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L Sacchetti

Publications and source records attributed to L Sacchetti.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphism p.402Y>H in the complement factor H protein is a risk factor for age related macular degeneration in an Italian population.

AIMS: To evaluate the complement factor H (CFH) p.402Y>H polymorphism as a risk factor in age related macular degeneration (AMD) in an Italian population. METHODS: 104 unrelated Italian AMD patients and 131 unrelated controls were screened for the CFH polymorphism p.402Y>H (c.1277 T>C), which has been associated with AMD. Retinography was obtained for patients and controls; the AMD diagnosis was confirmed by fluorescein angiograms. The c.1277 T>C polymorphism was genotyped with the TaqMan real time polymerase chain reaction single nucleotide polymorphism assay. RESULTS: The frequency of c.1277C allele was higher in AMD patients than in controls (57.2% v 39.3%; p<0.001). The odds ratio (OR; logistic regression analysis) for AMD was 3.9 (95% confidence interval (CI): 1.9 to 8.2) for CC homozygotes. The CC genotype conferred a higher risk for sporadic (OR 4.6; CI: 2.0 to 10.5) than for familial AMD (OR 2.9; CI: 1.0 to 8.4). Genotypes were not related to either age at AMD diagnosis or to AMD phenotype. However, geographic atrophy and choroidal neovascularisation were more frequent in sporadic than in familial AMD (p = 0.027). Overall, the percentage of population attributable risk for the CC genotype was 28% (95% CI:18% to 33%). CONCLUSION: The association between the p.402Y>H (c.1277T>C) polymorphism and AMD applies to the Italian population and the CC genotype is more frequent in sporadic than in familial AMD cases.

Aged↗
PubMed2005

Deferiprone: New insight.

Recent results from independent studies suggest that deferiprone is more cardioprotective than deferoxamine. Patients on long-term treatment with deferiprone have a better myocardial magnetic resonance imaging pattern and less chance to develop a new cardiac disease or worsen an existing one. Most of these observations are retrospective and require confirmation from randomized controlled trials. Other new observations regard the effects of combining the two chelators. Most results indicate an additional effect on iron excretion and a significant reduction of the time required to mitigate severe iron overload and to reverse clinical heart disease. Again, these data require confirmation, as they were mostly obtained on individual cases or small groups of patients treated with a wide range of combinations of the two chelators, but the univocity of results is impressive. After many years of controversy, deferiprone is emerging as a useful oral iron chelator that enhances the chances for the patient to have optimal treatment. Well-designed and -conducted studies will help in answering the questions still open.

Agranulocytosis↗
PubMed2002

The first large population based twin study of coeliac disease.

BACKGROUND AND AIMS: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study. METHODS: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules. RESULTS: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1-134), independent of the DQ at risk genotype. CONCLUSION: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.

Adolescent↗
PubMed2001

Characterization of two novel cell lines, DERL-2 (CD56+/CD3+/Tcry5+) and DERL-7 (CD56+/CD3-/TCRgammadelta-), derived from a single patient with CD56+ non-Hodgkin's lymphoma.

Two novel IL2-dependent cell lines, DERL-2 and DERL-7, were established from a patient with hepatosplenic gammadelta T cell lymphoma. This patient presented, at diagnosis, two discrete populations of CD56+ cells, one TCRgammadelta+, the second lacking T cell-restricted antigens. The cell lines derived displayed features corresponding to the two cellular components of the disease: DERL-2 was CD56+/CD3+/TcRgammadelta+ while DERL-7 was CD56+/CD3-/TcRgammadelta-. Along with CD56, the two cell lines shared the expression of CD7, CD2, CD158b and CD117. Karyotype analysis showed that both cell lines were near-diploid, with iso-7q and loss of one chromosome 10. In addition, DERL-2 showed 5q+ in all metaphases analyzed, while DERL-7 revealed loss of one chromosome 4. Genotypically, both cell lines shared the same STR pattern at nine loci and demonstrated an identical rearranged pattern of the T cell receptor genes beta, gamma and delta, with respect to the original tumor cells. These data indicated that both cell lines and the original neoplastic populations were T cell-derived and arose from a common ancestor. Among a large panel of cytokines tested, only SCF was able to substitute IL2 in supporting cell proliferation. Moreover, SCF and IL2 acted synergistically, dramatically enhancing cell growth. These cell lines may represent a model to further analyze the overlap area between T and NK cell malignancies, and may provide new information about the synergistic action of IL2 and SCF on normal and neoplastic T/NK cells.

Adult↗
PubMed2001

Site-specific atherosclerotic plaques in the carotid arteries of middle-aged women from southern Italy: associations with traditional risk factors and oxidation markers.

