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Biomedical subjects

F Locatelli

Publications and source records attributed to F Locatelli.

At least 235 records · Page 13Linked to original sources
PubMed1997

Angiotensin II (3-8) induces long-term memory improvement in the crab Chasmagnathus.

A shadow moving overhead acts as a danger stimulus and elicits an escape response in the crab Chasmagnathus that habituates after 15 trials and for a long period of time. Previous work showed that angiotensin II enhances this long-term memory. Present results indicate: (1) that the facilitatory effect of angiotensin II is not blocked by either losartan, DUP 753 or the Parke Davis compound PD 123177; (2) that the angiotensin II (3-8) fragment has an enhancing effect on crab's memory stronger than that reported for the integer octopeptide; (3) that the hypermnestic effect of angiotensin II (3-8) is dose-dependent and saralasin reversible. The possibility that the action of angiotensin II on crab's memory were not due to its own action but to that of the degradation fragment angiotensin II (3-8) is discussed.

Analysis of Variance↗
PubMed1997

Expression of G1-phase cell cycle genes during hematopoietic lineage.

Characterization of proteins that control the passage through the G1 phase of the cell cycle is of particular interest because virtually all stimuli regulating cell proliferation or differentiation act primarily during this phase. We have analyzed the G1 phase proteic machinery, including cyclin D types, cyclin-dependent kinases (CDKs) and CDK inhibitors, of cell populations obtained at different stages of hematopoietic cell lineage. In particular, five cellular phenotypes, namely CD34+ cells (which contain stem cells), BFU-E, CFU-E, CFU-GM and peripheral lymphocytes were studied as representatives of distinct differentiation pathways. The results obtained indicated that all the cellular preparations express cyclin D2 and D3, while cyclin D1, which is the major cyclin D occurring in mesenchimal tissues, is not expressed. Moreover, CDK6 (but not CDK4) was detectable in all the populations investigated. Among the CDK inhibitors studied, p18INK4C and p19INK4D signals were clearly evidentiable in the various cell types. Interestingly, high levels of p15INK4B, a putative tumor suppressor protein, were detectable especially in granulocyte-monocyte precursors. Our results indicate that a specific hematopoietic G1 phase machinery occurs, which is conserved during the various steps of the different maturation processes.

Carrier Proteins↗
PubMed1997

A trial of high-dose dexamethasone therapy for chronic idiopathic thrombocytopenic purpura in childhood.

OBJECTIVE: To determine the efficacy of high-dose dexamethasone in chronic idiopathic thrombocytopenic purpura of childhood. METHODS: Seventeen patients entered the protocol. Dexamethasone was to be given orally in two divided doses at a dosage of 20 mg/m2 for 4 consecutive days every 28 days for six courses. RESULTS: One month after the end of the sixth course, six patients (35%) had platelet values within the normal range. One year later, five patients (29%) still have normal platelet values. Five patients discontinued treatment before completion because of lack of response and in one case for important side effects. Duration of the disease before treatment was inversely correlated with response to dexamethasone: 5 of 10 patients who had had thrombocytopenia for 30 months or less went into remission, as opposed to none of the seven who had been sick for a longer period (p = 0.04). Side effects included fatigue or irritability, anxiety, abdominal pain, striae, hirsutism, acne, and weight gain. CONCLUSIONS: Contrary to what is observed in adults, in our patients pulsed dexamethasone therapy did not prove to be uniformly effective. However, in view of its effectiveness in a third of the patients, acceptable side effects, and low cost, we believe that this treatment could be considered in patients with chronic idiopathic thrombocytopenic purpura who do not tolerate the disease well, especially if no more than 3 years have elapsed since diagnosis. Larger studies will be necessary to define which patients will respond to this type of therapy.

Administration, Oral↗
PubMed1997

Ph-positive CML in blastic phase with monosomy 7 in a Down syndrome patient. Monitoring by interphase cytogenetics and demonstration of maternal allelic loss.

We report a case of Ph-positive chronic myelocytic leukemia in blastic phase in an 11-year-old boy with Down syndrome. Monosomy 7 was the only additional chromosomal anomaly in the blastic clone. Fluorescence in situ hybridization analysis on interphase nuclei with a centromeric probe specific to chromosome 7 proved to be efficient in disease monitoring, and showed, together with the results of chromosome analysis on metaphases, that B-lymphocytes at the origin of an EBV-established line were not part of the leukemic clone. The study of DNA polymorphisms showed that the origin of the constitutional trisomy 21 was a maternal anaphase I nondisjunction, that the chromosome 7 lost in the blastic marrow clone was the maternal one, and led us to postulate that the mother's chromosomes are prone to impairment of normal disjunction. The study of allelic losses of chromosome 7 loci proved to be a further possibility for disease monitoring.

