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Biomedical subjects

F Morabito

Publications and source records attributed to F Morabito.

At least 37 records · Page 2Linked to original sources
PubMed1998

In vitro drug-induced cytotoxicity predicts clinical response to fludarabine in B-cell chronic lymphocytic leukaemia.

We investigated the possible value of an in vitro drug-induced cytotoxicity assay in predicting clinical response to fludarabine (FAMP) in chronic lymphocytic leukaemia (CLL). The median FAMP-LD50 values for cases designated as complete response (CR), partial response (PR), no response (NR) and progressive disease (PD) were 1.43, 2.05, 24.8 and 77.9 microg/ml, respectively (P=0.013). A significant lower mean FAMP-LD50 value was observed in the in vivo responding cases as compared to non-responding ones (3.0 +/- 0.82 SEM v 42.3 +/- 12.6 SEM, P=0.001). Only FAMP-LD50 < or = 2.5 microg/ml and more than four FAMP courses significantly influenced the response rate in univariate and multivariate analyses. The MTT assay may be of value in predicting clinical response to FAMP in CLL patients.

Adult↗
PubMed1998

Reduced growth hormone (GH) responsiveness to combined GH-releasing hormone and pyridostigmine administration in the Prader-Willi syndrome.

OBJECTIVE: It is unclear whether the blunted GH secretion in Prader-Willi Syndrome (PWS) is a true deficiency, or merely secondary to obesity. We have investigated the role of obesity in the blunted GH secretion in PWS. DESIGN: We studied the GH response to a combined administration of GHRH (1 microgram/kg i.v. at 0 min) and pyridostigmine (PD) (60 and 120 mg by mouth for children and adults, respectively, at time -60 min), as well as the baseline IGF-I levels, in a group of patients with PWS. Two different control groups were studied with GHRH + PD using the same doses and methods as above: prepubertal and pubertal obese subjects, and prepubertal short normal children. Moreover, in 14 patients with PWS and in the group of short normals the GH response to at least two stimulation tests (insulin tolerance test, clonidine, L-dopa, arginine) had been previously determined. PATIENTS: Twenty-two PWS patients (10 males and 12 females), 21 with essential obesity (11 males and 10 females), and eight short normal children (4 males and 4 females) were studied after obtaining informed consent. MEASUREMENTS: Blood samples were taken at -60, -30 and 0 min and then 15, 30, 45, 60, 90 and 120 min after GHRH administration. Serum GH was measured in duplicate by IRMA, and IGF-I by RIA after acid ethanol extraction. Statistical analysis was performed by t-test for unpaired data, and analysis of variance for parametric or nonparametric data, where appropriate. RESULTS: The GH response to GHRH + PD was significantly lower in PWS patients (AUC: mean +/- SE: 599 +/- 99 micrograms/l/h) if compared with either short normal children (3294 +/- 461 micrograms/l/h: P < 0.0001) or obese subjects (1445 +/- 210 micrograms/l/h: P < 0.005). Low IGF-I concentrations were found in all PWS patients, so that PWS group had mean IGF-I levels significantly lower than the other groups. CONCLUSIONS: Our results showed that subjects with PWS had a reduced GH responsiveness to GHRH + PD associated with subnormal IGF-I levels. These findings suggested that short stature in PWS may be at least partially correlated to the presence of GH deficiency, and that impaired GH secretion is not secondary to obesity.

Adolescent↗
PubMed1998

Growth hormone response to hexarelin, growth hormone-releasing hormone plus pyridostigmine and arginine plus estrogen in prepubertal and early pubertal short children.

