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F Orlandi

Publications and source records attributed to F Orlandi.

At least 37 records · Page 2Linked to original sources
PubMed2000

First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency.

OBJECTIVE: To assess the effectiveness of free beta-hCG, pregnancy-associated plasma protein A, and nuchal translucency in a prospective first-trimester prenatal screening study for Down syndrome and trisomy 18. METHODS: Risks were calculated for Down syndrome and trisomy 18 based on maternal age and biochemistry only (n = 10,251), nuchal translucency only (n = 5809), and the combination of nuchal translucency and biochemistry (n = 5809). RESULTS: The study population included 50 Down syndrome and 20 trisomy 18 cases. Nuchal translucency measurement was done on 33 Down syndrome and 13 trisomy 18 cases. Down syndrome screening using combined biochemistry and ultrasound resulted in a false-positive rate of 4.5% (95% confidence interval [CI] 3.9%, 5.2%) and detection rate of 87.5% (95% CI 47%, 100%) in patients under age 35 years. In older patients, the false-positive rate was 14.3% (95% CI 12.7%, 15. 8%) and detection rate was 92% (95% CI 74%, 99%). For trisomy 18 screening, the false-positive rate was 0.4% (95% CI 0.24%, 0.69%) and detection rate was 100% (95% CI 40%, 100%) in younger patients, whereas in older patients the false-positive rate was 1.4% (95% CI 0. 9%, 2.0%) and detection rate was 100% (95% CI 66%, 100%). Using modeling, at a fixed 5% false-positive rate, the Down syndrome detection rate was 91%. Conversely, at a fixed 70% Down syndrome detection rate, the false-positive rate was 1.4%. CONCLUSION: First-trimester screening for Down syndrome and trisomy 18 is effective and offers substantial benefits to clinicians and patients.

Adult↗
PubMed1999

Intracellular pathways mediating Na+/H+ exchange activation by platelet-derived growth factor in rat hepatic stellate cells.

BACKGROUND & AIMS: The Na+/H+ exchanger is the main intracellular pH regulator in hepatic stellate cells (HSCs), and its activity is increased by platelet-derived growth factor (PDGF). Amiloride, an Na+/H+ exchange inhibitor, reduces PDGF-induced HSC proliferation, suggesting that the Na+/H+ exchanger plays a role in regulating HSC proliferative response. The aim of this study was to characterize the intracellular pathways mediating activation of the Na+/H+ exchanger by PDGF in HSCs. METHODS: The activity of the Na+/H+ exchanger and HSC proliferation rate were evaluated under control condition and after incubation with PDGF in the absence or presence of specific inhibitors of the main intracellular pathways of signal transduction. Na+/H+ exchange protein expression was evaluated by means of Western blot. RESULTS: PDGF induced a significant increase in the activity of the Na+/H+ exchanger without modifying protein expression. Inhibition of the calcium/calmodulin- and protein kinase C-dependent pathways resulted in a significant inhibition of both Na+/H+ exchange activity and of PDGF-induced HSC proliferation. The involvement of the two pathways was confirmed by showing that incubation of HSCs with both phorbol-12-myristate-13-acetate, a potent protein kinase C activator, and thapsigargin, which increases intracellular calcium levels, significantly increased both the Na+/H+ exchanger activity and HSC proliferation rate. Inhibition of the protein kinase A pathway did not modify either PDGF-induced Na+/H+ exchange activation or PDGF-induced HSC proliferation. On the contrary, inhibition of the mitogen-activated protein kinase- and of phosphatidylinositol 3-kinase-dependent pathways significantly reduced PDGF-induced HSC proliferation without affecting the activity of the Na+/H+ exchanger. CONCLUSIONS: Activation of the Na+/H+ exchanger by PDGF in HSCs is mediated by calcium/calmodulin- and protein kinase C-dependent pathways. PDGF-induced HSC proliferation is mediated by Na+/H+ exchange-dependent and -independent pathways.

Animals↗
PubMed1999

The Na+/H+ exchanger modulates the fibrogenic effect of oxidative stress in rat hepatic stellate cells.

