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Biomedical subjects

G Radetti

Publications and source records attributed to G Radetti.

At least 19 recordsLinked to original sources

Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake.

CONTEXT: Ghrelin, a natural GH secretagogue, is mainly characterized by nonendocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated with insulin secretion, enhanced in anorexia, and reduced in obesity. Ghrelin levels in newborns were shown to be similar to those found in children and adults without any gender-related difference. OBJECTIVE: The aim of this study was to evaluate ghrelin variations in preterm newborns as a function of fasting and feeding. METHODS: To this end, in 31 preterm neonates (13 males and 18 females) categorized as appropriate for gestational age, total ghrelin levels were measured in cord blood and then on the fourth day of life before and after meals. RESULTS: Ghrelin levels in cord blood [(median 25th-75th centile) 184; 122-275 pg/ml] were higher (P < 0.006) than levels measured in the mothers at delivery (167.0; 89-190 pg/ml). In newborns on the fourth day of life, ghrelin levels in fasting conditions (451; 348-649 pg/ml) were higher (P < 0.0004) than those in cord blood. The meal did not at all modify ghrelin levels (476; 302-775 pg/ml), which were unchanged, compared with those in fasting condition. Total ghrelin levels in cord blood were not associated with weight and length; conversely, on the fourth day of life ghrelin levels in newborns were negatively correlated to birth weight as well as the present weight (P = 0.05, r = -0.4). Ghrelin levels were independent of gender, type of delivery, and the kind of feeding regimen. CONCLUSIONS: The secretion of total ghrelin increases from delivery to the fourth day of life when it is refractory to the inhibitory effect of food intake, but it is negatively correlated to body weight.

Body Height↗

Menstrual disorders in adolescence.

Altered frequency of the menstrual cycle accompanied by pain are manifestations of functional anomalies of the female reproductive system. These symptoms require prompt and accurate diagnosis and therapy to prevent a chronic condition that can seriously disturb the adolescent's psychic well being. The most common anomalies of the menstrual cycle and the causes of altered cycle frequency are outlined, as are useful criteria for diagnosing premenstrual syndrome dysmenorrhea and for distinguishing the causes and alterations in frequency and amount of menstrual discharge from other disturbances, including amenorrhea and abnormal uterine bleeding. The treatment of dysmenorrhea and quantitative alterations of the menstrual cycle is the focus of this article.

Adolescent↗

Geometry and bone density.

Bone development is a key process in the growing child. It is, therefore, of paramount importance to survey this process, which is characterized by increasing length and size of the bone together with its progressive mineralization. The bone status can be evaluated by different techniques, each of them having its pros and cons. Furthermore, it should be underlined that the results of bone assessment depend not only from the employed technique but also from the auxological characteristics of the subjects. It is, therefore, the aim of this review to examine the characteristics of the various methods of bone evaluation, such as dual energy X-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), ultrasound and metacarpal index and to explain how changes in bone structure and geometry may influence the results.

Absorptiometry, Photon↗

From bone biology to bone analysis.

Bone development is one of the key processes characterizing childhood and adolescence. Understanding this process is not only important for physicians treating pediatric bone disorders, but also for clinicians and researchers dealing with postmenopausal and senile osteoporosis. Bone densitometry has great potential to enhance our understanding of bone development. The usefulness of densitometry in children and adolescents would be increased if the physiological mechanisms and structural features of bone were given more consideration in the design and interpretation of densitometric studies. This review gives an overview on the most relevant techniques of quantitative noninvasive bone analysis. Furthermore it describes the relationship between bone biology, selected surrogates describing the biological processes and the possibilities of measuring these surrogates specifically and precisely by the different devices. The overall recommendation for researchers in this field is to describe firstly the biological process to be analyzed (bone growth in length, remodeling or modeling, or all together), secondly the bone parameter which describes this process, and thirdly the reason for selecting a special device.

Absorptiometry, Photon↗

Growth hormone (GH) isoforms following acute 22-kDa GH injection: is it useful to detect GH abuse?

