Evaluation of growth hormone response to GHRH plus arginine test in children with idiopathic short stature: role of peak time.

PURPOSE: To describe the course of growth hormone response to growth hormone releasing hormone (GHRH) plus arginine provocative test in children with idiopathic short stature (ISS) and to evaluate the role of peak time. METHODS: A retrospective study was performed analyzing 344 GHRH plus arginine provocative tests performed in children and adolescents with short stature. Serum GH levels were measured at four-time points (T0', T30', T45' and T60') and GH peak was defined as the maximum value at any time point. Mean (T30'-T60') GH value and area under the curve (AUC) were calculated. RESULTS: When analyzing the time of peak at the provocative test, the most frequent peak time was T45' (53.8%) in the ISS group, with no differences in gender, age, and pubertal stage. Analyzing GHD subjects, the most frequent time of peak was T30 (50%). Analyzing the whole population, the GH T0' levels were significantly lower in subjects with the GH peak at T45' than those with the GH peak at T30' (1.7 ± 2.0 vs. 3.2 ± 4.0, p < 0.001). In subjects with GH peak at T45', the value of GH peak, AUC and mean GH were significantly higher than in those with GH peak at T30' and T60'. A direct correlation was found between the value of GH peak and growth velocity SDS (r = 0.127, p = 0.04) and a negative one between GH peak and GH level at T0' (r = - 0.111, p = 0.04), even when adjusted for gender, age, pubertal stage and BMI Z score. CONCLUSIONS: The time peak at 45 min seems to be associated with a better response to the test considering GH peak, mean and AUC. Patients with a GH peak at 30 min more probably could have a derangement in GH secretion showing worst growth pattern and/or a GH deficiency and should be carefully observed.

Lipid profile and nutritional intake in children and adolescents with Type 1 diabetes improve after a structured dietician training to a Mediterranean-style diet.

AIM: To evaluate if nutritional intakes and lipid profile fulfill international guidelines and recommendations before and after a structured dietician training to a Mediterranean- style diet in an Italian pediatric population with Type 1 diabetes. METHODS: A 6-month prospective cohort study. Baseline and after-intervention nutritional intakes, lipid profile, glycated hemoglobin (HbA(1c)), and clinical parameters of 96 children and adolescents with Type 1 diabetes were assessed. A comparative computerized system which was approved and validated by the Italian Diabetologist Association was used to define the amounts of nutrients. RESULTS: At baseline mean daily dietary intakes of carbohydrates, proteins, and lipids were respectively (mean ± SEM) 51.8 ± 0.5, 15.9 ± 0.2, 33.8 ± 0.6%, with a contribution of cholesterol of 248.7 ± 12.5 mg/day. Fiber assumption was 18.0 ± 0.4 g/day. The 64.5% and 29.1% (p<0.0001) of subjects had at least one lipid parameter higher than 75(th) and 95(th) percentiles, respectively, of selected cut points (American Diabetes Association guidelines for total and LDL-cholesterol and American Academy of Pediatrics standards for HDL-cholesterol and triglycerides). Six months after the dietician intervention, dietary lipids and cholesterol decreased (p<0.0001) while fibers (p<0.0001) increased. LDL-cholesterol, non-HDL-cholesterol, and total cholesterol:HDL-cholesterol ratios significantly decreased (p<0.001) with a reduction of rate of subjects with at least one pathological lipid parameter (p<0.01) independently by weight and glucose control. CONCLUSIONS: Italian pediatric subjects with Type 1 diabetes present a balanced diet with exception of lipids intake and a suboptimal lipid profile. A structured dietician training to a Mediterranean-style diet improves the quality of nutrient intakes being followed by a reduction of LDL-cholesterol, non- HDL-cholesterol, and total cholesterol:HDL-cholesterol ratios.

Not only for caregivers: intranasal glucagon for severe hypoglycaemia in a simulation study.

AIMS: To evaluate: (i) the propensity of paediatrics and emergency medicine residents to select different therapeutic options and (ii) the speed and administration success in a high-fidelity simulation of severe hypoglycaemia in a child with type 1 diabetes (T1DM). METHODS: In this single-centre high-fidelity simulation study, 51 paediatrics or emergency medicine residents were exposed to a scenario of severe hypoglycaemia in a T1DM child attending an ambulatory setting, before and after a training on the preparation and administration of both injectable and IN glucagon. Time for drug delivery and its effectiveness were collected. RESULTS: Before training, 45.1% of participants chose to administer injectable glucagon, 43.1% intravenous glucose solution, 5.9% intranasal (IN) glucagon, and 5.9% took no action. Administration was successful in 74% of injectable glucagon, 33.3% intravenous glucose solution, and 22.7% IN glucagon. After training, 58.8% of participants chose IN and 41.2% injectable glucagon, with 100% of successful administrations for IN glucagon and 90.5% for injectable glucagon. Time to successful administration was shorter for IN than injectable glucagon (23 ± 10 vs. 38 ± 7 s, p < 0.0001). CONCLUSIONS: IN glucagon is an easy and effective option for severe hypoglycaemia treatment, with an almost zero possibility of failure provided that adequate training is imparted.