BACKGROUND AND PURPOSE: Studies on cardiovascular disease have preferentially involved men because of the lower frequency of the disease in preelderly women. The aim of this analysis was to examine, with the use of a standardized ultrasound protocol, a cohort of women to differentiate early atherosclerotic lesions in different carotid segments in relation to traditional (lipoprotein abnormalities, high blood pressure, cigarette smoking) and nontraditional (oxidation markers) cardiovascular risk factors. METHODS: More than 5000 clinically healthy, middle-aged women (n=5062; age range, 30 to 69 years) living in the area of Naples in southern Italy participated in the Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in the female population. A subsample of 310 participants underwent high-resolution B-mode ultrasound to assess intima-media thickness of common carotid artery and carotid bifurcation. RESULTS: Early atherosclerotic plaques (intima-media thickness >1.2 mm) were detected within the common carotid arteries in 37 women, in the carotid bifurcations in 77 women, and in both sites in 91 women. After age adjustment, common carotid plaques were found to be associated with higher systolic blood pressure (143 versus 138 mm Hg; P<0.05) and higher body mass index (29 versus 27 kg/m(2); P<0.01), while lesions at the carotid bifurcations were associated with higher LDL cholesterol (4.3 versus 3.8 mmol/L; P<0.01) and with smoking habit. Multivariate odds ratios for the presence of common carotid plaques were related to antibodies against oxidized LDL (odds ratio, 2.72; 95% CI, 1.46 to 5.07), and those for plaques at the bifurcation were related to lipid peroxides (odds ratio, 1.90; 95% CI, 1.04 to 3.47), and both relationships were independent of age, LDL cholesterol concentrations, body mass index, smoking habit, and systolic blood pressure. CONCLUSIONS: In a cohort of clinically healthy, middle-aged women, we found a site-specific association of traditional risk factors and oxidation markers with early atherosclerotic lesions in arterial segments differing in geometry, shear stress, extracellular matrix composition, and cell type populations.

Adult↗
PubMed2001

Multivariate discriminant function based on six biochemical markers in blood can predict the cirrhotic evolution of chronic hepatitis.

BACKGROUND: Serologic markers have been proposed for monitoring hepatic fibrosis in chronic active liver disease. Because none of these markers, when used singly, is totally satisfactory, we developed and evaluated a multivariate approach. METHODS: We studied two cohorts of chronic hepatitis (54 patients) and cirrhosis patients (49 patients) to identify a panel of biochemical markers that discriminates between the two diseases. Using multivariate discriminant analysis, we selected a function, based on the concentrations of six biochemical markers (fibronectin, prothrombin, pseudocholinesterase, alanine aminotransferase, manganese superoxide dismutase, and N-acetyl-beta-glucosaminidase). We then prospectively validated this function on a second temporal cohort of patients. RESULTS: Multivariate discriminant analysis correctly classified 93.7% of patients (94.3% of chronic hepatitis and 92.9% of cirrhosis patients) in the first cohort and 85% of patients (89.5% of chronic hepatitis patients and 81% of cirrhosis patients) in the second cohort. CONCLUSIONS: Discriminant analysis of results of six inexpensive biochemical markers provides a high predictive value for differentiation between liver cirrhosis and chronic hepatitis. Consequently, these biochemical markers condensed into a multivariate discriminant analysis value for each patient provide information that can be contributory for subsequent options during the evolution of the natural history of chronic hepatitis.

Biomarkers↗
PubMed1999

IgA antibodies to tissue transglutaminase: An effective diagnostic test for celiac disease.

OBJECTIVE: Tissue transglutaminase (tTG) is the main autoantigen recognized by endomysial antibodies. The aim of this study was to assess sensitivity, specificity, and predictive value of IgA and IgG antibodies to tTG in the diagnosis of celiac disease compared with endomysial antibodies. STUDY DESIGN: We established enzyme-linked immunosorbent assay procedures to measure IgA and IgG antibodies to tTG in sera from 48 untreated and 33 treated patients with celiac disease and from 63 patients with gastrointestinal disease who were in a control group. Sera from 10 patients with celiac disease were examined at various times after gluten was reintroduced into the patients' diet. RESULTS: Both IgA and IgG to tTG were significantly (P <.001) higher in serum of untreated patients with celiac disease versus those in the control group; IgA but not IgG was significantly (P <.001) higher in untreated versus treated patients with celiac disease. IgA and IgG antitissue tTG had a diagnostic sensitivity, specificity, and positive predictive value of 92% and 21%, 98% and 97%, and 98% and 83%, respectively. The concordance rate of IgA anti-tTG with IgA antiendomysial antibodies was 95%. In 5 of the 10 patients undergoing gluten challenge, IgA antiendomysium antibodies were detected earlier than IgA anti-tTG antibodies. CONCLUSIONS: tTG-based enzyme-linked immunosorbent assay is an effective diagnostic test, although immunofluorescent-based assays are more sensitive, particularly during gluten challenge.

