Biomedical subjects

F Morabito

Publications and source records attributed to F Morabito.

169 records · Page 10Linked to original sources

PubMedDate not supplied

Clinical significance of sIL2R, sCD23, sICAM-1, IL6 and sCD 14 serum levels in B-cell chronic lymphocytic leukemia.

BACKGROUND: The aim of the study was to establish the role exerted by some soluble factors in B-CLL disease mechanisms. MATERIALS AND METHODS: Serum levels of sIL2R, sCD23, sICAM-1, IL6 and sCD14 were detected in 47 B-CLL patients. Thirty-seven out of the 47 cases were in advanced/progressive stage, while the remaining 10 patients were defined as smouldering B-CLL. Twenty normal controls provided the reference values. Serum samples of 24 out 37 advanced/progressive cases were measured before and six months after the start of chemotherapy. RESULTS: The advanced/progressive patients showed significantly higher levels of sIL2R, sICAM-1 and sCD23 as compared to normal subjects. Furthermore, sIL2R, sICAM-1 and IL6 values were significantly higher in advanced/progressive B-CLL than in smouldering B-CLL patients. A statistically significant difference was found between smouldering B-CLL and controls for sCD14 only. sIL2R and sICAM-1 levels directly correlated with total tumor mass (TTM) score, sCD23 with both TTM score and lymphocytosis, and sCD14 with IgG serum values. sIL2R and sCD23 levels lowered significantly after chemotherapy, but only sCD23 and TTM variations after chemotherapy were closely correlated. CONCLUSIONS: sCD23 may be considered the only indicator of tumor mass, while the other soluble factors can be released through different mechanisms. In particular, sICAM-1 seems to correlate with the ability of the tumor to spread, while the sCD14 increase could indicate a role for this soluble factor in preventing infections in B-CLL patients.

Aged↗

PubMedDate not supplied

Fractionated infusions of cryopreserved stem cells may prevent DMSO-induced major cardiac complications in graft recipients.

The amount of transfused dimethyl sulfoxide (DMSO) is indicated as the major cause of the cryoprotectant-related toxicity in autologous stem cell recipients, with a high incidence of major cardiac side effects. In this study we tried to discover whether fractionated infusion of the total graft volume could prevent the DMSO-related major cardiovascular side effects. We conclude that continuous cardiac monitoring during and after fractionated infusions of DMSO-containing graft documented no major arrhythmias, with only seven episodes of asymptomatic sinus bradycardia.

Adolescent↗

PubMedDate not supplied

Two consecutive courses of rh-G-CSF-mobilized peripheral blood stem cells for primary marrow alloengraftment failure: case report.

We describe herein a case of bone marrow failure in a 53-year-old patient affected by Ph1-positive chronic myeloid leukemia who received an HLA-identical AB0-mismatched bone marrow transplant from a 56-year-old sibling donor. Hematopoietic recovery after marrow failure was obtained following two consecutive courses of rh-G-CSF-mobilized peripheral blood stem cell infusions. No potential risk factors associated with graft failure, excluding recipient and donor age, were documented, whereas a relatively high number of progenitor cells were necessary to overcome the host-versus-graft barrier in our patient. Therefore we suggest that growth factor-stimulated peripheral blood should be considered as the first choice for allogeneic stem cells in order to avoid primary graft failure with donors over 50 years of age.

Blood Cell Count↗

PubMedDate not supplied

Bcl-2 protein expression and p53 gene mutation in chronic lymphocytic leukemia: correlation with in vitro sensitivity to chlorambucil and purine analogs.

BACKGROUND AND OBJECTIVE: Bcl-2 oncogenic protein expression plays a major role in blocking the apoptotic mechanism. p53 gene mutations have also been suggested to account for the chlorambucil resistance in CLL. Thus we studied the relationship between bcl-2 protein expression, p53 gene mutations and in vitro drug sensitivity in CLL. METHODS: Fifty-three samples from untreated CLL patients in early disease stages were tested in vitro for chemosensitivity to chlorambucil (CLB), fludarabine (FAMP) and 2-chlorodeoxyadenosine (2-CDA) using the MTT assay. Intracellular bcl-2 protein expression was evaluated by flow cytometry analysis. p53 gene mutations were detected by using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. RESULTS: The median LD50 values were 1.55 microM, 4.41 microM and 58.2 microM for 2-CDA, FAMP and CLB, respectively. About 23%, 41% and 11% of samples were defined as being sensitive to FAMP, 2-CDA and CLB, respectively, when samples were clustered for LD50 threshold values corresponding to the plasmatic levels of the drug. No statistically significant difference in bcl-2 protein expression was noted between sensitive and resistant samples for each drug. A p53 gene mutation was detected in 4 of the 30 cases studies and all of them were among samples resistant to CLB. INTERPRETATION AND CONCLUSIONS: Bcl-2 expression is not an indicator of in vitro response to drugs in CLL; similarly, although the four cases showing a p53 gene mutation were associated with CLB resistance, drug resistant samples were also observed in the group of patients showing wild type p53, suggesting multiple mechanisms of drug resistance in CLL.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

Clinical significance of HLA-DR+, CD19+, CD10+ immature B-cell phenotype and CD34+ cell detection in bone marrow lymphocytes from children affected with immune thrombocytopenic purpura.

