Subclinical chorioamnionitis: an unrecognised risk factor for severe pulmonary haemorrhage in extremely low birth weight infants.
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Chorioamnionitis↗
Biomedical subjects
Paolo Toti
Publications and source records attributed to Paolo Toti.
Human endometrium and decidua express follistatin-related gene (FLRG) mRNA and peptide.
Activin-A is expressed by human endometrium, and the actions are counteracted by follistatin, its binding protein. We evaluated the endometrial mRNA and peptide expression of follistatin-related gene (FLRG), a protein that binds activin-A, preventing its interaction. By reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, FLRG expression was evaluated in tissues collected at early proliferative (EP; n = 8) and late proliferative (LP; n = 8); early secretory (ES; n = 9) and late secretory (LS; n = 10); and in pregnancy, maternal decidua (MD; n = 12). FLRG mRNA was expressed by all samples, and semi-quantitative analysis showed that FLRG expression was significantly ( P < 0.001) higher in MD. FLRG was strongly immunolocalized in epithelial cells of glands and vessel walls (cytoplasma and nucleus), but only in the stromal cells nucleus. In MD, FLRG immunostaining was found in the nucleus and cytoplasm of vessel endothelium, gland epithelial, and decidualized stromal cells. In conclusion, FLRG is expressed by the human endometrium, and the different cellular localization suggests novel putative functions.
Activins↗
Skin reflectance changes in preterm infants with patent ductus arteriosus.
INTRODUCTION: Patent ductus arteriosus (PDA) is a common complication in preterm infants. While two-dimensional echocardiography is the method of choice for diagnosing a PDA, clinical signs are known to be of limited value. STUDY DESIGN: Haemodynamically significant PDA (hs-PDA) was defined as a ductal left-to-right shunt with elevated left atrial/aortic root ratio ( > 1.6:1), a ductal diameter > 2 mm, retrograde diastolic flow exceeding 30% of the anterograde flow and anterograde peak diastolic flow velocity in left pulmonary artery > 50 cm/s. A hs-PDA may affect the cerebral circulation and skin color is known to be related to local perfusion. In this study, we tested the value of a caudal-to-cephalic skin reflectance differential in detecting preterm infants with hs-PDA. The study was blinded and prospective. SUBJECTS: Fifteen infants with a hs-PDA (M: 8, F: 7; gestational age: 28.0 +/- 2.0 weeks, birth weight: 880 +/- 130 g) and 15 gender- and gestational age-matched infants without a haemodynamically significant PDA (M: 8, F: 7; gestational age: 28.2 +/- 2.3 weeks, birth weight: 885 +/- 135 g) participated to the study. OUTCOME MEASURE: Skin reflectance measurements were performed using a reflectance spectrophotometer (CM-2600d/2500d, Minolta, Osaka, Japan). Sole ("postductal" site) to forehead ("preductal" site) skin reflectance ratio (caudal-to-cephalic ratio). RESULTS: hs-PDA infants showed significantly lower forehead light reflectance values on for the whole visible spectrum (p < or = 0.043) with the exception of 580-590 nm (p = 0.058), whereas no statistically significant differences were observed for the sole skin reflectance between the two groups in the examined visible spectrum. Consequently, hs-PDA infants showed a significantly higher caudal to cephalic ratio in the 410-430 nm (p < or = 0.042), 460-530 nm (p < or = 0.027) and 590-700 nm (p < or = 0.011) wavelength ranges. CONCLUSIONS: These findings may provide a previously unrecognised clinical marker for haemodynamically significant PDA in preterm infants, thus predicting those preterm infants who may require intervention for PDA.
Blood Flow Velocity↗
Digital surface microscopy analysis of conjunctival pigmented lesions: a preliminary study.