The aim of the study was to investigate the influence of an acute administration of 22-kDa hGH (22-kDa GH) on 22-kDa GH and 20-kDa GH serum levels, biological activity of GH (Nb2-GH) and on 22-kDa/20-kDa GH ratio, in order to verify whether the assessment of the GH isoforms could be a potential tool for diagnosing GH abuse. Twenty-eight children (21 M, 7 F), age 10.4 +/- 0.8 y, affected by idiopathic isolated GH deficiency and 10 children (8 M, 2 F), age 9.2 +/- 2.3 y affected by constitutional growth delay, were evaluated. After an overnight fast, a basal blood sample was obtained between 8 a.m. and 9 a.m. and a dose of 22-kDa GH was then administered subcutaneously (0.1 U/Kg). Blood was drawn after 2, 4 and 6 h, for the evaluation of 22-kDa GH, Nb2-GH and 20-kDa GH serum levels. Similar results were obtained in patients and controls: a significant rise, although of variable amplitude, of 22-kDa GH and Nb2-GH was found (p < 0.001) and the maximum peak was detected after 4 h in the majority of subjects. No acute changes in 20-kDa GH serum levels were observed. The 22-kDa/20-kDa GH ratio increased progressively, due to the rising levels of 22-kDa GH. A positive correlation was seen between 22-kDa GH and Nb2-GH levels at baseline and at 2, 4 and 6 h (p < 0.014, r = 0.99). Since in normal subjects the ratio of endogenous 22-kDa GH and 20-kDa GH is constant, an altered ratio of 22-kDa/20-kDa GH is highly suggestive of GH abuse. The short period of time available for the evaluation however (within 3 h from GH injection), severely limits this investigational tool in athletes.

Analysis of Variance↗

Serum osteoprotegerin and receptor activator of nuclear factors kB (RANKL) concentrations in normal children and in children with pubertal precocity, Turner's syndrome and rheumatoid arthritis.

BACKGROUND: Osteoprotegerin (OPG) is a secreted member of the TNF receptor superfamily. OPG is made by osteoblastic cells and is expressed in a wide variety of cell and tissue types. It acts as a decoy receptor by binding the receptor activator of nuclear factors kB (RANKL) and preventing RANKL-induced osteoclast formation and differentiation. Numerous cytokines and hormones (TGF-beta, PTH, vitamin D, glucocorticoids and oestrogens) exert their effects on osteoclastogenesis by regulating the production of OPG. PATIENTS AND METHODS: In the present study we compared serum OPG and RANKL concentrations in a group of normal children (1-14 years old) with those of pair-aged children affected by different diseases [Turner's syndrome (TS), early/precocious puberty (PP) and rheumatoid arthritis (RA)]. OPG and RANKL concentrations were measured by an enzyme immunoassay method using a commercial kit. RESULTS: Mean (+/- SD) OPG level in normal children was 4.05 +/- 1.63 pmol/l with no difference between males and females. OPG values in children 1-4 years old (5.87 +/- 2.22 pmol/l) were significantly higher than in children 4-14 years old (3.55 +/- 0.97 pmol/l). OPG levels in children with RA were significantly higher than in controls (6.33 +/- 2.57 pmol/l vs. 4.05 +/- 1.63 pmol/l, P < 0.01); patients with TS or PP had OPG levels superimposable to those of controls (2.61 +/- 0.67 pmol/l and 3.99 +/- 0.85 pmol/l, respectively), but in TS OPG levels were significantly lower than in age-matched females. Mean RANKL concentration in normal subjects was 0.81 +/- 1.55 pmol/l; there was a slight decline in RANKL levels with age. RANKL concentrations in subjects with TS, PP, RA and controls did not differ significantly, and did not differ from those published in adult normal subjects. CONCLUSIONS: It appears from our data that OPG serum levels in healthy children aged > 4 years are similar to those present in young adult men, with higher levels in the first 4 years of life. Although the meaning of the alterations of OPG levels observed in pathological conditions is still obscure, they appear potentially interesting in view of a key role played by this protein in bone homeostasis.

