The factor structure of the General Health Questionnaire (GHQ): a scaled version for general practice in Spain.

BACKGROUND: The 28-item version of the General Health Questionnaire (GHQ-28) developed by Goldberg and Hillier in 1979 is constructed on the basis of a principal components analysis of the GHQ-60. When used on a Spanish population, a translation of the GHQ-28 developed for an English population may lead to worse predictive values. METHODS: We used our Spanish sample to replicate the entire process of construction of the GHQ-28 administered in a primary-care setting. RESULTS: Two shorter versions were proposed: one with six scales and 30 items, and the other with four scales and 28 items. CONCLUSIONS: The resulting GHQ-28 was a successful adaptation for use on the Spanish sample. When compared with the original version, only 21 items were the same. Moreover, contrary to the English version, which groups sleep problems and anxiety in the same scale, a scale with items related exclusively to 'Sleep disturbances' was found.

The inverse association of salmonellosis in infancy with allergic rhinoconjunctivitis and asthma at school-age: a longitudinal study.

BACKGROUND: Respiratory allergies are inversely related to early acquisition of food-borne and fecal-oral infections, consumption of unpasteurized milk, early exposure to stables and high endotoxin concentrations in a farming environment. We tested therefore if infection by Salmonella in early life can protect from development of respiratory allergies later in life. METHODS: During 2003, we studied two groups of Sardinian children (age 6-18 years) who had been hospitalized before 4 years of age (during 1989-2001) with non-typhoid salmonellosis (n = 148) or acute enteritis of nonbacterial etiology (NB-enteritis) (n = 167). Allergic rhinoconjunctivitis (AR) and asthma were evaluated by telephonic interview with a ISAAC questionnaire; participants reporting AR and/or asthma were further examined through a complete diagnostic work-up to objectively confirm or exclude current disease. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the role of different types of enteritis on the risk of developing allergic rhinoconjunctivitis or asthma over time. RESULTS: Children who had been hospitalized with salmonellosis had a lower prevalence of allergic rhinoconjunctivitis (eight of 148, 5.4%vs 23 of 167, 13.8%; P = 0.019) or asthma (five of 148, 3.4% vs 21 of 167, 12.6%; P = 0.006) than those who had been hospitalized with NB-enteritis. The proportional hazard of salmonellosis for asthma was 0.23 (95% CI: 0.08-0.67; P < 0.01) and for allergic rhinoconjunctivitis was 0.40 (95% CI: 0.17-0.95; P = 0.04), after adjusting for confounders. DISCUSSION: The strength of the observed associations suggests that Salmonella may contribute to shape the natural history of respiratory allergies. However, further studies are needed to test in other settings the association observed in Sardinian children. We speculate that clinical or subclinical infection by Salmonella may contribute to the atopy protective influence of a traditional farming environment or of areas endemic for food-borne and fecal-oral infections. Food hygiene and prevention of salmonellosis must remain however a public health priority.

[Adolescent nutrition promotion: real and false problems]. / Promozione nutrizionale nell'adolescenza: veri e falsi problemi.

This study shows the relationship between BMI of 3000 adolescents and their perceived-weight status, and the strategies for weight loss. The finding indicate that substantial numbers of teenage females perceive themselves as overweight when BMI suggest they are not, while males have a reasonably accurate weight. Diet was the most frequently selected method for losing weight especially among females that wrongly perceive themselves overweight (O.R. = 5.54 I.C. 95% 4.28-7.19); while males were as likely to use diet as a strategy to lose weight only if they were really overweight (O.R. = 6.00; I.C. 95% 2.26-15.92). Exercise was selected as a method for losing weight by males independently to be overweight and by females only that perceive themselves overweight. The study shows that the young people of Sardinia need a health program to empower their knowledge the difference between health and aesthetic.

Growth and puberty in thalassemia major.