The objective of this study was to investigate whether digital surface microscopy (DSM) could be used for the follow-up and comparison of malignant and benign conjunctival pigmented lesions (CPLs). Thirty-nine CPLs [16 de novo malignant melanomas (MMs), one MM arising from primary acquired melanosis (PAM), six PAMs and 16 naevi] were digitally analysed and biopsied. All of the PAMs and 10 naevi, which had not been surgically excised, were followed up using DSM. Thirty parameters were evaluated grouped into four categories: geometry, colour, texture and islands of colour. None of the CPLs that were followed up, which comprised 10 naevocytic naevi and seven PAMs, showed any morphological change at DSM analysis, except for one PAM which developed an MM 1 year later. Of the geometric variables examined, the area, maximum diameter and minimum diameter showed significantly higher values in MMs compared with benign CPLs. With regard to the colour of CPLs, MMs were significantly darker and bluer than naevi. In the texture group, contrast was significantly higher in MMs. In the islands-of-colour group, the imbalance of blue-grey regions and the presence of dark areas were significantly higher in MMs. DSM greatly simplified the follow-up of CPLs, such as PAMs with atypia, by providing satisfactory quality images with high reproducibility; this technique is also easy to use and well accepted by patients. Moreover, this preliminary study allowed us to determine which objective variables could be important for distinguishing between benign CPLs and conjunctival MMs.
Adolescent↗
Spleen depletion in neonatal sepsis and chorioamnionitis.
Neonatal sepsis and chorioamnionitis induce morphologic modifications and shrinkage of the thymus. We show fetal and neonatal morphologic modifications of the spleen in the same autopsy subjects as previously used to describe thymus shrinkage, including 10 preterm or full-term neonates who died of proven sepsis within 48 hours after birth and 20 fetuses spontaneously aborted because of extensive ascending chorioamnionitis. Control subjects included 10 fetuses from induced termination of pregnancy and 10 neonates who died suddenly during the perinatal period without evidence of chorioamnionitis. Spleen cell populations were studied by means of immunohistochemical analysis. Neonatal sepsis occurred with severe spleen depletion, involving both B and T lymphocytes (P < .001). Fetuses with chorioamnionitis also showed spleen cell depletion. These observations, to our knowledge not described before, indicate that preterm and term neonates show an inflammatory reaction similar to that of adult patients and that severe chorioamnionitis is associated with a nonspecific inflammatory response comparable to that of sepsis.
Antigens, CD20↗
Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma.
OBJECTIVE: Activin A is a multifunctional growth and cell differentiation factor produced by normal endometrium, and secreted in high amounts by endometrial adenocarcinoma. In the present study we evaluated the expression of two inhibitory activin A ligands, follistatin and follistatin-related gene (FLRG), in endometrial adenocarcinoma and in age-matched healthy human endometrium. DESIGN AND METHODS: Atropic menopausal (n=13) and tumoral (n=9 adenocarcinoma) tissues were processed to evaluate mRNA expression levels (by semiquantitative RT-PCR) and peptide localization (by immunohistochemistry). Differences were evaluated by the unpaired t-test and assumed to be statistically significant when P<0.05. RESULTS: Both control and tumoral endometrial samples express and localize follistatin and FLRG. However, whereas follistatin mRNA expression did not differ significantly, FLRG was significantly lower in endometrial adenocarcinoma than in healthy endometrial specimens (P<0.0001). With respect to the localization of proteins, follistatin was immunolocalized in endometrial epithelial and vascular cells both in tumoral and healthy endometrium without any significant difference in intensity. Nuclear and cytoplasmic FLRG immunolocalization was seen in glands, and only nuclear immunolocalization was found in stroma and vessels of healthy endometrium. FLRG was weakly immunostained in endometrial adenocarcinoma. CONCLUSIONS: Whilst follistatin expression is unchanged, FLRG is down-regulated in endometrial carcinoma. As activin A is a differentiation factor of human endometrium, the present findings support an imbalance between increased activin A and decreased FLRG expression in endometrial cancer, so that the failure of the activin A pathway through FLRG may be pivotal in endometrial tumorigenesis.
Adenocarcinoma↗
Retinoblastoma: Abnormal gadolinium enhancement of anterior segment of eyes at MR imaging with clinical and histopathologic correlation.
