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Background and purposeAtherosclerosis occurs later and is less extensive in intracranial arteries than in extracranial arteries. However, the mechanisms responsible are poorly understood. A previous study has suggested a better antioxidant protection of intracranial arteries.MethodsTo assess the influence of age on arterial activity of antioxidant enzymes and atherogenesis, we compared intracranial and extracranial arteries of humans of different ages who retrospectively lacked confounding classic risk factors (48 premature fetuses aged 6.4+/-0.8 months [mean+/-SD], 58 children aged 7.9+/-3.8 years, 42 adults aged 42.5+/-5.1 years, and 40 elderly subjects aged 71.8+/-3.4 years; all males). Lesions were quantified by computer-assisted imaging analysis of sections of the middle cerebral and basilar arteries, the left anterior descending coronary artery, the common carotid artery, and the abdominal aorta. Macrophages, apolipoprotein B, oxidized LDL, and matrix metalloproteinase-9 in lesions were determined by immunocytochemistry. The effect of aging on atherogenesis was then compared with that on the activity of 4 antioxidant enzymes in the arterial wall.ResultsAtherosclerosis was 6- to 19-fold greater (P

Background: Poland syndrome is a congenital nongenetic anomaly characterized by unilateral chest wall hypoplasia, ipsilateral hand abnormalities, and hemivertebrae. It has not ben described so far in the fetus. Case: The patient was referred for suspected left-arm hypomelia at 22 weeks of gestation. On ultrasonography, we confirmed the presence of severe left-sided hypomelia and detected an asymmetry of the rib cage and 3 thoracic hemivertebrae. The absence of heart defects led us to make the putative diagnosis of Poland syndrome. After termination of pregnancy, the diagnosis was confirmed by the pathologist. Conclusion: The possibility of diagnosing Poland syndrome in utero is important for proper management and counseling. If the syndrome is suspected in a fetus, counselors may refer to specific postnatal data to provide the couple with survival rates, treatment options, and results and morbidity figures. If the pregnancy is terminated, a detailed necropsy is warranted to confirm the diagnosis because familial transmission has been reported. [ABSTRACT FROM AUTHOR]