Adult↗
PubMed1997

Ten years experience of renal replacement treatment in the elderly.

UNLABELLED: Elderly patients constitute an increasing segment of the end-stage renal disease population beginning renal replacement therapy (RRT) in the Western Countries. In this study we studied 2447 end-stage renal disease (ESRD) patients who started renal replacement treatment (RRT) in Lombardy between 1983 and 1992 at the age of 65 or older, with particular emphasis on survival and morbidity. In the last decade the number of elderly patients admitted yearly to RRT increased from 113 [102 per million population (pmp), 20% of all accepted patients] in 1983 to 375 (282 pmp, 42% of all accepted patients) in 1992. The most frequent primary nephropathies in 1992 were glomerulonephritis (21% vs 25% in 1983), vascular diseases (18% vs 13%) and diabetes (12% vs 7%). The use of acetate HD and IPD declined over the 10 years period from 49 to 11% and from 26 to 5%; that of bicarbonate HD and CAPD increased from 3 to 46% and from 26 to 32%. Hospitalization rate was related to age, sex, presence of systemic nephropathies or malignancy, but not to treatment modality. The main causes of death in 1992 were cardiovascular diseases (53 vs 42% in 1983) and cachexia (24 vs 18%). The survival rate of all elderly patients was 64, 39 and 13% at 2, 4 and 8 years. The covariates affecting patient survival (Cox model) were the presence at the start of RRT of systemic nephropathies (Hazard ratio 1.7), systemic atherosclerosis (1.6), other comorbidity conditions (1.38) and peritoneal dialysis (1.31). CONCLUSIONS: (1) The progressive increase in the number of patients admitted to RRT in the last decade is due to loose criteria of acceptance of elderly patients (increase in the acceptance rate of diabetics and patients with vascular disease), (2) patients' survival is affected by the presence of comorbid conditions at the start of RRT, (3) the worse survival rate in peritoneal dialysis could result from a hidden negative selection of patients, unmeasured by Cox analysis.

Adult↗
PubMed1997

The role of occupation and a past history of malaria in the etiology of classic Kaposi's sarcoma: a case-control study in north-east Sardinia.

A case-control study was performed to determine the role of rural factors including occupation and previous malaria exposure in the development of classic Kaposi's sarcoma (CKS) in a high incidence area of Europe. The occurrence of CKS association with other malignancies was also examined. The results showed that the risk of having CKS was significantly increased in subjects farming cereals, while a previous history of malaria did not influence the risk of developing CKS. A near-significant increase in associated tumours was found.

Aged↗
PubMed1997

Transplant of bone marrow and cord blood hematopoietic stem cells in pediatric practice, revisited according to the fundamental principles of bioethics.

The two most widely used sources of hematopoietic stem cells for allogeneic transplants in pediatric practice are bone marrow (BM) and cord blood (CB). While bone marrow transplantation (BMT) is reaching its 30th year of application, human umbilical cord blood transplantation (HUCBT) is approaching its 10th. Although these procedures have basically the same purpose, a number of biological differences distinguish them. In particular, the intrinsically limited quantity of CB stem cells and their immunological naiveté confer peculiar characteristics to these hematopoietic progenitors. From a bioethical point of view, the problems which have repeatedly been raised when the BM donor is a child are well-known. Different but no less important ethical problems are raised when one considers HUCBT; in this regard the most important issues are the easier propensity of programming a CB donor in comparison with a BM donor (clearly due to the shorter time interval needed to collect the hematopoietic progenitors); the in utero HLA-typing; the implication of employing 'blood belonging to a neonate' for a third party; the need to perform a number of investigations both on the CB of the donor and on the mother and the implications that the discovery of disease may have for them, but also the need to establish banks for storing CB, with the accompanying administration and management problems. All these different aspects of UCBT will be discussed in the light of the four fundamental and traditional principles of bioethics, namely autonomy, nonmaleficence, beneficence and justice.

Bone Marrow Transplantation↗
PubMed1997

Transplantation of cord blood progenitor cells can promote bone resorption in autosomal recessive osteopetrosis.