In children with immune thrombocytopenic purpura (ITP), bone marrow lymphocytes can express the common acute lymphoblastic leukemia antigen (CALLA) pattern with no evidence of leukemia or lymphoma. Bone marrow lymphocytes from 23 children and 20 adults affected with ITP were studied to determine the incidence and the clinical impact of lymphocytes with the immature B-cell phenotype and CD34+ cell expression. In this investigation we identified a group consisting of 52% of the children who showed the immature B phenotype, while the remaining 48%, similarly to adult ITP displayed an increase of T-cell antigens. CD34 was positive in 53% of children, but it was present in only half of the patients with the immature B phenotype and it was always absent in adults. IgH genes disclosed a germline configuration in all six patients in the immature B phenotype group. No difference was found in the two groups of children in terms of age, presentation of the disease or final outcome. Finally, no patient in either children's group has developed an acute lymphoproliferative disorder.

Adult↗

PubMedDate not supplied

The in vitro cytotoxic effect of mitoxantrone in combination with fludarabine or pentostatin in B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVE: Clinical studies indicate that combination chemotherapy with mitoxantrone (Mitox) and a purine analog can improve the response rate in indolent lymphoproliferative disorders. We explored the in vitro Mitox- fludarabine (FAMP)- and pentostatin (Pento)-induced cytotoxicity and their interactions in CLL. METHODS: The peripheral lymphocytes of 24 CLL patients were tested at different drug concentrations, with Mitox, FAMP or their combinations in 22 cases, and with Mitox, Pento or their combinations in 20 cases, 18 of which were the same from the FAMP group. The MTT assay was chosen for the drug-induced cell cytotoxicity and flow cytometry analysis of the DNA hypodiploid peak for the study of the apoptotic process. Drug interactions were calculated in the MTT assay according to both multiplicative and maximum models. RESULTS: According to the lethal dose (LD) 50 values, when the three drugs were tested alone, 11 out of 22 and 8 out of 20 samples were sensitive to Mitox in the FAMP and Pento groups, respectively; on the other hand, 2 out of 22 and 0 out of 20 samples appeared sensitive to FAMP or Pento alone, respectively. Analyzing the MTT assay data with the multiplicative and maximum model, the combinations of Mitox+FAMP and Mitox+Pento at different drug concentrations were synergistic in 28.2% and 39.3%, respectively. At leukemic cell survival < or = 50%, 11.7% and 11.1% of all combinations were synergistic in the Pento and FAMP group, respectively. The number of synergistic interactions at a therapeutically achievable plasma-drug concentration was an inverse function of the Mitox concentration. In the FAMP group, a direct correlation was found between the LD50 values of both FAMP and Mitox and the number of synergistic interactions, while the Pearson correlation coefficient was not significant in the Pento group. Finally, as measured by the DNA hypodiploid peak, Mitox (0.25 microgram/mL) plus Pento (0.16 microgram/mL) showed a significantly enhanced apoptosis in comparison to each single drug, while Mitox failed to demonstrate an additive effect with FAMP (1 microgram/ml). INTERPRETATION AND CONCLUSIONS: This experience demonstrates the extent of the in vitro synergism of Mitox with FAMP and Pento in inducing cell cytotoxicity; it also shows an adjunctive apoptotic effect for the Mitox-Pento association only.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

[Circadian rhythm of melatonin in liver cirrhosis].

The liver plays an important role in the intermediate metabolism of numerous substances involved in hormonal action. Starting from the presupposition that the pineal has an inhibitory effect on the reproduction system through melatonin (aMT) and that hepatic cirrhosis can be included among the pathologies characterised by sexual disorders, the authors felt that it was interesting to evaluate the light/darkness rhythm of aMT in some patients suffering from hepatic cirrhosis in order to highlight the possible pathogenetic role of aMT in causing the altered sexual activity observed in this pathology. A total of 4 subjects (3 males and 1 female), with a mean age of 60.5 years, suffering from hepatic cirrhosis and a matched group of healthy controls were included in the study. Circadian changes in aMT plasma levels and plasma levels before and after TRH stimulus (200 micrograms) of aMT and PRL were studied in all subjects. The results revealed the presence of a circadian rhythm of aMT with a nocturnal peak secretion in both groups; in patients with cirrhosis, however, the rhythm appeared to be "out of phase" and presented a late and prolonged increase in aMT compared to controls. Responses to TRH did not show any differences in aMT between the two groups, but the response to PRL was higher and longer than in hepatopathic patients. These findings showed an alteration in the secretory pattern of aMT in cirrhotic patients which can be attributed to reduced hormone metabolism at an hepatic level. The altered response to PRL is attributable to an altered neurotransmitter function at the central level.

Aged↗