Search PubMed⌕ Search

Biomedical subjects

G Marotta

Publications and source records attributed to G Marotta.

At least 37 records · Page 2Linked to original sources

Favorable impact of low-dose fludarabine plus epirubicin and cyclophosphamide regimen (FLEC) as treatment for low-grade non-Hodgkin's lymphomas.

BACKGROUND AND OBJECTIVE: In recent years, conventional dose of fludarabine (FLU) alone or in combination with other drugs has been reported to be effective in the treatment of low-grade non-Hodgkin's lymphomas (LG-NHL). In particular, FLU and cyclophosphamide (CY) or FLU and mitoxantrone or idarubicin combined regimens have shown considerable therapeutic activity both as first line and salvage therapies, producing overall response rates ranging from 40-50% in previously treated patients and up to 70-90% in untreated ones. However severe neutropenia and infective complications have been reported in a significant number of patients. Based on these premises we evaluated the efficacy and toxicity of a new regimen combining low-doses of FLU with epirubicin (EPI) and CY (FLEC) in a group of advanced treatment-requiring LG-NHL patients. The aim of this study was to evaluate a strategy aimed at lowering therapy-related toxic effects without affecting the reported good response rate. DESIGN AND METHODS: Thirty patients with de novo, relapsed or refractory LG-NHL entered the study. FLEC regimen was as follows: EPI 60 mg/m(2) i.v. on day one, plus FLU 15 mg/m(2)/day i.v. (max 25 mg) and CY 250 mg/m(2)/day i.v. for four days. RESULTS: All 30 patients were evaluable for response, 13 (43%) fulfilled the criteria for CR and 11 (36%) for PR with an overall response rate of 79%. None of the 13 patients who achieved CR had relapsed after a follow-up of 2 to 23 months (median duration 13 months). With regard to age, 13/14 older patients (>/= 70 years) responded to the treatment and 9 of them maintained their response after a median of 13 months (range 2-22); six of the 14 (43%) obtained a CR. Therapy-related toxicity was mild regardless of age, neutropenia (43%) and fever of undetermined origin (26%) being the major side effects. Remarkably, a documented infection was recorded only in 2/30 (6%) patients. INTERPRETATION AND CONCLUSIONS: A low-dose FLU-based FLEC regimen appeared to be effective for advanced treatment-requiring LG-NHL, reproducing a similar overall response rate (79%) reported to have been achieved with other FLU based combination therapies. Toxic side effects were negligible and in particular documented infections were remarkably uncommon even in the group of elderly patients.

Adult↗

Post-prandial effects of gemfibrozil vs simvastatin in hypercholesterolemic subjects with borderline hypertriglyceridemia.

BACKGROUND AND AIM: Impaired triglyceride-rich lipoprotein metabolism is most probably related to an enhanced cardiovascular risk, and may be associated with a pro-coagulant state. A double-blind, randomized study was undertaken to evaluate two widely utilized hypolipidemic drugs in the post-prandial phase and their impact on lipid, coagulation and fibrinolytic parameters. METHODS AND RESULTS: Thirty middle-aged men selected according to their low density lipoprotein-cholesterol (LDL-C) > or = 160 and < or = 240 mg/dl and borderline hypertriglyceridemia (110-220 mg/dl) after at least one month of a lipid-lowering diet received gemfibrozil (600 mg bid) or simvastatin (20 mg qd) and the corresponding placebo. On enrollment and after 2 months of drug treatment, they were tested with a standard oral fat load (OFL) (35 g fat/m2 body surface). On both occasions plasma total-cholesterol, LDL-C, HDL-C, triglycerides, lipoprotein[a] (Lp[a]), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), antithrombin-III (AT-III), plasminogen and fibrinogen were determined just before the meal (t0) and at times 2 hours, 4 h, 6 h, 8 h after it (t2-t8). A two-factor (time and visit) multivariate analysis for repeated measurements was performed to evaluate the data. Total cholesterol, and LDL-C were significantly diminished 2 months after both gemfibrozil and simvastatin, the latter being more active. Plasma triglycerides showed a marked reduction with gemfibrozil at all times, while simvastatin regimen yielded only minor modifications. HDL-C was only slightly increased by simvastatin; Lp[a] plasma levels were almost unaffected. Small fibrinogen (t0, t2, t6, t8), PAI-1 (t6) and AT III (t0-t8) increases were observed after gemfibrozil, while simvastatin did not significantly modify these parameters. CONCLUSIONS: In the post-prandial phase, gemfibrozil and simvastatin induce different metabolic effects that beneficially influence the lipid pattern, whereas fibrinolytic and coagulative parameters display minor variations of undetermined significance.

