Biomedical subjects

G Macchia

Publications and source records attributed to G Macchia.

At least 19 recordsLinked to original sources

PubMed2005

D-aspartate and reproductive activity in sheep.

D-aspartic acid (D-Asp) has been isolated from neuroendocrine tissues of many invertebrates and vertebrates. Recently, it has been demonstrated that this D-amino acid may be converted to N-methyl-D-aspartic acid (NMDA), a neuromodulator associated with sexual activity. In this study, we determined D-Asp and NMDA concentrations in endocrine glands and other tissues in ewes after D-Asp administration and in controls. We also evaluated the effects of d-Asp administration on the reproductive activity of ewes by determining either progesterone concentrations or LH pulses in the presence or absence of estradiol benzoate. The pineal gland showed the highest natural content of D-Asp (1.47+/-0.22 micromol/g tissue), whereas the pituitary gland had the highest capability to store d-Asp, with a peak value (9.7+/-0.81 micromol/g tissue) 6 h after its administration. NMDA increased sharply 12 h following D-Asp administration, reaching values three times higher than the baseline in both the pituitary and brain. D-Asp was quickly adsorbed after subcutaneous administration, with a peak in plasma levels 2 h after administration and a return to baseline values after 6 h. D-Asp administration achieved a significant (P < 0.001) increase in LH values with respect to estradiol or estradiol + D-Asp treatments. d-Asp treatment once or twice a week did not successfully drive acyclic ewes into reproductive activity. In conclusion, the results obtained in this study demonstrated that D-Asp is endogenously present in sheep tissues and electively stored in endocrine glands and brain after its administration. NMDA and LH increase following D-Asp administration suggesting a role of this D-amino acid in the reproductive activity of sheep.

Animals↗

PubMed2005

Intraluminal brachytherapy without stenting in intrahepatic papillary cholangiocarcinoma: a case report.

A 46-year-old female patient, with mild cholestasis by a large papillary cholangiocarcinoma involving the left hepatic duct, received intraluminal brachytherapy (50 Gy at 1 cm from the source axis) with the aim to relieve biliary obstruction without stent positioning. The patient presented with haemobilia and vegetant lesions in the left main biliary duct, and thus she had a high risk of early stent obstruction. Eighteen months after the treatment the patient presented tumour progression in the controlateral hepatic lobe, but had a patent left hepatic duct, without signs of cholestasis and/or cholangitis. Based on this and other published reports, intraluminal brachytherapy may be tested in a setting different from standard setting with the aim to safely palliate jaundice in patients with intraductal tumour growth in the biliary tract.

Bile Duct Neoplasms↗

PubMed2003

Beta-dystrobrevin interacts directly with kinesin heavy chain in brain.

Beta-dystrobrevin, a member of the dystrobrevin protein family, is a dystrophin-related and -associated protein restricted to non-muscle tissues and is highly expressed in kidney, liver and brain. Dystrobrevins are now thought to play an important role in intracellular signal transduction, in addition to providing a membrane scaffold in muscle, but the precise role of beta-dystrobrevin has not yet been determined. To study beta-dystrobrevin's function in brain, we used the yeast two-hybrid approach to look for interacting proteins. Four overlapping clones were identified that encoded Kif5A, a neuronal member of the Kif5 family of proteins that consists of the heavy chains of conventional kinesin. A direct interaction of beta-dystrobrevin with Kif5A was confirmed by in vitro and in vivo association assays. Co-immunoprecipitation with a monoclonal kinesin heavy chain antibody precipitated both alpha- and beta-dystrobrevin, indicating that this interaction is not restricted to the beta-dystrobrevin isoform. The site for Kif5A binding to beta-dystrobrevin was localized in a carboxyl-terminal region that seems to be important in heavy chain-mediated kinesin interactions and is highly homologous in all three Kif5 isoforms, Kif5A, Kif5B and Kif5C. Pull-down and immunofluorescence experiments also showed a direct interaction between beta-dystrobrevin and Kif5B. Our findings suggest a novel function for dystrobrevin as a motor protein receptor that might play a major role in the transport of components of the dystrophin-associated protein complex to specific sites in the cell.

Animals↗

PubMed2003

Cyclooxygenase-2 (COX-2) expression in locally advanced cervical cancer patients undergoing chemoradiation plus surgery.