BACKGROUND/AIMS: Oxidative stress is associated with liver fibrosis in vivo and with hepatic stellate cell (HSC) activation in vitro, but the intracellular mechanisms mediating these effects are mostly unknown. The Na+/H+ exchanger plays a key role in regulating the cell cycle, and is involved in HSC proliferation. Its role in different HSC features, such as collagen accumulation, is still unknown. We thus evaluated if the Na+/H+ exchanger modulates the fibrogenic effect of oxidative stress in rat HSC. METHODS: HSC were incubated with 0.1 mM ferric nitrilotriacetate complex (FeNTA). Intracellular hydroperoxides and malonildialdehyde (MDA) levels in the culture media were measured by the dichlorofluorescein and TBARS method, respectively. Intracellular pH and Na+/H+ exchanger activity were measured using the fluorescent dye BCECF. Cell proliferation was measured by immunohistochemistry for bromodeoxyuridine incorporation. Collagen type I accumulation in the culture media was measured by ELISA. RESULTS: HSC incubation with FeNTA resulted in a significant production of intracellular hydroperoxides and MDA, associated with increased Na+/H+ exchange activity and baseline intracellular pH (pHi). Exposure of HSC to FeNTA significantly enhanced the number of proliferating HSC and collagen type I levels in the culture medium. All these effects were reversed by the antioxidant resveratrol and by the Na+/H+ exchanger inhibitor amiloride. CONCLUSIONS: This study indicates that the Na+/H+ exchanger might represent a common mediator of the different effects induced by oxidative stress on HSC. The reduction in cell proliferation and collagen synthesis induced by amiloride could represent a new therapeutic challenge in liver fibrosis.

Animals↗
PubMed1999

Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Th1-like response in chronic hepatitis C.

BACKGROUND/AIMS: The involvement of a direct viral cytopathic effect or an immune-mediated mechanism in the progression of hepatic damage in chronic hepatitis C is controversial. The type of immune response is itself a matter of controversy, and histological data are lacking. The aim of this study was to identify the factors associated with the progression of liver injury in 30 HCV/RNA-positive untreated patients with chronic hepatitis. METHODS: Necroinflammatory and architectural damage were evaluated using Ishak's score. Activated hepatic stellate cells (HSC) were visualized by immunohistochemistry for alpha-smooth muscle actin (alphaSMA) and quantitated by morphometry. Plasma HCV/RNA was evaluated using a competitive RT-PCR method. To study the type of immune response involved in the progression of liver injury, interferon gamma (IFNgamma)-positive cells (as expression of a Th1-like response) were evaluated by immunohistochemistry and quantitated by morphometry. RESULTS: HSC were mostly detected close to areas of lobular necroinflammation or lining fibrotic septa. The alphaSMA- and Sirius Red-positive parenchyma correlated significantly with necroinflammatory and architectural scores. IFNgamma-positive cells were detected in periportal areas associated with the inflammatory infiltrates and significantly correlated with architectural damage. No relationship was found between the histological features of liver injury and viral load. CONCLUSIONS: HSC activation and progression of liver injury are unrelated to viral load but associated with a Th1-like response, a plausible target for the treatment of chronic hepatitis C.

Actins↗
PubMed1999

Tubercular involvement of the thyroid gland: a report of two cases.

Thyroid tuberculosis is rare. In the last decade, however, the incidence of extrapulmonary forms of tuberculosis has increased. We report on 2 cases of thyroid tuberculosis. In case 1, a tubercular abscess mimicking acute thyroiditis was found which was correctly diagnosed by fine-needle aspiration biopsy (FNAb). No evidence of active disease was noticed. Pleural thickening on chest X-ray was the only sign compatible with a previous infection. In case 2, tubercular thyroiditis with lymph node enlargement was also diagnosed by FNAb in a reevaluation setting. In both cases treatment with antitubercular drugs resulted in complete recovery. Thyroid tuberculosis should be kept in mind in the differential diagnosis of thyroid nodules, notably in patients with a history of tuberculous disease. FNAb represents the main approach to making the diagnosis.

Abscess↗
PubMed1999

Wine: risk factors for liver disease and antifibrotic compounds.

