C) (67 patients). Overall, 57% of the patients achieved complete hematological response (CHR), and 7% obtained partial hematological response. Nineteen patients (15% of the 123 evaluable patients) had a cytogenetic response which was major (Ph-positive <35%) in 10 patients (8%). A trend for better responses was observed with shorter disease duration. The median overall survival from start of therapy was 49 months, with an estimated 5-year survival rate of 41%. Some common pretreatment prognostic factors associated with response did not show statistical associations when applied in late CP-CML; however, characteristics such as smaller spleen size, and lower percentages of peripheral blood and marrow blasts and basophils were associated with better survival experience. When patients were subgrouped according to risk, no significant differences in the incidence of cytogenetic response and in survival outcomes were observed among various risk groups. This study confirms that alpha-IFN-based regimens have a modest activity in late CP-CML, and supports the need to develop investigational strategies aimed at improving patient prognosis in this phase.

Adolescent↗
PubMed1996

Age-related and vasomotor stimuli-induced changes in renal vascular resistance detected by Doppler ultrasound.

Indirect measurement of renal vascular resistance by duplex Doppler waveform analysis was evaluated in relation to aging and some pathophysiological conditions. Baseline renal resistive index (RRI) (peak systolic frequency shift - lowest diastolic frequency shift/peak systolic frequency shift) was measured in healthy controls aged 20 to 85 years by analyzing the blood flow velocity waveform of interlobar arteries. RRI changes induced by sympathetic activation (cold pressor test and handgrip test) or by fluid load were evaluated. Both repeatability and reproducibility were very good, as the intra and interoperator variations were all less than their reproducibility coefficients. RRI showed a significant increase with aging (ANOVA P < .001), particularly evident in subjects older than 50 years. Both the cold pressor test and handgrip test induced in all the subjects (n = 16) a significant increase in RRI (P < .001), from 0.59 +/- 0.04 to 0.69 +/- 0.04 (12 +/- 6%) for the cold pressor test and from 0.57 +/- 0.03 to 0.66 +/- 0.03 (15 +/- 2%) for the handgrip test. In eight subjects intravenous fluid load (0.25 mL/kg/min of 0.9% NaCl for 120 min) caused a significant decrease in RRI (P < .001), from 0.62 +/- 0.02 to 0.53 +/- 0.01 (17 +/- 2%), which was inversely related to mean blood pressure rise (r = 0.71, P < .001). These data show that pulsed wave Doppler analysis is an accurate method for an indirect evaluation of changes in renal vascular resistance induced by common vasomotor stimuli.

Adult↗
PubMed1996

In vivo biological response following low-dose interleukin-2 in complete remission B-cell non-Hodgkin's lymphoma patients. Italian Lymphoma Study Group (GISL).

The aim of the present study is to verify whether recombinant interleukin-2 (rIL-2) at low doses is well tolerated in aggressive lymphoma in complete remission (CR), and if there may be a biological justification for its use as a remission-maintenance therapy able to reduce the percentage of relapses. We treated 6 patients with B-cell non-Hodgkin's lymphoma (B-NHL) in CR following PM-Cytabom with rIL-2 3 IMU s.c. x 5 d per wk, every other wk for 8 wk. Our results show that this treatment provokes statistically significant changes in the absolute number of lymphocytes, eosinophils, CD25+ and CD122+ cells and soluble IL-2 receptors; these doses, however, are not sufficient to modify CD3+, CD16+ and CD56+ cell values or natural killer and lymphokine activated killer cell activity. Thus these findings do not appear to constitute a biological rationale for the use of rIL-2 at this dose and schedule as a remission-maintenance therapy in B-cell NHL. Nevertheless, the results are a valid basis for further study of the use of the same rIL-2 doses for a longer period of time in combination with other cytokines, in the hope that the biological effects can be augmented without increasing the toxic side effects.

Cytokines↗
PubMed1995

Detection of PML-RAR alpha fusion transcript in Ph positive leukemia with acute promyelocytic phenotype lacking the t(15;17) cytogenetic abnormality.

A 39-year-old woman was diagnosed with acute promyelocytic leukemia (APL) with disseminated intravascular coagulation syndrome. The hematologic examination showed a morphologic, cytochemical, and immunophenotypic picture typical of an APL, with a marked leukocytosis and a mixed population of hypergranular and microgranular promyelocytes. The cytogenetic analysis showed a 46,XX,t(9;22) karyotype, without any alterations of chromosomes 15 and 17. The t(15;17) translocation was not evident in FISH experiments, while a molecular analysis revealed the presence of a PML-RAR alpha chimera.