PURPOSE: To investigate whether cyclooxygenase-2 (COX-2) could be a marker of clinical outcome in cervical cancer patients undergoing concomitant chemoradiation plus surgery. METHODS AND MATERIALS: The study included 33 locally advanced cervical cancer patients; all underwent neoadjuvant chemoradiation, and responsive patients underwent radical surgery. Immunohistochemistry was performed with rabbit antiserum against COX-2. RESULTS: COX-2 integrated density values (IDVs) in the tumor component ranged from 1.4 to 72.3 (median 15.0); in stromal inflammatory cells, COX-2 IDVs ranged from 1.4 to 96.0 (median 16.0). A statistically significant inverse relation was found between the COX-2 IDVs of the tumor vs. the stromal inflammatory component (r = -0.52, p = 0.0017). When the ratio between COX-2 IDV in the tumor vs. the stromal compartment was 1) tumor/stroma COX-2 IDV ratio. Patients with a high tumor/stroma COX-2 IDV ratio had a shorter disease-free survival than did those with a low tumor/stroma COX-2 IDV ratio (p = 0.030). Similarly, those with a high tumor/stroma COX-2 IDV ratio had a shorter overall survival (p = 0.033). CONCLUSION: The assessment of COX-2 status in both the tumor and the stromal compartment could provide additional information in the prognostic characterization of cervical cancer patients administered concomitant chemoradiation plus surgery.

Adult↗

PubMed2003

Concomitant gemcitabine (Gemzar) and extended nodes irradiation in the treatment of pancreatic and biliary carcinoma: a phase I study.

BACKGROUND: The rationale for combining cytotoxic agents, such as gemcitabine, and radiotherapy is based on their ability to act as radiation sensitizers and to improve overall response rate. Several studies on pancreatic or biliary carcinoma evaluated the maximum tolerated dose (MTD) of gemcitabine when combined with irradiation of the macroscopic tumor. However, most of these neoplasms metastasize to the regional lymph nodes. Aim of this report is to determine the MTD of weekly gemcitabine when combined with extended field irradiation (tumor plus nodal irradiation). PATIENTS AND METHOD: 15 patients entered the study. Of these 5 patients were treated with chemoradiation after radical surgical resection. External beam radiation (ERT) was delivered to the tumor (or tumor bed) and regional lymph nodes by using a three-field technique. The initial dose of gemcitabine was 100 mg/m(2) administered as short intravenous infusion once a week. At each dose level 3 patients were treated, and if no grade 3-4 toxicity (considered as dose-limiting toxicity, DLT) was recorded, dose escalation was applied with 50 mg/m(2) increments until the MTD was established. RESULTS: All patients were evaluable for acute toxicity. There were no treatment-related deaths. No DLT occurred at the first 4 dose levels (100-250 mg/m(2)). At the 5th dose level (300 mg/m(2)), 3 patients experienced DLT: 1 had grade 3 gastrointestinal toxicity (painful erosion of gastric mucosa), 1 had uncomplicated grade 3 leukopenia and 1 grade 3 change in liver biochemistry tests. In addition, all 10 unresected patients were evaluated for response, 4 of whom had progressive disease (1 local; 2 distant; 1 local and distant) and 6 had no change. The median follow-up was 21 months. CONCLUSION: Based on this study, the recommended dose for weekly short infusional gemcitabine combined with radiation therapy to the tumor and lymph nodes is 250 mg/m(2). This value is suggestive of a correlation between acute toxicity and inclusion of lymph nodes in the irradiated volume. Moreover, different infusion modalities, as continuous infusion gemcitabine, should be tested more accurately.

Aged↗

PubMed2002

Prevalence of increased QT interval duration and dispersion in type 2 diabetic patients and its relationship with coronary heart disease: a population-based cohort.

