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Biomedical subjects

M De Santis

Publications and source records attributed to M De Santis.

At least 55 records · Page 3Linked to original sources

[Hepatic arterial vascular anatomy and its variants].

PURPOSE: We investigated the frequency of anatomical variants of the hepatic artery, which can influence interventional angiographic procedures. MATERIAL AND METHODS: We reviewed 150 consecutive angiograms performed for the treatment of primary (112) or metastatic (38) liver tumors and evaluated the frequency of anatomical variants of the hepatic artery based on the classification proposed by Michels in 1955, which describes 10 variants. The so-called typical anatomy, which is in fact only found in 55% of cases, is indicated as type I. RESULTS: The typical anatomy (type I variant) was seen in 78 patients (52%) and variants were seen in the other 72 (48%). We found 15 type II variants (10%), 23 type III (15.5%), 1 type IV and 1 type V (0.6%), 3 type VI (2%), 1 type VII (0.6%) and finally 6 type IX (4%). There were no type VIII or X variants, but in 22 patients (14.7%) vascular anatomy did not fit Michaels' classification. DISCUSSION AND CONCLUSIONS: In our series the typical hepatic artery anatomy was found in 52%, which is in agreement with Michels' findings, while the frequency of the individual anatomical variants differed. Not all of the variants reported by Michels were seen in our series and we found 22 patients with different variants. Disagreement might be due to the fact that Michels' was an autoptic series while our patients were cancer patients only and thus variability could be at least partly accounted for by neoplastic neovascularization. We believe that thourough knowledge of the anatomical variants of the hepatic artery is fundamental to angiographic practice, in particular for interventional procedures, because such variants can influence the choice of vascular technique and of materials.

Angiography↗

[Reflux oesophagitis and risk factors. Results of a population study].

BACKGROUND: To evaluate the prevalence and endoscopic grade of reflux oesophagitis (RO) and to correlate them to symptoms and to a list of risk factors including age, sex, weight, smoking, alcohol, work, hiatus hernia. METHODS: This study was carried out in Roccacorga (LT), a little town of 3435 inhabitants in central Italy. The sample totalled 1084 volunteers, aged over 18 years old and enlisted in opened cohort. After filling in the questionnaire, all the patients were subjected to esophagogastroduodenoscopy without eating for at least six hours and diazepam pretreated (10 mg ev). Three biopsies were routine performed on the 3 biopsies on distal esophagous wall. The RO range was evaluated according to the Savary-Miller classification. RESULTS: The RO was found in 443 patients (188 M, 42%; 255 F, 58%) (p<0.0002), a large number of asymptomatic patients (39%). The prevalence of hiatus hernia was 7.2%, RO associated in 60.3% (p<0005). The prevalence of associated gastroduodenal injuries was pointed out (p<0.03). Patients affected only by RO were mostly female (p<0.02). Precancerous esophagous were 0,37%. CONCLUSIONS: According to this study the RO diagnosed through endoscopy is much more prevalent than supposed, especially among females and it affects a younger age than reported (31-50 years). Smoking and alcohol are among male risk factors, while, in female, agricultural works, weight and hormonal state could have a leading role (p=NS).

English Abstract↗

Cripto-1 induces phosphatidylinositol 3'-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3beta in human cervical carcinoma cells.

Cripto-1 (CR-1), a member of the epidermal growth factor-CFC peptide family, activates the ras/raf/mitogen-activated protein/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. In the present study, the role of CR-1 in the phosphatidylinositol 3'-kinase (PI3K)/AKT (protein kinase B)/glycogen synthase kinase 3beta (GSK-3beta)-dependent signaling pathway was evaluated in human SiHa cervical carcinoma cells. Our data demonstrate that CR-1 can enhance the tyrosine phosphorylation of the p85 regulatory subunit of PI3K and transiently induce the phosphorylation of AKT in a time- and dose-dependent manner. In addition, CR-1 was found to induce the phosphorylation of GSK-3beta. Phosphorylation of AKT and GSK-3beta by CR-1 can be blocked by LY294002, a specific inhibitor of PI3K, thus leading to apoptosis. Finally, the apoptotic effect of LY294002 can be partially rescued by exogenous CR-1. In summary, our data suggest that human CR-1 may function as a survival factor through a PI3K-dependent signaling pathway involving AKT and GSK-3beta.

Calcium-Calmodulin-Dependent Protein Kinases↗

Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor.

