Recognition of heat shock protein 60 epitopes in children with type 1 diabetes.

BACKGROUND: Treatment with a specific HSP60 epitope in new onset of type 1 diabetes (T1D) patients has been shown to preserve endogenous insulin production. Previously, recognition of pan HLA-DR-binding HSP60 epitopes in various autoimmune diseases was found; this study investigated recognition of these epitopes in newly diagnosed T1D patients and correlated findings to the occurrence of a partial remission. METHODS: Peripheral blood mononuclear cells of 18 children with T1D were prospectively collected at disease onset and a few months after diagnosis. Epitope-specific T-cell proliferation and cytokine production (intracellular and in culture supernatants) were measured. Results were compared with 31 longstanding T1D patients and ten healthy controls. RESULTS: Although HSP60 epitope-specific T-cell proliferative responses were detected, overall proliferative responses were low. At onset, epitope-specific intracellular IFN-γ production was higher in T1D patients compared with healthy controls (p < 0.05). At follow-up, both IL-10 and IFN-γ production were higher in those without a partial remission than in those with a partial remission (both p < 0.05). Also, IL-10 and IFN-γ production were higher compared with onset for patients without a PR (both p < 0.01). In supernatants of HSP60 epitope-specific T-cell cultures, no substantial differences in cytokine production were found between T1D patients with and without a partial remission, either at onset or a few months after onset. As patient numbers were small, results should be interpreted with caution. CONCLUSIONS: Pan-DR-binding HSP60 peptides induced low peptide-specific proliferative responses and peptide-specific production of some, mainly intracellular, cytokines in T1D patients. Recognition did not differ significantly between patient groups and various time points.

Long-term GnRH-agonist treatment does not postpone central development of the GnRH pule generator in girls with idiopathic precocious puberty.

Gonadotropin and estradiol secretion were studied in two groups of female patients with idiopathic central precocious puberty, at diagnosis (group 1, age 4.8-8.7 yr) and during recovery after long-term treatment with a GnRH agonist (group 2, age 6.5-9.4 yr). The protocol included 24-h sampling of blood at 10-min intervals just before GnRH-agonist treatment (group 1, n = 7), and at 4 and 10 months after discontinuation of treatment (group 2, n = 8). LH was estimated at 10-min intervals, and FSH and estradiol were estimated at 1-h intervals for 6-h periods during the day (wake) and during the night (sleep). In group 2, height was measured in the follow-up at 4 and at 10 months. In group 1, all the girls showed a pulsatile LH secretion with a clear wake-sleep difference in mean LH and LH pulse amplitude: mean LH daytime levels were 1.33 IU/L (range 0.57-7.34 IU/L) vs. nighttime levels of 3.12 IU/L (range 2.35-5.19 IU/L) (P < 0.05). Mean LH pulse amplitudes were 1.39 IU/L (range 0.35-1.76 IU/L) at daytime and 3.85 IU/L (range 1.10-12.37 IU/L) at night (P < 0.05). In group 2, all girls showed pulsatile LH patterns after 4 months as well as after 10 months. At both sampling periods, no wake sleep differences in LH pulse frequency, mean LH levels, or LH pulse amplitude were observed. Mean daytime LH levels increased from 1.66 IU/L (range 0.67-3.29 IU/L) at 4 months to 3.04 IU/L (range 0.73-5.59 IU/L) at 10 months, after therapy (P < 0.05). The number of LH pulses were not different at 4 and at 10 months. The mean LH pulse amplitude increased from 1.68 IU/L (range 0.54-2.04 IU/L) to 2.79 IU/L (range 1.01-3.41 IU/L), comparing 4 months with 10 months (P < 0.05) at daytime. The mean FSH level increased from 1.0 IU/L (range 0.5-2.1 IU/L) at discontinuation of treatment to 4.29 IU/L (range 3.15-5.12 IU/L) at 4 months (P < 0.01) and to 4.49 IU/L (range 2.72-6.50 IU/L) at 10 months (daytime = NS). The estradiol levels increased from less than 37-51 pmol/L at the end of treatment to 77.5 pmol/L (range < 37.0-102.4 pmol/L) and 96.8 pmol/L (range 61.8-169.8 pmol/L) (daytime) at 4 and 10 months, respectively (P < 0.05). Menarche occurred in five of the eight girls within 13 months after treatment. No pubertal growth spurt was observed after treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Eight years of growth hormone treatment in children with Prader-Willi syndrome: maintaining the positive effects.

