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Biomedical subjects

P Chatelain

Publications and source records attributed to P Chatelain.

At least 37 records · Page 2Linked to original sources
PubMed2000

Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment.

BACKGROUND: Growth hormone (GH) contributes to insulin resistance, but whether children treated with GH are at increased risk of diabetes has not been established. We undertook a retrospective analysis of data from an international pharmacoepidemiological survey of children treated with GH to find out the incidence of impaired glucose tolerance and types 1 and 2 diabetes mellitus. METHODS: Reports to the survey of abnormal glucose metabolism were investigated and classified. The incidence and age-distribution of type 1 diabetes were compared with values from a model of reference data. The incidence of type 2 diabetes was compared with data from two reports of children not treated with GH. FINDINGS: 85 (0.36%) of 23333 children were reported with abnormal glucose metabolism. After investigation, 43 had confirmed glucose disorders (11 with type 1 diabetes, 18 with type 2 diabetes, and 14 with impaired glucose tolerance). The incidence and age at diagnosis of type 1 diabetes in children treated with GH did not differ from expected values. The incidence of type 2 diabetes was 34.4 cases per 100000 years of GH treatment which was six-fold higher than reported in children not treated with GH. Type 2 diabetes did not resolve after GH therapy was stopped. INTERPRETATION: GH treatment did not affect the incidence of type 1 diabetes mellitus in any age group. We postulate that the higher than expected incidence of type 2 diabetes mellitus with GH treatment may be an acceleration of the disorder in predisposed individuals.

Adolescent↗
PubMed2000

Accuracy of coronary flow measurements performed by means of Doppler wires.

To estimate in patients the accuracy of coronary flow measurements performed by means of 0.014" Doppler wires, the time-averaged maximal blood velocity (APV) was recorded in the 3 branches of 36 angiographically normal coronary artery bifurcations selected in 21 patients undergoing cardiac catheterization for various diseases. Contrast medium injections filmed under two incidences allowed identification of the 3 sample volume locations and computing of the 3 corresponding vessel cross-sectional areas (CSA) at subsequent data analysis. Multiplication of the velocities APV/2 (range: 3 to 20.5 cm/s) by the CSA (obtained by averaging the two calibrated vessel diameters; range: 1.6 to 5.4 mm) yielded 108 flow rates (range: 5.4 to 169 mL/min). The average relative flow error was then estimated using the continuity equation (Q(in) = Q(out,1) + Q(out, 2)) and the central limit theorem. The result was that the relative flow error decreased from 30% at Q = 30 mL/min to 13% at Q = 160 mL/min. We conclude that coronary flow measurements are reasonably accurate, except perhaps for very low flows.

Blood Flow Velocity↗
PubMed2000

In-vivo measurements of wall shear stress in human coronary arteries.

BACKGROUND: Wall shear stress (WSS) is closely associated with arteriosclerosis. WSS values for various vessels and species are available, but fully in-vivo measurements in human coronary arteries have not yet been reported. OBJECTIVE: To measure WSS in undiseased coronary arteries of adult patients at rest. METHODS: We recorded the temporal average value (APV) of the instantaneous maximal blood velocity in the three vessel segments of angiographically normal coronary artery bifurcations in 21 patients undergoing cardiac catheterization to treat various diseases by means of a 0.036 cm Doppler wire (FloWire). In total, 36 bifurcations were examined. The 36 x 3 cross-sectional areas (CSA) were determined by means of a three-dimensional angiographic technique. The three flows, Q1 (inflow), Q2, and Q3 of each bifurcation were calculated according to Q=0.5 x APV x CSA. For each segment, WSS was calculated as WSS=32 eta Q/(pi D3) (where blood viscosity eta=3.5 mPa s and D is vessel diameter). Only the 54 WSS values obtained from the 18 flow triplets which satisfied the equation Q1/(Q2+Q3)=1 better than did the 18 other ones were retained. RESULTS: The 54 WSS values ranged from 0.33 to 1.24 Pa (mean 0.68 Pa, SEM, 0.027 Pa). They did not depend significantly on Q (r=0.07; P=0.60) and the CSA (r=0.24, P=0.08) but the second relationship approached significance. CONCLUSION: The obtained mean WSS value (0.68 Pa) is half the value predicted for coronary arteries from optimality principles. It is also smaller than many values reported for human carotid, renal, and femoral arteries.

