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Biomedical subjects

Giuseppe Rossi

Publications and source records attributed to Giuseppe Rossi.

16 recordsLinked to original sources

High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy.

PURPOSE: High-dose therapy (HDT) and peripheral-blood stem-cell transplantation (PBSCT) in HIV-associated lymphoma (HIV-Ly) has been recently reported in selected patients. We describe the results of a multi-institutional program of HDT and PBSCT as salvage therapy in HIV-Ly responsive to highly active antiretroviral therapy (HAART) in unselected patients. PATIENTS AND METHODS: Patients with resistant or relapsed HIV-Ly after first-line chemotherapy (CT) underwent PBSC collection after a course of second-line CT or cyclophosphamide and granulocyte colony-stimulating factor. Patients with chemotherapy-sensitive disease received carmustine, etoposide, cytarabine, and melphalan (BEAM regimen) and PBSC reinfusion. Effective HAART was maintained during the entire program. RESULTS: Sixteen consecutive patients entered the program. Adequate collection of PBSC was obtained in 80% of patients (median CD34+ cells 6.8 x 106/kg). Three patients had early progression. Ten patients (62%) received PBSCT with prompt engraftment in all patients (neutrophils and platelet engraftment after a median of 10 days [range, 8 to 10 days] and 13 days [range, 8 to 18 days], respectively). No patients died as a result of opportunistic or other infections or treatment-related complications. Eight of nine assessable patients achieved complete remission (one patient after radiotherapy for residual disease) and one patient achieved partial remission. Two patients experienced relapse and died at +10 and +14 months. Six patients are alive and disease free at a median of 8 months after transplantation. CONCLUSION: Our data confirm that HDT plus PBSCT is feasible and active as salvage therapy in HIV-Ly on a multi-institutional basis and in unselected HAART-responding patients. HIV infection should no longer preclude the opportunity of HDT in patients with lymphoma.

Anti-HIV Agents↗

Orthostatic hypotension in de novo Parkinson disease.

BACKGROUND: It is accepted that orthostatic hypotension is a clinical marker for the diagnosis of multiple system atrophy, but conflicting data indicate that it may also be present in Parkinson disease (PD). OBJECTIVES: To evaluate the prevalence of autonomic cardiovascular impairment and orthostatic hypotension in a large group of patients with de novo PD, followed up for at least 7 years, to clinically confirm the diagnosis of the disease. METHODS: During a 2-year recruiting period, 60 untreated patients diagnosed as having idiopathic PD underwent autonomic cardiovascular function evaluation using the Ewing test. Patients subsequently received dopaminergic therapy and their condition was followed up for at least 7 years. RESULTS: Nine (15%) of 60 patients were excluded from the study because during the follow-up period a parkinsonian syndrome was diagnosed (5 had multiple system atrophy and 4 had progressive supranuclear palsy). Data from 51 patients with PD underwent final statistical analysis and the results were compared with those of 51 age-matched healthy control subjects who had taken the same battery of autonomic tests. A statistically significant difference was found in postural hypotension (P =.02) and deep breathing test results (P =.03) between patients and controls. Seven (14%) of 51 patients with PD and 3 (60%) of 5 patients with multiple system atrophy had a decrease of more than 20 mm Hg in systolic blood pressure on standing. CONCLUSIONS: Data from this study indicate a high prevalence of sympathetic and parasympathetic failure in patients with de novo PD, and when using a decrease of at least 20 mm Hg in systolic blood pressure, manometric orthostatic hypotension was found in 7 (14%) of the 51 patients with de novo PD.

Autonomic Nervous System↗

Immune reconstitution and early infectious complications following nonmyeloablative hematopoietic stem cell transplantation.

