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Biomedical subjects

R Miniero

Publications and source records attributed to R Miniero.

At least 109 records · Page 6Linked to original sources

[Lipidemic alterations in a child with acute lymphoblastic leukemia in treatment with L-aspariginase].

The case of a child treated for Acute Lymphoblastic Leukemia (LLA) with high-dose L-asparaginase, (HD L-ase) presented alteration who of lipidemic values (rise of total cholesterol and triglyceride values) without toxicity is described. This finding has previously been reported in only a few patients. Parameters normalized with dietetic regimen. The authors underline the importance of the control, in patient during HD L-ase treatment of lipidic values too, especially when parents also have similar alterations.

Asparaginase↗

Expansion of cord blood progenitors and use for hemopoietic reconstitution.

A high number of stem cells migrate in fetal blood and, at birth, the number of progenitors in cord blood equals or exceeds that of adult bone marrow. Recently hemopoiesis has been successfully reconstituted with the infusion of cord blood cells. It is important to clearly define the quantity and quality of cord blood totipotent and multilineage progenitors to evaluate the possibility of their utilization in transplants. Our first aim was to study the growth characteristics of cord blood progenitors. We have evaluated the number of cycling cells with the thymidine suicide technique and the production, by phytohemagglutinin (PHA) stimulated cord blood mononuclear cells, of some cytokines involved in the proliferation of progenitor cells, such as granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6) and leukemia inhibitory factor (LIF). We have also studied by flow cytometry the CD34+CD33-, CD34+CD33+ cell subsets and the presence of the c-kit receptor in order to quantitate the number of earlier progenitors. Our second aim was to elucidate whether the cord blood totipotent stem cell population or the committed progenitors could be expanded in vitro. Our results showed that in cord blood the number of early progenitors, as evaluated by the number of mixed lineage colony forming units (CFU-Mix), by the CD34+CD33- subsets and the expression of the c-kit, is higher than in bone marrow. We have also demonstrated the possibility in vitro of increasing the number of progenitors by more than 30-fold by utilizing stem cell factor (SCF) in association with other cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

Umbilical cord blood stem cell transplantation.

Human umbilical cord blood as an alternative source of hematopoietic stem cells for bone marrow reconstitution, has recently been demonstrated to yield successful HLA-matched placental blood grafts in children. It has been shown that cord blood contains sufficient progenitor cells to effect hematological reconstitution. Since then, more than 25 cord blood stem cells (CBSCs) transplants have been performed worldwide for the treatment of a variety of malignant and nonmalignant diseases. The majority of the grafts performed thus far have utilized CBSCs from HLA-identical siblings. However, much of the interest in this setting is devoted to the potential use of CBSCs for HLA-mismatched and unrelated transplants. Preliminary results suggest that allorecognition and graft-versus-host disease may be less intense in CBSCs transplants than in recipients of similarly compatible bone marrow. This review summarizes the results and potential future applications of cord blood transplantation.

Child↗

Human cord blood progenitors: kinetics, regulation and their use for hemopoietic reconstitution.

The high number of cord blood (CB) hematopoietic progenitors made possible CB transplantation in children with hematologic diseases. We collected and cryopreserved CB from siblings of 11 hematologic pediatric patients for possible transplant. The number of BFU-E+CFU-GEMM and CFU-GM was adequate for engraftment. However the possibility of CB transplantation in adolescents and adults is limited by the amount of CB that can be collected. We studied the possibility of expanding the pool of CB hematopoietic progenitors by preincubation of CB CD 34+ cells with several cytokines. After pre-exposition to rhIL-3, IL-1 beta, rIL-6, GM-CSF and stem cell factor (SCF) and cloning with SCF the number of hematopoietic progenitors increased 14-18 fold compared to basal values.

Blood Cell Count↗

Graft-versus-host disease in children: the AIEOP-BMT Group experience with cyclosporin A.