OBJECTIVE: To evaluate the prevalence of prolonged QT interval and dispersion in a population-based cohort of type 2 diabetic patients and their relationship with clinical and metabolic variables. DESIGN: Cross-sectional population-based cohort. SETTING: Diabetes clinics and general practitioners in Casale Monferrato (Northern Italy). SUBJECTS: A total of 1357 patients with known type 2 diabetes (70% of the cohort). MAIN OUTCOMES MEASURES: Albumin excretion rate and coronary heart disease (CHD); a standard supine 12-lead electrocardiogram (ECG) was recorded and coded according to the Minnesota code criteria. QT interval corrected for heart rate (QTc) > 0.44 s and QTc dispersion > 0.080 s were considered abnormally prolonged. RESULTS: Prevalence of increased QTc duration and QTc dispersion were 25.8% (95% CI 23.5-28.3) and 33.1% (95% CI 30.6-35.7), with no sex differences. No metabolic differences were found, apart from fibrinogen and creatinine levels, which were higher in patients with increased QTc dispersion. Patients with CHD had higher mean adjusted values of QTc and QTc dispersion, whereas no association was found with albumin excretion rate (AER) and diabetes treatment. QTc duration and QTc dispersion were significantly correlated (0.17, P < 0.001). In multiple regression analysis, only CHD was independently associated with QTc, after adjustment for age and sex (beta=0.010, P < 0.001, R2=2.5%); as regards QTc dispersion, a similar association with CHD was found (beta=0.20, P < 0.001, R2=4.8%). CONCLUSIONS: This population-based study shows a considerably high prevalence of increased QTc and QTc dispersion in type 2 diabetic patients and their association with CHD. These findings have both epidemiological and clinical relevance, as they might be implicated in the excess mortality risk of type 2 diabetic patients.

Aged↗

PubMed2002

Adjuvant radiotherapy in resectable pancreatic carcinoma.

AIM: Pancreatic cancer is a near fatal disease. External beam radiotherapy and intraoperative radiation therapy (IORT) has been proposed with the aim to improve clinical outcome in resectable tumors. The aim of this study is to assess the feasibility and outcome in patients with cT1-3 pancreatic cancer, treated with surgery, external beam radiotherapy and IORT. METHODS: From 1990 to 1996, 17 patients with clinical stage T1-3N0-1M0 adenocarcinoma of the head of the pancreas were treated with pancreatectomy and pre- (nine patients: 5 Gy), intra- (all patients: 10 Gy) and post-operative (all patients: 50 Gy) radiotherapy. The pathologic T stages were: 4 pT2 and 13 pT3. The pathologic N stages were: 9 pN0 and 8 pN1. Minimum follow-up in living patients was 60 months. RESULTS: No perioperative mortalities were recorded. Two patients showed postoperative morbidity (11.8%) which required a subsequent laparotomy. The disease-free survival at 1, 3 and 5 years was 41, 23 and 18%, respectively (median: 9 months). The overall survival at 1, 3 and 5 years was 70%, 41% and 18%, respectively (median: 17.5 months). Three patients developed local failure (17.6%) and 12 patients showed distant metastases (70.6%). Univariate analysis (logrank) showed: a significant correlation between both N-stage and retroperitoneal involvement (RPI) with local control (N-stage: P=0.0155; RPI:P =0.0295), a significant correlation between maximum tumor size and metastases-free survival (P=0.0167) and overall survival (P=0.0241); the female gender was another predictor of prolonged survival (P= 0.0465). Multivariate analysis (Cox) showed a significant impact of N-stage and retroperitoneal involvement on local control and also a significant correlation between perineural involvement and tumor diameter with metastases-free survival. CONCLUSIONS: These results are similar to those of other published series and suggest that this approach is feasible with acceptable local control and survival, especially in patients with small tumors (<2.5 cm: 5 year survival=33.3%) and in female patients (5 year survival=30%). Due to the impact of gender, tumor diameter and N stage on prognosis, in the design of future trials a stratification of patients based on these categories should be considered. The search of effective chemotherapeutic agents is required, to reduce the high incidence of distant metastases, especially in larger tumors.

Aged↗

PubMed2002

Treatment of unresectable pancreatic carcinoma by intraluminal brachytherapy in the duct of Wirsung.

BACKGROUND AND STUDY AIMS: Our aim was to evaluate the feasibility and clinical outcome of intraluminal brachytherapy (ILBT) in the duct of Wirsung in patients with unresectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Nine patients (eight men, one woman; mean age 72.4 +/- 9.1, range 52 - 80) with unresectable pancreatic adenocarcinoma of the head or body underwent ERCP for biliary and/or pancreatic stent placement and placement of a nasopancreatic drain with/without nasobiliary drain. The ILBT dose administered was 30 - 50 Gy calculated at 1 cm from the iridium-192 wire axis. Seven patients received ILBT from the duct of Wirsung whereas two patients received dual-duct ILBT (duct of Wirsung and the common bile duct). Three patients received combined-modality treatment (ILBT with external beam radiotherapy and 5-fluorouracil). The patients were prospectively followed up. RESULTS: No endoscopy-related complications occurred. No radiation-related toxicity occurred in patients treated with ILBT alone. One patient undergoing combined-modality treatment developed gastric bleeding. Intraluminal source dislodgement occurred in three patients. Obvious tumor mass reduction of greater than 50 % was seen in three patients at 8 weeks after brachytherapy. Median survival was 11 months (range 6 - 37 months) and the 1-year and 3-year actuarial survival rates were 44 % and 15 %, respectively. CONCLUSION: Intraluminal brachytherapy in the duct of Wirsung in patients with unresectable pancreatic carcinoma is safe and feasible. Further clinical trials are warranted.