PURPOSE: To evaluate abnormal gadolinium enhancement of the anterior segment of eyes harboring retinoblastoma at magnetic resonance (MR) imaging and correlate this finding with clinical and histopathologic information. MATERIALS AND METHODS: Three neuroradiologists examined 46 eyes with 34 retinoblastomas in 25 children on gadolinium-enhanced T1-weighted orbital MR images obtained shortly after contrast material injection for evidence of abnormally high signal intensity in the anterior segment. Twenty-two of the 34 affected eyes were enucleated, and six of these 22 eyes were treated with preenucleation adjuvant therapy. Thus, correlation of the clinical, MR imaging, and histopathologic findings in 16 eyes was performed. Statistical analysis was performed with nonparametric methods (Fisher exact test). P <.05 indicated a statistically significant difference. RESULTS: Fourteen of the 34 affected eyes showed abnormal gadolinium enhancement of the anterior segment. Regarding the 16 eyes evaluated for statistical analysis, a significant correlation (P =.011) between abnormal gadolinium enhancement of the anterior segment and histopathologically documented optic nerve infiltration was noted. A trend toward an association between abnormal enhancement and elevated intraocular pressure (P =.215), tumor growth beyond the equator at MR imaging (P =.125), and histopathologically proved iris neoangiogenesis (P =.182) also was noted. Histopathologic evidence of optic nerve and/or choroid infiltration correlated significantly (P =.001; sensitivity, 100% [nine of nine eyes]; specificity, 86% [six of seven eyes]) with abnormal enhancement. CONCLUSION: Abnormal gadolinium enhancement of the anterior segments of eyes harboring retinoblastoma seems to indicate more aggressive tumor behavior.
Anterior Chamber↗
Nerve growth factor expression in human dystrophic muscles.
Nerve growth factor (NGF) is a neurotrophin that is expressed during muscle development and is also capable of favoring muscle regeneration in experimental studies. The presence of NGF in muscular dystrophies, such as Duchenne and Becker muscular dystrophies, has never been fully explored. By means of immunohistochemistry, we show that regenerating muscle fibers from such patients consistently express NGF, as do myofibroblasts and mast cells. By contrast, rest fibers from dystrophic patients, as well as muscle fibers from healthy, control patients and even regenerative muscle fibers in polymyositis do not show NGF immunoreactivity. The paracrine effect of NGF on muscle regeneration, as well as its chemoattractant capacities for mast cells, may contribute to explaining why regenerating fibers most frequently occur in clusters and why mast cells are more numerous in dystrophic muscles. Moreover, being a mediator of wound healing and tissue fibrosis, NGF may contribute to long-term muscle regeneration impairment by tissue fibrosis in the muscular dystrophies.
Biopsy↗
Expression of betaglycan in pregnant tIssues throughout gestation.
BACKGROUND: Betaglycan is a membrane-anchored proteoglycan involved in mediating the passage of transforming growth factor-beta (TGF-beta), inhibin and activin activities into cells. TGF-beta and inhibin-related proteins are growth factors that are expressed by several tIssues and in pregnancy. They have a function in modulating the growth, differentiation and invasion of the placental trophoblast. OBJECTIVE: To evaluate whether betaglycan is expressed by intrauterine tissues throughout gestation. DESIGN AND METHODS: Expression of betaglycan mRNA and protein was evaluated (by RT-PCR and immunohistochemistry, respectively) in trophoblast, decidua and fetal membranes collected during the first (n=6 elective terminations of pregnancy, between 8 and 12 gestational weeks) and third (n=6 elective caesarean sections, between 39 and 40 weeks) trimesters of pregnancy. RESULTS: Betaglycan mRNA was expressed by all gestational tIssues, independently of gestational age. Immunoreactive protein was found in decidual cells and in some chorionic, but not epithelial, amniotic cells. With respect to the placental localization, syncytiotrophoblast, but not cytotrophoblast, cells were intensively stained both in the placental bed and in the villous trophoblast, and in some cells within the stroma of terminal villi, of the first and third trimesters of pregnancy. Immunoreactive betaglycan was demonstrated in the endothelial cells of decidual vessels in both the first and third trimesters of pregnancy, whereas endothelial cells of fetal blood vessels in the villous were clearly represented only in first trimester samples, not in those of term placenta. CONCLUSIONS: Betaglycan mRNA and peptide are expressed by the trophoblast, the decidua and the fetal membranes, but the localization of the peptide in vessel walls is dependent on gestational age.