Aged↗
PubMed2000

Prediction of long-term response to recombinant human growth hormone in Turner syndrome: development and validation of mathematical models. KIGS International Board. Kabi International Growth Study.

It has become common practice to apply GH treatment in short Turner syndrome patients with the objective of promoting growth. The variability in response and the high costs of this treatment demand the individualization and optimization of therapy. Based on 686 prepubertal Turner patients from the Kabi International Growth Study (KIGS; Pharmacia & Upjohn, Inc. International Growth Database), we undertook a multiple regression analysis of height velocity (centimeters per yr) by using various parameters of potential relevance. Derived prediction models for the first 4 yr of GH treatment were validated with 76 additional KIGS patients and 81 patients from Tuebingen, Germany. Among the 6 predictors identified, the most influential variable for first year growth response was the natural log (ln) of the weekly GH dose. The first year growth response was also correlated with age and distance between height and target height (SD score; both negative) and body weight SD, number of GH injections per week, and oxandrolone treatment given additionally (positive). The first year model explains 46% of the variability, with 1 SD of 1.26 cm. For the second to fourth years, 5 predictors were identified: height velocity during previous years, weekly GH dose (ln), weight SD, oxandrolone therapy (all positive), and age (negative). These models explained 32%, 29%, and 30% of the variability, respectively, with SD scores of 1.1, 1.0, and 1.0 cm, respectively. When the models were applied to the other cohorts, no significant difference was noted between observed and predicted responses. Although the parameters used in our models do not entirely explain the variability in the growth response in Turner syndrome, the parameters themselves were clinically relevant to our present understanding and proved to be of high precision. Some of the tested markers, such as karyotype, do not contribute to the growth response. These variables make the models practical and suitable for planning beneficial and cost-effective therapy.

Anabolic Agents↗
PubMed2000

Growth hormone treatment of short children born small for gestational age: growth responses with continuous and discontinuous regimens over 6 years.

We report an epi-analysis of 6-yr growth responses obtained with GH treatment in short children born small for gestational age (SGA). Four randomized, multicenter studies explored the effects of continuous and discontinuous regimens of GH treatment in short, non-GH-deficient SGA children. A total of 49 untreated and 139 treated children were followed over 2 and 6 yr, respectively. At the start of the study, the age of these 188 children averaged 5.2 yr (range, 2-8 yr), height was -3.4 SD score, and height adjusted for parental height was -2.4 SD score. Onset of puberty was observed in 46% of the GH-treated cohort, on the average, at 10.7 yr in girls and 11.7 yr in boys. Two studies essentially investigated the effects of continuous GH treatment at a dose of 33 or 67 microg/kg, day, and two studies focused on the growth characteristics during an initial GH treatment for 2-3 yr (dose range, 33-100 microg/kg x day), followed by a withdrawal phase of 1-2 yr, and then by either no or 1 or more episodes of further GH treatment (33 or 67 microg/kg x day). Continuous GH treatment for 6 yr resulted in height increments of 2.0 +/- 0.2 SD (33 microg/kg x day; n = 35) and 2.7 +/- 0.2 SD (67 microg/kg x day; n = 27). Discontinuous GH treatment was given to 77 children, most of them experiencing only 1 (n = 47) or 2 (n = 26) treatment phases with an average duration of 2.0 yr. All these children received GH during the first 2 yr; the dose was only 32 microg/kg x day when averaged over 6 yr. Some individualization of treatment schedules was allowed, and the majority of investigators seemed to aim for a low normal height level, adjusted for parental height. After 2 yr, the mean adjusted height SD score had increased to -0.4 +/- 0.1 and stabilized thereafter. Bone maturation progressed similarly in all treatment subgroups, and after 6 yr of study, bone age remained slightly delayed compared to chronological age. Multivariate analysis identified the average GH dose over 6 yr, parental-adjusted height SD score, and age at start as prime predictors of the growth response. GH treatment was well tolerated. In conclusion, this epi-analysis of growth responses over 6 yr confirms the administration of GH as an effective approach to normalize the stature of short, non-GH-deficient SGA children, at least during childhood and early puberty. In addition, it is now increasingly apparent that a relatively broad spectrum of GH regimens is effective, and this experience should facilitate the design of more individualized treatment schedules in the future, in particular for young children.