Cripto-1 (CR-1) is a recently discovered protein of the epidermal growth factor family that fails to directly bind to any of the four known erb B type 1 receptor tyrosine kinases. The present study demonstrates that CR-1 indirectly induces tyrosine phosphorylation of erb B-4 but not of the epidermal growth factor-related receptors erb B-2 and erb B-3 in different mouse and human mammary epithelial cell lines. In addition, down-regulation of erb B-4 in NMuMG mouse mammary epithelial cells and in T47D human breast cancer cells, using an anti-erb B-4 blocking antibody or a hammerhead ribozyme vector targeted to erb B-4 mRNA, impairs the ability of CR-1 to fully activate mitogen-activated protein kinase. Finally, chemical cross-linking of 125I-CR-1 to mouse and human mammary epithelial cell membranes results in the labeling of two specific bands with a molecular weight of 130 and 60 kDa, suggesting that the CR-1 receptor represents a novel receptor structurally unrelated to any of the known type I receptor tyrosine kinases. In conclusion, these data demonstrate that CR-1, upon binding to an unknown receptor, can enhance the tyrosine kinase activity of erb B-4 and that a functional erb B-4 receptor is required for CR-1-induced MAPK activation.

Animals↗

Cancer risk among female agricultural workers: a multi-center case-control study.

BACKGROUND: Cancer risk among women engaged in farming has been poorly investigated. This group of female workers is of particular interest, however, since they may experience exposure to several potential agricultural hazards. METHODS: A hospital-based case-control study was conducted in five Italian rural areas to examine the association between cancer and farming among women. The areas selected were located in three different regions (i.e., Piedmont, Tuscany, and Emilia-Romagna). The following cancer sites were selected for the study: stomach, colon, rectum, lung, skin melanoma, skin non-melanoma, breast, cervix and corpus uteri, ovary, bladder, kidney. Cases of non-Hodgkin's lymphoma were also included. Altogether, 1,044 newly diagnosed cases aged 20-75 years were ascertained from hospital records from March 1990 to September 1992, and for 945 of them detailed information was collected by a standard questionnaire. The analyses of data were performed comparing each case series to a reference group drawn from among the other sites. Unconditional logistic regression models were used in the statistical analyses. RESULTS: Statistically significant increased risks in association with farming were estimated for skin melanoma (OR 2.7, 95% CI 1.2-5.8) and bladder cancer (OR 2.7, 95% CI 1.2-6.1). Lung cancer was also found increased but not at a statistically significant level (OR 1.7, 95% CI 0.7-4.4). An OR lower than unity was observed for postmenopausal breast cancer (OR 0.4, 95% CI 0.3-0.7). CONCLUSIONS: The present study suggests that women in farming might experience increased risk of cancers, not usually found in excess among male farmers, as well as a protective effect for postmenopausal breast cancer. The role of different patterns of exposure or gender specific responses should be considered in further studies.

Adult↗

Cripto: a novel epidermal growth factor (EGF)-related peptide in mammary gland development and neoplasia.

Growth and morphogenesis in the mammary gland depend on locally derived growth factors such as those in the epidermal growth factor (EGF) superfamily. Cripto-1 (CR-1, human; Cr-1, mouse)--also known as teratocarcinoma-derived growth factor-1--is a novel EGF-related protein that induces branching morphogenesis in mammary epithelial cells both in vitro and in vivo and inhibits the expression of various milk proteins. In the mouse, Cr-1 is expressed in the growing terminal end buds in the virgin mouse mammary gland and expression increases during pregnancy and lactation. Cr-1/CR-1 is overexpressed in mouse and human mammary tumors and inappropriate overexpression of Cr-1 in mouse mammary epithelial cells can lead to the clonal expansion of ductal hyperplasias. Taken together, this evidence suggests that Cr-1/CR-1 performs a role in normal mammary gland development and that it might contribute to the early stages of mouse mammary tumorigenesis and the pathobiology of human breast cancer.

Amino Acid Sequence↗

Ontogeny of the fetal immune system: study on pregnancies with Rh-isoimmunization and nonimmune fetal hydrops.

This study aims at observing and comparing the antigen expression of some fetal T- and B-lymphocyte subpopulations in Rh-isoimmunization, which determines anemic hypoxia in the fetus, and nonimmune fetal hydrops (NIFH) which, even if there are some etiological factors involved, causes hipoxic hypoxia in the fetus. Twelve fetuses were studied by way of 30 fetal blood samples obtained by ultrasound-guided cordocentesis between the 20th and 36th gestational week. Twenty-four blood samples in all where taken from the eight fetuses with Rh-isoimmunization. Six blood samples were obtained from the four fetuses with NIFH. The lymphocyte phenotypes studied by monoclonal antibodies and flow cytometry were the following: CD3, CD4, CD8, expression of T-lymphocyte subpopulations; BsIg, CD19, expression of B-lymphocyte subpopulations. We observed a near-normal maturation process in fetuses with Rh isoimmunization, whereas in fetuses with NIFH we observed inhibition and/or delayed expression of T-lymphocytes. An early and increased B-lymphocyte activation marked a cooperation between the two systems in the early gestational periods.