Adenocarcinoma↗

PubMed2000

Characterization of the beta-dystroglycan-growth factor receptor 2 (Grb2) interaction.

The beta-dystroglycan/Grb2 interaction was investigated and a proline-rich region within beta-dystroglycan that binds Grb2-src homology 3 domains identified. We used surface plasmon resonance (SPR), fluorescence analysis, and solid-phase binding assay to measure the affinity constants between Grb2 and the beta-dystroglycan cytoplasmic tail. Analysis of the data obtained from SPR reveals a high-affinity interaction (K(D) approximately 240 nM) between Grb2 and the last 20 amino acids of the beta-dystroglycan carboxyl-terminus, which also contains a dystrophin-binding site. A similar K(D) value (K(D) approximately 280 nM) was obtained by solid-phase binding assay and in solution by fluorescence. Both Grb2-SH3 domains bind beta-dystroglycan but the N-terminal SH3 domain binds with an affinity approximately fourfold higher than that of the C-terminal SH3 domain. The Grb2-beta-dystroglycan interaction was inhibited by dystrophin in a range of concentration of 160-400 nM. These data suggest a highly regulated and dynamic dystrophin/dystroglycan complex formation and that this complex is involved in cell signaling.

Animals↗

PubMed2000

Bcl-2, bax, bcl-x(L) and bcl-x(S) expression in neoplastic and normal cervical tissue.

We simultaneously assessed bcl-2, bax, bcl-x(L) and bcl-x(S) expression levels by Western blotting on 53 primary untreated cervical cancers and 15 normal samples. Bcl-2 showed a trend to be lower in neoplastic than in normal samples (P<0.01), while no significant difference was observed for bax and bcl-x(L). Bcl-x(S) was barely detectable in only a few samples. Interestingly, in cervical cancer, bcl-2 and bcl-x(L) were directly correlated (P<0. 01). A significant association of bcl-2 levels with age (P<0.021) and menopausal status (P<0.041) in cervical cancer patients as well as in control patients was observed. Bcl-2, bax and bcl-x(L) levels in responding and non-responding patients were not differently distributed. Bcl-2, bax and bcl-x(L) are likely to play a role in the natural history of cervical tumors, but their clinical significance in predicting response to treatment and clinical outcome needs long-term follow-up studies.

Adult↗

PubMed2000

Combined modality treatment in unresectable extrahepatic biliary carcinoma.

PURPOSE: Cancers of the extrahepatic biliary tract are rare. Surgical resection is considered the standard treatment, but is rarely feasible. Several reports of combined modality therapy, including external beam radiation, often combined with chemotherapy and intraluminal brachytherapy, have been published. The purpose of this study was to evaluate the effect of chemoradiation plus intraluminal brachytherapy on response, local control, survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. METHODS AND MATERIALS: From February 1991 to December 1997, 20 patients (14 male, 6 female; mean age 61 +/- 12 years; median follow-up 71 months) with unresectable (16 patients) or residual (4 patients), nonmetastatic extrahepatic bile tumors (common bile duct, 8; gallbladder, 1; Klatskin, 11) received external beam radiation (39.6-50.4 Gy); in 19 patients, 5-fluorouracil (96-h continuous infusion, days 1-4 at 1,000 mg/m(2)/day) was also administered. Twelve patients received a boost by intraluminal brachytherapy using (192)Ir wires of 30-50 Gy, prescribed 1 cm from the source axis. RESULTS: During external beam radiotherapy, 8 patients (40%) developed grade 1-2 gastrointestinal toxicity. Four patients treated with external-beam plus intraluminal brachytherapy had a clinical response (2 partial, 2 complete) after treatment. For the total patient group, the median survival and time to local progression was 21.2 and 33.1 months, respectively. Distant metastasis occurred in 10 (50%) patients. Two patients who received external beam radiation plus intraluminal brachytherapy developed late duodenal ulceration. Two patients with unresectable disease survived more than 5 years. CONCLUSION: Our data suggest that chemoradiation plus intraluminal brachytherapy was relatively well-tolerated, and resulted in reasonable local control and median survival. Further follow-up and additional research is needed to determine the ultimate efficacy of this regimen. New chemoradiation combinations and/or new treatment strategies (neoadjuvant chemoradiation) may contribute, in the future, to improve these results.

