C De Felice

Exposure to Di(2-ethylhexyl)phthalate in Humans during Pregnancy

Background: Di(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer, is a widespread ubiquitous environmental contaminant. The potential health hazards from exposure to DEHP and its main metabolite, mono(2-ethylhexyl)phthalate (MEHP), have been well documented. Exposure to DEHP and MEHP in humans at risk, such as pregnant women and human fetuses, has not been tested. Methods: Plasma DEHP and MEHP concentrations were measured in a total of 24 consecutive mother-infant pairs by high performance liquid chromatography. Associations between DEHP/MEHP and infant characteristics were tested using Fisher’s exact test, unpaired t tests and univariate linear regression analysis. Results: Measurable DEHP and MEHP concentrations were found in 17/24 (70.8%) and 18/24 (75%) maternal plasmas, respectively, and in 11/25 (44%) and 18/25 (72.0%) cord samples, respectively. Either DEHP or MEHP were detectable in 21/24 (87.5%) maternal plasmas and 19/25 (76%) cord samples. The mean DEHP concentrations in maternal and cord plasmas were 1.15 ± 0.81 and 2.05 ± 1.47 µg/ml, respectively. The mean MEHP concentrations were 0.68 ± 0.85 and 0.68 ± 1.03 µg/ml, respectively. No significant correlations were found between maternal and cord blood DEHP, maternal and cord blood MEHP, maternal DEHP and cord blood MEHP, or maternal MEHP and cord blood DEHP plasma concentrations. Conclusion: Although the effects of perinatal exposure to phthalates need further research, our findings: (i) confirm the high frequency of DEHP and/or MEHP exposure in human pregnancies; (ii) indicate that the exposure to these environmental contaminants begins during intrauterine life, and (iii) suggest that fetal exposure is closely related to the maternal exposure.

Early postnatal changes in the perfusion index in term newborns with subclinical chorioamnionitis.

Background: Chorioamnionitis (HCA) in term newborns is often subclinical and associated with neonatal morbidity and mortality. Objective: To assess the value of the pulse oximetry perfusion index (PI) in the early prediction of subclinical HCA in term newborns. Methods: PI cut-off values were first identified in 51 term newborns with HCA and 115 matched controls, retrospectively categorised on the basis of placental histology (study phase 1). The PI thresholds obtained were subsequently tested on an unselected case series of 329 prospectively recruited, term newborns (study phase 2). PI was evaluated during the first five minutes after delivery. Initial illness severity and short term clinical outcomes were determined. Results: In study phase 1, newborns with HCA had lower PI one and five minutes (p<0.0001) after delivery, lower one minute Apgar score (p  =  0.017), lower cord blood base excess (p  =  0.0001), together with higher rates of admission to neonatal intensive care unit (p  =  0.0001) and endotracheal intubation (p  =  0.017), and higher SNAP-PE (p<0.0001) and NTISS (p<0.0001) scores than those without HCA. In the prospective validation phase of the study, the PI cut-off values generated (one minute ⩽1.74, five minutes ⩽2.18) showed 100% sensitivity, 99.4% specificity, 93.7% positive predictive value, and 100% negative predictive value in identifying subclinical HCA. Early identification of HCA was associated with a decreased rate of admission to intensive care (p  =  0.012), as well as lower initial illness severity (p⩽0.0001) and therapeutic intensity (p  =  0.0006) than the newborns with HCA in phase 1. Conclusion: These findings suggest that early PI monitoring is helpful in identifying HCA in term newborns.

Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome

Background: Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch cancer family syndrome I (LCFS1) and II (LCFS2)) is one of the most common hereditary cancer disorders. HNPCC results from dominantly inherited germline mutations in mismatch repair (MMR) genes, leading to genomic instability and cancer. No predictive physical signs of HNPCC are available to date. Aims: Increased complexity in tumour associated vascular growth has been reported. Here, we tested the hypothesis that an increased vascular network complexity is a phenotypic marker for LCFS2. Methods: Fourteen subjects from an LCFS2 kindred (gene carriers, n = 5; non-carriers, n = 9) and 30 controls were examined. Fractal dimension (D) at two scales (D (1–46), and D (1–15), tortuosity (minimum path dimension, Dmin), and relative Lempel-Ziev complexity (L-Z) of the vascular networks from the lower gingival and vestibular oral mucosa were measured. Results: LCFS2 networks exhibited a significantly increased overall complexity at both larger (D (1–46): 1.82 (0.04) v 1.68 (0.08); p<0.0001) and smaller (D (1–15): 1.51 (0.11) v 1.20 (0.09); p<0.0001) scales, increased destructured randomness (L-Z: 0.77 (0.09) v 0.56 (0.03); p<0.0001), and decreased vessel tortuosity (Dmin: 1.02 (0.03) v 1.07 (0.04); p = 0.0005) compared with control patterns. The vascular networks of LCFS2 gene carriers showed higher complexity at the smaller scale (D (1–15): 1.59 (0.12) v 1.47 (0.07); p = 0.034), and higher destructured randomness (L-Z: 0.85 (0.11) v 0.73 (0.05); p = 0.013) than those of non-carriers. Conclusions: Increased oral vascular network complexity is a previously unrecognised phenotypic marker for LCFS2, and is related to gene mutation carrier status.

Different effects of interferon-alpha on melanoma cell lines: a study on telomerase reverse transcriptase, telomerase activity and apoptosis

Summary Background Although the antiproliferative and proapoptotic effects of interferon (IFN)‐α are widely recognized, its antitumour mechanisms are not completely known. Recent studies indicate that the derepressed expression of the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), and telomerase activity (TA) are involved in the process of human carcinogenesis. Only a few studies have investigated the effects of IFN‐α on hTERT and TA, with controversial results.

Quantitative in situ evaluation of telomeres in fluorescence in situ hybridization‐processed sections of cutaneous melanocytic lesions and correlation with telomerase activity

Summary Background Telomere length is correlated with cellular ageing and immortalization processes. In some human cancers telomere length measurement has proved to be of diagnostic and prognostic value. Results comparable with the traditional terminal restriction fragment length determination by Southern blotting have been obtained in metaphase and interphase cells in some studies by fluorescence in situ hybridization (FISH) analysis; FISH additionally allows for the quantification of telomeres at the cellular level.

Fordyce granules and hereditary non-polyposis colorectal cancer syndrome

Background: Germline mutations in mismatch repair (MMR) genes are found in only about half of clinically diagnosed families with hereditary non-polyposis colorectal cancer syndrome (HNPCC) (or Lynch syndrome). Early identification of gene carriers is essential to reduce cancer incidence and overall mortality. Aims: Recent evidence indicates an increase in size and number of sebaceous glands following activation of the hedgehog pathway, a crucial signalling pathway for animal development that is aberrantly activated in several types of cancer. Here we sought to assess a possible association between Fordyce granules (FGs—that is, ectopic sebaceous glands on the oral mucosa) and HNPCC. Methods: A total of 15 members of five different genetically unrelated HNPCC kindreds (MLH1 gene mutation n = 8; undetectable MLH1 protein at immunochemistry n = 4; clinical diagnosis n = 3) and 630 genetically unrelated age and sex matched healthy controls were examined. Following examination of the oral mucosa surface, subjects were categorised as either FGs positive or FGs negative. Results: Evidence of FGs was significantly associated with HNPCC (13/15 (86.7%) affected patients v 6/630 (0.95%) controls; p<0.0001), with a relative risk of 91.0 (95% confidence interval 40.05–206.76). The observed difference remained significant when carriers of germline mutations in MMR genes were considered (8/15 v 6/630; p<0.0001). The most common site for the FGs in HNPCC patients was the lower gingival and vestibular oral mucosa. Conclusions: Our findings suggest that a previously unrecognised activation of the sebaceous glands system occurs in HNPCC. The observation could be of value for attending physicians in identifying affected families and/or increase the accuracy of the currently available molecular genetics screenings.

