P Chatelain

Claude Bernard University Lyon 1, Villeurbanne, Rhône-Alpes, France

Are you P Chatelain?

Claim your profile

Publications (21)30.25 Total impact

  • MB Ranke · MO Savage · P Chatelain · MA Preece · RG Rosenfeld · P Wilted

    No preview · Article · Apr 2008 · Acta Paediatrica
  • [Show abstract] [Hide abstract]
    ABSTRACT: A mathematical model for predicting the growth response in patients with Turner syndrome who received growth hormone (GH) therapy was developed by analysing data from KIGS, the Pharmacia & Upjohn International Growth Database. A Model for year 1 of GH therapy explained 46% of the variability of the growth response, with GH dose being the most important of the predictors of height velocity. In years 2-4 of therapy, height velocity during the previous year was the most important predictor, suggesting that an individual's initial response to GH may determine the height outcome of treatment. Additional treatment with oxandrolone. The predictions in all 4 years were highly accurate, as indicated by the low error SDs. However, relatively low predictive power (R) during years 2-4 of treatment suggests the models are missing other parameters that would explain more of the variability of the growth response. These growth prediction models could help clinicians to design individualized treatment regimens, provide realistic expectations of therapy outcomes, and adjust treatment on the basis of detected differences between observed and predicted height velocities.
    No preview · Article · Apr 2008 · Acta Paediatrica
  • K Yuen · D Cook · K Ong · P Chatelain · L Fryklund · P Gluckman · M B Ranke · R Rosenfeld · D Dunger
    [Show abstract] [Hide abstract]
    ABSTRACT: GH treatment has demonstrated favourable effects on most features of GH deficiency in hypopituitary adults. However, most studies employed supraphysiological GH doses, resulting in deterioration in insulin sensitivity (SI). The short-term metabolic effects of physiological doses of GH therapy in GH deficient (GHD) adults are largely unknown. We therefore compared the effects of short-term administration of two 'physiological' ('lowest' dose: 0.0017 mg/kg/day; 'low' dose: 0.0033 mg/kg/day) with two 'supraphy-siological' ('high' dose: 0.010 mg/kg/day; 'highest' dose: 0.025 mg/kg/day) GH doses on SI, beta-cell function, IGF-1 and IGFBPs -1 and -3 in a group of GHD adults. Thirteen GHD adults were recruited (seven men, aged 23-63 years). For each of the four doses, six patients (three men) were allocated randomly to undergo a 7-day treatment phase. Fasting blood samples were collected daily (days 1-8), and SI and beta-cell function were calculated using the homeostasis model assessment (HOMA). All four GH doses increased IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio, and decreased IGFBP-1 from day 3 onwards (P < 0.05). The highest dose increased fasting glucose (P < 0.001), insulin (P < 0.001) and beta-cell function (P < 0.001), but decreased SI (P < 0.001). The high and low doses did not modify fasting glucose and insulin, SI or beta-cell function, whereas the lowest dose enhanced beta-cell function (P < 0.05). The overall increase in the GH dose increased IGF-1, IGFBP-3, fasting glucose and insulin (P < 0.001), demonstrated a positive correlation with the final change in fasting glucose (r = 0.5, P < 0.05) and insulin (r = 0.8, P < 0.001) and a negative correlation with final SI (r = -0.5, P < 0.05). Our results suggest that short-term administration of the highest GH dose induced insulin resistance, whereas the lowest dose (0.0017 mg/kg/day) could represent the optimal starting dose in GHD adults due to its beneficial effects on beta-cell function without compromising SI. It is, however, yet to be determined whether the positive effects of the lowest GH dose on beta-cell function can be demonstrated over a longer period of time.
    No preview · Article · Sep 2002 · Clinical Endocrinology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this retrospective analysis was to evaluate the effects of growth hormone (GH) treatment on testicular development in boys with idiopathic short stature (ISS) and isolated GH deficiency (IGHD) followed in the KIGS (Pharmacia International Growth Database). For inclusion in the study, the patients had to have received more than 1 year of prepubertal GH treatment, at least 4 consecutive years of GH treatment in total, and to have attained their final height, defined as a height velocity of less than 2 cm/year. Data on 107 boys in the KIGS database have been analyzed. No significant differences in duration of GH treatment and testicular volume at the start of treatment or at final height were found between the boys with ISS and those with IGHD. The progression of testicular volume in boys with ISS or IGHD during GH treatment did not differ from the reference population. This analysis shows that GH treatment does not alter testicular growth in boys with ISS or IGHD. However, prospective controlled studies are needed to rule out moderate attenuating or stimulating effects.