Adult↗

PubMed2000

Bcl-2, Bax, Bcl-x(L) and Bcl-x(S) expression in neoplastic and normal endometrium.

The two anti-apoptotic proteins Bcl-2 and Bcl-x(L), and the two pro-apoptotic proteins Bax and Bcl-x(S) were measured by Western blotting in 51 neoplastic and 8 normal endometrial samples. The corresponding mRNA levels were analyzed by semiquantitative reverse transcriptase-polymerase chain reaction in a subgroup of 19 endometrial carcinomas. Neoplastic tissues had higher amounts of Bcl-2 protein than normal tissues (p < 0.051). Bcl-x(L) followed the same trend since its levels were higher in tumor than in normal samples (p < 0.048). Interestingly, Bcl-2 and Bcl-x(L) protein content showed a trend towards an inverse correlation (r = 0.27, p < 0.052). mRNA and protein levels directly correlated only with Bcl-2 (r = 0.63, p < 0.0032). Despite the fact that the amounts of Bcl-2, Bax and Bcl-x(L) proteins in the neoplastic population were not significantly differently distributed according to the clinicopathological features of the patients, the differences observed between normal and neoplastic samples suggest that these proteins may play a role in endometrial carcinoma: long-term follow-up studies will be required to confirm this hypothesis.

Adult↗

PubMed1999

Cardiovascular risk profile of type 2 diabetic patients cared for by general practitioners or at a diabetes clinic: a population-based study.

The aims of this study were to compare the cardiovascular risk profiles of patients with type 2 diabetes mellitus cared for by general practitioners and those regularly attending a diabetes center. Out of an Italian population-based cohort of 1967 diabetic patients, 1574 (80%) were investigated. Patients exclusively cared for by general practitioners (23.8%) were older and showed lower prevalence of hypertension (79.0% vs 85.9%, P < 0.001), poor blood glucose control (HbA1c >8.0, 33.4% vs 47.9%, P < 0.001) and coronary heart disease (18.1% vs 22.3%, P = 0.003), and lower plasma fibrinogen (3.5 +/- 0.8 vs 3.7 +/- 0.9 g/L, P < 0.001). In logistic regression analysis, they had significantly lower ORs for HbA1c >8.8% (OR 0.67, 95% CI 0.45-0.99), hypertension (OR 0.53, 95% CI 0.36-0.78), fibrinogen >4.1 g/L (OR 0.50, 95% CI 0.32-0.77), smoking (OR 0.60, 95% Cl 0.36-1.00), and coronary heart disease (OR 0.65, 95% CI 0.45-0.93), after adjustment for age, sex, duration of diabetes, BMI, and antidiabetic treatment. Patients regularly cared for at a diabetes clinic had a higher cardiovascular risk profile, suggesting selective referral to the clinics of patients with more difficult management and/or severity of the disease. These findings have implications in the interpretation of morbidity and mortality clinic-based studies.

Aged↗

PubMed1999

Peroxynitrite induces tryosine nitration and modulates tyrosine phosphorylation of synaptic proteins.

Peroxynitrite, the product of the radical-radical reaction between nitric oxide and superoxide anion, is a potent oxidant involved in tissue damage in neurodegenerative disorders. We investigated the modifications induced by peroxynitrite in tyrosine residues of proteins from synaptosomes. Peroxynitrite treatment (> or =50 microM) induced tyrosine nitration and increased tyrosine phosphorylation. Synaptophysin was identified as one of the major nitrated proteins and pp60src kinase as one of the major phosphorylated substrates. Further fractionation of synaptosomes revealed nitrated synaptophysin in the synaptic vesicles, whereas phosphorylated pp60src was enriched in the postsynaptic density fraction. Tyrosine phosphorylation was increased by treatment with 50-500 microM peroxynitrite and decreased by higher concentrations, suggesting a possible activation/inactivation of kinases. Immunocomplex kinase assay proved that peroxynitrite treatment of synaptosomes modulated the pp60src autophosphorylation activity. The addition of bicarbonate (CO2 1.3 mM) produced a moderate enhancing effect on some nitrated proteins but significantly protected the activity of pp60src against peroxynitrite-mediated inhibition so that at 1 mM peroxynitrite, the kinase was still more active than in untreated synaptosomes. The phosphotyrosine phosphatase activity of synaptosomes was inhibited by peroxynitrite (> or =50 microM) but significantly protected by CO2. Thus, the increase of phosphorylation cannot be attributed to peroxynitrite-mediated inhibition of phosphatases. We suggest that peroxynitrite may regulate the posttranslational modification of tyrosine residues in pre- and postsynaptic proteins. Identification of the major protein targets gives insight into the pathways possibly involved in neuronal degeneration associated with peroxynitrite overproduction.