Decidua↗
Orbital solitary fibrous tumor with aggressive behaviorThree cases and review of the literature.
BACKGROUND: Solitary fibrous tumor (SFT) is a rare spindle cell tumor that arises most often in the visceral pleura; however, a review of the literature shows at least 31 cases occurring in the orbit. METHODS: A retrospective case series of three patients with orbital SFT: a 50-year-old man, observed in 1997, with an angioma-like lesion in the upper half of the orbit causing osteolysis of the orbital roof; a 24-year-old man, observed in 1992, with a superotemporal mass in the right orbit occupying the lacrimal gland region, firstly diagnosed as schwannoma, recurring 4 years after dacryoadenectomy; a 70-year-old man, with a retrobulbar mass diagnosed on a biopsy as hemangiopericytoma, recurring and infiltrating the orbital roof 4 years after surgery. RESULTS: A review of the literature and presentation of three cases of SFT which showed infiltration of the orbital roof and/or recurrence. CONCLUSIONS: Our cases provide evidence of how orbital SFT can behave aggressively and mimic other orbital tumors, thus making mandatory the consideration of this relatively new entity in common clinical practice as well as careful follow-up. Their aggressive growth is unusual, described in only 6 of the 31 cases so far reported in the literature. Immunohistochemistry is of importance for the diagnosis, since CD34 immunoreactivity is peculiar to SFT.
Adult↗
Small thymus at birth and gestational age.
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Chorioamnionitis↗
CD-34 stromal expression pattern in normal and altered human corneas.
OBJECTIVE: To test CD-34 immunoreactivity in stromal cornea cells in normal and pathologic samples obtained from penetrating keratoplasty. DESIGN: Prospective, consecutive histopathologic human tissue study. PARTICIPANTS AND CONTROLS: One hundred two cornea buttons from patients with different diseases, submitted for cornea transplant, were examined. Controls were expired corneas from healthy donor patients who died (n = 4), and globes enucleated for primitive intraocular neoplasias, that is, retinoblastomas (n = 8), and malignant choroidal melanomas (n = 2). METHODS: The expression of CD-34 in stromal cornea cells was examined by immunohistochemistry analysis. Other immunohistochemical stains included an endothelial cell marker (CD-31), common leukocyte antigen, and alpha-smooth muscle actin. MAIN OUTCOME MEASURES: Different diseases that may cause blindness and require penetrating keratoplasty have been tested for CD-34 immunoreactivity. RESULTS: In control corneas, keratocytes present strong and consistent CD-34 immunoreactivity. Diseases leading to the loss of transparency and penetrating keratoplasty, such as keratoconus, herpes keratitis, trauma, and heredofamilial dystrophies, are associated with focal or diffuse loss of CD-34 expression, whereas pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy show normal CD-34 immunoreactivity in most cases and patchy unstained stromal areas in a few cases. CONCLUSIONS: Scar tissue formation in the cornea, as in herpes keratitis and trauma, is always associated with loss of CD-34 immunoreactivity, which may otherwise be a primary event in keratoconus and heredofamilial dystrophies. Both in the pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy, CD-34 immunoreactivity may be normal or lost, hence these two diseases may be considered as one and part of the same group with regard to CD-34 expression, as revealed by immunohistochemistry analysis.
Actins↗
Predictive value of skin color for illness severity in the high-risk newborn.
The relationship between skin color and illness severity in the newborn remains untested. We have evaluated the predictive value of skin color readings for illness severity in a population of high-risk newborn infants. A prospective study was conducted on 107 white newborns in the intensive care unit, which were categorized as either high or low severity of illness, defined by the presence of severe neonatal morbidity. Illness severity was also determined using a Score for Neonatal Acute Physiology (SNAP). Color readings were obtained at 10 different body sites using a portable tristimulus colorimeter during the first 24 h, and color was expressed using the standard CIE L*a*b* system. Skin CIE b* values were significantly lower in the high severity group (p < 0.0001), and a significant inverse correlation with SNAP was observed (r(s) range, -0.37 to -0.71, p < 0.0001). In particular a low b* value for the abdomen was found to be a significant predictor of illness severity (92.6% sensitivity; 96.6% specificity; 96% positive predictive value; 93.7% negative predictive value; adjusted odds ratio, 14.7; 95% confidence interval, 6.4 to 33.8). Our findings indicate that skin color reflects clinical severity in the newborn and that skin colorimetry can accurately identify higher risk infants.