We retrospectively analyzed the data base of the Italian Association of Pediatric Hematology/Oncology BMT Group on the incidence and severity of GVHD in children given allogeneic BMT from HLA-identical sibling and receiving cyclosporin A (CsA) alone as GVHD prophylaxis. The study population included 145 patients for acute GVHD and 114 children at risk for chronic GVHD. Twelve patients had non-malignant diseases and 133 patients were affected by malignant disorders. Among the 145 patients (50 females, 95 males), 107 (74%) presented acute GVHD and 38 (26%) had no sign of disease. In the group of patients with acute GVHD, 38 children (26% of the whole study population) were found to have grade II disease, 9 (6% of the whole) grade III, 4 (3%) grade IV. Donor-recipient sex pairs had no significant influence on incidence of acute GVHD neither did donor-recipient age class stratification. Of the 114 patients evaluated for chronic GVHD, 86 (76%) developed no disease while 23 patients (20%) presented secondary chronic GVHD and 5 (4%) had de novo chronic GVHD. The incidence of chronic GVHD was higher in F-M than in M-M donor-recipient sex pairs (33% vs 11%, p < 0.05), with no difference between F-F and M-F. In patients of > 10 years, a higher incidence of chronic GVHD was observed in both female donors and recipients compared with male donors and recipients (48% vs 20% and 47% vs 19%, respectively, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Pulmonary complications after bone marrow transplantation].

Pulmonary toxicity occurs in approximately 10 to 50% of patients undergoing bone marrow transplantation (BMT). Bacterial pneumonia very commonly affects patients within the first 6 months post-BMT. Etiologic factors include neutropenia and the presence of graft-versus-host disease (GVHD). Pulmonary fungal infections, due to candida and aspergillus, may develop in 16% of patients receiving BMT, with a high mortality rate, being about 80%. A prolonged neutropenia as well as GVHD and associated immunosuppressive treatments are important factors in predisposing a patient to develop fungal pneumonitis. Interstitial pneumonitis occurs in 10-40% of patients; herpes viruses are the most commonly documented cause, with cytomegalovirus (CMV) being the most common pathogen. No causative organism is identified in up to 60% of the cases. It is likely that some of these cases may result from drug or radiation toxicity. Lung shielding and fractionation of the dose have decreased the incidence of interstitial pneumonitis to less than 5%. Patients with GVHD are predisposed to lung infections because of the immunosuppression that accompanies GVHD and its treatment. In addition, GVHD itself appears to have a direct effect on pulmonary epithelium. Cultural and serologic studies as well as radiographic investigations and other diagnostic procedures (ie bronchoalveolar lavage) are needed for appropriate management of pulmonary complications.

Bone Marrow Transplantation↗

ABMT for early isolated extramedullary relapse of childhood ALL.

From July 1987 to July 1991, 12 children underwent AMBT following high-dose cytarabine (HD Ara-C) plus 14.4 Gy hyperfractionated total body irradiation (hyfr-TBI) for early isolated extramedullary relapse of ALL, while in first BM remission. No patient received intrathecal prophylaxis following AMBT. One patient died on day +5 due to sepsis and three patients, two of them transplanted in second and third CNS relapse, respectively, died from BM relapse occurring 1.5, 4 and 5 months after AMBT. Eight of the 12 survive disease-free with a median follow-up of 24 months (range 14-62 months). The toxicity of HD Ara-C plus hyfr-TBI was acceptable and well controlled with supportive therapy. These results suggest that ABMT following HD Ara-C plus hyfr-TBI may eradicate leukemia from extramedullary sites of ALL relapse.

Adolescent↗

Rebound thymic hyperplasia following high dose chemotherapy and allogeneic BMT.

We describe a child with acute lymphoblastic leukemia who showed mediastinal widening 8 months after allogeneic BMT. Total thymectomy was carried out by the transcervical approach. Histologic examination showed only thymic hyperplasia. The immunohistologic investigation revealed a normal distribution of thymic cell elements, without evidence of clonal proliferation of lymphocytic subpopulations. This case supports the hypothesis that thymic hyperplasia following chemotherapy may be merely a rebound phenomenon. The patient had an uneventful postoperative recovery and remains in remission more than 1 year after BMT.

Antigens, Differentiation, T-Lymphocyte↗

Low incidence of GvHD and rejection after pharmacological ex vivo modulation of bone marrow in 2-3 antigens mismatched BMT.

