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Biomedical subjects

F Locatelli

Publications and source records attributed to F Locatelli.

At least 361 records · Page 20Linked to original sources
PubMed1993

A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome.

To compare the efficacy (induction of remission) and safety of cyclosporine (CsA) with those of supportive therapy in patients with steroid-resistant idiopathic nephrotic syndrome (INS), we organized an open, prospective, randomized, multicentric, controlled study for parallel groups, stratified for adults and children. Forty-five patients with steroid-resistant INS were randomly assigned to supportive therapy or CsA (5 mg/kg/day for adults, 6 mg/kg/day for children) for six months, then tapered off by 25% every two months until complete discontinuation. Four patients were lost to follow-up. During the first year 13/22 CsA-treated patients versus three of 19 controls attained remission of the nephrotic syndrome (P < 0.001). A symptom score was assessed at time 0 and at six months. The mean score significantly decreased in the CsA group (P < 0.001), but remained unchanged in the controls. At month 6 the mean urinary protein excretion, the mean serum proteins and plasma cholesterol had significantly improved in the CsA group but were not changed in the controls. There were no significant differences in serum creatinine and creatinine clearance between treatments (interaction time* treatments, P = 0.089 and P = 0.935, respectively) at month 6 versus basal. The CsA-related side-effects were mild; no significant difference in blood pressure between the two groups was seen at any time. This study shows that CsA can bring about remission in some 60% of patients with steroid-resistant INS. In patients with normal renal function and without severe hypertension, CsA at the therapeutic scheme adopted did not produce severe renal or extrarenal toxicity.

Adolescent↗
PubMed1993

Antibodies to hepatitis C virus (HCV) and transaminase concentration in chronic haemodialysis patients: a study with second-generation assays.

We used first- and second-generation assays such as Ortho 1, Ortho 2 and 4-RIBA to define prevalence and risk factors for anti-HCV antibodies in haemodialysed patients. Forty-nine (24%) subjects were found to be anti-HCV positive. Anti-HCV positivity was related to duration of dialysis and past or current elevations of GOT and GPT; the frequency of transfused patients was greater in HCV-positive than in HCV-negative subjects; there were 31 patients (prevalence of 20%) with anti-HCV antibodies among non-transfused patients. These findings show that, tested by second-generation assays, HCV infection is detected more than twice as commonly in haemodialysis patients and may be responsible for a significant proportion of liver disease in this clinical setting. Acquisition of hepatitis C virus by dialysis patients is not only through blood transfusions but also secondary to hepatitis C virus presence within the unit itself.

Adolescent↗
PubMed1993

Accelerated erythroid repopulation with no stem-cell competition effect in children treated with recombinant human erythropoietin after allogeneic bone marrow transplantation.

We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) to accelerate erythropoietic engraftment in paediatric patients undergoing allogeneic BMT. rHuEPO was administered intravenously at a dose of 75 U/kg per day for 30 d after transplant. Erythroid repopulation, evaluated sequentially through the serum transferrin receptor, was faster in 15 patients receiving rHuEPO than in 16 historical controls (P = 0.0003). This faster erythroid engraftment resulted in a reduction in the total number of red blood cell units required to reach transfusion independence (2.7 +/- 1.2 v 4.2 +/- 2.3, P = 0.027). No significant difference in leucocyte or platelet regeneration was observed. These findings indicate that rHuEPO administration can accelerate erythroid recovery after allogeneic BMT and reduce red cell transfusion requirements with no stem-cell competition effect.

Adolescent↗
PubMed1993

Growth in children after bone marrow transplantation.