Body Height↗
PubMed2000

Children born with intra-uterine growth retardation (IUGR) or small for gestational age (SGA): long term growth and metabolic consequences.

Intra Uterine Growth Retardation (IUGR) refers to insufficient fetal growth diagnosed either by two direct intrauterine growth assessment (ultra-sonography) or when the fetus or newborn length (height) is less than two standard deviations (or third percentile) below the mean for gestational age (NIKLASSON et. al. 1991; DE ZEGLER 1997). When the fetus or newborn body size (wight or length) is insufficient for gestational age, that is less than 2 standard deviations below the mean (or third percentile) for gestation during the situation is referred to as Small for Gestational Age (SGA). Since both fetal weight and length (height) gains are closely related, there is much overlap between SGA and IUGR. The proportion of newborn with normal birth weight and overlap between SGA and IUGR, isolated low birth weight, isolate low birth length and combined low birth weight and length is presented in Tab. 1, according to the most recent series reported nb NIKLASSON (1991). SGA/IUGR is a public health problem, since 2.5-3.0 % of newborns are affected by definition, and 8-10 % of them do not catch up postnatally, presenting with a persistent severe height deficiency, developmental difficulties and poor outcome (UNDERWOOD 1991; SIEGEL et al. 1991; Albertson-WICKLAND et. al. 1993; LAKEMAN et al. 1994).

Body Height↗
PubMed2000

[Paroxysmal atrioventricular block during coronary revascularization with ultrasound. A case report].

The authors report the case of advanced atrioventricular block during a procedure of right coronary revascularisation with ultrasound. The different possible physiopathological mechanisms are discussed. Although no formal conclusions can be drawn, certain features suggest a paroxysmal nodal conduction defect secondary to transient parasympathetic stimulation by the ultrasound, a stimulation triggered by a Bezold-Jarish type of cardiac reflex or by direct local excitation of vagal fibres of the atrioventricular node.

Coronary Disease↗
PubMed1999

Quantification of myocardial perfusion with FAST sequence and Gd bolus in patients with normal cardiac function.

The present study reports on a new calibration of the magnetic resonance imaging (MRI) signal intensity of a fast gradient-echo sequence used for in vivo myocardial perfusion quantification in patients. The signal from a FAST sequence preceded by a arrhythmia-insensitive magnetization preparation was calibrated in vitro using tubes filled with various gadolinium (Gd) solutions. Single short-axis views of the heart were obtained in patients (n = 10) with normal cardiac function. Myocardial and blood signal intensity were converted to concentration of Gd according to the in vitro calibration curve and fitted by a one-compartment model. K1 [first-order transfer constant from the blood to the myocardium for the gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA)] and Vd (distribution volume of Gd-DTPA in myocardium) obtained from the fit of the MRI-derived perfusion curves were 0.72+/-0.22 (mL/min/g) and 15.3+/-5.22%. These results were in agreement with previous observations on animals and demonstrated that a reliable measurement of myocardial perfusion can be obtained by MRI in patients with an in vitro calibration procedure.

Calibration↗
PubMed1999

Final height in idiopathic growth hormone deficiency: the KIGS experience. KIGS International Board.

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.

Adolescent↗
PubMed1999

Predicting the response to recombinant human growth hormone in Turner syndrome: KIGS models. KIGS International Board. Kabi International Growth Study.

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.

Body Height↗
PubMed1999

Derivation and validation of a mathematical model for predicting the response to exogenous recombinant human growth hormone (GH) in prepubertal children with idiopathic GH deficiency. KIGS International Board. Kabi Pharmacia International Growth Study.

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.

Child↗
PubMed1998

Evaluation of growth hormone bioactivity using the Nb2 cell bioassay in children with growth disorders.

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.

