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Biomedical subjects

M De Santis

Publications and source records attributed to M De Santis.

At least 19 recordsLinked to original sources
PubMed2003

Scintimammography with 99mTc-MIBI and magnetic resonance imaging in the evaluation of breast cancer.

This study was performed to evaluate the sensitivity and specificity of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintimammography (SMM) and contrast-enhanced magnetic resonance imaging (MRI) in patients with breast masses, using the histological findings as the gold standard. Forty-five consecutive patients with a breast lesion, detected by self-examination, physical examination or screening mammography, underwent SMM and MRI. In 38 cases (84.5%), the histopathology was malignant; the breast cancers ranged from 3 to 100 mm in diameter (mean 22 mm). In the overall patient group, MRI showed a slightly higher sensitivity than SMM (92% vs 84%), but SMM showed a better specificity: 71% vs 42%. The accuracy was 82% and 84% for SMM and MRI respectively. To evaluate the influence of lesion size on the results, patients with lesions < or =20 mm and < or =15 mm were examined. In patients with lesions < or =20 mm, the sensitivity of SMM and MRI decreased to 64% and 82% respectively, while SMM again displayed considerably better specificity: 83% vs 50% for MRI. The accuracy of SMM and MRI was 64% and 82% respectively. In patients with lesions < or =15 mm, SMM again showed better specificity (75% vs 50%), while MRI displayed better sensitivity and accuracy (sensitivity, 81% vs 62%; accuracy, 75% vs 65%). In this study the specificity of SMM in patients with breast lesions was thus superior to that of MRI. The combination of SMM and MRI may be used in those patients with equivocal findings at mammography and ultrasound to reduce the number of unnecessary surgical biopsies.

Adult↗
PubMed2003

Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies.

The 22q11.2 deletion (del22q11.2) syndrome is a genetic condition with wide interfamilial and intrafamilial variability in clinical expression. The aim of the present study was to review the prevalence of parental transmission in our series of patients with del22q11.2, and to analyse clinical findings of the affected parents. Parental transmission of del22q11.2 in our series was 17.2% (15/87), with a preferential maternal transmission (10/15). One or more major features of del22q11.2 were found in all deleted parents, but one of the mothers showed extremely mild clinical anomalies. The present data demonstrate that it should be current policy to test both parents of patients with del22q11.2, irrespective of the parental phenotype, in view of the fact that extremely mild clinical features can be detected in parents of deleted patients. This would provide accurate genetic counselling to del22q11.2 families, as relatively asymptomatic parents must be advised of the 50% risk of transmitting the deletion in a subsequent pregnancy. Various genetic and non-genetic factors, including modifier genes at separate loci, mosaicism, unstable mutations, allelic variations at the haploid locus, chance and environmental interaction, can be hypothesized to be involved in variable clinical expression, even in the same family.

Chromosomes, Human, Pair 22↗
PubMed2002

Highly strained structure of a four-layer deposit of Pd on Ni(110): a coupled theoretical and experimental study.

The structure of a four monolayer deposit of Pd on Ni(110) has been determined by a combination of x-ray diffraction experiments and density-functional theory calculations. This Pd film presents, after annealing at 500 K, a (Nx2) reconstruction associated with a large enhancement of its catalytic activity. The N superstructure, along the dense [11;0] direction, comes from periodic edge dislocations initiated by a vacancy in the first Pd layer. In the perpendicular direction, the doubling of the period originates in a pairing-buckling displacement of the rows. This study evidences a new Pd atoms arrangement with quasi-four-fold hollow sites on the surface, which could play an important role in the exceptional catalytic activity.

Journal Article↗
PubMed2002

Two-dimensional oxide on Pd(111).

The oxidation of Pd(111) leads to an incommensurate surface oxide, which was studied by the use of scanning tunneling microscopy, surface x-ray diffraction, high resolution core level spectroscopy, and density functional calculations. A combination of these methods reveals a two-dimensional structure having no resemblance to bulk oxides of Pd. Our study also demonstrates how the atomic arrangement of a nontrivial incommensurate surface can be solved by molecular dynamics in a case where experimental techniques alone give no solution.

Journal Article↗
PubMed2002

Fertility rate evaluation by laparoscopic approach in the experimental animal.