BACKGROUND: Hexarelin (HEX), a synthetic hexapeptide with a strong GH-stimulating activity, has been suggested as a stimulus for evaluating GH secretion. However, in childhood it has never been compared with other stimuli capable to reduce the effect of the somatostatinergic tone and of the low production of gonadal steroids. METHODS: We evaluated GH response (expressed as the maximum value after stimulus [Cmax] and as area under the curve [AUC], mean +/- SD) to HEX at a dose of 2 micrograms/kg i.v., in comparison with those obtained after GHRH (1 microgram/kg i.v.) + pyridostigmine (PD, 60 mg p.o.) and arginine + ethynylestradiol (E2, 1 mg/day p.o. for 3 days before the test), in 5 subjects with familial short stature (FSS), 11 with constitutional growth delay (CGD), prepubertal (Tanner's stage I) and early pubertal (stage II), and in 8 healthy children age-matched as controls. RESULTS: HEX induced a Cmax of 31.9 +/- 18.4 micrograms/l and an AUC of 1511 +/- 923 micrograms/min x l in stage I, of 36.7 +/- 12.3 micrograms/l and 1938 +/- 903 micrograms/min x l in stage II (ns). GHRH + PD induced a Cmax of 33.8 +/- 14.6 micrograms/l and an AUC of 2072 +/- 1233 micrograms/min x l in stage I, of 29.6 +/- 15.6 micrograms/l and 1901 +/- 1252 micrograms/min x l in stage II (ns). ARG + E2 induced a Cmax of 17.8 +/- 7 micrograms/l and an AUC of 1157 +/- 505 micrograms/min x l in stage I, of 15.6 +/- 11.6 micrograms/l and 649 +/- 452 micrograms/min x l in stage II (ns). The Cmax of HEX was higher than that of ARG + E2 in both stages I and II (p < 0.05); AUC of HEX, was higher than that of ARG + E2 only in stage II (p < 0.01); the Cmax and the AUC of GHRH + PD were higher than those of ARG + E2 both in stage I (p < 0.01 and p < 0.05, respectively) and in stage II (p < 0.05). No difference, neither in the extent of GH response to HEX and GHRH + PD nor in that to stimuli between subjects and controls, was found. HEX has given 32% false positives in stage I and 17% in stage II, GHRH + PD 12% and 15%, while ARG + E2 provided 20% in stage I and 32% in stage II. On the whole, specificity was 76% for HEX and ARG + E2 and 89% for GHRH + PD. CONCLUSIONS: HEX induced greater GH response than that of ARG + E2 but similar to that of GHRH + PD and its specificity was not different to that of ARG + E2 and lower than that of GHRH + PD: then its use does not show a diagnostic advantage in respect to the other two stimuli in peripubertal age.

Adolescent↗
PubMed1998

[Leptin and neuropeptide Y serum levls in young obese during weight loss].

BACKGROUND AND AIM: Correlations between serum leptin (LEP) and BMI and the percentage of fat mass (FM), as well as differences between male and female serum levels and their behaviour during weight loss have already been extensively described in adult obesity, whereas few cases have been examined in child and adolescent obesity. There are also few studies of the alterations in NPY in peripheral blood in obese subjects during weight loss. METHODS: This study aimed to evaluate the correlations between LEP and BMI, FM% and NPY in 72 obese subjects, with BMI > 35 (29 males and 43 females) aged between 9.6 and 19.8 years old, during weight loss together with any differences between the sexes. RESULTS: LEP was positively correlated in both sexes with BMI and FM%, whereas no correlation emerged with NPY; LEP levels decreased gradually during weight loss, whereas no changes were observed in NPY except during the first phases of weight loss in males when the decrease was significant. LEP concentrations were significantly higher in females, who also showed a higher FM% with equal BMI. No difference was observed between NPY levels in both sexes. CONCLUSIONS: The authors conclude that: 1) the behaviour of LEP in child-adolescent obesity is broadly comparable to that described in adult obesity; 2) the highest LEP concentrations with equal BMI in females appear to reflect the different body composition of the two sexes given that females have a higher FM%; 3) the control exerted by LEP on hypothalamic NPY cannot be seen in peripheral blood and no differences emerged between the two sexes.

Adolescent↗
PubMed1998

Chlorambucil synergizes with purine analogs in inducing in vitro cytotoxicity in B-cell chronic lymphocytic leukemia.

Combinations of different drug concentrations of CLB + FAMP and CLB + 2-CDA were synergistic in, respectively, 42.9% and 34.8%. At leukemic cell survival < or = 50%, 16.4% and 23.4% of all combinations were synergistic in the 2-CDA and FAMP groups, respectively. A significantly higher mean value of antagonistic interactions was observed in the 2-CDA group (p = 0.037).

Antimetabolites, Antineoplastic↗
PubMed1998

Retrospective analysis of mantle cell lymphoma: experience of the "Gruppo Italiano per lo Studio dei Linfomi" (GISL).

