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Biomedical subjects

L Iughetti

Publications and source records attributed to L Iughetti.

At least 37 records · Page 2Linked to original sources

[A case of female pseudohermaphroditism caused by maternal androluteoma].

Female pseudohermaphroditism is a condition characterized by various degree of external genitalia virilization in a patient with female internal genitalia and karyotype (XX). External genitalia is masculinized congenitally when female fetus is exposed to excess androgenic environment. Fetal metabolic abnormalities, like congenital adrenal hyperplasia, are the most common causes of female pseudohermaphroditism, however there is a low incidence of gestational hyperandrogenism caused by maternal pathology. We report a case of female pseudohermaphroditism secondary to a maternal ovarian luteoma of pregnancy producing androgenic hormones. The newborn presented a severe degree of external genitalia virilization with high urogenital sinus (stage Prader V). Moreover we describe the main steps of diagnostic iter that are necessary both to exclude other causes of virilization and to study all anatomical aspects in view of the surgical correction. The operation consists in two phases of action: an early clitorisvulvoplasty according to Passerini-Glazel and a late vaginal pull-through with anterior saggital transanorectal approach (ASTRA).

Disorders of Sex Development↗

Circulating antibodies recognizing oxidatively modified low-density lipoprotein in children.

The occurrence of circulating antibodies (IgG) against oxidatively modified LDL was investigated in a group of normocholesterolemic, healthy, cardiovascular risk-free children and in a comparable group of normal adults. An increased titer of IgG recognizing Cu++-oxidized or malondialdehyde (MDA)-derivatized LDL (MDA-LDL) was a constant feature in children. The antigenic epitopes recognized by these antibodies were generated rather late in the process of copper-mediated LDL oxidation, concomitantly with the formation of fluorescent adducts between reactive aldehydes (including MDA) and apo B100. MDA-LDL was not the only antigen recognized: derivatization of other structurally unrelated proteins, such as HDL, serum albumin, fibrinogen, and transferrin with MDA led to generation of recognizable epitopes. However, among the various modified proteins, LDL exhibited the highest binding activity for IgG present in the group of children. This was associated with an enhanced propensity of LDL isolated from children to undergo in vitro oxidation, despite normal levels of the endogenous antioxidant alpha-tocopherol. These findings indicate that circulating antibodies recognizing proteins modified with end-products of lipid peroxidation (including LDL) are present in healthy cardiovascular risk-free children. The possibility that LDL oxidation occurs in vivo already in childhood and may act as the real immunogen is an attractive but still unproven hypothesis.

Adolescent↗

[Prader-Willi syndrome].

Prader-Willi syndrome (PWS) is the most frequent cause of secondary obesity, characterized by neonatal hypotonia, dysmorphic facies, acromicria, hypogonadism, stunted growth, obesity, behavioural disturbances and cognitive impairment. Clinical diagnosis is confirmed by alteration of imprinted genes on the proximal long arm of chromosome 15 (15q11-13) for deletion, translocation, uniparental disomy for maternal chromosome 15 or imprinting center defect. Methylation test is the most reliable test for diagnosis. This issue explains diagnostic tests, clinical, metabolic, endocrinological features, and the most frequent complications observed in this syndrome. Precocious diagnosis and multidisciplinary approach allow in these patients to prevent the severe obesity and linked complications.

Diagnosis, Differential↗

Oral health in children and adolescents with IDDM--a review.

Children with insulin-dependent diabetes mellitus have a lower salivary flow rate, pH and buffer capacity, but a higher glucose content and peroxidase, IgA, magnesium and calcium concentration, in comparison with healthy children. Nevertheless the incidence of caries is lower than normal in diabetic children with good metabolic control. Periodontal disease usually starts at puberty as mild gingivitis with bleeding and gingival recession, and it may develop into severe periodontitis, especially in children with poor control of diabetes. Microangiopathy, impaired immune response, different bacterial microflora and collagen metabolism are involved in the pathogenesis of diabetic periodontal disease. The gingival flora is mostly composed of Gram-negative, anaerobic bacteria, while collagen has a lower solubility and is atrophic and inadequate to support the occlusion forces. For these reasons, prevention of periodontitis is important in diabetic children; they should receive oral hygiene instruction and visit a dentist at least twice a year.