Present transfusional regimen protocols increase the life expectancy of patients with beta-thalassemia major, but cause a progressive iron overload that can be prevented or limited only by appropriate iron chelation. Siderosis is responsible for the clinical complications of the disease. Short stature and hypogonadism are extremely frequent in patients with thalassemia. Many factors are responsible for short stature in patients with thalassemia, the most important of which are dysfunction of the GH-IGF-I axis and desferoxamine (DFX)-induced bone dysplasia. Hypogonadism is the most frequent endocrine complication, mostly due to gonadotrophins deficiency secondary to iron overload. Sex steroid treatment for induction of puberty and/or maintenance of sexual characteristics is necessary. Both short stature and hypogonadism are present in a significant percentage of bone marrow transplanted patients with thalassemia. Factors responsible for short stature are previous iron overload, liver impairment, DFX treatment, and toxicity of chemotherapeutic agents. In some patients absence of pubertal development is due to gonadotropin insufficiency, probably secondary to previous iron overload; other patients exhibit hypergonadotrophic hypogonadism due to the toxic effect of chemotherapeutic agents on the gonads. Both groups need hormonal replacement therapy. These data support the need for vigilant follow-up of patients with thalassemia before and after transplantation, in order to treat endocrine dysfunctions at the appropriate age.

[Communication in adolescence: how to transmit prevention]. / La comunicazione nell'adolescente: comunicare la prevenzione.

We propose some considerations about adolescence, a topic that starts from the know-how of paediatricians and then includes other meanings. One of the most boisterous periods of our life and at the same time one of the most fascinating ones is adolescence. Complex changes characterize this age and these can lead to suffering and confusion even in normal conditions. The age of adolescence is at risk mostly for drug addiction, boredom, uneasiness. A safe basis and a good environment are the necessary conditions enabling adolescents to overcome this critical period for their mental space and to integrate into the adult world so as to reach a new stability. Nevertheless, young people have to confront quick changes, multiple subcultures, the transiency of the intergenerationsl conflict scheme. The dynamics of adolescents reflect some aspects of a society, in which the crisis of the limits and the extreme plurality are the factors that make the elaboration of coherent sense problematic. Today the young encounter many difficulties in relating to their parents due to the complexity of the familiar dynamics. During the long and tiring way to adulthood young people show a huge need of information and attention from the adults. Our duty as paediatricians is to detect, understand and pay attention to these messages. The method is to provide effective information to adolescents. In order to acquire this ability, we think that some conditions are fundamental: professional support and training, listening, networked services. In conclusion, adolescence needs a multiprofessional approach.

The growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, in short normal and obese children and in hypopituitary subjects.

Hexarelin (Hex) is a new synthetic hexapeptide with potent growth hormone (GH)-releasing activity in both animals and men. We evaluated the GH response to a maximal dose of Hex (2 micrograms/kg iv) and GH-releasing hormone (GHRH) (1-29, 1 microgram/kg iv) in 45 short normal children (24 males and 21 females, age 5.9-14 yr, 24 prepubertal and 21 in Tanner stage 2 or 3 of pubertal maturation), in 10 prepubertal obese children (7 males and 3 females, age 7.5-12 yr), and in 5 subjects with organic hypopituitarism (4 males and 1 female, age 8.4-21 yr). In 5 male subjects with constitutional growth delay (age 12.0-13.7 yr), the GH response to Hex was reevaluated 1 week after priming with testosterone enanthate (100 mg im). In all short normal children Hex caused a prompt and clear-cut increase of serum GH concentrations, with peaks occurring between 15-30 min from injection. The GH response to Hex was significantly higher than that observed after GHRH and was not different between males and females or between prepubertal and pubertal subjects. Priming with testosterone resulted in an increased GH response to Hex in all 5 subjects studied. No GH increase was observed in the hypopituitary subjects after either GHRH or Hex administration. In the obese children the GH responses to GHRH and to Hex were significantly lower than in the prepubertal children. Also, in the obese, the GH response to Hex was significantly higher than that observed after GHRH. In all short normal and obese children, but not in the hypopituitary subjects, Hex administration caused a slight but significant increase from baseline of both cortisol and PRL concentrations that returned to the baseline values within 2 h. None of the subjects experienced adverse side effects after Hex administration. This study shows that, in short normal and obese children, Hex is a potent GH-releasing stimulus with potential clinical utility.