Wine can be considered an integral part of the Mediterranean diet and moderate alcohol intake can be beneficial for health. This health-promoting effect is presumably due to the presence of antioxidant substances. It is also known that excessive alcohol intake can lead to liver cirrhosis. A main pathogenetic mechanism in liver cirrhosis is the activation of hepatic stellate cells which acquire a myofibroblast-like phenotype. Excessive production of oxidative stress products may initiate the activation process. Phenolic compounds contained in red wine have been shown to have antifibrotic properties on activated hepatic stellate cells. In vitro and in vivo studies are needed for a better evaluation of the clinical relevance of these findings.

Antioxidants↗
PubMed1999

[The accuracy of the fine needle aspiration biopsy in 1250 thyroid nodules].

Between 1989 and 1998 a total of 1250 thyroid nodes underwent Fine Needle Aspiration Biopsy (FNAB). Of these 150 went on to surgery with subsequent histological examination which proved positive for malignant neoplasm in 35 nodes. The remaining 115 nodes presented benign lesions. The cytological diagnoses were preventatively broken down into three groups: a) benign; b) malignant; c) suspected malignancy. Group a) included 53 nodes; histology confirmed the diagnosis of a benign lesion in 50 of these nodes (True Negatives), while 3 proved malignant (False Negatives). The cytological diagnosis of malignancy was reached in 24 nodes (group b) and subsequent histology confirmed the malignancy in 18 cases (True Positives) while the remaining 6 nodes tested negative for neoplasm (False Positives). Group c) included those thyroid nodes which cytology classified as follicular neoplasms and for which histology was required to reach a diagnosis of malignancy or benignity; for this reason these cases were not used in the evaluation of diagnostic reliability. Of these 15 (20.5%) proved malignant and 58 (79.5%) benign (44 follicular adenomas and 14 micro-macrofollicular struma nodes). On the basis of the above data, the diagnostic accuracy of FNAB is 88.3%, sensitivity 85.7% and specificity 89.3%. These findings are substantially in agreement with the international literature which considers cytological testing highly reliable. In analyzing the cases which were not confirmed by histology, it was interesting to note that among the 4 false positives--defined as the "presence of atypical cells in a lymphocyte infiltration context"--a full three were thyroadenitis nodes for which the presence of atypical cells is quite common. The three false negative nodes, on the other hand, included two cysts for which cytology did not reveal neoplastic cells. The present experience suggests the following: 1) FNAB is still the most reliable technique for the diagnosis of thyroid neoplasms; 2) the presence of atypical cells in thyroid node lesions is not always indication of a malignancy; 3) cysts must be subject to careful follow-up since they can mask a malignant neoplasm.

Adolescent↗
PubMed1998

Galectin-3 is a presurgical marker of human thyroid carcinoma.

Galectin-3 is a carbohydrate-binding protein endowed with an affinity for beta-galactosides. It has been shown to play an important role in cell-cell and cell-matrix interactions and in pre-mRNA splicing. Furthermore, it is involved in the control of cell growth, neoplastic transformation, and metastasis. Interestingly, high levels of galectin-3 expression have been recently described in malignant thyroid neoplasias, but not in adenomas or in normal thyroid tissue. We investigated galectin-3 expression in human presurgical specimens obtained by fine-needle aspiration biopsy. We analyzed galectin-3 expression by immunoperoxidase staining in both paraffin-embedded cytological thyroid sediments (cell blocks) obtained by fine-needle aspiration biopsy and their histological counterparts. A total of 64 samples were examined: 17 follicular carcinomas; 18 papillary carcinomas; and 29 follicular adenomas. All cell blocks and histological samples of papillary carcinomas expressed high levels of galectin-3 at either the cytoplasmic or nuclear level. Among follicular carcinomas, all histological samples expressed galectin-3, whereas 14 of 17 corresponding cell blocks were positive in the cytoplasm. No evidence of cytoplasmic galectin-3 expression was observed in 26 of 29 follicular adenomas. Hence, cytoplasmic galectin-3 staining seems to be a reliable, easy, and cheap marker for presurgical diagnosis of follicular carcinomas and an even more suitable one for papillary carcinomas.

Adenocarcinoma, Follicular↗
PubMed1998

Comparison of urinary free beta (hCG) and beta-core (hCG) in prenatal screening for chromosomal abnormalities.