Adolescent↗

Insulin pulsatility in obese and normal prepubertal children.

OBJECTIVE: To assess whether in prepubertal children insulin secretion is pulsatile as in adults and to study the influence of body weight on the pattern of insulin secretion. DESIGN AND PATIENTS: Insulin profiles were obtained by 4-min sampling for 2 h, starting at 08.00 a.m. after an overnight fast in 10 prepubertal obese children (BMI-SDS 4.9 +/- 1.6) and in 6 healthy age-matched controls. Five of the obese children were also studied after weight reduction (Delta BMI-SDS 1.6 +/- 0.4). The data have been analyzed by the Pulsar program. RESULTS: Obese children had higher mean insulin levels, insulin secretory areas under the curve above 0 (AUC0), and AUC above baseline (AUCb), with more frequent peaks of larger amplitude and duration compared to controls. Following weight reduction there was a normalization of AUC0 and mean insulin levels while AUCb, peak frequency, amplitude and duration did not change significantly. Correlation analysis revealed that BMI-SDS was strictly related to the parameters of pulsatile insulin secretion such as AUC0, AUCb, mean insulin level, peak amplitude and peak frequency. CONCLUSIONS: Insulin secretion in children is pulsatile and its secretory pattern is influenced by body weight.

Adult↗

Neonatal and maternal levels of lipid-soluble antioxidants.

Lipid peroxidation plays an important role in the pathogenesis of several neonatal complications. To improve the knowledge on the antioxidant lipid-soluble defenses in neonatal age, we investigated a group of healthy full-term infants and their mothers measuring by high-pressure liquid chromatography the levels of vitamin E and carotenoids. Our data demonstrate that neonatal levels of lipid-soluble anti-oxidants are lower than the maternal ones. Moreover we show that neonatal Vitamin E and carotenoid concentrations are respectively unrelated and strictly related to maternal levels of the same lipid-soluble anti-oxidants.

Adult↗

Growth hormone treatment in short normal children.

The efficacy of growth hormone (GH) therapy in short normal children (i.e. children without classical growth hormone deficiency [GHD]) is still under debate. This paper presents the preliminary data of a retrospective Italian multicenter study on children treated with GH until adult height was reached. Final adult height (FAH), however, is not significantly different from the predicted adult height (PAH) calculated at the beginning of treatment. This result is in agreement with those reported in the majority of other similar international surveys. In conclusion, GH should be administered to short normal children only within the framework of well designed prospective experimental studies, which should consider several auxological, clinical and biochemical parameters capable of influencing the therapeutic results.

Adolescent↗

Changes in dopaminergic control of circulating melanocyte-stimulating hormone-related peptides at puberty.

Desacetyl alpha-melanocyte-stimulating hormone (MSH) (ACTH 1-13) is the main form of immunoreactive alpha-MSH circulating in human plasma. This study evaluates the possibility that a dopaminergic inhibitory mechanism could be operative during human development. Thus, alpha-MSH and ACTH 1-13 plasma levels were measured after dopaminergic blockade (domperidone (0.3 mg/kg body weight, maximum 10 mg, p.o.) in 13 prepubertal (aged 4.5-12.3 y) and 12 pubertal (aged 10.2-16.9 y) children. Both peptides were measured by RIA after plasma extraction on Sep-pak C-18 cartridges and reverse phase HPLC. The chromatographic profile of alpha-MSH immunoreactivity falls into two main peaks, corresponding to the retention time of alpha-MSH and ACTH 1-13. Moreover, in prepubertal children domperidone induced a significant increase of alpha-MSH from 1.7 (median) to 5.0 pmol/L, whereas no changes in alpha-MSH plasma levels were found in pubertal subjects (from 5.0 to 4.1 pmol/L). Similarly, ACTH 1-13 plasma levels significantly increased from 3.0 to 19.8 pmol/L in prepubertal children remaining stable in pubertal ones (from 7.8 to 4.6 pmol/L). Moreover, a significant negative correlation was found between basal DHEA-S levels and the plasma alpha-MSH increase after domperidone. These data demonstrate that: 1) ACTH 1-13 is the main form of immunoreactive alpha-MSH in prepubertal life and 2) the dopaminergic inhibition of both ACTH 1-13 and alpha-MSH plasma levels is apparent only in prepubertal subjects.