Adult↗
PubMed1995

Uraemic pruritus is not related to plasma histamine concentrations.

Pruritus is a common symptom in uraemic patients and its aetiology is poorly understood, although several factors have been implicated, including high histamine plasma levels. The aim of the study was to evaluate plasma levels of histamine in patients on maintenance haemodialysis in relation to the presence of itching (35 pruritic patients = group A; 50 non-pruritic patients = group B). Furthermore, we compared the values obtained with those of a healthy control group (64 subjects). We observed increased plasma histamine levels in uraemic patients compared with healthy controls. However, no relationship was found between plasma histamine values and itching because groups A and B showed overlapping values and there was no correlation between the intensity of pruritus and plasma histamine concentrations in group A patients. In conclusion, we suggest that there is no evidence for plasma histamine playing a significant part in uraemic pruritus.

Adolescent↗
PubMed1995

Immune-mediated and unusual complications during interferon alfa therapy in chronic myelogenous leukemia.

PURPOSE: Long-term treatment with interferon alfa (IFN alpha) can produce or exacerbate immune-mediated complications (IMC). The purpose of this study was to analyze the experience with IMC and unusual complications in patients with chronic myelogenous leukemia (CML) undergoing IFN alpha treatment. PATIENTS AND METHODS: The occurrence of IMC and unusual complications was evaluated in patients with Philadelphia chromosome (Ph)-positive CML. RESULTS: Well-documented and clinically evident complications developed in 35 patients after a median of 14 months of IFN alpha treatment. These included 28 (5%) of 581 patients with Ph-positive CML treated with IFN alpha-containing regimens at M.D. Anderson Cancer Center (MDACC) and seven patients referred for opinion or problems who were on other studies. Hypothyroidism occurred in 11 patients (2%), immune-mediated hemolysis in seven (1%), and connective tissue diseases in 11 (2%). Other unusual occurrences included congestive heart failure (CHF; n = 4), porphyria cutanea tarda (PCT; n = 3), membranous glomerulonephritis (MGN; n = 1), and vitiligo (n = 1). IFN treatment was discontinued in 19 patients and the dose was reduced in five. Ten of 11 patients (91%) with immune-mediated hypothyroidism and eight of 11 (73%) with connective tissue diseases had some degree of cytogenetic response at the time of the event. CONCLUSION: Although the frequency of IMC is low, patients treated with IFN alpha should be monitored for signs and symptoms of autoimmunity.

Adolescent↗
PubMed1995

P-glycoprotein expression in acute myeloblastic leukemia analyzed by immunocytochemistry and flow cytometry.

Using the APAAP technique, we assessed the reactivity of five monoclonal antibodies, JSB1, C219, Mab 57, 2F8 and MRK16, to gp 170 in 60 cases of de novo acute myeloid leukemia (AML) and 13 relapses. Reactivity, varied between the five antibodies, and positivity was obtained with 2F8 > JSB1 > MRK16 > Mab57 > C219. Sixteen of the 60 cases were also studied by flow cytometry. In 10 cases, the results with the two techniques corresponded, in the other 6 cases, flow cytometry proved more sensitive than APAAP in detecting small amounts of gp170. In the flow cytometry analysis, the cells fixed in methanol and paraformaldehyde were more fluorescent than unfixed samples or those fixed in paraformaldehyde or methanol alone. Our results thus reveal that positivity for gp 170 depends on various factors, including the specificity of the monoclonal antibodies, the techniques used and the preservation of the samples. This suggests the need for a clear standardization of the methods to detect gp170.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

The role of alpha-interferon in essential thrombocythaemia, polycythaemia vera and myelofibrosis with myeloid metaplasia (MMM): a concise update.