Aging↗

Circulating ghrelin levels in the newborn are positively associated with gestational age.

OBJECTIVE: Ghrelin exerts potent GH-releasing activity and stimulates food intake. Circulating ghrelin levels are increased in anorexia and cachexia, reduced in obesity and restored by weight recovery. Newborns are characterized by GH hypersecretion associated with low IGF-I levels reflecting peripheral GH resistance. STUDY DESIGN: The aim of our study was to measure cord ghrelin levels in 117 newborns appropriate for gestational age, born either at term or preterm. RESULTS: Ghrelin levels in cord blood (median; 25th-75th centile: 327.6; 206.0-413.0 pg/ml) were higher (P < 0.0001) than those in maternal blood at delivery (133.0; 89.0-173.7 pg/ml), without gender differences. A positive correlation between ghrelin levels in mothers and newborns (r = 0.26, P < 0.01) was observed. Ghrelin levels in newborns born at term (399.0; 229.0-438.0 pg/ml) were remarkably higher (P < 0.0001) than those in born preterm (208.0; 144.5-278.9 pg/ml). A clear positive association was present between ghrelin levels and gestational age. No association between ghrelin and GH, IGF-I, insulin, glucose and leptin levels were found. CONCLUSIONS: Cord ghrelin levels show clear gestational age-related dependency. The lack of any direct relationship between ghrelin and anthropometric or biochemical parameters in adequate for gestational age newborns does not support the hypothesis that ghrelin has major role in foetal GH secretion and growth.

Adult↗

Diagnostic effectiveness of simultaneous thyroxine and thyroid-stimulating hormone screening measurements. Thirteen years' experience in the Northeast Italian Screening Programme.

OBJECTIVES: To evaluate the effectiveness of thyroid-stimulating hormone (TSH) and thyroxine (T4) measurements at neonatal screening for congenital hypothyroidism, we compared our false-negative results with those we would have obtained if we had used TSH screening alone. SUBJECTS AND METHODS: Between January 1989 and December 2001 745,258 newborns were screened (98.3% of total born) for congenital hypothyroidism in northeast Italy. T4 and TSH were measured simultaneously on blood spots collected after birth. Between 1989 and 1998, semi-quantitative total T4 (tT4) and TSH concentrations were measured by radiolabelled immunological assay and, from 1999 to 2001, using time-resolved fluorometer Delfia instruments (EG&G Wallac Oy, Finland) and fluoroimmunometric assay (Delfia neonatal hTSH and T4 kits). RESULTS: Ten neonates were missed by our screening programme (normal tT4 and TSH) and classified as false negatives; these infants were diagnosed later in life with central hypothyroidism. If we had measured TSH alone in our screening programme, we would have missed an additional 21 patients with low tT4 and normal TSH; of these, four were affected by central hypothyroidism and 17 were diagnosed within the second month of life as affected by primary hypothyroidism with delayed TSH rise. CONCLUSIONS: Simultaneous T4 and TSH measurements at neonatal screening can miss patients affected by central hypothyroidism. However, this screening procedure allows identification of cases of central hypothyroidism with low T4 values and those neonates affected by primary hypothyroidism with delayed TSH rise who we would have missed by using the TSH measure alone.

Birth Weight↗

Hyperparathyroidism.

Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (>12 <13.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (>13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca >13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.

Calcium↗

Circulating ghrelin levels in newborns are not associated to gender, body weight and hormonal parameters but depend on the type of delivery.

Ghrelin, a new gastric-derived hormone, probably plays a major role in managing energy balance and the neuroendocrine response to starvation. Information about the age-related variation in ghrelin secretion is scanty. We measured circulating ghrelin levels in 93 full term newborns adequate for gestational age, in 39 normal children and in 19 lean healthy adults. Our findings demonstrate that ghrelin levels are independent of age and gender from birth to adulthood. Interestingly, ghrelin secretion at birth is not associated to body weight and hormonal parameters such as GH, insulin and leptin levels. On the other hand, ghrelin levels seem dependent on the type of delivery, being lower in newborns after caesarean section with respect to those after normal delivery.

