Giuseppe Latini

Increased Bone Turnover in Prepubertal, Pubertal, and Postpubertal Patients Receiving Carbamazepine

Summary:  Purpose: To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy.

Systemic oxidative stress in classic Rett syndrome

Rett syndrome (RS), a progressive severe neurodevelopmental disorder mainly caused by de novo mutations in the X-chromosomal MeCP2 gene encoding the transcriptional regulator methyl-CpG-binding protein 2, is a leading cause of mental retardation with autistic features in females. However, its pathogenesis remains incompletely understood, and no effective therapy is available to date. We hypothesized that a systemic oxidative stress may play a key role in the pathogenesis of classic RS. Patients with classic RS (n=59) and control subjects (n=43) were evaluated. Oxidative stress markers included intraerythrocyte non-protein-bound iron (NPBI; i.e., free iron), plasma NPBI, F2-isoprostanes (F2-IsoPs, as free, esterified, and total forms), and protein carbonyls. Lung ventilation/perfusion (V/Q) ratio was assessed using a portable gas analyzer, and RS clinical severity was evaluated using standard scales. Significantly increased intraerythrocyte NPBI (2.73-fold), plasma NPBI (x 6.0), free F(2)-IsoP (x1.85), esterified F2-IsoP (x 1.69), total F2-IsoP (x 1.66), and protein carbonyl (x 4.76) concentrations were evident in RS subjects and associated with reduced (-10.53%) arterial oxygen levels compared to controls. Biochemical evidence of oxidative stress was related to clinical phenotype severity and lower peripheral and arterial oxygen levels. Pulmonary V/Q mismatch was found in the majority of the RS population. These data identify hypoxia-induced oxidative stress as a key factor in the pathogenesis of classic RS and suggest new therapeutic approaches based on oxidative stress modulation.

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.

The pulse oximeter perfusion index as a predictor for high illness severity in neonates

Following the first development in its modern form in 1972 by Takuo Aoyagi [1], pulse oximetry has become invaluable for monitoring oxygenation and pulse rate [4]. A constant amount of light (DC) from the pulseoximeter is absorbed by skin, other tissues, and nonpulsatile blood, while a variable amount of light (AC) is absorbed by pulsating arterial inflow. The pulsatile signal indexed against the non-pulsatile signal and expressed as a percentage (AC/DC · 100) is commonly referred to as the perfusion index (PI). Skin colourimetry is related to illness severity in newborns [2] but its utility as a monitoring tool is partially limited by requiring direct caregiver assessment. As local skin vasoconstriction can be associated with skin colour changes, the usefulness of PI for assessing neonatal illness severity was similarly tested. A prospective study was carried out on 101 inborn or outborn Caucasian neonates (52 males, 49 females; gestational age 34.7±4.0 weeks, range 24.7–41.1 weeks; birth weight 2310±950 g, range 410–4170 g) during the first 24 h after admission. Illness severity was determined using the Score for Neonatal Acute Physiology (SNAP) [5] and the infants were categorised as either high or low severity of illness, defined by the presence of severe neonatal morbidity and/or a 24 h SNAP score >10 [2]. PI values were assessed using a Masimo SET Radical pulse-oximeter (Masimo Corp., Irvine, Calif., USA) with the sensor placed randomly on either foot. After the pulse wave was verified to be artifact-free, the PI values were manually captured by an operator, who was unaware of the infant illness severity group, at least every 0.3 min for a duration of 10.6±2.3 min (95% CI 9.9–11.4 min, range: 10–15 min). SpO2, pulse rate, body (skin and core) temperature, and blood pressure were also measured. Out of a total of 2,571 measurements, 2,546 (99.02%) artifact-free readings were obtained. The higher severity group showed a significantly higher frequency of severe neonatal morbidity (P=0.025), as determined by the presence of at least one of the following: sepsis or pneumonia; bronchopulmonary dysplasia; intraventricular haemorrhage grade 3 or more; periventricular leukomalacia grade 3 or more; retinopathy of prematurity grade 3 or more; and necrotising enterocolitis [2]. Predictive accuracy for identifying newborns with higher severity for different cut-off values of PI, SpO2, and pulse rate was calculated using receiver operating characteristic (ROC) curve [3]. Model calibration was evaluated using v to compare the expected values (according to the classification of infants into two severity categories) with the expected values (according to the SpO2, pulse rate and PI values). According to the predefined criteria, 43 neonates (42.6%) were allocated to the high severity group and 58 to the low severity group. Male to female ratio, gestational age, birth weight, body temperature, mean blood pressure, and use of peripheral vasoconstrictors and vasodilators were not significantly different between the two severity groups (P‡0.50). Mean PI values were 1.54±0.80 (range: 0.22–5.22). Significantly lower PI values (0.86±0.26 versus 2.02±0.70; P<0.0001), lower SpO2 (93.3±5.4% versus 95.1±3.9%, P<0.0001) and higher pulse rate Eur J Pediatr (2002) 161: 561–562 DOI 10.1007/s00431-002-1042-5