Interleukin-10 and transforming growth factor-beta1 in cord blood: relationship with paternal allergy and cesarean section.

AIM: To measure Interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1) in cord blood and assess their relationship with parental allergy and perinatal characteristics. METHODS: In a neonatal care unit 212 consecutive full-term and appropriate for gestational age newborns were recruited. IL-10 and TGF-beta1 levels were determined in cord blood by high sensitivity ELISA. Perinatal characteristics, mode of delivery and presence of allergy in parents were recorded. RESULTS: Out of 212 newborns, 136 were of non-allergic parents and 76 (35.8%) of one or both allergic parents. In newborns of allergic fathers median IL-10 levels tended to be lower (0.67 vs. 1.06 pg/mL, p = 0.07) and TGF-beta1 levels were significantly lower (40.9 vs. 45.3 ng/mL, p = 0.008) than in newborns of non-allergic parents. Multiple general regression analysis showed that presence of paternal allergy (beta=-0.19, p = 0.003) to be born by cesarean section (beta=-0.21, p = 0.03) and younger gestational age (beta= 0.14, p = 0.04) independently contributed to decrease TGF-beta1 levels (multiple R = 0.38, p < 0.0001). CONCLUSION: Paternal allergy and cesarean section are associated to decreased TGF-beta1, which might be the mediator of the increased risk of atopy development. Cord blood IL-10 and TGF-beta1 levels of our newborn series could be used as reference values for further studies on these relationships.

Prevalence and risk factors for overweight and obesity in a population of Italian schoolchildren: a longitudinal study.

Prevalence of childhood overweight and obesity have dramatically increased worldwide in the last decades. Overweight and obesity are the result of a complex interaction between genetic and environmental factors. The aim of our longitudinal study was to assess the prevalence of overweight and obesity in a population of Italian schoolchildren followed for 2 years and to identify main risk factors for obesity onset and persistence in childhood. We enrolled 632 children (males /females= 345/287), aged 3 to 8 yr.Weight and height were measured at time 0, 1 (1 yr later), and 2 (2 yr later). Overweight and obesity were defined using body mass index (BMI) (Italian growth charts). Data collected included: birth weight, gestational age,maternal weight gain during pregnancy, breast feeding, parents' BMI, educational level, and occupation type. At time 0, 1, and 2 the prevalence of overweight was 22%, 22%, and 25%, respectively, and the prevalence of obesity was 7%, 8%, and 8%, respectively. During follow-up 62%of children remained normal weight, 24% was always overweight or obese, 9% became overweight, while only 5% of overweight subjects became normal weight. Male gender, maternal weight gain during pregnancy >10 kg, parental overweight/obesity were positively associated with the presence of overweight during the entire follow-up. On the contrary, being small for gestational age at birth was negatively related to persistence of overweight. No influence was found for being breastfed, for parental low educational level, and manual occupation. A large prevalence of overweight/obesity was observed in Italian schoolchildren. Gender, maternal weight gain during pregnancy, and parents' BMI were the strongest predictors of the persistence of child overweight and obesity.

Vitamin D status and type 1 diabetes in children: evaluation according to latitude and skin color.

AIM: We aim to investigate vitamin D (25OHD) levels in children with or without type 1 diabetes (T1D) according to latitude and skin color. METHODS: We compared 25OHD levels in children with T1D living in Piedmont, of Caucasian or Moroccan origin, with healthy control subjects matched for age and ethnicity. Data of resident children in Morocco, with and without T1D, were used for comparison. RESULTS: Caucasian (21.4±1.5 vs. 24.0±0.5 ng/mL, P<0.05) and Moroccan children with T1D (12.0±2.6 vs. 17.1±1.7 ng/mL, P<0.05) living in Piedmont had lower 25OHD levels than their counterparts without diabetes. Moroccan children living in Morocco with and without T1D had similar 25OHD levels. Vitamin D deficiency was associated with T1D in Caucasian and Moroccan children living in Piedmont (OR: 1.720, CI95% 1.034-2.860, P<0.03), CONCLUSION: Lower vitamin D levels were associated with T1D in Piedmont. Further studies are necessary to explain a possible relationship between vitamin D and T1D.

Evidence of luteinizing hormone secretion in hypothalamic amenorrhea associated with weight loss.