    No preview · Article · Feb 2002 · Hormone Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Various prediction models have been developed, based on data documented within KIGS (Pharmacia International Growth Database), for use in the growth hormone (GH) treatment of children with short stature resulting from GH deficiency (GHD) or other causes. In addition to the practical value of such models as part of a 'forward strategy' guiding GH treatment, we now propose that prediction models may also be useful for the identification of individual variance in responsiveness. In a comparison involving 1,800 children with idiopathic GHD (IGHD), 151 children who acquired GHD after treatment for medulloblastoma and 192 children with GHD accompanying craniopharyngioma, it was shown that the responsiveness to GH of patients with craniopharyngioma equalled that of IGHD patients, whereas patients with medulloblastoma were less responsive. These observations and the identification of 'good' and 'poor' responders to GH have practical clinical consequences (e.g. modification of treatment), and will, in the future, lead to the identification of those factors which determine the variability of sensitivity to GH. This will improve the efficacy and safety of GH treatment as well as reducing the costs involved.
    No preview · Article · Feb 2001 · Hormone Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: The advent of unlimited supplies of recombinant human growth hormone (rhGH) since 1985 has certainly led to improvements in the treatment of short children with classical growth hormone deficiency (GHD). However, it has also enabled enrolment of many short children in numerous uncontrolled trials of GH treatment in non-GHD states (e.g. idiopathic short stature, IUGR, skeletal dysplasias, osteogenesis imperfecta, Prader-Willi syndrome, Down syndrome, Noonan syndrome, glucocorticoid-induced growth failure, and post-renal transplantation), in which sufficient data regarding effect of treatment on height or metabolic indices as well as safety aspects are still lacking. Current registered indications in most European countries include classical GHD (children and adults), chronic renal failure and Turner syndrome in children. There is concordance between FDA and European licensing authorities with respect to approved use of GH in children and adults apart from the fact that AIDS-related wasting in adults has also become a registered indication in the USA. In Japan, achondroplasia has become a registered indication of GH treatment.
    No preview · Article · Jan 2000 · Hormone Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: A mathematical model for predicting the growth response in patients with Turner syndrome who received growth hormone (GH) therapy was developed by analysing data from KIGS, the Pharmacia & Upjohn International Growth Database. A model for year 1 of GH therapy explained 46% of the variability of the growth response, with GH dose being the most important of the predictors of height velocity. In years 2-4 of therapy, height velocity during the previous year was the most important predictor, suggesting that an individual's initial response to GH may determine the height outcome of treatment. Additional predictors of height velocity in years 1-4 of GH therapy included age (negative), weight SDS and additional treatment with oxandrolone. The predictions in all 4 years were highly accurate, as indicated by the low error SDs. However, relatively low predictive power (R) during years 2-4 of treatment suggests the models are missing other parameters that would explain more of the variability of the growth response. These growth prediction models could help clinicians to design individualized treatment regimens, provide realistic expectations of therapy outcomes, and adjust treatment on the basis of detected differences between observed and predicted height velocities.
    No preview · Article · Jan 2000 · Acta paediatrica (Oslo, Norway: 1992). Supplement
  • [Show abstract] [Hide abstract]
    ABSTRACT: Postmarketing surveillance studies of recombinant human GH therapy, such as the Kabi Pharmacia International Growth Study (KIGS; Pharmacia & Upjohn, Inc., International Growth Database), have accumulated extensive data concerning the characteristics and growth outcomes of children with various causes of short stature. These data provide an opportunity to analyze the factors that determine responsiveness to GH and allow the development of disease-specific growth prediction models. We undertook a multiple regression analysis of height velocity (centimeter per yr) with various patient parameters of potential relevance using data from a cohort of 593 prepubertal children with idiopathic GH deficiency (GHD) from the KIGS database. Our aim was to produce models that would have practical utility for predicting prepubertal growth during each of the first 4 yr of GH replacement therapy. These models were validated by a prospective comparison of predicted and observed growth outcomes in an additional 3 cohorts of prepubertal children with idiopathic GHD: 237 additional KIGS patients, 29 patients from the Australian OZGROW study, and 33 patients from Tubingen, Germany. The most influential variable for first year growth response was the natural log (ln) of the maximum GH response during provocation testing, which was inversely correlated with height velocity. The first year growth response was also inversely correlated with chronological age and height SD score minus midparental height SD score. First year growth was positively correlated with body weight SD score, weekly GH dose (ln), and birth weight SD score. Two first year models were developed using these parameters, 1 including and 1 excluding the maximum GH response to provocative testing. The former model explained 61% of the response variability, with a SD of 1.46 cm; the latter model explained 45% of the variability, with a SD of 1.72 cm. The two models gave similar predictions, although the model excluding the maximum GH response to testing tended to underpredict the growth response in patients with very low GH secretory capacity. For the second, third, and fourth year growth responses, 4 predictors were identified: height velocity during the previous year (positively correlated), body weight SD