BACKGROUND AND OBJECTIVE: Mantle cell lymphoma is a recently recognized histologic entity with specific biological and clinical features. Clinically, the reported unfavorable outcome of these patients has focused attention on this category of non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: The slide specimens of 69 NHL patients, originally classified as Working Formulation (WF) group B and E, were reviewed. The clinical features at presentation, response to therapy, response duration and survival were analyzed in cases reclassified as MCL. The correlation between clinical and histologic characteristics and the final outcome was evaluated. RESULTS: Out of 69 cases, 34 specimens were reclassified as MCL; in 6 patients, previously classified as WF group B, the nodular pattern was confirmed; in 2 instances the blastoid form was recognized. After a median follow-up of 35.7 months, the entire series displayed a median overall survival of 41.2 months; a significantly longer survival was associated with the nodular histologic pattern, IPI score < 2, response achievement, and a higher Hb level. The vast majority of patients received anthracycline-containing combination chemotherapy. Complete remission rate was 38.8% and overall response rate was 67.6%; response achievement was significantly influenced only by Hb level. Median response duration was 23.3 months. INTERPRETATION AND CONCLUSIONS: The present study confirms the unfavorable clinical course of MCL and the possible need for an alternative therapeutic strategy for this NHL category. Therefore, the correct identification of MCL at diagnosis appears of relevance.

Adult↗
PubMed1998

In vitro modulation of bcl-2 protein expression, drug-induced apoptosis and cytotoxicity by interleukin-10 in chronic lymphocytic leukemia.

Interleukin-10 failed to modify either the percentage of bcl-2+ cells or the number of bcl-2 molecules, or to reduce 2-chlorodeoxyadenosine- and fludarabine-induced apoptosis. The cytokine at 0.1 ng/mL induced an increase of cell survival both in the absence or in the presence of 2-chlorodeoxyadenosine, while no difference was appreciated with fludarabine.

Antimetabolites, Antineoplastic↗
PubMed1997

High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. International Society for Chemo-Immunotherapy, Vienna.

BACKGROUND: In recent years, much attention has been paid to the possible efficacy of intensive chemotherapy in the treatment of advanced, progressive B-cell chronic lymphocytic leukemia (CLL) patients. For this reason, the International Society for Chemo-Immunotherapy, Chronic Lymphocytic Leukemia Cooperative Group, has begun a randomized multicenter trial comparing Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with continuous high dose chlorambucil (HD-CLB). METHODS: During the period January 1987 to May 1993, 228 previously untreated CLL patients from 7 cooperative institutions were randomized to this trial. Advanced and/or progressive disease was defined by high Total Tumor Mass (TTM) score (> 9), and/or short doubling time (DT) (< 12 months), and/or bone marrow failure. The response to therapy was defined by reduction of the initial TTM score. The end points of the trial were response rate, survival, and toxicity. RESULTS: HD-CLB resulted in a higher response rate than CHOP in evaluable cases, with 89.5% overall responses (complete response+partial response) versus 75%, respectively (P < 0.001). At the time of an analysis performed in July 1995 (after a median follow-up period of 37 months), overall survival was also longer in the HD-CLB treatment arm (median survival, 68 months) than in the CHOP treatment arm (median survival, 47 months) (P < 0.005). Toxicity was acceptable and comparable in the two treatment arms. CONCLUSIONS: The current study showed that HD-CLB is an effective and well-tolerated therapeutic option for patients with advanced and/or progressive CLL. Therefore, the authors recommend its wider use, possibly in comparison with and/ or in combination with new therapeutic agents, such as purine analogues.

Aged↗
PubMed1997

Long-term clinical outcome of B-cell chronic lymphocytic leukaemia patients in clinical remission phase evaluated at phenotypic level.