Pulsatile secretion of thyrotropin in children.

To examine pulsatile TSH secretion, serum TSH was determined every 30 min for 24 h in eight short normal prepubertal children (3 males and 5 females, age 4.0-12.6 yr). All children exhibited a clear circadian pattern of TSH secretion. Pulsatile TSH secretion was identified in all subjects with a mean (+/- SD) TSH pulse frequency of 6.9 +/- 1.2 pulses/24 h. The group mean TSH pulse amplitude was 1.4 +/- 0.3 mU/L. Mean TSH concentration was higher during the night hours (2.1 +/- 0.8 mU/L) than during the day hours (1.3 +/- 0.4 mU/L, p < 0.005), and significantly more pulses were detected during the night (mean 4.7 +/- 1.4) than during the day hours (2.1 +/- 0.6, p < 0.005). On average, 62 to 68% of the peaks were detected in the night hours. Mean TSH pulse amplitude during the night hours was not significantly different from that during the day hours. Our findings indicate that, as previously shown in adults, a pulsatile pattern of TSH secretion is present in children. In our study group, the nocturnal TSH surge is associated with an increase in pulse frequency but not amplitude.

Growth hormone response to oral clonidine test in normal and short children.

We evaluated the growth hormone (GH) response to an acute clonidine test (0.15 mg/m2 po) in 30 normal prepubertal children (stature between the 3rd and 97th centile), in 29 short children (stature < 3rd centile for age) with height velocity (HV) > 10th centile and in 20 short children with HV < 10th centile. The three groups had comparable chronological ages. After clonidine administration mean peak GH levels were similar in the three groups (19.4 +/- 9.8, 17.7 +/- 8.8 and 14.6 +/- 8.9 micrograms/l, mean +/- SD, respectively). By choosing 10 micrograms/l as the limit for a normal response we found that stimulated GH levels had a sensitivity of 50% and a specificity of 83% in identifying children with suspected GHD (short children with subnormal HV). The diagnostic accuracy was almost superimposable, for cut-off values of 10 and 12 micrograms/l. Eight of the 10 children with subnormal HV and a GH peak < 10 micrograms/l had a GH peak < 10 micrograms/l also after a second stimulation test. Six of the 29 short children with normal HV had a GH peak < 10 micrograms/l. Only one of them had a GH peak < 10 micrograms/l after a second stimulation test. Five of the normal children had peak GH levels < 10 micrograms/l. These results indicate that HV is a useful variable to predict the GH response to an acute GH stimulus, since the great majority of children with a normal growth rate had a normal GH response to at least one stimulation test.

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children.

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an i.v. bolus injection of growth hormone releasing hormone 1-29, 1 microgram/kg, significantly enhanced the growth hormone response to the neuropeptide, confirming the results of previous studies which used the i.v. route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.

Secretion of growth hormone releasing hormone in obese children.

We have evaluated baseline and l-dopa-stimulated peripheral growth hormone releasing hormone (pGHRH) secretion in 6 obese pre-pubertal children and in 7 age-matched controls. Baseline pGHRH levels were no different between obese (36.6 +/- 9.8 pg/ml, mean +/- SE) and control children (40.6 +/- 10.1 pg/ml). Administration of l-dopa (500 mg po) caused a significant increase of pGHRH levels in both the obese (65.3 +/- 19.8 pg/ml, p less than 0.05) and the control children (84.1 +/- 10.0 pg/ml, p less than 0.003). Mean peak pGHRH levels after l-dopa were not significantly different between the two groups, whereas mean peak GH levels were significantly lower (p less than 0.05) in the obese (7.9 +/- 1.9 ng/ml) than in the control children (20.5 +/- 4.9 ng/ml). We conclude that despite reduced GH secretion, obese children have normal baseline and l-dopa stimulated pGHRH levels.