Allogeneic BMT has been reported to be the only curative therapy for children with juvenile autosomal recessive osteopetrosis. We report the case of a 14-month-old child in whom bone resorption was observed after cord blood transplantation (CBT). The patient was given CBT from an unrelated newborn matched for five of six HLA antigens. At the time of transplantation, the child presented with neurological symptoms, with feeding problems and visual impairment. A successful engraftment of donor hematopoiesis was demonstrated and the child experienced grade I acute GVHD. Progressive bone clearing was achieved and a bone marrow trephine demonstrated signs of osteoclast function. Despite full engraftment and bone resorption, neurologic deterioration did not improve. This experience documents that CBT can promote the correction of juvenile osteopetrosis. The shorter time needed both to identify an unrelated donor and to perform the transplant, as well as the lower incidence of GVHD make this procedure more appealing than BMT in children lacking an HLA-compatible relative.

Bone Resorption↗
PubMed1997

Second allogeneic bone marrow transplantation in acute leukemia: a multicenter study from the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO).

Thirty-eight second allogeneic bone marrow transplants (BMT) for acute leukemia relapsed after first BMT were performed in 13 Italian centers between 1987 and 1994. Twenty-one patients had acute myelogenous leukemia (AML), 17 acute lymphoblastic leukemia (ALL); at second BMT 24 patients were in complete remission (CR) and 14 in relapse. The median time to relapse after first BMT was 10 months (range 1-70). Grade II or greater acute graft-versus-host disease (GVHD) after second transplant occurred in 34.2% of patients and a chronic GVHD in 31.5% of patients. Twenty-four patients died: seven from early transplant-related mortality (TRM), 13 from relapse and four from late toxicity. As of 31 July 1996, at a median follow-up of 47 months (range 22-85), there are 14 survivors. The three-year probability of TRM, relapse and event-free survival (EFS) is 28%, 40% and 42% respectively. In 20 of 27 evaluable patients, remission duration after second BMT was longer than after the first BMT. A diagnosis of AML was correlated with a better outcome. These data support the usefulness of second allograft in selected patients with AML relapsing after a first BMT.

Adolescent↗
PubMed1997

Infusion of donor-derived peripheral blood leukocytes after transplantation of cord blood progenitor cells can increase the graft-versus-leukaemia effect.

We describe the case of a child affected by acute lymphoblastic leukaemia who received adoptive immunotherapy after cord blood transplantation (CBT). The patient, transplanted in second relapse resistant to chemotherapy, still showed lung and costal leukaemic nodular lesions 2 months after CBT. For this reason, three infusions of donor peripheral blood leukocytes 1 x 10(7)/kg each were administered on days +60, +80 and +100. The procedure was well tolerated by both patient and donor, and a complete disappearance of the lung lesions was documented 2 months after the last infusion. The patient remains in continuous complete haematological remission 13 months after CBT. This experience suggests that adoptive immunotherapy may be safely employed after CBT in order to increase the contribution of immune-mediated anti-leukaemia effect.

Adoptive Transfer↗
PubMed1997

Photopheresis in paediatric patients with drug-resistant chronic graft-versus-host disease.

Photopheresis (ECP) is a new type of photochemotherapy, used for the treatment of oncological and autoimmune diseases. Lymphocytes are drawn from the patients by leukapheresis, treated with 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) in an extracorporeal system and then reinfused. Skin exposure to 8-MOP and UVA (PUVA) has been shown to relieve cutaneous symptoms of graft-versus-host disease (GVHD) in bone marrow transplant (BMT) recipients. ECP, which is similar in some ways to PUVA, has been used in this study to treat four paediatric patients who developed chronic GVHD following BMT and in whom GVHD had failed to respond to conventional immunosuppressive therapy. Following ECP, skin lesions cleared almost completely and pulmonary function tests improved in two of three patients with cutaneous and lung involvement. Serum bilirubin and transaminases gradually normalized, and gammaGT decreased considerably in the remaining patient who had a severe cholestatic hepatopathy. The Karnofsky performance score increased to 90% in the three patients with positive responses to ECP and remained unchanged (40%) in the patient who did not respond. Immunosuppressive therapy was reduced in three patients and eventually discontinued in two. No significant side-effects were observed during the treatment. Our results suggest that ECP is a non-aggressive treatment that may benefit patients with chronic GVHD who do not respond to standard immunosuppressive therapy.

Adolescent↗
PubMed1997

Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission. Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study. All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation (n = 25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59-3.24), 0.69 (CI 0.27-1.77) and 0.35 (CI 0.06-1.91), with an overall non-significant difference between the two groups (P = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR). The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.

Antineoplastic Agents↗
PubMed1997

A moderate transfusion regimen may reduce iron loading in beta-thalassemia major without producing excessive expansion of erythropoiesis.

BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL is still considered by many to be the mainstay of conservative therapy for beta-thalassemia major. However, this regimen is frequently associated with manifestations of transfusion iron overload, despite regular chelation therapy with subcutaneous desferoxamine. STUDY DESIGN AND METHODS: To verify whether a transfusion regimen with a target pretransfusion hemoglobin level between 9 and 10 g per dL can allow a significant reduction in blood consumption, while still effectively suppressing erythropoiesis, the records were reviewed of 32 beta-thalassemia major patients, who were maintained at a pretransfusion hemoglobin of 11.3 +/- 0.5 g per dL between 1981 and 1986. These patients were switched at the beginning of 1987 to a transfusion regimen with pretransfusion hemoglobin of 9.4 +/- 0.4 g per dL. The degree of erythroid marrow activity was evaluated in these patients and in 32 subjects with beta-thalassemia intermedia through the simple measurement of serum transferrin receptor. RESULTS: After the adoption of the moderate transfusion regimen, transfusion requirements decreased from 137 +/- 26 to 104 +/- 23 mL per kg per year of red cells (p < 0.0001), and mean serum ferritin decreased from 2448 +/- 1515 to 1187 +/- 816 micrograms per L (p < 0.0001), with one-half of patients achieving serum ferritin levels lower than 1000 micrograms per L. The proportion of patients having spontaneous pubertal development increased significantly (p < 0.01), as a result of less iron-related gonadotropin insufficiency. At the lower pretransfusion hemoglobin, erythroid marrow activity did not exceed two to three times normal levels in most subjects. CONCLUSION: As compared with hypertransfusion, moderate transfusion may allow more effective prevention of iron loading, with higher likelihood of spontaneous pubertal development and without producing excessive expansion of erythropoiesis.

Adolescent↗
PubMed1997

Hepatitis E virus infection in haemodialysis patients: a seroepidemiological survey.

BACKGROUND: Hepatitis E virus (HEV) is the causative agent for enteric non-A, non-B hepatitis. Transmission is via the faecal route but the possibility of transmission by blood has been raised. Data concerning anti-HEV prevalence among chronic haemodialysis (HD) patients are few and give conflicting results. METHODS: We tested for anti-HEV antibody 204 chronic HD patients attending a single dialysis unit. A specific solid-phase enzyme-linked immunoassay (Abbott HEV EIA) was used. RESULTS: We found six anti-HEV-positive patients, the anti-HEV prevalence was 3% (95% CI 0-6%). The prevalence rates of HBV and HCV infections were 39% (31-45%) and 22% (16-28%) respectively. No anti-HEV-positive patient showed past or current biochemical signs of liver damage. One of six (17%) anti-HEV-positive patients was an immigrant; no risk factor for anti-HEV antibody was identified in the other anti-HEV-positive individuals. CONCLUSIONS: We observed a low anti-HEV prevalence: there was no association between HEV and blood-borne infections (HBV, HCV, and HIV) in our HD patients; most anti-HEV-positive patients we found were probably related to a local infection by HEV. This is one of the first reports concerning seroepidemiology of HEV infection in a large cohort of chronic HD individuals.

Adult↗
PubMed1997

Serologic survey for control of hepatitis C in haemodialysis patients: third-generation assays and analysis of costs.

There is little information about the serologic survey for control of hepatitis C by using third-generation assays among chronic haemodialysis (HD) patients, and no analysis of costs has been made to this end. A serologic survey for control of hepatitis C was performed in 190 HD patients attending a single dialysis unit, using second- and third-generation assays. Costs of both serologic surveys were calculated. Anti-HCV prevalence tested by third-generation assays increased from 25% (48/190) to 28% (53/190) compared to second-generation testing; 56% (9/16) of patients showing uncertain findings by second-generation tests gave unequivocal results by third-generation assays; median duration of HD treatment and raised aminotransferase levels were positively associated (P = 0.004 and P = 0.012, respectively) with anti-HCV detected by third-generation assays. The serologic survey for control of hepatitis C in HD patients at our centre was slightly more expensive by third-generation assays compared to second-generation testing (US$18866 vs US$17200 per year). In summary, the use of third-generation tests largely clarified the uncertain results of second-generation tests; new additional positive patients were detected by third-generation assays compared to second-generation testing. Third-generation assays showed the association of duration of HD treatment and raised aminotransferase levels with anti-HCV antibody, as previously found by first- and second-generation assays. To date, third-generation screening and confirmatory assays seem extremely useful in the serologic survey for control of hepatitis C in HD centres without a considerable outlay.

Adult↗