score (positively correlated), chronological age (negatively correlated), and weekly GH dose (ln; positively correlated). The models for the second, third, and fourth year responses explained 40%, 37%, and 30% of the variability, respectively, with SDs of 1.19, 1.05, and 0.95 cm, respectively. When the models were applied prospectively to the other cohorts, there were no significant differences between observed and predicted responses in any of the cohorts in any year of treatment. The fourth year response model gave accurate prospective growth predictions for the fifth to the eighth prepubertal years of GH treatment in a subset of 48 KIGS patients. Analyses of Studentized residuals provided further validation of the models. The parameters used in our models do not explain all of the variability in growth response, but they have a high degree of precision (low error SDs). Moreover, the parameters used are robust and easily accessible. These properties give the models' practical utility as growth prediction tools. The availability of longitudinal, disease-specific models will be helpful in the future for enabling growth-promoting therapy to be planned at the outset, optimized for efficacy and economy, and individualized to meet treatment goals based on realistic expectations.
    No preview · Article · Apr 1999 · Journal of Clinical Endocrinology & Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: Final height was evaluated in 369 patients with idiopathic growth hormone deficiency (IGHD) enrolled in KIGS--the Pharmacia & Upjohn International Growth Database. At the start of growth hormone (GH) therapy, the patients were 9.8 years of age, their mid-parental height SDS was -0.8, and their height SDS was -3.1. Of the 369 patients, 50% had multiple hormone deficiencies, and puberty was induced in 31%. Patients were 18 years of age at completion of GH therapy, and had received GH at a dose of 0.49 IU/kg/week (0.16 mg/kg/week), with a mean of 5.2 injections/week for 8.1 years. Final height SDS was -1.5, final minus initial height SDS was 1.7 and final minus mid-parental height SDS was -0.5. A Swedish subgroup (n = 69) received conventional GH therapy throughout at 0.65 IU/kg/week (0.22 mg/kg/week), with seven injections/week for a mean of 9.4 years. These patients achieved their genetic potential (final minus mid-parental height SDS, 0.03), with a normal final height SDS of -0.3. For the total group, the following variables were associated with final height: mid-parental height SDS (r = 0.62), injection frequency (r = 0.37), duration of GH treatment (r = 0.28), peak stimulated GH concentration (r = -0.25), age (r = -0.19) (all p < 0.001) and height velocity SDS in the first year of treatment (r = 0.20, p = 0.004). In conclusion, genetic potential, expressed as the mid-parental height, is the variable with the greatest identified influence on final height during GH treatment in IGHD. Current GH regimens will lead to a normal height and attainment of mid-parental height. However, higher dose, individualized GH regimens are likely to be necessary for patients with IGHD who are disadvantaged at the time of commencing GH therapy, such as those with short parents, those whose treatment began in late childhood or adolescence and those with less severe GHD.
    No preview · Article · Mar 1999 · Acta paediatrica (Oslo, Norway: 1992). Supplement
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cutfield W, Lindberg A, Albertsson Wikland K, Chatelain P, Ranke MB, Wilton P, on behalf of the KIGS International Board. Final height in idiopathic growth hormone deficiency: the KIGS experience. Acta Pædiatr 1999; Suppl 428: 72–5. Stockholm. ISSN 0803–5326 Final height was evaluated in 369 patients with idiopathic growth hormone deficiency (IGHD) enrolled in KIGS - the Pharmacia & Upjohn International Growth Database. At the start of growth hormone (GH) therapy, the patients were 9.8 years of age, their mid-parental height SDS was -0.8, and their height SDS was -3.1. Of the 369 patients, 50% had multiple hormone deficiencies, and puberty was induced in 31%. Patients were 18 years of age at completion of GH therapy, and had received GH at a dose of 0.49 IU/kg/week (0.16 mg/kg/week), with a mean of 5.2 injections/week for 8.1 years. Final height SDS was -1.5, final minus initial height SDS was 1.7 and final minus mid-parental height SDS was -0.5. A Swedish subgroup (n= 69) received conventional GH therapy throughout at 0.65 IU/kg/week (0.22 mg/kg/week), with seven injections/week for a mean of 9.4 years. These patients achieved their genetic potential (final minus mid-parental height SDS, 0.03), with a normal final height SDS of -0.3. For the total group, the following variables were associated with final height: mid-parental height SDS (r= 0.62), injection frequency (r= 0.37), duration of GH treatment (r= 0.28), peak stimulated GH concentration (r= -0.25), age (r= -0.19) (all p < 0.001) and height velocity SDS in the first year of treatment (r= 0.20, p= 0.004). In conclusion, genetic potential, expressed as the mid-parental height, is the variable with the greatest identified influence on final height during GH treatment in IGHD. Current GH regimens will lead to a normal height and attainment of mid-parental height. However, higher dose, individualized GH regimens are likely to be necessary for patients with IGHD who are disadvantaged at the time of commencing GH therapy, such as those with short parents, those whose treatment began in late childhood or adolescence and those with less severe GHD. □Final height, growth hormone treatment, height, idiopathic growth hormone deficiency, KIGS
    No preview · Article · Feb 1999 · Acta Paediatrica