Adult↗

Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases.

Triggering of the Fas receptor induces T cell apoptosis and is involved in shutting-off the immune response. Inherited defects impairing Fas function cause the autoimmune lymphoproliferative syndrome, and may play a role in other autoimmune diseases. The aim of this work was to analyse the Fas function in paediatric patients with thyroid autoimmunities. We found that T cells from 24/28 patients with Graves' disease (GD) and 12/35 patients with Hashimoto's thyroiditis (HT) displayed defective Fas function. In HT, the defect was more frequent in patients requiring replacement therapy (11/20) than in those not requiring (1/15); moreover, in untreated HT the highest defect was displayed by patients with the highest levels of autoantibodies. Fas was always expressed at normal levels and no Fas mutations were detected. Analysis of the healthy parents of seven Fas-resistant patients showed that several of them were Fas-resistant, which suggests a genetic component. Fusion of Fas-resistant T cells with the Fas-sensitive HUT78 T cell line generated Fas-resistant hybrid cells, which suggests the presence of molecules exerting a dominant negative effect on Fas function. Analysis of Fas-induced activation of caspase-8 and -9 showed decreased activity of both caspases in HT, whereas activity of caspase-9 was increased and that of caspase-8 was decreased in GD. These data suggest that heterogeneous inherited defects impairing Fas function favour the development of thyroid autoimmunities.

Adolescent↗

Chronic treatment with inhaled corticosteroids does not modify leptin serum levels.

AIM: To assess the influence of a short-term treatment with low-dose inhaled corticosteroids on leptin serum levels. PATIENTS: 14 prepubertal children, mean age 5.1 +/- 2.4 years, treated with inhaled fluticasone propionate 100 microg b.d. and 16 prepubertal children, mean age 8.3 +/- 1.3 years, treated with inhaled budesonide 200 microg b.d. METHODS: All children underwent a CRH test with evaluation of leptin, cortisol and ACTH levels before and after 3 months of treatment. RESULTS: Fluticasone group: no difference was found between basal cortisol level, delta and area under the curve (AUC) before and after treatment, though cortisol peak was significantly lower following treatment. Basal ACTH level, peak and AUC were significantly lower after treatment. Budesonide group: no statistically significant difference in any of the parameters regarding cortisol and ACTH secretion was observed before and after treatment. No significant changes in basal serum leptin levels and AUC were observed following treatment in both groups. Furthermore no significant variation in leptin level was observed during both CRH tests. DISCUSSION: Leptin secretion does not seem to be affected by low-dose inhaled corticosteroids; moreover leptin does not seem to be involved in the response of the HPA axis to stress.

Administration, Inhalation↗

Systemic activity of inhaled corticosteroid treatment in asthmatic children: corticotrophin releasing hormone test.