Female↗
The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions.
Hurthle cell adenomas and carcinomas, characterized by the presence of oncocytic cells, are unusual thyroid neoplasms, the treatment of which is still controversial. We analyzed specimens from 49 patients with oncocytic cell nodular lesions including 20 adenomas, 19 carcinomas, and 10 hyperplasias for RET/PTC (papillary thyroid carcinoma) activation, which is the most frequent genetic alteration in PTCs. RET/PTC activation was detected in a significant number of cases of Hurthle cell adenomas and carcinomas, but in 0 of 10 patients with hyperplastic nodules. In particular, the RET/PTC1 isoform was found in 7 of 12 adenomas and 4 of 7 carcinomas. These results would indicate that RET/PTC is a genetic event common to papillary carcinomas and to Hurthle cell neoplasias.
Adenoma, Oxyphilic↗
Small thymus at birth: a predictive radiographic sign of bronchopulmonary dysplasia.
OBJECTIVE: Emerging evidence indicates a relationship between bronchopulmonary dysplasia (BPD) and chorioamnionitis. Recent data provide evidence of an acute thymic involution in very low birth weight (VLBW) preterm infants and fetuses with histologic chorioamnionitis. We tested the hypothesis that a small thymus detected at birth on the routine chest radiograph is a predictor of BPD in VLBW infants. METHODS: A prospective study was conducted on 400 VLBW preterm infants who survived >4 weeks (mean gestational age: 27.5 weeks [range: 24-30]; mean birth weight: 1010 g [range: 450-1450]). Thymic size was measured on routine chest radiographs taken in the first 6 hours after birth and expressed as the ratio between the transverse diameter of the cardiothymic image at the level of the carina and that of the thorax (CT/T). The accuracy of CT/T for identifying infants with BPD was tested using receiver operating characteristic curve analyses and multivariate logistic regression. RESULTS: Fifty-one VLBW infants (12.7%) subsequently developed BPD. A small thymus (CT/T <0.28) was observed in 94.1% of the infants with BPD versus 2.9% of the infants without BPD. A small thymus at birth identified infants with BPD with 94.1% sensitivity and 98.3% specificity (odds ratio: 17.8; 95% confidence interval: 5.7-55.4). CONCLUSIONS: A small thymus at birth on the standard chest radiograph can accurately identify VLBW infants who subsequently develop BPD.
Bronchopulmonary Dysplasia↗
Missing expression of pRb2/p130 in human retinoblastomas is associated with reduced apoptosis and lesser differentiation.
PURPOSE: Although the retinoblastoma gene (RB/p105) has been intensely investigated as a prototype suppressor gene in humans, mutational data on the Rb family member pRb2/p130 (p130) has only recently been reported. A protective role against apoptosis has been suggested for pRb/p105, both in vitro and in vivo. However, only limited information is available on the role of pRb2/p130 in controlling apoptosis. The purpose of this study was to determine the extent of a role of this gene in the neoplasms that give the Rb family its name. METHODS: Forty-two human retinoblastomas were retrospectively examined by immunohistochemical labeling of the Rb-related proteins and the results compared with cellular kinetic characteristics: the apoptotic index (AI) and the mitotic index (MI). RESULTS: The retinoblastomas that did not express p130 showed a significantly lower AI than those that expressed p130. This result was also supported by flow cytometry on a human Saos-2 cell line that was transiently transfected with RB2/p130. The p130(-) tumors displayed a lesser degree of differentiation than the p130(+) ones. CONCLUSIONS: These observations give evidence that expression of p130 is inversely correlated with higher rates of apoptosis in human retinoblastomas and give an additional example of this regulator's role in cellular differentiation.
Apoptosis↗