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E Arbustini

Publications and source records attributed to E Arbustini.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral CD4+ CD25+ Treg cell expansion in lung transplant recipients is not affected by calcineurin inhibitors.

CD4+CD25+ regulatory T (Treg) cells have been shown to play a role in allograft tolerance and their peripheral counts vary according to the degree of graft acceptance in lung transplant recipients (LTR). Recent studies demonstrate that certain drugs might modulate generation, expansion and activity of Treg cells. Aim of this study was to evaluate the effect of therapeutic regimens used in our institution on peripheral CD4+CD25(high)CD69- Treg cell numbers in a group of 51 LTR with stable clinical conditions. They were treated with standard immunosuppression: calcineurin inhibitor (CNI)+azathioprine (AZA)+steroids (n=28) or with CNI+mycophenolate mofetil (MMF)+steroids (n=11) or with CNI+steroids (n=12). These stable LTR were compared with age-matched healthy controls (n=35) and with 19 LTR who developed bronchiolitis obliterans syndrome (BOS) and were treated analogously. Stable LTR showed higher peripheral Treg cell counts with respect to age-matched healthy controls (59.9+/-31.8/mul versus 42.1+/-16.9/mul, respectively; p<0.05). This increase was detectable in all patients treated with CNI either in association with AZA or MMF. During these treatments a significant expansion of Treg cell counts was detectable during acute rejection (AR) episodes (86.03+/-26.6/mul during AR versus 36.34+/-7.6 before AR; p<0,05). Moreover, the development of BOS was associated to a significant decrease of Treg cell counts irrespective to the immunosuppressive regimen used. In conclusion, therapeutic regimens based on CNI seem to allow a certain degree of peripheral Treg cell expansion in stable LTR.

Adult↗
PubMed2006

Immunosuppression and cancer: A comparison of risks in recipients of organ transplants and in HIV-positive individuals.

The comparison of cancers occurring excessively among HIV-infected and transplanted individuals may help to elucidate the relationship between immune surveillance, viral infections, and cancer. A longitudinal study was conducted on 2002 HIV-infected Italian subjects, 6072 HIV-infected French individuals, and 2878 Italian recipients of solid organ transplants. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed to quantify the risk for cancer, compared with the French and Italian general populations. The SIRs for all cancers were 9.8 (95% CI: 9.0-10.6) for HIV-infected individuals versus 2.2 (95% CI: 1.9-2.5) for transplant recipients. In both groups, most of the excess risk was attributable to virus-related cancers, such as Kaposi's sarcoma (KS; SIR = 451 in HIV-positive individuals, 125 in transplant recipients), non-Hodgkin's lymphoma (NHL; SIR = 62.1 and 11.1, respectively), and liver cancer (SIR = 9.4 and 4.1, respectively). Significantly increased SIRs for anal cancer and Hodgkin's lymphoma were found only among HIV-positive individuals. Among women younger than 40 years of age, a more than 10-fold increase in cervical cancer risk was found in both groups. Among HIV-infected individuals treatment with highly active antiretroviral therapies drastically reduced SIRs for KS and NHL only. These results show that HIV-infected individuals and transplant recipients share a similar pattern of cancer risk, largely due to virus-related cancers.

Cohort Studies↗
PubMed2004

The FBN1 (R2726W) mutation is not fully penetrant.

The R2726W mutation in the fibrillin 1 (FBN1, Marfan syndrome) gene segregates with isolated skeletal features of Marfan syndrome and/or high stature. Here we report a family in which two out of four individuals, an 18-year-old son and his mother, a 41-year-old woman, had the R2726W mutation of FBN1. Both family members carrying the mutation were of average height. The son had a Marfan-like phenotype, but his mother did not. The FBN1 R2776W mutation, which is associated with skeletal features of Marfan syndrome, appears incompletely penetrant. Consequently, genetic counselling in the presence of this mutation is difficult.

Adolescent↗
PubMed2003

Utility of biochemical markers in the follow-up of heart transplant recipients.