Lung Ultrasound Characteristics of Community-Acquired Pneumonia in Hospitalized Children

The diagnosis of community‐acquired pneumonia (CAP) is based mainly on the patients medical history and physical examination. However, in severe cases a further evaluation including chest X‐ray (CXR) may be necessary. At present, lung ultrasound (LUS) is not included in the diagnostic work‐up of pneumonia.

DI-2-ethylhexyl phthalate and endocrine disruption: a review.

Esters of o-phthalic acid are widely distributed in the ecosystem. The phthalate acid esters (PAEs) are used as plasticizers in enormous quantities for a variety of industrial uses in the formulation of plastics. They are also used as solvents in certain industrial processes and as vehicles for pesticides and have been described as being among the most abundant man-made environmental pollutants. Plasticizers have been shown to elute at a constant rate from plastic products to the environment. Increasing chemical use needs a better understanding of how these pollutants may affect human health. In particular, certain members of this chemical class, such as di-[2-ethylhexyl]-phthalate (DEHP), have been shown to cause reproductive and developmental toxicity and are suspected to be endocrine disruptors.

Di-(2-Ethylhexyl) Phthalate and Autism Spectrum Disorders:

ASDs (autism spectrum disorders) are a complex group of neurodevelopment disorders, still poorly understood, steadily rising in frequency and treatment refractory. Extensive research has been so far unable to explain the aetiology of this condition, whereas a growing body of evidence suggests the involvement of environmental factors. Phthalates, given their extensive use and their persistence, are ubiquitous environmental contaminants. They are EDs (endocrine disruptors) suspected to interfere with neurodevelopment. Therefore they represent interesting candidate risk factors for ASD pathogenesis. The aim of this study was to evaluate the levels of the primary and secondary metabolites of DEHP [di-(2-ethylhexyl) phthalate] in children with ASD. A total of 48 children with ASD (male: 36, female: 12; mean age: 11±5 years) and age- and sex-comparable 45 HCs (healthy controls; male: 25, female: 20; mean age: 12±5 years) were enrolled. A diagnostic methodology, based on the determination of urinary concentrations of DEHP metabolites by HPLC-ESI-MS (HPLC electrospray ionization MS), was applied to urine spot samples. MEHP [mono-(2-ethylhexenyl) 1,2-benzenedicarboxylate], 6-OH-MEHP [mono-(2-ethyl-6-hydroxyhexyl) 1,2-benzenedicarboxylate], 5-OH-MEHP [mono-(2-ethyl-5-hydroxyhexyl) 1,2-benzenedicarboxylate] and 5-oxo-MEHP [mono-(2-ethyl-5-oxohexyl) 1,2-benzenedicarboxylate] were measured and compared with unequivocally characterized, pure synthetic compounds (>98%) taken as standard. In ASD patients, significant increase in 5-OH-MEHP (52.1%, median 0.18) and 5-oxo-MEHP (46.0%, median 0.096) urinary concentrations were detected, with a significant positive correlation between 5-OH-MEHP and 5-oxo-MEHP (rs = 0.668, P<0.0001). The fully oxidized form 5-oxo-MEHP showed 91.1% specificity in identifying patients with ASDs. Our findings demonstrate for the first time an association between phthalates exposure and ASDs, thus suggesting a previously unrecognized role for these ubiquitous environmental contaminants in the pathogenesis of autism.