Animals↗

PubMed1999

Association of the dystroglycan complex isolated from bovine brain synaptosomes with proteins involved in signal transduction.

Dystroglycan is a transmembrane heterodimeric complex of alpha and beta subunits that links the extracellular matrix to the cell cytoskeleton. It was originally identified in skeletal muscle, where it anchors dystrophin to the sarcolemma. Dystroglycan is also highly expressed in nonmuscle tissues, including brain. To investigate the molecular interactions of dystroglycan in the CNS, we fractionated a digitonin-soluble extract from bovine brain synaptosomes by laminin-affinity chromatography and characterized the protein components. The 120-kDa alpha-dystroglycan was the major 125I-laminin-labeled protein detected by overlay assay. This complex, in addition to beta-dystroglycan, was also found to contain Grb2 and focal adhesion kinase p125FAK (FAK). Anti-FAK antibodies co-immunoprecipitated Grb2 with FAK. However, no direct interaction between beta-dystroglycan and FAK was detected by co-precipitation assay. Grb2, an adaptor protein involved in signal transduction and cytoskeleton organization, has been shown to bind beta-dystroglycan. We isolated both FAK and Grb2 from synaptosomal extracts by chromatography on immobilized recombinant beta-dystroglycan. In the CNS, FAK phosphorylation has been linked to membrane depolarization and neurotransmitter receptor activation. At the synapses, the adaptor protein Grb2 may mediate FAK-beta-dystroglycan interaction, and it may play a role in transferring information between the dystroglycan complex and other signaling pathways.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Presence of antibodies against Helicobacter pylori and its heat-shock protein 60 in the serum of patients with Sjögren's syndrome.

OBJECTIVE: Helicobacter pylori infection elicits a local and systemic immune response against bacterial antigens, including a heat-shock protein of 60 kDa (HSP60). The homology between microbial and human HSP suggests that the immune response to bacterial HSP may play a role in the pathogenesis of autoimmune disorders. Since gastric involvement and H. pylori have been reported in Sjögren's syndrome (SS), we investigated the prevalence of antibodies against H. pylori and its specific HSP60 in sera from patients with SS. METHODS: Four groups of patients were studied. Group 1, 34 patients with primary SS (pSS); Group 2.19 patients with secondary SS; Group 3, 22 patients with various autoimmune diseases and Group 4, 43 healthy controls. Serum IgG levels against HSP60 were determined by an ELISA using recombinant full length HSP60 expressed in Escherichia coli, as the antigen. To confirm the H. pylori infection, a commercial ELISA was used. RESULTS: Out of 34 patients in Group 1, 27 (79.4%) and 30 (88.2%) had antibodies against H. pylori and its HSP60, respectively. The prevalence was significantly higher than that found in Group 3 (18.2%, p < 0.0001 and 27.3%, p < 0.0001) and in Group 4 (48.8%, p < 0.005 and 37.2%, p < 0.0001) but not than that of Group 2 (48.8% and 37.2%). If the prevalence of patients either positive or negative for both antibodies was considered, a statistically significant difference was found between Group I and respectively Groups 3 and 4. CONCLUSION: The hypothetical role of HSP60 in the development of the immune response both in pSS and secondary SS seems strictly linked to the prevalence rate of H. pylori infection.

Adolescent↗

PubMed1999

[Positive predictive value of radiologic features in mammography and contribution of assessment procedures].