Endomyocardial biopsy (EMB) is currently the standard method to diagnose acute graft rejection. However, considering the potential complications of this procedure, a noninvasive marker of rejection would be an ideal alternative or at least a helpful adjunct to posttransplant management. We measured myoglobin (Myo), creatine kinase MB mass (CK-MBm), troponin T (cTnT), serum amyloid A (SAA), and C-reactive protein (CRP) in 57 patients (mean age 37.5 years) who underwent orthotopic heart transplantation for end-stage cardiac failure between January and December 2001.Endomyocardial biopsies were performed routinely after surgery and histologically diagnosed rejection was graded according to the criteria of the International Society of Heart and Lung Transplantation. Concomittant with the biopsies, blood samples were drawn from the coronary sinus (central blood samples) and from a peripheral vein (peripheral blood samples) to assay biochemical markers. Among 149 EMB evaluated, 87 were negative (grade 0); 28 showed grade 1a rejection; 26 showed grade 1b; and 8 showed grade > 1b (2 were grade 2, 6 were grade 3a). Grades 0 and 1a were considered to be negative, while grades 1b and >1b were considered positive indicating potential acute graft rejection. cTnT, Myo, CK-MBm, SAA, and CRP levels were measured in 149 central blood samples and 149 peripheral blood samples. Myo and CK-MBm did not show significant changes. cTnT seems to be a potentially useful addition to the EMB results, while SAA and CRP showed variations with respect to EMB grade both in central and peripheral samples.

Adult↗
PubMed2003

Eccentric atherosclerotic plaques with positive remodelling have a pericardial distribution: a permissive role of epicardial fat? A three-dimensional intravascular ultrasound study of left anterior descending artery lesions.

AIMS: The transversal distribution of coronary atherosclerotic plaques (AP) (myocardial vs pericardial) affects vessel remodelling. The aim of this study was to define the impact of transversal lesion distribution on vessel remodelling in proximal and distal coronary segments using a 3D intravascular ultrasound (IVUS) reconstruction. METHODS: The study group included 70 lesions located in the left anterior descending artery within 5mm of the septal take-off, and imaged using 3D-IVUS. The take-off of the septal branch was used to divide the plaque into a myocardial and pericardial surface. The IVUS index of vessel remodelling was calculated as: [narrowest external elastic membrane (EEM) site cross-sectional area (CSA)-reference EEM CSA)/reference EEM CSAx100]. The lesions with an intermediate vessel remodelling index (between -25% and +15%) were excluded from analysis. RESULTS: Of the 38 APs with a pericardial distribution, 34 (89%) showed positive remodelling (P<0.001). The distal lesions had a positive vessel remodelling index regardless of transversal plaque distribution. At multivariate analysis, pericardial distribution and the distal location of AP were the only independent variables predictive of positive remodelling. CONCLUSIONS: The transversal distribution of atherosclerotic plaque affects vessel remodelling in left anterior descending coronary lesions, probably because of an extravascular splinting effect. Distal lesions usually show positive remodelling regardless of transversal plaque distribution.

Adipose Tissue↗
PubMed2002

Plaque composition in plexogenic and thromboembolic pulmonary hypertension: the critical role of thrombotic material in pultaceous core formation.