Non-myeloablative stem cell transplantation (NMT) has been increasingly used in compromised patients who would otherwise have been unable to undergo allotransplant. There is little understanding of the kinetics of immune reconstitution and its influence on infective complications following NMT. The aim of present study was to evaluate lymphocyte subset reconstitution over the first 12 months post-transplant in 15 adult patients receiving NMT with comparison to that of 30 patients grafted with a conventional hemopoietic stem cell transplantation (HSCT). NMT recipients were conditioned with fludarabine-based conditioning regimens. Peripheral blood stem cell (PBSC) was the source of stem cells in 13 NMT recipients and in 24 conventional HSCT recipients. Absolute numbers of helper (CD4+) T cells, naive (CD4+ CD45RA+) and memory (CD4+ CD45RO+) T cells as well as suppressor (CD8+) T cells, CD19+ B cells and NK cells were comparable in the two groups at all time points after transplantation. A median value of 200 CD4+ T cells/microl was achieved at 2 months post-transplant by the NMT and HSCT recipients. The CD4:CD8 ratio remained severely depressed throughout the study period. Almost all CD4+ lymphocytes expressed CD45RO antigen in the both groups of patients B lymphocytes showed low counts throughout the entire study period in both groups. Bacteremia and CMV antigenemia occurred respectively in 13 and 36% of the patients in the NMT group and in 15 and 39% of the patients in the HSCT group. Our preliminary data indicate that patients receiving a NMT have a lymphocyte reconstitution similar to that observed in patients who received a conventional HSCT. The incidence of bacteremia and CMV infection were not significantly different between the groups. Nevertheless, due to the small sample size, these results should be considered suggestive rather than definitive.

Adult↗

Prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with hemato-oncological neoplasias treated with chemotherapy.

Reactivation of hepatitis B virus (HBV) infection is well documented complication of cytotoxic or immunosuppressive therapy in asymptomatic HBV carriers. Its clinical manifestation include fulminant hepatitis which may result in fatal liver failure. With the more widespread use of chemotherapy and hematopoietic stem cell transplantation, the problem of delivering potentially harmful treatment to HBV carriers is becoming increasingly frequent. Until recently the management of HBV reactivation has been mainly supportive. With the introduction of lamivudine, a highly effective nucleoside analogue against HBV with an excellent toxicity profile has become available. However, in light of the possibility that its prolonged use may foster the emergence of mutant lamivudine-resistant HBV strain, caution is required before recommending its widespread use. The present review briefly addresses the epidemiological, pathogenetic and clinical aspects of HBV reactivation as well the predisposing factors to its development. The results obtained with lamivudine both as treatment and as prophylaxis of hepatic flares are analysed in detail in order to provide a rational basis for clinical decisions before treating HBV carriers with chemotherapy.

Antineoplastic Agents↗

Treatment of type II amiodarone-induced thyrotoxicosis by either iopanoic acid or glucocorticoids: a prospective, randomized study.

Amiodarone-induced thyrotoxicosis (AIT) may occur either in the presence of underlying thyroid disease (type I AIT) or in apparently normal thyroid glands (type II AIT). Type II AIT, a destructive thyroiditis, often favorably responds to glucocorticoids. Iopanoic acid (IopAc) is an iodinated cholecystographic agent that inhibits deiodinase activity and reduces the conversion of T(4) toT(3). It has recently been reported that cholecystographic agents restore euthyroidism in patients with type II AIT. We describe the results of a prospective randomized study conducted in 12 patients with type II AIT treated with either iopanoic acid (group A, n = 6) or glucocorticoids (group B, n = 6). Serum free T(3) levels normalized rapidly in both groups after 7 d, from 0.75 +/- 0.20 ng/dl (11.5 +/- 3.1 pmol/liter) to 0.46 +/- 0.10 ng/d (7.1 +/- 1.7 pmol/liter), P < 0.01, and from 0.58 +/- 0.10 ng/dl (9.0 +/- 1.2 pmol/liter) to 0.34 +/- 0.03 ng/dl (5.2 +/- 0.5 pmol/liter), P < 0.003, in groups A and B, respectively (P = NS). Serum free T(4) levels reduced at 6 months in group B [from 2.70 +/- 0.32 ng/dl (35.1 +/- 4.1 pmol/liter) to 1.0 +/- 0.04 ng/dl (13.4 +/- 0.6 pmol/liter), P < 0.0001] but not in group A (from 2.90 +/- 0.6 ng/dl (38.0 +/- 7.5 pmol/liter) to 2.30 +/- 0.4 ng/dl (35.6 +/- 6.1 pmol/liter, P = 0.39; P = 0.005 group B vs. group A). All patients in both groups became euthyroid and had their amiodarone-induced destructive thyroiditis cured as defined by normalization of both serum free T(4) and free T(3) levels, during both drugs therapy. However, patients in group B were cured more rapidly than patients in group A (43 +/- 34 d vs. 221 +/- 111 d, respectively, P < 0.002). This study shows that, albeit both drugs are effective, glucocorticoids are probably the drug of choice for more rapidly curing type II AIT.