The effect of atenolol on the growth hormone response to growth hormone-releasing hormone in obese children.

We have evaluated the effect of acute administration of atenolol, a selective beta-adrenergic antagonist, on the GH response to GHRH in nine obese children and in eight age-matched controls. The GH response to GHRH (1-29, 1 microgram/kg iv), evaluated both as the GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with atenolol (50 or 100 mg orally in subjects with body weight less than or greater than 40 kg, respectively, administered 120 min before the GHRH injection) significantly increased the GH response to GHRH in the obese subjects, such that their mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were similar to those of the control children after GHRH. Also in control children, atenolol caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were significantly higher in the controls than in the obese children given the same treatment. These data show that inhibition of central beta-adrenergic receptors counteracts the blunted GH response to GHRH present in the obese children. In view of the alleged mechanism of action of beta-adrenergic blockade (inhibition of endogenous SRIH release), our data suggest that the somatostatinergic system is intact in obesity, and that the suppressed GH secretion is due to other causes.

The effect of short-term growth hormone or low-dose oxandrolone treatment in boys with constitutional growth delay.

We evaluated the effect of six-month treatment with growth hormone (GH) or low-dose oxandrolone in a group of boys with constitutional growth delay (CGD). Sixteen boys were randomly assigned to two treatment groups. Group 1 received GH (0.6 U/kg/week sc 5-6 times/week) and Group 2 received oxandrolone (0.07 mg/kg po). The boys of the two groups were closely matched for age (13.7 +/- 0.5 and 12.8 +/- 0.4 years) (mean +/- SE), chronologic age/bone age ratio (1.15 +/- 0.04 and 1.16 +/- 0.02), height standard deviation score (SDS; -2.7 +/- 0.4 and -2.5 +/- 0.3) and pretreatment height velocity (HV) (3.7 +/- 0.8 and 4.0 +/- 0.4 cm/year). Other known causes of short stature were excluded in all subjects, and none had taken long-term medication prior to the study. After 6 months of treatment HV increased to 7.5 +/- 0.4 and to 8.1 +/- 0.5 cm/year in group 1 and 2, respectively. Plasma IGF-I concentrations rose significantly after treatment in both groups. Predicted adult height was not significantly affected by either GH or oxandrolone treatment. We conclude that a short-term course of low-dose oxandrolone is as effective as GH to accelerate growth in boys with CGD. Low-dose oxandrolone represents an effective, cheap, and convenient therapeutic approach in boys with CGD.

Involvement of brain catecholamines and acetylcholine in growth hormone deficiency states. Pathophysiological, diagnostic and therapeutic implications.