Adolescent↗

Growth hormone response to growth hormone-releasing hormone (GHRH), insulin, clonidine and arginine after GHRH pretreatment in obese children: evidence of somatostatin increase?

To clarify the possible neuroendocrine mechanisms underlying the impairment in growth hormone (GH) secretion present in obesity, the GH response to GH-releasing hormone (GHRH, N = 6), insulin hypoglycemia (N = 6), clonidine (N = 7) and arginine (N = 8) after GHRH pretreatment (1 microgram/kg iv 2 h before the tests) was evaluated in 27 obese peripubertal children and in a group of normal-weight short-normal children (N = 26). Growth hormone-releasing hormone pretreatment and all further stimuli elicited a statistically significant GH response in both obese and short-normal children; in the latter group arginine did not induce a significant GH response. No differences were found among the GH responses after the second stimuli in obese children, while in short-normal children the arginine peak and area values were lower than after GHRH and clonidine. Comparison between the two groups showed similar baseline but higher stimulated GH levels in normal-weight children after all tests except arginine, after which no difference was present. In conclusion, the neuroregulation of GH release seems to be similar qualitatively in normal-weight and obese youngsters; the different behavior observed after arginine, which is supposed to act through somatostatin inhibition, might be due to a chronic increase in somatostatinergic tone responsible for the lower stimulated GH levels in obesity.

Adolescent↗

Dynamics of 24-hour pulsatile cortisol, 17-hydroxyprogesterone, and androstenedione release in prepubertal patients with nonclassic 21-hydroxylase deficiency and normal prepubertal children.

To assess whether the quantitative and qualitative aspects of cortisol, 17-hydroxyprogesterone (17-OHP), and androstenedione (D4A) secretion in patients with nonclassic congenital adrenal hyperplasia (NCCAH) differ from those in normal children, 24-hour serum concentrations of these steroids were measured in five prepubertal patients with NCCAH and five normal prepubertal children. Adrenal steroid profiles obtained by 30-minute sampling were analyzed by the Pulsar program. In comparison to normal children, the 24-hour quantitative parameters of 17-OHP and D4A secretion were significantly greater in NCCAH patients, but serum cortisol concentrations were similar in the two groups. When daytime and nighttime hormone releases were separately analyzed, a significant nocturnal elevation of the cortisol area under the curve above zero level (AUCo) and 12-hour mean and 17-OHP AUCo, AUC above baseline, mean peak height, amplitude, area, and 12-hour mean was detected in normal subjects only. Conversely, NCCAH patients exhibited an increased frequency and number of 17-OHP secretory peaks at night together with a reduction of the interpeak interval. No significant day/night differences in D4A concentrations were detected either in normals or in the patients. In conclusion, the results of the present study indicate that patients with NCCAH have a distinct pattern of adrenal steroid secretion characterized by a high-frequency 17-OHP release accompanied by a relative nocturnal cortisol deficiency.

17-alpha-Hydroxyprogesterone↗

Absent B-endorphin response to clonidine in obese children.

Plasma B-Endorphin (B-EP), Growth Hormone (GH) and cortisol response to 100 mcg/m2 b.s., i.v. clonidine (an alpha 2-adrenergic agonist) were evaluated in 17 normal weight children (8 prepubertal and 9 pubertal) and in 15 children with simple exogenous obesity (7 prepubertal and 8 pubertal, weight excess ranging from 29% to 97%). All the hormones were measured by radioimmunoassay either directly in the plasma (GH and cortisol) or after extraction and chromatography (B-EP). Obese prepubertal and pubertal children showed basal B-EP levels significantly higher than in controls and no differences were found in GH and cortisol levels. While in controls clonidine stimulated a significant release of plasma GH and B-EP in obese patients, irrespective of pubertal development, no changes were found. Cortisol levels decreased in both groups. These data suggest an impaired adrenergic control of GH and B-EP secretion in children with simple exogenous obesity.