The lack of plasma luteinizing hormone (LH) pulsatile pattern or episodic LH secretory bursts during night have been demonstrated in hypothalamic amenorrhea. The availability of both sensitive and specific immunofluorimetric assay and algorithm for pulse detection enabled us to reanalyze the question of whether or not patients with hypothalamic amenorrhea secrete LH in a pulsatile fashion. Seven women with secondary amenorrhea associated with weight loss and four normally cycling women were studied, sampling every 5 minutes for 8 hours. Control subjects were studied during four different phases of the menstrual cycle. In all amenorrheic patients, a frequent LH pulsatile secretion, with pulses of low amplitude, was found (10.7 +/- 1.4 peaks/8 h; mean +/- SEM). The pulse frequency was significantly higher (P less than 0.05) than any phases of the control group (early follicular: 7 +/- 0.4 peaks/8 h; late follicular: 6.8 +/- 0.6 peaks/8 h; early luteal: 4.3 +/- 0.4 peaks/8 h; late luteal: 7 +/- 0.3 peaks/8 h). The LH pulsatile release in amenorrheic patients showed a mean pulse duration and amplitude shorter than in any phase of the menstrual cycle of the controls. In conclusion, in weight-loss-related-amenorrhea, the major change was not the absence of the LH pulsatile release but its increased frequency with reduced pulse amplitude.

[Epidemic outbreak of tegumentary leishmaniasis in Puerto Esperanza, Misiones, 1998]. / Brote epidémico de leishmaniosis tegumentaria en Puerto Esperanza, Provincia de Misiones, 1998.

The province of Misiones reported 205 leishmaniasis cases during 1998, 98% of them from the locality of Puerto Esperanza. The reports of Puerto Esperanza Hospital (January to September 1998) for leishmaniasis were analysed (n: 129). The mainly reported lesion was the single cutaneous ulcer (97.2%), localized in the inferior limbs (72.5%), without any mucosa involvement. The results are consistent with the knowledge from other Argentinean leishmaniasis foci due to Leishmania (V.) braziliensis. The difference in incidence among sexes was not significant, leishmaniasis was reported in all age groups, and it was susceptible to the conventional treatment. The main focus was located in Km 1 neighbourhood, the transmission peak was during April 1998. The Montenegro skin test among general population (n: 205) did not show reactivity among asymptomatic people. The prevalent Phlebotominae species were Lutzomyia intermedia (79.7%) and Lu. whitmani (10.9%), among the 577 individuals belonging to 8 species collected. The Phlebotominae were abundant in peridomestic habitats of Km 1 neighbourhood, close to human dwellings, in places associated with residual primary forest and secondary vegetation. The results are discussed in the frame of surveillance and possible control strategies.

Follow-up of methylmercury concentration in brain areas of developing rats exposed during prenatal life using cold-vapor absorption spectrometry.

The concentration and the distribution of mercury in six different brain areas of developing rats (21 and 60 days of age) exposed to methylmercury (MMC) during prenatal life were determined by using pressure decomposition of the tissues and cold-vapor atomic absorption spectrometry. The distribution of mercury in brain samples showed that the metal distributes to all brain areas, but with different levels. The amount of mercury in the brain areas was about 10-100 times higher, depending on the tested area, in MMC exposed rats than in control, at day 21 of age, while it was practically equal to controls at 60 days of age. These data seem to be of importance in order to correlate the presence of mercury in the brain and its distribution to brain areas after a single exposure to MMC with transient or permanent changes in specific neurotransmitter system and altered behaviors.

Survey of total and bioavailable chromium in grain and cereal products by atomic absorption spectrophotometry.

The chromium content of samples of cereals, legumes, oil seeds, and alimentary pastes (in the latter, bioavailable chromium as well) was determined by atomic absorption spectrophotometry. The chromium content in whole cereals differs substantially and is mostly concentrated in pericarps. Variations occur not only among different types of cereals, but also among cereals of the same type, depending on the areas of origin. Concentration varies substantially even in samples of legumes and oil seeds. The content of bioavailable chromium (ethanol-extractable) is, in most cases, more than 50% of the total chromium amount. This makes these products particularly interesting as dietary supplements.

[Bromination of 3-amino-1,2,4-benzothiadiazine-1,1-dioxide]. / Sulla bromurazione del 3-amino-1,2,4-benzotiadiazin-1,1-diossido.

The bromination of 3-amino-1,2,4-benzothiadiazine-1,1-dioxide (1) in N,N-dimethylformamide has been studied. Depending on the operating conditions the reaction produces 7-bromo-3-amino-1,2,4-benzothiadiazine-1,1-dioxide (II) or 5,7-diabromo-3-amino-1,2,4-benzothiadiazine-1,1-dioxide (III). Derivatives halogenated at the nitrogen were not isolated in any of the experiments.