Growth velocity pattern and growth hormone (GH) secretion were evaluated in 18 prepubertal patients (13 males, 5 females), receiving an allogeneic (7 patients) or autologous (11 patients) bone marrow transplantation (BMT). Children were affected by oncological or hematological malignancies and the age range was between 2 and 11 years. Nine patients received a conditioning regimen consisting of chemotherapy and fractionated total body irradiation (TBI) (12 Gy in 6 fractions over 3 days), whereas 9 children also received previous prophylactic cranial irradiation during first-line chemotherapy. GH secretion in response to pharmacological stimuli (insulin, arginine and/or L-Dopa) was evaluated when growth failure occurred. The 9 prepubertal patients who had received previous prophylactic cranial irradiation during first-line chemotherapy, showed a significant decrease in growth rate already 1 year after BMT and this reduced growth rate presented a progressive further decrease in the 2nd and 3rd year after BMT. On the contrary, in the 9 prepubertal children treated with TBI and chemotherapy alone, growth rate presented an impressive decrease only during the 3rd year. In the two groups of patients, pretransplantation growth rates were comparable, while, due to the earlier growth failure in children receiving TBI and previous prophylactic cranial irradiation, mean standard deviation score (SDS) significantly differed at 1 and 2 years following BMT. Such a difference disappeared at 3 years after BMT, because of the late decrease in growth rate in patients given TBI and chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMed1993

IgA nephropathy: remission during pregnancy and relapse in the puerperium.

A 39-year-old woman, with proteinuria and microhematuria, at about the 8th week of pregnancy showed a reduction in proteinuria. After the 16th week, proteinuria disappeared. In the 40th week, the patient spontaneously delivered a 1.990-kg still-born female. Six days later, blood pressure increased (to 150/100 mm Hg), and laboratory examinations showed that proteinuria was 2.7 g/24 h. Given that urinalysis confirmed the presence of proteinuria, 6 weeks later, a renal biopsy was performed. The final diagnosis was IgA nephropathy. It is possible that the presence of the fetus may have led to changes in the maternal immunological system which may have attenuated the immunopathogenic mechanisms responsible for IgA nephropathy.

Adult↗
PubMed1993

Controlled trials on low-protein diet: effects on chronic renal insufficiency progression.

The effect of a low-protein diet (LPD) on chronic renal insufficiency (CRI) progression was investigated by reviewing the published studies. Only three of these fulfilled the main methodological criteria of being randomized, prospective, and controlled: those of Rosman, Ihle and Locatelli. These trials involved 811 patients (671 evaluated: 338 on a LPD, 333 as controls) and had a mean follow-up of 29 months (range 18-48), for an estimated total of about 17,335 patient-months. The only trial whose results showed that LPD had a positive effect on chronic renal failure (CRF) progression was Ihle's study, with the lowest weight (6.7%) and involving the most severe CRF; effects limited to the patients with more advanced CRF were found in the Rosman study, with an intermediate weight (41.8%); and little effect, if any, was found in the Locatelli trial, accounting for 51.5% of patient-months, with less severe CRI. In conclusion, analysis of published randomized, prospective, and controlled trials offers little or no support for the hypothesis that a LPD has a clinically significant effect on the early CRI progression, although a very low protein diet seems to postpone the need for dialysis.

Adult↗
PubMed1993

High-dose sequential (HDS) chemotherapy with blood and marrow cell autograft as salvage treatment in very poor prognosis, relapsed non-Hodgkin's lymphoma.

We tested the feasibility and efficacy of a novel high-dose sequential chemoradiotherapy programme (HDS) in 14 relapsed or refractory non-Hodgkin's lymphoma patients with very poor prognostic features, i.e. transformed histology, marrow invasion, low performance status. This regimen included the sequential administration of high-dose cyclophosphamide (CY) 7 g/m2 followed by high-dose methotrexate (MTX) 8 g/m2 and high-dose VP16 2 g/m2 and finally by total body irradiation (TBI)-melphalan and autograft of bone marrow and peripheral blood progenitor cells. No hemopoietic growth factor support was employed in any phase. There was one treatment-related death during the high-dose phase; three other patients did not complete the programme. All 10 patients concluding the programme achieved complete remission, with four patients in complete clinical remission at a median follow up of 34 months. Median overall survival was 27 months and median failure-free survival (FFS) was 12 months. Twenty-six well comparable patients received conventional salvage therapy during the same period. Their projected median overall survival (8 months) and median FFS (4 months) were shorter than in the HDS group (p = 0.06 for overall survival and p = 0.03 for FFS). Thus, HDS is a feasible programme and may offer superior results than conventional therapy in poor-prognosis NHL patients.