Child↗

Impaired beta-endorphin response to human corticotropin-releasing hormone in obese children.

In order to evaluate the secretion of beta-endorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 microgram/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 +/- 1.8 vs 6.0 +/- 0.6 pmol/l; mean +/- SEM). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.

Adolescent↗

Naloxone-induced luteinizing hormone secretion in normal, precocious, and delayed puberty.

The aim of the present study was to evaluate the activity of opiate receptors involved in the control of LH secretion during pubertal development, as determined by the LH response to naloxone. Normal children (n = 28) of both sexes, subdivided according to breast (girls) or testicular (boys) development, and patients with idiopathic precocious puberty (n = 7), delayed puberty (n = 8), or hypergonadotropic hypogonadism (n = 4) were studied. Plasma LH levels were measured after the administration of naloxone (NLX; 0.08 mg/kg BW, iv), GnRH (50 micrograms, iv) or placebo. In healthy subjects, NLX significantly increased plasma LH levels only in girls and boys at the most advanced stage of gonadal maturation. NLX was ineffective in prepubertal and early pubertal children, and it did not significantly alter LH levels in children with delayed puberty or hypogonadism or in most of the children with precocious puberty. GnRH injection consistently increased plasma LH levels in healthy subjects as well as in the children with pubertal disturbances. These results indicate that the LH response to NLX occurs only at the most advanced stages of pubertal maturation when normal or precocious and is absent in early puberty or in children with pubertal disturbances. Furthermore, the results suggest that opioid regulation of LH secretion in humans changes during puberty, reaching an adult-like functional state with maturation of the hypothalamus-pituitary-gonadal axis.

Adolescent↗

Endogenous opioid inhibitory tone on LH secretion in normal puberty and in several pubertal disturbances.

To further evaluate the role exerted by endogenous opioids on LH secretion a naloxone challenge (0.08 mg/Kg b.w. i.v.) was performed in 23 healthy children at different stages of puberty, in 5 adolescents in different period of menstrual cycle, in 3 case of idiopathic precocious puberty (PP), in 7 cases of delayed puberty (DP), in 4 females affected by hypogonadotropic hypogonadism (HH) and in 6 patients affected by polycystic ovary disease (PCOD). Naloxone does not induce any significant change on LH plasma levels in prepubertal healthy children and in all the cases of PP and DP. Similarly there was no LH response in healthy adolescents neither in HH nor in PCOD, the response to naloxone appears only in preovulatory and luteal phases. These data indicate that the central opioid system regulating LH secretion in humans is active only at more advanced stages of puberty and it does not seem to play a role in the beginning of sexual maturation. Moreover gonadal steroids seem to play a fundamental modulatory role on opioid-controlled LH secretion.

Adolescent↗

Is fasting insulin associated with blood pressure in obese children?

PRIMARY OBJECTIVE: We tested whether fasting insulin levels are associated with blood pressure in a large sample of obese children. SUBJECTS AND METHODS: Three hundred and fifty obese children (F:M ratio = 1.03) of 10.1 +/- 2.7 y of age (mean +/- SD) were consecutively enrolled at an Outpatient Paediatric Clinic. Obesity was diagnosed on the basis of a relative weight for age > 120% and hypertension on the basis of a systolic (SBP) or diastolic (DBP) blood pressure > 95th percentile for age after adjustment for height (Ht). MAIN OUTCOME AND RESULTS: Insulin was significantly higher in hypertensive (n = 202, 58%) than normotensive (n = 148, 42%) children (16 vs 14 microU mL(-1), geometric mean, p < 0.01, ANOVA) but the difference was not clinically relevant. Moreover, (log-transformed) insulin explained only 7 and 4% of SBP and DBP variance, respectively (p < 0.0001 for both) and this contribution disappeared after the confounding effects of age, weight or other anthropometric dimensions were taken into account (p = ns, ANCOVA). CONCLUSIONS: This study does not support the hypothesis of a clinically relevant association between fasting insulin and blood pressure in obese children.