Objective: To assess the accuracy of expert neurosonography (two- and three-dimensional NSG) in the characterization of major fetal central nervous system (CNS) anomalies seen at a tertiary referral center and to report the differential clinical usefulness of magnetic resonance imaging (MRI) used as a second-line diagnostic procedure in the same cohort., Methods: This was a retrospective analysis of all 773 fetuses with confirmed CNS abnormalities referred to our center between 2005 and 2012. The following variables were analyzed: gestational age at NSG and MRI, NSG and MRI diagnoses, indication for MRI (confirmation of NSG findings; diagnostic doubt; search for possible additional brain anomalies), association with other malformations, diagnostic accuracy of NSG vs MRI (no additional clinical value for either MRI or NSG; additional information with clinical/prognostic significance on MRI relative to NSG; additional information with clinical/prognostic significance on NSG relative to MRI, NSG and MRI concordant but incorrect) and final diagnosis, which was made at autopsy or postnatal MRI/surgery., Results: CNS malformations were associated with other anomalies in 372/773 (48.1%) cases and were isolated in the remaining 401 (51.9%) cases. NSG alone was able to establish the diagnosis in 647/773 (83.7%) cases. MRI was performed in 126 (16.3%) cases. The indication for MRI was: confirmation of NSG diagnosis in 59 (46.8%) cases; diagnostic query (in the case of inconclusive or uncertain finding on NSG) in 20 (15.9%) cases; search for possible additional brain anomalies in 47 (37.3%) cases. NSG and MRI were concordant and correct in 109/126 (86.5%) cases. Clinically relevant findings were evident on MRI alone in 10/126 (7.9%) cases (1.3% of the whole population) and on NSG alone in 6/126 (4.8%) cases; in all six of these cases, MRI had been performed at < 24 weeks of gestation. In one case, both NSG and MRI diagnoses were incorrect. The main type of malformation in w ich MRI played an important diagnostic role was space-occupying lesions, MRI identifying clinically relevant findings in 42.9% (3/7) of these cases., Conclusions: (1) In a tertiary referral center with good NSG expertise in the assessment of fetal CNS malformations, MRI is likely to be of help in a limited proportion of cases; (2) MRI is more useful after 24 weeks of gestation; (3) the lesions whose diagnosis is most likely to benefit from MRI are gross space-occupying lesions., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess the incidence of aberrant right subclavian artery (ARSA) and other strong markers of Down syndrome and their correlation in a large population of second-trimester Down syndrome fetuses assessed in a tertiary referral center., Methods: Presence or absence of ARSA and other major ultrasound markers of Down syndrome was assessed in a population of 106 second-trimester Down syndrome fetuses referred to our unit for expert assessment and/or termination of pregnancy after karyotyping performed for positive first- or second-trimester screening or advanced maternal age or on maternal request. All cases in which the diagnosis of Down syndrome followed the ultrasound detection of major anomalies or soft markers were excluded from the study, as were all cases with a gestational age less than 14 + 0 weeks. We searched for the ARSA on the three vessels and trachea view using color or power Doppler. All fetuses underwent a thorough anatomic assessment and fetal echocardiography. The other Down syndrome markers assessed were: absent or hypoplastic nasal bone (NB-), defined as length < 5(th) centile; nuchal fold ≥ 5 mm; and mild pyelectasis (> 5 mm). In addition, the presence of major cardiac and extracardiac defects was recorded. A correlation analysis was then performed in order to investigate possible associations between markers and/or major anomalies. Postmortem or postnatal diagnostic confirmation was available in all cases., Results: The mean (SD) gestational age at ultrasound assessment was 20.4 (4.1) weeks. The incidence of the various variables in the population of Down syndrome fetuses was: ARSA, 25%; NB-, 43%; nuchal fold ≥ 5 mm, 16%; pyelectasis, 17%; major heart defects, 41%; atrioventricular septal defect, 25%; and extracardiac anomaly, 24%. The presence of ARSA did not correlate with any of the other variables. The only positive correlations (P < 0.05) were between NB- and pyelectasis, and between cardiac and extracardiac defects., Conclusions: This represents the largest Down syndrome population assessed for ARSA. In this series, the incidence of ARSA was 25%, lower than previously reported in much smaller series. Its presence did not correlate with the presence of any other marker or major anomaly, including heart defects., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Background and Aim: Tissue transglutaminase contributes to liver damage in the development of hepatic fibrosis. In a model of neurodegeneration, the therapeutic benefit of cystamine has been partly attributed to its inhibition of transglutaminase activity. Garlic extract contains many compounds structurally related to cystamine. We investigated the anti-fibrotic effect of garlic extract and cystamine as specific tissue transglutaminase inhibitors., Methods: Rat liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl(4)) for 7 weeks. Cystamine or garlic extract was administrated by daily intraperitoneal injection, starting from the day after the first administration of CCl(4). Hepatic function, histology, tissue transglutaminase immunostaining and image analysis to quantify Red Sirius stained collagen deposition were examined. Reverse transcription-polymerase chain reaction to detect alpha-SMA, IL-1beta and tissue transglutaminase expression and Western blot for tissue transglutaminase protein amount were performed. Transglutaminase activity was assayed on liver homogenates by a radio-enzymatic method., Results: Transglutaminase activity was increased in CCl(4) group and reduced by cystamine and garlic extract (p<0.05). Treatment with cystamine and garlic extract reduced the liver fibrosis and collagen deposition, particularly in the garlic extract group (p<0.01). Moreover, the liver damage improved and serum alanine aminotransferase was decreased (p<0.05). Tissue transglutaminase immunolocalised with collagen fibres and is mainly found in the ECM of damaged liver. Alpha-SMA, IL-1beta, tissue transglutaminase mRNA and tissue transglutaminase protein were down-regulated in the cystamine and garlic extract groups compared to controls., Conclusion: These findings concurrently suggest that transglutaminase may play a pivotal role in the pathogenesis of liver fibrosis and may identify garlic cystamine-like molecules as a potential therapeutic strategy in the treatment of liver injury., (Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: We sought to assess the role of ultrasound in the prenatal characterization of fetal malformations of the upper extremities (MUE)., Study Design: Ultrasound findings, associated anomalies, pregnancy, and fetoneonatal outcome were analyzed in 100 fetuses with MUE, categorized after Swanson classification of hand congenital abnormalities. Follow-up information was available in all., Results: Twelve cases had an isolated defect, while 88 showed associated abnormalities involving other organ systems. Fetuses with multiple malformations showed a 76% syndromic risk (32% chromosomal, 41% nonchromosomal), with unfavorable outcome in almost all cases (only 4 survivors, 2 with neurodevelopmental delay). In 27% of syndromic fetuses, the sonographic evidence of the MUE represented the key finding leading to the final diagnosis. The prognosis was usually favorable in cases of isolated defects., Conclusion: A thorough prenatal ultrasound characterization of fetal MUE can assist in the differential diagnosis of many syndromic conditions. When isolated, MUE tend to have a good outcome., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: Preoperative chemoradiation is now standard treatment for stages II-III rectal cancer. Capecitabine (CAP) and oxaliplatin (OX) are synergistic with radiotherapy (RT) and active in colorectal neoplasms., Patients and Methods: Two cycles of CAP 825 mg/m(2) b.i.d. (days 1-14) and OX 50 mg/m(2) (days 1 and 8) every 3 weeks were given concomitantly with pelvic conformal RT (45 Gy). Patients with a > or =T3 and/or node-positive rectal tumour were eligible. The pathologic tumour response was defined according to the tumour regression grade (TRG) scale., Results: Forty-six patients were enrolled. Gastrointestinal adverse events were mostly G1-G2; only two patients experienced G3 vomiting and diarrhoea and six patients had G1 peripheral neuropathy. Haematological toxicity was rare. G2 proctitis and anal pain occurred in two patients. Pathological complete response (TRG1) was observed in nine patients (20.9%; 95% CI 8.7%-33.1%); TRG2 in 19 patients (44.2%); TRG3 in 12 patients (27.9%); and TRG4 in three patients (7%). Overall, nine patients recurred: five with distant metastases, one with local recurrence, and three with both local recurrence and distant metastases., Conclusions: CAP-OX-RT as preoperative treatment for rectal cancer induces a remarkable rate of complete or near-complete pathologically documented response and is well tolerated.

