T lymphocyte maturation is impaired in healthy young individuals carrying trisomy 21 (Down syndrome).

Cytokine production, immune activation, T lymphocytes maturation, and serum IL-7 concentration were examined in 24 youngsters with Down syndrome and no acquired diseases (healthy Down syndrome [12 prepubertal, 13 pubertal]) and 42 age- and gender-matched controls (20 prepubertal, 22 pubertal). Results showed that a complex immune and impairment is present in healthy individuals with Down syndrome in whom interferon gamma, interleukin (IL) IL-10 production, as well as serum IL-7 concentrations and activation markers-bearing T lymphocytes were significantly augmented. Additionally, a complex skewing of post-thymic lymphocyte maturation pathways was observed in patients: significant reduction of CD4+ and CD8+ naive (RA+CCR7+) lymphocytes, significant increase of CD4+ and CD8+ central memory (RA-CCR7+), and terminally differentiated (TD) (RA+CCR7-) lymphocytes.

[Usefulness of the 5-6-yrs-old anthropometric health report for the evaluation of childhood overweight and obesity: pilot study in Lombardia (Italy)]. / Utilità della scheda bilancio di salute per la rilevazione di sovrappeso e obesità nei bambini tra 5 e 6 anni: esperienza pilota in Lombardia.

OBJECTIVE: To verify the possibility to use the Anthropometric Health Report (AHR), containing the BMI value, for overweight/obesity evaluation in 5-6-years-old children. DESIGN: Between January 2001 and December 2004, 4619 AHR had been examined. BMI values were compared with age and sex-specific BMI cutoffs, according to Cole, as well as with a single BMI value, calculated as the mean between boys and girls cutoff at 5.5 yrs of age. SETTING: 4619 children of ASL Provincia di Milano 2, aged 5-6 years were examined. PARTECIPANTS: 81 Family Pediatricians working in the area of Provincia di Milano 2. MAIN OUTCOME MEASURES: An easily available and low cost method for epidemiological studies on overweight and obesity in childhood. RESULTS: During the study period the number of examined children increased constantly (from 8% to 30% of the overall resident population). Also the correct compilation of the AHR raised (from 47% to 95%). The elevated percentage of overweight children (range 17-23%) and obese children (range 5-7%) in the study group confirms other published data in this age group. The use of a single BMI cutoff did not affect significantly (p > 0.05) the results with regard to the use ofage and sex-specific cut offs. Required time for carrying out the study was limited. Efficiency increased during the study: the number ofAHRs analyzed per hour increased from 37.5 in 2001 to 103.5 in 2004. Some critical points about current uses of AHR are discussed CONCLUSIONS: AHR could be used for epidemiological purposes. It could be considered an useful method in monitoring overweight/obesity in 5-6 years old children as well as in checking the efficacy of prevention and therapeutic strategies.

A novel deletion in the GH1 gene including the IVS3 branch site responsible for autosomal dominant isolated growth hormone deficiency.

CONTEXT: The majority of mutations responsible for isolated GH type II deficiency (IGHD II) lead to dominant negative deleteriously increased levels of the GH1 exon 3 skipped transcripts. OBJECTIVE: The aim of this study was the characterization of the molecular defect causing a familial case of IGHD II. PATIENTS: A 2-yr-old child and her mother with severe growth failure at diagnosis (-5.8 and -6.9 sd score, respectively) and IGHD were investigated for the presence of GH1 mutations. RESULTS: We identified a novel 22-bp deletion in IVS3 (IVS3 del+56-77) removing the putative branch point sequence (BPS). Analysis of patients' lymphocyte mRNA showed an excess exon 3 skipping. The mutated allele transfected into rat pituitary cells produced four differently spliced products: the exon 3 skipped mRNA as the main product and lower amounts of the full-length cDNA and of two novel mRNA aberrant isoforms, one with the first 86 bases of exon 4 deleted and the other lacking the entire exon 4. A mutagenized construct lacking exclusively the 7 bp of the BPS only generated the exon 4 skipped and the full-length isoforms. The presence of the full-length transcript in the absence of the canonical BPS points to an alternative BPS in IVS3. CONCLUSION: The IVS3 del+56-77 mutation, causing IGHD II in this family, has two separate effects on mRNA processing: 1) exon 3 skipping, analogous to most described cases of IGHD II, an effect likely caused by the reduction in size of the IVS3, and 2) partial or total exon 4 skipping, as a result of the removal of the BPS.

Effects of recombinant growth hormone on visceral fat accumulation: pilot study in human immunodeficiency virus-infected adolescents.