[Iodo-derivatives of 2-aminobenzensulfonamide and 1,2,4-benzothiadiazine-1,1-dioxide]. / Iodioderivati della 2-aminobenzensolfonamide e dell'1,2,4-benzotiadiazin-1,1-diossido

A series of iodo derivatives of 2-aminobenzensulfonamide and its derivatives has been prepared by reaction with iodine chloride in N,N-dimethylformamide or N,N-dimethylacetamide. The structure of each compound was confirmed by transformation with formic acid into the corresponding 1,2,4-benzothiadiazine and comparison with the same compounds prepared via the Sandmeyer reaction starting form amino derivatives of known structure. It was found that the iodination reaction in N,N-dimethylformamide, can lead, depending on the nature of the starting material, to the formation of benzothiadiazine derivatives apparently generated from sulfonamide via a formylation reaction due to N,N-dimethylformamide.

[Cardiovascular effect of 1,2,4-benzothiadiazine-1,1-dioxide derivatives. VIII]. / Azione cardiovascolare di derivati dell'1,2,4-benzotiadiazin-1,1-diossido nota VIII.

A series of carboxy- and carbomethoxyalkyl derivatives of 3-amino-1,2,4-benzothiaidazin-1,1-dioxide either substituted or unsubstituted in the benzene ring [compounds (I leads to XVIII)] was prepared and tested for cardiovascular activity. It was found that the introduction of a carboxy-or carbalkoxy-group in the omega position of 3-alkylamino derivatives of 1,2,4-benzothiadiazine-1,1-dioxide usually causes marked decrease or abolition of the cardiovascular activity shown by the parent compounds. The negative effect on the pressor trace (hypotension and increase in differential pressure) is more frequent and significant than that on bradycardial activity.

Cerebrospinal fluid corticotropin-releasing factor levels and stimulation test in dementia of the Alzheimer type.

Experimental findings have recently suggested a toxic role for glucocorticoids in hippocampus, the main brain target for the adrenocortical hormones. In this study, we explored the activity of the hypothalamus-pituitary-adrenal (HPA) axis in a group of patients with dementia of the Alzheimer's type (DAT) and in a control group of age-matched subjects. We measured the corticotropin-releasing factor (CRF) levels in cerebrospinal fluid (CSF) and evaluated the plasma cortisol response to a CRF stimulation test. While no differences were observed in the results of the CRF test for two groups, CSF CRF values in DAT patients were found to be significantly higher than in controls. Bearing in mind the bidirectional relationships between the neuroendocrine and immune systems and the changes in some immunological parameters reported in DAT, the possible role of HPA axis hyperactivity in the pathogenesis of primary dementia is discussed.

[Sulfonamides with central nervous system action. V]. / Solfonamidi ad azione sul sistema nervoso centrale. Nota V.

A series of 2-nitro and 2-aminobenzenesulfon-N-acylamides variously substituted on the benzene ring were prepared and tested for anticonvulsant activity (electro shock, pentamethylenetetrazole). Some of the compounds tested gave some measure of protection against convulsions induced by electric shock. The importance of the trifluoromethyl substituent in this effect was demonstrated.

[Antimicrobial effect of derivatives of 1,2,4-benzothiadiazin-1,1-dioxide. VII]. / Azione antimicrobica di derivati dell'1,2,4-benzotiadiazin-1,1-diossido. Nota VII.

Series of alkyl derivatives of the following have been prepared: 5,7-dichloro- [compounds (II leads to V)], 6-methyl- [compounds (VI leads to IX)] and 6-methoxy-3-mercapto-1,2,4-benzothiadiazine-1,1-dioxide [compounds (X leads to XIII)]. The products were tested for antimicrobial activity. Studies were also made of the corresponding 3-mercapto precursors (XIV, XV, XVI) and the relative 3-picolinium salts (XVII, XVIII, XIX) and also of the 3-picolinium salts of 6-chloro-, 7-chloro- and 6,7-dichloro-3-mercapto-1,2,4-benzothiadiazine-1,1-dioxide (XX, XXI, XXII). Some of the 3-alkylmercapto compounds, and especially the 5,7-dichloro derivative, inhibited various strains of Gram-positive bacteria of the genus Staphylococcus, while the same substances proved much less effective against the genera Streptococcus and Diplococcus. Antimicrobial activity appeared to be influenced by the length of the alkyl chain as well as by the nature and position of the substituents on the benzene ring. The compounds proved inactive against the Gram-negative schizomycetes (Salmonella, Shigella, Escherichia, Proteus, Pseudomonas. Enterobacter, Klebsiella, Serratia, Yersinia, Providencia) and against yeasts (Candida) with the exception of compound (V) which showed slight bacteriostatic action against three strains of Candida albicans.