PURPOSE OF INVESTIGATION: The aim of the present study was to evaluate the effect of laparoscopic insemination (LAP) and natural mating (NM) on fertility rate in experimental animal (Ovis Aries Comisana) during the month of June. METHODS: For the experiment, 97 ewes were used. Laparoscopic insemination was performed with the frozen semen of three different Romanov rams: Laparoscopic insemination I (n = 24); Laparoscopic insemination 2 (n = 26); and laparoscopic insemination 3 (n = 28), and natural mating was performed with two different Ovis Aries Comisana rams with proven fertility: Natural mating I (n = 10); Natural mating 2 (n = 9). Estrus was synchronized with fluorogestone acetate impregnated intravaginal sponges (40 mg, 14 days). Pregnant mare serum gonadotrophin (Folligon, Intervet International) at a dose of 400 UI was given intramuscularly at sponge removal. Artificial insemination was carried out 60 hours after the removal of the sponges in the laparoscopic insemination groups. RESULTS: The mean pregnancy rate at ecographic diagnosis performed at about 36 days from sponge removal for the laparoscopic insemination and natural mating groups were respectively, 62.8% and 78.9% with no significant difference. CONCLUSION: The mean fertility rates for the LAP and NM groups were 56.0 and 73.4, respectively, with no significant difference.

Animals↗
PubMed2002

The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk.

This report presents the preliminary results of the first phase (21 months) of a multi-centre, non-randomised, prospective study, aimed at evaluating the effectiveness of contrast-enhanced magnetic resonance imaging (MRI), X-ray mammography (XM) and ultrasound (US) in early diagnosis of breast cancer (BC) in subjects at high genetic risk. This Italian national trial (coordinated by the Istituto Superiore di Sanità, Rome) so far recruited 105 women (mean age 46.0 years; median age 51.0; age range 25-77 years), who were either proven BRCA1 or BRCA2 mutation carriers or had a 1 in 2 probability of being carriers (40/105 with a previous personal history of BC). Eight cases of breast carcinomas were detected in the trial (mean age 55.3 years, median age 52.5; age range 35-70 years; five with previous personal history of BC). All trial-detected BC cases (8/8) were identified by MRI, while XM and US correctly classified only one. MRI had one false positive case, XM and US none. Seven "MRI-only" detected cancers (4 invasive, 3 in situ) occurred in both pre- (n = 2) and post-menopausal (n = 5) women. With respect to the current XM screening programmes addressed to women in the age range 50-69 years, the global incidence of BC in the trial (7.6%) was over ten-fold higher. The cost per "MRI-only" detected cancer in this particular category of subjects at high genetic risk was substantially lower than that of an XM-detected cancer in the general women population. These preliminary results confirmed that MRI is a very useful tool to screen subjects at high genetic risk for breast carcinoma, not only in pre-, but also in post-menopausal age, with a low probability of false positive cases.

Adult↗
PubMed2002

Usefulness of breast MRI in a patient with genetic risk.

We describe an interesting case-report represented by a patient carrying BRCA1 mutation, recruited for the study "Multicenter evaluation of Magnetic Resonance Imaging (MRI) in early diagnosis and prevention of breast cancer in high risk population", diagnosed with breast cancer on the basis of MRI findings but not with conventional mammography and ultrasound (US). She was already affected at 53 years of age by a multifocal Ductal Infiltrating Carcinoma (DIC) in the left breast; then, she had an axillary and sovraclavear nodal recurrence of the disease, three years after the initial diagnosis. Since other relatives were affected by breast cancer (mother, sister and niece) and two arose at early age (< 40 years), BRCA1 mutational analysis was offered to the patient, identifying a nonsense mutation on the exon 13. Furthermore, this patient was recruited to study contralateral breast and at the second round, two little foci, suspicious of malignancy, were identified only with MRI, but not with mammography and ultrasonography. The final diagnosis was multifocal Ductal Carcinoma in situ (DCIS); the major focus measured 3 mm. In our patient MRI has shown a major sensitivity with respect to conventional radiology and US and has provided a very early diagnosis in this woman at genetic risk.

Biopsy, Needle↗
PubMed2002

Ovine fetal growth curves in twin pregnancy: ultrasonographic assessment.

PURPOSE OF INVESTIGATION: The fetal-lamb model is a fundamental tool for developing clinical applications for the treatment of human fetal pathology (e.g., open fetal surgery). Accurate estimation of gestational age is important to avoid size-related problems during surgery. METHODS: To evaluate the effect of twinning on ovine fetal growth, we followed seven twin pregnancies in Comiso ewes from mating through parturition. Fetal growth indexes (muzzle-occipital and mean abdominal diameters, abdominal circumference, femoral and humeral length) were measured weekly using perimammary ultrasonography and analyzed with a linear quadratic regression model based on natural logarithms of each parameter and fetal age. RESULTS: The model explained > 90% of the variability observed, with determination coefficients of 95% (femoral length, abdominal circumference), 94% (abdominal diameter, humeral length), and 89% (muzzle-occipital diameter). CONCLUSION: Mean birth weight was lower than that reported for singleton fetal lambs, as it is in bigeminal pregnancies in humans, despite the uterine and placental differences between these two species. With the exception of slightly earlier growth deceleration, curves for head and long-bone growth resembled those for singleton ovine fetuses. Ovine fetal growth patterns (like those of humans) in singleton and twin pregnancies are similar.