Aged↗

Uncontrolled-rate freezing of peripheral blood progenitor cells allows successful engraftment by sparing primitive and committed hematopoietic progenitors.

BACKGROUND AND OBJECTIVES: Uncontrolled-rate freezing (URF) techniques, which are fast and easy, could represent an attractive alternative to controlled-rate cryopreservation procedures which are time consuming and require high-level technical abilities. It was the aim of the present study to evaluate, on a routine basis, whether URF might spare primitive hematopoietic progenitors and maintain engrafting capacity. DESIGN AND METHODS: One-hundred and nineteen peripheral blood progenitor cells (PBPC) collections from 104 patients with hematologic malignancies were cryopreserved in bags, with an URF procedure, in a cryoprotectant solution consisting of PBS, HSA and 10% DMSO and stored in liquid nitrogen. PBPC bags were tested before cryopreservation and at thawing for primitive (LTC-IC) and committed hematopoietic progenitors (CFU-Mix, BFU-E, CFU-GM) by means of long- and short-term culture assays, respectively. In addition, PBPC bags were evaluated for CD34+ cell numbers. RESULTS: Although thawing was associated with a statistically significant reduction of the absolute number of nucleated cells, recovery of LTC-IC, CFU-Mix, BFU-E, CFU-GM and CD34+ cells was not affected by the freezing/thawing procedures. No adverse effects were reported at thawing and only mild transient reactions were recorded in 22 patients during reinfusion of cryopreserved PBPC. All the patients underwent myeloablative therapy followed by reinfusion of PBPC, and prompt and rapid hematopoietic recovery was obtained in all patients. INTERPRETATION AND CONCLUSIONS: Our freezing procedure is fast and easy, and allows rapid hematopoietic recovery after myeloablative therapy by sparing primitive and committed hematopoietic progenitors. Our study strongly supports technical improvements aimed at cost reduction and feasibility of routine freezing procedures.

Adolescent↗

Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection.

A phase 2 prospective study was performed to evaluate the feasibility and activity of a short, dose-intensive chemotherapy regimen and radiotherapy (the Stanford V regimen) plus highly active antiretroviral therapy (HAART) and granulocyte colony-stimulating factor (G-CSF) support in patients with Hodgkin disease and HIV infection. Fifty-nine patients were enrolled. Stanford V was well tolerated and 69% of the patients completed treatment with no dose reduction or delayed chemotherapy administration. The most important dose-limiting side effects were bone marrow toxicity and neurotoxicity. Complete remission was achieved by 81% of the patients, and after a median follow-up of 17 months 33 patients (56%) were alive and disease-free. The estimated 3-year overall survival (OS), disease-free survival (DFS), and freedom from progression (FFP) were 51%, 68%, and 60%, respectively. Probability of FFP was significantly (P =.02) higher among patients with an International Prognostic Score (IPS) of 2 or lower than in those with an IPS higher than 2, and the percentages of FFP at 2 years in these groups were 83% and 41%, respectively. Similarly, the probability of OS was significantly (P =.0004) different in the 2 groups, and the percentages of OS at 3 years were 76% and 33%, respectively. Our data confirm that the Stanford V regimen with concomitant HAART is feasible and active in an HIV setting. However, a more intensive approach should be considered in patients with high IPSs.

Adult↗

Severe pancytopenia and hemophagocytosis after HHV-8 primary infection in a renal transplant patient successfully treated with foscarnet.

We report the occurrence of human herpesvirus (HHV)-8 primary infection in an adult male kidney recipient. Four months after transplantation, the patient developed visceral Kaposi sarcoma, and 1 month later he presented with progressive and severe peripheral cytopenia, in the presence of a normocellular or hypercellular bone marrow (BM) with hemophagocytosis. HHV-8 was the sole pathogen detected by polymerase chain reaction either in the serum or in the BM. HHV-8 latent nuclear antigen was detected in immature progenitor cells from the BM. Immunosuppressive therapy was reduced, and the patient was treated with foscarnet for 2 weeks, leading to a dramatic normalization of blood cell counts, concomitantly with the disappearance of HHV-8 viremia. At the end of antiviral therapy, the patient received chemotherapy, and Kaposi sarcoma regressed in 2 months. Severe peripheral cytopenia may be a posttransplant complication after HHV-8 infection, for which treatment with foscarnet seems appropriate.

