Inhaled nitric oxide and oral nifedipine in a preterm infant with bronchopulmonary dysplasia and pulmonary hypertension.
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Administration, Inhalation↗
Biomedical subjects
Giuseppe Latini
Publications and source records attributed to Giuseppe Latini.
Phthalate exposure and male infertility.
Phthalates have been used as additives in industrial products since the 1930s, and are universally considered to be ubiquitous environmental contaminants. The general population is exposed to phthalates through consumer products, as well as diet and medical treatments. Animal studies showing the existence of an association between some phthalates and testicular toxicity have generated public and scientific concern about the potential adverse effects of environmental changes on male reproductive health. In particular, prenatal exposure to phthalates seems to play a relevant role in determining these adverse effects given that human exposure has been demonstrated to begin during the intrauterine life. Unprecedented declines in fertility rates and semen quality of antenatal origin have been reported during the last half of the 20th century in developed countries and increasing interest exists on the potential relationship between exposure to environmental contaminants, including phthalates, and human male reproductive health. Here we review the data that support or discounts the evidence existing to date linking phthalate exposure and the decline of human male fertility, especially in developed countries.
Adult↗
Abnormal oral mucosal light reflectance in achondroplasia.
No markers for the unaffected parents of children with achondroplasia (ACH) are known to date. Here, the value of oral mucosal reflectance in identifying unaffected parents of ACH patients with sporadic mutations was assessed. The study involved ACH children (n = 30), unaffected ACH parents (n = 60), and a sex- and age-matched controls (control children, n = 30; control parents, n = 60). Light reflectance of the lower gingival and vestibular oral mucosa was measured using an imaging reflectance system in the optical spectrum (400-700 nm wavelengths). Significantly higher reflectance values in the 410 to 630 nm wavelength range were observed in ACH patients (P < or = .0063), whereas significantly lower reflectance values over the whole optical spectrum were observed in ACH parents (P < or = .0001). A reflectance cutoff value < or =4.71% at the 430 nm wavelength identified ACH parents with 100% sensitivity and 96.4% specificity. These findings indicate the presence of previously unrecognized oral mucosal reflectance abnormalities in unaffected ACH parents of ACH children.
Achondroplasia↗
Abnormal oral vascular network pattern geometry: a new clinical sign of down syndrome.
Down syndrome is a leading genetic cause of mental retardation. Here, we show high fractal dimensions and Lempel-Ziv complexity and lower minimum path fractal dimension (P < or = .0006) for the oral vascular networks of patients (n = 14) and their unaffected parents. This newly recognized sign may provide a useful phenotypical marker for identifying couples potentially at risk for offspring with Down syndrome.
Adolescent↗
Low serum concentrations of di-(2-ethylhexyl)phthalate in women with uterine fibromatosis.
Di-(2-ethylhexyl)phthalate (DEHP) is the most commonly used plasticizer in flexible polyvinylchloride formulations, and is a widespread ubiquitous environmental contaminant. A potential role of exposure to DEHP and its primary metabolite, monoethylhexylphthalate (MEHP), on women's reproductive function is suggested in the current study. The aim of the study was to test serum concentrations of DEHP and/or MEHP in women with uterine fibromatosis. Two groups of women were enrolled in the study: (i) women with uterine fibromatosis undergoing surgical menopause (n = 15) and (ii) healthy women (n = 20). Serum DEHP and MEHP concentrations were measured by high-performance liquid chromatography. Serum MEHP distribution was found to be non-Gaussian (p = 0.001) while serum DEHP distribution was compatible with a normal curve (p = 0.141). Patients with uterine fibromatosis showed significantly lower serum MEHP concentrations (median [interquartile range]: 0 [0-0] microg/ml, range: 0-0.57 microg/ml) than controls (0.42 [0-0.51] microg/ml, range: 0-1.20 microg/ml, z = -2.93, p = 0.0034). Likewise, serum DEHP concentrations in women with fibromatosis were found to be significantly lower than in controls (patients: 0.27 +/- 0.096 microg/ml (mean +/- standard deviation (SD)), range: 0.14-0.59 microg/ml vs. controls: 0.30 +/- 0.14 microg/ml (mean +/- SD), range: 0-0.63 microg/ml; t = 3.212, df = 33, difference: -0.325 (95% confidence interval: -0.5309, -0.1191), p = 0.0029). In conclusion, the present findings indicate for the first time that serum DEHP and MEHP concentration are lower in women with uterine fibromatosis, suggesting a possible correlation between phthalate esters and fibromatosis pathology.