A cohort of brain neurotransmitters, especially catecholamines and acetylcholine, play a crucial role in the control of neurosecretory growth hormone-releasing hormone (GH-RH)- and somatostatin (SS)-producing neurons, and hence growth hormone (GH) secretion. Stimulation of alpha 2-adrenoceptors or of muscarinic cholinergic receptors in the hypothalamus stimulates GH release, probably via stimulation of GH-RH and inhibition of somatostatin release, respectively. Additionally, stimulation of dopamine receptors is stimulatory to GH release, while activation of beta-receptors inhibits GH release via stimulation of hypothalamic somatostatin function. As a corollary, in GH deficiency states drugs affecting catecholaminergic and cholinergic functions may be exploited for diagnostic and/or therapeutic purposes, and may be useful for a better understanding of the underlying pathophysiology. Levodopa (L-dopa) [125 to 500mg orally], the physiological precursor of the catecholamines, administered either alone or in combination with carbidopa (50mg orally), to prevent its peripheral decarboxylation to dopamine, and/or the beta-adrenoceptor antagonist propranolol (0.75 mg/kg orally), and the alpha 2-adrenoceptor agonist clonidine (0.15 mg/m2 orally), are a fairly reliable stimulus of GH release. In normal subjects, however, false-negative GH responses and wide inter-individual variability may occur with these drugs. Additionally, the GH secretory response to these provocation tests is a poor predictor of endogenous 24-hour GH secretion, since levodopa or clonidine may elicit a response within normal limits in children of short stature with reduced 24-hour GH secretion and good responsiveness to GH therapy. The availability of GH-RH, a direct probe of pituitary somatotrophs, held out promise of unravelling the hypothalamic or pituitary origin of GH secretory disturbance. It soon became apparent, however, that this was not the case, because of the wide inter- and intraindividual variation in the GH response. However, the coadministration of GH-RH and muscarinic cholinergic agonists, for example pyridostigmine (which deprive the pituitary of hypothalamic SS inhibitory influences), is a useful diagnostic probe. In a large group of normal children and adolescents who received an intravenous injection of GH-RH, preceded by oral administration of pyridostigmine (60mg orally), none gave a false-negative response; this was also true for a group of short children with different forms of GH disturbances, in whom 8-hour nocturnal GH secretion was within normal limits. However, some false-negative responses occurred in children following testing with GH-RH, clonidine or pyridostigmine alone. Interestingly, the cut-off point for normality following pyridostigmine + GH-RH was as high as 20 ng/ml, while for the other provocation tests it is only 5 to 10 ng/ml. Responses lower than 20 ng/ml were present in all children with organic and most of the children with idiopathic GH deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

The growth hormone response to pyridostigmine plus growth hormone releasing hormone is not influenced by pubertal maturation.

We have evaluated the effect of pubertal maturation on the GH response to growth hormone releasing hormone (GHRH), pyridostigmine (PD) and the combined administration of PD + GHRH in a group of short normal children. Fifteen were prepubertal (13 boys and 2 girls, age 5.0 - 12.5 yr), 10 were early pubertal (8 boys and 2 girls, age 11.5 - 16.9 yr in Tanner stage 2-3 of pubertal maturation), and 6 were late pubertal (6 boys and 2 girls, age 13.6 - 17.1 yr in Tanner stage 4-5 of pubertal maturation). All subjects were tested on three occasions with GHRH 1-29 (1 microgram/Kg iv), PD (60 mg po) and PD + GHRH (60 mg PD administered orally 60 min before GHRH). Peak GH levels after GHRH, PD, and PD + GHRH in the prepubertal children (16.0 +/- 2.8, 8.1 +/- 1.3 and 51.1 +/- 5.5 ng/ml, mean +/- SE, respectively) were not different from those observed in the early pubertal (18.4 +/- 2.1, 9.1 +/- 1.9 and 41.2 +/- 5.6 ng/ml, respectively) and in the late pubertal group (14.9 +/- 2.3, 13.1 +/- 2.4 and 42.6 +/- 2.9 ng/ml, respectively). Evaluation of the area under the curve (AUC) also showed no difference in the GH response to GHRH, PD and PD + GHRH between the three groups studied. These results confirm that the combination PD + GHRH is a powerful test to study the GH secretory capacity of the pituitary, and show that pubertal maturation has no effect on the GH response to this test.

The effect of galanin on baseline and GHRH-induced growth hormone secretion in obese children.

We have evaluated the effect of the administration of galanin (Gal), a newly identified hypothalamic peptide, on baseline and GHRH-induced GH rise in five obese children and in seven controls. The GH response to GHRH (hpGRF(1-29), 1 microgram/kg i.v.), and to Gal (15 micrograms/kg/h for 1 h), evaluated both as the maximum GH peak and as integrated area under the curve (AUC), was significantly lower in the obese children than in the controls. Simultaneous administration of Gal plus GHRH significantly increased the GH response to GHRH in all the obese subjects, so that their mean peak GH levels and AUC after Gal plus GHRH were similar to those of the control children after GHRH. Also, in control children Gal caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean AUC after Gal plus GHRH were significantly higher in the controls than in the obese children given the same treatment. Our data indicate that obese children have a blunted GH response to Gal, which, however, is able to enhance the GH response to GHRH. This observation strengthens the view that the mechanism of action of Gal involves modulation of endogenous somatostatin (SRIH) release. In addition, similarity between the effects of Gal and pyridostigmine on baseline and GHRH-stimulated GH release in obese children may indicate the existence of a cholinergic link in the action of Gal.