Aging↗

Sensitivity and specificity of body mass index and skinfold thicknesses in detecting excess adiposity in children aged 8-12 years.

PRIMARY OBJECTIVE: The study aimed to evaluate the sensitivity (SN) and specificity (SP) of body mass index (BMI) and skinfold thicknesses in detecting excess adiposity in children. RESEARCH DESIGN: Cross-sectional. MATERIALS AND METHODS: 986 children (500 females and 486 males) aged 10 +/- 1 years (mean +/- SD; range: 8-12 years) were studied. All underwent anthropometric measurements and bioelectrical impedance analysis (BIA). Dual-energy X-ray absorptiometry (DXA) was performed in 52 children to develop a population-specific algorithm for the assessment of fat-free mass (FFM) from BIA. The algorithm was applied to the remaining 934 children to estimate their FFM. Fat mass (FM) was obtained by subtracting FFM from weight (Wt). Values of FM:Wt were transformed in Z-scores and converted into 19 percentile categories (from 5 to 95 in steps of 5). The same procedure was performed with BMI and the log-transformed sum of four skinfold thicknesses (triceps, biceps, subscapular and suprailiac; lt-4SF). Excess adiposity was defined as a level of FM:Wt greater than the internally derived 85th percentile. SN and SP of each internally derived percentile of BMI and lt-4SF in detecting excess adiposity were calculated. RESULTS: In the pooled sample (n = 934), SN and SP were 0.39 and 0.99 for the 95th percentile of BMI, 0.65 and 0.95 for the 85th percentile of BMI, and 0.75 and 0.94 for the 85th percentile of lt-4SF. CONCLUSIONS: BMI percentiles employed in the present study have a high SP but a low SN in detecting excess adiposity in 8-12-year-old children. The use of the sum of four skinfolds has the potential to increase the SN of a screening programme for excess adiposity in children of this age.

Absorptiometry, Photon↗

Relationship between body mass index and insulin measured during oral glucose tolerance testing in severely obese children and adolescents.

PRIMARY OBJECTIVE: The study evaluated the accuracy of body mass index (BMI) in detecting hyperinsulinaemia during oral glucose tolerance testing (OGTT) in severely obese children. RESEARCH DESIGN: A cross-sectional study was carried out. MATERIALS AND METHODS: A total of 118 obese children and adolescents (49 females and 69 males) aged 6-19 years were consecutively studied at an outpatient paediatric clinic. Hyperinsulinaemia was defined as a value of log-transformed fasting insulin >/= 80th percentile and OGTT hyperinsulinaemia as a value of the log-transformed area under the curve (AUC) of insulin >/= 80th percentile. The study hypothesis was tested using a logistic regression model with hyperinsulinaemia as the outcome variable and the z-score of BMI corrected for age (z-BMI(age)) as the predictor variable. Receiver-operator characteristic (ROC) curves were used to evaluate accuracy. RESULTS: The mean (SD) BMI for age of the children was 28.6 (4.0) kg m(-2), corresponding to 2.2 (0.5) standard deviation scores. The odds ratio (OR) of OGTT hyperinsulinaemia was 2.0 (95% CI 1.2-3.3; p = 0.007) for each unit increase of z-BMI(age) and the corresponding ROC-AUC was 0.74 (95% CI 0.61-0.86; p = 0.0001). In comparison, the OR of fasting hyperinsulinaemia was 1.1 (95% CI 0.7-1.7; p = 0.716) for each unit increase of z-BMI(age) and the corresponding ROC-AUC was 0.49 (95% CI 0.35-0.62; p = 0.863). CONCLUSION: BMI is reasonably accurate in detecting OGTT hyperinsulinaemia in severely obese children.

Adolescent↗