Femoral hypoplasia-unusual facies syndrome (FHUFS) is a rare condition characterized by a variable degree of unilateral or bilateral femoral hypoplasia associated with facial clefting and other minor malformations. The prenatal diagnosis of this condition is possible, but so far has been reported prospectively in only two cases. We review all cases of FHUFS reported in the literature and also describe three cases detected prenatally in the mid-trimester, underlining the variable expression of the syndrome. The reported association with maternal diabetes mellitus and differential diagnosis with other syndromes characterized by femoral hypoplasia are also discussed., (Copyright 2007 ISUOG. Published by John Wiley & Sons, Ltd.)

We have previously reported that the thyroid-targeted expression of the RET/PTC3 oncogene (Tg-RET/PTC3) in transgenic mice induces follicular hyperplasia with papillary architecture, resulting in a modest increase of the thyroid gland volume, followed by the appearance of papillary carcinomas in approximately 1-year-old animals. In order to analyze the genetic alterations that may cooperate with RET/PTC3 in the development or progression of thyroid tumors, we interbred Tg-RET/PTC3 mice with Tg-E7 transgenic mice, which express the E7 oncogene of the human papilloma virus 16 in thyroid cells. Tg-E7 mice develop large colloid goiters with small papillae and well-differentiated thyroid carcinomas in older animals. Here we show that thyroid lesions in Tg-RET/PTC3-Tg-E7 double transgenics were morphologically different from those occurring in Tg-RET/PTC3 mice, while they were virtually indistinguishable from those occurring in Tg-E7 mice. In addition, the coexpression of RET/PTC3 and E7 oncogenes neither enhanced the malignant phenotype nor reduced the latency period of thyroid lesions with respect to parental transgenic lines. We conclude that the coexpression of RET/PTC3 and E7 lacks any cooperative effect in the neoplastic transformation of thyroid cells and that the E7-induced thyroid phenotype is dominant with respect to the RET/PTC3 one.

A case of Holoacardius is reported by the authors. The literature is reviewed, and a pathogenetic sequence responsible for the syndrome is proposed on the basis of the pathologic data.

We describe a kindred with medullary thyroid carcinoma and phaeochromocytoma (MEN 2A or Sipple's syndrome) in which a cutaneous manifestation is only present in affected members. These members felt an intense itching in an area 5-10 cm in length and passing through the scapular region where, after long-term scratching, the skin appears hyperkeratotic and pigmented. Cutaneous biopsies proved negative for dermis nerve abnormality. This restricted itching strongly suggests dominant transmitted hereditary localized pruritus which was described many years ago in a family which was apparently free from inherited diseases. In the examined kindred this skin peculiarity was said to have appeared before the patients reached 10 years of age and, therefore, prior to the biochemical manifestation of the thyroid tumour. Three children of the last generation, aged 4 to 11 years, all of whom presented this cutaneous manifestation, were considered unaffected because of normal basal and stimulated calcitonin, but thyroid C-cell hyperplasia was recently proved in the eldest. In this MEN 2A kindred the presence of such a characteristic hereditary itch in affected members may be considered as a phenotypic marker giving advance warning of medullary thyroid carcinoma.