This retrospective study aimed to evaluate the long-term prognostic impact of phenotypic remission in B-cell chronic lymphocytic leukaemia (CLL) patients who have achieved clinical, haematological and bone-marrow complete remission (CR) after conventional chemotherapy. The clinical and phenotypic data of 77 CLL patients in CR with a median follow-up from CR achievement of 54 months (range 5-127) were analysed. 32 patients (42%) displayed a normalized phenotype as evaluated by k:lambda ratio or by CD5+/CD19+ cell numbers. Patients with normalized phenotype demonstrated a significantly higher incidence of female sex, a lower relapse rate, a trend for higher prevalence of stage A and a lower occurrence of CLL-related deaths. The relapse-free survival of patients with normalized phenotype was significantly longer (P = 0.02), whereas no difference in overall survival was found between the two groups. Interestingly, Binet's stage at diagnosis was highly predictive of the overall survival following CR achievement. From the results of the present study we conclude that a phenotype normalization at CR obtained with conventional chemotherapy indicates a higher probability of a longer CR but it does not translate into prolonged survival. Clinical features at diagnosis, such as stage distribution, are apparently stronger predictors of the final outcome. These results emphasize, however, the need for a routine assessment of the quality of response since this information could be crucial in designing therapeutic strategies for young patients suffering from advanced CLL.

Adult↗
PubMed1997

In vitro improvement of chlorambucil-induced cytotoxicity by deflazacort and 6-methylprednisolone in B-cell chronic lymphocytic leukaemia.

We examined whether CLL cell chemosensitivity to in vitro exposure to chlorambucil (CLB) might be improved by the presence of deflazacort (DFZ) in comparison to 6-methylprednisolone (PDN). The PDN lethal dose (LD)50 values were low in 5 samples, intermediate in 4 and high in 7. Low, intermediate and high DFZ-LD50 values were detected in 3, 2 and 11 samples, respectively. The CBL-LD50 mean values were significantly reduced at all PDN and at the 4 highest DFZ concentrations. However, a dose-response effect was seen only in the DFZ group. Both CLB-DFZ and CLB-PDN interactions were analysed in 16 samples at 25 different dose-combinations, resulting in 400 comparisons between expected and observed leukaemic cell survival (LCS) values for each group. In particular, 45.75% and 40% dose combinations were synergistic in CLB-DFZ and CLB-PDN groups, respectively. A relatively higher number of antagonistic interactions were observed among CLB-PDN dose combinations, while analogous number of additive interactions were detected. At concentrations of CLB x1 microgram/ml the phenomenon of synergism, regardless of the steroid concentration, did occur more frequently. On the other hand, a more elevated number of antagonistic interactions were counted at CLB 100 micrograms/ ml. In conclusion, both DFZ and PDN synergize in vitro with CLB, especially at low concentrations of the alkylating agent.

Analysis of Variance↗
PubMed1997

Evaluation of Taxol cytotoxicity on B-CLL cells in vitro.

Taxol is a new antimicrotubule agent that, besides a well known efficacy against solid tumors, has shown activity in non-Hodgkin's lymphomas too. We therefore investigated its in vitro cytotoxic activity against cells from patients affected by chronic lymphocytic leukemia (CLL). Peripheral blood lymphocytes from 46 CLL patients were incubated for four days with Taxol at doses ranging from 0.01 to 10 mM and the cytotoxicity was evaluated by a colorimetric method (XTT). In most samples Taxol was inactive and the IC50 was > 10 mM in 40 out of 46 patients. It is worthwhile noting that four of the six in vitro responsive patients had unfavourable clinical features. In three unresponsive patients we also observed that Taxol was not able to induce apoptosis in vitro. In conclusion, based on in vitro data, it seems that Taxol is not an active drug in standard CLL but we cannot exclude some efficacy in other more rapidly proliferating lymphoproliferative disorders.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Dexfentluramine in the treatment of juvenile obesity.