To evaluate the potential utility of free beta (hCG) and beta-core (hCG) in a prenatal screening protocol for Down syndrome we analysed these markers in dried maternal urine specimens from 163 control, 13 Down syndrome and 5 trisomy 18 pregnancies from 8 to 25 weeks' gestation. All results are reported after normalization for urinary creatinine determined by modified Jaffe reagent assay. The correlation of urinary free beta (hCG) and urinary beta-core (hCG) was 0.61 in controls and 0.93 in Down syndrome. Median MoM values in Down syndrome were 2.42 for urinary free beta (hCG) and 2.40 for beta-core (hCG). In trisomy 18 the Median MoM was 0.35 and 0.34 for free beta (hCG) and beta-core (hCG), respectively. The degree of elevation observed in DS cases with urinary free beta (hCG) is consistent with previous reports. Studies of beta-core (hCG) in Down syndrome have yielded discrepant results. In this study, beta-core (hCG) in Down syndrome is lower than values observed in early reports but consistent with more recent reports.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1998

Observer agreement in endoscopic assessment of ulcerative colitis.

BACKGROUND: Colonoscopy is the investigation of choice to evaluate ulcerative colitis, but the reliability of the assessment of endoscopic signs is not clear. AIMS: The aim of this study was to evaluate interobserver agreement for the identification of endoscopic lesions typical of ulcerative colitis, and the influence of training. MATERIAL AND METHODS: Four experienced observers and 11 endoscopists under training assessed 49 still images selected from endoscopic video recordings. RESULTS: The agreement rate between experienced observers was excellent or good (k > 0.39) for recognition of 10 out of 14 signs or patterns (loss of vascular pattern, erythema, oedema, granular mucosa, blood, pseudopolyp, erosion, ulcer, normal pattern, severe activity), and was poor for pus, stricture, mild activity, moderate activity. The rates between endoscopists under training were excellent or good for 6 items (loss of vascular pattern, erythema, oedema, pseudopolyp, normal pattern, severe activity). CONCLUSIONS: Trained observers can reproducibly record most endoscopic signs of ulcerative colitis. A reliable overall scoring of severity should be based on a simple three-grading scale, i.e. normal pattern, moderate activity, severe activity. Acceptable agreement rates can be obtained by endoscopists under training on some well-defined endoscopic appearances.

Colitis, Ulcerative↗
PubMed1997

First-trimester screening for fetal aneuploidy: biochemistry and nuchal translucency.

Maternal dried whole-blood specimens were collected prospectively from 2010 singleton pregnancies between 9 + 0 and 13 + 4 weeks that included 18 chromosomally abnormal pregnancies (11 Down's syndrome, four trisomy 18, two trisomy 13 and one triploidy). A subset of 744 pregnancies underwent ultrasound nuchal translucency measurement and included seven Down's syndrome, four trisomy 18, two trisomy 13 and one triploidy. Patients were evaluated for risk of Down's syndrome and trisomy 18 based on biochemistry (free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A), nuchal translucency and the combination of both. In prospective biochemical screening, false-positive rates for Down's syndrome and trisomy 18 were 5.1% (66/1297) and 1.9% (25/1297) in women < 35 years of age and 14.2% (99/695) and 1.6% (11/695) in women > or = 35 years of age, respectively. The detection efficiency of aneuploidy was 6/6 (100%) in women < 35 years and 11/12 (92%) in women > or = 35 years. Nuchal translucency measurement alone detected 57% (8/14) of cases of aneuploidy at a 5.8% (42/730) false-positive rate. Modelling with the age distribution of live births, a 5% false-positive rate resulted in Down's syndrome detection efficiency of 61% by biochemistry, 73% by nuchal translucency and 87% by combining both methods. The data in this study demonstrate that combined biochemical and ultrasound evaluation for Down's syndrome and other chromosomal abnormalities in the first trimester of pregnancy yield a detection capability that may exceed that of current second-trimester prenatal screening protocols. The potential for enhanced detection coupled to an earlier alert of fetal complications could represent a substantial advantage to both clinician and patient.

Adolescent↗
PubMed1996

Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies.