Leptin, ghrelin, and adiponectin in epileptic patients treated with valproic acid

The authors studied 40 epileptic patients treated with valproate and 40 healthy controls for at least 2 years. At the end of follow-up, 15 epileptic patients (37.5%) had development of obesity. They showed circulating leptin and insulin levels significantly higher and ghrelin and adiponectin levels significantly lower than those of patients who did not gain weight.

Foetal growth of kidneys, liver and spleen in intrauterine growth restriction: "programming" causing "metabolic syndrome" in adult age.

Background/aims: Epidemiological studies in humans link adult disease to abnormal growth in utero. In addition to general malnutrition of the foetus, preferential blood flow to the brain and heart may furthermore deprive organs such as the liver, spleen and kidneys of oxygen and macroand micronutrients. As a consequence, these organs may not develop normally, which predisposes the individual to the so‐called metabolic syndrome (syndrome X) in later life. The effects of foetal undernutrition on the growth of some abdominal organs were investigated by comparing the volume of the kidneys, spleen and liver in small‐for‐gestational‐age (SGA) newborn infants with that in appropriate‐for‐gestational‐age (AGA) newborn infants. Methods: In 25 randomly selected AGA infants and 25 SGA infants, who were subdivided into three gestational age groups (<30, 30–36 and 37–40 wk) the volumes of the liver, kidneys and spleen were determined by ultrasonography. Organ volumes were estimated using the standard ellipsoid formula (longitudinal × anteroposterior × transverse diameter ×π/6). Liver/kidney, liver/spleen and kidney/spleen volume ratios were also determined. Results: The volumes of the kidneys and liver differed significantly between AGA and SGA infants in all three gestational age groups (p≤ 0.0018 and p≤ 0.029, respectively). The fact that the spleen volume differed only in the 37–40 wk group (p= 0.0002) may indicate that there is a graded relationship across the whole range of normal birthweight. The correlation between the liver volume and birthweight differed significantly between SGA and AGA infants (r= 0.56 vs 0.84, p= 0.04). On the other hand, the volume ratios between the three organs were the same in all groups (p≥ 0.15).

Lung ultrasound in bronchiolitis: comparison with chest X-ray

The diagnosis of bronchiolitis is based mainly on the patient’s medical history and physical examination. However, in severe cases, a further evaluation including chest X-ray (CXR) may be necessary. At present, lung ultrasound (LUS) is not included in the diagnostic work-up of bronchiolitis. This study aimed to compare the diagnostic accuracy of LUS and CXR in children with bronchiolitis, and to evaluate the correlation between clinical and ultrasound findings. Only patients with a diagnosis of bronchiolitis, who had undergone a CXR, were enrolled in the study. Fifty-two infants underwent LUS and CXR. LUS was also performed in 52 infants without clinical signs of bronchiolitis. LUS was positive for the diagnosis of bronchiolitis in 47/52 patients, whereas CXR was positive in 38/52. All patients with normal LUS examination had a normal CXR, whereas nine patients with normal CXR had abnormal LUS. In these patients, the clinical course was consistent with bronchiolitis. We found that LUS is a simple and reliable tool for the diagnosis and follow-up of bronchiolitis. It is more reliable than CXR, can be easily repeated at the patient’s bedside, and carries no risk of irradiation. In some patients with bronchiolitis, LUS is able to identify lung abnormalities not revealed by CXR. Furthermore, there is a good correlation between clinical and ultrasound findings. Given the short time needed to get a US report, this technique could become the routine imaging modality for patients with bronchiolitis.