Chromatography, High Pressure Liquid↗
Early dynamic changes in pulse oximetry signals in preterm newborns with histologic chorioamnionitis.
OBJECTIVE: No reliable clinical markers of histologic chorioamnionitis (HCA), a major and often subclinical cause of prematurity leading to high neonatal morbidity and mortality, are available to date. Increasing evidence indicates myocardial dysfunctions in affected fetuses and newborns. We sought to assess the value of nonlinear dynamics from pulse oximetry signals in identifying affected newborns. DESIGN: Prospective case-control study. SETTING: Tertiary level neonatal intensive care unit, Brindisi Hospital. PATIENTS AND INTERVENTION: Pulse oximetry-derived signals (pulse rate, oxygen saturation, and perfusion index), recorded within the first 1.5 hrs of life, were analyzed for 110 very low-birth-weight infants, of whom 54 had histopathological evidence of HCA. MEASUREMENTS AND MAIN RESULTS: Four different time series parameters were determined for nonlinear dynamical (NLD) analysis. Significantly decreased Lempel-Ziv, Lyapunov largest exponent, and correlation dimension, with significantly increased Hurst values for heart rate and perfusion index (p < .00001), were observed in newborns with HCA. Heart rate Lempel-Ziv </=0.218 showed 100% sensitivity (95% confidence interval, 98.8-100) and 100% specificity (95% confidence interval, 98.6-100) in distinguishing cases from controls, with positive and negative predictive values of 100% and 95.7%, respectively. CONCLUSIONS: Our findings indicate that early autonomic tone balance abnormalities are present in newborns with HCA and suggest that early dynamic analysis of pulse oximetry signals could be useful in identifying affected infants.
Case-Control Studies↗
In utero exposure to phthalates and fetal development.
The diesters of benzene-1,2-dicarboxylic (phthalic) acid, commonly known as phthalates, are a family of industrial compounds, primarily used as plasticizers in enormous quantities for a variety of industrial uses in the formulation of plastics. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer. These plasticizers are not covalently bound to the polymer and leach out into the environment, thus becoming ubiquitous environmental contaminants. Cumulating evidence points out on the adverse effects of phthalate exposure during intrauterine life. Recently, it has been documented that in utero phthalate exposure is associated with a shorter duration of pregnancy. Phthalates induce and activate a subset of peroxisome proliferator-activated receptors (PPARs) and have an intrinsic pro-inflammatory activity, while some natural PPAR agonists induce cyclooxygenase (COX)-2 expression. To this regard, COX-2 is thought to be overexpressed in chorioamnionitis (CA), a fetal systemic inflammatory response syndrome and a leading cause of preterm birth. An adequate maternal dietary intake of essential fatty acids, well known anti-inflammatory agents, is indispensable to fetal development. Recently, it has been shown that phthalates alter the placental essential fatty acids (EFAs) homeostasis so potentially leading to abnormal fetal development. Likewise, a possible down-regulation of COX-2 by omega-3 fatty acids has been suggested. As a consequence, maternal supplementation with omega 3 during pregnancy could counteract the adverse effects of phthalates exposure in the human fetus. Here, we analyze the existing evidence on the link between antenatal phthalate exposure and abnormal fetal development, as well as on possible therapeutic tools to fight the adverse effect of this exposure.
Animals↗
Recent advances on neural tube defects with special reference to Valproic Acid.
Epilepsy is a common medical problem and many studies have demonstrated that infants of women with epilepsy (WWE) have a two to threefold higher risk of congenital malformations compared with the background population. The majority of WWE have normal, healthy children. However, WWE have an increased risk of congenital malformations. Congenital malformations are twice as common in infants exposed to antiepileptic drugs in utero. A variety of congenital malformations have been reported, with a particular preponderance of orofacial clefts. Valproate is often associated with the development of neural tube defects. In this review, we analyse the problem of neural tube defects and report in detail the main pathogenetic theories about the onset of this type of congenital malformation. There is strong evidence for a protective effect of adequate folate consumption.