Abdomen↗
PubMed2002

Complementary therapy for severe Rh-alloimmunization.

PURPOSE OF INVESTIGATION: This report describes successful treatment, using invasive and noninvasive techniques, of a 36-year-old woman (gravida 10, para 0) referred to our center at 13 weeks' gestation for severe Rh alloimmunization. Pre-pregnancy indirect Coombs titers ranged from 1:1024-2048. All nine past pregnancies (conceived with three different partners) had ended in abortion, intrauterine death or neonatal death METHODS: The patient was treated with a single session of plasmapheresis (week 14) immediately followed by five days of immunoglobulin therapy and immunosuppressive therapy based on azathioprine and prednisone (weeks 15-22). Seven fetal transfusions (one intraperitoneal, six intravascular) were performed beginning at 16 weeks. RESULTS: The pregnancy, which was characterized by insulin-dependent gestational diabetes, spontaneously resolving polyhydramnios and peak indirect Coombs titers of 1:65,536, ended at 27 weeks with cesarean section delivery of a viable female weighing 1,000 g. In spite of numerous neonatal complications, the child is physically well at age 3, with normal intellectual and psychomotor development. CONCLUSION: In light of the negative outcomes of the patient's nine past pregnancies, our experience suggests that the early initiation of an integrated approach based on noninvasive and invasive techniques can play a potentially decisive role in the management of severe Rh-alloimmunization.

Adult↗
PubMed2001

Predictive impact of 2-18fluoro-2-deoxy-D-glucose positron emission tomography for residual postchemotherapy masses in patients with bulky seminoma.

PURPOSE: To establish the predictive potential of 2-18fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) for detecting viable tumor tissue in residual postchemotherapy masses of seminoma patients. PATIENTS AND METHODS: In this prospective multicenter trial, results of FDG PET studies in seminoma patients with postchemotherapy masses > or = 1 cm were correlated with either the histology of the resected lesion or the clinical outcome on follow-up without resection. Negative PET scans of residual lesions that were devoid of viable tumor tissue on resection or disappeared, shrunk, or remained stable in size for at least 2 years were rated as true-negative (TN). Positive scans without histologic or clinical evidence of tumor tissue were classified as false-positive. In patients with histologically positive or progressive lesions, positive PET scans were defined as true-positive (TP) and negative scans, false-negative (FN). RESULTS: Thirty-seven PET scans of 33 patients were assessable at a median follow-up time of 23 months (range, 2 to 46 months). Histologic data were available from nine patients who had undergone resection. Twenty-eight patients were followed-up clinically and radiologically. Twenty-eight scans were TN, eight were TP, and one was FN. All 14 residual lesions more than 3 cm and 22 (96%) of the 23 < or = 3 cm were correctly predicted by FDG PET. The specificity (100%; 95% confidence interval [CI], 87.7% to 100%), sensitivity (89%; 95% CI, 51.7% to 99.7%), positive predictive value (100%), and the negative predictive value (97%) of FDG PET were superior to data obtained by assessing residual tumor size (< or = or > 3 cm). CONCLUSION: FDG PET is a clinically useful predictor of viable tumor in postchemotherapy residuals of pure seminoma, especially those greater than 3 cm.

Adult↗
PubMed2001

Regulation of heparin-binding EGF-like growth factor expression in Ha-ras transformed human mammary epithelial cells.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA and protein expression is induced by EGF in MCF-10A nontransformed and Ha-ras transfected human mammary epithelial cells. The anti-EGF receptor (EGFR) blocking monoclonal antibody (MAb) 225 and the EGFR tyrosine kinase inhibitor PD153035 were able to inhibit the induction of HB-EGF mRNA levels in MCF-10A cells. However, the Ha-ras transformed MCF-10A cells were more refractory to inhibition by these agents and only a combination of the 225 MAb and PD153035 was able to significantly abrogate HB-EGF induction by EGF. The anti-erbB2 MAb L26 which interferes with heterodimer formation was able to block HB-EGF induction in response to EGF in MCF-10A cells and in the Ha-ras transformed cells only when used in combination with either the 225 MAb or PD153035. The MEK inhibitor PD90859 completely blocked EGF induction of HB-EGF mRNA levels in the nontransformed and Ha-ras transformed MCF-10A cells, which indicates that MAPK is involved in the signaling pathway of HB-EGF induction by EGF. An increase in the levels of HB-EGF may, therefore, be an important contributor to oncogenic transformation that is caused by Ha-ras overexpression in mammary epithelial cells. J. Cell. Physiol. 186:233-242, 2001. Published 2001 Wiley-Liss, Inc.

Antibodies, Monoclonal↗
PubMed2001

Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+ rectal cancers: a phase I study.