Anemia↗

Reliability of visual and quantitative hepatobiliary scintigraphy in the follow-up of patients who have undergone cholecystectomy and transduodenal sphincteroplasty.

A noninvasive scintigraphic technique to assess the efficacy of a surgical procedure (e.g., cholecystectomy and transduodenal sphincteroplasty) depends on the development of reliable and accurate qualitative or quantitative diagnostic criteria that allow early recognition of the occurrence and site of complications. For this purpose, the authors divided biliary flow into a four-step progression process and analyzed transit times from the peripheral vein to the gallbladder, common bile duct, and duodenum and the transit time from the common bile duct to the duodenum. These quantitative parameters were assessed in nine healthy volunteers and 31 asymptomatic patients who had previous cholecystectomy to validate their reliability. The results indicate that the four-step Tc-99m HIDA progression analysis provides a reliable, noninvasive evaluation of biliary flow, so that it can be applied to patients who have had cholecystectomy.

Adult↗

Multimodal approach in invasive fetal therapy.

BACKGROUND: Integrated fetal therapy is a new approach to prenatal management consisting of a combination of invasive procedures which complement each other to provide as much information as possible on the fetal compartments. METHODS: We carried out a study on 50 fetuses of singleton pregnancies undergoing invasive procedures -- at least three per fetus -- for diagnostic and therapeutical purposes. A total of two hundred and fifty invasive procedures were adopted. The study population was divided into two groups, those studied between 1988 and 1992 and those studied between 1993 and 1995. RESULTS: The diagnostic and therapeutic utility of complementary invasive procedures in fetuses with nonimmune fetal hydrops and urinary tract malformations was assessed. In fetuses with nonimmune fetal hydrops integrated invasive procedures markedly affected the fetal-neonatal survival rate, whereas in those with urinary tract malformations scheduled for postnatal surgery these procedures made it possible to limit intrauterine renal damage. CONCLUSIONS: Complementary invasive procedures in NIFH fetuses particularly influence the fetal-neonatal survival rate. Since urinary tract malformations must be treated by postnatal surgery, complementary invasive procedures serve to limit intrauterine renal damage in the meantime and to reduce cesarean section rate.

Female↗

[Magnetic resonance with endorectal coil in the local staging of prostatic carcinoma. Comparison with histologic macrosections in 40 cases].

PURPOSE: Endorectal coil MRI is widely used in the diagnostic workup of prostate cancer, but diagnostic accuracy rates reported in the literature are quite variable. We report our personal experience with endorectal coil MRI in the local staging of prostate carcinoma. MATERIAL AND METHODS: Forty consecutive patients with histologically proved prostate carcinoma were examined with endorectal coil MRI at high field strength (1.5 T). All patients underwent a sagittal T1-weighted SE location sequence (TR 400, TE 20), an axial T1-weighted SE (TR 400, TE 20), two axial T2-weighted FSE sequences (TR 3000, TE 102, ETL 8) with and without fat suppression, and a coronal T2-weighted FSE sequence (TR 3000, TE 102, ETL 8); an axial Fast Multiplanar Spoiled Gradient Recalled (FMSPGR) dynamic sequence after Gd-DTPA injection was also performed in 18 patients. MR staging of local tumor spread was done according to the current literature criteria. All patients were submitted to radical prostatectomy, and histologic macrosections on the same plane as MR images were obtained from surgical specimens. MR and histologic staging were compared to assess MR accuracy in detecting capsular infiltration, seminal vesicles and apex involvement. The diagnostic yield of Gd-DTPA was also investigated. RESULTS: MRI correctly staged 31 of 40 cases (77.5%). MR accuracy was 80% in detecting capsular infiltration (85.7% sensitivity and 73.6% specificity), 90% in seminal vesicle involvement (91.6% sensitivity, 89.2% specificity) and 72.5% in apex involvement (79.1% sensitivity, 62.5% specificity). Dynamic studies with Gd-DTPA did not improve staging accuracy in any case. DISCUSSION AND CONCLUSIONS: In agreement with most of the current literature, MRI showed moderate overall accuracy in the local staging of prostate carcinoma. Particularly, MRI had good accuracy in detecting seminal vesicle involvement but moderate sensitivity and specificity in demonstrating capsular infiltration and apex involvement. Due to its high cost, MRI should not be routinely used in prostate cancer staging but should be reserved to the patients whose clinical and serological data suggest extraprostatic tumor spread, whose preoperative demonstration could avoid noncurative surgery.

