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Remigio Moratti

Publications and source records attributed to Remigio Moratti.

12 recordsLinked to original sources
PubMed2006

Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL.

N-terminal natriuretic peptide type B (NT-proBNP) is a marker of cardiac dysfunction in light chain amyloidosis (AL) and a powerful prognostic determinant. Serum NT-proBNP and circulating free light chains (FLCs) were measured at enrollment and after 3 cycles of chemotherapy in 51 patients with cardiac AL. In patients (n = 22, 43%) in whom FLCs decreased by more than 50% (hematologic response), NT-proBNP concentration decreased by a median of 48%, whereas in the remaining patients it increased by 47% (P = .01). The reduction of NT-proBNP was greater in patients (n = 9) in whom amyloidogenic FLCs disappeared at immunofixation (median 53%), than in the remaining responding patients (median 31%, P = .04). Left ventricular wall thickness decreased by at least 2 mm in 3 of 20 patients in whom NT-proBNP improved. Fifteen patients died. Thirteen of them, in whom NT-proBNP and FLCs did not improve, died after a median of 1.8 months. The decrease of FLCs translates into a simultaneous decrease of NT-proBNP and improved survival. Patients in whom chemotherapy fails to induce such a decrease are at risk of early death. Cardiac function in AL can rapidly improve due to a reduction of the circulating amyloidogenic precursor, despite the amount of cardiac amyloid deposits remaining apparently unaltered, as measured by echocardiography.

Adult↗
PubMed2006

Increased serum inflammatory markers as predictors of airway obstruction.

Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. The purpose of this study was to evaluate whether eosinophil cationic protein and/or myeloperoxidase (ECP/MPO) serum levels differ between patients with chronic obstructive and nonobstructive bronchitis during an exacerbation-free period and if they represent clinical gravity indicators of disease. To identify a correlation between ECP/MPO values in serum and bronco-obstruction, a statistical analysis by logistic regression was used. Study results show that there is a relationship between increased serum levels of ECP and log MPO and an increased risk for forced expiratory volume in 1 second (FEV1) pathologic values associated with obstructive chronic bronchitis, with an ECP odds ratio = 1.04 and logMPO = 4.45.

Adult↗
PubMed2005

Interferon-gamma- and interleukin-4-producing T cells in Down's syndrome.

Down's syndrome (DS) associates with genetic-dependent dysregulation of the interferon (IFN) system. We used intracellular cytokine staining to analyse the percentages of IFN-gamma- and interleukin (IL)-4-producing T cells in the peripheral blood of patients with DS, individuals with mental retardation (MR), and healthy controls (HCs). The percentages of IFN-gamma-producing CD4(+) and CD8(+) T cells (IFGCs), namely Th1 (mean, 21.4+/-S.D. 1.3) and Tc1 (12.6+/-1.1), and the Th1/Th2 ratio (6.1+/-0.2) in DS were significantly higher than in MR (15.9+/-1.3, 7.9+/-0.6, 4.8+/-0.3) and in HCs (15.6+/-1.9, 7.2+/-1.1, 4.6+/-0.6). Most of the DS patients with high IFGC percentages were seropositive for anti-transglutaminase IgA. We found no correlation between sex, age, APOE genotypes, coexisting autoimmune diseases, susceptibility to infections, or degree of cognitive impairment and high IFGC percentages. This abnormality might thus contribute to immune dysfunction in DS without manifest clinical correlates.

Adult↗
PubMed2005

Clinical aspects of systemic amyloid diseases.

Amyloidosis is a protein misfolding disorder in which soluble proteins aggregate as insoluble amyloid fibrils. Protein aggregates and amyloid fibrils cause functional and structural organ damage respectively. To date, at least 24 different proteins have been recognized as causative agents of amyloid diseases, localized or systemic. The two most common forms of systemic amyloidosis are light-chain (AL) amyloidosis and reactive AA amyloidosis due to chronic inflammatory diseases. beta(2)-microglobulin amyloidosis is a common complication associated with long-term hemodialysis. Hereditary systemic amyloidoses are a group of autosomal dominant disorders caused by mutations in the genes of several plasma proteins. Heterogeneity in clinical presentation, pattern of amyloid-related organ toxicity and rate of disease progression is observed among systemic amyloidoses. In particular, beta(2)-microglobulin presents unique clinical features compared to the other systemic forms. The phenotypic features of hereditary systemic amyloidoses may instead overlap those of the two more common forms of acquired amyloidoses mentioned above and therefore a correct diagnosis can not rely only on clinical grounds. Unequivocal identification of the deposited protein is essential in order to avoid misdiagnosis and inappropriate treatment. Amyloid deposits can be reabsorbed and organ dysfunction reversed if the concentration of the amyloidogenic protein is reduced or zeroed. At present, the most effective approach to treatment of the systemic amyloidoses involves shutting down, or substantially reducing the synthesis of the amyloid precursor, or, as in the case of beta(2)-microglobulin, promoting its clearance.

Adult↗
PubMed2005

Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure.

