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8 toll adolescents (4 boys and 4 girls) had accepted to bo treated by SMS 201-995 for 12 Months in order to reduce their growth velocity and therefore their adult height. This treatment had been submitted to the local ethical committee. Afc present time 5 patients had undergone 3 months treatment (4 boys and one girl), mean chronological age was 14 years 6 months ± 1 year 2 months, mean SD for height was + 3.1 ± 0.42 SD, mean bone age was 14 years 6 Months ± 1 year 3 months, pubertal development was scored Tanner stage III (n=l) and IV (n=4). Before treatment, physiological 24 hour GH secretion, GH response to TRH and GHRH stimulation tests, SmC levels and others pituitary functions were evaluated. SMS 201-995 was given twice daily using 2 subcutaneous injection of 250 ug at 8.00 AM and 8.00 PM. For the whole group, growth velocity had strongly decreased (2 ± 2.82 cm/y versus 6.9 ± 2.35 cm/y), growth was completely blocked in 3 patients. One boy aged 15 years 9 months had the same growth velocity before and after treatment. The last patient had previously been treated unsuccessfully by bromocryptine during one year and after 3 months of SMS 201-995 therapy growth velocity had decreased (6cm/y versus 10 cm/y before treatment). Tolerance of this therapy was good however transient diarrhea and nausea during the first ten days had occured in all cases. Routine biological parameters remained normal. CONCLUSION : These preliminary results suggest the efficacy of SMS 201–995 in reducing growth velocity in children with constitutional tall stature without major side effects.

Basic Fibroblast growth factor (FGF) is a polypeptide of 17.000 PM, isolated from various bovine and human tissues. This factor has a strong mitogenic activity and maintains differenciation of mesodermic cells in vitro, but its physiological role remains unknown. We used a radioimmunoassay (RIA) developped by Guillemin et al. Using antibodies raised against a synthetic replicate of |Tyr10| FGF (1-10). Our RIA intraassay and interassay coefficients of variation were 14% and 7% respectively. 83 children, 44 boys and 39 girls aged from 1 year 1 month to 15 years 10 months (m : 6 years 6 months) were studied. FGF mean value was 20,01 ± 6,18 pmol|ml. A great disparity of individual values was found. No significative difference was found between boys (18,76 ± 6,28 pmol/ml) and girls (20,87 ± 5,84 pmol/ml). FGF values did not correlated with chronological age, but analysis of the results showed a slightly increase of FGF values with a maximum peak in prepubertal stage (10-12 years) followed by a slow decrease in pubertal children (12-16 years). We had previously studied 135 adults men and women. Adult FGF levels were lower than in children (m : 18,34 ± 4,44 pmol/ml, p

SMS 201-995 was used in a 4 month-old boy presenting hypoglycemic seizures with hyperinsulinism. The dose of SMS 201-995 was rapidly increased during the first week from 10 ug/kg/day to 100 ug/kg/day, and was administrated using continuous subcutaneous infusion (CSI) during 8 months and then 3 or 2 daily subcutaneous infusion per day for 1 month. Capillary blood glucose was measured every 3 hours. Plasma insulin was evaluated twice daily on the first weeks and when blood glucose was lower than 50 mg/dl. Mean blood glucose levels was dramatically and rapidly increased by therapy, frequency of hypoglycemia was strongly reduced, blood glucose/insulin ratio increased;carbohydrate needs were reduced (0.6g/kg/day). CT Scan of the pancreas performed before therapy noticed a global increase of the volume of the gland which was no more observed after one month of therapy. Growth velocity remained in a normal range for age. Measure of plasma GH every 20 min during 5 hours had shown a normal spontaneous GH peak of 50 ng/ml. Neurologic development was normal. Others endocrine functions remained normal. Tolerance of this treatment was good excepted for transient diarrhea and vomiting during the first 2 weeks of therapy and transient moderate increase of Gamma GT. Treatment had been interrupted after one and 6 months of therapy with reccurrent hypoglycemia after 3 and 6 days respectively. 3 or 2 subcutaneous injections resulted in a worstly glycemic control than CSI therapy.