Antiviral Agents↗

Platelet kinetic study in patients with idiopathic thrombocytopenic purpura (ITP) refractory or relapsing after corticosteroid treatment.

BACKGROUND: A platelet kinetic study (PKS) is not indicated in the evaluation of adult patients with idiopathic thrombocytopenic purpura (ITP) at presentation. However, in ITP patients refractory to or relapsing after corticosteroid therapy, its appropriateness is considered uncertain. METHODS: We prospectively performed a PKS with (111)In oxine-labeled autologous platelets in 93 consecutive adult ITP patients failing steroid treatment. RESULTS: In 22 patients (24%) a primary condition accounting for thrombocytopenia was identified (17 with myelodysplastic syndrome and three aplastic anemia). Non-ITP patients had significantly longer platelet circulating life span (P=0.0001), lower splenic platelet uptake (P=0.008) and higher liver platelet uptake (P=0.05) compared to 71 patients with confirmed ITP. Among ITP patients with platelets persistently <50 x 10(9)/L, splenectomy was considered in 48 cases. In 23 (48%) it was prospectively excluded because of platelet life span > or = 7 days (11 cases), no splenic platelet uptake together with high liver uptake (10 cases), or both conditions (two cases). Splenectomy was successfully carried out in the other 25 patients, obtaining a response rate of 100% (22 complete responses; three partial responses). Persistent relapse occurred in six of 25 (24%) splenectomized patients after a median of three months (range 1-8). PKS parameters were not able to predict post-splenectomy relapse, although relapsed patients had lower splenic/hepatic platelet uptake ratio (2.6 in relapsed vs 4.9 in persistently responsive patients; P=0.08). CONCLUSIONS: It was concluded that in patients with chronic ITP failing steroid therapy, some PKS parameters may be prospectively used to increase the short term success rate of splenectomy.

Adolescent↗

Isolated bone marrow manifestation of HIV-associated Hodgkin lymphoma.

Human immunodeficiency virus-associated Hodgkin lymphoma frequently involves the bone marrow and is usually recognized at staging after Hodgkin lymphoma diagnosis on a lymph node or other tissue biopsies, but occasionally the marrow involvement is the only apparent manifestation of disease. In the latter setting, diagnosis can be problematic. From a total of 42 patients with newly diagnosed human immunodeficiency virus-associated Hodgkin lymphoma, 22 subjects had positive marrow involvement at diagnosis; 16 of them had additional substantial histological and/or clinical extramedullary Hodgkin lymphoma. In the remaining 6 patients the bone marrow was the only site of disease at diagnosis. In all six cases, bone marrow biopsy revealed obvious lymphomatous involvement. Reed-Sternberg cells were identified both morphologically and immunophenotypically in all cases. Spared marrow tissue consistently showed fibrosis. All patients were males with a median age of 35 years (range, 31-58 years). All presented with fever, blood cytopenias, and severe CD4+ lymphocyte depletion (median, 70 cells/mm(3)). After diagnosis, all staging procedures were negative, and all patients were treated with chemotherapy. Median survival was 4 months (range, 2-118 mo). Longer survival was achieved in the patients who completed chemotherapy regimens; three subjects, however, died shortly before the full completion of chemotherapy, two of them from Hodgkin lymphoma. Isolated bone marrow HIV-associated Hodgkin lymphoma may be an underestimated condition in HIV-infected patients; in those individuals with unexplained fever and blood cytopenias, bone marrow biopsy should be performed with the aim of assessing for Hodgkin lymphoma, even in the absence of nodal and visceral lymphomatous involvement. A rapid diagnosis of isolated bone marrow HIV-associated Hodgkin lymphoma could expedite therapy.

Adult↗

Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with Graves' disease.