Treatment of essential thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis with myeloid metaplasia (MMM) patients is frequently a difficult issue. To date, there is no generally accepted treatment for these diseases which can reduce the risk of thromboembolism and/or haemorrhagic events, avoid any increase in the frequency of secondary myelofibrosis and terminal blast transformation and decrease the reticulin content in the bone marrow of MMM patients. The most frequently used myelosuppressive agent is hydroxyurea (HU), but widespread application has failed to demonstrate that is not leukaemogenic. In patients with MMM, conflicting results have been obtained following alpha-IFN treatment. Haematological responses have been seen in 50% of the patients. Usually the patients showing good responses had a hyperproliferative type of disease. In only one case was a reduction of reticulin content of the bone marrow observed. Thus, these findings do not indicate alpha-IFN as a first-line therapy. On the other hand, the results of several reports in ET and PV patients have shown a reduction in the abnormal proliferation of megakaryocytes and erythroid elements, following alpha-IFN treatment. A reduction in spleen size has also frequently been seen. Together with the improvement of haematological parameters, clinical symptoms have also responded positively. Long term control of these diseases can be obtained with a well-tolerated low dose of alpha-IFN. However, PV and ET are not usually characterized by cytogenetic abnormalities, making it very difficult to demonstrate the disappearance of clonal haemopoiesis following alpha-IFN therapy, even if this does occasionally occur, as evident from the two cytogenetic convertions described in the literature. As compared to myelosuppressive drugs or phlebotomy, alpha-IFN thus represents an attractive new treatment, able to exert a fundamental influence on these diseases, presumably without any untoward leukaemogenic or gonadotoxic activity.

Humans↗
PubMed1994

A prospective comparison between treatment with phlebotomy alone and with interferon-alpha in patients with polycythemia vera.

Interferon alpha (alpha-IFN) is increasingly used for the treatment of patients affected by polycythemia vera (PV). As prior studies are difficult to interpret in view of the lack of appropriate controls, we undertook a randomized comparison of lymphoblastoid alpha-IFN (alpha n-1 IFN) treatment against venesection treatment alone. In a crossover trial, we treated 22 PV patients alternatively for 5 months each with 3 MU/day sc of alpha n-1 IFN and phlebotomy alone. During IFN treatment, red blood cell count and hematocrit level were well controlled in both trial groups, reducing or eliminating the need for phlebotomy in all patients; furthermore, platelet number and white blood cell count declined during alpha-IFN therapy. In addition, the number of symptomatic patients was greatly reduced, and in six patients a reduction in splenic size was observed. Finally, the only patient with chromosomal abnormalities showed a complete cytogenetic conversion after 5 months of alpha-IFN therapy. Thus, for the first time, our results provide the unequivocal demonstration that alpha-IFN is superior to phlebotomy in controlling the pathologic expansion of erythroid elements and all the clinical aspects of this disease.

Adult↗
PubMed1994

Cytogenetic conversion in a case of polycythaemia vera treated with interferon-alpha.

Polycythaemia vera is a clonal disorder of the haemopoietic stem cell causing a pathologic expansion of the erythroid and sometimes the megakaryocytic and myeloid elements. In order to avoid the possible mutagenic effects of radioactive phosphorus, alkylating agents and hydroxyurea, since 1988 alpha-IFN has been used for the treatment of PV and has been shown to induce and maintain haematological remission. We describe a 24-year-old PV patient with chromosomal abnormalities who achieved not only a reduction of the proliferation of erythroid elements and reticulin content in the bone marrow, but also a complete cytogenetic remission after IFN treatment.

Adult↗
PubMed1993

Sustained complete hematological remission in essential thrombocythemia after discontinuation of long-term alpha-IFN treatment.

In essential thrombocythemia patients alpha-IFN rapidly reduces platelet count, and it is also able to maintain a low count during long-term treatment. In order to verify if long-term IFN treatment can produce sustained remission in selected patients, we decided to suspend IFN treatment in two subsets of 21 patients on long-term alpha-IFN treatment: (a) all six patients who had shown a platelet count below 450 x 10(9)/l for at least 2 months with 3 MU once a week; (b) three patients who had shown the same platelet count for at least 2 months with 3 MU three times a week. After withdrawal of alpha-IFN treatment, a rapid increase in the platelet count was observed in all three patients requiring 3 MU three times a week. Three of the six patients treated with 3 MU once a week are still free of symptoms and have been in complete hematological remission (platelet count below 450 x 10(9)/l) for 9+, 13+, and 14+ months, respectively. As far as the three remaining cases are concerned, one was not assessable because of loss to follow-up, while the other two relapsed after 1 and 2 months. We believe that the three cases of sustained remission might be the result of a long-term tumor load reduction produced by the alpha-IFN treatment. Finally, the factor best able to predict sustained, unmaintained remission seems to be the clinical response to a low dose of alpha-IFN during the maintenance phase, rather than disease features prior to treatment.