Abnormal oral mucosal light reflectance: a new clinical marker of high risk for colorectal cancer

Background: A familial predisposition to colorectal cancer (CRC) has been clearly established, consisting of familial clustering in 15–20% and clear hereditary aetiology in 5–10% of overall CRC cases. Early identification of families and individuals at high risk is essential as intensive surveillance has been demonstrated to reduce cancer incidence and overall mortality. In the present study, the value of oral mucosal light reflectance in identifying hereditary non-polyposis colorectal cancer (HNPCC) carriers was investigated. Methods: Twenty members of six different genetically unrelated HNPCC kindred and 30 genetically unrelated age and sex matched healthy controls were examined. Lower gingival and vestibular oral mucosal reflectance was measured using an imaging spectrophotometer. Results: HNPCC carriers showed significantly lower values in the 590–700 nm wavelength range (p⩽0.0004). A reflectance cut off value ⩽47.9% at the 700 nm wavelength discriminated between HNPCC carriers and controls, with 100% sensitivity and 100% specificity. Conclusions: These findings may provide an additional phenotypic sign in HNPCC carriers, which could be used in first level CRC population screening programmes.

Congenital cystic adenomatoid malformation of the lung associated with esophageal atresia and tracheoesophageal fistula

Abstract Bronchopulmonary malformations associated with esophageal atresia (EA) and tracheoesophageal fistula (TEF) are extremely rare. The authors describe a case of type II congenital cystic adenomatoid malformation (CCAM) of the right lower lobe associated with EA and TEF (Vogt-Gross type C) in a full-term female infant. The CCAM presented as an incidental radiologic finding, and a contralateral tension pneumothorax developed shortly after surgical repair of the EA. Early recognition of this rare association is essential for correct operative management.

First Day of Life Reference Values for Pleth Variability Index in Spontaneously Breathing Term Newborns

Background: The perfusion index (PI), derived from the pulse oximetry signal, has been shown to be an accurate predictor for identifying high illness severity in neonates. The plethysmographic variability index (PVI) is a measure of the dynamic change in PI occurring during a complete respiratory cycle. Objectives: The aim of this study was to establish the reference range of PVI in spontaneously breathing term newborns. Methods: PI and PVI values were assessed in 242 term newborns during the first day of life. Results: The median PVI value on the first day of life was 20% [95% confidence interval (CI) for the mean 19–20%; inter-quartile range 15 (95% CI 15–16) – 24 (95% CI 23–24)]. The 10th and 90th percentile cutoff values were 12% (95% CI 11–12) and 28% (95% CI 27–29), respectively, with the 97.5th percentile of 35% (95% CI 34–38). PVI was also significantly influenced by the behavioral status of the newborn, and was positively correlated with PI and pulse rate, while it was inversely correlated with oxygen saturation (p < 0.0001). Conclusions: Our findings suggest: (1) evaluation of PVI values is an easily applicable, noninvasive procedure for monitoring early postnatal respiratory changes in newborns, and (2) the feasibility of a noninvasive pulse-oximeter postnatal screening for early identification of adverse neonatal cardiorespiratory outcomes.

Prenatal diagnosis of OEIS (omphalocele, bladder exstrophy, imperforate anus, clubfeet) variant associated with increased nuchal translucency and OEIS complex with ambiguous genitalia associated with corrected transposition of the great arteries: case series and review of the literature

IntroductionThe OEIS complex refers to a combination of defects consisting in omphalocele, bladder exstrophy, imperforate anus and spinal defects and represents a rare nosologic entity (from 1:200,000 to 1:400,000 pregnancies). The defect probably occurs in early blastogenesis or in mesodermal migration during the primitive streak period.Materials and methodsTwo cases of OEIS complex diagnosed prenatally by ultrasound are reported. The medical record regarding differential diagnosis, associated anomalies, treatment and prognosis has also been sought and reported. ConclusionDifferential diagnosis with exstrophy-epispadias complex and/or cloacalexstrophy complex may be difficult antenatally by means of ultrasound. However, color Doppler has been proved to aid the diagnosis of bladder exstrophy by depicting the urine flow in direct communication with the abdominal cavity and has been useful in showing the course of the perivesical umbilical arteries. Prenatal 3D ultrasound with tomographic ultrasound imaging (TUI) and antenatal MR imaging might be useful adjuncts to conventional 2D scan in aiding the prenatal diagnosis of such malformation.