Aged↗

[The antioxidants (coenzyme Q10) in materno-fetal physiopathology].

BACKGROUND: Coenzyme Q10 (ubidecarenone) is a torpeniod molecule mainly located in bacterial and mitochondrial membranes. It is a part of a specific enzyme system and acts primarily on the transport of electrons in the mitochondrial respiratory chain. It performs an antioxidant action. We studied both fetal and maternal coenzyme Q10 plasma levels in physiological conditions and also in the presence of some pathologies. METHODS: As regards the maternal side, we selected 483 pregnancies, performing 615 blood samples, and divided them into four groups: A: physiological pregnancies; B: spontaneous abortions; C: threatened abortions; D: threatened late abortions and threatened pre-term deliveries. We then selected 61 pregnancies which differed from the previous ones and determined Q10 levels in fetal samples obtained by cordocentesis. We divided a control group from pathological groups: intra-uterine growth retardation (IUGR); Rh-isoimmunization (with intra-uterine transfusion), non immune fetal hydrops, fetal malformations. Coenzyme Q10 levels were determined in only one laboratory by high-performance liquid chromatography (HPLC). Coenzyme Q10 concentrations were expressed as mg/ml, the data as the mean + SD. Statistical analysis was performed employing a linear regression model and the student "t"-test. RESULTS: After working out a normality curve of CoQ10 levels in maternal blood, we noticed that the levels of Coenzyme Q10 were low in spontaneous abortions, in threatened late abortions and in threatened pre-term deliveries. We determined the value of 0.3 mg/ml as a cutoff to differentiate the fetal from the adult values. Moreover, CoQ10 values turned out to be increased only in fetuses affected by non-immune fetal hydrops. CONCLUSIONS: Accordingly, we can say that maternal CoQ10 plasma levels can be considered as a marker of pathological uterine contractile activity. There is a substantial increase in CoQ10 fetal plasma levels in fetuses affected by hypoxic hypoxia and also in those affected by non-immune fetal hydrops.

Abortion, Spontaneous↗

Magnetic resonance imaging evaluation of myocardial perfusion.

Noninvasive qualitative/quantitative assessment of myocardial perfusion is considered to be fundamental in the management of known and suspected coronary artery disease patients, as shown by the widespread utilization of thallium-201- and technetium-99m-labeled agents in myocardial single-photon emission computed tomography (SPECT) scintigraphy for diagnostic as well as prognostic purposes. Recently, the availability of subsecond ultrafast magnetic resonance imaging (MRI) sequences (FLASH, TurboFLASH, EPI) has provided new avenues for assessing myocardial perfusion by MRI in conjunction with contrast-agent bolus administration (contrast-enhanced first-pass MRI). MRI contrast agents can be classified into relaxation agents (T1 "positive") and susceptibility agents (T2 star [T2*] "negative"). All the commercially available MRI contrast agents used in clinical practice are relaxation agents employing the T1 shortening effect of metal ions like gadolinium (paramagnetism), thus producing a tissue signal-intensity increase on T1-weighted images (positive enhancement). On the other hand, T2* agents induce mainly susceptibility effects, i.e., rapid dephasing of spins with resultant signal loss on T2*-sensitive sequences (negative enhancement). Unfortunately, both relaxation and susceptibility agents are, by definition, "extracellular" contrast media, as they rapidly diffuse into the interstitial space, thus hampering the simple application of indicator-dilution kinetics for myocardial perfusion assessment. Blood pool agents are therefore needed to obtain predictable relations between the concentration of contrast medium in the myocardium and the change in signal intensity. In addition, newer MRI techniques for tissue perfusion quantitation have been recently reported, based on blood-sensitive sequences, thus without intravenous contrast administration.

Contrast Media↗

Three-dimensional echocardiographic assessment of the extension of dysfunctional mass in patients with coronary artery disease.