  • No preview · Chapter · Jan 1999

  • No preview · Chapter · Jan 1999
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Nb2 cell bioassay could be a useful tool for evaluating human growth hormone (hGH) bioactivity, but is not specific for hGH since it relies on the ability of the hormone to produce effects by cross-reacting with the lactogenic receptor on Nb2 cells. We studied the biological activity of both endogenous and exogenous hGH in short patients using the Nb2 bioassay after inhibiting the mitogenic effect of the other lactogenic hormone, that is human prolactin (hPRL), by adding a specific antibody against hPRL to each assay. The in vitro study showed a significant (p<0.0001) increase in Nb2 cell proliferation when increasing concentrations of highly purified hGH were added to the cell culture. A complete inhibition of Nb2 cell replication was observed after adding a specific antibody against hGH. The in vivo study showed a significantly (p<0.0001) lower hGH bioactivity (4.90+/-0.28 ng/ml) evaluated during stimulation tests in 9 children with total idiopathic GH deficiency, mean age 9.25+/-1.99 years, in comparison with that found in 11 short children with normal growth velocity, mean age 8.22+/-1.41 years (12.25+/-1.19 ng/ml). Likewise, serum GH levels measured by immunofluorometric assay IFMA in the same serum samples were significantly (p<0.001) lower in the 9 GH-deficient (1.97+/-0.37 ng/ml) than in the 11 short children (21.85+/-2.71 ng/ml). Moreover, we evaluated GH concentrations using both IFMA and the Nb2 cell bioassay in serum samples collected from another 11 idiopathic GH-deficient children, mean age 10.71+/-1.18 years, before and then, 6 and 24 hours following the 1 st injection of r-hGH (0.1 IU/kg sc). Serum GH values measured by both IFMA and Nb2 bioassay significantly (p<0.0001) increased 6 hours after r-hGH administration and decreased to reach basal levels after 24 hours. In conclusion, the Nb2 cell bioassay with minor modifications seems to provide a specific and sensitive assessment of hGH bioactivity.
    No preview · Article · Jan 1999 · Journal of endocrinological investigation