Humans↗
PubMed1993

Progression of essential thrombocythemia to blastic crisis via idiopathic myelofibrosis.

We report a 61-year-old man with essential thrombocythemia (ET) whose clinical course was followed for 12 years. The ET evolved into true idiopathic myelofibrosis (IM) 6 years after the initial diagnosis and progressed to myeloid blastic transformation 6 years later. The cytogenetic analysis showed a normal karyotype during the ET phase but subsequent analysis revealed an abnormal karyotype during the IM phase which evolved clonally at blastic crisis with constant involvement of chromosome 13q and chromosome 7. The close monitoring of essential events, using clinical, morphologic, immunologic and cytogenetic parameters, allowed us to carefully identify the transition from one chronic myeloproliferative disease (MPD) to another. This is only the second case reported showing a clinical evolution of this nature. The clinical and biological aspects of the disease are briefly discussed.

Blast Crisis↗
PubMed1992

Sinus histiocytosis with massive lymphadenopathy.

To date, the morphological aspects of sinus histiocytosis with massive lymphadenopathy (SHML) have been fully described. The disease is characterized by an enlargement of lymph nodes in which the sinuses are dilated and infiltrated by histiocytes, often phagocytosing lymphocytes. Even if the prognosis is usually benign and not requiring therapy, several fatal cases have been reported. The etiology is still obscure and the biology is not yet completely clear. Recent immunophenotypical studies suggest that histiocytes may belong to the T-zone associated histiocyte lineage. They may be cytologically homogeneous, but can express different antigenic patterns according to their stage of differentiation. Cytogenetic and molecular aspects of the disease have only been sporadically investigated. In order to better understand the pathogenesis of SHML, which seems to be a disorder lying in between the fields of infections, immunological disease and neoplasia, it is considered very useful to systematically employ a variety of immunophenotypical, cytogenetic and molecular techniques to study the disease, particularly in cases which are clinically atypical or with a more aggressive evolution.

Antigens, CD↗
PubMed1991

Prevalence of dermatophytes and yeasts (Candida spp., Malassezia furfur) in HIV patients. A study of former drug addicts.

The prevalence of dermatophytes and yeasts (Candida spp. and Pityrosporum spp.) was studied in 40 former drug-addicts, all of whom were HIV seropositive but otherwise had no other symptoms (2nd Stage CDC Atlanta, 1987). We considered 7 skin areas for dermatophytes and Pityrosporum spp. (scalp, forehead, nose, back, chest, groin, toe webs) and the mouth for yeasts. Dermatophytes were found in 8 (20%) and tinea pedis was the most common dermatophytosis: Tricophyton rubrum was the fungus most frequently isolated (6 cases or 15%). The HIV+ group showed almost the same rate of dermatophytes colonisation compared to a group of 121 athletes and to the control group. Candida spp. was present in 27 cases (67.5%) but clinical oral lesions were evident only in 5 patients (12.5%). Statistically significant differences were found in the presence of Candida spp. in HIV patients and controls (p less than 0.05). The lipophilic yeast Pityrosporum ovale was evaluated with quantitative and qualitative methods. Quantitative variations were evident between HIV patients and controls. P. ovale was present in 10 cases: 3 (7.5%) of them showed dischromic lesions while in 7 cases (17.5%) no clinical symptoms were evident.

Adult↗
PubMed1991

Interferon alpha-2b in the long-term treatment of essential thrombocythemia.

We treated 35 patients affected with essential thrombocythemia (ET) with interferon (IFN) alpha-2b. Our treatment scheme consisted of (a) a 6-month induction phase and (b) a continuous maintenance phase. During the induction phase, our results showed that using 21 million units (mu) of IFN weekly platelet counts fell below 600 x 10(9)/1 in about 90% of patients. These data demonstrate that well-tolerated doses of IFN can rapidly correct excessive thrombocytosis. During the continuous maintenance phase, 61% of patients required 3 mu three times a week, 15% once a week, and 24% daily. Thus the minimal IFN doses able to maintain platelet count below 600 x 10(9)/l varied between 3 and 21 mu per week. During long-term treatment, subjective side effects were tolerable, especially using 3 mu three times a week. We conclude that IFN alpha-2b is an effective drug in the long-term treatment of ET.

Adult↗