Two-dimensional (2D) echocardiographic estimation of infarcted mass is limited by having only a few selected nonparallel views for data analysis. Volume-rendered three-dimensional (3D) echocardiography may be able to overcome the above limitations, because it uses multiple, parallel 2D images to derive quantitative data. Previous experimental studies demonstrated that 3D echocardiography is an accurate and reproducible method to assess dysfunctional mass. To estimate the accuracy of 3D echocardiography in humans, we evaluated 10 patients who had a single myocardial infarction. All patients underwent 2D and 3D echocardiography using the transesophageal approach, and contrast (gadolinium) magnetic resonance imaging (MRI), considered a reference standard for infarcted tissue detection. The mean extent of dysfunctional mass by MRI was 28 +/- 13 g and by 3D echocardiography was 30 +/- 12 g; the mean difference was 1.9 +/- 2.3 g (p = not significant). Linear regression analysis between the 2 measurements was y = 0.97x - 1.12, r = 0.98. Dysfunctional mass derived from 3D echocardiography reflects the real site and extension of damaged myocardium.

Coronary Disease↗

Asbestos-related lung cancer mortality in Piedmont, Italy.

This study investigates the association between pleural neoplasm mortality, a possible proxy for asbestos exposure, and lung cancer mortality among males resident in Piedmont (northwestern Italy). Pleural neoplasm mortality was estimated in the 1,209 municipalities of the region for the period 1980-1992, applying Bayesian methods. The association with lung cancer mortality for municipalities was studied using Poisson regression. Urban/rural indicators and altitude were also included in the analysis. A positive, statistically significant association was found between pleural neoplasm and lung cancer mortality (beta = 0.025, P < 0.001); lung cancer risk was associated also with urban status (vs. rural, beta = 0.223, P < 0.001) and altitude (P = 0.01). The proportion of lung cancer deaths attributable to living in municipalities with increased pleural neoplasm mortality was 3.9% (95% confidence interval, 2.1-5.7%). The observed association and the presence of a dose-response relationship at the municipality level underscore the dangers of asbestos for human health.

Adult↗

Cohort study of art glass workers in Tuscany, Italy: mortality from non-malignant diseases.

This investigation studies cause-specific mortality of art glass workers employed in 17 industrial facilities in Tuscany, Italy. A cohort of 3,390 workers employed for at least 1 year was enumerated from company payrolls. Follow-up was between the start of employment in each factory and 31 December 1993. The cause-specific expected mortality was computed relative to Tuscany rates and specified for gender, 5-year age groups and calendar year. Separate analyses were carried out for the jobs of makers and formers and for batch mixers. Among males (3, 180 individuals) observed mortality for non-cancer causes was higher than expected for hypertensive disease [standardized mortality ratio (SMR) = 178, 90% confidence interval (90% CI) = 96-301], pneumoconiosis (SMR = 200, 90% CI = 94-376) and diseases of the genitourinary system (SMR = 169, 90% CI = 95-279). Increases for the above causes were shown also among makers and formers: hypertensive disease (SMR = 182, 90% CI = 85-341), pneumoconiosis (SMR = 250, 90% CI = 109-493) and diseases of the genitourinary system (SMR = 224, 90% CI = 121-380). For batch mixers an increase was present for cerebrovascular disease. The observed mortality for cancer causes was above the expected for cancers of the larynx, lung, stomach and brain. This study points to the existence for Tuscan glass workers of health effects in addition to cancer; previously observed carcinogenic effects were also confirmed.

Adult↗

Cancer mortality of art glass workers in Tuscany, Italy.

OBJECTIVES: This study considers the cause-specific mortality from cancer among art glass workers employed in 17 industrial facilities in Tuscany, Italy. METHODS: A cohort of 3390 workers, 3180 men and 210 women, employed at least 1 year, was taken from company payrolls. It was followed between the year each factory started operation, mostly the mid-1950s, and 31 December 1993. The cause-specific expected mortality from cancer was computed for men relative to Tuscany rates, specified for gender, 5-year age groups, and calendar year. Separate analyses were carried out for the job title of maker and former and for batch mixers. RESULTS: For 3180 men, the observed mortality was above the expected for larynx [standardized mortality ratio (SMR) 166, 90% confidence interval (90% CI) 90-282], lung (SMR 123, 90% CI 100-151), stomach (SMR 105, 90% CI76-142), and brain (SMR 150, 90%CI 71-282) cancer. Increases for these causes were also found for the makers and formers. Mortality from larynx and lung cancer increased with latency, and significantly increased SMR values were observed for > or =21 years since first exposure. The increasing pattern was also present after adjustment for smoking. CONCLUSIONS: The results showed consistently increased mortality from larynx and lung cancer in the overall cohort and among makers and formers. Stomach and brain cancer was also increased in the overall cohort and among the makers and formers.

Adult↗