BACKGROUND: Patients with pulmonary hypertension develop intimal plaques in large pulmonary arteries. OBJECTIVE: To test the hypothesis that the composition of such plaques differs depending on whether the aetiology of the disease is thromboembolic or hypertensive. DESIGN: Chronic thromboembolic and plexogenic pulmonary hypertension (primary and secondary (Eisenmenger syndrome)) were investigated. These are spontaneous human models and were used to examine the independent role of thrombus and hypertension in plaque composition. SETTING: A national tertiary referral centre for lung transplantation and pulmonary thromboendoarterectomy. PATIENTS: Thirty nine patients with chronic thromboembolic pulmonary hypertension who had undergone thromboendoarterectomy (n = 32) or lung transplantation (n = 7), 28 with plexogenic diseases (nine primary and 19 Eisenmenger), and three with Eisenmenger syndrome complicated by thromboembolic events. INTERVENTIONS: The lung and thromboendoarterectomy samples were sectioned, stained with Movat pentachrome, and immunostained with antibodies for fibrin, platelets, inflammatory cells, smooth muscle cells, and erythrocyte membrane glycophorin A. MAIN OUTCOME MEASURE: Composition of the plaques affecting large pulmonary arteries. RESULTS: Two types of intimal lesion were distinguished in chronic thromboembolic pulmonary hypertension: fibrous plaques with angioneogenesis; and core-rich atherosclerotic plaques with pultaceous cores largely consisting of glycophorin immunoreactive material, with cholesterol clefts (61.5%), CD68 positive macrophages (84.6%), T lymphocytes (87%), and calcification (46.1%). The samples from the patients with Eisenmenger syndrome and thromboembolic complications had similar characteristics, whereas those from patients with uncomplicated primary pulmonary hypertension had core-free fibrous plaques, spotted with macrophages and T lymphocytes. CONCLUSIONS: Chronic thromboembolic pulmonary hypertension is associated with atherosclerotic plaques with glycophorin-rich pultaceous cores, and plexogenic pulmonary hypertension with fibrous plaques. Thromboembolic material thus plays a critical role in the formation of pultaceous cores, of which erythrocyte membrane derived glycophorin is a major component.

Adult↗
PubMed2001

In situ characterization of human cytomegalovirus infection of bronchiolar cells in human transplanted lung.

Distal airway cell infection by human cytomegalovirus (HCMV) in transplanted lung has been occasionally reported but not systematically investigated. The present study aimed at testing the prevalence of HCMV bronchiolar infection in human transplanted lung. We identified and immunophenotyped, with double labeling, infected lung cells in 31 transbronchial biopsies with HCMV infection, containing distal airways (7 HCMV pneumonias, 7 HCMV infection without inflammation, and 17 morphologically occult, non-cytopathic HCMV infection). HCMV-infected cells in pneumonias, localizations, and occult infections were alveolar epithelia (32.8%, 42.8%, and 53.5%, respectively), endothelia (22.9%, 24.7%, and 26.4%, respectively), macrophages (0.006%, none, and none, respectively), airway epithelia (0.01%, 8.9%, and none, respectively), and bronchiolar smooth muscle cells (0.011%, 14.6%, and 16.1%, respectively). Ciliated and bronchiolar smooth muscle cells in transplanted lung only occasionally harbored viral infection and never showed viral cytopathy. On the basis of our morphological observations, HCMV infection of bronchiolar wall cells is rare, while alveolar epithelia and capillary endothelial cells are the major targets of lung infection.

Adult↗
PubMed2001

Apoptosis and the systolic dysfunction in congestive heart failure. Story of apoptosis interruptus and zombie myocytes.

Although previously it was believed that apoptosis could not occur in the terminally differentiated tissue, such as adult heart muscle cells, recent studies in endomyocardial biopsies from patients with dilated cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histologic evidence of apoptosis. Whereas neurohormonal activation during heart failure leads to compensatory hemodynamic alterations, coupled with ventricular dilatation, it induces transcription factors and myocyte hypertrophy. Persistent growth stimulation in terminally differentiated cells may lead paradoxically to apoptotic cell death. The apoptosis in cardiomyopathic hearts is associated with cytochrome c release from mitochondria to cytoplasm and activation of proteolytic caspase-8 and -3. Although the caspases are duly processed, the fragmentation of the nuclear proteins (including DNA) is completed less frequently, and only a variable degree of fragmentation of cytoplasmic proteins (including contractile proteins) is observed. It is hypothesized that release of cytochrome c from mitochondria should interfere with energy production and lead to functional impairment and variable loss of contractile proteins in a living heart muscle cell should contribute to systolic dysfunction. Because a nuclear blueprint is retained, however, the dysfunctional cell may continue to exist and in favorable conditions, such as with LVAD support, the apoptotic process may subside. Potential feasibility of reversal of heart failure should renew efforts to develop more targeted pharmaceutical intervention within the apoptotic cascade and allow newer paradigm for the management of heart failure.

Animals↗
PubMed2001

Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure.