  • No preview · Chapter · Jan 1999

  • No preview · Article · Jan 1999

  • No preview · Chapter · Jan 1999
  • [Show abstract] [Hide abstract]
    ABSTRACT: In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV). Included were 223 patients who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard]. During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant. During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest.
    No preview · Article · Mar 1998 · Journal of Pediatrics
  • [Show abstract] [Hide abstract]
    ABSTRACT: We studied short- and long-term responses to growth hormone (GH) treatment and adverse medical events (AE) in 488 patients with craniopharyngioma who were entered into the Kabi International Growth Study (KIGS). First-year growth response and responsiveness (n = 394) were similar to those seen in children with idiopathic GH deficiency. The growth response over 5 years (n = 152) was unaffected by the recurrence of tumour and prior tumour management, but was greater in those receiving thyroxine. Mean height standard deviation scores (SDS) at the end of GH treatment (n = 129) was -0.7+/-1.2, and 79% achieved a height over -2 SD of target height, with evidence of further growth potential. Final height SDS correlated positively with height SDS at the start of treatment and with target height SDS, whereas gain in height SDS was inversely correlated with height SDS and bone age at the start of GH treatment. The rate of recurrence of tumour, 0.045/treatment year, was greater in those who had been treated with surgery alone compared to surgery and cranial irradiation. Other AE included headaches, fluid retention and convulsions occurring at rates of 0.025, 0.005 and 0.004/treatment year, respectively. We concluded that GH treatment is safe and effective in children with craniopharyngioma and provide data for counselling of parents about outcome during GH treatment.
    No preview · Article · Feb 1998 · Hormone Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. A previous metanalysis of four trials revealed that GH treatment over a period of 2 years induced a dose-dependent acceleration of linear growth and, to a lesser extent, of the rate of bone maturation in short, prepubertal children born SGA. The rate of bone maturation and the change in height SDS for bone age from the previous 2-year metanalysis have been re-analysed according to chronological age (two prepubertal age groups: group A, 3.0-5.9 years old; group B, 6.0-8.9 years old). The rate of bone maturation was slower in younger than in older prepubertal children; this difference was more marked in children receiving high-dose (0.2 or 0.3 IU/kg/day) GH treatment (p < or = 0.01). Accordingly, the change in height SDS for bone age was increased by high-dose GH treatment in both age groups (p < or = 0.01), and was more pronounced in younger than in older children (1.45 +/- 0.28 versus 0.63 +/- 0.20; p < or = 0.01). Height SDS data from 100 short, prepubertal children born SGA have been analysed over 4 years. The change in height SDS appeared to be related to the average dose of GH. A mean GH dose of 0.1 IU/kg/day over 4 years was administered either as 0.1 IU/kg/day for 4 years (continuous) or as 0.2 IU/kg/day for 2 years, followed by 2 years without GH treatment (discontinuous). After 4 years of treatment, the increase in height SDS for the continuous and discontinuous treatment schedules was similar, being 1.42 +/- 0.10 SDS and 1.58 +/- 0.17 SDS, respectively. In a second regimen, a mean GH dose of 0.2 IU/kg/day over 3 years was administered either as 0.2 IU/kg/day for 3 years (continuous) or as 0.3 IU/kg/day for 2 years, followed by 1 year without GH treatment (discontinuous). After 3 years, the increase in height SDS with the continuous and discontinuous treatment schedules was similar, being 2.01 +/- 0.18 SDS and 2.22 +/- 0.16 SDS, respectively. GH administration was well tolerated in all treatment groups. In conclusion, the rate of bone maturation in short, prepubertal children born SGA treated with GH appeared to depend not only on the dose of GH, but also on the age of the child. GH treatment resulted in a prolonged increase in height SDS, the magnitude of the rise being dependent on the average GH dose rather than on the continuous or discontinuous mode of GH administration.
    No preview · Article · Nov 1997 · Acta paediatrica (Oslo, Norway: 1992). Supplement
  • P Chatelain · JC Carel · M Nicolino · MO Savage · JL Chaussain

    No preview · Article · Dec 1996 · Archives de Pédiatrie

Publication Stats

494 Citations
30.25 Total Impact Points

Institutions

  • 1999-2008
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
  • 2001
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 1997
    • University of Leuven
      Louvain, Flemish, Belgium
  • 1996
    • University of Lyon
      Lyons, Rhône-Alpes, France