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy. In one fetus with alpha-thalassemia, one with sickle cell anemia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11. The fetus with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4 x 10(8) cells/kg) and in the 31st weeks of gestation (1.2 x 10(8) cells/kg), and is now two years of age. One fetus with sickle cell anemia received its transplant in the 13th week of gestation (16.7 x 10(8) cells/kg), and is now one year old. The fetus with beta-thalassemia was transplanted in 18th week (8.6 x 10(8) cells/kg), and is now three months old. Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PCR (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alpha- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 months of age, respectively. In neither of these cases were we able to detect convincing evidence of stem cell engraftment. Thus, the administration of fetal stem cells to fetal recipients after the 12th week of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earlier transplantations and/or higher cell doses.

Adult↗
PubMed1996

Changes in integrin and E-cadherin expression in neoplastic versus normal thyroid tissue.

UNLABELLED: BACK: The functional organization of polarized epithelia depends mostly on adhesion molecules belonging to the integrin and cadherin families. These molecules either recognize basement membrane components, such as laminins, or form intercellular junctions via homotypic interactions. Such tissue organization is often disrupted upon neoplastic transformation, and the resulting loss of functional polarization and cell cohesion might be a prerequisite for the invasive and metastatic behavior of carcinomas. PURPOSE: We studied modifications on thyroid adhesive mechanisms at various stages of neoplastic progression in terms of adhesion molecule expression, topography, and functional regulation by tyrosine kinases. Starting from this working hypothesis, we sought to identify one or more biological markers that would be suggestive of malignant transformation and poorer prognosis and that could be developed as a reliable indicator(s) in early diagnostic steps. METHODS: The study was carried out on both surgical samples and the corresponding fine-needle aspiration biopsy smears (numbers of specimens collected: 19 adenomas, seven follicular carcinomas, 13 papilary carcinomas, and 39 normal tissues). Immunohistochemistry of tissue sections and smears and immuno-precipitation and western blot analysis of protein extracts were done with a battery of monoclonal and polyclonal antibodies. Northern blotting was performed on RNA extracts from frozen tissue samples and use of an integrin subunit beta4 complementary DNA probe. RESULTS: Our findings can be summarized as follows: 1) In normal thyroid cells, the cooperative role of integrin alpha6beta4 and laminin 5/kalinin in hemidesmosome-mediated adhesion adhesion is missing, and recognition of the basal lamina occurs via integrin alpha3beta1 and laminin 1 and/or 2 (this pattern being maintained in adenomas but altered in carcinomas regardless of their histotype or differentiation grade); 2) only in carcinomas with clinical and/or histologic aggressiveness do neoexpression of integrin subunit beta4 and loss of laminin 2/merosin occur, indicating de novo assembly of integrin alpha6beta4; 3) pericellular redistribution and cytoskeletal disconnection of the E-cadherin-catenin complex occur; and 4) basal E-cadherin tyrosine phosphorylation decreases in carcinomas as compared with that in normal and adenomatous tissue. CONCLUSION: The malignant progression of thyroid tumors involves marked rearrangement of cell-basement membrane and cell-cell adhesion molecules and changes in their cytoskeleton linkage. These rearrangements are also easily and reproducibly detected on fine-needle aspiration biopsy smears. IMPLICATIONS: Immunodetection of adhesion molecules in sections and/or fine-needle smears may complement the toolbox of thyroid surgical pathologists; it may expand the possibilities of achieving a correct early diagnosis of thyroid tumors and of gaining some prognostic information on thyroid tumors.

Adenocarcinoma, Follicular↗
PubMed1996

Evidence of induced non-tolerance in HLA-identical twins with hemoglobinopathy after in utero fetal transplantation.

Fetus-to-fetus transplantation has been suggested for the treatment of hemoglobinopathies in utero. However, dissimilar results have to date been obtained by different groups. We describe a case in which fetus-to-fetus transplantation in HLA-identical twins was performed at the 19th week of gestation by infusion of 0.8 ml of fetal blood from normal to beta-thalassemia affected fetus with the main aim of inducing tolerance. No evidence of engraftment, determined by KM19 polymorphism, was present after 2 years of the procedure. Moreover, an alloreactive cytotoxic T lymphocyte precursor (CTLp) study of affected fetus vs donor and other different stimulators showed that immunization vs tolerance was the real effect of the procedure.

Adolescent↗