Serum thyroid hormone concentrations increase after radioiodine (RAI) therapy for Graves' disease. This phenomenon has been ascribed to either antithyroid drug withdrawal before RAI therapy or release of preformed thyroid hormones into the bloodstream from the RAI-damaged thyroid. Lithium blocks the release of iodine and thyroid hormones from the thyroid, thus enhancing the effectiveness of RAI therapy. Changes in serum-free thyroxine (FT4) and triiodothyronine (FT3) levels after methimazole (MMI) discontinuation and RAI therapy were evaluated in a prospective, randomized, control study of 36 patients with Graves' disease. After a 3- to 4-month course of MMI, patients were assigned to one of three groups: G1 (RAI alone); G2 (RAI plus lithium for 6 d starting on the day of RAI therapy); or G3 (RAI plus lithium for 19 d starting on the day of MMI withdrawal). G1-G2 patients had an increase in serum FT4 and FT3 levels from 13.5 +/- 6.5 to 19.8 +/- 9.2 pmol/liter and 5.0 +/- 2.0 to 8.0 +/- 4.8 pmol/liter, respectively (P < 0.0001), 2-5 d after MMI withdrawal, but G3 patients showed no changes. In the 30 d after RAI therapy, mean serum FT4 values increased in G1 patients (P = 0.02), peaking at 3-7 d (P < 0.05) but not in G2 and G3 patients. Serum FT3 levels decreased in G1, G2, and G3 (P = 0.03, P = 0.001, P = 0.02, respectively). Hyperthyroidism was cured in 8 of 12 G1 patients, 11 of 12 G2 patients, and 11 of 12 G3 patients (P = 0.31). Control of hyperthyroidism was prompter in G2 (P = 0.08) and G3 (P < 0.05) than in G1 patients. Patients in the three groups received a similar dose of RAI, but the committed radiation to the thyroid was higher in G3 (563 +/- 174 Gray) and G2 (588 +/- 347 Gray) than in G1 (429 +/- 204 Gray) (P < 0.03). In conclusion, the results of the present study demonstrate that: 1) MMI withdrawal is associated with a slight rise in serum thyroid hormone levels; 2) a further increase occurs after RAI therapy; 3) changes in serum thyroid hormone concentrations are prevented by lithium; and 4) the increased effectiveness of RAI therapy in lithium-treated patients is related to the increased RAI retention in the thyroid gland. Accordingly, a short course of lithium therapy can be considered a useful adjunct to RAI therapy to obtain a prompter control of thyrotoxicosis and avoid its transient exacerbation because of MMI withdrawal and RAI administration.

Antithyroid Agents↗

Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia.

It has been established that cytokines play a critical role in the regulation of the CNS and recent studies have suggested that dysfunctions of both pro-inflammatory (IL-1beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-1RA and IL-10) cytokines could be involved in the pathophysiology of schizophrenia. Previous studies have reported that functional polymorphisms in some cytokines genes may have important regulatory effects on such system. Therefore, the aim of the present study was to explore the possible role of the IL-1beta -511C/T and IL-1RA (86bp)(n) repeats polymorphisms in schizophrenia. A case control association study comparing genotype and allele frequencies in 346 northen Italian subjects (169 schizophrenic patients and 177 unrelated healthy volunteers) was performed. The frequencies of IL-1beta -511C and IL-1RA allele 1 (86bp)(4) are significantly higher in schizophrenic patients compared to controls (IL-1beta -511 P=0.047; IL-1RA (86bp)(n) P=0.002). Moreover our data show a protective effect of the IL-1RA allele 2 (86bp)(2) against schizophrenia (OR=0.59 95%CI:0.388-0.910; P=0.016) and this effect is enhanced by the concomitant presence of IL-1beta -511T (OR=0.48 95%CI:0.30-0.76; P=0.002). Our findings support the hypothesis that genetically determined changes in IL-1 metabolism regulation may contribute to the pathogenesis of schizophrenia confirming a role of IL-1 gene cluster in disease susceptibility.

Adult↗

[Efficacy of the "VADO" approach in psychiatric rehabilitation: a controlled study].

AIMS: Assessment of the efficacy of the rehabilitation approach that is recommended by the manual VADO (AAOS in English: Abilities Assessment and Objectives Setting) in schizophrenic syndromes. METHODS: Controlled trial, partly with individual randomisation. Centres were invited to recruit 10 patients who in most centres were randomly allocated either to the VADO approach or to usual rehabilitation practice. At least two professionals for each centre attended a brief intensive training course. Patients were assessed at baseline and six months later with a) the FPS scale, which is an improvement on the DSM-IV SOFAS; b) the BPRS 4.0; c) AR, a clinical tool that is contained in VADO. RESULTS: 55 patients received the experimental interventions and 40 the control one. Six months later greater significant improvements were observed in the experimental group, both in social functioning and in psychopathology. CONCLUSIONS: The dissemination of structured rehabilitation approaches that are based on personalized definition of objective, intensive progress monitoring, patient's therapeutic education and validated strategies and do not imply additional costs, may be warranted. A longer follow-up is under way.

Adult↗