Adolescent↗
PubMed1999

Efficiency of two different nine-loci short tandem repeat systems for DNA typing purposes.

BACKGROUND: Genotyping based on short tandem repeat (STR) regions is widely used in human identification and parentage testing, in gene mapping studies, and as an approach to studies on the etiopathogenesis and diagnosis of hereditary diseases. We wished to study a new analytical approach that uses capillary electrophoresis and multicolor fluorescence in place of slab gel electrophoresis. METHODS: We evaluated the efficiency for parentage and forensic purposes of the AmpFLSTR Profiler PlusTM typing kit that is used with the ABI Prism 310 Genetic Analyzer (System-2 STR), and that of a widely used panel of nine STRs analyzed with conventional slab-gel electrophoresis followed by radioactive detection (System-1 STR). System-2 STR, based on automated capillary electrophoresis and automated sizing of the alleles by Genotyper 2.0 software, was used to determine the allele frequency of the nine loci in 157 Caucasian subjects from southern Italy. On the basis of the data obtained, we submitted 40 trios to parentage testing. RESULTS: A higher median probability of paternity attribution and power of exclusion were obtained with System-2 STR vs System-1 STR: respectively, 99.99% and 99.95% (P <0.05) for attribution; and five and four excluding loci (P <0.05) for exclusion. The most informative and highly discriminating loci were D18S51, D21S11, and FGA. The combined probability of matching-by-chance for all nine STRs was 1.36 x 10(-12) for System-2 compared with 1.11 x 10(-7) obtained with the other system. The internal standard and allelic ladder of the System-2 STR facilitated accurate and precise genotyping; furthermore, System-2 STR and was faster than the conventional System-1 STR. CONCLUSIONS: The System-2 STR allows rapid testing with higher probabilities of attribution and a higher power of exclusion than with the comparison method with slab-gel electrophoresis.

Alleles↗
PubMed1998

Effect of N-acetyl-cysteine on lymphomonocyte glutathione and response to interferon treatment in C-virus chronic hepatitis.

BACKGROUND/AIM: Much controversy exists concerning effect of N-acetyl-cysteine, a precursor of glutathione, on the response to interferon treatment in patients with C-virus chronic hepatitis. The aim of this study was to evaluate the efficacy of interferon therapy with and without oral N-acetyl-cysteine. We also measured glutathione concentrations in lymphomonocytes of 25 patients with chronic C-virus hepatitis before and after interferon treatment and correlated the results with treatment response. METHODS: Glutathione was extracted from lymphomonocytes and measured with a modified high performance liquid chromatographic method in the 25 hepatitis patients and 12 healthy controls. RESULTS/CONCLUSIONS: 1) Hepatitis patients and controls had similar basal concentrations of lymphomonocytic glutathione; 2) neither interferon nor N-acetyl-cysteine significantly affected glutathione concentrations in patients; and 3) N-acetyl-cysteine did not affect response to interferon.

Acetylcysteine↗
PubMed1997

Multivariate discriminant analysis of biochemical parameters for the differentiation of clinically confounding liver diseases.

We describe a series of studies on the contribution of laboratory medicine to the differential diagnosis of clinically confounding diseases in the field of chronic hepatobiliary diseases. Ascitic cholesterol and lactate dehydrogenase (LD), selected by multivariate discriminant analysis (MDA) from a multitude of serum and ascitic analytes, correctly classified 100% of patients with malignant ascites or non-malignant ascites. In addition, ascitic pseudouridine differentiated hepatocarcinoma (HC) from cirrhotic ascites with a diagnostic effectiveness (overall discrimination power) of 90%. A panel of analytes constituted by serum gamma-glutamyltransferase (GGT), the GGT isoenzyme complexed with low- and very low-density lipoprotein, aspartate aminotransferase, copper, hepatic alkaline phosphatase (AP), the LD-5 isoenzyme and alpha-fetoprotein (AFP), selected by the MDA, correctly classified 93% of about 200 cases of cirrhosis or HC. Finally, MDA also identified an equation, based on serum values of the LD-4/LD-5 and carcinoembryonic antigen/AFP ratios, AP and iron that correctly classified 96% of HC or secondary liver neoplasia cases in 100 patients. This approach based on panels of analytes selected by a sophisticated statistical analysis is a rapid and non-invasive contribution to the differential diagnosis of chronic liver disease including neoplasia.

Chemistry, Clinical↗