2-3 antigens mismatched BMT were performed on 32 children without a matched sibling donor. In the light of previous in vitro studies, which suggested a role of Vincristine and Methilprednisolone ex vivo treatment in modulating alloreactivity of T cells, bone marrow was treated with such a pharmacological cocktail before being infused. Acute GVHD 2 degrees to 4 degrees degree occurred in 46% of cases, chronic GVHD in 28%, graft failure in 13%. There was no significant difference between 2- and 3-antigens mismatched BMT as far as GVHD and graft failure are concerned.

Bone Marrow↗

Anti-hepatitis C virus antibodies amongst Italian homo-bisexual males.

The authors report on an anti-hepatitis C virus antibody (HCV Ab) prevalence (6.9%) in 622 homo-bisexual males from Northern Italy, voluntarily attending an HIV and STDs screening program in the period 1984-89. The anti-HCV antibody prevalence shows a significant correlation with: i) presence of serological markers for HBV (O.R. = 3.12, 95% C.I. = 1.53-6.52) and HIV (O.R. = 12.09; C.I. = 6.52-22.52) infection; ii) a stable relationship with an anti-HCV antibody positive partner (O.R. = 7.79; 95% C.I. = 2.50-23.90); iii) more than twenty different male partners per year (O.R. = 2.55; 95% C.I. = 1.17-5.66). These data demonstrate the existence of a sexual transmission of HCV among homosexuals. This route might contribute in maintaining endemic levels of HCV infection in the homo-bisexual population and it might represent an important way of spreading the virus in the general population too.

Adult↗

Monosomy 20 in childhood acute lymphoblastic leukemia.

We report two cases of acute lymphoblastic leukemia (ALL) with loss of chromosome 20 as the only karyotypic abnormality detected in the blast cells. The first patient is a 12-year-old boy studied at diagnosis. He represents the only case of monosomy 20 in our series of 90 pediatric ALL successfully karyotyped at diagnosis. In the second patient, monosomy 20 was detected at the second hematologic relapse, 12 years after the initial diagnosis; cytogenetic studies were not performed at disease onset.

Bone Marrow Cells↗

Cellular response and anti-HBs synthesis in vitro after vaccination with yeast-derived recombinant hepatitis vaccine.

Two groups of subjects receiving two different doses of yeast-derived recombinant hepatitis B surface antigen (rHBsAg) (10 micrograms Gen-HB-Vax, Merck Sharp and Dohme and 20 micrograms Engerix-B, Smith Kline and French) were investigated for in vitro specific humoral and cellular response to the native protein. In vitro proliferative response was dependent on the following critical variables: (1) antigen-specific precursor lymphocytes were present in the peripheral blood for a very short time; (2) the number of circulating specific precursors was dependent on the dose of HBsAg used for vaccination; (3) the presence of antigen-presenting cells was necessary to obtain a blastogenic response in vitro. In vitro proliferation was enhanced by the addition of recombinant interleukin 2 (rIL-2). Spontaneous and stimulated (anti-CD3, pokeweed mitogen) anti-HBs antibody production in vitro was obtained in only eight out of 20 subjects after the fourth boost. Although a different immunogenicity of the two vaccines cannot be excluded, these data strongly suggest that T and B cells responsive to HBsAg present different kinetics of recirculation in the peripheral blood, depending on the antigen dose used for immunization.

Adult↗

Treatment of primary refractory or relapsed acute lymphoblastic leukemia (ALL) in children.

Thirty-one intensively pretreated children with ALL in first bone marrow relapse or refractory to initial therapy were treated with a combination of intermediate-dose Ara-C and idarubicin (IDA). Twenty-four patients (77%) achieved complete remission (CR), 8 patients relapsed early and 2 were removed from the study. Fourteen (45% of the original 31 patients) underwent bone marrow transplant (BMT) and 7 of them (22%) are still in continuous CR (CCR) with a median follow-up of 18 months. These results confirm that it is possible to achieve CR even in ALL children who failed on an initial intensive regimen. Newer modalities of post-remission therapy, especially for children lacking an HLA donor, should be considered.