CONTEXT: Recombinant human GH (rhGH) reduces excess accumulation of intraabdominal adipose tissue (IAT) in lipodystrophic HIV-infected adults, whereas data in pediatric patients are lacking. OBJECTIVE: The objective of this study was to assess the efficacy of rhGH treatment on lipodystrophy in HIV-infected adolescents. DESIGN: The study is a prospective, 24-wk open-label study of rhGH. SETTING: The study was conducted at a referral center for pediatric HIV infection. PATIENTS AND OTHER PARTICIPANTS: Eight HIV-infected adolescents (ages, 13.7-18.5 yr), with abnormal IAT accumulation (>41 cm(2) at L4-magnetic resonance imaging) and 97 healthy controls (HC) (ages, 9.5-19.9 yr) were enrolled. INTERVENTION: rhGH was given by sc injection at a daily dose of 0.028 mg/kg. MAIN OUTCOME MEASURES: The main outcome was change in IAT at L4-magnetic resonance imaging. Body composition by dual-energy x-ray absorptiometry, glucose and lipid metabolism, and IGF-I changes were also evaluated. RESULTS: All patients completed the study period; none of them showed adverse event, and no change in the daily dose of rhGH was required. The treatment was associated with a mean height increase of 2.4 cm. From baseline to wk 24, IAT area decreased significantly by a median of 34.5% (-19.2 to -70%). Fat mass decreased significantly in patients, compared with HC, with a median loss of total, trunk, and arm and leg fat mass of 10.4, 10.9, 12.7, and 5.4%, respectively. Total, arm, and leg lean masses increased significantly, compared with HC. IGF-I increased significantly, but supraphysiological values of mild degree (2-23% over the upper normal limit) were detected in only nine of 24 samples. No significant effects on glucose metabolism, triglyceride, and cholesterol levels were observed. CONCLUSIONS: Our data showed that rhGH 0.028 mg/kg daily for 24 wk in HIV-infected adolescents reduces IAT, trunk, and also limb fat and increases lean mass. Overall, short-term rhGH is well tolerated and is not associated with a worsening of glucose and lipid metabolism.

Growth hormone in T-lymphocyte thymic and postthymic development: a study in HIV-infected children.

OBJECTIVES: Growth hormone (GH) plays a role in thymic function, and recombinant GH may stimulate thymopoiesis in HIV-infected individuals. We performed immunologic analyses in 26 antiretroviral-treated children matched for age, pubertal status, clinical parameters, and antiretroviral exposure who did or did not show an impaired response to GH-release stimulation tests with arginine + GH-releasing hormone. RESULTS: The following abnormalities were found in GH-deficient compared with GH-nondeficient children after >4 years of therapy: CD4 count ( P = .02) and percentage ( P = .03), CD4 as percentage of normal cells for age ( P = .003), serum interleukin-7 concentration ( P = .02), and thymic volume ( P = .01). Naive CD4 (4+62+RA+ and 4+CCR7+RA+) and CD8 (8+CCR7+RA+) lymphocytes were lower in GH-deficient children ( P = .003; P = .007; and P = .02, respectively). Postthymic pathways were also impaired in GH-deficient children. Thus, central memory (4+CCR7+RA-) CD4+ cells were reduced ( P = .006), whereas effector memory (4+CCR7-RA-) CD4+ cells ( P = .002) and late effector CD8+ lymphocytes (8+CCR7-RA+ and 8+27-28-) ( P = .009 and P = .002, respectively) were increased in these children. CONCLUSIONS: Growth hormone plays a role in thymic and postthymic pathways, and defective GH production may be associated with incomplete immunoreconstitution. Immunomodulant agents (including GH) could be useful in patients with defective GH production.

Thyroid dysfunction in antiretroviral treated children.

BACKGROUND: A high rate of thyroid disorders has been described in HIV-infected adults treated with highly active antiretroviral therapy (HAART), but data on children are lacking. We aimed to assess thyroid function in pediatric patients. METHODS: Fifty-two HIV-infected children receiving HAART were assessed for signs of thyroid dysfunction and serum concentrations of thyrotropin (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroglobulin (TG), reverse triiodothyronine (rT3), anti-TG and antimicrosomal (anti-TSM) antibodies. RESULTS: Eighteen (35%) children showed thyroid abnormalities: isolated low FT4 value in 16; subclinical hypothyroidism in 1; and symptomatic hypothyroidism in 1. Children with low FT4 values as compared with the 34 children without thyroid dysfunction were similar for stage of disease, number of patients with undetectable HIV-RNA, FT3, TSH, TG, rT3, anti-TSM and anti-TG values, whereas they had shorter duration of HAART exposure (P = 0.019) and lower CD4 cell percentage (P = 0.035). The thyrotropin-releasing hormone (TRH) test was normal in all children with low FT4 values. Among children with low FT4, FT4 concentrations correlated positively with CD4 cell percentage (P < 0.05) and duration of HAART exposure (P < 0.05). The case with subclinical hypothyroidism had high basal TSH (7.3 microunits/ml), normal TSH response to TRH test and normal FT4, FT3, TG, rT3, anti-TG and anti-TSM antibodies. The case with symptomatic hypothyroidism had low FT4 (6.6 pg/ml) and high TSH (44 microunits/ml), TG (55 ng/ml), anti-TG (666 IU/ml) and anti-TSM (123 IU/ml). CONCLUSION: Thyroid abnormalities occur frequently in HAART-treated children even in the absence of clinical symptoms. These data suggest a need of regular thyroid function monitoring.