Adult↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Bone marrow transplantation from unrelated donors: the Italian experience. GITMO, AIEOP and IBMDR.

We report on 24 patients with leukemia (19 pts), congenital disorders (4 pts) or severe aplastic anemia (1 pt) who received bone marrow transplantation from unrelated volunteer donors in 8 Italian Institutions. All the donor/recipient pairs were serologically HLA-A,B,DR matched; MLR was non reactive in 21 out of 24 cases. Preparative regimens were in accord with standards for diagnosis and disease status and included TBI in 15 patients, busulfan in 8, cyclophosphamide alone in one patient with SAA. GvHD prophylaxis consisted of cyclosporine/methotrexate in the majority of cases; 6 patients received additional immunotherapy with anti-lymphocyte globulin and 1 patient in vivo Campath-1G. The bone marrow was T-cell depleted in 2 cases. Acute GvHD grade II-IV occurred in 87% of patients (gr.III-IV: 57%) and was the main cause of death in 8 cases. Six patients (25%) survive with a median follow-up of 9 months, (16% actuarial survival at 3 years). A trend in favour of a better outcome has been found for age < 20 yrs at BMT (33% vs 22%), intensified GvHD prophylaxis (33% vs 22%) and transplants performed in more recent years (31% vs 18%).

Adolescent↗
PubMed1992

Sinus histiocytosis with massive lymphoadenopathy (Rosai-Dorfman disease). Clinico-pathological analysis of a paediatric case.

Histochemical and immunohistochemical studies performed in only a few cases of sinus histiocytosis with massive lymphoadenopathy (SHML) indicated that SHML cells belong to the macrophage--histiocyte system, though their exact origin is still uncertain. We analyzed the morphological, antigenic and enzymatic characteristics of the histiocyte-like cells in one paediatric case of SHML (also named Rosai-Dorfman disease). The SHML cells expressed the S-100 protein, lectins concanavalin A, peanut agglutinin and monocyte-macrophage related antigens CD 11c, CD 14, CD 33, CD 68 and LN 5. Reactivity with other anti-macrophage antibodies (MAC387, lysozyme, alpha-1 anti-chymotrypsin) was variable. The CD1a antigen was present only in scattered cells, whereas HLA-DR and the HLA-DR associated invariant chain were absent. Cytochemistry demonstrated an intense activity of acid phosphatase and non specific esterase of SHML cells. A large amount of medium sized mononuclear cells were located in the sinuses and intersinusoidal tissue. Our findings suggest that SHML cells have intermediate features between phagocytes and Langerhans cells/interdigitating reticulum cells. The heterogeneity of marker expression on SHML cells might be related to the local content of factors (e.g., cytokines), capable of modulating the phenotype of monocyted and derived cells.

Child↗
PubMed1992

Recombinant human erythropoietin is effective in correcting erythropoietin-deficient anaemia after allogeneic bone marrow transplantation.

Two children affected by severe aplastic anaemia (SAA) underwent allogeneic bone marrow transplantation (BMT) using partially matched family donors. In both cases there was a successful engraftment of donor haemopoietic stem cells. However, after an initial erythropoietic recovery, 5 months following BMT both children became severely anaemic. Although multiple factors were responsible for anaemia, in both cases there was a markedly impaired erythropoietin response to anaemia, as indicated by the inappropriately low levels of serum erythropoietin (EPO). Treatment with recombinant human erythropoietin (rHuEPO) induced a sustained erythropoietic response with complete correction of anaemia. This pilot study suggests that rHuEPO can be effective in correcting long-lasting anaemia after marrow transplantation, characterized by inadequate erythropoietin production.

Anemia↗