BACKGROUND: The most important reason for treating children with Prader-Willi syndrome (PWS) with GH is to optimize their body composition. OBJECTIVES: The aim of this ongoing study was to determine whether long-term GH treatment can counteract the clinical course of increasing obesity in PWS by maintaining the improved body composition brought during early treatment. SETTING: This was a multicenter prospective cohort study. METHODS: We have been following 60 prepubertal children for 8 years of continuous GH treatment (1 mg/m(2)/d ≈ 0.035 mg/kg/d) and used the same dual-energy x-ray absorptiometry machine for annual measurements of lean body mass and percent fat. RESULTS: After a significant increase during the first year of GH treatment (P < .0001), lean body mass remained stable for 7 years at a level above baseline (P < .0001). After a significant decrease in the first year, percent fat SD score (SDS) and body mass index SDS remained stable at a level not significantly higher than at baseline (P = .06, P = .14, resp.). However, body mass index SDSPWS was significantly lower after 8 years of GH treatment than at baseline (P < .0001). After 8 years of treatment, height SDS and head circumference SDS had completely normalized. IGF-1 SDS increased to +2.36 SDS during the first year of treatment (P < .0001) and remained stable since then. GH treatment did not adversely affect glucose homeostasis, serum lipids, blood pressure, and bone maturation. CONCLUSION: This 8-year study demonstrates that GH treatment is a potent force for counteracting the clinical course of obesity in children with PWS.

The effect of prolonged administration of an anabolic steroid (oxandrolone) on growth in boys with constitutionally delayed growth and puberty.

UNLABELLED: Short-term oxandrolone treatment is used to stimulate growth in boys with constitutional delay of growth and puberty (CDGP). Oxandrolone stimulates growth, but a beneficial effect on final height has not been established. In our study, we report the effect of long-term treatment (30-57 months) with oxandrolone in 18 boys with CDGP, compared with nine puberty-matched, untreated controls (group 1). The oxandrolone-treated boys were divided into two groups: four boys who received oxandrolone before onset of puberty (group 2), and 14 boys who started oxandrolone therapy during Tanner stage 2 (group 3). Height standard deviation scores for calender age (HSDSCA) between the three groups of patients at Tanner stage 2 (G2) were not different: -2.86 (SD 0.56) in the controls and -2.60 (SD 0.52) in group 2 and -2.81 (SD 0.59) in group 3. Age at G2 was 15.1 (SD 1.4) years (controls), 14.6 (SD 0.5) years (group 2) and 14.0 (SD 0.9) years (group 3). Height velocity in the time span from G2 to G5 was more pronounced in the oxandrolone-treated boys: 7.7 (SD 0.5) cm/year in group 2 and 7.7 (SD 1.4) cm/year in group 3 versus 5.1 (SD 0.9) cm/year in the controls. Height gain was significantly increased in the oxandrolone treated groups: 25.8 (SD 3.8) in group 2 and 25.2 (SD 3.7) in group 3 versus 19.8 (SD 4.9) in the controls (P < 0.05). Final height did not differ significantly among the three groups: 168.5 (SD 7.0) cm in the controls and 173.0 (SD 4.0) cm in group 2 and 167.8 (SD 5.3) cm in group 3. HSDSCA increased during puberty in all three groups. At final height, HSDSCA (calculated at age = 20 years) was -2.01 (SD 1.05), -1.34 (SD 0.59) and -2.12 (SD 0.79) respectively in groups 1, 2 and 3. An effect of oxandrolone on HSDSCA was not found. Target height was neither reached by the controls nor by the treated groups. Tempo of pubertal development was not different in the three groups, and delta BA/delta CA did not alter after start of oxandrolone treatment in groups 2 and 3. CONCLUSION: Boys with CDGP may benefit from oxandrolone treatment in terms of increased height gain. Starting treatment before the onset of puberty may be favourable.

Bioactivity of luteinizing hormone during normal puberty in girls and boys.

In order to evaluate the in vitro bioactivity of LH during normal puberty compared to LH immunoactivity measured in a highly sensitive immunoassay, blood plasma samples from healthy children were analyzed in a mouse Leydig cell assay (MLCA). Blood samples were obtained from 60 healthy girls and boys during normal pubertal development. Samples were taken on two occasions with a 1-year interval. Three daytime samples and three nighttime samples were analyzed. The correlation of the LH immunoradiometric assay (IRMA) activity with the LH activity in the MLCA varied from 0.60 to 0.96 in the different pubertal stages. During pubertal development, a gradually increase in the activity of LH in both the IRMA and MLCA was found. The ratio of the in vitro bioactivity compared to the immunoreactivity (B/I ratio) did not change significantly during puberty: it was 0.84 (SD 0.58) and 0.66 (SD 0.40) during the first and second sampling period in girls and 0.88 (SD 0.38) and 0.91 (SD 0.46, NS) in the boys. The B/I ratio of LH does not change during puberty. With a high sensitivity and specificity, measurement of LH by IRMA gives representative measurements of the LH in vitro bioactivity in children during pubertal development. Copyrightz1999S. KargerAG,Basel