The use of raltitrexed ('Tomudex') as concomitant chemotherapy during preoperative radiotherapy in chemonaïve patients with stage II/III rectal cancer has been examined in this study and its recommended dose in conjunction with radiotherapy investigated. Forty-five Gray (Gy) of radiotherapy (1.8 Gy daily, 5 days per week) was delivered to the posterior pelvis, followed by a 5.4 Gy boost. Single doses of raltitrexed (2.0, 2.5 and 3.0 mg/m(2)) were administered on days 1, 19 and 38. Only 1 of the 15 patients entered experienced a dose limiting toxicity (DLT) (grade 3 leucopenia) at the 3.0 mg/m(2) dose level. The overall response rate was 80% (five complete responses, seven partial responses). These preliminary data suggest that raltitrexed is a well tolerated and effective treatment when combined with preoperative radiotherapy in patients with stage II/III rectal cancer. The recommended dose of raltitrexed for future phase II studies will be 3.0 mg/m(2).

Adenocarcinoma↗
PubMed2001

Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry.

Although vinyl chloride is an established cause of liver angiosarcoma, the evidence is inconclusive on whether it also causes other neoplastic and nonneoplastic chronic liver diseases as well as neoplasms in other organs. Furthermore, the shape of the dose-response relation for angiosarcoma is uncertain. We have extended for approximately 8 years the mortality and cancer incidence follow-up of 12,700 male workers in the vinyl chloride industry in four European countries. All-cause mortality was lower than expected, whereas cancer mortality was close to expected. A total of 53 deaths from primary liver cancer (standardized mortality ratio 2.40, 95% confidence interval = 1.80-3.14) and 18 incident cases of liver cancer were identified, including 37 angiosarcomas, 10 hepatocellular carcinomas, and 24 liver cancers of other and unknown histology. In Poisson regression analyses we observed a marked exposure response for all liver cancers, angiosarcoma, and hepatocellular carcinoma. The exposure-response trend estimated for liver cancer in analyses restricted to cohort members with cumulative exposures of <1,500 parts per million-years was close to that estimated for the full cohort (relative risk of 2.0 per logarithmic unit of cumulative dose). No strong relation was observed between cumulative vinyl chloride exposure and other cancers. Although cirrhosis mortality was decreased overall, there was a trend with cumulative exposure.

Carcinogens↗
PubMed2001

Drug-induced congenital defects: strategies to reduce the incidence.

Approximately 1% of congenital anomalies relate to pharmacological exposure and are. in theory, preventable. Prevention consists of controlled administration of drugs known to have teratogenic properties (e.g. retinoids, thalidomide). When possible, prevention could take the form of the use of alternative pharmacological therapies during the pre-conception period for certain specific pathologies, selecting the most appropriate agent for use during pregnancy [e.g. haloperidol or a tricyclic antidepressant instead of lithium; anticonvulsant drug monotherapy in place of multitherapy; propylthiouracil instead of thiamazole (methimazole)], and substitution with the most suitable therapy during pregnancy (e.g. insulin in place of oral antidiabetics; heparin in place of oral anticoagulants; alpha-methyldopa instead of ACE inhibitors). Another strategy is the administration of drugs during pregnancy taking into account the pharmacological effects in relation to the gestation period (e.g. avoidance of chemotherapy during the first trimester, avoidance of nonsteroidal anti-inflammatory drugs in the third trimester, and avoidance of high doses of benzodiazepines in the period imminent to prepartum).

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

RAS transformation causes sustained activation of epidermal growth factor receptor and elevation of mitogen-activated protein kinase in human mammary epithelial cells.

Activation of the ras oncogene is an important step in carcinogenesis. Human MCF-10A mammary epithelial cells were transformed with a point-mutated form of the Ha-ras oncogene. Epidermal growth factor receptor (EGFR) phosphorylation levels were chronically elevated after EGF induction and the EGFR ligand-driven internalization rate was slower in Ha-ras transformed MCF-10A cells. Additionally, basal levels of p42/44 mitogen-activated protein kinase (MAPK) expression and enzyme activity were significantly higher in Ha-ras transformed cells, localized predominantly in the nucleus. The anti-EGFR monoclonal antibody (MAb) 225 and the EGFR tyrosine kinase inhibitor PD153035 blocked anchorage-independent growth of Ha-ras transformed cells in soft agar and were more effective when used in combination. The MEK inhibitor PD98059 and anti-erbB-2 MAb L26 also suppressed colony formation of Ha-ras transformed cells in soft agar. Therefore, Ha-ras transformation leads to an augmentation in signaling through the EGFR as a result of an increase in ligand-dependent phosphorylation, a decrease in its internalization and an up-regulation in basal p44/42 MAPK levels. These effects may contribute to uncontrolled growth of Ha-ras-transformed human mammary epithelial cells.

Antibodies, Monoclonal↗