OBJECTIVES: We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. BACKGROUND: Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. METHODS: Right heart catheterization was performed in 377 consecutive patients with heart failure. RESULTS: During a median follow-up period of 17 +/- 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r = 0.66, p < 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p < 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. CONCLUSIONS: These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.

Adult↗
PubMed2001

Neoplastic disease after heart transplantation: single center experience.

OBJECTIVES: Mandatory use of prolonged immunosuppression in organ transplantation is complicated by an increased incidence of cancer. The current study represents a retrospective analysis of the incidence of neoplasms in our heart transplantation program. METHODS: Four-hundred and seventy-four patients (403 male and 71 female; mean age, 48.6+/-12.1 years), with at least 30 days of follow-up, were enrolled in this study. Patients received triple immunosuppression with cyclosporin A, azathioprine and steroids. Moreover, as a prophylactic anti-lymphocyte therapy, 388 patients (82%) were administered RATG, 67 patients (14%) received ALG and 19 patients (4%) OKT3. The mean follow-up time was 71.1+/-43.0 months. RESULTS: Fifty-five patients (11.6%) developed malignant neoplasms. The cancer frequencies were: solid tumors, 55%; non-Hodgkin lymphomas (NHL), 20%; Kaposi's sarcomas, 11%; skin cancers, 9%; undifferentiated sarcomas and myelomas, 5%. Solid tumors mainly affected the lung (39%), bowel (16%), stomach (6.5%), liver (6.5%), pancreas (6.5%) and oral cavity (6.5%). The times to the onset of cancer from transplantation were: Kaposi's sarcoma, 12.7+/-16.8 months; skin cancers, 34.5+/-23.8 months; solid tumors, 54.3+/-38.7 months; NHL, 60.1+/-36.4 months; undifferentiated sarcomas and myelomas, 90.0+/-15.6 months. As determined by univariate and multivariate analyses, sex, number of treated rejections, previous history of tumor, average dose of cyclosporine and prednisone and cyclosporine blood levels did not increase the incidence of malignancies. Univariate analysis suggests a significant correlation between the type of prophylactic immunoglobulins and the average dose of azathioprine with the incidence of neoplasms. Both univariate and multivariate analyses demonstrated a significant correlation between patient's age at the time of transplantation and risk of cancer occurrence (risk increased by 1.074/year; P=0.0056 with multivariate Cox regression). CONCLUSIONS: Cancer is a strong limitation for long-term survival after heart transplantation. The only risk factor recognized is the patient's age at the time of transplant. Furthermore, the type of prophylactic globulins used for induction therapy and some specific immunosuppressant agent (azathioprine) may play a significant role in the development of malignancies after transplantation.

Adult↗
PubMed2001

The mitochondrial DNA mutation T12297C affects a highly conserved nucleotide of tRNA(Leu(CUN)) and is associated with dilated cardiomyopathy.

Mitochondrial DNA (mtDNA) mutations have been causally linked with cardiomyopathies, both dilated (DCM) and hypertrophic. We identified the T12297C mutation in the mtDNA-tRNA(Leu(CUN)) of a 36-year-old male patient diagnosed with DCM. The mutation was heteroplasmic, with high amount (88%) of mutant DNA in the myocardium, and was absent in normal (n = 120) and disease (n = 150) controls. It affects a highly conserved nucleotide (adjacent to the anticodon triplet) that allows the phospho-ribose backbone to turn and form the loop. The potential pathological role of T12297C mutation is further supported by its recent identification in another unrelated Italian family with DCM associated with endocardial fibroelastosis. In the variable loop of the same tRNA, our patient also carried the A12308G transition that is debated as pathological mutation or neutral polymorphism in progressive external ophthalmoplegia: the two defects could exert a synergistic effect on the tRNA structure and function. The endomyocardial biopsy study showed abnormal ring-like mitochondria and occasional cytochrome c oxydase negative myocytes. Overall, the heteroplasmy, the highly conserved position of the mutated nucleotide, the absence of the mutation in large series of diseased and normal controls, and the cardiac mitochondrial changes support a causative link of the mutation with the disease.

Adult↗