Adult↗
Abnormal oral mucosal light reflectance in bronchopulmonary dysplasia.
BACKGROUND: Bronchopulmonary dysplasia (BPD) is an important cause of mortality and morbidity in preterm infants. A disordered vascular development and a decreased production of angiogenic factors have been recently reported in the condition. Extracellular matrix (ECM) is known to play an important role on angiogenesis and blood vessel geometry and changes in ECM components have been previously reported in experimental models and patients with BPD. Here, we aimed to assess the potential value of light reflectance on the oral mucosa in detecting infants who will develop BPD. METHODS: A total of 75 preterm newborns (gestational age: 27.7 +/- 2.8 weeks, birth weight: 870 +/- 145 g) were recruited to the study, of whom 25 developed BPD (gestational age: 26.9 +/- 3.0 weeks, birth weight: 855 +/- 150 g). Reflectance was measured on the postnatal days 1 and 28, using high-resolution photographs of the lower gingival and vestibular oral mucosa, using imaging spectrophotometry in the 400-700 nm wavelength electromagnetic spectral range. The median of artefact- and vessel-free areas was n = 78 (interquartile range: 59-88). Median range values were comparable for both groups: BPD-positive infants, median 77 (interquartile: 60-90) vs. control infants, median 74 (interquartile: 62-92). The predictive accuracy of oral spectrophotometry was calculated using receiver operating characteristic curve analysis. RESULTS: BPD patients showed significantly lower light reflectance values in the red (610-700 nm, P < 0.0001), with higher values in the violet (400 nm, P = 0.0056; 430 nm, P=0.014), and blue-green (480-500 nm, P < or = 0.024) sections of the spectrum already on the first day of life. A low reflectance value in the 640-700 nm wavelengths interval was found to identify BPD patients with 100% sensitivity and 100% specificity (640 nm: cutoff < or = 44.91%; 650 nm: < or = 45.64%; 660 nm: < or = 46.56%; 670 nm: < or = 47.14%; 680 nm: < or = 47.56%; 690 nm: < or = 48.95%; 700 nm: < or = 50.81%). CONCLUSIONS: These findings indicate the presence of previously unrecognised, early abnormalities in the average optical properties of the oral mucosa from infants developing BPD.
Bronchopulmonary Dysplasia↗
Incidental detection of neuroblastoma and "wait and see" strategy.
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Humans↗
Prenatal exposure to phthalates and intrauterine inflammation: a unifying hypothesis.
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Animals↗
Monitoring phthalate exposure in humans.
The dialkyl- or alkyl/aryl esters of 1,2-benzenedicarboxylic acid, commonly known as phthalates, are high-production-volume synthetic chemicals and ubiquitous environmental contaminants because of their use in plastics and other common consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate in the environment. Humans are exposed to these compounds through ingestion, inhalation, and dermal exposure for their whole lifetime, since the intrauterine life. Public and scientific concern has increased in recent years about the potential health risks associated with exposure to phthalates. The main focus has moved away from the hepatotoxic effects to the endocrine disrupting potency of these chemicals. To date, although the consistent toxicologic data on phthalates is suggestive, information on sources and pathways of human exposure to phthalates is limited. Recently, exposure to phthalates has been assessed by analyzing urine for their metabolites. This approach is contrary to the determination of the parent phthalates in air, water and foodstuff and not subject to contamination. Furthermore, these metabolites and the parent phthalates are considered the toxic species. However, accurate methods and models for measuring the amount of phthalates absorbed by the various pathways of exposure have to be developed. In fact, a frequent biological monitoring of phthalates in body fluids and tissues would be highly advisable, both in helping physicians to perform health risk assessments for exposure in the general population and in guiding governments to provide regulations concerning the maximum allowed concentrations in the environment, plasticized products, medications and medical equipment.
Animals↗
Evaluating illness severity for very low birth weight infants: CRIB or CRIB-II?