BACKGROUND: The aim of this study was to investigate the potential of dexfenfluramine (dF) for reducing cardiovascular risk factors and improving compliance towards diet in a group of young patients hospitalized for essential obesity of high degree (BMI > or = 35). METHODS: 103 adolescents (mean age 15.4 +/- 0.2) participated in a nine-week randomized double-blind study of dF (15 mg bid) versus placebo. All patients received a VLCD (2,512 kJ/day = 600 kcal/day) for two months. In basal conditions, and after 30 and 60 days of treatment, anthropometric variables (height, weight, BMI, and W/H) and cardiovascular risk factors (blood glucose concentration, total cholesterol, HDL-cholesterol, triglycerides, systolic and diastolic blood pressure) were monitored. Modifications in hunger and satiety were also assessed. RESULTS: During the treatment period, both the dF group and the placebo group presented a similar pattern of weight loss (BMI = dF: 36.7 +/- 0.5 vs 32.5 +/- 0.4 vs 30.1 +/- 0.4; placebo: 37.0 +/- 0.6 vs 33.1 +/- 0.5 vs 30.8 +/- 0.5). No important side-effects were recorded in either group. Blood pressure and metabolic markers decreased significantly in both groups. Earlier reductions in total cholesterol and diastolic blood pressure in dF-treated subjects were the only significant differences observed as compared to the patients receiving placebo (day 30 = total cholesterol: 120 +/- 2 (dF) vs 132 +/- 3 (placebo) mg/dI; p < 0.005; diastolic blood pressure: 73 +/- 1 (dF) vs 77 +/- 1 (placebo) mmHg; p < 0.01). However, after 60 days, these values were similar in the two groups. As far as non-parametric data are concerned, dF determined a reduction in hunger and an increase in satiety in a significantly higher number of subjects than did the placebo, not only after 30 days of treatment (92.8% vs 55.3% and 92.8% vs 45.5%, respectively; p < 0.0001), but also after two months of treatment (97.8% vs 67.4% and 97.8% vs 45.8%, respectively; p < 0.0001). CONCLUSIONS: These findings demonstrate that dF represents a useful support in the treatment of juvenile obesity and might ensure a better individual compliance towards restrictive diets, particularly in the initial "critical" stages, in the absence of important side-effects.

Blood Pressure↗
PubMed1997

[Knemometry in the assessment of short term effects of growth hormone therapy in children with several growth disorders].

BACKGROUND: Knemometer is a non invasive device for measuring the leg length and evaluating statural variations otherwise not disclosed by means of Harpenden stadiometer. In several clinical conditions of short stature, knemometer allows to evaluate the short-term effect of growth promoting agents, as well as the role of infections on growth dynamics. METHODS: The short-term (37-56 days) variability of the leg length in subjects with isolated growth hormone deficiency (1 case), Turner syndrome (2 cases) and Silver-Russel syndrome (1 case) treated with rhGH have been evaluated. The measurements were performed weekly by the same operator, at the same weekday and daytime. RESULTS AND CONCLUSIONS: The results show a correlation between intercurrent illnesses and growth failure, as well as a growth resumption at the end of the former, despite the etiology of short stature. Growth hormone treatment seems to exert an influence on growth only in the subject with GH deficiency, whereas a similar short term effect is not found in the cases of Turner syndrome and Silver Russel syndrome. This fact suggests that, also by knemometry, a most prolonged follow-up is required to evaluate the effect of GH on short term growth.

Adolescent↗
PubMed1996

2-Chlorodeoxyadenosine treatment in non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia resistant to conventional chemotherapy: results of a multicentric experience. International Society for Chemo-Immunotherapy.

Among the purine analogs, 2-chlorodeoxyadenosine (2-CDA) is particularly effective for the treatment of hairy cell leukemia and Waldemstrom's macroglobulinemia. Both efficacy and toxicity of 2-CDA were evaluated in previously treated patients affected with chronic lymphoproliferative disorders such as low-grade non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). Thirty cases, mainly refractory, 16 affected with CLL, were included from six centers of the International Society for Chemo-Immunotherapy (IGCI). 2-CDA was administered in a 2 h i.v. infusion for 5-7 days at the standard dose of 0.1 mg/kg/day every 4 weeks. The median number of cycles was 3. Of 30 cases, eight (26.7%) achieved a complete remission (CR), nine (30%) a partial remission (PR), and two (6.7%) a minor response, while five cases (16.6%) did not respond, and six (20%) were considered early deaths. The overall response rate (CR + PR) was 56.7%, with a median response duration of 12 months (range 3-28 +) and a better response in CLL patients. Considering that the majority of patients were heavily pretreated, toxicity was acceptable, with 40% of cases not presenting any toxic effect. The main toxicity consisted in infectious complications. Based on the results of the present study, we confirm that 2-CDA is an effective drug in these lymphoproliferative disorders, suggesting its possible use either alone or in combination, also as first-line therapy.

Adult↗