Adult↗

Minimally invasive surgery for Zenker diverticulum: analysis of results in 95 consecutive patients.

OBJECTIVE: To assess the effectiveness of transoral stapled diverticulum esophagostomy in relieving symptoms and decreasing outflow resistance at the pharyngoesophageal junction in patients with Zenker diverticulum. DESIGN: Cohort study. From April 1, 1992, until May 31, 1996, the operation was attempted in 95 patients. The median follow-up was 23 months (range, 13-48 months). SETTING: Tertiary care university hospital. PATIENTS: There were 74 men and 21 women, with a median age of 64 years (age range, 37-92 years). All complained of dysphagia and pharyngo-oral regurgitation, and 18 (20%) suffered from recurrent aspiration pneumonia. The median size of the pouch measured by flexible endoscopy was 4 cm (range, 2.5-8 cm). INTERVENTION: The septum between the diverticulum and the esophageal lumen was divided under general anesthesia using a linear endostapler introduced through a Weerda endoscope. In most patients, 2 applications of the endostapler with a modified anvil were used. Operative time averaged 23 minutes. MAIN OUTCOME MEASURES: Morbidity, symptom score, patient's satisfaction, videofluorographic barium transit, hypopharyngeal intrabolus pressure, upper esophageal clearance of radioisotope. RESULTS: A switch to open surgery was required in 3 patients (3.1%), due to difficult exposure of the common wall in 2 cases and a mucosal tear in the other. No postoperative morbidity or mortality was recorded. Oral feeding was started the following day and the median hospital stay was 3 days (range, 2-8 days). Five patients complained of persistent symptoms; 3 of them underwent another endosurgical operation, 1 underwent laser treatment by means of flexible endoscopy, and 1 eventually required open surgery. All patients are asymptomatic at the latest follow-up visit. Postoperative radiologic studies showed free flow of barium in all patients. Manometry showed a significant reduction of hypopharyngeal intrabolus pressure over preoperative values (P=.003). Radionuclide studies showed a significant reduction of upper esophageal residual activity at 1 minute compared with preoperative values (P=.006). CONCLUSIONS: Endosurgical approach to hypopharyngeal diverticula larger than 2 cm is safe and effective. Symptom relief, elimination of the pouch, and decreased outflow resistance at the pharyngoesophageal junction can be obtained without morbidity and with a short hospital stay.

Adult↗

CD4+/CD45RA+ 'naive' T cells and immunological response to influenza virus vaccine in B-cell chronic lymphocytic leukaemia patients.

B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by a high frequency of infections, including those of viral aetiology. Previous reports have demonstrated a specific immunologic response to influenza virus vaccine in B-CLL patients with normal IgG levels. In this study, we have evaluated different immunophenotypically defined B and T cell subsets in 18 B-CLL patients before immunization with killed-influenza-virus vaccine. A correlation between immunological response to vaccination and both absolute numbers of CD4+/CD45RA+ naive T cells and CD5- B cells was found. These data may suggest a supporting role of the CD4+/CD45RA+ T cell subset in the specific antibody response to vaccination with influenza virus vaccine in B-CLL patients.

Adult↗

Long-term follow-up of non-Hodgkin's lymphoma patients treated with ProMACE-CytaBOM: an effective regimen for the intermediate grade subtype.

Long-lasting results achieved in 54 patients with aggressive non-Hodgkin lymphoma treated with Pro-MACE-CytaBOM regimen were evaluated. Twenty-four out of 54 (45%) patients achieved a complete remission and 13 of them are still in continuous remission with a median survival of 53.5 months. Interestingly, in 16 patients with intermediate grade histology we obtained an overall response rate of 100%.

Adult↗

Long-lasting complete remission in patients with hairy cell leukemia treated with 2-CdA: a 5-year survey.