BACKGROUND: A study was undertaken to assess the function of the hypothalamic-pituitary-adrenal axis (HPA) in a group of asthmatic children before and after treatment with inhaled corticosteroids. METHODS: Thirty prepubertal patients of mean (SD) age 6.7 (1.8) years were treated with inhaled corticosteroids. All children underwent a corticotrophin releasing hormone (CRH) test with evaluation of serum cortisol and adrenocorticotrophin hormone (ACTH) levels before and after 3 months of treatment. Twenty four hour urine samples were also collected to measure free cortisol (UFC) excretion. RESULTS: Subjects showed no difference between basal serum cortisol levels (mean change -18; 95% CI -41 to 5; p=0.118) and delta (peak minus basal) levels (mean change -13; 95% CI -38 to 12; p=0.308) before and after treatment, whereas the peak cortisol level (mean change -31; 95% CI -55 to -7; p=0.013) and area under the curve (AUC) (mean change -175; 95% CI -288 to -63; p=0.003) after CRH were significantly lower following treatment. Basal, peak and AUC ACTH were significantly lower after treatment (p<0.05, p=0.004 and p=0.003, respectively), while delta ACTH was similar before and after treatment ((mean change -12; 95% CI - 31 to -7; p=0.199). No significant reduction in 24 hour UFC was observed after the treatment period (before 14.9 (7.1), after 15.0 (11.6); mean change 0.1, 95% CI -5.2 to 5.4; p=0.967). No correlation was found between UFC and any of the parameters of cortisol excretion following the CRH test, either before or after treatment. CONCLUSIONS: These data suggest that, at the dosage and for the treatment period used, inhaled steroids do not seem to suppress the HPA axis in the majority of patients. The CRH test may be more sensitive than 24 hour UFC and morning plasma cortisol levels in evaluating systemic activity of inhaled corticosteroid treatment.

Administration, Inhalation↗

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome: time to review diagnostic criteria?

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive syndrome defined by two of the following conditions: chronic mucocutaneous candidiasis, hypoparathyroidism, or Addison's disease. Other autoimmune conditions may be associated, such as hypothyroidism, hypogonadism, insulin-dependent diabetes mellitus, chronic active hepatitis, pernicious anemia, vitiligo, alopecia, biliary cirrhosis, and ectodermal dysplasia. APECED is caused by mutations in the autoimmune regulator gene, mapping to 21q22.3. We report on three patients whose clinical and molecular features challenge the currently used diagnostic criteria for APECED. AR presented at 15 yr of age with a history of recurrent infections and mucocutaneous candidiasis. He is now 21 yr old, and no other signs or symptoms of APECED have appeared to date. DR presented at 7 yr of age with hypocalcemia and a prolonged Q-T interval on the electrocardiogram. He also had minor facial dysmorphisms and mild mental retardation. Serum calcium levels were low, PTH levels were undetectable, and hypoparathyroidism was therefore diagnosed. All other biochemical, immunological, and endocrinological tests were normal. DR is now 8 yr old with no other signs or symptoms of APECED. ST presented at 14 yr of age for alopecia aerata and pitted nail dystrophy and goiter. Thyroid function was normal in the presence of thyroid-specific antibodies. No other signs or symptoms of APECED have appeared to date. Genetic analysis revealed a typical mutation (R257X) on a single allele in both AP and DR; in ST, heterozygosity for a novel mutation (V484M) involving one of the zinc fingers of the plant homeodomain of the protein was found. The finding of a typical APECED mutation in two patients presenting with one isolated major clinical APECED feature and of a novel mutation in a patient presenting with atypical features of APECED onset suggests that the time might have come for updating the diagnostic criteria of this syndrome.

Adolescent↗

Serum leptin levels are not influenced by arginine and insulin infusion and by acute changes of GH.

The aim of this study was to evaluate the relationship between GH and leptin in a group of short children and adolescents. Leptin and GH serum levels were measured before and during pharmacological stimulation tests (arginine and insulin) in a group of 45 children (30 male, 15 female), mean age 8.6+/-3.9 yr, affected by idiopathic isolated GH deficiency (GHD), and in a group of 27 children (15 male, 12 female), age 10.9+/-3.3 yr, with constitutional growth delay. Results showed that basal and peak leptin levels as well as the AUC were significantly higher in GHD patients compared to controls (p<0.05) and correlated with BMI SDS (p<0.0001) in GHD patients. No change in leptin serum levels was observed during either stimulation test. No correlation was found, however, between basal leptin serum levels and basal, peak and the AUC of GH during the tests. Moreover, no correlation was found between the acute changes of serum GH concentration during both stimulation tests and leptin serum levels. The results suggest that leptin and GH secretion is not correlated and that leptin serum levels mainly reflect the amount of fat tissue, which is higher in GHD patients.

Arginine↗