[Show abstract][Hide abstract] ABSTRACT: Celiac disease may lead to various degrees of growth retardation. In general, catch-up growth is completed in the first 2 years after the start of therapy. A mathematical model for catch-up growth in celiac disease can be useful as a reference to which the growth pattern observed during treatment of other conditions can be compared. In this study we performed a non-linear regression analysis on individual growth data of 16 celiac disease patients using a monomolecular growth function. The goodness of fit was significant in all cases (p < 0.05), which illustrates that this function adequately describes catch-up growth in individuals with celiac disease. From the individual models we have composed a cross-sectional curve and a longitudinal description of the pattern of catch-up growth for the entire population.
[Show abstract][Hide abstract] ABSTRACT: Spontaneous growth and growth responses to GH therapy vary considerably among girls with Turner's syndrome. In an attempt to clarify this variability, we assessed growth parameters, 24-h GH profiles, arginine-stimulated serum GH levels, and plasma insulin-like growth factor-I (IGF-I) concentrations in a group of 41 girls with Turner's syndrome with a mean (+/- SD) age of 13 +/- 3 yr (range, 6.7-18.9). We subsequently treated all girls with biosynthetic GH (24 IU/m2 x week) and documented the growth response after 1 yr of therapy. GH profiles were analyzed according to Pulsar and Cluster, and GH secretion rates were calculated by waveform-independent deconvolution (Pulse). Factor analysis selected the mean 24-h GH secretion rate and number of GH peaks according to Cluster and Pulse as the principal GH profile variables to be used for further analysis. The mean (+/- SD) daily pituitary GH secretion rate was 127 +/- 47 micrograms/L.24 h (range, 37-232). The GH secretion rate correlated inversely with body mass index (r = -0.45; P < 0.01; n = 41). There was no relationship between the GH secretion rate and the growth parameters before or after GH therapy. However, the number of GH peaks (Pulse) correlated negatively with baseline height velocity (r = -0.53; P = 0.03) and was a positive predictor for height velocity increment during the first year of GH therapy (r = 0.71, P = 0.001). The mean (+/- SD) IGF-I level was 217 +/- 91 ng/mL (range, 87-413). There was no relationship between GH secretion rate or growth parameters and IGF-I. However, the number of GH peaks correlated negatively with IGF-I (r = -0.49; P = 0.04; n = 17). We conclude that an elevated spontaneous GH pulse frequency pattern is associated with relatively low IGF-I levels and slow baseline growth in girls with Turner's syndrome and that girls with such a pulse pattern may benefit most from exogenous GH therapy.
[Show abstract][Hide abstract] ABSTRACT: A multicenter dose-response study evaluated the effect of two different doses of biosynthetic GH on auxological and biochemical parameters in 38 prepubertal children with GH deficiency (GHD). Twenty-one were newly diagnosed, while 17 transfer patients had been on GH treatment for at least 1 yr before the study. New and transfer patients alike were treated with either 2 or 4 IU GH/m2.day sc. At evaluation all new patients had completed 1 yr of treatment, while transfers had completed 2 yr of treatment under study. In the new patients both doses resulted in a significant increase in height velocity (HV) and height SD score (SDS), with comparable bone maturation. After correction for the severity of GHD, the increase in HV SDS was significantly greater with 4 IU than with 2 IU (P less than 0.01). In the transfer patients HV, height SDS, and predicted adult height only increased significantly with 4 IU (P less than 0.05). Bone maturation was comparable for the two doses. There was a significant correlation between first year growth response and GH dose. In the new patients, the plasma insulin-like growth factor-I (IGF-I) concentration increased significantly without a significant difference between dosage groups. There was a positive correlation between growth response and increment of plasma IGF-I SDS. In new and transfer patients alike, above normal plasma IGF-I levels were observed, particularly with 4 IU. Hemoglobin-A1 remained constant with both GH doses in both groups, while cholesterol and LDL levels tended to decrease. In the new patients, the mean apolipoprotein-A1 level was lower than the control value after 1 yr on 4 IU GH. Treatment with 4 IU GH/m2.day led to a greater growth response than a dose of 2 IU in newly diagnosed as well as previously treated GHD patients. Bone maturation was comparable for both doses. No adverse effects were observed with the higher GH dose, but the long term effects on IGF-I and lipid metabolism need further attention.
[Show abstract][Hide abstract] ABSTRACT: To study platelet activation as a phenomenon that may precede development of angiopathy in diabetes mellitus, we compared platelet adhesion and thrombus formation in a flow system with blood from insulin-dependent (type I) diabetic subjects with and without macroangiopathy and age- and sex-matched control subjects. Adhesion and thrombus formation on matrix of cultured human endothelial cells (ECM) and adhesion on matrix of human fibroblasts (FBM) were studied after exposure to flowing blood at shear rates of 300 and 1300 s-1 and exposure times of 1, 3, 5, and 10 min (and 20 min in adhesion experiments). Blood was anticoagulated with trisodium citrate (1:10 vol/vol, 110 mM) or low-molecular-weight heparin ([LMWH] 20 U/ml). Endothelial cell cultures were either unstimulated or stimulated with 4 beta-phorbol 12-myristate 13-acetate (PMA) 16 h before isolating their matrix. Platelet adhesion on ECM and FBM in citrated and LMWH-anticoagulated blood was identical in diabetic patients and control subjects, with comparable increases of adhesion with increasing perfusion times. Platelet aggregate formation on ECM of PMA-stimulated cells with LMWH-anticoagulated blood was similar in diabetic patients, whether macroangiopathy was present, compared with control subjects. Fibrin deposition and fibrinopeptide A generation during perfusion were comparable in diabetic and control subjects. Platelet thromboxane B2 formation after stimulation with arachidonic acid was increased in diabetic patients without macroangiopathy compared with age- and sex-matched control subjects. In the perfusion system, the patterns of platelet adhesion and aggregate formation on extracellular matrix in flowing blood of diabetic patients (with or without macroangiopathy), and healthy age- and sex-matched control subjects followed a similar pattern.(ABSTRACT TRUNCATED AT 250 WORDS)