Between January 1991 and January 1994, 40 patients with hairy-cell leukemia (HCL), 30 males and 10 females, with a median age of 54 years, were treated with a single course of 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg/day continuous infusion for 7 days. Thirteen patients were untreated and 27 had previously received alpha-interferon. Thirty out of 40 patients (75%) achieved complete remission (CR) and 10 (25%) partial remission (PR). The median follow-up duration for patients in CR has been 48 months (range 30-66). Five of the complete responders (17%) relapsed at 12, 24, 26, 30 and 36 months after treatment as documented by the increase of hairy cells (Hc) in the bone marrow and two of them, who were retreated with 2-CdA after showing an initial impairment of peripheral blood values, obtained a second CR. The remaining three relapsed patients were never retreated and still show normal peripheral counts after 30, 38 and 40 months. Twelve of the continuous complete responder patients are still in CR after more than 5 years. In contrast, 8 out of 10 partial responders progressed after 8-36 months and all of them were retreated with 2-CdA at a dose of 0.15 mg/kg/day for 5 days i.v. Four of them (50%) achieved a CR, three a better PR and one patient died 6 months after the second 2-CdA course because of infectious complications. Two additional patients, both in CR, died after 28 and 37 months because of a second neoplasm. Toxic side-effects consisted of febrile episodes recorded in 16 patients: in seven of them, fever lasted only 24-48 h after the end of treatment and was apparently not infection-related. In the remaining nine patients, showing in addition severe neutropenia (neutrophils less than 1.0 x 10(9)/l), fever was related to bacterial infection requiring systemic antibiotics in all of them and G-CSF in three cases. In conclusion, 2-CdA induces a very high proportion of complete and long-lasting remissions in patients with HCL. In a number of cases relapse at bone marrow level may not affect peripheral blood values for prolonged time. However, in those patients with initial pancytopenia a retreatment with 2-CdA is still effective in inducing a durable second CR.

2-Chloroadenosine↗

Reduction of antithrombin III, protein C, and protein S levels and activated protein C resistance in polycythemia vera and essential thrombocythemia patients with thrombosis.

Patients with polycythemia vera (PV) or essential thrombocythemia (ET) show a high frequency of thrombosis. The reduction of hematocrit after phlebotomy and normalization of platelet counts do not completely eliminate thrombotic risk. Some preliminary studies reported a reduction in the concentration of natural anticoagulants (NA) in this group of patients. For this reason we evaluated protein S (PS) total antigen, antithrombin III (AT III), and protein C (PC) activity in 81 patients with chronic myeloproliferative disorders (33 with PV and 48 with ET). Data were compared with those obtained in 70 healthy sex- and age-matched subjects. Fifty-seven percent of patients (46 out of 81) showed one or more thrombotic episodes at diagnosis or during follow-up. Interestingly, we found a NA deficit in 43.5% of patients with thrombosis versus only 5.7% in the group of patients without thrombosis. These results may suggest new interpretations about the pathogenesis of thrombosis in PV or ET patients.

Adult↗

Differential attachment of human neoplastic B cells to purified extracellular matrix molecules.

Recirculation of normal and neoplastic lymphocytes occurs via binding to the endothelial luminar surface, followed by extravasation and the subsequent interaction of the cells with components of the underlying basement membrane and stromal extracellular matrix (ECM). To identify matrix constituents that could be involved in the tissue dissemination of neoplastic B cells, we have examined the ability of three lymphoma B-cell lines and one Philadelphia chromosome (Ph1)-positive cell line established from the lymphoid transformation of a chronic myeloid leukemia (CML) to adhere to a range of purified ECM molecules. Immunophenotyping with a panel of markers suggested that the lines derived from cells that had undergone transformation at distinct stages of B-cell maturation. The four cell lines displayed a differential ability to adhere to the ECM molecules tested. BV-173, Ci-1, and Sc-1 cells attached to various degrees to fibronectin (FN). Ri-1, Ci-1, and Sc-1 cells attached to human laminin (LN) variants, whereas only Ci-1 and Sc-1 cells showed some affinity for collagen (Col) type VI. All four cell lines interacted with fibrillar Col I, but only BV-173 and Ri-1 cells attached to fibrillar Col III. The subendothelial Col VIII only was active as a substratum for BV-173 cells. In all cases, cells bound to fibrillar collagens when they were assembled into polymeric fibrils, and were incapable of adhering to monomeric and denatured collagen. In contrast to cell adhesion to FN and LN, which showed a plateau at high substrate concentrations, adhesion to fibrillar Col I reached a peak at intermediary concentrations and decreased thereafter, suggesting that cells respond to a definite macromolecular arrangement of collagenous fibrils. Adhesion to individual ECM molecules was not directly correlated with the apparent maturation state of the cells, nor with the relative density of known ECM receptors. Taken together, these results suggest that interaction of neoplastic B cells with selected matrix components may influence their dispersion throughout tissues. We further suggest that the use of quantitative cell adhesion assays in vitro may provide means of defining the behavioral traits of neoplastic B cells in vivo.