AIMS: Anaemia is often observed in patients with chronic heart failure (CHF), and it may be associated with a worse prognosis. Aim of this study was to identify the individual mechanisms of anaemia in CHF patients. METHODS AND RESULTS: One hundred and forty-eight consecutive patients with haemoglobin concentration <13 g/dL (if males) or <12 g/dL (if females) were enrolled. Factors responsible for anaemia were investigated by evaluating endogenous erythropoietin (Epo) production, serum cytokines levels, body iron status, and iron supply for erythropoiesis. Most patients (57%) presented anaemia of chronic disease and among them, 92% showed evidence of a defective endogenous Epo production. This was indicated by an observed/predicted log(serum Epo) ratio less than 0.8 and/or a defective iron supply for erythropoiesis diagnosed by low transferrin saturation and/or increased value of soluble transferrin receptor. According to regression analysis sex, renal failure, and serum Epo were correlated with anaemia. CONCLUSION: According to our study, about half of anaemic CHF patients showed anaemia of chronic disease with blunted endogenous Epo production and/or a defective iron supply for erythropoiesis. Determination of the individual mechanisms of anaemia in CHF could justify a rational therapeutic approach to anaemia.

Anemia↗
PubMed2005

Antibodies to cyclic citrullinated peptides in psoriatic arthritis.

OBJECTIVE: To determine the presence and clinical significance of antibodies to cyclic citrullinated peptides (anti-CCP) in psoriatic arthritis (PsA). METHODS: We performed a cross-sectional study on 102 outpatients (56 men) with PsA consecutively recruited from a tertiary referral center. Median disease duration was 36 months (interquartile range 21-81). All patients were investigated for peripheral joint and axial involvement, enthesitis, and dactylitis. Laboratory investigations included anti-CCP, assessed by enzyme-linked immunosorbent assay and IgM rheumatoid factor (RF). Plain radiographs of pelvis, wrists, hands, and feet were performed in all cases. RESULTS: Anti-CCP were detected in 16/102 patients, 8/68 with symmetric polyarthritis, 1/8 with asymmetric polyarthritis, 2/20 with mono-oligoarthritis, 1/2 with mutilating arthritis, and 0/4 with exclusive axial or distal interphalangeal (DIP) involvement. The male:female ratio as well as frequency of dactylitis, enthesitis, and nonexclusive axial or DIP joint involvement were similar in the anti-CCP positive and negative groups. Anti-CCP positive patients were more frequently treated with disease modifying antirheumatic drugs and showed higher number of involved joints, and higher frequency of erosive arthritis and positive RF. Using multiple logistic regression, anti-CCP (but not RF) were significantly associated with erosive arthritis (odds ratio 9.8; 95% confidence interval 1.87-51.8) and > or = 10 involved joints (17.99; 3.6-89.2). CONCLUSION: Anti-CCP can be found in a small but significant proportion of patients with a clinical picture of PsA and are associated with erosive arthritis and multiple joint involvement.

Adult↗
PubMed2005

Pro-neoangiogenic cytokines (VEGF and bFGF) and anemia in solid tumor patients.

Using a commercial ELISA assay, we evaluated circulating VEGF and bFGF levels in 203 consecutive patients with solid tumors, and sought a correlation between them and with the grade of anemia. Serum VEGF values were within the normal range in 128 patients (63.05%), with a mean value of 675.04 pg/ml (median, 571.00; range, 0-2796.54). The analysis of VEGF values per tumor group did not provide any statistically significant difference. Regarding bFGF, 143 patients (70.44%) had measurable, and thus abnormal, bFGF values. Overall, mean bFGF serum value was 57.14 pg/ml (median, 8.30; range, 0-4334.71), with the highest bFGF levels found in breast carcinoma patients. As expected, a large number of our patients was fairly anemic, mean hemoglobin level being 11.47 g/dl (median, 11.30; range, 7.1-19.20), the lowest titers being observed in prostate carcinoma patients. No statistically significant correlation was found between serum VEGF and hemoglobin values (r=0.004) but a significant negative correlation was seen between serum bFGF and hemoglobin (r=-0.22, p<0.05). Considering the different tumor groups, a statistically significant negative correlation between bFGF and hemoglobin becomes even more apparent in the subgroup of renal carcinoma patients (r=-0.55, p<0.05). In conclusion, our results demonstrate that there is a statistically significant correlation between systemic hypoxia (evaluated in terms of hemoglobin levels) and circulating bFGF values, but not VEGF; this correlation may lead to therapeutic interventions.

Aged↗
PubMed2004

Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction.