Evidence for involvement of endogenous somatostatin in the galanin-induced growth hormone secretion in children.

We have evaluated the effects of the combined administration of Galanin (Gal) plus growth hormone-releasing hormone (GHRH) and of pyridostigmine (PD), a cholinergic agonist, plus Gal on GH secretion in 15 children (12 males and three females, age 7.7-14.5 y) with short stature. Children were subdivided into two groups. In group 1 (n = 7) Gal (15 micrograms/kg h i.v.) plus GHRH (1 microgram/kg i.v.) administration induced a higher GH rise (peak = 73.1 +/- 10.2 ng/mL, mean +/- SD; area under the curve (AUC) = 531.9 +/- 78.7 ng.min.mL-1) than did GHRH alone (peak = 38.9 +/- 26.5 ng/mL, p less than 0.05; AUC = 256.9 +/- 165.6 ng/mL/min-1, p less than 0.005). Gal had a synergistic effect on the GHRH-induced GH response because the GHRH plus Gal AUC response was significantly higher (p less than 0.01) than the sum of the areas of response to GHRH and Gal alone. In group 2 (n = 8) PD administration (60 mg/kg p.o.) had no significant effects on the Gal-induced GH secretion (peak = 14.9 +/- 8.8 and 16.0 +/- 9.8 ng/mL after Gal and PD + Gal, respectively; AUC = 91.2 +/- 52.1 and 125.2 +/- 83.6 ng.mL.min-1 after Gal and PD + Gal, respectively). Our results confirm the ability of Gal to stimulate GH secretion in children, and strengthen the view that its mechanism of action involves modulation of endogenous somatostatin release.

The effects of galanin on growth hormone secretion in children of normal and short stature.

We have evaluated the effect of galanin (Gal), a newly identified hypothalamic peptide, on growth hormone (GH) secretion in 10 children with normal stature (NS), nine with constitutional growth delay (CGD), and five with isolated GH deficiency (IGHD). Gal was infused intravenously at a rate of 8 or 15 micrograms/kg/h. All children also underwent an acute oral clonidine test (0.15 mg/m2). In CGD children the mean plasma GH peak after 8 micrograms/kg/h of Gal infusion (13.3 +/- 1.7 ng/mL; mean +/- SEM) was higher (p less than 0.02) than in NS children (8.5 +/- 0.8 ng/mL). When the dose of Gal was increased to 15 micrograms/kg/h the mean plasma GH peak in CGD children (18.5 +/- 3.5 ng/mL) was still higher than in the NS group (13.2 +/- 2.9 ng/mL), although not significantly so. In IGHD children the mean plasma GH peak elicited by 8 or 15 micrograms/kg/h of Gal (3.8 +/- 0.7 and 3.9 +/- 0.5 ng/mL, respectively) was lower than that obtained in either CGD (p less than 0.0002) or NS children (p less than 0.001). In NS children the mean plasma GH peak after acute clonidine administration (22.3 +/- 3.0 ng/mL) was higher than that observed after either dose of Gal used (p less than 0.001 and p less than 0.05 with 8 and 15 micrograms/kg/h, respectively). In CGD or IGHD children mean plasma GH peak after acute clonidine (14.8 +/- 2.6 and 4.1 +/- 1.2 ng/mL, respectively) was not significantly different from that observed after either dose of Gal.(ABSTRACT TRUNCATED AT 250 WORDS)