Burkitt Lymphoma↗

Long term metabolic effects of two dietary methods of treating hyperlipidaemia.

OBJECTIVES: To compare the long term metabolic effects of two diets for treating hyperlipidaemia. DESIGN: Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months. SETTING: Lipid clinic of tertiary referral centre in Naples. SUBJECTS: 63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30. INTERVENTIONS: Two test diets with reduced saturated fat (8%) and cholesterol (approximately 200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats. MAIN OUTCOME MEASURES: Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal. RESULTS: In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/l, P < 0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P < 0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P < 0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P < 0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet. CONCLUSIONS: Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.

Cholesterol↗

A comparison of antioxidant status and free radical peroxidation of plasma lipoproteins in healthy young persons from Naples and Bristol.

Ischaemic heart disease mortality is much lower in Southern Italy than in the U.K. and this is not entirely explained by differences in classical risk factors. Differences in antioxidant intake, affecting free radical peroxidation of plasma lipoproteins, may be relevant. Therefore, dietary intake, antioxidant status and plasma lipid peroxidation were compared in healthy young persons eating typical regional diets from Naples (22) and Bristol (26). The Naples group consumed more fresh tomatoes, more fat as monounsaturates (from olive oil) and had higher plasma levels of the lipid antioxidants vitamin E (mean (SD; 95% CI) 29.1 (4.5; 26.8 to 31.3) vs 25.1 (3.86; 23.4 to 26.8) mumol.l-1, P = 0.005) and beta-carotene (4.74 (1.2; 4.14 to 5.34) vs 2.85 (0.8; 2.5 to 3.2) mumol.l-1, P < 0.001). Intakes of vitamin C, total uncooked fruit and vegetables, plasma vitamin A, serum selenium and copper levels were similar. All indices of plasma lipid peroxidation were significantly lower in the Naples group: conjugated dienes (median (interquartile range; non-parametric 95% CI)) 29 (21.5-39.9; 24 to 36.7) vs 41.5 (37-48.5; 38 to 44.5) mumol.l-1, P < 0.001; diene conjugation index 1.38 (1.02-1.55; 1.06 to 1.49) x 10(-2) vs 1.57 (1.43-1.74; 1.44 to 1.71) x 10(-2), P = 0.019; lipid peroxides (geometric mean (95% CI) 1.24 (1.12 to 1.37) vs 4.58 (3.84 to 5.46) mumol.l-1, P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunological abnormalities in patients with chronic fatigue syndrome.

Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation. One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4-55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months-10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression. The fatigue was so severe that it required 102 patients to stop their working activities for a period of time ranging from 3 months to 2 years (range 7 months). In 40 consecutive patients a comprehensive immunologic testing by single and two-colour flow cytometry was performed and results compared with a group of 35 healthy, age- and sex-matched controls. Whilst no significant differences were found in the absolute numbers of circulating total T cells (CD3+) and of total helper/inducer (CD4+) or suppressor/cytotoxic (CD8+) T cells, an evident reduction in CD3-/CD16+ and CD57+/CD56+ NK lymphocytes along with an expansion of the CD8+/CD56+ and CD16-/CD56+ NK subsets, were found in the CFS group. In addition, CD56+ NK cells from CFS subjects were found to express an increased amount of cell adhesion molecules (CD11b, CD11c, CD54) and activation antigens (CD38). Both the percentage and absolute numbers of CD4+ T cells bearing the CD45RA antigen appeared significantly reduced in CFS patients, and CD4+ T lymphocytes from CFS subjects displayed an increased expression of the intercellular adhesion molecule-1 (ICAM-1/CD54). Finally, the total numbers of circulating (CD19+) B lymphocytes, were significantly higher in CFS cases than in controls, and in 11 out of 30 CFS patients the increase in circulating B cells was sustained by the expansion of the CD5+/CD19+ subset of B lymphocytes. We conclude that CFS is a syndrome not previously described in Italy, with already known clinical characteristics and appears to be associated with several immunologic abnormalities, including those reported previously in cohort of patients from different countries. We also show for the first time that CD56- NK cell subsets from CFS patients display an abnormally increased expression of cell adhesion molecules and activation markers.