Endothelial progenitor cell (EPC) mobilization has been reported following tissue damage, whereas no data are available regarding the mobilization of hematopoietic progenitor cells (HPCs). We performed the phenotypic and functional analysis of circulating CD34+ progenitor cells in patients with acute myocardial infarction (AMI), assessed from admission up to 60 days, in patients with stable angina pectoris (SA), and in healthy controls (CTRLs). In patients with AMI at admission (T0), the number of circulating CD34+ cells was higher (P < .001) than in CTRLs and became comparable with CTRLs within 60 days. Both the number of CD34+ cells coexpressing CD33, CD38, or CD117 and the number of HPCs was higher (P < .02 for all) in patients with AMI at T0 than in CTRLs, as was the number of hematopoietic colonies (P < .03). Patients with AMI (T0) had a significantly increased number of CD34+ vascular endothelial growth factor receptor 2-positive (VEGFR-2+) cells (P < .002) with respect to CTRLs, including CD34(+) CD133(+)VEGFR-2+ and CD34+ CD117(+)VEGFR-2+ EPCs. The number of endothelial colonies was higher in patients with AMI (T0) than in CTRLs (P < .05). No significant difference was documented between patients with SA and CTRLs. Spontaneous mobilization of both HPCs and EPCs occurs within a few hours from the onset of AMI and is detectable until 2 months.

Adult↗
PubMed2003

Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis.

BACKGROUND: Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure and after myocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). We investigated the prognostic value of NT-proBNP and its utility in monitoring amyloid heart dysfunction. METHODS AND RESULTS: NT-proBNP was quantified at diagnosis in 152 consecutive patients seen at the coordinating center of the Italian Amyloidosis Study Group (Pavia) from 1999 throughout 2001. Heart involvement was estimated on the basis of clinical signs, electrocardiography, and echocardiography. NT-proBNP concentrations differed in patients with (n=90, 59%) and without (n=62, 41%) heart involvement (median: 507.8 pmol/L versus 22.1 pmol/L, P=10(-7)). The best cutoff for heart involvement was at 152 pmol/L (sensitivity: 93.33%, specificity: 90.16%, accuracy: 92.05%) and distinguished two groups with different survival (P<0.001). The Cox multivariate model including NT-proBNP was better than models including echocardiographic and clinical signs of heart involvement. NT-proBNP appeared to be more sensitive than conventional echocardiographic parameters in detecting clinical improvement or worsening of amyloid cardiomyopathy during follow-up. CONCLUSIONS: NT-proBNP appeared to be the most sensitive index of myocardial dysfunction and the most powerful prognostic determinant in AL amyloidosis. It adds prognostic information for newly diagnosed patients and can be useful in designing therapeutic strategies and monitoring response. NT-proBNP is a sensitive marker of heart toxicity caused by amyloidogenic light chains.

Adult↗
PubMed2002

Determination of free and total (free plus protein-bound) melatonin in plasma and cerebrospinal fluid by high-performance liquid chromatography with fluorescence detection.

A simple, sensitive and accurate method for the estimation of free and total (free plus protein-bound) melatonin (MLT) in human plasma and cerebrospinal fluid (CSF) is described. Via Chem-Elut cartridges, free and total MLT (the latter obtained after a deproteinization step) were quantified in dichloromethane-extracted samples and analyzed in one chromatographic run by high-performance liquid chromatography (HPLC) with fluorimetric detection. The column used was an Extrasil ODS-2 (3 microm, 150 x 4.6 mm I.D.), while the mobile phase consisted of 75 mM sodium acetate-acetonitrile (72:28, v/v) (pH 5.0). Repeatability and reproducibility of the method were 3.24 and 9.4%, respectively. The recovery of melatonin from plasma and CSF was 99.9+/-4.0% for non-deproteinized samples and 93.2+/-4.8% for deproteinized samples. The detection limit of the assay was 0.5 pg/ml. In human plasma, the mean+/-SD concentrations in the darkness period were 23.18+/-7.44 pg/ml for free melatonin and 82.5+/-36.48 pg/ml for total melatonin, while the lowest concentrations detected during daytime were 2.23+/-2.22 and 7.40+/-5.68 pg/ml, respectively. Detection of MLT in CSF was 5.01+/-2.31 and 28.55+/-6.95 pg/ml for the free and total fraction, respectively.

Chromatography, High Pressure Liquid↗
PubMed2002

Intramyocardial troponin-T monitoring with microdialysis in coronary artery bypass surgery.

OBJECTIVE: To investigate the time course of troponin-T release into the extracellular fluid of the myocardium and to distinguish between a rise in troponin-T due to implantation trauma and an increase due to cardiac arrest during coronary surgery. DESIGN: Microdialysis probes were implanted in the heart of seven patients soon after sternotomy. Troponin-T was measured in the microdialysates and in peripheral blood from 3 h before to 24 h after heart arrest. RESULTS: The troponin-T concentration in the microdialysates increased immediately after probe implantation and decreased to baseline within 70 min. This early peak is interpreted to reflect a local trauma. Three hours after cross-clamp release, a second peak of microdialysate troponin-T was recorded; 50 times higher than in serum. Eight to 24 h later a third peak occurred in five patients. Serum troponin-T was below the detection level at the beginning of the operation but increased linearly during the first 3 h of reperfusion and remained at that level thereafter. CONCLUSION: Microdialysis is a safe technique providing more information on myocardial metabolism during and after bypass surgery than can be obtained from peripheral blood. The release of troponin-T in response to cardiac arrest can be distinguished in time from the local tissue response to probe implantation.

Adult↗