BACKGROUND: Estimating the risk of in-hospital mortality provides essential information in the neonatal intensive care unit (NICU). The clinical risk index for babies (CRIB) is a widely used, risk-adjustment instrument to determine illness severity in infants of gestational age <or=31 wks, or birth weight <or=1,500 g, recently updated and simplified into a five-items scoring system (CRIB-II).Aim. The accuracy values of CRIB and CRIB-II scores in predicting in-hospital mortality were compared in a tertiary level, minimal intubation policy NICU setting. METHODS: A total of 147 very low birth weight (VLBW) infants were examined. Both CRIB and CRIB-II scores were calculated for each newborn, and death before hospital discharge was selected as the outcome measure. Comparisons were performed by receiver-operating characteristic (ROC) curve analysis, and the area under the curve (AUC) was used as a measure of predictor accuracy. RESULTS: Mean AUCs for CRIB, CRIB-II, gestational age and birth weight in identifying neonatal mortality in VLBW infants ranged from 0.924 (CRIB) to 0.869 (gestational age). No significant differences were found for the AUCs of CRIB versus CRIB-II, CRIB versus gestational age, CRIB versus birth weight, CRIB-II versus gestational age, or CRIB-II versus birth weight. CONCLUSIONS: Our findings show that; 1) CRIB and CRIB-II show similar accuracy values in predicting in-hospital neonatal mortality in VLBW infants; and 2) neither score offers an advantage in predicting mortality, as compared to gestational age or birth weight, thus suggesting that treatment modalities may modify predictive accuracy.
Female↗
Histologic chorioamnionitis and severity of illness in very low birth weight newborns.
OBJECTIVE: Estimating the risk of in-hospital mortality in the neonatal intensive care unit provides important information for health care providers, and several neonatal illness severity scores have been developed. Histologic chorioamnionitis (HCA) is a known cause of neonatal morbidity and mortality. To date, the relationship between HCA and neonatal illness severity scores has not been rigorously tested. In this study, the relationships among HCA, initial illness severity, and neonatal outcomes were analyzed in very low birth weight (VLBW) newborns admitted to the neonatal intensive care unit. DESIGN: Prospective. SETTING: Neonatal intensive care unit. PATIENTS: A total of 116 VLBW inborn infants (gestational age, 28.1 +/- 2.82 wks; birth weight, 1009 +/- 312 g) were categorized as HCA-positive (n = 67) and HCA-negative (n = 49). INTERVENTIONS: Placental histology was performed to identify HCA. Illness severity evaluation included several different neonatal illness severity scores-Clinical Risk Index for Babies (CRIB), CRIB-II, Score for Neonatal Acute Physiology-II (SNAP-II), and Score for Neonatal Acute Physiology Perinatal Extension-II (SNAPPE-II)-as well as the recording of severe morbidity and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: HCA-positive VLBW newborns showed significantly lower gestational age (p < .0001) and birth weight (p = .0010), together with higher CRIB, CRIB-II, SNAP-II, and SNAPPE-II scores at admission to the NICU (p </= .0001) and mortality rate (p = .0018) than HCA-negative infants. After adjustment for gender and gestational age in a multivariable logistic regression analysis, HCA was found to be an independent predictor of high illness severity: CRIB > 5 (odds ratio [OR], 21.37; 95% confidence interval [CI], 6.24-73.21); CRIB-II > 10 (OR, 56.17; 95% CI, 6.75-467.2); SNAP-II > 22 (OR, 43.05; 95% CI, 11.9-155.7), and SNAPPE-II > 42 (OR, 48.95; 95% CI, 10.18-235.4) (all p values <.0001). CONCLUSIONS: Our findings indicate that HCA is a major predictor of morbidity and mortality in VLBW newborns.
Chorioamnionitis↗
Endocrine and metabolic changes in epileptic patients receiving valproic acid.
It has been well known for many years that valproic acid (VPA) therapy can induce obesity and important endocrine dysfunctions; among these dysfunctions, the most common are hyperandrogenism, menstrual disorders, polycystic ovary syndrome, hyperinsulinism, and changes in LH, FSH, and sexual and thyroid hormones. Moreover, abnormalities in pubertal development and impaired skeletal growth have been reported. The aim of this review is to analyze the main effects of VPA on endocrinological functions in patients with epilepsy in order to understand in depth the pathophysiological mechanisms and, consequently, to improve the care of these patients.
Anticonvulsants↗
Indications and limitations for a neonatal pulse oximetry screening of critical congenital heart disease.