Animals↗
PubMed1998

Low dose linomide in Type I juvenile diabetes of recent onset: a randomised placebo-controlled double blind trial.

The quinoline-3-carboxamide, linomide, protects non-obese diabetic mice from diabetes. The effects of linomide on insulin needs and beta cell function were studied in recent juvenile Type I diabetes in a double-blind trial. Patients with recent onset diabetes were randomly assigned to treatment with a fixed dose of 2.5 mg linomide (42 patients) or placebo (21 patients) for 1 year, in addition to insulin and diet. Glycated haemoglobin was 10-15% lower at 9 months (p = 0.003) and 12 months (p < 0.05) in the linomide group. The insulin dose was 32-40% smaller in the linomide group at 3 (p < 0.03), 6 (p < 0.02), 9 (p < 0.001) and 12 months (p = 0.01). Insulin doses correlated negatively with C peptide values (p = 0.001-0.002). The trend for higher C peptide values in the linomide group did not reach significance. In a post hoc subgroup analysis performed in 40 patients (25 from the linomide group and 15 from the placebo group) who still had detectable residual beta cell function at entry, linomide was associated with 45-59% higher C peptide value at 6 months (p < 0.05), 9 months (p < 0.05) and 12 months (p < 0.05). The main adverse effects of linomide were mild transitory anaemia (45 vs 10% in the linomide and placebo groups), thrombocytopenia (24 vs 10%), and mild joint discomfort (45 vs 5%) with no clinical signs. In conclusion, low-dose linomide reduced the insulin needs in patients with juvenile Type I diabetes of recent onset and improved beta cell function in patients who still had detectable beta cell function at entry. These results support further clinical and experimental studies to define the effects of linomide in Type I diabetes provided the safety of linomide is reliably established.

Adjuvants, Immunologic↗
PubMed1998

Dual energy X-ray absorptiometry of the hand and wrist--a possible technique to assess skeletal maturation: methodology and data in normal youths.

Ninety five normal Caucasian subjects (51F, 44M) aged from 2 to 25 y were measured at the hand and wrist level with a small DXA system (pDEXA) in order to obtain the normal values of the bone mineral content (BMC), density (BMD) and projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065 +/- 0.007 g/cm2 to 0.365 +/- 0.035 g/cm2 in females and 0.425 +/- 0.040 g/cm2 in males. It presented a sharp change of increase rate at 15.5 and 17 y of age in girls and boys, respectively. Ac presented the same kind of evolution as BMDc, but had a larger value dispersion. The second metacarpal bone had the highest BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i = 1-5) and the projected mean density of the 5 metacarpal bones was well correlated with BMCc, Ac and BMDc, respectively (r > 0.90). A volumetric mineral density, dmi, calculated for each of these bones, approximated to a cylinder, was correlated with age (r > 0.85).

Absorptiometry, Photon↗
PubMed1998

Efficacy and safety of growth hormone treatment in children with prior craniopharyngioma: an analysis of the Pharmacia and Upjohn International Growth Database (KIGS) from 1988 to 1996.

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.

Body Height↗
PubMed1998

Erdheim-Chester disease: a primary macrophage cell disorder.

Erdheim-Chester disease (ECD) is a rare focal or systemic infiltrative disorder resulting from xanthogranulomatous tissue deposition. Usually, bone marrow involvement affects long bone metaphyses symmetrically, but it spares the epiphyses. Retroperitoneal space, periaortic area, skin, and brain involvement have been described. Pulmonary involvement is frequent, occurring in 20% of cases. Reported histologic features in the lung include an infiltration of so-called lipid-laden macrophages and granulomatous lesions with fibrosis. Lung function outcome is unpredictable, but terminal respiratory failure is the most frequent cause of death. No effective treatment strategies have been described. We report a new case with lung and bone involvement occurring in a symptomatic woman. Histologic and electron microscopic analysis of the pulmonary infiltrate showed abnormal macrophages devoid of lipids forming nodular granulomas and rendering the previous hypothesis of this disease as a primary lipid storage disorder unlikely. These findings suggest that ECD histogenesis is instead based on a primary macrophage cell disease.

Adult↗