Adolescent↗

Serum autoantibodies and the diagnosis of type-1 autoimmune hepatitis in Italy: a reappraisal at the light of hepatitis C virus infection.

Antinuclear antibodies with the homogeneous pattern (ANA-H) and smooth muscle antibodies with antiactin specificity (SMA-AA) are regarded as the serum markers of type-1 autoimmune chronic hepatitis. Their diagnostic relevance, however, has been questioned recently after the detection of signs of hepatitis C virus infection in autoimmune chronic hepatitis patients. To further evaluate this point, antihepatitis C virus antibodies were sought by two second generation assays (ELISA 2 and RIBA 2) in 100 Italian patients with chronic liver disease of unknown aetiology, including 46 with (autoimmune chronic hepatitis) and 54 without the above antibodies (cryptogenic). By ELISA 2, antihepatitis C virus, although significantly prevalent in cryptogenic (83%), were found also in a substantial proportion of autoimmune chronic hepatitis patients (46%) (p < 0.0001), their occurrence was confirmed by RIBA 2 in almost all cases (96% and 86%, respectively). Autoimmune patients with either ANA-H or SMA-AA exhibited similar antihepatitis C virus prevalences (59% and 52%, respectively); by contrast, the eight cases positive for both the autoantibodies were consistently antihepatitis C virus negative. These findings confirm that in countries with high hepatitis C virus circulation (like Italy) an overlap between autoimmune chronic hepatitis and hepatitis C virus infection, reflected by 'true' antihepatitis C virus antibodies, does occur. The detection of ANA-H or SMA-AA, in fact, identifies chronic liver disease patients with a relatively low prevalence of antihepatitis C virus, but does not exclude hepatitis C virus infection. Positive findings for both ANA-H and SMA-AA, however, is an appropriate marker for hepatitis C virus free 'primary' autoimmune chronic hepatitis.

Actins↗

Epidemiology of hepatitis C in a population of hemodialysis patients.

A search for antibodies against hepatitis C virus (HCV) was performed in 185 patients on chronic hemodialysis by means of 1st and 2nd generation ELISA tests. Immunoblot assays were performed on positive sera. This study shows a 38% prevalence of HCV-positive patients in our dialysis population according to the 2nd generation ELISA test which shows a higher specificity and sensitivity when compared to the 1st generation one (38 vs. 20%). A correlation was found between the prevalence of HCV-positive patients and how long they had been on dialysis and how many blood transfusions they had received.

Cross Infection↗

[Increased serum levels of IgA and C4 in atherosclerosis: the absence of a correlation with the arteriographic picture].

We have previously shown that an increase in serum IgA and C4 is often detectable in presence of diffuse atherosclerotic disease. The present study was performed to verify such results in a different and larger sample of subjects, and to ascertain whether the above immunologic variables are correlated with the severity of atherosclerotic disease. Seventy-three atherosclerotic subjects with at least 1 significant (> 75%) stenosis in a major arterial branch were selected according to the reports of arterial panangiographies performed previously. Among them, 36 subjects (24 men and 12 women, mean age 63 +/- 7 years) were singled out, who matched by age and sex 36 control subjects (mean age 63 +/- 7 years). In all of these subjects the following serum immunologic and lipid variables were measured: IgG, IgA, IgM, IgE, C3, C4, total cholesterol, HDL-cholesterol and triglycerides. With respect to the controls, the 36 matched atherosclerotic subjects had higher levels of IgA (263.0 +/- 119.8 vs 334.3 +/- 130.5 mg/dl; p = 0.0126), C4 (25.7 +/- 5.8 vs 30.4 +/- 9.1 mg/dl; p = 0.0297) and triglycerides (153.1 +/- 77.3 vs 209.7 +/- 141.3; p = 0.0500). No correlation was found between the number of arterial stenoses (range 1-8, mean 2.9 +/- 1.5) and any of the immunologic or lipid parameters in all the 73 atherosclerotic subjects. Only the daily cigarette consumption was correlated with the disease extension (tau = 0.1984; p = 0.0392).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