AIMS: Critical congenital cardiovascular malformations (CCVMs) require surgical correction during the first month of life, physical examination is unable to detect >50% of affected infants. An oximetry screening has been previously proposed. Our aim was to verify the usefulness and consistency of a pulse oximetry screening for early detection of CCVMs in a small size nursery. METHODS: A single determination of SpO2 was performed on 5292 consecutive apparently healthy newborns, discharged from nursery at a median age of 72 h during the period May 1, 2000 and November 30, 2004. Infants showing signs of congenital heart disease before the screening and those with a prenatal diagnosis were excluded. Cardiac ultrasound was performed on all infants with SpO2< or =95% at >24 h. The accuracy of the screening in identifying CCVMs was assessed by receiver-operating characteristic (ROC) curves analysis. RESULTS: We found 2 (0.038%) true positives, 1 (0.019%) false negative, 1 (0.019%) false positive, and 5288 (99.92%) true negatives. Prevalence of critical CCVMs was 1 in 1764. Clinical follow-up showed no evidence of CCVMs in the negative cases. A pulse-oximetry cut-off value of < or =95% showed 66.7% sensitivity (95% CI: 11.6-94.5), 100% specificity (95% CI: 99.9-100.0), 50% positive predictive value, 100% negative predictive value and AUC of 0.833 (standard error: 0.145) (95% CI: 0.823 to 0.843) in identifying CCVMs. CONCLUSIONS: Our findings indicate that pulse oximetry is a non-invasive and specific screening tool for an early detection of CCVMs, and is easily applicable to a small size nursery.
Female↗
Transient hypothyroxinemia of prematurity and histological chorioamnionitis.
BACKGROUND: Transient hypothyroxinaemia of prematurity (THOP) is a common condition of preterm infants whose causes remain unclear. We tested the hypothesis that THOP is associated with histological chorioamnionitis (HCA). METHODS: Whole blood T4 and TSH concentrations on day 4 and at 40 weeks' postmenstrual age (rtx-T4 and rtx-TSH), placental histology and illness severity were prospectively evaluated in 155 very low birth weight (VLBW) infants. RESULTS: HCA-positive infants showed significantly decreased blood total T4 concentrations on day 4, as compared to the HCA-negative population (P<0.0001), along with comparable TSH, rtx-T4, and rtx-TSH blood concentrations. None of the infants showed evidence of hypothyroidism during the study. A total T4 < or = 4.4 microg/dL on postnatal day 4 identified HCA-positive newborns with 90.8%, sensitivity, 94.7%, specificity, 96.7% positive predictive and 85.7% negative predictive values. HCA (OR: 32.19; 95% CI: 8.95-115.64), birth weight < or = 880 g (OR: 4.1; 1.15-14.64), and RDS (OR: 3.71, 95% CI: 1.13-12.25) were independently associated with evidence of hypothyroxinaemia on day 4. CONCLUSION: Our findings indicate a previously un-recognized relationship between HCA and THOP, hence suggesting a predominant role for a fetal systemic inflammatory response syndrome in the pathogenesis of THOP.
Age Factors↗
Oral mucosal microvascular abnormalities: an early marker of bronchopulmonary dysplasia.
An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD). We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD. Fifteen infants with BPD (nine boys and six girls; gestational age 27.5 +/- 2.0 wk; birth weight 850 +/- 125 g) and 15 sex- and gestational age-matched infants (nine boys and six girls; gestational age 27.6 +/- 2.6 wk; birth weight 865 +/- 135 g) were examined on postnatal days 1 and 28. BPD infants showed a significantly higher prevalence of histologic chorioamnionitis (p = 0.009), as well as higher intubation duration (p = 0.0004), oxygen supplementation (p < 0.0001), and initial illness severity (p = 0.0002) than the BPD-negative population. The lower gingival and vestibular oral mucosa was chosen as the study area. The blood vessel area was determined, and the oral vascular networks were characterized by analyzing their complexity (D, at two scales: D 1-46, D 1-15), tortuosity (Dmin), and randomness (L-Z) of the vascular loops. Infants with BPD showed a significantly lower blood vessel area as well as a higher vascular network complexity (D 1-46, D 1-15, and L-Z) than control subjects (p < 0.0001). Our findings provide a new early clinical sign in BPD and stress the importance of an early disorder in the oral mucosal vascularization process in the disease pathogenesis.
Adult↗