PURPOSE: To investigate the positive predictive value for cancer of abnormal mammographic findings and the role of assessment procedures. MATERIALS AND METHODS: We reviewed a series of 962 patients recalled and examined in the 1st Breast Screening Center of Turin, out of 18; 996 women aged 50-59 screened for the first time from 1991 to 1995, within a population-based mammography program. The diagnostic assessment procedures included one or more of the following: physical examination, additional mammographic views (detail or magnification), ultrasonography, and ultrasonography/X-ray-guided fine needle aspiration cytology. Surgical biopsies detected 152 cancers. RESULTS: The positive predictive value for screening mammography with abnormal findings steadily grew from 10.9% in 1991-92 to 15.6% in 1993, topping 21.1% in 1994 and 20.1% in 1995. The highest positive predictive value for cancers was observed among cases referred for opacities with irregular margins (88.2%) and isolated calcifications (23.8%). The benign/malignant biopsy ratio was .54 in 1991-92, .31 in 1993, .27 in 1994 and .25 in 1995. The accuracy of assessment procedures was different for each abnormal radiologic sign: the accuracy of cytology was high for opacities, intermediate for calcifications, low for architectural distortions; ultrasonography and physical examination had low sensitivity among cases referred for calcifications or opacities with regular margins. The positive predictive value of surgical indications was high for opacities, intermediate for calcifications, low for architectural distortions. The role of assessment procedures in excluding surgery was different for each abnormal radiologic sign. DISCUSSION AND CONCLUSIONS: The results of this study confirm the accuracy of mammography in the early detection of breast cancer and the different role of assessment procedures in the various abnormal mammographic findings. The improvement in positive predictive value for screening recalls from about 10% (close to recommended European standards) up to about 20% (well above European standards) demonstrates the importance of the "learning curve" within the screening team. Most of this improvement could be referred to refined diagnostic criteria for calcifications, as shown by an increase in positive predictive value for calcifications from 13.7% in 1991-92 to 40.5% in 1995.

Breast Neoplasms↗

PubMed1999

Role of lipid, apolipoprotein levels and apolipoprotein E genotype in young Italian patients with myocardial infarction.

BACKGROUND AND AIM: Studies of young patients with acute myocardial infarction (AMI) have demonstrated that conventional risk factors are usually responsible for their premature atherosclerosis. No account has yet been published of the risk profile of young Italians surviving an AMI. In this study, the conventional risk factors, lipids and apolipoproteins, and apolipoprotein E (APOE) allele distribution were evaluated in 98 consecutive AMI survivors (94 males, 4 females) aged 40.1 +/- 3.9 for at least three months after their acute event. These survivors were matched for age, sex, body mass index and presence of diabetes mellitus with 98 controls selected from subjects admitted to the same hospital for other reasons. METHODS AND RESULTS: Lipid profiles and APOE polymorphism were determined in both groups. Coronary angiography during hospitalization showed the absence of critical stenosis in 6.6% of the survivors, mono-vessel disease in 57.7%, and multi-vessel disease in 35.5%. The survivors had a higher frequency of smoking, hypertension, family history for coronary artery disease (CAD) and dyslipidemia, and a much greater frequency of 3 or more risk factors than the controls: Odd ratios (OR) 7.4, 95% confidence interval (CI) 2.5-18.6, p = 0.0000. Significant differences were found between the groups for triglycerides (p = 0.000002), total cholesterol (p = 0.003), LDL-cholesterol (p = 0.012), HDL-cholesterol (p = 0.0002), apolipoprotein AI (p = 0.00001), and Apolipoprotein B (p = 0.000001). No differences were observed in APOE allele distribution (APOE*4 0.11 vs 0.08, APOE*3 0.86 vs 0.89, APOE*2 0.03 vs 0.03), nor in lipid profile when both higher risk genotype (E3/4, E4/4, E2/4) and lower risk genotype groups (E2/2, E2/3, E3/3) were analysed. OR were calculated as measures of the association of the E4-positive genotypes with AMI. They indicated a non-significant increase in risk of AMI when the survivors were compared with the controls (OR 1.78, 95% CI 0.84-3.70, p = 0.13). CONCLUSIONS: This study provides further evidence that conventional coronary risk factors are usually present in young AMI patients. The APOE*4 allele was associated with a 1.8 non-significant increase in the risk of AMI in our group with premature CAD. Comparison with controls showed that the presence of three or more risk factors sharply increased the probability of premature CAD and that hyper-triglyceridemia is an independent risk factor. The data on APOE polymorphism are less certain and a larger study is needed.

Adult↗