Adolescent↗

[The utilization of dry chemistry methods in a campaign to identify risk factor of cardiovascular diseases].

Dry chemistry methods on a Kodak Ektachem DT 60 instrument have been evaluated during a large scale (60,000 employees of the Italian Telephone Company) screening for the prevalence of cardiovascular risk factors. Comparison between dry chemistry methods on serum samples and liquid phase methods on the same samples yielded the following correlation coefficients: .991 (n = 100) for total cholesterol, .962 (n = 50) for high density lipoprotein (HDL) cholesterol, .987 (n = 100) for triglycerides, .997 (n = 50) for glucose, and .991 (n = 50) for uric acid. A 12% overestimation of serum triglycerides was observed with dry chemistry methods as compared to liquid phase methods. Accuracy and precision of these dry chemistry methods were evaluated by daily (n = 271 days) determinations of all the above parameters on each of two reference sera (low and high concentration). Dry chemistry methods average bias estimates (observed value - expected value)/expected value) x 100, measuring method's accuracy, were: 4.2% for total cholesterol, 1.2% for HDL cholesterol, 3.6% for triglycerides, 3.0% for glucose, 4.6% for uric acid. Average coefficients of variation (standard deviation/mean x 100, measuring method's precision, were: 5.0% for total cholesterol, 6.3% for HDL cholesterol, 5.9% for triglycerides, 3.6% for glucose, 7.2% for uric acid. Dry chemistry methods by Kodak Ektachem DT 60 proved highly comparable with liquid phase methods. Considering their level of accuracy and precision they can be recommended as quick and simple methods for population screenings.

Blood Glucose↗

Differential expression of cell adhesion molecules in B-zone small lymphocytic lymphoma and other well-differentiated lymphocytic disorders.

BACKGROUND: Cell adhesion molecules (CAM) may determine the patterns of growth and dissemination of lymphoproliferative disorders. METHODS: The authors have studied, by flow cytometric and immunohistochemical examination, the expression of several CAM, mediating cell-cell and cell-microenvironment interactions, on B-zone small lymphocytic lymphoma (BZSLL) and other B-cell low-grade non-Hodgkin lymphomas (NHL), including intermediate lymphocytic/mantle zone lymphoma (ILL/MZL), small lymphocytic lymphoma (SLL), and chronic lymphocytic leukemia (CLL). RESULTS: Relevant differences in the "adhesion phenotype" of BZSLL compared with other low-grade NHL examined were evidenced. Cells from BZSLL displayed a higher rate of expression and/or a stronger intensity of LFA-1, LFA-3, ICAM-1, and BL-CAM and a lower density of H-CAM and LAM-1 homing receptors, as opposed to SLL or CLL. A lower intensity of H-CAM along with a stronger expression of LFA-1, LFA-3, ICAM-1, and BL-CAM were also detected by comparing BZSLL with ILL/MZL: Malignant cells from BZSLL expressed Leu-CAMb determinants in three cases. BZSLL cells lacked VLA-alpha 5-integrins as opposed to CLL lymphocytes and displayed a stronger reactivity with anti-VLA-alpha 4 antibodies with respect to ILL/MZL and CLL. beta 1-integrins were consistently detected on BZSLL lymphocytes as opposed to ILL/MZL: CONCLUSIONS: These data suggest that the adhesion phenotype of BZSLL, by favoring homotypic and heterotypic adhesive interactions of tumor cells, might account at least in part for the peculiar intranodal compartmentalization leading to a deceptively benign (reactive) histologic appearance, and for the smoldering clinical course of this lymphoma. The pattern of CAM expression detected by the authors on malignant lymphocytes also is suggestive for a cellular origin of BZSLL from a rare subset of interfollicular or external mantle B-lymphocytes.

Cell Adhesion Molecules↗